Transactions of the Royal Society of Tropical Medicine and Hygiene 106 (2012) 273–282

Contents lists available at SciVerse ScienceDirect

Transactions of the Royal Society of

Tropical Medicine and Hygiene
journal homepage: http://www.elsevier.com/locate/trstmh

Review

Fifty years of dