Journal 2

Private circulation only
Health Sciences
The Official Journal of
Kerala University of Health Sciences
Thrissur, Kerala
April - June 2016

Issue 2 Volume 1
KERALA UNIVERSITY OF HEALTH SCIENCES

Thrissur 680 596, Kerala
The Chancellor
JUSTICE (RETD.) P. SATHASIVAM
Pro-Chancellor
SMT. K K SHYLAJA TEACHER
Editorial Board
Patrons Prof (Dr) M K C Nair, Vice Chancellor, KUHS.
Prof (Dr) A Nalinakshan, Pro Vice Chancellor, KUHS
Editor in Chief Dr. Paul Swamidhas Sudhakar Russell,
Professor of Psychiatry, CMC,Vellore. (on leave)
Guest Editor Dr. Harikumaran Nair G S
Professor, Department of Radiodiagnosis, Government T D
Medical College, Alappuzha, Faculty CERTC, GMC, Thiruvananthapuram
Managing Editor Dr Mangalam M K, Registrar
Executive Editor Dr. Sudhir P K, Controller of Examinations, KUHS.
Associate Editors Dr. Ajithkumar K, Dean Research, KUHS.
Dr. Manojkumar A K, Dean Student Affairs, KUHS.
Dr. Unnikrishnan V V, Dean Academic
Assistant Editor Dr. Leena M L, Program Officer (Academic)
Advisors
Chief Advisor Dr. N K Arora, Executive Director INCLEN, New Delhi.
Ethics Justice (Rtd) M Hariharan Nair, Chairman, University Ethics Committee.
Epidemiology Dr. K T Shenoy, Formerly Director, CERTC, Government Medical College,
Thiruvananthapuram.
Medical Social Science Dr. S Remadevi, Senior Faculty, CERTC, Government Medical College,
Thiruvananthapuram.
Basic Science Dr. P R Sudhakaran, Emeritus Scientist, Department of Computational
Science and Bio-informatics, University of Kerala, Kariyavattom.
Biostatistics Dr. Jayaseelan L, Professor of Biostatistics, CMC, Vellore.
Health Management Dr. Fazal Gafoor, Professor and Head, Department of Neurology,
MES College, Perinthalmanna.
AYUSH Research Dr. Rajasekaran Nair, Advisor, State Medicinal Plant Board,
Poojappura, Thiruvananthapuram.
Dean Medicine Dr. Mohanan K, Professor and Head, Department of Radiodiagnosis,
GMC, Thrissur.
Dean Ayurveda Dr. Krishnan Nair CK, Professor, Government Ayurveda College,
Thripunithura.
Dean Homoeopathy Dr. Sunil Raj P, Professor and HOD, Government Homeopathic Medical
College, Thiruvananthapuram.
Dean Dental Dr. Thomas Manjooran, Professor and Head, Department of Paedodontics,
PSM College of Dental Sciences, Thrissur.
Dean Nursing Dr. Valsamma Joseph, Department of Child Health Nursing, Government
College of Nursing, Kottayam.
Dean Pharmacy Dr. Kuppuswamy S, Professor and Head, Department of Pharmaceutics,
Nirmala College of Pharmacy, Muvattupuzha.
Dean Allied Science Dr. Sankar S, Professor and Head, Department of Pathology, GMC,
Thiruvananthapuram.
Finance Management Mr. Gloyee Augustin, Finance Officer, KUHS.
Editorial Committee
1 Dr. Asokan N, Additional Professor, Department of Dermatology and Venereology, Government
Medical College, Thrissur.
2 Dr. Atanu Bhattacharjee, Assistant Professor, Department of Biostatistics, MCC, Thalassery.
3 Ms. Athira Rani, Assistant Professor, Government Nursing College, Thiruvananthapuram.
4 Dr. Bindu R Nayar, Professor, Department of Periodontology, Dental College, Thiruvananthapuram.
5 Dr. Harikumaran Nair G S, Professor, Department of Radiodiagnosis, Government T D Medical
College, Alappuzha, Faculty CERTC, GMC, Thiruvananthapuram.
6 Dr. Indu P V, Associate Professor, Department of Psychiatry, Government Medical College,
Thiruvananthapuram.
7 Dr. Kavitha Ravi, Associate Professor, Department of Pathology, Medical College,
Thiruvananthpuram.
8 Dr. Krishnakumar, Principal, St.James College of Pharmacy, Chalakudy.
9 Dr. Mansoor Ali K R, Associate Professor, Government Homeopathic College, Kozhikode.
10 Dr. Murali K, Professor, Government Ayurveda College, Thripunithura.
11 Dr. Pradeep S, Professor of Pharmacology, Medical College, Thiruvananthapuram.
12 Dr. Rajamohanan K, Professor of Paediatrics, Dr SMCSI Medical College, Karakonam,
Thiruvananthapuram, Formerly Director, CERTC, GMC, Thiruvananthapuram.
13 Dr. Sathidevi V K, Additional Professor, Department of Anatomy, Government Medical College,
Thrissur.
14 Dr. Sujith J Chandy, Professor of Pharmacology, Pushpagiri Medical College, Thiruvalla.
15 Dr. Vidhukumar K, Additional Professor, Department of Psychiatry, Medical College,
Thiruvananthapuram.
16 Dr. Zinia T Nujum, Associate Professor, Department of Community Medicine, Medical College,
Thiruvananthapuram.
4 Health Sciences The Official Journal of Kerala University of Health Sciences

CONTENTS
Vice Chancellor’s Page: Prof (Dr) M K C Nair. 07

Editorial: Harikumaran Nair G S 09
Original articles
1. Prevalence of Obesity among high school girls in Thiruvananthapuram City-
A Cross Sectional Study - Geetha S, Nair M K C 11
2. Association of overweight and insulin resistance with polycystic ovary
syndrome (PCOS). - Sreekumari R, Nair M K C, Nirmala C. 17
3. Diagnostic test evaluation of IgM ELISA and Lepto Tek Dri-Dot in the
serodiagnosis of Leptospirosis - Kavita Raja, Rema Devi S, Soja V, Shenoy KT. 23
Review articles
1. Cancer Vaccines - A Novel Approach in Immune Therapy
Krishnakumar U, Girish HC, Vinay Chandra R. 29
2. Hot Tooth: Dooming Dare of the Dentist
Bindu R Nayar, Sheeba P, Sudheer Kumar Prabhu 40
3. Scrub typhus- Alert
Devraj Ramakrishnan, Zinia T Nujum, Sara Varghese 44
Concept Paper
‘Concept of Family Health’ as an innovative health delivery strategy
Nair MKC, Leena ML, Manoj Kumar AK, Remadevi S, Rajamohanan K 49
Perspectives
1. Experiential Learning: Unnikrishnan VV 53
2. Changing Trends in Nursing Research: Nirmala L, Athirarani MR 57
3. Allied Health Sciences – Revisited: Sankar S 59
Research Methodology
Diagnostic Test Evaluation- An introduction: Harikumaran Nair GS 62
Health Education
Prevention of Lifestyle Diseases among Young Adults
i. Introduction: MKC Nair 66
ii. Dyslipidaemia - A Quick Guide: Sajan Ahmad Z 67
iii. Dyslipidaemia in the Young - Diet Therapy: Zulfikar Ahamed M 68
iv. Hypertension in Adolescents and Children: Krishnakumar R 70
v. Diabetes Mellitus: Ranjit Sanu Watson 71
vi. Obesity and Poly-cystic Ovarian Disease - A Growing Concern
among the Youth: Reshmi CR 72
Instructions to Authors 74
Authorship Statement 77
Copyright Form 79
Health Sciences April - June 2016 5

Vice Chancellor’s Page
Happy to write few lines for the second issue of Health Sciences as a
print journal and let me put on record my sincere thanks to the editorial
team. The Kerala University of Health Sciences (KUHS) believe in three
principles; (i) go by rulebook, (ii) no compromise on quality of examina-
tion, and (iii) respecting students’ right to be heard.
KUHS is in the process of establishing four Schools, namely,
i School of Health Policy and Planning Studies at Thiruvananthapuram,
where, we have started a ‘Research Guidance Clinic’ on Saturdays
and here post graduate students and PhD scholars are encouraged to
seek methodological assistance at every stage of their study. Formal
methodology training programs for Post Graduate students are also
being held at regular intervals,
ii School of Ayurveda (AYUSH) at Thripunithura, where, we have
initiated four multi-centric studies on different aspects of Ayurveda,
iii Academic Staff College at Thrissur, where faculty capacity building
programs are going on, in research methodology, biostatistics and
health science education technology,
iv School of Family Health Studies at Kozhikode, with the intention of
promoting family health related research studies.
This issue of Health Sciences, ably edited by Prof (Dr) Harikumaran Nair,
Faculty, Clinical Epidemiology Resource and Training Centre (CERTC)
at Medical College, Thiruvananthapuram and Professor and Head,
Department of Radiology, Government TD Medical College, Alappuzha,
reflect some of the epidemiological work done at CERTC and contributions
from faculty of affiliated colleges. From next issue onwards we are
planning to have a separate section for articles based on postgraduate
thesis work, from all health science streams. I sincerely hope that
postgraduates and faculty would come forward to submit their original
work to Health Sciences, an official peer reviewed publication of KUHS.
Prof (Dr) M K C Nair

Editorial
We have an array of research methodology designs at our disposal,
from high-end meta- analysis of randomized controlled trials to case
reports at the lower end. Diagnostic test evaluation is a commonly
used method in both clinical and laboratory services. Whereas it is
easier to get an appropriate gold standard in laboratory studies,
getting the appropriate gold standard is a challenge in clinical studies
and yet we may have to make compromises at times.
In this issue, we are trying to highlight some of the aspects on
Diagnostic test evaluation methods, based on the article titled
“Diagnostic test evaluation of IgM ELISA and Lepto Tek Dri-Dot
in the Serodiagnosis of Leptospirosis” by Kavita Raja et al, which
is evaluating two new tests, a latex agglutination test (Lepto Tek
Dri-Dot) and IgM ELISA and assessing the usefulness of these tests
in clinical settings, when used separately and in combination. Here
the authors have taken a fairly adequate sample and reference
standard (micro-agglutination test, MAT, combined with CDC
clinical criteria for leptospirosis). The authors have adequately
succeeded in avoiding many of the biases like selection bias,
reference test bias and spectrum bias. They have rightly highlighted
on how one of these tests, IgM ELISA, when repeated after one
week enable us to improve the sensitivity without compromising
much on specificity. They also highlights on an issue of a limitation
in calculations, due to dropouts, in the estimation in repeat sample
after a week, which is a usual limitation in many studies, where a
repeated estimations are required.
The article on ‘Prevalence of obesity among high school girls
in Thiruvananthapuram City-A cross sectional study’ by Geetha S
et al and ‘Association of overweight and insulin resistance with
polycystic ovary syndrome’ by Sreekumari R et al discuss the current
twin problem of obesity and PCOS and highlight the strength of
association between the two. The perspectives presented here on
‘experiential learning’, ‘changing trends in nursing research’ and ‘
Allied sciences’ make reading, interesting. The health education
section on ‘prevention of lifestyle diseases among young adults’
focusing on obesity and PCOS, dyslipidaemia, diabetes mellitus and
hypertension is part of KUHS strategy to empower our students and
faculty to internalise the simple messages for themselves and for
the community.
Harikumaran Nair G S
Professor of Radiology, Govt. TD Medical College, Alappuzha.
Faculty CERTC, Govt. Medical College, Thiruvananthapuram,
E-mail: harikumarannair@msn.com

Original Article
PREVALENCE OF OBESITY AMONG

HIGH SCHOOL GIRLS IN
THIRUVANANTHAPURAM CITY -
A CROSS SECTIONAL STUDY
Geetha S1, Nair MKC2
Abstract hyperinsulinemia, hypertension, and early

The prevalence of obesity is increasing atherosclerosis1. These risk factors may operate
rapidly worldwide among children. WHO has through the association between child and adult
declared it as a global epidemic and no country is obesity, but they may also act independently.
free from this problem. American Heart Association has upgraded obesity
Objectives: To estimate the prevalence of obesity to a status of major risk factor for coronary artery
among high school girls in Thiruvananthapuram disease. No country is free from this problem.
city as measured by BMI using IOTF, NCHS and Moreover, as the problem is increasing in children
Agarwal (Indian) recommended cut off values. as well as in adults, the true health consequences
will only become apparent in future. Truly, WHO
Methods: A cross sectional survey conducted
in 1998 has called obesity a “global epidemic”.
through multi-stage random sampling in high
schools in Thiruvananthapuram city. There has been increase in childhood obesity
worldwide2. In United States, a doubling of the
Results: By using 95 th centile of NCHS, the
prevalence of children with a body mass index
prevalence of obesity was 2.4% (95% CI; 1.9 - 3),
(BMI) of greater than 95th percentile occurred
using IOTF cut off 1.4% (95% CI; 1.0 -1.8),
between 1963 and 1991. This trend was reported
Agarwal cut-off 2.04% (95% CI 1.6 -2.6). There is
from many countries3. It was seen that obesity was
a significant difference in prevalence of obesity
increasing rapidly in Latin America, South East
between government and private school girls using
Asia, Pacific, South Africa and Middle East.
NCHS cut-off (WHO), Government school: 1.1%
Overweight children are twice as likely as normal
(95%. CI 0.7-1.7) and private school: 4.2% (95%
children to be obese adults. Therefore, with almost
CI 3.2-5.4).
40% of India’s population, being constituted by
Conclusion: The prevalence rates of obesity adolescents, the burden of this problem is very
depending on the different BMI cut offs shows that high4. Few available Indian studies also point to
the IOTF cut off provides a lower prevalence with growing menace of obesity. Limited information
NCHS and Agarwal cut off providing slightly is available from India on this nutritional disorder.
higher prevalence rates. However, the prevalence Umesh Kapil et.al using the international cut off
in affluent girls was high. (95 th centile of BMI distribution) reported a
Keywords: obesity, adolescent girls, prevalence. prevalence of obesity among school children from
Introduction affluent families as 7.4%5. In a study of school
The prevalence of obesity is increasing going girls in Chennai in 1991, V Subramanyam et
rapidly worldwide. It is associated with several risk al reported a prevalence of 6% in affluent schools6.
factors for later heart disease and other chronic There has been no published data on the prevalence
diseases including hyperlipidaemia, of overweight and obesity in Kerala. Kerala with
1 Additional Professor of Paediatrics, SAT Hospital. Medical College, Thiruvananthapuram

2 Founder Director, Child Development Centre, Medical College, Thiruvananthapuram.
Corresponding author: Geetha S: E-mail: geethapmohan@yahoo.com

its unique health indices and control of Methods
communicable diseases, now faces the threat of This study was a cross sectional survey
non-communicable diseases like diabetes and conducted in the setting of high schools in
coronary artery disease in epidemic proportions in Thiruvananthapuram city in Kerala. Girls in the age
adults, both conditions being associated with group 13-15 belonging to schools of
obesity. There is a real need to find out the Thiruvananthapuram city was taken as the source
prevalence of obesity in this context. Knowledge population and study population was obtained by
of the level and distribution of obesity is useful multistage random sampling. Thus in the first stage
for: (i) identifying populations at risk for obesity schools and in the second stage classes were
and its associated health and economic randomly selected. The sample size for the survey
consequences, (ii) help policy makers and public was calculated using prevalence estimate of 7%
health planners in the mobilization and reallocation obtained from previous study conducted in urban
of resources and (iii) provide baseline data for setting by Umesh Kapil, Delhi5. With prevalence
monitoring the effectiveness of possible national of 7%, alpha error fixed at 0.05 and precision of
programs for control of obesity. 1%, sample size required for a simple random
There seem to be three crucial periods that survey was found to be 2500. The sample size was
determine if there is a high likelihood of persistence increased by 20% to 3000, taking into consideration
of obesity into adulthood; (i) the gestational period, the fact that all students from a randomly selected
(ii) the adiposity rebound period (there is normally class were included for measurements (cluster
a decrease and then, at approximately 5 to 7 years effect). The number of schools to be randomly
of age), an increase in the BMI during childhood, selected was found to be 8, which was obtained by
with an earlier rebound predicting persistent and dividing sample size of 3000 with average number
adulthood obesity and (iii) adolescence. The older of students in a school. Assuming class strength of
a child and he or she remains or becomes 40 students, 75 classes from these eight schools
overweight, the greater the likelihood that were randomly selected for conducting the survey.
overweight will be present in adulthood also. A proforma was used to record the personal
In addition, there is a growing awareness of information and the measurements obtained from
the importance of the period of adolescence as the each student. The technique of measurements was
time during which healthy life style interventions standardized, study equipments were calibrated and
could be instilled into the next generation. single trained observer took accurate
Adolescent obesity is assuming more importance measurements. Height was measured using
in the context of market economy and resultant Stadiometer corrected to 0.1cm. Standing height
social environment, which favours sedentary life was measured with the student standing with arms
style and unhealthy eating practices. The at side, buttocks and heel touching the rod with
transformation of these ideas into ideal practices head held erect and plane passing through the lower
requires program strategies based on an border of orbit and Frankfurt plane parallel. Weight
understanding of the magnitude of the problem, was measured using weighing machine corrected
consequences and feasibility of simple to 0.5 kg, machine was checked for zero error prior
interventions in the target population. This is more to measurement. The data collected was entered in
so with girls as they hold the key to future excel worksheets and analysed using SPSS 11. The
generations. Thus, girls in age group 13-15 years body mass index (BMI) was calculated using the
have been selected as the target group for this study. height and weight recorded. The distribution of
This aspect is also relevant as interventions can be BMI was then analysed and results were presented.
planned through the Reproductive, Maternal, New- Results
born, Child and Adolescent Health program, which
Out of the total study sample of 3339
now has special emphasis on adolescent health. The
students, 58.2% came from government schools and
present study was done to measure the prevalence
41.8% came from private schools, with almost
of obesity, as measured by body mass index (BMI)
equal number of girls in each of the age groups,
in high school girls in the age group 13-15 and
making it a representative sample (Table 1).
compare using three cut-offs; 95th centile of NCHS
(WHO), IOTF cut-off, and Agarwal cut-off7.

Table 1: Distribution of sample according to age groups and school category
School category
Age Government schools Private schools
Total
group
No. % of sample No. % of sample
13 years 1104 599 17.9 505 15.1
14 years 1192 688 20.6 504 15.1
15 years 1043 656 19.7 387 11.6
Total 3339 1943 58.2 1396 41.8
The BMI distribution of the study sample is groups, the 85th percentile were 21.6, 22.4 and 22.8
shown in Table 2. The mean values for ages 13, 14 respectively. Similarly, the 95th percentiles were
and 15 were 18.32 (SD3.2), 19.13 (SD3.3), and 24.2, 25.1 and 25.9 respectively.
19.61(SD3.3) respectively. For the above age
Table 2: BMI distribution of the study sample
Summary statistics 13 years 14 years 15 years

Mean 18.32 19.13 19.61
Median 17.79 18.59 19.14
Mode 17.54 18.49 18.73
S.D 3.20 3.26 3.34
85th Percentile 21.60 22.37 22.78
95th Percentile 24.23 25.10 25.99
Comparison of prevalence rates using different than 95th centile of NCHS (7.5%,2.4%), using IOTF
cut-off values (Table 3) showed that the prevalence value (8.7%, 1.4%) and using Agarwal cut off
rates of overweight and obesity respectively were; (9.2%, 2%).
using distribution of sample (10%, 5%), using more
Table 3: Comparison of Prevalence rates using different cut-off values
Prevalence Confidence
Reference Classification Number Denominator
rate Intervals
Distribution Overweight 335 3339 10% 9.03-11.10
of sample Obesity 167 3339 5% 4.28-5.79
More than 95th Overweight 250 3339 7.5 6.6-8.4
centile(NCHS) Obesity 80 3339 2.4% 1.9-3
Overweight 291 3339 8.7% 7.78-9.72
IOTF values
Obesity 46 3339 1.4% 1.01-1.83
Overweight 308 3339 9.2% 7.8-10.2
Agarwal
Obesity 68 3339 2% 1.58-2.57

Comparison of BMI between school categories for the age group 13 years (17.6, 19.2), for 14 years
(Table 4) showed that for the government and (18.5,20.1) and for 15 years (19.3, 20.2).
private school respectively, the mean BMI were;
Table 4: Comparison of BMI between school categories

Government schools Private schools
Age group Significance
N Mean S.D N Mean S.D
13 599 17.6 2.8 505 19.2 3.5 <0.001
14 688 18.5 2.9 504 20.1 3.5 <0.001
15 656 19.3 3.2 387 20.2 3.5 <0.001
Comparison of Prevalence rates in government the four cut-offs the private school had consistently
and private schools (Table 5) showed that using all higher prevalence of overweight and obesity.
Table 5: Comparison of Prevalence rates in government and private schools
Prevalence with confidence interval

Reference Classification
Govt. school Private schools
Overweight 7.6(6.4-8.9) 13.5 (11.7-15.4)
Using Distribution
Obesity 3(2.3-3.9) 7.8(6.5-9.4)
Overweight 5.7(4.7-6.8) 13 (11.3-14.9)
IOTF values
Obesity 0.7(0.4-1.2) 2.4(1.7-3.3)
Overweight 6.1(5.1-7.3) 13.4 (10.7-14.3)
Agarwal et al
Obesity 0.9(0.5-1.4) 3.7(2.8-4.8)
Over weight 5.1(4.2-6.2) 10.7(9.2-12.50)
NCHS Obesity 1.1(0.7-1.7) 4.2 (3.2-5.4)
Discussion girls in the Reproductive, Maternal, New-born,

The purpose of this study was to estimate Child and Adolescent Health program approach
the prevalence of obesity among school going girls setting, these findings assume greater importance,
in the age group 13- 15 years in an urban setting. as it offers real opportunity for intervention.
The study was conducted in Thiruvananthapuram Education of girls up to standard 10 is almost
city, typical of an urban setting in Kerala and universal in Kerala; exceptions to this can be
covering an area of 141.74 Sq. km with a population expected only in remote rural areas. Therefore,
of 7,44747. Although under-nutrition among selecting a sample for the study from the school-
adolescents is still a national priority, it is suggested going girls would be representative of the
that in the near future morbidity due to childhood community setting. Due to constraints of time and
onset adult diseases is likely to increase and in this man-power, it was thought more appropriate to use
context, knowing the prevalence of obesity assumes a multi-stage random sampling to estimate the
significance. Also with increasing attention given prevalence of obesity. In the general population,
to adolescent issues especially that of adolescent the proportion of girl students in the government

schools (including government-aided private which would help in comparison of obesity
schools) and private schools are 60.6% and 39.4% prevalence estimates across different strata of the
respectively. Out of the total study sample of 3339 population within the country.
students, 58.2% came from government schools and The prevalence of obesity obtained in this study,
41.8% came from private schools, with almost using 95th centile NCHS cut-off is reflective of the
equal number of girls in each of the age groups, situation in the urban setting. However, there was
making it a representative sample (Table 1). difference in the prevalence in government and
The prevalence of obesity among school going private schools. The study sample represented a
girls of the age group 13 to 15 was determined using proportionate population from government schools
the standard reliable and easy measurement of body and private schools (Table 1). It is a fact that
mass index. Unlike adult obesity, there is no generally students admitted to private schools
uniformity in defining obesity in children and belong to higher socioeconomic status. The mean
adolescents. Hence, in this study different BMI cut- values of BMI were found to be significantly
off criterion for defining obesity was used. Taking different between the two groups of schools (Table
the 95th percentile of the age appropriate distribution 4). Therefore, it would be of interest to compare
of BMI (Table 2) as the cut-off for obesity and 85th the prevalence of obesity in government schools
percentile as the cut-off for overweight the and private schools. The prevalence rates were
prevalence rates were compared between significantly higher (i.e. 4.2% compared to 1.4%)
government and private school settings. The 95% in girls belonging to the private schools compared
CI using these cut-off values, for obesity prevalence to government schools. The prevalence of 4.2%
and overweight prevalence in the study sample were among girls from private schools was less than that
4.28-5.7 and 9.03-11.10 respectively. of results obtained from studies done in similar
Using 3 different BMI cut-off criteria the setting (Delhi) However, these findings are
prevalence of obesity was estimated (Table 3). By indicative of the fact that there is a trend for increase
using 95th centile of NCHS, the prevalence was in prevalence of obesity with affluence and
2.4% (95% CI; 1.9 - 3.0). This method for changing lifestyles, which is more marked in urban
identifying obesity based on 95 th percentile is situations.
commonly used and the study conducted by U The observation that 7.6% girls were
Kapil et al utilized the same to get a prevalence of underweight in this study as against 2.4% with
7.4% among affluent school girls of Delhi. Similar obesity and 7.5% with overweight suggests that any
methods were also used for obesity prevalence adolescent nutrition program in Kerala should
estimation in USA, showing a prevalence of 10.9%. equally focus on under nutrition and over nutrition
The IOTF in its recommendations have provided (Dual burden). This also suggests the importance
cut-off points for international comparison using of growth monitoring during adolescence using
representative data from six countries, in which Adolescent Health Card developed by Child
India was not included. However using this method Development Centre, Kerala and adopted by Indian
the prevalence of obesity was 1.4% (95% CI; 1.01- Academy of Paediatrics. In the setting of universal
1.83). Agarwal has defined cut-off in affluent Indian high school education and the high level of
urban girls using representative sample from 12 enrolment of girls in our state, it was thought
Indian cities. By using this cut-off, the prevalence appropriate to do a school survey to study the
of obesity was 2.04% (95% CI 1.58-2.57). It is prevalence of obesity in the age group of 13-15
evident that these prevalence rates obtained by years. The trend of higher rates for overweight and
different cut off provided us with similar estimates. obesity more so in affluent groups necessitates
But it is relevant to consider that this similarity in interventions at school level focusing on formation
rates while using different cut-offs may change in of Adolescent Clinics, use of Adolescent Health
a population with higher prevalence rates as Card, Nutrition Education and Physical Fitness
evidenced by the obesity prevalence rates estimated programmes, utilizing the provisions in the
among private school students; the subgroup in Reproductive, Maternal, New-born, Child and
which the prevalence was high (Table 5). Thus, it Adolescent Health (RMNCH+A) program of
is necessary to have a reference cut off standardized, Government of India.

Conclusions adolescence. In: World health organization, ed.
The prevalence rates of obesity based on the Obesity preventing and managing the global
epidemic. Geneva: WHO, 1998; 231-247.
different BMI cut offs showed that the IOTF cut
off provided a lower prevalence (1.4%), whereas 3. W. Philip T James. Obesity in Childhood. Annales
Agarwal (2.0%) and NCHS (2.4%) cut-off provided Nestle Global trends of obesity, 2001; 59: 2
slightly higher prevalence rates. There was a 4. Freedman DS, Khan LK, Dietz WH, Srinivasan SR,
significant difference in prevalence of obesity Berenson GS. Relationship of childhood obesity to
between government (1.1%) and private (4.2%) coronary heart disease, risk factors in adulthood:
schoolgirls using NCHS cut-off (WHO). The The Bogalusa Heart Study. Pediatrics, 2001;
108:712-718.
prevalence of obesity (4.2%) observed among
affluent private high school girls in this study was 5. Kapil U, Singh P, Pathak P, Dwivedi SN, Bhasin S.
less than that observed for Chennai (6.0%) and New Prevalence of obesity amongst affluent adolescent
school children in Delhi. Indian Pediatr. 2002;
Delhi (7.4%) affluent girls.
39(5):449-52.
6. Subramanyam V, Rafi, Jayasree. Prevalence of
References Overweight and obesity among Affluent adolescent
1. The WHO MONICA Project: Risk factors of girls in Chennai in 1981 and 1998. Indian Pediatr.
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(Suppl 1): S46-S55 7. Agarwal KN, Saxena A, Bansal AK, Agarwal DK.
2. WHO consultation on obesity. Special issues in the Physical growth assessment in adolescent. Indian
management of obesity in childhood and Pediatr. 2001; 38: 1217-1235.

Original Article
ASSOCIATION OF OVERWEIGHT AND

INSULIN RESISTANCE WITH
POLYCYSTIC OVARY SYNDROME (PCOS)
Sreekumari R1, Nair M K C2, Nirmala C3
Abstract abdominal circumference more than 88 cms was

Polycystic ovary syndrome (PCOS) is the associated with PCOS; OR=7.45 (CI: 2.77-20.08).
most common endocrine disorder affecting 6-10% Insulin resistance, calculated by HOMA IR > 2, was
of women in reproductive age group. also associated with PCOS; OR=15.98 (CI: 6.48-
39.41). Insulin resistance was also seen in 30% of
Objective: To determine the strength of association
normal weight and lean PCOS. Multivariate
of overweight, including obesity, and insulin
analysis showed that BMI, OR=3.52 (CI: 1.72-7.2)
resistance, with polycystic ovary syndrome (PCOS)
and HOMA IR, OR=10.75 (CI: 4.23-27.29) were
in the age group 18-24 years.
also significantly associated with PCOS.
Methods: This case control study was done in a
Conclusion: This study showed that in the age
government medical college in Kerala. Women in
group of 18-24 years, overweight, upper body
the age group of 18-24 years with menstrual
obesity and insulin resistance are strongly
dysfunction, either in the form of oligovulation or
associated with PCOS. The main policy implication
anovulation clinical and /or biochemical signs of
of this study is that, there is an urgent need for
hyperandrogenism, and polycystic ovaries on
promoting weight reduction in the adolescent age
ultrasonography formed the cases. Controls were
group by regular physical training programs in the
women in the age group of 18-24 years with regular
school settings.
menstrual cycles and normal ovaries on
ultrasonography. Evaluated 113 cases and 113 Key words: Polycystic ovary syndrome (PCOS),
controls. Using a pretested schedule, socio Body mass index (BMI), abdominal circumference,
demographic variables and anthropometric Homeostatic model assessment of insulin resistance
measurements were collected. Fasting blood (HOMA-IR).
glucose and insulin levels were estimated to Introduction
calculate insulin resistance. Polycystic ovary syndrome (PCOS) is the most
Results: Overweight, defined as more than 25 of common endocrine disorder affecting 6-10% of
Body Mass Index (BMI), was significantly women in reproductive age group1. Research over
associated with PCOS; OR=5.96 (CI: 2.99-11.98). the past two decades has vastly improved our
There was a linear increase in the risk as BMI knowledge and understanding of PCOS, but there
increased. Upper body obesity, as measured by is a lack of Indian studies on PCOS among young
1 Additional Professor of Obstetrics and Gynaecology, GMC Thiruvananthapuram

2 Formerly Director CDC and Professor of paediatrics, GMC Thiruvananthapuram
3 Professor and HOD of Obstetrics and Gynaecology, GMC Thiruvananthapuram
Corresponding Author: Sreekumari R: E-mail: anilsree83@gmail.com

adults (15-24 years). In addition to reproductive changes would settle down. PCOS was diagnosed
health problems, it also exhibits major metabolic by having any two of the following three criteria;
and cardiovascular risks2. On the contrary, although oligovulation/ anovulation, clinical and /or
predominantly a genetic condition, the syndrome biochemical signs of hyper-androgenisation and
may be modified by environmental, dietary and polycystic ovaries on ultrasonography (Rotterdam
other factors3. Insulin resistance and compensatory Consensus Criteria)12,13. Related disorders like
hyperinsulinemia have direct and indirect roles in hypothyroidism, hyperprolactinemia, adult onset
the pathogenesis of PCOS4. Obesity, especially congenital adrenal hyperplasia and androgen
central obesity, is also related to PCOS 5. In secreting tumours were excluded. The study was
adolescents and young adults, PCOS is a leading done after obtaining ethical clearance from
risk factor for type II diabetes6, which further Institutional Ethical Committee.
enhances obesity7. Study on North Indian women Women in the age group of 18-24 years, with
reported that, in newly diagnosed women with type regular menstrual cycles, no clinical /or
II diabetes 30% are having polycystic ovaries on biochemical signs of hyperandrogenism and normal
Ultrasonography (USG)8. It is reported that women ovaries on USG were taken as controls. Regular
with PCOS have 11 fold increase in metabolic menstrual cycle was taken as a surrogate measure
syndrome 7,9. Thus, it seems that PCOS and of ovulatory cycles. Women on oral contraceptive
overweight/insulin resistance are associated, pills and metformin were excluded. Abdominal
although the direction of association is less clear. ultrasound was done by a trained sonologist, both
The two key factors which are modifiable in in cases and controls. Although, abdominal
this syndrome are obesity and insulin resistance. ultrasound is less superior to vaginal ultrasound
Moderate weight loss (5-10%) can cause examination, abdominal ultrasound was resorted
improvement in clinical, metabolic and endocrine to, since the study population included unmarried
effects10. This is likely to yield better results in girls. Both cases and controls were chosen from
adolescents and young adults before they develop nulliparous women to eliminate the effect of
the full-blown syndrome. The potential public pregnancy and childbirth on weight.
health impact of this intervention is high, given that Pre tested interview schedule was used to
the prevalence of oligomenorrhoea, important in collect the data which included information on
terms of early detection of polycystic ovary anthropometric measurements, fasting blood
syndrome is 11.3% in our population11. It is in this glucose and insulin in addition to the socio
context that the present study was done to find out demographic variables. Height was measured with
the strength of association of obesity and insulin the Stadiometer corrected to 0.1 cm. For measuring
resistance with PCOS in the age group 18-24 years. weight, weighing machine corrected to 0.5 kg was
Methods used. Machine was checked for zero error prior to
A case control study was done in a Government each measurement. Waist circumference was
medical college. For a prevalence of 20% measured at a point midway between costal margin
overweight, including obesity in our population, and anterior superior iliac spine, using a non-
80% power, α-error of 0.05 and an expected odds stretchable tape (rigid tape). Cut off of BMI>25
ratio of 3, sample size was calculated to be 113 was taken to categorise overweight14.
cases and controls each. Cases were selected from Study subjects were asked to report in a fasting
women in the age group of 18-24 years who were state on a day convenient for them within 5 days
reporting with menstrual problems. This age group after menstruation (follicular phase of menstrual
was selected to study the association in the early cycle). Fasting blood glucose and insulin were
part of the disease, as preventive strategies will be checked for all subjects. HOMA-IR (Homeostatic
more effective before they develop the full-blown model assessment of insulin resistance) was
picture of the syndrome. In the early adolescent calculated using the same computer program used
period, anovulatory cycles are very common and at diabetic trial unit, Oxford University. HOMA15,
ovary may appear cystic due to the excessive is the oldest, most widely used and published test,
responsiveness to gonadotrophins. To overcome and has the advantage of providing an assessment
this, lower limit was taken as 18 years when these of cell function. Calculation is based on a

physiologically based structural model. The output research laboratory, which is under external quality
of the model is calibrated to give normal cell control of Christian Medical College, Vellore, a
function of 100% and normal IR of 1. Validation WHO recognized centre for quality control. Blood
of HOMA has been done with euglycemic clamp sample was taken in laboratory, after overnight
technique with a correlation coefficient more than fasting and did not require any transportation. Ultra-
0.815. Estimation of a cell function using HOMA sensitive immuno assay method was used
has been shown to correlate well with continuous (Beckman and Coulter) with same batch of assay
infusion glucose model assessment (r=0.88). Ethnic kit. Data was entered on Microsoft-excel, and after
variations are very important in interpreting insulin data cleaning analysed using SPSS-11 version. For
resistance. In this study the 75 th centile, as continuous variables means were calculated and
recommended by European Study group for insulin compared by ‘t’ test. Categorical variables were
resistance, has been used16. compared and tested by chi-square test. Univariate
Apart from clinical examination, TSH, and multivariate analysis (Logistic regression) were
prolactin, 17 OH progesterone and serum also used.
testosterone were done to rule out other causes of Results
menstrual dysfunction like hypothyroidism, Data on 113 cases and 113 controls were analysed
hyperprolactinemia, adult onset congenital adrenal in this study. Mean age was 21.22 years for cases
hyperplasia and androgen secreting tumours. Blood and 21.25 for controls (p= 0.92).
investigations were done in an advanced clinical
Table 1: Socio-Demographic variables and family history
Cases Controls Test P value

Variable
N (%) N (%) Chi-square
Religion Hindu 83 (73.5) 91 (80.5) 2.53 0.28

Muslim 15 (13.3) 14 (12.4)
Christian 15 (13.3) 8 (7.1)
Education High School 48 (42.5) 60 (53.1) 2.55 0.11

College 65 (57.5) 53 (46.9)
Occupation Unemployed 101 (89.4) 105 (92.9) 0.89 0.35

Employed 12 (10.6) 8 (7.1)
Income Rs <3000. 77 (68.1) 85 (75.2) 2.07 0.56 Rs

3000-6000 19 (16.8) 17 (15)
Rs>6000 17 (15) 11 (10.2)
Odds Ratio
Family history Yes 9 (8) 3 (2.7) 3.17 0.07

of Irregular No 104 (92) 110 (97.3)
periods
Family history Yes 21 (18.6) 12 (10.6) 1.92 0.09

of Diabetes No 92 (81.4) 101 (89.4)
Table1 shows that cases and controls were Irregular periods in mother/sister was higher in
comparable. Family history of diabetes and cases but statistically not significant.

Table 2: Study Variables
Variable Cases Controls p value
BMI (kg/m2 )- Mean 24.81 21.26 0.000
Std. Dev (4.11) (3.68)
Waist circumference(cm)- Mean 80.46 71.43 0.000
Std dev (9.94) (8.95)
Fasting glucose (mg/dl)- Mean 83.13 82.01 0.330
Std dev (7.98) (9.23)
Fasting Insulin(μU/ml)- median 15.27 7.23 0.000
HOMA – IR - Mean 1.88 1.07 0.000
Std dev (0.84) (0.56)
Table 2 shows that all the study variables are significantly higher in cases except fasting glucose levels.
Table 3: Case-control comparison

Cases Controls Test P-
N (%) N (%) Value
BMI <23 40 (35.4) 82 (72.6) (Chi. Sq.) 38.5 0.000
(South Asian Guidelines) 23 – 27.5 45 (39.8) 28 (24.8)
>27.5 28 (24.8) 3 (2.7)
Odds Ratio
(95% CI)
BMI (WHO) <18.5 7 (6.2) 25 (22.1) 0.4 (0.15 - 1.08)
18.5 - 24.9 50 (44.2) 72 (63.7) 1.0
25 - 29.9 41 (35.4) 13 (11.5) 4.54 (2.04 - 9.76)
>30.0 15 (13.3) 3 (2.7) 7.2 (1.82 - 33.18)
Waist Circumference <88 cm 84 (74.3) 108(95.6) 7.46 (2.76-20.08)
>88cm 29 (25.7) 5 (4.4) 0.000
Waist Circumference <80 cm 47 (41.6) 95 (84.1) 7.41 (3.96-13.88)
(South Asian Guidelines) >80cm 66 (58.4) 18 (15.9) 0.000
HOMA IR <2 67 (59.2) 108(95.5) 15.98 (6.48-39.41)
>2 46 (40.7) 5 (4.4) 0.000
HOMA IR comparison among lean and obese PCOS
HOMA IR (BMI < 25) <2 39(69.7%) 90(95.7%) - -
>2 17(30.3%) 4 (4.3%) - -
HOMA IR (BMI >25) <2 27(48.2%) 14(93.3%) - -
>2 29(51.8%) 1 (6.7%) - -
Table 3 shows the case- control comparison. 7.46 (2.77 - 20.08). Insulin resistance by HOMA-
When the South Asian guidelines for BMI were IR was seen in 40.7% of the cases. A stratified
considered, 64.6 % of cases were overweight and analysis with BMI showed that 30.3 % of lean
obese. Odds ratio for the different category of BMI PCOS were insulin resistant and 51.8% of the
showed a linear trend, chi square for trend being PCOS in the overweight obese group were insulin
21.82 (p=0.000). Upper body obesity was seen in resistant.
25.7% of cases and 4.4% of controls; odds ratio =

Table 4: Logistic regression adjusted odds ratio
Name of Variable Odds ratio 95% CI P value
BMI 3.52 1.72 - 7.2 0.03
HOMA IR 10.75 4.23 - 27.29 0.000
Waist circumferences 2.2 0.55 - 8.88 0.26
Family history of diabetes 1.35 0.521 - 3.49 0.53
Family h/o irregular periods 1.64 0.33 - 8.02 0.54
Acanthosis nigricans 1.72 0.42 - 7.00 0.45
Logistic regression was done to determine the milder forms of disease might have been picked up.
adjusted Odds ratio for the study variables. Along The current study also showed that abdominal
with the major study variables, other clinically or obesity as measured by upper waist circumference
statistically significant variables were included. >88cm is seen in 25.7% of cases compared to 4.4%
Statistical significance level was set as <0.1 for in controls (p=0.000). Odds of PCOS were 7.5
inclusion in the analysis. Age, though not times more in patients with abdominal obesity.
statistically significant, was included because of Insulin resistance as measured with HOMA IR >2,
the possibility of confounding with other variables. the odds ratio of PCOS was 15.98 (6.48-39.41).
Adjusted OR for BMI >25 was 3.52 (1.72- 7.2) Catherine Marin et al19 in a case control study of
p=0.001 and for HOMA-IR >2 was10.75 (4.23 – 271 PCOS women and 260 eumenorrhoeic women
27.29) p =0.000. as control reported prevalence of insulin resistance
Discussion as 64%.
The objective of this study was to determine the Generally, obesity is an important factor in
strength of association of overweight and insulin determining insulin resistance. In PCOS, obesity
resistance with PCOS in the age group of 18-24 increases the propensity for insulin resistance. In
years. This study results showed that 48.7% of cases this study insulin resistance was shown among 30%
were overweight and obese compared to 14.2% in of cases who were normal weight or lean (BMI
controls. If we take the South Asian guidelines cut <25). Lean patients with PCOS also have insulin
off for BMI, this increased to 64.6% in cases. The resistance and insulin resistance is independent of
odds of disease in the different strata of BMI BMI. Dunaif et al had reported similar findings20.
showed a linear increasing trend (chi-square for This indicates that metabolic risk due to insulin
trend 21.82p = 0.000). resistance can occur in normal weight patients also.
No study with the same age group was available Hence life style modification, specifically weight
for comparison. However, various studies in the reduction programs should be an integral part of
reproductive age group reported frequency of management of obese PCOS.
overweight and obesity between 40 and 60%. In Limitation of this study was that it was
an Indian study Shringi M, Vaidya RA et al has conducted in a tertiary care centre and hence mild
reported obesity in 37.8%17. A cohort study from form of disease may not have come into the study.
Northern Finland (n=2007) showed increased risk A community-based study can only deal with this
of PCOS in women, who were having normal problem. The study population was evaluated by
weight at adolescence and were overweight or fasting glucose levels only and hence the chance
obese at 31 years18. The relative risk reported was of missing impaired glucose tolerance and diabetes.
1.44 (1.10 – 1.89) and this risk increased to 1.71 A glucose challenge test would have been useful
(1.32-2.24) if they were overweight and obese at to overcome this. Ideally, apart from clinical
14 years and 31 years. In the above study, cases screening, blood investigations done for the cases
were identified by self-reported symptoms of PCOS have to be done for the controls also. In the present
and biochemical investigations and ultrasound study, the controls were having regular periods and
examination was not done. PCOS who had been hence for logistic reasons, investigations to rule out
on oral contraceptive pills were excluded, so only related disorders were not done.

Conclusion 9 Cook S, Weitzman M. Prevalence of metabolic
syndrome phenotype in adolescent findings of
The study revealed that overweight was strongly NHNES survey 1988-1994.Arch. Paed. Adol
associated with polycystic ovary syndrome with a Medicine 2003; 157: 821-827
linear increase in the measure of association as BMI
10 Hamilton-Fairley D, Kiddy D, Response of SHBG
increased. The study found that insulin resistance and IGF-1 to an oral glucose tolerance test in obese
was also strongly associated with polycystic ovary PCOS before and after calorie restriction. Clinical
syndrome. However, insulin resistance was seen Endo.1993; 39 (3): 363-367
in normal weight and lean PCOS also. These 11 Nair MKC, Chacko DS, Manju RD, Padma K, Babu
associations suggest that weight reduction strategies George, Russell PS. Menstrual disorders and
must be included in the management of obese menstrual hygiene practices in Higher Secondary
PCOS. School girls. Indian J Pediatr. 2012; 79(suppl 1):
S74-S78.
References 12 The Rotterdam consensus workshop group –
Revised 2003 consensus on diagnostic criteria and
1 Knochenhauer E, Key TJ, Aziz R et al. Prevalence
long term risk related to PCOS. Fertility sterility.
of polycystic ovary Syndrome in unselected black
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& white women of South eastern U.S. – Prospective
study. J Clin Endo Metabolism. 1998; 83: 3078-82 13 Balen AH, Laven JS. Ultrasound assessment of
polycystic ovaries – International consensus
2 Dokras A, Jagesia DH, Michelle M et al. Obesity
definition. Human reproduction update. 2003; 9:
insulin resistance, but not hyperandrogenism is an
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important indicator of vascular dysfunction in
PCOS. Fertility sterility. 2006; 86 (6) 1702-1709 14 WHO. Obesity: Preventing and Managing the
Global Epidemic. WHO Technical Report Series
3 Frank S, Mc Carthy MI. Development of polycystic
894. Geneva: 2000
ovary syndrome. Involvement of genetic and
environmental factors, Int J Andrology. 2006; 29 15 HOMA – The best bet for the simple determination
(1) 278-285 of insulin sensitivity until something better comes
along. Editorial Diabetes care. Sept. 2007; 30 (9)
4 Legro RS, Blanche, Krauss RM, Lobo RA.
2411-2413
Alteration in low density lipoprotein and HDL
among Hispanic women with PCOS – influence of 16 Balkau B, Charles MA. Comment on the
insulin and genetic factors. Fertility sterility. 1999; provisional report from WHO Consultation.
72 (6) 990-995 European Group for the study of Insulin Resistance
(EGIR). Diabet Med. 1999; 16: 442-3.
5 Gambineri A, Pelusi C, Vincennati V et al. Obesity
and PCOS (review) Int J of Obesity and Metabolic 17 Shringi M, Vaidya RA et al. Insulin resistance in
disorders. 2002; 26: 883-896 PCOS. A study of 90 patients. Indian J Endo Metab.
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6. Driscoll DA. Polycystic ovary syndrome in
adolescence. Ann. N.Y. Acad. Sci. 2003; 977: 49- 1 Laitinen J, Taponen S et al. Body size from birth to
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symptoms. Int J obesity. 2003; 27: 710-715.
7. O. Valkenburg R, PM Steges.Study of insulin
resistance and dyslipidemia in women with PCOS. 19 Catherine marin De Ugarte, Alfred A Bartolucci et
Fertility sterility. 2007; 88 Suppl. 1. -224. al. Prevalence of insulin resistance in PCOS using
the homeostasis model assessment. Fertility and
8 Abdul H Zargar, Vipin K Gupta, Arsha W et al.
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35 Diabetic. 1989: 38; 1165-1174.

Original Article
DIAGNOSTIC TEST EVALUATION OF Ig M

ELISA AND LEPTO TEK DRI-DOT
IN THE SERODIAGNOSIS OF LEPTOSPIROSIS
Kavita Raja1, Rema Devi S2, Soja V3, Shenoy KT4
Abstract Results: A total of 100 patients were selected. Of

In the past few years, the state of Kerala has these 64 were positive for leptospirosis by the gold
been experiencing an emergence of Leptospirosis, standard. The Lepto Tek Dri-Dot had a sensitivity
with occasional outbreaks. Diagnosis by of 59% and a specificity of 67%. The IgM ELISA
demonstration of the organism in blood is difficult. (Serion Classic) has a sensitivity of 64% (increases
On culture, it requires a minimum of 3 weeks. to 74% on repeating after 5 days) and a specificity
Serology is positive by the 6th-7th day. An IgM of 47%. The tests done in series with Dri-Dot done
ELISA test, which detects a wide range of serovars, first, has a sensitivity of 50% and a specificity of
is now available. A rapid test the Lepto Tek Dri- 72%.
Dot is also introduced. It takes only 5 minutes to Conclusions: Lepto Tek Dri-Dot has a higher
do and interpret. So these tests are evaluated here. specificity and lower sensitivity compared to IgM
Objectives: The present study was done with ELISA, repeat samples increase the sensitivity of
the objective of evaluation of a latex agglutination the IgM ELISA (by 10%) and combining the tests
test (Lepto Tek Dri-Dot) in the laboratory diagnosis in series increases the specificity (by 12%). Though,
of leptospirosis, done in the first week of fever, these tests are not useful for screening purposes or
against a Gold Standard of micro-agglutination test for ruling out disease in cases of fever of unknown
(MAT) combined with CDC clinical criteria for origin, they can be used very effectively on a
leptospirosis and also (i) evaluation of IgM ELISA spectrum of patients with leptospirosis encountered
and (ii) evaluation of Lepto Tek Dri-Dot and IgM in a tertiary referral centre.
ELISA done in series. Key words: Leptospirosis, IgM ELISA, Lepto
Methods: This study aims to evaluate IgM Tek Dri-Dot, Diagnostic test evaluation.
ELISA and Lepto Tek Dri-Dot in a tertiary care Introduction
referral hospital, namely Government Medical Leptospirosis, a zoonosis, caused by Leptospira
College, Thiruvananthapuram, Kerala, India. All interrogans, is now identified as one of the
cases of fever ≤ 8days, with a clinical suspicion of emerging infectious diseases, exemplified by recent
Leptospirosis were selected. Lepto Tek Dri-Dot, large outbreaks in India, Nicaragua, Brazil,
IgM ELISA (Serion Classic) and Micro- Southeast Asia and the United States. Man acquires
agglutination Test (MAT) were done on 5ml blood the infection by the contact of small abrasions on
drawn on admission. A second sample was taken the extremities with water contaminated by the
after 1week or before discharge. IgM ELISA and urine of infected animals. L.interrogans, which is
MAT were repeated to look for rise in titre or sero- pathogenic, has over 230 serovars. This results in
conversion. a great deal of cross-reactivity between serogroups
1 Formerly Professor of Microbiology, Govt. Medical College, Thiruvananthapuram, Kerala and currently Professor and
Head, Department of Microbiology, SCTIMST, Trivandrum-695011, Kerala
2 Formerly Associate Professor of Community Medicine, Govt Medical College, Thiruvananthapuram.
3 Professor of Biochemistry, Govt. Medical College, Thiruvananthapuram, Kerala,
4 Formerly Professor of Gastroenterology, and Director CERTC, Govt. Medical College, Thiruvananthapuram, Kerala.
Corresponding author: Kavita Raja: E mail: kavita_raja@yahoo.com

and serovars1,2. In the past few years, from 2000 a Gold Standard of micro-agglutination test (MAT)
onwards, the state of Kerala, South India, has been combined with CDC clinical criteria for
experiencing an emergence of the disease, with leptospirosis. The secondary objective was (i)
occasional outbreaks3. Diagnosis by demonstration evaluation of IgM ELISA and (ii) evaluation of
of the organism in blood is difficult, as they are Lepto Tek Dri-Dot and IgM ELISA done in series.
found only in the first 4-5 days of illness and a Methods
high degree of skill is required to definitely identify
Patients admitted in the Medical College,
them under the Dark-ground microscope. On
Thiruvananthapuram, a tertiary care referral centre,
culture, it requires a minimum of 3 weeks to grow
for three months with clinical suspicion of
and repeated cultures on consecutive days may be
Leptospirosis. All incident cases of acute febrile
required. Serology is positive by the 6th-7th day. The
illness admitted in the six medical units and in the
standard reference test is the Micro agglutination
Infectious Diseases unit, with a clinical suspicion
test (MAT). An IgM ELISA test, which detects a
of leptospirosis, warranting a laboratory test for
wide range of serovars, is now available. A rapid
leptospirosis was the inclusion criteria. Acute
test, the Lepto Tek Dri-Dot, which can be done
illness lasting for more than 8 days, chronic liver
separately for each patient, has also been
disease, heart disease, renal failure and suspected
introduced. It takes only 5 minutes to do and the
malignancies formed the exclusion criteria. Sample
interpretation is very simple. These tests have not
size was calculated based on the formula described
been evaluated in the low endemic conditions
in the article by Simel et al4. The prevalence,
prevailing in Kerala.
sensitivity and specificity of the tests was taken
While sensitivity and specificity are the from the information given by the Leptospirosis
cornerstones of any diagnostic test’s accuracy, Reference Centre at Port Blair5.
prevalence of the disease is reflected if the positive
The LR + has to be high and LR- has to be low
and negative predictive values are taken into
for a good test. However to calculate sample size a
account. Likelihood ratios with a narrow
series of LR+ and LR- were considered. Of these
confidence interval go further to make clearer the
the minimum LR+ we could be comfortable with
real use of the test in the context of the study4.
and the maximum LR- we could tolerate were set
Kerala is low endemic for leptospirosis, and a wide
at 2 and 0.35. With these values, the adequate
spectrum of clinical manifestations is seen here.
sample size for patients with disease was 39 and
For a diagnostic test to be valid in such conditions,
43 respectively. Hence, the sample size was fixed
it has to differentiate between commonly prevalent
at least 45 patients with disease. The protocol of
diseases and be sensitive enough to detect milder
the study was submitted to the Institute’s ethical
manifestations.
Committee and ethical clearance obtained. From
The Gold standard: A combination of MAT and/ the selected patients 5 ml blood was collected by
or typical clinical features makes a more efficient venepuncture, using aseptic techniques. After
Gold standard, as culture is difficult, tedious and clotting, the serum was separated and stored at –
takes a long time for positivity. When positive it is 20oC. Dri-Dot and IgM ELISA were done on the
quite specific, but negative cultures can never rule acute sample. Sample was repeated after 1 week or
out disease. Moreover, both MAT and the tests to before the patient was discharged. IgM ELISA was
be evaluated are serological tests, i.e. they measure done on all the repeat serum samples, to detect any
antibody levels, while culture measures the amount late rise of antibody levels. MAT was done on both
of bacteria in peripheral blood. It is in this context the paired sera, regardless of the results of the above
that a study is planned to evaluate these two tests, tests. This was performed at the Institute of
available commercially, for their accuracy in the Microbiology, Madras Medical College, Chennai.
clinical setting, using a combination of the disease
A proforma was used for the collection of socio-
as defined by the 1997 CDC clinical criteria and
demographic and clinical data from the patient, to
the Micro agglutination test as the gold standard.
record the laboratory results and follow up. The
The present study was done with the primary
Lepto Tek Dri-dot (Developed by the Royal
objective of evaluation of a latex agglutination test
Tropical Institute, Amsterdam) is a latex
(Lepto Tek Dri-Dot) in the laboratory diagnosis of
agglutination test. The IgM ELISA is SERION
leptospirosis, done in the first week of fever, against
ELISA Classic and the results are expressed as

units/ml (derived from the colorimetric readings). the negatives. Among the positives, the commonest
MAT was performed in microtitre plates using 3 clinical feature was myalgia (96.8%), followed by
live cultures as antigens, namely serovars patoc, icterus (71.8%) and conjunctival congestion
ictero haemorrhagiae and louisiana. A single high (56.2%). Renal parameters were abnormal in
titre of 80 or above or a rise in titre between the 34.3%. The main complications that occurred in
first sample and the second or a seroconversion was the patients were renal failure, bleeding and
taken as confirmation of positivity. The procedure, respiratory failure diagnosed as adult respiratory
serovars and titres were based on a study by distress syndrome (ARDS), followed closely by
Sumathy et al, which described the common hepatic encephalopathy and myocarditis. There
enzootic serovars and the baseline titres in the were 6 deaths among the positives, and none among
population and another study by the Leptospirosis the negatives. Among the six deaths, the most
Reference centre at Port Blair, which described the frequent cause of death was hepatic encephalopathy
cut-off titres in low endemic areas of Kerala and in two followed by coexistent renal failure in three
Tamil Nadu5,6. and respiratory distress in two. There was one case
For the purpose of this study, a positive case of alveolar haemorrhage; however, he died of acute
was described as MAT positive (titre of ≥ 80, as renal failure.
per the Madras study) on at least one serum sample Lepto Tek Dri-Dot was done in all patients on
and/or at least three clinical features in addition to admission only. There were 50(50%) positives,
fever, described in the CDC clinical criteria. All including 8 weak positives. IgM ELISA was done
patients with MAT positivity alone were considered in all patients. There were 60(60%) positives. IgM
positive as also all patients with the defined three ELISA was repeated in 65 patients, and an
clinical features in addition to fever, even if MAT additional 11 positives were detected of which, two
negative. For certain disorders, there is no positives showed a fall to become seronegative, but
traditional gold standard. In such cases, one one of them, proved to be positive by Gold standard.
approach is to select one or more logical The Micro agglutination test (MAT) was done in
consequences of the target disorder and make these all the 100 patients and repeated in the 65 patients
the gold standard. The same gold standard has to on whom IgM ELISA was repeated. A repeat could
be used to diagnose disease and exclude it in those not be done on 35 patients either because they were
without the disease 7. Here MAT and clinical discharged thus lost to follow-up, or because they
features if taken in combination, is a gold standard died soon after admission. MAT was positive in 52
and those with mild disease even if MAT positive patients (52%). The first sample itself was positive
may be excluded. Hence, it was decided to have a in 37 and the second sample alone was positive in
gold standard of MAT and/or clinical features. 15. Seven paired positive samples showed a rise in
Sensitivity and specificity were calculated titre. A total of 12 patients with clinical features
separately for Dri-DOT, IgM ELISA (first sample typical of leptospirosis were negative by MAT. Of
alone and for the results of repeat ELISA), as were these, four were repeatedly negative, while the other
all the other parameters. The two tests used in series eight had only the first sample tested. Of the six
were also analysed to see if they could be improved who died, MAT was positive only in two. A second
by combining them. sample had been taken in one of them and showed
Results a rise in the MAT titre, but in the other, MAT was
positive in the single sample itself. All six showed
A total of 100 patients were included in the
signs of hepato-renal dysfunction.
study. Of these 64 were positive for leptospirosis
by the gold standard of MAT positivity and/or CDC Diagnostic test evaluation: Table 1 summarizes
clinical criteria for leptospirosis. Of 64 patients with the performance of the Dri-Dot test. It has a
leptospirosis, 53 were males (82.8%) and 11 were sensitivity of 59% and a specificity of 67%. For a
females (17.2%). Majority of the positives were in prevalence of 64%, there is a slight increase to a
the active working age group of 35 years to 54 years post-test probability of 76%. However the negative
and males, indicating the increased exposure among test returns a post-test probability of only 50%.
them. While there were 12(18.7%) farmers and Table 2 summarizes the performance of the IgM
10(15.6%) labourers among the positives, there ELISA against the Gold standard. It has a sensitivity
were no farmers and only 4(11%) labourers among of 64% and a specificity of 47%. For a prevalence

of 64%, there is a slight increase to a post-test 57%.
probability of 68%. A negative test returns a post- Table 4 shows the performance of the tests in
test probability of 57%. series against the Gold standard. It has a sensitivity
Table 3 shows the performance of a paired IgM of 50% and a specificity of 72%. For a prevalence
ELISA against the Gold standard. Out of 65 of 64%, there is a slight increase to a post-test
samples, a rise in titre to become positive occurred probability of 76%. A negative test returns a post-
in 11 samples. It has a sensitivity of 74% and a test probability of 55%.
specificity of 50%. For a prevalence of 72%, there Table 5 shows the summary of the above tables,
is a slight increase to a post-test probability of 80%. for easy comparison.
A negative test returns a post-test probability of
TABLE 1: Evaluation of Lepto Tek Dri-Dot

Gold Std+ Gold Std-
Dri-Dot + 38 12 50
Dri-Dot
Dri-Dot - 26 24 50
64 36 100
Sensitivity Specificity PPV NPV LR+ LR-
0.59 0.67 0.76 0.48 1.78 0.61
TABLE 2: Evaluation of IgM ELISA

Gold Std+ Gold Std-
ELISA 1 + 41 19 60
IgM ELISA
ELISA 1 - 23 17 40
64 36 100
0.64 0.47 0.68 0.43 1.21 0.76
TABLE 3: Evaluation of paired IgM ELISA using the Gold standard

Gold Std+ Gold Std-
ELISA+ 35 9 44
IgM ELISA
paired ELISA- 12 9 21
47 18 65
0.74 0.50 0.80 0.43 1.49 0.51
PPV =positive predictive value, NPV= negative predictive value, LR+ = Positive likelihood ratio, LR- = Negative likelihood
ratio, CI = Confidence interval of Likelihood ratio.

TABLE 4: Evaluation of tests in series using the gold standard
Gold Std+ Gold Std-
SERIES+ 32 10 42
Dri-Dot + IgM ELISA
SERIES - 32 26 58
64 36 100
0.50 0.72 0.76 0.45 1.80 0.69
TABLE 5: Summary table comparing the parameters of the various tests.
Tests Sensitivity Specificity PPV NPV LR+ LR-

Dri-Dot 0.59 0.67 0.76 0.48 1.78 0.61
IgM ELISA 0.64 0.47 0.68 0.43 1.21 0.76
IgM ELISA
(repeats)* 0.74 0.5 0.8 0.43 1.49 0.51
Series** 0.5 0.72 0.76 0.45 1.8 0.69
*Any one positive taken as test positive.

**Dri-dot first and if positive, followed by IgM ELISA.
Discussion following results at one week of illness: Sensitivity-
Leptospirosis, an established public health 67.6%, Specificity- 66%. The PPV was 74.6% and
problem in India and other developing countries, the NPV was 57.9 %( post-test probability of
is difficult to diagnose due to the protean clinical disease 42.1%)9. The positive likelihood ratio is
presentations and complexities in the diagnostic near 2. Hence, its false positive rate is lower
techniques. Culture techniques are slow and compared to other tests, whatever the prevalence.
unreliable. Hence the laboratory diagnosis depends There is a weak positive reaction, which has been
on serology. Patients admitted with a differential taken as positive in this analysis as recommended.
diagnosis of leptospirosis, including cases where In the presence of clinical suspicion, it can be used
the treating physician considered a laboratory on individual patients in the first week of illness,
investigation for leptospirosis mandatory, were for a rapid result, to start specific therapy. As a
chosen. This helped to include the actual spectrum screening test, it has limited application.
of patients where these tests are applied routinely. The IgM ELISA (Serion Classic) was evaluated
In most multi centric studies, either of two methods in a study in Hawaii10. The overall prevalence of
for selection of cases is employed. The first is positive cases was 22%. They had the following
choosing two groups, one definitely proved to have findings: SERION ELISA classic Leptospira has a
leptospirosis by culture or MAT, the other proved sensitivity of 48%; Test sensitivity was particularly
having another disease 8. In such cases, most low (<25%) for all tests on specimens collected
diagnostic tests perform very well. This however during the first week of illness. i.e. first week results
does not reflect the actual cases on whom the test (<25%) compared with paired sera (48%). In the
will be applied. The second is choosing all cases present study, there was a higher sensitivity of 64%,
of fever 9. This is akin to screening. With low and a PPV of 68%. Paired ELISA was also analysed
prevalence, in such a situation, tests with high to see if there is improvement in the values if a
sensitivity are required. In the diagnostic situation, second sample is taken for confirmation. The reason
however, specificity is preferred. for the low number of second samples is the
The Dri-Dot test has a high specificity, but low inadequate reviewing of patients who have been
sensitivity. The study by the National Leptospirosis discharged. There is a 10% increase in sensitivity
Reference Centre evaluated this test and gave the if a second sample is taken. A 3% increase in

specificity may be due to the selection bias. A ii Dr. Sumathy. Professor and Head, Institute
selection bias may be possible here since the of Microbiology, Madras Medical College,
dropouts for second sample may belong more, to Chennai.
any one group. PPV increases by 10%, while the iii All staff, CERTC, Govt. Medical College,
NPV remains at 43%. Hence, it is certainly worth Thiruvananthapuram.
taking a second sample, if there is a negative first
sample in the presence of a strong clinical References
suspicion. 1. Gordon Cook. Leptospirosis. Manson’s Tropical
The tests were evaluated when done in series Diseases.20th Edition1996; 964.
with the Dri-Dot being done first. Compared to the 2. Faine S. Guidelines for the control of
Dri-Dot or IgM ELISA done alone, the specificity Leptospirosis; Offset Publication No 67.
has increased to 72%. When there is an epidemic Geneva: World Health Organization; 1982.
situation with a large number of cases, this 3. Sehgal SC, Sugunan AP. Leptospirosis: current
manoeuvre may be useful, to confirm disease and status and the need for surveillance in India.51st
institute public health measures in areas with annual conference of IAPM, Dec. 2002
clustering of cases. More complex tests will take 4. Simel DL, Samsa GP, Matchar DB. Likelihood
more time, and confirmation, if delayed, will result ratios with confidence: Sample size estimation
in a larger mortality. for diagnostic test studies. J Clin Epidemiol.
Conclusions 1991; 44(8): 763-770.
This study has been done to find the accuracy 5. Vijayachari P, Sugunan AP & Sehgal SC.
of the serological tests used routinely in the Medical Evaluation of microscopic agglutination test as
College Hospital, Thiruvananthapuram, in the early a diagnostic tool during acute stage of
diagnosis of clinically suspected leptospirosis. The Leptospirosis in high and low endemic areas.
Indian Journal of Medical Research. 2001; 114:
comparatively low sensitivity and specificity of
99-106
both tests is mainly due to the protean clinical
manifestations and the large number of prevalent 6. Sumathy G et al. Serodiagnosis of Leptospirosis:
A Madras study. Indian Journal of Medical
serotypes of the organism. The conclusions of the
Microbiology. 1995; Volume 13: 192-195.
study were the following:
i The Lepto Tek Dri-Dot has a high specificity 7. Valenstein PN. Evaluating diagnostic tests with
imperfect standards. Am J Clin Pathol. 1990;
(67%) and low sensitivity (59%), compared to
93:252-258
the IgM ELISA.
8. Smits HL, van der Hoorn MA, Goris MG,
ii The two tests may be combined in series e.g.
Gussenhoven GC, Yersin C, Sasaki DM,
in an epidemic situation, the Dri-Dot being done Terpstra WJ, HartskeerlRA. Simple latex
first, to achieve a rapid confirmation, to institute agglutination assay for rapid serodiagnosis of
containment measures. human leptospirosis. Department of Biomedical
iii Repeat samples increase the sensitivity of the Research, Royal Tropical Institute, 1105 AZ
IgM ELISA. Hence it may be repeated in the Amsterdam, The Netherlands. J Clin Microbiol.
presence of clinical suspicion. Repeated tests 2000 Mar; 38(3):1272-5.
may have to be done in severe cases with poor 9. Vijayachari P, Sugunan AP, Sehgal SC.
antibody response. Evaluation of Lepto Dri Dot as a rapid test for
iv These tests are not useful for screening the diagnosis of leptospirosis. National
purposes or for ruling out disease in cases of Leptospirosis Reference Centre, Regional
Medical Research Centre (Indian Council of
fever of unknown origin. The Lepto Tek Dri-
Medical Research), Port Blair, Andaman &
dot and the IgM ELISA can be used very Nicobar Islands, India. Epidemiol Infect. 2002
effectively on a spectrum of patients with Dec; 129(3):617-21
leptospirosis encountered in a tertiary referral
10. Effler P et al. Evaluation of eight rapid screening
centre.
tests for acute leptospirosis in HAWAII. Journal
Acknowledgements of Clinical Microbiology. 2002; 40(4): 1464-
i Dr. Indu P, Professor and Head, Dept. of 1469
Microbiology, Medical College,
Thiruvananthapuram
Review Article
CANCER VACCINES -
A NOVEL APPROACH IN
IMMUNE THERAPY
Krishnakumar U1, Girish HC2, Vinay Chandra R3
Abstract responds to them, eliminates them from the body,

Vaccines are medicines that boost the natural and develops a memory of them. This vaccine
ability to protect the body against foreign invaders, induced memory enables the immune system to act
mainly infectious agents that may cause disease. quickly to protect the body if it becomes infected
The immune system is a complex network of by the same microbes or agents in the future. The
tissues, specialized cells that act collectively to immune system’s role in defending against disease-
defend the body. Research in molecular biology causing microbes has long been recognized.
and immunology has resulted in the development Scientists have also discovered that the immune
of a range of recombinant vaccines. As of yet, system can protect the body against threats posed
success with cancer vaccines is limited. Evidence by certain damaged, diseased, or abnormal cells
is emerging that vaccines will work synergistically including cancer cells1.
with established cancer therapies such as Role of immune response cells
chemotherapy, surgery, immunotherapy, and Neutrophils and leucocytes play the main role
radiation. This article focuses on uses of recent in immune responses. These cells carry out the
research highlights, reviews and perspectives to many tasks required to protect the body against
illustrate how our new and improved understanding disease-causing microbes and abnormal cells. Some
of the function of the immune system in patients types of leukocytes patrol the circulation seeking
with cancer can be used to develop successful foreign invaders and diseased, damaged, or dead
strategies for the utilization of effective cancer cells. These white blood cells provide a general or
vaccines. nonspecific level of immune protection. Other types
Key words: Cancer Vaccine, Immune therapy, of leukocytes, known as lymphocytes provide
Tumour cells targeted protection against specific threats, whether
Introduction from a specific microbe or a diseased or abnormal
cell. The most important groups of lymphocytes
When an infectious microbe invades the body,
responsible for carrying out immune responses
the immune system recognizes it as foreign body,
against such threats are B cells and cytotoxic (cell-
destroys it, and remembers it to prevent another
killer) T cells.
infection should the microbe invade the body again
in the future. Vaccines take advantage of this B cells make antibodies that bind to, inactivate,
response and act good to health. Traditional and help destroy foreign invaders or abnormal cells.
vaccines usually contain harmless versions of Most preventive vaccines, including those aimed
microbes, killed or weakened or parts of microbes at hepatitis B virus, human papilloma virus
that do not cause disease, but able to stimulate stimulate the production of antibodies that bind to
immune response. When the immune system specific, targeted microbes and block their ability
encounters these substances through vaccination it to cause infection. Cytotoxic T cells, which are also
1 Reader, Department of Prosthodontics.
2 Professor and HOD, Department of Oral Pathology and Microbiology.
3 Professor, Department of Conservative Dentistry and Endodontics Rajarajeswari Dental College and Hospital, Bangalore.
Corresponding author: Krishnakumar U

known as killer T cells, kill infected or abnormal of certain self-antigens than normal cells. Because
cells by releasing toxic chemicals or by prompting of their high abundance, these self-antigens may
the cells to self-destruct a process known as be viewed by the immune system as being foreign
apoptosis. Other types of lymphocytes and and, therefore, may trigger an immune response
leukocytes play supporting roles to ensure that B against the cancer cells3-6.
cells and killer T cells do their jobs effectively. Types of cancer vaccine
These supporting cells include helper T cells and
There are two broad types of cancer vaccines:
dendritic cells which help activate killer T cells and
enable them to recognize specific threats. • Preventive vaccines, which are intended to
prevent cancer from developing in healthy
Cancer vaccines are designed to work by
people; and
activating B cells and killer T cells and directing
them to recognize and act against specific types of • Treatment vaccines, which are intended to treat
cancer. This is done by introducing one or more an existing cancer by strengthening the body’s
molecules known as antigens into the body, usually natural defence against the cancer7.
by injection. An antigen is a substance that The FDA has approved a cancer preventive vaccine
stimulates a specific immune response. An antigen that protects against HBV infection, (chronic HBV
can be a protein or another type of molecule found infection can lead to liver cancer). The original
on the surface of or inside a cell. Microbes are HBV vaccine was approved in 1981, making it the
recognized by the immune system as a potential first cancer preventive vaccine to be successfully
threat that should be destroyed because they carry developed and marketed. Today, most children in
foreign or non self-antigens. In contrast, normal the United States are vaccinated against HBV
cells in the body have antigens that identify them shortly after birth8. The International Agency for
as self. Self-antigens are recognized by immune Research on Cancer (IARC) has classified several
system that normal cells are not a threat and should microbes as carcinogenic (causing or contributing
be ignored2. Cancer cells can carry both self- to the development of cancer in people), including
antigens and cancer-associated antigens. The HPV and HBV9. These infectious agents – bacteria,
cancer-associated antigens mark the cancer cells viruses and parasites and the cancer types with
as abnormal, or foreign, and can cause B cells and which they are most strongly associated are listed
killer T cells to mount an attack against them. in the table below (Table 1).
Cancer cells may also make much larger amounts
Table 1: Infectious Agents and Cancer types
Infectious Agents Type of Associated Cancers
Organism
Hepatitis B virus (HBV) Virus liver cancer
(HCV) Hepatitis C virus Virus Hepatocellular carcinoma
Human papilloma virus (HPV) cervical cancer; vaginal cancer; vulvar cancer;
types 16 and 18, as well as oropharyngeal cancer (cancers of the base of the
Virus
other HPV types tongue, tonsils, or upper throat); anal cancer; penile
cancer; squamous cell carcinoma of the skin
EB Virus Virus Burkitt’s, Hodgkin’s, Non-Hodgkin’s
Lymphoma(cancer of the upper respiratory tract)
Human herpes virus (HHV8) Virus Kaposi sarcoma
(HTLV1) Virus Adult T-cell leukaemia/lymphoma
Helicobacter pylori Bacterium Gastric carcinoma; mucosa-associated lymphoid
tissue (MALT) lymphoma
Schistosomes
Parasite Bladder cancer
(Schistosoma hematobium)

Many scientists believe that microbes cause or cancer and precancerous anal lesions caused by
contribute to between 15 percent and 25 percent of these HPV types. It is also approved for use in males
all cancers diagnosed worldwide each year, with and females to prevent genital warts caused by HPV
the percentage being lower in developed than types 6 and 11. The vaccine is approved for these
developing countries 10. All cancer preventive uses in females and males ages 9 to 26. Bivalent
vaccines approved by the FDA to date have been type of vaccine is approved for use in females ages
made using antigens from microbes that cause or 9 to 25 to prevent cervical cancer caused by HPV
contribute to the development of cancer. These types 16 and 18.
include antigens from HBV and specific types of Cancer Treatment Vaccines
HPV. These antigens are proteins that help make
Cancer treatment vaccines are designed to treat
up the outer surface of the viruses. Because only
cancers that have already developed. They are
part of these microbes is used, the resulting vaccines
intended to delay or stop cancer cell growth; to
are not infectious and, therefore, cannot cause
cause tumour shrinkage to prevent cancer from
disease.
recurring or to eliminate cancer cells that have not
The U.S. Food and Drug Administration (FDA) been killed by other forms of treatment. Developing
has approved two variants of vaccines namely effective cancer treatment vaccines requires a
quadrivalent and bivalent types that protect against detailed understanding of how immune system cells
infection by the two types of HPV-types 16 and 18 and cancer cells interact. The immune system often
that cause approximately 70 percent of all cases of does not see cancer cells as dangerous or foreign,
cervical cancer worldwide. At least 17 other types as it generally does with microbes. Therefore, the
of HPV are responsible for the remaining 30 percent immune system does not mount a strong attack
of cervical cancer cases11. HPV types 16 and 18 against the cancer cells.
also cause some vaginal, vulvar, anal, penile, and
Several factors may make it difficult for the
oropharyngeal cancer 12. Quadrivalent type of
immune system to target growing cancers for
vaccine is based on HPV antigens that are proteins.
destruction. Most important, cancer cells carry
These proteins are used in the laboratory to make
normal self-antigens in addition to specific cancer-
four different types of virus like particles, or VLPs,
associated antigens. Furthermore, cancer cells
that correspond to HPV types 6, 11, 16, and 18.
sometimes undergo genetic changes that may lead
The four types of VLPs are then combined to make
to the loss of cancer-associated antigens. Finally,
the vaccine13. In contrast with traditional vaccines,
cancer cells can produce chemical messages that
which are often composed of weakened whole
suppress anticancer immune responses by killer T
microbes, VLPs are not infectious. However, the
cells. As a result, even when the immune system
VLPs in quadrivalent vaccine are still able to
recognizes a growing tumour as a threat, the tumour
stimulate the production of antibodies against HPV
may still escape a strong attack by the immune
types 6, 11, 16, and 18. In addition, quadrivalent
system14.
type of vaccine protects against infection by 2
additional HPV types, 6 and 11, which are Producing effective treatment vaccines has
responsible for about 90% of all cases of genital proven much more difficult and challenging than
warts in males and females, but do not cause developing cancer preventive vaccines15. To be
cervical cancer. effective, cancer treatment vaccines must achieve
two goals. First, like traditional vaccines and cancer
Bivalent vaccine is composed of VLPs made
preventive vaccines, cancer treatment vaccines
with proteins from HPV types 16 and 18. In
must stimulate specific immune responses against
addition, there is some initial evidence that this
the correct target. Second, the immune responses
vaccine provides partial protection against a few
must be powerful enough to overcome the barriers
additional HPV types that can cause cancer.
that cancer cells use to protect themselves from
However, more studies will be needed to understand
attack by B cells and killer T cells. Recent advances
the magnitude and impact of this effect.
in understanding how cancer cells escape
Quadrivalent vaccine is approved for use in females
recognition and attack by the immune system are
to prevent cervical cancer and some vulvar and
now giving researchers the knowledge required to
vaginal cancers caused by HPV types 16 and 18
design cancer treatment vaccines that can
and for use in males and females to prevent anal
accomplish both goals16,17.

In April 2010, the FDA approved the first cell surface, triggering its destruction by the
cancer treatment vaccine for use in men with immune system. Another group of MAbs stimulates
metastatic prostate cancer. It was designed to an anticancer immune response by binding to
stimulate an immune response to prostatic acid receptors on the surface of immune cells and
phosphates (PAP), an antigen that is found on most inhibiting signals that prevent immune cells from
prostate cancer cells. In clinical trial, this vaccine attacking the body’s own tissues, including cancer
increased the survival rate of men with certain type cell and such MAb, has been approved by the FDA
of prostate cancer by about four months18. The for treatment of metastatic melanoma, and others
vaccine was created by isolating immune system are being investigated in clinical studies19. MAbs
cells called antigen-presenting cells. (APCs) from interfere with the action of proteins that are
a patient’s blood through a procedure called necessary for tumour growth and targets vascular
leukapherisis. The APCs are sent to Dendreon, endothelial growth factor, a protein secreted by
where they are cultured with a protein called PAP- tumour cells and other cells in the tumour’s
GM-CSF. This protein consists of PAP linked to microenvironment that promotes the development
another protein called granulocyte-macrophage- of tumour blood vessels. When bound to vaccine,
colony stimulating factors (GM-CSF). The latter VEGF cannot interact with its cellular receptor,
protein stimulates the immune system and enhances preventing the signalling that leads to the growth
antigen presentation. APC cells cultured with PAP- of new blood vessels. Similarly, MAbs that bind to
GM-CSF constitute the active component of the cell surface growth factor receptors prevent the
vaccine. Each patient’s cells are returned to the targeted receptors from sending their normal
patient’s treating physician and infused into the growth-promoting signals. This may also trigger
patient. Patients receive three treatments, usually apoptosis and activate the immune system to
2 weeks apart. Although the precise mechanism of destroy tumour cells. Another group of cancer
action of this vaccine is not known, it appears that therapeutic MAbs are the immunoconjugates.
the APCs that have taken up PAP-GM-CSF These MAbs, which are sometimes called
stimulate T cells of the immune system to kill immunotoxins or antibody-drug conjugates, consist
tumour cells that express PAP. of an antibody attached to a cell-killing substance,
Monoclonal antibodies or MAbs, are such as a plant or bacterial toxin, a drug, or a
laboratory-produced antibodies that bind to specific radioactive molecule. The antibody latches onto its
antigens expressed by cancer cells, such as a protein specific antigen on the surface of a cancer cell, and
that is present on the surface of cancer cells but is the cell-killing substance is taken up by the cell.
absent from normal cells. To create MAbs, Adjuvants and versions of cancer vaccine
researchers inject mice with an antigen from human Researchers are also creating synthetic versions
cancer cells. They then harvest the antibody- of antigens in the laboratory for use in cancer
producing cells from the mice and individually fuse preventive vaccines. The chemical structure of the
them with a myeloma cell (cancerous B cell) to antigens is modified to stimulate immune responses
produce a fusion cell known as a hybridoma. Each that are stronger than those caused by the original
hybridoma then divides to produce identical antigens. Similarly, cancer treatment vaccines are
daughter cells or clones hence the term monoclonal made using antigens from cancer cells or modified
and antibodies secreted by different clones are versions of them. Antigens that have been used thus
tested to identify the antibodies that bind most far include proteins, glycoproteins or glycopeptides
strongly to the antigen. Large quantities of and (carbohydrate lipid- combinations).
antibodies can be produced by these immortal
Cancer treatment vaccines are also being
hybridoma cells. Because mouse antibodies can
developed using weakened or killed cancer cells
themselves elicit an immune response in humans,
that carry a specific cancer-associated antigen or
which would reduce their effectiveness, mouse
immune cells that are modified to express such an
antibodies are often humanized by replacing as
antigen. These cells can come from a patient called
much of the mouse portion of the antibody as
an autologus vaccine, or from another patient called
possible with human portions, done through genetic
an allogenic vaccine. Adoptive cell transfer is an
engineering. MAbs stimulate an immune response
experimental anticancer therapy that attempts to
that destroys cancer cells. MAbs coat the cancer
enhance the natural cancer-fighting ability of a

patient’s T cells. Researchers harvest cytotoxic T adjuvants. Cytokines are substances that are
cells that have invaded a patient’s tumour. The cells naturally produced by white blood cells to regulate
with the greatest antitumor activity are identified and fine-tune immune responses. Some cytokines
and grow large populations of these cells are given increase the activity of B cells and killer T cells,
in a laboratory. The patients are then treated to whereas other cytokines suppress the activities of
deplete their immune cells, and the laboratory- these cells. They help mediate and regulate immune
grown T cells are infused into the patients. Adoptive response, inflammation, and haematopoiesis (new
T-cell transfer was first studied for the treatment blood cell formation). Two types of cytokines are
of metastatic melanoma. Adoptive cell transfer with used to treat patients with cancer interferon’s (INFs)
genetically modified T cells is also being and interleukins (ILs). A third type, called
investigated as a treatment for other solid tumours, hematopoietic growth factors, is used to counteract
as well as for hematologic cancers20-25. some of the side effects of certain chemotherapy
Antigens and their substances are often not regimens. They help mediate and regulate immune
strong enough inducers of the immune response to response, inflammation, and haematopoiesis (new
make effective cancer treatment vaccines. blood cell formation). Two types of cytokines are
Researchers often add adjuvants, to treatment used to treat patients with cancer interferon’s (INFs)
vaccines. These serve to boost immune responses and interleukins (ILs). A third type, called
that have been set in motion by exposure to antigens hematopoietic growth factors, is used to counteract
or by other means. Patients undergoing some of the side effects of certain chemotherapy
experimental treatment with a cancer vaccine regimens. Cytokines frequently used in cancer
sometimes receive adjuvants separately from the treatment vaccines or given together with them
vaccine itself26. Adjuvants used for cancer vaccines include interleukin 2, interferon alpha (INF–α), and
come from many different sources. Some microbes, GM–CSF, also known as sargamostim interferon
such as the bacterium (BCG) originally used as a alpha.
vaccine against tuberculosis, is used as adjuvants27. Researchers have found that one type of INF,
Bacillus Calmette-Guérin (BCG) was the first INF-α, can enhance a patient’s immune response
biological therapy to be approved by the FDA. It to cancer cells by activating certain white blood
is a weakened form of a live tuberculosis bacterium cells, such as natural killers and dendritic cells32.
that does not cause disease in humans. When INF-α may also inhibit the growth of cancer cells
inserted directly into the bladder with a catheter, or promote their death33,34. INF-á has been approved
BCG stimulates a general immune response that is for the treatment of melanoma, Kaposi sarcoma,
directed not only against the foreign bacterium itself and several haematological carcinomas
but also against bladder cancer cells. How and why Like INFs, ILs plays important role in the
BCG exerts this anticancer effect is not well body’s normal immune response and in the immune
understood, but the efficacy of the treatment is well system’s ability to respond to cancer. Researchers
documented. Approximately 70 percent of patients have identified more than a dozen distinct ILs,
with early stage bladder cancer experience a includingIL-2, which is also called T-cell growth
remission after BCG therapy28. BCG is also being factor. IL-2 is naturally produced by activated T
studied in the treatment of other types of cancer29- cells and increases the proliferation of white blood
31
. Substances produced by bacteria, such as Detox cells, including cytotoxic T cells and natural killer
B, are also frequently used as immune therapy cells, leading to an enhanced anticancer immune
vaccine. Biological products derived from response35. IL-2 also facilitates the production of
nonmicrobial organisms can be used as adjuvants, antibodies by B-cells to further target cancer cells.
for e.g. keyhole limpet hemocyanin (KLH), which Aldesleukin, IL-2 that is made in a laboratory, has
is a large protein produced by a sea animal. been approved for the treatment of metastatic
Attaching antigens to KLH has been shown to kidney cancer and metastatic melanoma.
increase their ability to stimulate immune Researchers are currently investigating whether
responses. Even some nonbiological substances, combining Aldesleukin treatment with other types
such as emulsified oil known as montanide ISA– of biological therapies may enhance its anticancer
51, are also used as adjuvants. effects.
Natural or synthetic cytokines are also used as Hematopoietic growth factors are a special class

of naturally occurring cytokines. All blood cells inflammatory disease, and certain autoimmune
arise from hematopoietic stem cells in the bone diseases, including arthritis and systemic lupus
marrow. Because chemotherapy drugs target erythematosus.
proliferating cells, including normal blood stem Vaccine in combination with other form of
cells, chemotherapy depletes these stem cells and therapy
the blood cells that they produce. Loss of red blood
Several studies have suggested that cancer
cells, which transport oxygen and nutrients
treatment vaccines may be most effective when
throughout the body, can cause anaemia. A decrease
given in combination with other forms of cancer
in platelets, which are responsible for blood
therapy36. In addition, in some clinical trials, cancer
clotting, often leads to abnormal bleeding. Finally,
treatment vaccines have appeared to increase the
lower white blood cell counts leave chemotherapy
effectiveness of other cancer therapies. Additional
patients vulnerable to infections.
evidence suggests that surgical removal of large
Several growth factors that promote the growth tumours may enhance the effectiveness of cancer
of these various blood cell populations have been treatment vaccines37. In patients with extensive
approved for clinical use. Erythropoietin stimulates disease, the immune system may be overwhelmed
red blood cell formation, and IL-11 increases by the cancer. Surgical removal of the tumour may
platelet production. Granulocyte –macrophage make it easier for the body to develop an effective
colony stimulating factors (GM-CSF) and immune response. Researchers are also designing
granulocyte colony stimulating factors G-CSF) clinical trials to answer questions such as whether
both increase the number of white blood cells, a specific cancer treatment vaccine works best when
reducing the risk of infections. Treatment with these it is administered before chemotherapy, after
factors allows patients to continue chemotherapy chemotherapy, or at the same time as chemotherapy.
regimens that might otherwise be stopped Answers to such questions may not only provide
temporarily or modified to reduce the drug doses information about how best to use a specific cancer
because of low blood cell numbers. G-CSF and treatment vaccine but also reveal additional basic
GM-CSF can enhance the immune system’s principles to guide the future development of
specific anticancer responses by increasing the combination therapies involving vaccines.
number of cancer-fighting T cells. Thus, GM-CSF
Current approaches and research progress in
and G-CSF are used in combination with other
cancer vaccine therapy
biological therapies to strengthen anticancer
immune responses. Dendritic cells (DCs) represent unique antigen-
producing cells capable of sensitizing T cells to both
Side effects of cancer vaccine
new and recall antigens. In fact, these cells are the
Vaccines intended to prevent or treat cancer most potent antigen-producing cells. The goal of
appear to have safety profiles comparable to those DC based cancer immunotherapy is to use the cells
of traditional vaccines. However, the side effects to prime specific antitumor immunity through the
of cancer vaccines can vary among vaccine generation of effector cells that attack and lyses
formulations and from one person to another. The tumours. The first attempt to use DCs as cancer
most commonly reported side effect of cancer vaccines in humans was made by isolating DCs
vaccines is inflammation at the site of injection, from patients with non-Hodgkin’s lymphoma who
including redness, pain, swelling, warming of the had failed conventional chemotherapy, loaded the
skin, itchiness, and occasionally a rash. People cells with immunoglobulin idiotype obtained from
sometimes experience flu-like symptoms after the patient’s tumour, and reinjected the antigen-
receiving a cancer vaccine, including fever, chills, loaded cells back into the patients. Remarkably,
weakness, dizziness, nausea or vomiting, muscle most of the treated patients developed T cell
ache, fatigue, headache, and occasional breathing mediated immune responses to their tumour-
difficulties. Blood pressure may also be altered. specific antigen. Since then, a larger number of
Other, more serious health problems have been patients with non-Hodgkin’s lymphoma have been
reported in smaller numbers of people after treated with idiotype-pulsed DCs and the efficacy
receiving a cancer vaccine. These problems may confirmed. In addition, pilot clinical trials of
or may not have been caused by the vaccine. The antigen-pulsed DCs have been conducted in various
reported problems have included asthma, pelvic types of cancer, including prostate cancer,

colorectal cancer, multiple myeloma, and non-small antigen-presenting cells (APCs) through CD91 and
cell lung cancer. These studies, and other studies other receptors, eliciting a cascade of events that
carried out elsewhere, show that antigen-loaded DC includes representation of HSP-chaperoned
vaccinations represent a safe and promising form peptides MHC, translocation of NFê b into the
of immunotherapy for a wide range of nuclei, and maturation of dendritic cells. These
malignancies. consequences point to a key role of HSPs in
DC Loading and Activation - However, the fundamental immunologic phenomena such as
current approaches are far from optimal in that activation of APCs, indirect presentation (or cross
many patients treated with DC vaccines have failed priming) of antigenic peptides, and chaperoning of
to respond. Moreover, ex-vivo manipulation of DCs peptides during antigen presentation. The properties
is time consuming and costly, requires the use of of HSPs also allow them to be used for
numerous cytokines and exposes the patient to immunotherapy of cancers and infections in novel
increased risk of infection. To avoid manipulation ways38.
of DCs in-vitro and increase the potency of DC Few studies reported demonstrate that
vaccination, researchers has been working on immunogenic HSP-peptide complexes can also be
approaches to load and activate DCs in vivo. By reconstituted in vitro. One of the studies show that
administering a DC growth factor, Fms like tyrosine (a) complexes of hsp70 or gp96 HSP molecules
kinase 3 Ligand (Flt3L), to tumour bearing mice, with a variety of synthetic peptides can be generated
followed by subcutaneous injection of oligodeoxy in vitro; (b) the binding of HSPs with peptides is
nucleotides containing unmethylated CG motifs specific in that a number of other proteins tested
(CpG) together with a defined tumour Ag, they do not bind synthetic peptides under the conditions
were able to induce significant anti-tumour in which gp96 molecules do; (c) HSP-peptide
responses in mice challenged with B16 melanoma. complexes reconstituted in vitro are
The induction of a strong and durable immune immunologically active, as tested by their ability
response was dependent on the accumulation in skin to elicit antitumor immunity and specific CD8+
of high numbers of Flt3L -mobilized DCs that cytolytic T lymphocyte response; and (d) synthetic
facilitated their loading and activation with a local peptides reconstituted in vitro with gp96 are capable
injection of a mixture of tumour antigen and CpG. of being taken up and re-presented by macrophage
These results suggested that access of DCs to in the same manner as gp96- peptides complexes
tumour antigens, as well as the ability of these cells generated in vivo. These observations demonstrate
to mature, are critical for the induction of an that HSPs are CD8+ T cell response-eliciting
efficient immune response. More recently the adjuvants39.
researchers have attempted to increase the uptake The immune factors heat shock protein (HSP)/
of tumour antigens by DCs, in vivo, by directing peptides (HSP/Ps) can induce both adaptive and
circulating DCs to tumours rather than delivering innate immune responses. Treatment with HSP/Ps
exogenous tumour antigens to Flt3L mobilized in cancer cell-bearing mice and cancer patients
DCs. CCL20/macrophage inflammatory protein-3 revealed antitumor immune activity. A Study was
a MIP-3 chemokine, a potent chemo-attractant for conducted to develop immunotherapy strategies by
a subset of DCs in both humans and mice, was used vaccination with a mixture of HSP/Ps (mHSP/Ps,
alone or in combination with CpG to activate HSP60, HSP70, Gp96 and HSP110) enhanced with
tumour DCs in mice. cyclophosphamide (CY) and interleukin-12 (IL-
Heat shock protein (HSP) preparations derived 12). In the mice tumour model, vaccination with
from cancer cells and virus infected cells have been mHSP/Ps combined with low-dose CY plus IL-12
shown previously to elicit cancer-specific or virus- induced an immunologic response and a marked
specific immunity. The immunogenicity of HSP antitumor response to autologous tumours. The
preparations has been attributed to peptides regimen may be a promising therapeutic agent
associated with the HSPs. Heat-shock proteins against tumor40. A new clinical research study is
(HSPs) are the most abundant and ubiquitous underway to assess the safety and efficacy of a
soluble intracellular proteins. Members of the HSP novel immunotherapy approach to treating
family bind peptides, including antigenic peptides advanced melanoma. The investigational vaccine
generated within cells. HSPs also interact with shows promise for treating tumours in patients with

stage III/stage IV melanoma, and perhaps as a future the tumour cells44,45,46,47.
therapy for other solid-tumour cancers as well. No oncolytic virus has been approved for use
Although researchers have identified many in the United States, although H101, a modified
cancer-associated antigens, these molecules vary form of adenovirus, was approved in China in 2006
widely in their capacity to stimulate a strong for the treatment of patients with head and neck
anticancer immune response. Two major areas of cancer. Several oncolytic viruses are currently
research aimed at developing better cancer being tested in clinical trials. Researchers are also
treatment vaccines involve the identification of investigating whether oncolytic viruses can be
novel cancer-associated antigens that may prove combined with other types of cancer therapies or
more effective in stimulating immune responses can be used to sensitize patients’ tumours to
than the already known antigens and the additional therapy.
development of methods to enhance the ability of In another, more recently developed form of
cancer-associated antigens to stimulate the immune this therapy, which is also a kind of gene therapy;
system. Research is also under way to determine researchers isolate T cells from a small sample of
how to combine multiple antigens within a single the patient’s blood. They genetically modify the
cancer treatment vaccine to produce optimal cells by inserting the gene for a receptor that
anticancer immune responses41. New technologies recognizes an antigen specific to the patient’s
are being created as part of this effort. For example, cancer cells and grow large numbers of these
a new type of imaging technology allows modified cells in culture. The genetically modified
researchers to observe killer T cells and cancer cells cells are then infused into patients whose immune
interacting inside the body42. cells have been depleted. The receptor expressed
Oncolytic virus therapy is an experimental form by the modified T cells allows these cells to attach
of biological therapy that involves the direct to antigens on the surface of the tumour cells, which
destruction of cancer cells. Oncolytic viruses infect activates the T cells to attack and kill the tumour
both cancer and normal cells, but they have little cells. Cancer treatment vaccines are made using
effect on normal cells. In contrast, they readily molecules (DNA/RNA) that contain the genetic
replicate, or reproduce, inside cancer cells and instructions for cancer-associated antigens. The
ultimately cause the cancer cells to die. Some DNA or RNA can be injected alone into a patient
viruses, such as reo virus, Newcastle disease virus, as a “naked nucleic acid” vaccine, or researchers
and mumps virus, are naturally oncolytic, whereas can insert the DNA or RNA into a harmless virus.
others, including measles virus, adenovirus, and After the naked nucleic acid or virus is injected
vaccinia virus, can be adapted or modified to into the body, the DNA or RNA is taken up by cells,
replicate efficiently only in cancer cells. In addition, which begin to manufacture the tumour-associated
oncolytic viruses can be genetically engineered to antigens. Researchers hope that the cells will make
preferentially infect and replicate in cancer cells enough of the tumour-associated antigens to
that produce a specific cancer-associated antigen, stimulate a strong immune response. A large
such as EGFR or HER-243. number of cancer-associated antigens, several of
One of the challenges in using oncolytic viruses which are now being used to make experimental
is that they may themselves be destroyed by the cancer treatment vaccines. Some of these antigens
patient’s immune system before they have a chance are found on or in many or most types of cancer
to attack the cancer. Researchers have developed cells. Others are unique to specific cancer types.
several strategies to overcome this challenge, such Still an experimental form of treatment, gene
as administering a combination of immune- therapy attempts to introduce genetic material
suppressing chemotherapy drugs like cyclo (DNA or RNA) into living cells. Gene therapy is
phosphamide along with the virus or “cloaking” being studied in clinical trials for many types of
the virus within a protective envelope. However, cancer. In general, genetic material cannot be
an immune reaction in the patient may actually have inserted directly into a person’s cells. Instead, it is
benefits: although it may hamper oncolytic virus delivered to the cells using a carrier, or “vector.”
therapy at the time of viral delivery, it may enhance The vectors most commonly used in gene therapy
cancer cell destruction after the virus has infected are viruses, because they have the unique ability to

recognize certain cells and insert genetic material Introducing “suicide genes” into a patient’s
into them. Scientists alter these viruses to make cancer cells. A suicide gene is a gene whose
them more safe for humans (e.g. by inactivating product is able to activate a “pro-drug” (an
genes that enable them to reproduce or cause inactive form of a drug), causing the toxic drug
disease) and/or to improve their ability to recognize to be produced only in cancer cells in patients
and enter the target cell. A variety of liposomes given the pro-drug. Normal cells, which do not
(fatty particles) and nanoparticles are also being express the suicide genes, are not affected by
used as gene therapy vectors, and scientists are the pro-drug.
investigating methods of targeting these vectors to
Inserting genes to prevent cancer cells from
specific cell types.
developing new blood vessels
Researchers are studying several methods for
Proposed gene therapy clinical trials, or
treating cancer with gene therapy. Some approaches
protocols, must be approved by at least two review
target cancer cells, to destroy them or prevent their
boards at the researchers’ institution before they
growth. Others target healthy cells to enhance their
can be conducted. Gene therapy protocols must also
ability to fight cancer. In some cases, researchers
be approved by the FDA, which regulates all gene
remove cells from the patient, treat the cells with
therapy products. Some cancer cells produce
the vector in the laboratory, and return the cells to
chemical signals that attract white blood cells
the patient. In others, the vector is given directly to
known as regulatory T cells, or Tregs, to a tumour
the patient. Some gene therapy approaches being
site48. Tregs often release cytokines that suppress
studied are described below.
the activity of nearby killer T cells 49 . The
Replacing an altered tumour suppressor gene combination of a cancer treatment vaccine with a
that produces a non-functional protein (or no drug that would block the negative effects of one
protein) with a normal version of the gene. or more of these suppressive cytokines on killer T
Because tumour suppressor genes (e.g. TP53) cells might improve the vaccine’s effectiveness in
play a role in preventing cancer, restoring the generating potent killer T cell anti-tumour
normal function of these genes may inhibit responses.
cancer growth or promote cancer regression. Conclusion
Introducing genetic material to block the Perhaps the most promising avenue of cancer
expression of an oncogene whose product vaccine research is aimed at better understanding
promotes tumour growth. Short RNA or DNA the basic biology underlying how immune system
molecules with sequences complementary to cells and cancer cells interact. Researchers are
the gene’s messenger RNA (mRNA) can be trying to identify the mechanisms by which cancer
packaged into vectors or given to cells directly. cells evade or suppress anticancer immune
These short molecules, called oligonucleotides, responses. A better understanding of how cancer
can bind to the target mRNA, preventing its cells manipulate the immune system could lead to
translation into protein or even causing its the development of new drugs that block those
degradation. processes and thereby improve the effectiveness
Improving a patient’s immune response to of cancer treatment.
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Review Article
HOT TOOTH: DOOMING

DARE OF THE DENTIST
Bindu R Nayar1, Sheeba P2, Sudheer Kumar Prabhu3
Introduction such as Electric Pulp Tester (EPT) / the application

Achieving profound pulpal anaesthesia is a of a cold refrigerant are more reliable. There are
corner stone in endodontic practice and dentistry. numerous reasons put forward for explaining pulpal
About 30% of all dental emergencies are anaesthetic failure after IANB.
endodontic. In 90% of painful emergencies, pain They include:
is pulpal or periapical. However, every dentist has 1. Central core theory4: This theory states that the
had the unfortunate experience of being unable to nerve on the outside of the nerve bundle supply
achieve local anaesthesia, especially when dealing molar teeth while the nerve on the inner side supply
with an irreversibly inflamed dental pulp. The term the anterior teeth. The anaesthetic solution may not
“hot tooth” generally refers to tooth that is difficult diffuse into the nerve trunk to reach all the nerves
to anaesthetise. Inflammatory changes within the to produce an adequate block even if deposited at
pulp progressively become worse as a carious lesion the correct site. This theory may explain the higher
nears the pulp. Chronic inflammation takes on an failure rates in the anterior teeth with IANB but
acute exacerbation with an influx of neutrophils not posterior teeth.
and the release of inflammatory mediators
2. Central sensitization: When inflammation and
(Prostaglandins and Interleukins) and pro-
pain occur for an extended period, this results in
inflammatory neuropeptides 1 (Substance P,
an increased excitability of the CNS. Increased
Bradykinin and Calcitonin gene related peptide).
sensitization may amplify incoming signals from
These mediators in turn, sensitize the peripheral
sensory nerves. Under these conditions, the IANB
nociceptors within the pulp of the affected tooth,
may permit for sufficient signalling to occur,
which increases the pain production and neuronal
leading to the perception of pain. The excited CNS
excitability2.
may be responsible for otherwise innocuous
Of all the teeth with Symptomatic Irreversible stimulus presenting as anaesthetic failure.
Pulpitis (SIP), mandibular posteriors pose the most
3. Altered membrane excitability of peripheral
severe challenge. 15-20%3 patients failed to achieve
nociceptors: Inflamed tissue have altered resting
pulpal anaesthesia after a successful Inferior
potential5 and decreased excitability threshold,
Alveolar Nerve Block (IANB). Single IANB
Wallace et al5 demonstrated that the LA are not
injection of LA (1.8cc) is ineffective in 30-80%3
sufficient to prevent impulse transmission as a result
patients with irreversible pulpitis. Effectiveness of
of these lower excitability threshold.
IANB has traditionally been confirmed by asking
the patient if their lip feels numb, probing or 4. Inflammation: In the presence of inflammation,
sticking the gingiva or simply starting treatment a number of changes occur to the actual nociceptors
and waiting for patient response. Objective tests or pain receptors. The receptors become both
1 Professor and Head, Department of Periodontics, Govt. Dental College, Thiruvananthapuram.

2 House Surgeon, Govt. Dental College, Thiruvananthapuram.
3 Senior Resident, Department of Conservative Dentistry and Endodontics, Govt. Dental College, Thiruvananthapuram.
Corresponding author: Bindu R Nayar: E-mail: brnsai@gmail.com

activated and sensitized. Sensitization of of receptors is the reason. According to Kenneth
nociceptors occurs due to other inflammatory Hargreaves there is little evidence for this7.
mediators, such as PGE2, Bradykinin etc. This 6. Tetradotoxin resistant channels: Tetradotoxin
result in the threshold for the nerve firing reduced. (TTx) is a potent neurotoxin that block Voltage
The result is that the nociceptors will activate with Gated Sodium Channels (VGSc). VGSc can be
much milder stimulus. It has been shown that both classified as TTx sensitive (TTx-S) and TTx
activation and sensitization result in a decreased resistant (TTx-R) channels8 according to their
level of resistance to anaesthetic. sensitivity to this toxin. These are located on ‘c’
Another thing that occurs in response to fibres. Sodium channel expression shifts from TTx
inflammation is nerve sprouting. Inflammatory sensitive to TTx resistant during neuro-
mediators6 actually cause nerves to grow into the inflammatory reactions (Reverting Back
inflamed area and this has been shown to happen phenomenon). These channels are 5 times more
in human dental pulp. Inflammation also causes an resistant to anaesthetic than TTx sensitive channels.
increase in the production of proteins by After a mandibular block, a patient may describe
nociceptors, such as substance P and calcitonin gene profound anaesthesia of the ipsilateral lip and
related peptide. These proteins play a role in the tongue. However entering the vital pulp chamber
regulation of inflammation in the pulp. may initiate pain because TTx resistant sodium
There is a concept that IAN blocks failed channels have not been adequately blocked by the
because of the increased pH in the region of an anaesthetic. Exposing a nerve to PGE2 doubles the
inflamed pulp (by acidic inflammatory products) activity of TTx-R. There is another concept that
which prevented dissociation from the acid form PG might only operate on these channels locally
of the LA to the base form( Ion trapping); so most as mentioned in the pH change theory.
anaesthetic molecules remain in inactive cationic 7. Psychological factors: Patient anxiety may
form. A prime question that can arise concerned contribute to LA failure. Apprehensive patient have
with this topic is the inflammation at the site of a lower pain threshold. Other possible causes are
tooth may affect the dissociation of an LA molecule anatomic variations, cross innervations and
deposited near the mandibular foramen. The change abnormal tolerance to anaesthetic drug.
in pH in inflamed tissues is not large, and inflamed Pre-emptive strategies to improve success of the
tissues possess a greater buffering ability than IANB injection
normal tissues. In addition, any change in the tissue
In a study conducted by Ianiro and colleagues,
pH is likely to be localised.
by premedicating9 these patients prior to Root Canal
The next possible mechanism is through the Treatment (RCT), significantly improved the
increased blood flow that occurs in inflamed success rate of IANB. In this study, patients
tissues. This could potentially result in increased received either 600 mg of ibuprofen or gelatin as
removal of LA from a site. Again, this is likely to placebo 1 hour prior to IANB. The ibuprofen group
be a localised tissue and should not affect regional had a success rate of 72% as against only 36% for
block anaesthesia. Theoretically, increasing the the placebo. The findings in this study contradict
concentration of vasoconstrictor in LA should the result obtained in previous studies. Other
counter act this mode of failure, but to date, there articles show there was no significant difference
are only a few studies available, comparing between the groups taking placebo or medication.
different concentrations of adrenaline in pulpitis But it seems that the pre-operative administration
case. In normal pulps, the results have been a little of ibuprofen or other NSAIDs is a sensible
contradictory with some studies showing equivalent approach as the LA failure is basically due to
results for different concentrations of Adrenaline. inflammation. Decreasing pulpal level of PGE2
Accessory innervations from mylohyoid, lingual, would be beneficial in 2 ways: (i) decreasing pulpal
buccal, transverse cervical nerve are also implicated nociceptors sensitization would mitigate an
as a reason for LA failure. increased resistance to LA, (ii) it may diminish a
5. Tachyphylaxis: Another possible method prostanoid induced stimulation of TTx-R channel.
mentioned in the literature is resistance or Some research points to the use of either intra
tachyphylaxis. Subsequent administration may ligamentary, intra-osseous or intra-pulpal
cause tolerance to the drug. Reduced susceptibility

supplementary injections. The learning curve, along comparing various Local anaesthetic agents
with the added cost of these products may become such as 3% Mepivacaine Plain, 4% Prilocaine
a factor for the practitioner. However, in Plain, Prilocaine with epinephrine, 2%
approximately 5-10% 10 of mandibular teeth Mepivacaine with Levonordephrine, 4%
diagnosed with irreversible pulpitis, supplemental Articaine with epinephrine, 2% Lidocaine with
injections (Intra-ligamentary and Intraosseous) do Epinephrine showed that there was no
not produce adequate anaesthesia, even when difference in success rates.
repeated, to enter the pulp chamber painlessly. This 2. Using solutions with higher epinephrine
is a prime indication that an intra-pulpal injection concentration16: Increasing the concentration of
is necessary. The intra-pulpal injection works well epinephrine (1:50, 000), showed no advantage
when it is given under back-pressure10. Onset of in the IANB
action is immediate. A disadvantage is its short
3. Changing injection techniques: Controlled
duration of action (15-20 minutes). Once
clinical studies failed to prove the superiority
anaesthesia is achieved, the practitioner must work
of Gow Gates17 and Vazirani Akinosi18 injection
quickly to remove all the tissue from the pulp
techniques over IANB
chamber and the canals.
4. Depositing the anaesthetic solution in close
Supplementary articaine 11 infiltration is a
proximity to inferior alveolar nerve.
simple solution for that. In a study, success rate of
supplemental infiltration after an incomplete IANB 5. Adding a mylohyoid injection: Clarke19 and
by using lidocaine was 29%, whereas by using colleagues when combining the IANB with a
articaine it was 71%. In earlier studies mylohyoid injection after locating the
Bupivacaine 12 was used. It can inhibit central mylohyoid nerve with a peripheral nerve
sensitization leading to diminution of pain. Because stimulator found no significant improvement
of its increased lipid solubility and neuronal protein in anaesthesia.
binding, Bupivacaine induces local anaesthesia 6. Increasing the volume of anaesthetic delivered
lasting 2.5 to 3 times longer than lidocaine. Even via IANB20.
brief exposure (15 minutes) of chondrocytes to 7. Accurate injection technique: Hannan 21 and
0.5% Bupivacaine has been found to be cytotoxic, colleagues used medical ultrasound to guide an
and chondrocytes viability in human articular anaesthetic needle to its target. They concluded
cartilage explants was reduced significantly by that accuracy of the injection technique is not
Bupivacaine after 30 minutes of exposure. a big factor.
Bupivacaine must be acidified to remain soluble, Conclusion
and this may be a source of its differential toxicity
Dentists usually find themselves filled with
compared with other local anaesthetics. These may
self-doubt and feeling helpless, when they need to
be the reasons behind limited usage of Bupivacaine
remove pulp from a patient with hot tooth and it is
as LA. Intraosseous injection of Ketorolac or 40
a quiet challenging issue. It leads to development
mg methyl prednisolone13 is also seems to be
of a plan to deal with the eventual failures found
effective
with the IANB injection. Use of supplemental
Reducing anxiety14 by S/L Triazolam/nitrous injection techniques like, Premedication,
oxide is also an effective method. 3% mepivacaine Alkalinisation of LA and Hypnosis, seems to be
may be useful in patients with irreversible pulpitis. quiet effective. These techniques ensure confidence
Alkalinisation using Sodium bicarbonate may also to the dentist to provide relatively pain-free
be useful. Devitalizing the pulp before proceeding treatment for the patient having a hot tooth.
with treatment using Formocresol also seems to be
effective. Dental analgesia like Electronic dental
analgesia, TENS, using opioids are other References
alternatives. Nusstein et al discusses literature 1 Byers MR, Narhi MV. Dental injury models;
suggesting that anaesthetic success rate will not experimental tools for understanding
improve when treating hot teeth by, neuroinflammatory interactions and polymodal
nociceptor functions. Crit Rav Oral Biol Med. 1999;
1. Using different anaesthetic solution:-Research15 10(1): 4-39

2 Dray A. Inflammatory Mediators of pain. Br. J. of Bupivacaine and lidocaine for IANB. JOE. 2005;
Anesth.1995; 75(2); 125-31. 31: 499-503.
3 Endodontic anaesthesia in mandibular molars: a 13. Gallatin E, Reader A, Nist R, et al. Pain reduction
clinical study. J Endod. 1993; (19): 370-373. in untreated irreversible pulpitis using an
4 De Jong R. Neural blockade by local anaesthetics. intraosseous injection of Depo-Medrol. J Endod.
JAMA. 1977; 238(13): 1383-5. 2000; 26(11):633-8.
5 Wallace J, Michanowicz A, Mundel R. et.al, A pilot 14. Lindmann M, Reader A, Nusstein J, et al. Effects of
study of the clinical problem of the regionally sublingual Triazolam on the success of IANB in
anesthetising the pulp of an acutely inflamed patients with irreversible pulpitis. JOE. 2008;
mandibular molars. Oral Surg Oral Med Oral 34(10): 1167-70.
Pathol. 1985; 59(5): 517-21. 15 Hinkley SA, Reader A, Beck M, et al. An evaluation
6 Byers M, Taylor P, Khayat B, et al. Effects of injury of 4% prilocaine with 1:200, 000 epinephrine and
and inflammation on pulpal and periapical nerves. 2% mepivacaine with1:200, 000 levonordefrin
JOE. 1990; 16 (2):78-84. compared with 2% lidocaine with1:100, 000
epinephrine for inferior alveolar nerve block Anesth
7 Kenneth M, Hargreaves, Karl Keiser. Local Prog.1991; 38(3):84-9.
Anesthetic failures in endodontics: Mechanisms and
management. Endodontic Topics. 2002; I: 26-39. 16 Yared G, Dagher F Evaluation in Lidocaine in
human IANB. JOE. 1997; 23(9):575-8.
8 Roy M, Narahashi T. Differential properties of
tetradotoxin sensitive and tetradotoxin resistant 17 Agren E, Danielsson K. Conduction block analgesia
sodium channels in rat dorsal root ganglion neurons. in the mandible. A comparative investigation of the
J Neuro Sci. 1992; 12(6): 2104-11. techniques of Fischer and Gow-Gates. Swed Dent
J1981; 5(3):81-9.
9 Ianiro S, Jeansonne B, McNEAL S, et al, The effect
of pre-operative acetaminophen or a combination 18 Sisk A. Evaluation of the Akinosi mandibular block
of acetaminophen and ibuprofen on the success of technique in oral surgery. J Oral Maxillofac Surg.
IANB for teeth with irreversible pulpitis. JOE. 1986; 44: 113-5.
2007; 33(1):11-4. 19 Clark S, Reader A, Beck M, et al. Anaesthetic
10 VanGheluwe J, Walton R. Intrapulpal injection: efficacy of the mylohyoid nerve block and
factors related to effectiveness. Oral Surg Oral Med combination of IANB/ Mylohyoid nerve block.
Oral Pathol Oral Radiol Endod. 1997; 83(1): 38- Oral Surg Oral Med Oral Pathol Oral Radiol Endod.
40. 2001; 92:132-5.
11 Matthews R, Drum M, Reader A. et al. Articaine 20 Nusstein J, Reader A, Beckam, Anaesthetic

for supplemental buccal mandibular infiltration efficiency of different volumes of Lidocaine with
anaesthesia in patients with irreversible pulpitis epinephrine for IANB Gen Dent. 2002; 50(4):3725.
when IANB fails. JOE. 2009; 35(3):343-6. 21 Hannan L, Reader A, Nist R, et al. The use of
12 Fernandez C, Reader A, Beck M, Nusstein J. A ultrasound for guiding needle placement for IANB.
Prospective, randomized, double blind comparison OralSurg Oral Med Oral Radiol Oral Pathol
Endod.1999; 87(6): 658-65.

Review Article
SCRUB TYPHUS: ALERT

Devraj Ramakrishnan1, Zinia T Nujum2, Sara Varghese3
Scrub typhus is an acute febrile illness, which is The disease is transmitted by the bite of infected
being increasingly reported in Kerala. Cases have chiggers of trombiculid mites. These mites are
been reported from Medical colleges since 1998 usually found in areas of shrub vegetation between
through the State Prevention of Epidemic and the forests and clearings, called scrubs and hence
Infectious Diseases cell. Reporting of cases by the the name. But some endemic areas are sandy and
directorate of health services started in 2012. The even desert-like3. Mammals such as rats, dogs and
numbers have gone up alarmingly (table 1) over cats, including man, visiting these areas get
the past couple of years1. In the world it is estimated infested, even in a single instance7. Transfer of the
as high as 1 billion people are at risk of contacting mites from the infested domestic animals to man is
scrub typhus and about one million cases occur not reported but their presence can act as an
annually2 indicator of the agent. Humans are accidental hosts3.
Of the total reported 433 cases and 6 deaths in The mite is very small ranging in size from 0.2-
2014, 366 cases and 3 deaths were reported from 0.4mm. The life cycle comprises of four stages;
Thiruvananthapuram district alone. The distribution egg, larvae, nymph and adult. The larvae are the
of cases in Thiruvananthapuram district is shown infective form (chigger) as it feeds on vertebrate
in figure 1. Kozhikode district reported 32 cases animals. Nymph and adult are free living in the
and no deaths. The other 3 deaths were from soil. The mites act as excellent reservoirs too
Kollam, Pathanamthitta and Palakkad. Maximum through transovarial transmission and transtadial
number of cases in a single month occurred in transmission3.
December with 82 cases and 1 death1. People who are exposed to these areas of shrub
Historical Perspective vegetation are at an increased risk, like those who
Scrub typhus was first described in 1899, from depend on forests for a living, those who are
Japan3. Scrub typhus came into limelight during engaged in sanitation works of clearing these shrubs
the second world war when it killed almost 36,000 and those who visit such places as tourists.
soldiers4. In India, during the second world war, Agricultural occupation is presumed as a risk as
scrub typhus was the second most important threat the rice fields can be active Poor personal hygiene
in Assam and Bengal, surpassed only by Malaria5. can be an added factor, which will help the mite in
staying longer on the body. More number of cases
Epidemiology: The known facts.
are being reported in winter season, in southern
Scrub typhus is an emerging zoonotic bacterial India3,8. But a study from Dehradun showed an
infectious disease caused by Orientia tsutsugamushi increase in the number of cases with the onset of
(earlier Rickettsia tsutsugamushi), the vector being rains and a decrease in winter9.
trombiculid mites. The geographical distribution
Diagnosis – the dilemmas
of scrub typhus is limited to a triangular area bound
between Pakistan, Japan and Australia, often Four possible overlapping clinical presentations
referred to as ‘the tsutsugamushi triangle4,6. of scrub typhus has been reported: mild disease,
1 Senior resident, Department of Community Medicine, Govt, Medical College, Thiruvananthapuram.

2 Associate Professor of Community Medicine, Govt, Medical College, Thiruvananthapuram.
3 Professor of Community Medicine, Govt, Medical College, Thiruvananthapuram.
Corresponding author: Zinia T Nujum: E-mail: drzinia@gmail.com

respiratory predominant disease, central nervous It is difficult to differentiate scrub typhus from
system predominant disease (meningoencephalitis), other diseases like leptospirosis, typhoid, murine
and sepsis syndrome10. typhus and meningococcal infections initially20.
Scrub typhus presents as acute febrile illness Hanta IgM Elisa test might also give a positive
with many nonspecific symptoms such as chills and result in scrub typhus due to unexplained antigen
rigors, myalgia, headache, abdominal pain, throat cross reactivity. Scrub typhus can also present as a
pain, dry cough, chest pain, breathlessness etc. co-infection with Dengue, Malaria or Hanta fever
Clinical signs that might be present are conjunctival which posses a diagnostic challenge and worsens
congestion, rashes, lymphadenopathy and clinical response to treatment21,22. All cases of acute
hepatosplenomegaly. The mean incubation period febrile illness not having any other definite
is 10-12 days but can range from 5-20 days9,11. diagnosis or not responding well to treatment as
expected, should be immediately screened for IgM
The ‘eschar’ which is pathognomonic for scrub
Elisa. Early diagnosis and treatment is the key to
typhus is present only in up to 60% of the cases3,
prevent mortality.
45.5% in one study10, and another study in India
reported the proportion to be as low as 14.5%9. It Endemicity of scrub typhus can be determined
is most often present in axilla, groin, genitalia and by checking the seroprevalence of scrub typhus
neck12. People from south east Asia and endemic antibodies in a defined population. This will help
areas often get only a mild disease without any rash in identifying the high-risk areas and focusing on
or eschar13. There was a significant difference prevention activities. Surveillance using standard
between the genders on developing an eschar and case definitions should be carried out. The use of
also the areas involved. In a study, 55.8% of male Sentinel surveillance in specific areas including
cases had an eschar but only 42.3% females high and low risk areas will enable the estimation
developed the same. In males, the eschar was seen of true burden of disease and a better community
mostly in groin, axilla and genitalia whereas in diagnosis. The diagnostic kits for scrub typhus need
females abdomen and chest14. This makes the case to be made available at least in selected sentinel
detection very difficult. A high index of suspicion surveillance sites of National Vector Borne Disease
is very much essential for clinching a diagnosis. Control Program (NVBDCP).
An acute scrub typhus infection is seen to decrease Disease Management
the viral load of HIV patients. The mechanism is Morbidity or mortality is not significant in those
unknown15,16. who receive timely and appropriate treatment3.
Blood routine investigations show leucopoenia, Prompt antibiotic therapy should be started. In high
relative lymphocytosis and thrombocytopenia. risk areas, acute febrile illness are started on
Serum bilirubin may be mildly elevated and SGOT doxycycline, a broad spectrum antimicrobial agent
and SGPT may be moderately elevated. Alkaline effective against scrub typhus, given 100 mg twice
phosphatase can also show a rise. Renal function daily for 5-7 days. Chloramphenicol is an
tests are usually normal except in the cases having alternative effective drug. For children less than 8
renal involvement which can be detected by years and pregnant women, azithromycin 500 mg
monitoring of renal parameters3,11. once daily for 5-7 days is given (10 mg/kg/day for
The earlier diagnostic test - Weil Felix reaction children). A combination therapy of doxycycline
had low sensitivity and specificity, and is now with Rifampicin is used in areas where response to
replaced by IgM and IgG Elisa for scrub typhus. A doxycycline is poor23. Rifampicin 450 mg twice
single high IgM titre of more than 1:32 or a fourfold daily for 5-7 days can be used alone in resistant
increase between paired sera is taken as cases11. Incomplete treatment can result in a relapse.
confirmatory11. The rapid defervescence produced by antibiotics
is very much characteristic and can be used as a
Gold standard investigation is indirect
confirmation of scrub typhus24.
immunofluorescence antibody (IIFA)3. Commercial
rapid diagnostic kits are available but cost is a Prevention of complications is an integral part
limiting factor17. Standard PCR, Nested PCR, Real of the management of scrub typhus. Main
time PCR can be used to demonstrate the organism complications that must be addressed are
from skin rash biopsies, lymph node biopsies and pneumonitis, myocarditis and encephalitis. Also
EDTA treated blood18,19. other complications we should watch out for are

shock, acute renal failure and disseminated and mite) chigger index should be found. The
intravascular coagulation3,11. So chest X ray ( with procedure involves identification of rat, taking 2-3
features of pneumonitis like non-homogenous ml blood from rat either by syringe or cutting the
patchy opacities with/without air-bronchogram) throat, serum separation and collection in vial to
and ECG ( features of myocarditis are tachycardia be sealed. Combing has to be done for ecto-parasite
and diffuse ST, T wave changes ) should be done collection (Mite) and the rodent ear is to be cut and
in scrub typhus cases and suspected brain preserved in 70% alcohol. The material after proper
involvement warrants an EEG or MRI scan11. labelling can be sent to National Centre for Disease
Guidelines on management of scrub typhus Control for identifying the vector species and
developed for Kerala is available at Directorate of antibodies in serum sample for Scrub typhus.
Health Services (DHS) website11. Need for research: filling the gaps
Prevention Cheaper rapid diagnostic kits can help a lot in
Doxycycline 100 mg once weekly after food early diagnosis and is an important area requiring
for 6 weeks following exposure is an effective research. The mechanism of interaction between
chemoprophylaxis in special cases11. There is no HIV virus and scrub typhus infection is still
vaccine yet and development of one is hampered unknown. The seasonality of scrub typhus in this
by the vast antigenic variation shown by part of the world needs to be established. Host and
O.tsutsugamushi strains25. In endemic areas, people vector studies should be undertaken in collaboration
engaged in risky occupations having exposure to with veterinary doctors for understanding the
shrub vegetation should always wear protective natural history better. The real burden of the disease
clothing including shoes and socks. Insect is still grey. The reported cases may be only the tip
repellents can be used containing the chemicals of the iceberg.
such as dibutyl phthalate, benzyl benzoate, diethyl Health systems strengthening: The need of the
toluamide and others. Contact with bare ground or hour
grass should be avoided even if clothed. Chemical
Capacity building of the health personnel
treatment of the soil and clearing off the vegetation
should be done at the earliest which is key for rapid
can help in interrupting the transmission cycle3.
case detection. Those in the private sector must also
Early diagnosis and treatment through rapid case
be targeted through organizations like Indian
detection, public education and awareness, and
Medical Association (IMA). Strengthening of lab
rodent control and habitat modification are the three
facilities is required especially in the government
main pillars of scrub typhus prevention put forward
sector, prioritizing the endemic areas. Scrub typhus
by WHO. Public awareness about how to prevent
should be included in the fever surveillance and
the disease, the symptoms and signs of the disease
sentinel surveillance for understanding the true
(such as eschar, lymphadenopathy and rash), and
burden, distribution and trend of the disease.
seeking care, diagnosing and treatment will
Integrated Disease Surveillance Program (IDSP)
drastically reduce the mortality due to scrub
case definitions should be updated, including
typhus3.
definitions of scrub typhus for S, P and L forms
Rodent control and habitat modification is also and it should be disseminated to the health
put forward as a measure and should be done mainly professionals immediately. Reported cases should
by the agricultural sector. The methods suggested be epidemiologically investigated for the source,
are trapping, poisoning and using natural predators. mode and route of infection as a routine for a better
Habitat modification will make the rodents not to community diagnosis. Inter-sectorial co-ordination
prefer that area anymore; environment hygiene and is a must for accomplishing this and should include
proper waste management (especially food waste) the Medical and Veterinary specialist doctors from
can restrict the growth of rodent population. various departments of academic institutions, the
Animal studies may be required for more Health department staff, local hospital staff and
informed control measures. Objective of such field workers. Community participation should be
studies will be to identify the antibodies from sera ensured in all these activities and involvement of
of infested rodents, predominant species of rats local associations should be encouraged. Public
involved and degree of infestation of rodents in Private Partnership should also be entertained with
terms of the chigger index. Species specific (rat defined roles.

Summary Points
Scrub typhus is being increasingly reported Early diagnosis and treatment is the key to
in Kerala. prevent mortality.
Eschar, if present, is pathognomonic of scrub Doxycycline is the treatment of choice. For
typhus, but its absence does not rule out scrub children less than 8 years and pregnant
typhus. women azithromycin is given.
All cases of acute febrile illness not having High-risk areas should be identified to focus
any other definite diagnosis or not responding on the preventive activities.
well to treatment as expected, should be
Sentinel surveillance, health system
screened for scrub typhus using IgM Elisa,
strengthening and focused research are the
especially in endemic areas.
need of the hour
Table 1 shows the number of scrub typhus cases reported in Kerala by the Directorate of Health Services.
Table 1: Scrub typhus reported in Kerala
Year Cases Deaths
2015 (till May ) 356 6
2014 433 6
2013 68 0
2012 39 4
2011 Not reported
Fig 1: Spot Map of cases of scrub typhus in the Thiruvananthapuram district
Source: State PEID cell, Government Medical College, Thiruvananthapuram, 2014

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Concept Paper
‘CONCEPT OF FAMILY HEALTH’

AS AN INNOVATIVE HEALTH
DELIVERY STRATEGY
Nair MKC1, Leena ML2, Manoj Kumar AK3,

Remadevi S4, Rajamohanan K5
The public health delivery system, as was institution has as it’s core relationship, two parents
envisaged in the ‘Bhore Committee’ report1 has tied together in an emotional axis from which stem
been institutionalized in India with good results in many needs. The family is a nodal point in a web
many parts of the country, particularly in Kerala. of human relationships involving parents and
However, there is a recent trend to depend more on children, in-laws, friends and neighbours2. Each
medical colleges and super speciality hospitals even family evolves its own emotional atmosphere, and
for primary and secondary level care, thus the emotional climate may have either a
undermining the relevance of our primary care constructive or destructive effect upon the child’s
institutions. As a society we have achieved good health during the early years of his/her
health care standards, well appreciated by rest of development. Out of the complicated fabric that is
the world. In Kerala, the socio-economic structure the family comes overall family health, a concept
of the community have changed so much that to be understood and seen in the setting of the
neighbourhood households do not have similarity community, the character of geographic region, the
in their health indices and social indicators. Even general standards of living, the cultural patterns and
the western world that had always focussed on the present health practices.
individual’s health, is now coming around to the Family as a system
need for enhancing the capacity of the family to
Any system may be defined as a bounded set
support the individual members of the family and
of interrelated elements exhibiting coherent
capacity of the community to protect the family.
behaviour as a trait or as an assemblage of objects
The concept of family health envisages (i)‘family’
related to each other by some regular interaction
as the smallest unit for all support services from a
or interdependence. Families are considered
policy perspective, (ii) introduction of ‘family
systems because (i) they are made up of interrelated
health card’ from a health perspective, (iii) ‘family
elements or objectives, (ii) they exhibit coherent
safety net’ from a social perspective and (iv) ‘family
behaviours, (iii) they have regular interactions, and
doctor concept’ from an economic perspective. But
(iv) they are interdependent on one another3.
before we proceed further, we need to understand
the key elements of the concept. Family safety net: The family safety net is a
concept of safeguarding family members against
The Concept of Family
possible hardship or adversity, keeping the family
The concept of family is unique not only to as the centre point of all actions for optimal
humans but also to all members of the animal development of individuals in the family and in
kingdom. It is a social unit of two or more related turn the community. The safety net include a
persons having a shared commitment to the mutual collection of services provided by the state or other
relationship and for continuity of the next institutions to safeguard the institution of family
generation – the children. The family as a social and its members, including welfare, unemployment
1 Vice Chancellor, 2 Program Officer, 3 Dean Student Affairs, 4 Project Officer, 5 Consultant. KUHS. Thrissur.

benefit, universal healthcare, homeless shelters, possibilities. An expert in public health should
and sometimes subsidized services such as public recognize the role of sound public policy directed
transport, which prevent individuals in the family towards the overall picture of health determinants,
from falling into poverty beyond a certain level. A and should also master the knowledge and skills
practical example of how the safety networks would for implementing integral programmes.
be a single mother with children, unable to work, Although it has also been pointed out that “our
receiving money from the government to support understanding of what makes and keeps people
her children. Along with universal health care and healthy continues to evolve and will be further
free education, she can give her children a better refined”, the key determinants of health as on today
chance at becoming successful members of society, include; (i) biology and genetic endowment, (ii)
rather than be caught up in the hopelessness of gender, (iii) healthy child development, (iv)physical
extreme poverty. environments, (v) family Income, (vi) social status,
Concept of Family health (vii) social support, (viii) social networks, (ix)
Although the literature reflects wide use of the social environments, (x) educational status, (xi)
term family health, the concept is ambiguous and employment status, (xii) working conditions, (xiii)
lacks conceptual clarity. Family health may be personal health practices, (xiv) coping skills to
described as a dynamic and complex construct reduce stress, (xv) availability, accessibility and
consisting of multiple member interactions within affordability of health services and (xvi) the
and across the boundaries of households nested cultural context5.
within social contexts. Family members use Family Interventions
communication, cooperation, and caregiving to All members of the family need health care,
develop and sustain individual and family health socio-economic support and opportunity for
routines. Family health is influenced by the personal growth, at the same time making the
participants’ embedded cultural context and family as the basic health care and support unit. Of
characterized by highly interactive functional, course, children, women, elderly, disabled and other
contextual, and structural perspectives. Implicit in marginalized groups would require additional
the concept of family health is the bio-psycho- support irrespective of the social strata they belong
social view of man as a social creature, living in a to. The approach would be giving more emphasis
family and in a society with other human beings. on preventive and promotive health care, even
Determinants of health: Determinants of health while optimally utilizing the existing curative
are the range of personal, social, economic and services. The services could be planned under the
environmental factors which determine the health following headings;
status of individuals and populations4. The concept 1. Interventions at child level –
of health determinants denotes a comprehensive Child right perspective
synthetic approach in explaining the complex
i Survival – National programs like IMNCI,
mechanisms by which various factors exert
immunization, RCH, ICDS etc
influence upon health. They represent a framework
for explaining the genesis of health and ways of ii Development – Rashtriya Bal Swasthya
preserving them, far larger than the one in which Kariyakram (District Early Intervention
health services are given the most prominent place. Centres)
The concept of determinants has been changing iii Protection – Child line, Child Welfare
through history. Actual knowledge states that Committee, POSCO Act
determinants act within complex mutual iv Participation – Education, Sarva Shikhsha
interactions and that they have different effects at Abhiyan, adolescent programs
different periods of life. Studies about effects and 2. Intervention at parents’ level –
interactions between determinants apply Need perspective
knowledge gained in public health, sociology,
i Biological and physiological needs - air, food,
psychology, neurology, immunology, biochemistry
water, shelter, warmth, sex, sleep, etc.,
and other sciences. Lately, researches in the area
of human genetics are exploring a new field of ii Safety needs - protection from bad elements,
determinants of health and thereof new preventive security, order, law, stability, etc,

iii Love and belonging needs – friendship, government authorities. The goal of the program
intimacy, affection and love, - from work group, is to develop and implement individualized skill
family, friends, romantic relationships etc, teaching and behavioural strategies with the family
iv Esteem needs – self-esteem, achievement, to achieve positive gains in health and social
mastery, independence, status, dominance, protection. A referral for the service can be made
prestige, managerial responsibility, etc, to the regional health authority by the family or a
service provider (with the consent of the family)
v Cognitive needs - knowledge, meaning of life,
as soon as a problem is suspected or identified by
etc,
community health workers, ASHA workers,
vi Aesthetic needs - appreciation and search for Anganwadi teachers and panchayat/ward members.
beauty, Home support services are intended to supplement,
vii Self-Actualization needs - realizing personal not replace, service provided by the individual
potential, self-fulfillment, seeking personal family and/or any community support network.
growth and peak experiences etc, Community Behavioural Interventions: The
viii Transcendence needs - helping others to Community Behavioural Interventions should be
achieve self-actualization6. a voluntary community-based behavioural support
3. Intervention at grandparents’ level – program modelled on the lines of palliative care,
Quality care perspective that is available to individuals in the family needing
i Family Centered Care: Providing care and special care – disabled, elderly, living alone, single
services that are responsive to the needs mothers, homeless, abused, destitute and other
marginalized groups. The Community Behavioural
ii Ethical Behavior and Consumer Rights:
Interventions should be based on strengths and
Upholding high standards of ethical conduct
weakness of the family and guided by a set of ideals
and advocating for the rights of elderly and their
that promote community inclusion, positive
family caregivers.
programming and least restrictive treatment
iii Safety and Clinical Excellence: Promoting principles. Appropriate community health workers
safety standards of practice while ensuring visit the individual on a regular basis to complete a
appropriate clinical care functional assessment and to develop and monitor
iv Inclusion and Access: Promoting inclusiveness a suitable approach to address behavioural concerns
in our community services, by ensuring that of the individuals. Referral to any Government
all elderly regardless of religion, caste, gender, supported program can be made by the family, a
disability, age or other characteristics have service provider or any empathetic individual in
access to community services. the community.
v) Caregiver Excellence: Fostering a collaborative, 5. Socio-political level interventions –
interdisciplinary environment that promotes Ecologic/social-systems perspective
inclusion, individual accountability and Health and behaviour is an interplay of biological,
workforce excellence, through professional behavioral, and societal influences in the context
development, training, and support to all staff of socio-political realities prevalent at any period.
and volunteers. At the individual level, there is clear evidence of
vi Compliance with Laws and Regulations: efficacy of interventions (i) to establish health-
Ensuring compliance with all applicable laws, protective or health-enhancing behaviors, such as
regulations, and professional standards of diet and physical activity, (ii) to reduce health-risk
practice, and implementing systems and behaviors, such as smoking; and (iii) to facilitate
processes that prevent abuse of the elderly. adaptation to chronic illness, including cancer and
4. Community level interventions – Social justice heart disease. Yet the behavior changes frequently
perspective are difficult to maintain at individual level and the
challenge then is to make it a community behaviour
Home Based Services: The home based services
change model, which in turn requires ecological
should be a combination of government-funded
research and field action research supported by
programs in health, education, social justice, social
epidemiologically sound evidence based health
security mission and others that are delivered by
policy.
the community outlets under the local self-
Conclusion by providing them opportunities to do
The time has come to re-invent, re-focus and postgraduates studies in family medicine.
re-invest in the concept of family doctor, probably References
the cheapest community acceptable mode of 1. Report of the Health Survey and Development
primary care, as has been practiced in many Committee. http://www.nhp.gov.in/sites/default/
developing countries. Family physician or more files/pdf/Bhore_Committee_Report_VOL-1.pdf.
popularly known as family doctor is the specialist Accessed on 5.8.2016
in family medicine devoted to comprehensive 2. Robert D. Mooney. Marriage and Family Living.
health care for people in the family for all ages, Vol. 19, No. 2, Health and Family Welfare (May,
genders, diseases, and systems of the body. Apart 1957), pp. 133-135
from disease prevention and health promotion, most 3. Family Systems Theory. http://web.pdx.edu/~cbcm/
of their time would have to be spent in caring and CFS410U/Family Systems Theory.pdf. Accessed on
counselling family members. Family Medicine 5.8.2016
came to be recognized as a medical specialty in 4. Determinants of health. https://
India only in the late 1990s, and according to the www.healthypeople.gov/ 2020/ about/foundation-
National Health Policy - 2002, there is an acute health-measures/Determinants-of-Health. Accessed
shortage of specialists in family medicine in India. on 5.8.2016
Realizing the fact that family physicians play very 5. Lidia Georgieva, Genc Burazeri, Mariana Dyakova,
important role in providing affordable and universal Bosiljka Ðikanoviæ (eds). Health Determinants in
health care to people, the Government of India is the Scope of New Public Health.http://
now promoting the practice of family medicine by www.snz.unizg.hr/phsee/Documents/Publications/
introducing post graduate training through DNB PH-SEE_Book3_Full_HealthDeterminants.pdf
(Diplomat National Board) programs and MD in 6. Maslow, A. H. Various meanings of transcendence.
family medicine. We have the greatest opportunity In A. H. Maslow, The farther reaches of human
to convert all primary health centres as family nature 1993. (pp. 259–269). New York: Penguin/
health centres manned by doctors in health service, Arkana. (Reprinted from Journal of Transpersonal
Psychology, 1969, 1(1), 56–66.

Perspectives
EXPERIENTIAL LEARNING
Unnikrishnan V V1
Experiential Education is a complex relational model of the experiential learning process and a
process that involves balancing attention to the multi-dimensional model of adult development.3
learner and to the subject matter while reflecting Core concepts in Experiential Learning
on the deep meaning of ideas with the skill of
Experiential Learning Theory4 is built up on
applying them. In its simplest form, experiential
six basic propositions-
learning means learning from experience or
learning by doing. Experiential education first 1. Learning is best conceived as a process, and
immerses learners in an experience and then not in terms of outcomes.
encourages reflection about the experience to 2. All learning is re-learning.
develop new skills, new attitudes, or new ways of 3. Learning requires the resolution of conflicts
thinking. It does this by engaging students in critical between dialectically opposed modes of
thinking, problem solving and decision making in adaptation to the world.
contexts that are personally relevant to them. This 4. Learning is a holistic process of adaptation to
approach to learning also involves making the world.
opportunities for debriefing and consolidation of
5. Learning results from synergetic transactions
ideas and skills through feedback, reflection, and
between the person and the environment.
the application of the ideas and skills to new
situations1,2. 6. Learning is the process of creating knowledge.
Experiential Learning is a philosophy and Experiential Learning occurs when carefully
methodology in which educators purposefully chosen experiences are supported by reflection,
engage with students in direct experience and critical analysis and synthesis. Experiences are
focused reflection in order to increase knowledge, structured to require the student to take initiative,
develop skills, and clarify values. Experiential make decisions and be accountable for results.
Learning Theory provides a comprehensive Throughout the experiential learning process, the
framework to guide the experiential educator in student is actively engaged in posing questions,
enhancing learning and development. It is a investigating, experimenting, being curious,
compendium on the work some of the greatest solving problems, assuming responsibility, being
minds among the educationists of the 20th century, creative and constructing meaning. Students are
namely John Dewey, William James, Jean Piaget, engaged intellectually, emotionally, socially and
Lev Vygotsky, Carl Jung, Paulo Freire, Carl Rogers physically. Relationships are developed and
Kurt Lewin and Mary Parker Follett [Gestalt nurtured: student to self, student to others and
theorists]. Experience is assigned a central role in student to the world at large. The instructor and
human learning and development. A pragmatic mix student may experience success, failure, adventure,
of Philosophical foundations and concrete action risk-taking and uncertainty, because the outcomes
plans helped this theory to develop into a holistic of the experience cannot totally be predicted.
1 Additional Professor of Physiology and Co-ordinator of Medical Education Unit, Govt. Medical College, Thrissur.
Corresponding author: Unnikrishnan V V: E-mail: drvvuk@gmail.com

Opportunities are nurtured for students and Experience and the Learning Cycle
instructors to explore and examine their own values. Learning is defined as “the process whereby
Haynes 5 describes the following steps that knowledge is created through the transformation
comprise experiential learning. of experience. Knowledge results from the
1. Experiencing/Exploring “Doing” combination of grasping and transforming
Students will perform or do a hands-on minds- experience6. ‘Grasping Experience’ refers to the
on experience with little or no help from the process of taking in information. ‘Transforming
instructor. Examples might include: Making Experience’ is how individuals interpret and act on
products or models, role-playing, giving a that information.
presentation, problem-solving, playing a game. A Experiential Learning Cycle is a dynamic view
key facet of experiential learning is what the student of learning driven by the resolution of the dual
learns from the experience rather than the quantity dialectics of action/reflection and experience/
or quality of the experience. abstraction.
2. Sharing/Reflecting “What Happened?” Learning arises from the resolution of creative
Students will share the results, reactions and tension among these four learning modes. In a
observations with their peers. Students will also Learning Cycle or Learning Spiral, the learner goes
get other peers to talk about their own experience, through all these four aspects, namely,
share their reactions and observations and discuss 1. Experiencing
feelings generated by the experience. The sharing 2. Reflecting
equates to reflecting on what they discovered and 3. Thinking
relating it to past experiences which can be used
4. Acting
for future use.
3. Processing/Analyzing “What’s Important?” Immediate or concrete experiences are the basis
for observations and reflections. These reflections
Students will discuss, analyze and reflect upon are assimilated and distilled into abstract concepts
the experience. Describing and analyzing their from which new implications for action can be
experiences allow students to relate them to future drawn.
learning experiences. Students will also discuss
Teacher’s Role in Experiential Learning
how the experience was carried out, how themes,
problems and issues emerged as a result of the The instructor’s primary roles include setting
experience. Students will discuss how specific suitable experiences, posing problems, setting
problems or issues were addressed and to identify boundaries, supporting students, insuring physical
recurring themes. and emotional safety, and facilitating the learning
process. The instructor recognizes and encourages
4. Generalizing “So What?”
spontaneous opportunities for learning. Instructors
Students will connect the experience with real strive to be aware of their biases, judgments and
world examples, find trends or common truths in pre-conceptions, and how these influence the
the experience, and identify “real life” principles student. The design of the learning experience
that emerged. includes the possibility to learn from natural
5. Application “Now What?” consequences, mistakes and successes.
Students will apply what they learned in the In experiential learning, the instructor guides
experience (and what they learned from past rather than directs the learning process where
experiences and practice) to a similar or different students are naturally interested in learning7. The
situation. Also, students will discuss how the newly instructor assumes the role of facilitator and is
learned process can be applied to other situations. guided by a number of steps crucial to experiential
Students will discuss how issues raised can be learning (Wurdinger & Carlson). Accordingly, the
useful in future situations and how more effective Teacher should:
behaviors can develop from what they learned. The 1. Be willing to accept a less teacher-centric role
instructor should help each student feel a sense of in the classroom.
ownership for what was learned.
2. Approach the learning experience in a positive,
non-dominating way.

3. Identify an experience in which students will debriefing9. Once students have been provided with
find interest and be personally committed. the necessary skills and information, the instructor
4. Explain the purpose of the experiential learning then steps back and serves as a resource person,
situation to the students. cheerleader, and facilitator.
5. Share feelings and thoughts with students so Assessment of Experiential Learning
that are learning from the experience is mutual. Assessment is an integral part of the
6. Tie the course learning objectives to course experiential learning process. It provides a basis
activities and direct experiences so students for participants and instructors alike to confirm and
know what they are supposed to do. reflect on the learning and growth that has occurred
and is occurring. The assessment of experiential
7. Provide relevant and meaningful resources to
activities presents a unique problem to instructors.
help students succeed.
It is important to understand that outcomes are
8. Allow students to experiment and discover important to measure, they reflect the end product
solutions on their own. of assessment, not a complete assessment cycle10.
9. Find a sense of balance between the academic Methods for Assessing Experiential Activities
and nurturing aspects of teaching.
There are many potential ways to assess
10. Clarify students and instructor roles. experiential activities, both external and internal.
Student Roles in Experiential Learning These methods are tied to reflection, helping
Students are actively participating in their own learners to focus their learning while also producing
learning in EL. Qualities of experiential learning a product for assessment purposes.
are those in which students decide themselves to Qualters10 recommends the use of Alexander Astin’s
be personally involved in the learning experience. I-E-O (Input-Environment-Output) model for
Students are not completely left to teach assessment:
themselves; the instructor assumes the role of guide
Input: Assess student’s knowledge, skills, and
and facilitates the learning process. Wurdinger lists
attitudes prior to a learning experience
the following roles for students8:
1. Students will be involved in problems which Environment: Assess students during the
are practical, social and personal. experience
2. Students will be allowed freedom in the Output: Assess the success after the experience
classroom as long as they make headway in Moon lists several examples for assessment in EL:
the learning process. • Maintenance of a learning journal or a portfolio
3. Students often will need to be involved with • Reflection on critical incidents
difficult and challenging situations while
• Presentation on what has been learnt
discovering.
• Analysis of strengths and weaknesses and
4. Students will self-evaluate their own
related action planning
progression or success in the learning process
which becomes the primary means of • Essay or report on what has been learnt
assessment. (preferably with reflective writing)
5. Students will learn from the learning process • Self-awareness tools and exercises (e.g.
and become open to change. This change questionnaires about learning patterns)
includes less reliance on the instructor and more • A review of a book that relates the work
on fellow peers, the development of skills to experience to own discipline
investigate (research) and learn from an • Short answer questions of a ‘why’ or ‘explain’
authentic experience, and the ability to nature
objectively self-evaluate one’s performance. • A project that develops ideas further (group or
In addition to these, to enhance these skills, Warren individual)
suggests ways to help students develop their • Self-evaluation of a task performed
capabilities in thinking as a group, decision-
• An article (e.g. for a newspaper) explaining
making, leadership, problem solving, feedback and
something in the workplace

• Recommendation for improvement of some Learning. In: Law B. Learning for a
practice (a sensitive matter) Sustainable Environment. Paris: United Nations
• An interview of the learner as a potential worker Educational, Scientific and Cultural
in the workplace Organization; 2012. Available from: http://
www.unesco.org/education/tlsf/mods/theme_d/
• A story that involves thinking about learning
mod20.html
in the placement
• A request that students take a given theory and 3. Cantor J A. Experiential Learning in Higher
observe its application in the workplace Education. Washington, D.C.: ASHEERIC
Higher Education Report No. 7; 1995.
• An oral exam
4. Kolb DA. Experiential Learning: Experience
• Management of an informed discussion
as the source of learning and development.
• A report on an event in the work situation Englewood Cliffs, N. J.: Prentice-Hall, 1984.
(ethical issues)
5. Bassett DS, Jackson L. Applying the Model to
• Account of how discipline (i.e. subject) issues
a Variety of Adult Learning Situations. In
apply to the workplace
Jackson L, Caffarella, RS (Eds.), Experiential
Experiential Learning Opportunities in Higher Learning: A New Approach. San Francisco:
Education Jossey-Bass. 1994. pp. 73-86.
There are numerous experiential learning 6. Kolb A Y, Kolb D A. The Kolb Learning Style
opportunities in higher education that can be found Inventory 4.0: A Comprehensive Guide to the
in most disciplines. Apprenticeship Experiences, Theory, Psychometrics, Research on Validity
Cooperative Education Experiences, Fellowship and Educational Applications. Boston, MA:
Experiences, Field Work Experiences, Internship Hay Resources Direct; 2013. Available from
Experiences, Service Learning Experiences, www.haygroup.com/leadership and talent on
Student Teaching Experiences, Study Abroad demand
Experiences, and Volunteer Experiences are some
7. Gurpinar E, Bati H, Tetik C. Learning styles of
of the areas of EL in higher education.
medical students change in relation to time.
Conclusion Advances in Physiology Education, 2011,
Experiential Learning help student learn 35(3), 307-311.
through student- centered experiences rather than 8. Wurdinger SD. Using Experiential Learning in
instructor-centered experiences by doing, the Classroom. Lanham: Scarecrow Education;
discovering, reflecting and applying. Through these 2005
experiences, students develop communication
skills, self confidence and decision making skills, 9. Warren, K. The Student-Directed Classroom:
in response to real world problems and processes. A Model for Teaching Experiential Education
This requires thorough planning before Theory. In Warren, K. (Ed.). The Theory of
implementation and careful follow-up thereafter for Experiential Education. Dubuque: Kendall/
ideal results. Hunt Publishing Company; 1995. pp. 249- 258
References 10. Qualters D. M. Bringing the Outside in
Assessing Experiential Education: New
1. Lewis L H, Williams C J. In: Jackson L,
Directions for Teaching and Learning, 2010,
Caffarella R S, Editors. Experiential Learning:
(124), 55-62. Accessed from http://
A New Approach. San Francisco: Jossey-Bass;
ezproxy.lib.ryerson.ca/login?url=http://
1994. pp. 5-16.
search.ebscohost.com/login.aspx?direct=true
2. Cox B, Margaret Calder M, Fien J. Experiential &db=eric&AN=EJ912853&site=ehost-live

Perspectives
CHANGING TRENDS IN
NURSING RESEARCH
Nirmala L1, Athirarani M R2
Introduction administrative and academic levels started the

Florence Nightingale was the pioneer of research activities in an intense manner. The
nursing research and her practice was based on the important studies that came out during1970s were;
evidences from her own observations. The (i) Activity study to define nursing and non-nursing
modernization of nursing profession was possible functions of nurses in health care institutions in
due to her basic understanding of epidemiology and India by Dr Marie Ferguson, a public health nurse
biostatistics. The term evidence based practice was in RAK College of Nursing, and (ii) Trained Nurses
not in use at that time but it was the central concept Associations (TNAI) study on ‘Time utilization and
of her actions. Thus, she was known as the founder socioeconomic status of nurse in India’. In 1986,
of ‘modern nursing’. Nightingale was keen not only the Nursing Research Society of India (NRSI) was
to get the evidences but also to make it established to promote research. Indian Nursing
comprehensible to lay people, politicians and senior Council has introduced research process in BSc
civil servants involved in legislation. Nevertheless, nursing curriculum in the same year. In 2002 INC
somewhere along the line, the research in nursing included nursing research in General Nursing
had lost its momentum and nursing was Midwifery courses and Post Basic BSc nursing
marginalised as an art rather than science. programs.
The past Present
Nightingale’s observations and interpretations Research is part of the basic curriculum in
on mortality conditions during Crimean war nursing. In no other discipline research is
somehow benefited the Indian public health system incorporated in under graduate level. Research is a
also. She educated the army on sanitary conditions separate subject and one has to complete a thesis
in India during and after the Indian Mutiny of 1857, as partial fulfilment of the Master’s Degree course
which led to the establishment of a Sanitary in Nursing. Although the intention of senior nurse
Department within the Indian government. In 1946, educators to uplift the research capabilities in
Bhore Committee recommended the development students are appreciable, most of the time the
of research in nursing. In 1953, the first nurse from quantum of academic research reports produced in
India was sent to Columbia University to earn the state is questionable in terms of its scientific
Doctorate in Education under a WHO fellowship rigor. Thus, the practice of evidence-based nursing
programme. Along with the initiation of MSc could not achieve its applicability in day-to-day
Nursing in Rajkumari Amrit Kaur College of activities in nursing education as well as in nursing
Nursing, New Delhi in 1960, research was included service.
as a full subject with thesis work. Research in Before 2000 there were very few PhD holders
nursing sprouted and the nurses in the in nursing profession but there was a rapid increase
1 Principal, Govt College of Nursing, Thiruvananthapuram

2 Assistant Professor, Govt College of Nursing, Thiruvananthapuram
Corresponding author: Athirarani MR: E-mail-athiraaparna@gmail.com

in the number of PhD scholars. University of Kerala international study on “One Million Global
is offering full time and part time PhD in Nursing. Catheters PIVC Worldwide Prevalence Study”. For
As many nursing faculty were awarded PhD, in turn the first time in India, a senior nursing faculty from
they were qualified as the guides of many Kerala, Prof. Kochuthresiamma Thomas was
universities in Kerala. The National Consortium for awarded ‘emeritus scientist’ status in 2014. I n
PhD in Nursing by Indian Nursing Council in recent years, research in the service side was ably
collaboration with Rajiv Gandhi University of promoted by the nurse administrators in reputed
Health Sciences, Karnataka is a welcome step institutes like Regional Cancer Centre and Sree
forward. Many faculties also pursued higher studies Chitra Thirunal Institute of Medical Science and
in nursing research from universities in and outside Technology. These institutions are conducting
Kerala. research methodology workshop, in-service
From 2009 onwards, faculty from Government training and also mobilizing funds from ICMR and
nursing colleges under Medical Education other national agencies for the conduct of research
Department are being deputed for higher studies studies.
in Clinical Epidemiology at Clinical Epidemiology Future - prospects and challenges
Resource and Training Centre (CERTC), Medical As research is an evidence building enterprise,
College, Thiruvananthapuram. It opened a new nurses are expected to adopt rigorous scientific
arena for research in nursing, providing an inquiry that yield valid and reliable results to bring
opportunity to familiarise and apply methodologies about clinical excellence. Now there is a conducive
like case control studies, diagnostic test evaluation, environment for the growth of research in nursing
process evaluation and tool development, which as the government is providing increments for
were seldom used in nursing studies earlier. In order MPhil and PhD holders, the funding from SBMR
to safeguard the safety and rights of study is more easily accessible, and in all nursing
participants Institutional Research Committee institutions there are IRCs and IECs in place to look
(IRC) and Institutional Ethics Committee (IEC) after the scientific rigor of studies.
were formulated in all Nursing Colleges in Kerala.
The challenges faced by nurse researchers go
These committees assured more elaborate vetting
along a continuum. Some are having only limited
of protocols submitted by the students and faculty.
knowledge in research methodology and
New mandates on research and publication for biostatistics and hence uncomfortable about
the career advancement by UGC and the stipulations of IRCs and IECs. We are in a physician
establishment of State Board of Medical Research dominant healthcare system and nurse is viewed
also benefited the nursing faculty for pursuing as a dependable assistant by most physicians. Some
projects. From 2011-2012 onwards State Board of physicians may still perceive them as one lacking
Medical Research (SBMR) funds were allotted for critical thinking skills. Due to limited autonomy,
nursing faculty. The protocols from nursing faculty the nursing colleges are often poorly funded by the
were also reviewed by the Institutional Research funding agencies and the research evidences
Committee of Medical Colleges. This in turn helped brought by the nurse educators may not always be
to increase the visibility of research in nursing recognized by the medical community. Hence the
among all health professionals. All these facilitated bulk of research results done by nursing graduates
the nursing studies to move forward from the and post graduates are not fully utilized. The
monotypic educational interventions to new traditional system of keeping education, research
methodologies. and practice in compartments is a major challenge.
Since the last 5 years, there was a tremendous Hence we need to build stronger research base in
increase in the number of paper presentations and producing new knowledge specific to nursing and
publications from the nursing faculty all over make sure that they are incorporated as best
Kerala. Before that there were few stalwarts practices. We are hopeful that establishment of a
engaged in research activities. The research works full-fledged Kerala University of Health Sciences
of nursing faculty were appreciated and awarded with constituent Schools and Centres would go a
by the International Research Networking agencies long way in mitigating our apprehensions and
of reputed universities abroad. In 2014 for the first concerns.
time in Kerala, the faculty took part in an

Perspectives
ALLIED HEALTH SCIENCES -

REVISITED
Sankar S*
Introduction medical sonographers, dieticians, medical

The explosion of scientific knowledge that technologists, occupational therapists, physical
followed World War-II ended with many therapists, radiographers, respiratory therapists, and
sophisticated and complex medical, diagnostic and speech language pathologists. AHPs work
treatment procedures. There was increasing public collaboratively with physicians, nurses, dentists,
demand for medical services but it was combined and pharmacists in providing comprehensive and
with higher health care costs. This provoked a trend patient-centred care.
toward expansion of service delivery from treating Challenges and role of allied health professionals
patients in hospitals to care in physician’s private It is generally observed that allied health
and group practices, ambulatory medical and professionals’ (AHPs) contribution to care is often
emergency clinics, and mobile clinics and hidden, overlooked or potentially undervalued.
community-based care. What followed has been an There is little systematic information available at a
increase in the need for skilled health care delivery national level about the quality of care AHPs
personnel worldwide for enhancing these activities. deliver. However, the demand for healthcare
The emphasis on cost-efficient solutions to health workers is growing fast. These points to the value
care delivery also continued to encourage the of the health care workers belonging to this
expansion of the allied health workforce. category. Career opportunities in allied health cover
Allied health professions are a distinct group a wide range and as a result attract a diverse
of health professionals who apply their expertise population of students and practitioners. These
to prevent disease transmission, diagnose, treat and professions face significant future challenges
rehabilitate people of all ages and all specialities. ranging from shortages to demands for new
Together with a range of technical and support staff competencies. Allied health professionals need to
they may deliver direct patient care, rehabilitation, be practical and have a good academic background,
treatment, diagnostics and health improvement including a science-based qualification.
interventions to restore and maintain optimal AHPs will be helping patients to become as
physical, sensory, psychological, cognitive and independent as possible. In order to achieve the
social functions. The Association of Schools of goals, they will work with patients’ needs as a
Allied Health Professions defines allied health priority and on a one-to-one basis. They have to
professionals as the segment of the workforce that deal with patients with maturity, tact and friendly
delivers services involving the identification, approach. Communication skills are vital and they
evaluation and prevention of diseases and disorders; have to be alert to changes in patients’ conditions.
dietary and nutrition services; and rehabilitation and AHPs have to act as part of a team whose collective
health systems management. Allied health focus is the health of people and hence need to be
professionals include dental hygienists, diagnostic able to educate and train other healthcare staff to
* Professor of Pathology, Medical College, Thiruvananthapuram

Corresponding author: Sankar S: E-mail: sankarradhika@rediffmail.com

develop their skills. In short, they have to develop ix Clinical psychology, counselling and
empathy to all patients at all times. The major psychiatric social work – enables training in
challenges faced include a heavy workload, lack psychotherapy, counselling and psychosocial
of adequate skill training, remuneration not work related to mental health and behavioural
commensurate with the work carried out, need for issues and these professionals are important
opportunities for career development and members in the psychiatry team.
development of various subspecialties. x Clinical child development – deals with the
Medical Sub-specialities and functions clinical aspects of child adolescent
Public health needs development of skilled development, early intervention and parent
personnel for handling public health issues in counselling.
hospitals and community. Public Health is an xi Medical physiology, nutrition, microbiology
important area of medical science in which AHPs and biochemistry – concerned with the various
have a major role. They work as team members in clinical aspects of the science of physiology,
hospital clinical work and also major public health nutrition, microbiology and biochemistry.
related programs envisaged by international xii Hospital management – impart skills in hospital
agencies like WHO and several national / administration and management and help the
institutional agencies. The major medical sub- medical director in routine hospital
specialities now available in most hospital settings administration.
include;
Apart from the above, there are many other areas
i Physiotherapy – deals with techniques of in modern medicine and AYUSH where AHPs have
exercise therapy, electro therapy and manual a significant role now and the list is ever expanding
therapy. Similarly, occupational therapists deal as the medical practice progress from art of
with the functional aspect of small muscles, e.g. medicine to science and technology in medicine.
Hand functioning.
Biomedical Engineering sub-specialities
ii Audiology and speech language pathology –
With an aging population and a growing focus
audiology is the science of hearing and
on health-care issues, the demand for more
balancing, the art of its assessment and the
sophisticated medical equipment and procedures
rehabilitation of individuals with hearing and
along with a need for more cost-effective care
balancing disorders. Speech language
delivery is high and hence the need for
pathology deals with speech and language,
bioengineers. They are needed to bridge traditional
deglutition and its disorders.
engineering skills with medical applications,
iii Optometry – deals with diagnostic tests related working hand-in-hand with health-care
to eye disorders and assist ophthalmologists. professionals including physicians, nurses,
iv Dental technology – deals with the science and therapists, and technicians to solve a wide variety
technology of dentistry and support the dental of problems. They are involved in designing
surgeon. instruments, devices, and software to develop new
v Laboratory technology – deals with the procedures or solve clinical problems. In fact,
diagnostic laboratory services in the fields of bioengineering is behind many of the most modern,
biochemistry, pathology and microbiology. ground breaking health-care techniques that are
commonplace today, such as ultrasound, MRI, and
vi Cardiovascular technology – mainly concerned
other imaging techniques, and the development of
with functioning of Cath Labs and other tests
artificial hips, knees, and other prosthetic implants.
in cardiology and assist cardiologists.
They can also take credit for developing
vii Perfusion technology – mainly handles the pacemakers, dialysis machines, and diagnostic
equipment related to perfusion e.g.: heart lung equipment, all for the enhancement of health care.
machines and assist cardiothoracic surgeons. The biomedical engineering society has developed
viii Radiation physics – mainly relates to the a list of the major specialty areas in bioengineering.
applications and maintenance of various They include;
equipment related to radiation therapy and, their i Bioinstrumentation – the application of
safety aspects in assisting radiotherapists. electronics and measurement techniques to

develop devices used in diagnosis and treatment vi Medical Imaging – combines knowledge of a
of disease. unique physical phenomenon (sound, radiation,
ii Biomaterials – includes both living tissue and magnetism, etc.) with high-speed electronic
artificial materials used for implantation. data processing, analysis, and display to
Understanding the properties and behaviour of generate an image.
living material is vital in the design of implant vii Orthopaedic Bioengineering – the specialty in
materials. The selection of an appropriate which methods of engineering and
material to place in the human body may be computational mechanics have been applied for
one of the most difficult tasks faced by the the understanding of the function of bones,
biomedical engineer. joints, and muscles, and for the design of
iii Biomechanics – applies classical mechanics artificial joint replacements. Orthopaedic
(statics, dynamics, fluids, solids, bioengineers analyse the friction, lubrication,
thermodynamics, and continuum mechanics) to and wear characteristics of natural and artificial
biological or medical problems. It includes the joints; they perform stress analysis of the
study of motion, material deformation, flow musculoskeletal system; and they develop
within the body and in devices, and transport artificial biomaterials (biologic and synthetic)
of chemical constituents across biological and for replacement of bones, cartilages, ligaments,
synthetic media and membranes. tendons, meniscus, and intervertebral discs.
iv Genetic engineering and molecular biology – viii Rehabilitation Engineering – a growing
involve more recent attempts to attack specialty area of biomedical engineering.
biomedical problems at the microscopic level Rehabilitation engineers enhance the
utilizing the mechanics of cellular, subcellular capabilities and improve the quality of life for
and genetic structures in order to understand individuals with physical and cognitive
disease processes and to be able to intervene at impairments. They are involved in prosthetics,
very specific sites. the development of home, workplace, and
transportation modifications and the design of
v Clinical Engineering – the application of
assistive technology that enhance seating and
technology to health care in hospitals. Clinical
positioning, mobility, and communication.
engineers are responsible for developing and
maintaining computer databases of medical Systems Physiology – the term used to describe that
instrumentation and equipment records and for aspect of biomedical engineering in which
the purchase and use of sophisticated medical engineering strategies, techniques, and tools are
instruments. They may also work with used to gain a comprehensive and integrated
physicians to adapt instrumentation to the understanding of the function of living organisms
specific needs of the physician and the hospital. ranging from bacteria to humans.

Research Methodology
DIAGNOSTIC TEST EVALUATION-

AN INTRODUCTION
Harikumaran Nair G S1
The diagnostic test design is useful in many for a clinic or a community. Whether these new
situations including validation of a new test, a new tests are useful in a given setting and, if so, which
tool, or even a clinical finding itself. Diagnostic test is most appropriate are questions that can be
test evaluation though often used, is not generally answered only through evaluations in the
being mentioned or highlighted along with the appropriate laboratory, clinical or community
study designs usually listed or discussed. These can settings.
be cross-sectional in design, generally. A test can There are two general approaches to evaluate a
be any method for obtaining additional information new test, a cohort approach and case-control
on health status of a patient. Here, in this design, approach. In a cohort approach, a group of patients
we are trying to categorise subjects with and suspected of having the disease (not proved) is
without disease using both tests, by the new test subjected to both the tests, the new test (index test)
being evaluated (“index test”) and a reference and reference standard test. In a case-control
standard (gold standard) test and estimating approach, the researcher identifies a group of
performance of the new test using the reference patients with known disease and then identifies a
standard (gold standard) considering it as the different group with no known disease. The groups
“truth”. A gold standard (reference standard) is are defined based on symptoms in cohort approach,
nothing but, a scientific method, which is likely to and on disease in case-control approach. Case-
tell us “truth” or “reality” regarding a patient’s control approach though faster and cheaper, is prone
health status as diseased or not diseased. It is true for more biases.
that Gold standards are not error free and not telling
A diagnostic test for a suspected infectious
us “truth” in all situations. At least it has to tell us
condition can be used to demonstrate the presence
“truth” in most of the times. The natural question
or absence of infection, or to detect evidence of a
usually come to our mind is, why do we opt for a
previous infection (like the presence of antibodies).
new test/tool when the gold standard is likely to
Recent technological developments have led to
tell us the “truth” or “reality”. We do research on a
new, rapid diagnostic tests that hold promise for
new test when our gold standard is too expensive,
the improved control of infectious diseases.
not readily available and/or it is invasive and
generally not acceptable under general conditions. Relevance of the new test is an important factor
when we plan to do an evaluation. Polymerase
This is not only true for a new laboratory test,
Chain Reaction (PCR) tests can give us many useful
but for a new tool, we developed, which is designed
1 Professor of Radiology, Govt. T D Medical College, Alappuzha.

Faculty CERTC, Govt. Medical College, Thiruvananthapuram.
Corresponding author: E-mail:harikumarannair@msn.com

information, but it is not readily available in the are usually expressed as percentages. But these are
community and is very expensive. To be relevant, expressed as fractions or as decimals also.
the test should be feasible in the community setting, The accuracy of a test is sometimes used as an
in a clinic, or in a hospital. Scientifically, brain overall measure of its performance and is defined
biopsy may be accurate for diagnosing dementia, as the percentage of individuals for whom both the
but not possible for live patients. test and the reference standard give the same result,
Once the relevance of the new test is assessed, either as positive or negative. Accuracy is the
the researcher has to assess the validity of the test/ proportion of total true positives and true negatives
tool. The basic performance characteristics of a test out of the total patients, usually calculated as a
designed to distinguish infected/diseased from percentage. It is mathematically as, Accuracy =
uninfected/non-diseased individuals are Sensitivity, [(TP+TN)/(TP+FN+FP+TN)] x 100. It is the ability
Specificity, Positive predictive value, Negative of the index test to tell us the truth, whether the
predictive value, Accuracy, Diagnostic Odds Ratios subjects are either truly disease positives or disease
and Likelihood ratios. negatives. These measures of diagnostic accuracy
Sensitivity is the proportion of diseased patients is of limited value and is often difficult to interpret,
reported as new test positive. It denotes the ability simply because, it depends not only on the
of a test to identify correctly all those who have sensitivity, specificity but also on prevalence of
the disease. In other words, sensitivity is the infection/condition under evaluation.
probability that a truly infected/diseased individual Paired indicators, like Sensitivity-Specificity
will have test positivity. Thus, sensitivity, also is pair or PPV-NPV pair, can be a disadvantage in
true positive rate, is usually expressed as a comparing the performance of competing tests,
percentage. Sensitivity = [TP/ (TP+FN)] x 100, especially if one test does not outperform the other
where TP is the number of true positives, and FN on both indicators. Diagnostic Odds Ratio (DOR)1
the false negatives. Specificity is the proportion of is considered as a single measure to assess the
disease-free patients who are reported as test diagnostic performance. It is calculated as DOR =
negative by the new test. It denotes the ability of a (TP/TN)/(FP/TN). Diagnostic odds ratio is a single
test to identify correctly all those who do not have measure of diagnostic accuracy, used for general
the disease. Specificity, is, the probability that a estimation of discriminative power of diagnostic
truly uninfected/non-diseased individual will have procedures/tests. DOR of a test is the ratio of the
test negativity. Thus, specificity is true negative odds of test positivity in subjects with disease to
rate, usually expressed as a percentage. Specificity the odds in subjects without disease (1). DOR
= [TN/ (FP+TN)] x 100, where TN is the number depends significantly on the sensitivity and
of true negatives, and FP is the false positives. specificity of a test. DOR does not depend on
Positive Predictive Value is the proportion of disease prevalence significantly.
patients, really having the disease under evaluation, Likelihood Ratios are more important
out of the total reported as test positives. It indicates parameters than positive predictive value and
the probability that a patient with a positive result negative predictive value. Likelihood Ratio positive
has the disease in question. Positive Predictive (LR+) is the ratio of probability of test positive, in
Value = [TP/(TP+FP)] x 100. Negative Predictive people with disease and probability of positive test,
Value is the proportion of patients, really not having in people without disease. (LR+) = sensitivity/[1-
the disease under evaluation, out of the total specificity]. Likelihood ratio negative (LR-) is the
reported as test negatives. It indicates the ratio of probability of negative test in people with
probability that a patient with a negative result does disease and probability of test negative, in people
not have the disease in question. Negative without disease. Likelihood Ratio (LR-) = [1-
Predictive Value = [TN/(FN+TN)] x 100. PPV and sensitivity]/specificity.
NPV depend not only on the sensitivity and
These performance characteristics of a new test
specificity of the test, but also on the prevalence of
(index text) will have errors if the ‘gold standard’
infection in the sample studied. All these measures
test by itself does not have 100% of sensitivity and

specificity. In other words if the ‘gold standard’ is in this design, like selection bias, reference test bias,
not showing us the ‘truth’. This is particularly spectrum bias, work up bias/verification bias,
challenging when there is no recognized reference measurement bias etc. Spectrum bias and
standard (‘gold standard’) test and when we are verification bias are the most important threats to
forced to take an imperfect gold standard. New tests validity. Spectrum bias is worth mentioning here.
under evaluation that are more sensitive than the A study, which only includes very too ill patients
existing reference standard usually require a (who have more hard findings) and perfectly
composite reference standard than usual. If a healthy patients (like those working) will make a
reference standard (‘gold standard’) is not available test look better than reality. This is “spectrum bias”.
and a composite standard difficult to construct, an Common circumstances in which the diagnostic
appropriate approach will be to report the levels of test evaluation methods are used are: to validate a
‘agreement’ between different tests. In a masterly new tool, to evaluate a screening test or a diagnostic
article on ‘Evaluation of diagnostic tests when there test or to design the same test as a diagnostic test
is no gold standard’, Rutjes AWS et al2 have or as a screening with different suitable cut offs
discussed successfully the difficulties of finding an using a Receiver Operating Characteristic (ROC)
appropriate gold standard in validation studies. curves (ROC) analysis, when a test result is
After reviewing a number of methods that can be obtained as continuous or a discrete variable. If
used to evaluate the index tests in the absence of a more than one test is being evaluated, the
gold standard, they have offered good guidelines evaluations can be sequential or simultaneous and
for researchers on these difficult situations. the tests can be analysed as if we are doing a serial
The reliability of a test is a measure of the testing or parallel testing.
closeness of agreement between test results when The test has to be validated in a second
the conditions for testing change. Reliability in independent group of patients. This step is usually
general, can be measured between observers or two omitted but is required to show that the test is
tests (inter-observer reliability), between two reliable and replicable. When a new test is
observations by same observer or a test (intra- evaluated, there is a risk that the results in the initial
observer reliability) between different test sites, assessment are caused by other factors, as
using different instruments, between different kit something related to the specific group of patients
lots (lot-to-lot reliability) or on different days. The included. Thus, to prove the reliability of the test,
Kappa statistic is a useful measure of agreement of the new diagnostic test requires evaluation in a
tests. This allows the measurement of agreement second independent group of patients. If the results
between sets of observations or test results above in this second group of patients are similar to the
chance alone. results in the first group, then we are comfortable
Lack of resources and expertise limit the ability with the test performance. To make it more
of many developing countries to perform adequate acceptable, the new test (index test) has to be
evaluations of diagnostic tests, and many new tests evaluated under the circumstances in which it is
are marketed directly to end-users who lack the likely to be used in practice. The performance of
ability to assess their performance. tests in different settings can be influenced by many
There are several key indicators, of quality of factors. The differences in the characteristics of the
study, like ensuring adequate reference standard, population or the infectious agent, including the
masking or blinding of test results from one another, prevalence of the condition under study and genetic
adequate sample size, prospective data collection, variation of the pathogen or host, as well as the
avoiding biases and ensuring independence of tests. test methodology are some of the factors.
The decision to perform the reference standard The Standards for Reporting of Diagnostic
should ideally be independent of the results of the Accuracy (STARD) initiative has developed a
test being studied. checklist to ensure that all relevant information are
There are different types of bias that can occur included when the results of studies on diagnostic

accuracy are reported. STARD initiative published 2. Rutjes AWs, Reitsma JB, Coomarasamy A, Khan
in 2003 was an important step to improve the KS, Bossuyt PMS. Evaluation of diagnostic tests
quality of reporting of studies of diagnostic when there is no gold standard. A review of
methods. Health Technology Assessment. 2007
accuracy 3,4. The study is likely to be greatly Dec; 11(50): iii-ix, 1-47.
improved, though some difference of opinion by
3. Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA,
some authors do exist, if approached systematically Glasziou PP, Irwig LM, et al. Towards complete
along the standards including STARD standards, and accurate reporting of studies of diagnostic
for reporting of diagnostic accuracy. accuracy: the STARD initiative. Clin Chem 2003;
49:1-6.
References 4. Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA,
Glasziou PP, Irwig LM, et al. The STARD statement
1. Glas AS, Lijmer JG, Prins MH, Bonsel GJ, Bossuyt for reporting studies of diagnostic accuracy:
PM. The diagnostic odds ratio: a single indicator explanation and elaboration. Clin Chem. 2003;
of test performance. J Clin Epidemiol. 2003 Nov;
49:7-18.
56(11):1129-35.

Health Education
LIFESTYLE DISEASES
AMONG YOUNG ADULTS
major biological and behavioural risk factors
I. INTRODUCTION
emerge and act in early life, and continue to have a
MKC Nair negative impact throughout the life course. The
Vice Chancellor, KUHS. monitoring or tracking of growth pattern and blood
Lifestyle related diseases - including obesity, pressure pattern in children and adolescents is
diabetes mellitus, cardiovascular disease (CVD), important against a background of unhealthy
hypertension and stroke, and some types of cancer lifestyles, including excessive intakes of total and
- are becoming increasingly significant because of saturated fats, cholesterol and salt, inadequate
the changes in dietary and lifestyle patterns among intakes of potassium, and reduced physical activity,
young people. Dietary adjustments may not only often accompanied by high levels of television
influence present health, but may determine viewing. In adolescents particularly, habitual
whether or not an individual will develop diseases alcohol and tobacco use contributes to a raised
such as cardiovascular disease and diabetes much blood pressure.
later in life. In many developing countries including Low birth weight, followed by subsequent adult
India, food policies remain focused only on under obesity, has been shown to impart a particularly
nutrition and are not addressing the prevention of high risk of CHD, as well as diabetes. Risk of
lifestyle related diseases adequately enough. In impaired glucose tolerance has been found to be
order to achieve the best results in preventing highest in those who had low birth weight, but who
lifestyle related diseases, the following strategies subsequently became obese as adults. A number of
must be recognized as the essential policy elements: recent studies have demonstrated that there is an
(i) life course (birth to death) (ii) birth to increased risk of adult disease when intra uterine
adolescence growth pattern (iii) nutrition and growth restriction (IUGR) is followed by rapid
dietary practices (iv) physical activity (v) stress catch-up growth in weight and height. Conversely,
level. there is also fairly consistent evidence of higher
From the available evidence, it may be stated risk of CHD, stroke, and probably adult onset
that; (i) unhealthy diets, physical inactivity and diabetes with shorter stature. Further research is
smoking are confirmed risk behaviours for chronic needed to define optimal growth in infancy in terms
diseases, (ii) the biological risk factors of of prevention of chronic disease. Clustering of risk
hypertension, obesity and dyslipidaemia are firmly factors is an important phenomenon to be taken
established as risk factors for coronary heart seriously.
disease, stroke and diabetes, (iii) an adequate and Although psychologists would say that some
appropriate postnatal nutritional environment is amount of stress is necessary for accomplishing
important, (iv) globally, trends in the prevalence tasks, stress has been postulated to be an important
of many risk factors are upwards, especially those factor in the pathogenesis and development of
for obesity, physical inactivity and, in the lifestyle-related diseases. As a health problem,
developing world particularly, smoking (v) the stress occurs when a person feels that the demands

made on them exceed their ability to cope. When ATP III Classification of LDL, Total, and HDL
we feel under stress, our body kicks into high gear Cholesterol (mg/dL)
to deal with the threat. The more often we are placed LDL Cholesterol – Primary Target of Therapy
under stress, the more often we have to use energy
to cope. There is growing evidence that stress may <100 Optimal
contribute to physical illness such as high blood 100-129 Near optimal/above optimal
pressure, proneness to infection, chronic fatigue and 130-159 Borderline High
even cardiovascular disease. 160-189 High
>=190 Very high
Total Cholesterol
II. DYSLIPIDAEMIA: A QUICK GUIDE <200 Desirable
Sajan Ahmad Z 200-239 Borderline high
Assistant Professor of Cardiology, Pushpagiri >=240 High
Medical College, Thiruvalla.
HDL Cholesterol
Life requires fats. Along with proteins, <40 Low
carbohydrates, vitamins and minerals, lipids are >=60 High
also essential for normal human life and function.
The ‘lipid profile’ of an individual is expressed in ATP III Classification of Serum
terms of the following components: Total Triglycerides (mg/dL)
cholesterol, LDL (Low Density Lipoprotein)
<150 Normal
cholesterol, VLDL (Very Low Density
150-199 Borderline high
Lipoprotein), TG (Triglycerides) and HDL (High
200-499 High
Density Lipoprotein) cholesterol.
>=500 Very high
Definition and diagnosis
Any abnormality in the levels of the lipid Causes of dyslipidaemia
fractions in the blood is referred to as Dyslipidaemia is mostly a genetic disease, with
dyslipidaemia. It may indicate high levels of ‘bad’ a positive family history being found in many
(LDL) cholesterol or low levels of ‘good’ (HDL) patients. However, lifestyle influences are very
cholesterol. Traditionally, dyslipidaemia is important too, especially diet and physical activity
diagnosed by estimating the ‘fasting’ lipid profile. levels. Obesity, diabetes mellitus, insulin resistance,
However, even non-fasting lipid profile can give and metabolic syndrome can lead to dyslipidaemia.
sufficient information. Secondary causes like hypothyroidism, liver
Risks disease, renal disease and drug effects should
Dyslipidaemia is strongly associated with always be excluded in patients detected to have
atherosclerosis and vascular disease, including dyslipidaemia.
coronary artery disease, myocardial infarction, Prevention
stroke and peripheral arterial disease. The adverse A healthy lifestyle is the best way for
consequences of dyslipidaemia can be amplified prevention. Adequate physical activity, a low – fat
by the coexistence of other cardiovascular disease diet and avoidance of smoking are required. Healthy
risk factors like diabetes mellitus, systemic adults of all ages should have 2.5 – 5 hours a week
hypertension, obesity and smoking. of aerobic physical activity of at least moderate in
Classification system of lipid levels based on the intensity. It is preferable to do this in multiple
Adult Treatment Panel III (ATP III) guidelines sessions each lasting at least 10 minutes and evenly
(Source: Third Report of the National Cholesterol spread throughout the week (at least 4-5 days/
Education Program (NCEP) Expert Panel on week).
Detection, Evaluation, and Treatment of High ESC/EAS Recommendations for a ‘Healthy diet’
Blood Cholesterol in Adults - Adult Treatment
Panel III, Circulation 2002) (Source: European Society of Cardiology/European

Atherosclerosis Society Guidelines for the the plaque, can appear as early as 15 years in the
management of dyslipidaemias, European Heart coronaries, implying that atherosclerosis starts in
Journal 2011). adolescence and accelerates in the adult, leading
Saturated fatty acids to account for <10% of to CVD.
total energy intake, through replacement by While dyslipidaemia, which is the biochemical
polyunsaturated fatty acids. forerunner of atherosclerosis, causes adverse events
Trans-unsaturated fatty acids: as little as immediately in an adult, it may not do so in children
possible, preferably no intake from processed and adolescents. But its effect may operate late in
food, and <1% of total energy intake from adulthood and hence a case be made in picking up
natural origin and treating dyslipidaemia in the young.
<5 g of salt per day. Dyslipidaemia can be defined as an abnormality
where Total Cholesterol is high; LDL cholesterol
30-45 of fibre per day, from wholegrain
is high and HDL cholesterol low, with high
products, fruits and vegetables.
triglycerides. The NCEP values for S. Cholesterol
200 g of fruit per day (2-3 servings). in the young are as follows.
200 g of vegetables per day (2-3 servings).
NCEP values for S. Cholesterol
Fish at least twice a week, one of which to be
oily fish. Total LDL
Consumption of alcoholic beverages should Cholesterol Cholesterol
be limited to two glasses per day (20 g/day of
Normal <170 mg/dl <130 mg/dl
alcohol) for men and one glass per day (10 g/
day of alcohol) for women. Borderline 170- 200 mg/dl 130-160 mg/dl
Treatment of dyslipidaemia High >200 mg/dl >160 mg/dl
The primary target of treatment is to optimize
the LDL level. Therapeutic lifestyle changes (TLC) *HDL cholesterol should be normally above 35 mg/dl
form the cornerstone of treatment. This involves and triglyceride below 150 mg/dl.
reduction of cholesterol content in food to <200 We cannot ‘screen’ all children or adolescents.
mg/day and saturated fat content in diet to <7% of The reasonable method is to screen high risk
calories. Increased intake of viscous soluble fibre individuals. Usually total cholesterol is used as an
in diet to 10-25 g/day is also recommended. Weight initial tool for screen and if required, a full lipid
reduction and regular physical activity are helpful profile can be ordered. Once we get a full lipid
too. The major drugs used for treatment are the profile, if abnormalities are picked up, one must
HMG CoA Reductase inhibitors or ‘statins’ (e.g. look for secondary causes of dyslipidaemia like
atorvastatin, rosuvastatin). Medications should be hypothyroidism, Chronic Kidney Disease and
started only under supervision of a qualified Nephrotic syndrome. In the management of
medical practitioner. Dyslipidaemia, one can use: (i) diet, (ii) exercise,
(iii) drugs, (iv) a combination of above.
Diet Management
III. DYSLIPIDAEMIA IN THE YOUNG: It can be (a) Modification, (b) Supplementation.
DIET THERAPY Modification involves appropriate amount of
Zulfikar Ahamed M carbohydrate, proteins and fat. Fat content can be
Professor of Paediatric Cardiology, Medical College, modified / restrained in total fat, saturated fat, Poly
Thiruvananthapuram. Unsaturated Fatty Acid (PUFA) and Medium Chain
Cardiovascular Diseases (CVD) account for at Fatty Acid (MCFA). Cholesterol content is also
least 35% of death in India and is increasing in modified. Diet supplementation involves use of
prevalence, both in rural and urban settings. The fibre, plant sterols/ stanols and omega 3 fatty acid.
single final common pathway to CVD is The basic premise of diet manipulation can be Step
atherosclerosis, which is intimately linked to lipid I diet and step II diet. They are also called Child I
metabolism. The sine qua non of atherosclerosis, and Child II diet.

Child I Child II Diet The drugs work, especially the statins. There must
be close monitoring when statin is used on
Child I Child II
childhood.
CHO (as %) 50-55 50-55 <2 years : Statins contraindicated
Fat (as %) 30 25-30 2-10 years : Statins relatively contraindicated
Saturated fat 10 7 >10 years : Statins can be given
Cholesterol <300 mgm/day <200 mgm/day There should be no fat restriction below 2 years.
<10 <10 Treating specific situations
PUFA
1. Hyper-Trigyceridemia: One must look for co
Trans fat None None morbidity like diabetes and obesity.
These dietary steps can be translated into practical Hypertriglyceridemia is not usually directly treated.
diet prescription by dieticians and adhered to. The One must achieve glycaemic control, control of BP,
diet prescribed should be culturally acceptable and stop smoking and modify diet. Diet management
may vary from place to place. is by following Child 1 & Child II diets.
The general guidelines in diet management can Fibre could be added to the diet. Fibric acid is added
be. only when S.TG is>1000 mg /dl.
Skimmed milk to be used. 2. Polygenic Hyperlipoproteinaemia: Start with
step I diet (Child I) and move over to Child 2 diet.
Vegetable oils low in trans-fat and saturated fat
Fibre can be incorporated with addition of Omega
to be used
3 fatty acids. Additional measures will include
No or minimal animal fat
exercise, weight reduction and stopping smoking.
Consumption of more fish and legumes
Drugs are used as a last resort. Statins are given
Consumption of less meat and poultry only when LDL cholesterol is >190mg/in spite of
Egg yolk<3 /week 6 months of lifestyle modification or >160 with
Vegetables and fruits additional risk factors. The other drugs are Niacin,
No refined sugars Bile acid sequestrants (BAS) and Ezetemibe.
Diet Supplementation: It involves use of 3. Familial Hyper Cholesterolemia: Should be
(a) Fiber: Can be oat bran, psyllium or Isabgol managed aggressively with initial Child II diet,
husk. Use of fiber may reduce cholesterol level fibre and Omega 3 fatty acids. Statins may have to
by 8-10% be administered depending on the age and LDL
cholesterol values.
(b) Sterol/Stanol: These supplements may also
reduce lipid values Diet manipulation, either by modification and/
or supplementation is the leading choice for treating
(c) Omega 3 fatty acids: can be useful in reducing
almost all forms of dyslipidaemia in children. There
lipid levels (10% reduction)
is a substantial (10%) reduction in target lipids with
Drug Therapy: It has been evaluated by trials, this regimen. This should logically reduce future
mostly in familial hypercholesterolemia and adult lipid values and thereby prevent acceleration
familial combined hypolipoproteinaemia. Niacin, of atherosclerosis. Drugs are used only sparingly
bile acid sequestrants and statins have been used. in childhood dyslipidaemia.
Intervention
Intervention Familial Non- Hyper

Hypercholesterolemia Familial Triglyceridemia
Diet Child I& II ++ +++ ++
Fibre ++ ++ +
Omega 3 Fatty Acid ++ ++ +
Statin ++ + +
Fibric Acid _ _ +

IV. HYPERTENSION IN Magnitude of the problem
ADOLESCENTS AND CHILDREN Several school surveys have documented the
Krishnakumar R, prevalence of high blood pressure among children
Professor and Head, Department of Pediatric and adolescents. Hypertension in normal weight
Cardiology, AIMS, Cochin. children can be in the range of 3% to 5%. The same
Hypertension or high blood pressure is a major can be as high as 15% to 25% among children and
contributor to the global burden of disease. adolescents who are overweight or obese.
Worldwide, approximately 8 to 10 million Causes of High blood pressure in children and
premature deaths are attributed to high blood adolescents
pressure annually. Roughly half of stroke and High blood pressure in children younger than
ischemic heart disease events worldwide are 10 years old is usually caused by other medical
attributable to high blood pressure. The significance conditions like kidney diseases, hormonal
of high blood pressure in childhood and abnormalities and certain cardiovascular diseases.
adolescence is based on observations that confirm In addition, high blood pressure in these young
a strong tracking of blood pressure levels from children can also develop for the same reasons it
childhood to adulthood. does in adults like being overweight, eating a poor
Blood pressure is the force of blood as it flows diet and not exercising adequately. Hypertension
through the body’s vessels. Under normal in older children and adolescents are most
conditions, the heart pumps blood through the commonly caused by being overweight, poor diet
vessels all over the body. The vessels widen and and sedentary behaviour. A family history of high
contract as needed to keep blood flowing well. In a blood pressure increases the chance of hypertension
person with hypertension, however, the blood in children and adolescents.
pushes too hard against the blood vessels, which Preventing high blood pressure in children and
can cause damage to blood vessels, the heart, the adolescents
kidneys and other organs. Hypertension in children Lifestyle changes, such as eating a heart-
is blood pressure that’s the same as or higher than healthy diet and exercising more, can help reduce
95% of children who are the same sex, age and high blood pressure in children. But, for some
height. There isn’t a simple target blood pressure children, medications to lower blood pressure levels
reading that indicates high blood pressure in all ages may be necessary. Medications are indicated if the
for children, because what’s considered normal blood pressure levels are too high or if lifestyle
blood pressure changes as children grow. interventions fail to reduce blood pressure even
after a trial of 6 months.
Lifestyle Modification Strategies
Lifestyle modification Comment

Weight reduction if overweight Interventions required for weight reduction include dietary
restrictions, exercise programs or both.
Regular physical activity Engage in 60 minutes or more of moderate aerobic physical activity
on most days a week e.g. jogging, running, cycling, swimming.
Eat a healthy diet Emphasize adequate consumption of fresh fruit and vegetables,
fibre, non-fat dairy
Diet restrictions Reduce the intake of sodium to less than 1.5 grams/ day. Avoid
salty foods like chips and pickles. Avoid junk food items like high
calorie sugar drinks, pastries and fried foods.
Healthy Habits Avoid tobacco and alcohol.
Family based interventions Involving the family for diet and physical activity changes for the
entire household has been shown to improve success rates than
targeting individual adolescents/children.

V. DIABETES MELLITUS dysfunction. It is rising to epidemic proportions in
Ranjit Sanu Watson India.
Associate Professor of Medicine, Medical College, Types
Thiruvananthapuram There are three main types of diabetes mellitus:
Diabetes mellitus is a group of metabolic Type 1 DM
diseases in which there is hyperglycaemia over a Type 2 DM
prolonged period and leads to multi-organ Gestational diabetes
Criteria for diagnosis of diabetes and pre-diabetes

ADA Goal for
Diabetes Test* Diagnosis of Increased risk
Diabetes [Prediabetes]/IFG
HbA1c or using a method certified by NGSP

>=6.5% 5.7-6.4%
and standardized to the DCCT assay
Fasting Plasma Glucose or Fasting is defined >= 126 mg/dL 100-125 mg/dL
as no caloric intake for at least 8 hours.or (7.0 mmol/L) (6.9 mmol/L)
2 Hour Plasma Glucose [OGTT] or the test

should be performed as described by the >=200 mg/dL 140-199 mg/dL
WHO, using a glucose load containing the (11.1 mmol/L) (7.8-11.0 mmol/L)
equivalent of 75 g anhydrous glucose
dissolved in water.
Source: American Diabetes Association Diabetes Guidelines, Diabetes Care 2015*
In addition, Random plasma glucose >200 mg/ Triglyceride level >= 250 mg/dl
dL (11.1 mmol/L) in persons with symptoms of Polycystic ovary syndrome
hyperglycaemia or hyperglycaemic crisis is also History of vascular disease
included in the criteria for diagnosis.
The recommended lifestyle interventions
Risk Factors for Diabetes include:
(Source: ADA 2015 Guidelines)
Taking two and a half hours each week of
Age >= 45 years moderate intensity physical activity or one hour
Overweight (BMI > 25 kg/m2) and 15 minutes of high intensity exercise.
Family history of diabetes (i.e. parents or Losing weight gradually to achieve a healthy
siblings with diabetes) BMI
Habitual physical inactivity Replacing refined carbohydrates with whole
Race/ethnicity (e.g. African Americans, grain foods and increase intake of vegetables
Hispanic Americans, Native Americans, Asian and other foods high in dietary fibre
Americans and Pacific Islanders) Reducing the amount of saturated fat in the diet
Previously identified as pre-diabetes: Impaired Control hypertension, dyslipidaemia
fasting glucose (IFG) or Impaired glucose Exercise options
tolerance (IGT)
Brisk walking
History of gestational diabetes or delivery of a
baby weighting > 9 lb Cycling on relatively flat terrain
Hypertension (>= 140/90 mmHg in Adults) Water aerobics
HDL cholesterol <= 35 mg/dl and/or a Using a manual lawnmower

Jogging and obesity are defined using age and sex specific
Football nomograms for body mass index (BMI). Body mass
index is calculated using the formula, BMI =
Skipping
Weight in kilograms divided by height in meters
A healthy BMI range is: squared. Children with BMI equal to or exceeding
Between 18.5 and 24.9 the age-gender-specific 95th percentile are defined
Or between 18.5 and 22.9 for people of South obese. Those with BMI equal to or exceeding the
Asian descent 85th but are below 95th percentiles are defined
For those with a BMI above the healthy range, overweight and are at risk for obesity related
aim to achieve weight loss gradually, with a comorbidities.
target to reduce weight by 5 to 10% over a Some common co-morbid conditions related to
period of a year. obesity in adolescents and children are
A higher amount of fibre in the diet should be cardiovascular (high blood pressure, early
encouraged by including wholegrain foods in the atherosclerosis) endocrine (Insulin resistance,
diet and consuming more vegetables, fruits and Diabetes, menstrual abnormalities, polycystic
beans. The advice on fat is to reduce overall fat ovarian syndrome) gastrointestinal (gall stones,
intake, and particularly to reduce intake of saturated cirrhosis, non-alcoholic steato-hepatitis)
fat as found in chips, crisps, pastries, biscuits and neurological, orthopaedic and psychosocial.
samosa. Choosing lean meats, such as skinless Metabolic syndrome defined as a group of risk
chicken and turkey helps to cut down on saturated factors, including obesity, dyslipidaemia, impaired
fat. It is recommended to eat less processed meats. glucose metabolism and elevated blood pressure
Grilling and steaming food will cut down on fat (all major predictors for cardiovascular disease is
intake in comparison with cooking methods frequently encountered.
involving frying or roasting. Reducing portion sizes The causes of obesity are multifactorial
will also help to lower calorie intake. The Diet Plate including genetic, neuroendocrine, metabolic,
is an excellent solution if you are looking to control psychological, and environmental and socio-
your calorie intake. cultural factors. It is now seen that obesity is more
Stress has been recognised a risk factor for type prevalent in children of low socioeconomic status
2 diabetes. When an individual is stressed their in developed countries and high socioeconomic
body responds with the threat response. The human status in developing countries. Environmental risk
body undergoes a number of changes; stress factors include poor food choices, less consumption
hormones are released that increase blood pressure, of fruits and vegetables, less physical activity and
a surge in blood glucose levels and activates the sedentary hobbies and recreation. The management
immune system. of obesity include dietary management,
enhancement of physical activity, restriction of
sedentary habits, and in selected cases
VI. OBESITY AND POLY-CYSTIC pharmacological and surgical management. The
OVARIAN DISEASE: A GROWING ideal option would be preventive strategies for
CONCERN AMONG THE YOUTH obesity, which means preventing children and
Reshmi CR young adults with BMI within range of normal or
Associate Professor of Gynaecology, Govt overweight from reaching obese range.
Medical College, Thrissur
PCOS is a heterogeneous disorder of uncertain
Obesity has become a colossal epidemic cause with a strong evidence of genetic
causing serious public health concern among predisposition and is the most common endocrine
children and young adults, in most parts of the disorder among women between the ages of 18 and
world. The last two decades have witnessed a 44. It affects approximately 5% to 10% of this age
dramatic increase in healthcare costs due to obesity group. It is one of the leading causes of poor
and related issues among children and youth in both fertility. Symptoms include irregular or no
developed and developing countries of all socio- menstrual periods, heavy periods, excess body and
economic groups, irrespective of age, sex or facial hair, acne, pelvic pain, difficulty in getting
ethnicity. For children and adolescents, overweight pregnant, and patches of thick dark skin especially

over neck. The Rotterdam consensus is the most Hirsutism and male pattern balding consistent
widely accepted criteria for diagnosis across with hyper-androgenism
Europe, Asia and Australia. The Rotterdam Criteria Irregular or absent menstrual cycles
require the presence of two of the following:
Sub fertility or infertility
1. Oligo/anovulation
Psychological symptoms – anxiety, depression,
2. Hyper-androgenism psychosexual dysfunction, eating disorders
clinical (hirsutism or less commonly male Metabolic features – obesity, dyslipidaemia,
pattern alopecia) or diabetes
biochemical (raised FAI or free testosterone) Management of PCOS
3. Polycystic ovaries on ultrasound Management of PCOS requires identification
Other aetiologies must be excluded such as and management of current symptoms, attention
congenital adrenal hyperplasia, androgen secreting to fertility and emotional concerns, as well as
tumours, Cushing syndrome, thyroid dysfunction preventive activities to minimize the risk of future
and hyper prolactinaemia. associated health problems. Polycystic ovary
Clinical Presentation syndrome is a common, lifelong condition that
appears to be increasing in prevalence with
There is a range of symptoms that women may
increasing obesity, and is more common in Asian
experience and present with if they have PCOS and
women. The focus should be on accurate diagnosis,
these can vary with age.
prevention and management of excess weight gain,
In younger women, reproductive symptoms as well as long-term support and management of
predominate. The prevalence of metabolic features psychological, metabolic and reproductive health.
increases with age but can also occur in younger A team approach is often required for
women who are overweight. psychological, nutritional and behavioural support.

Health Sciences
The Official Peer Reviewed Journal of Kerala University of Health Sciences
INSTRUCTIONS TO AUTHORS
About Health Sciences
Health Sciences is the official publication of the Kerala University of Health
Sciences (KUHS). The permanent Editorial Office of the Health Sciences is situated
at KUHS, Thrissur, Kerala. It is published quarterly and is provided complimentary
to all institutions under KUHS and on subscription to individuals and institutions.
The journal gives priority to clinical and experimental studies important contributions
related to health problems in India.
Objectives of Health Sciences
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practice of Health Sciences.” The specific key objectives are:
1. To publish original, peer reviewed articles, which are relevant and well
researched on issues related to health from all health science streams under
KUHS.
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including inter disciplinary areas such as ethics, law, environment and social
sciences, politics economics etc.
4. To report KUHS policy, as appropriate, maintaining editorial independence,
objectively and responsibly.
5. To practice ethical medical journalism and to produce a credible, enjoyable
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All submitted manuscripts should be original, done using appropriate
methodogy, data used is sound. The conclusions arrived should be reasonable,
important and supported by the data provided in the manuscript. The article
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serious scientific flaws, major ethical issues to be addressed. The articles without
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or not in accordance with the current priorities of the journal will be rejected.
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Articles can be submitted as Research Papers, Reviews, Perspectives, short
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manuscript should be accompanied with structured Abstract in not more than
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and Methods, Results and Discussion (IMRAD). Number of tables is limited to a
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need to be followed: (i) the topic should be health related and specific (ii) word
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communication: Submissions as Short write-ups on recent guidelines /
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April - June 2016

KERALA UNIVERSITY OF HEALTH SCIENCES

4 Health Sciences The Official Journal of Kerala University of Health Sciences

Vice Chancellor’s Page: Prof (Dr) M K C Nair. 07

Health Sciences April - June 2016 5

Health Sciences April - June 2016 7

Health Sciences April - June 2016 9

PREVALENCE OF OBESITY AMONG

Geetha S1, Nair MKC2

Abstract hyperinsulinemia, hypertension, and early

1 Additional Professor of Paediatrics, SAT Hospital. Medical College, Thiruvananthapuram

Health Sciences April - June 2016 11

12 Health Sciences The Official Journal of Kerala University of Health Sciences

Table 2: BMI distribution of the study sample

Summary statistics 13 years 14 years 15 years

Table 3: Comparison of Prevalence rates using different cut-off values

Health Sciences April - June 2016 13

Table 4: Comparison of BMI between school categories

Table 5: Comparison of Prevalence rates in government and private schools

Prevalence with confidence interval

Discussion girls in the Reproductive, Maternal, New-born,

14 Health Sciences The Official Journal of Kerala University of Health Sciences

Health Sciences April - June 2016 15

16 Health Sciences The Official Journal of Kerala University of Health Sciences

ASSOCIATION OF OVERWEIGHT AND

Sreekumari R1, Nair M K C2, Nirmala C3

Abstract abdominal circumference more than 88 cms was

1 Additional Professor of Obstetrics and Gynaecology, GMC Thiruvananthapuram

Health Sciences April - June 2016 17

18 Health Sciences The Official Journal of Kerala University of Health Sciences

Table 1: Socio-Demographic variables and family history

Cases Controls Test P value

Religion Hindu 83 (73.5) 91 (80.5) 2.53 0.28

Education High School 48 (42.5) 60 (53.1) 2.55 0.11

Occupation Unemployed 101 (89.4) 105 (92.9) 0.89 0.35

Income Rs <3000. 77 (68.1) 85 (75.2) 2.07 0.56 Rs

Family history Yes 9 (8) 3 (2.7) 3.17 0.07

Family history Yes 21 (18.6) 12 (10.6) 1.92 0.09

Health Sciences April - June 2016 19

Table 3: Case-control comparison

20 Health Sciences The Official Journal of Kerala University of Health Sciences

Health Sciences April - June 2016 21

22 Health Sciences The Official Journal of Kerala University of Health Sciences

DIAGNOSTIC TEST EVALUATION OF Ig M

Kavita Raja1, Rema Devi S2, Soja V3, Shenoy KT4

Abstract Results: A total of 100 patients were selected. Of

Health Sciences April - June 2016 23

24 Health Sciences The Official Journal of Kerala University of Health Sciences

Health Sciences April - June 2016 25

TABLE 1: Evaluation of Lepto Tek Dri-Dot

TABLE 2: Evaluation of IgM ELISA

TABLE 3: Evaluation of paired IgM ELISA using the Gold standard

26 Health Sciences The Official Journal of Kerala University of Health Sciences

TABLE 5: Summary table comparing the parameters of the various tests.

Tests Sensitivity Specificity PPV NPV LR+ LR-

Series** 0.5 0.72 0.76 0.45 1.8 0.69

*Any one positive taken as test positive.

Health Sciences April - June 2016 27

Krishnakumar U1, Girish HC2, Vinay Chandra R3

Abstract responds to them, eliminates them from the body,

Health Sciences April - June 2016 29

30 Health Sciences The Official Journal of Kerala University of Health Sciences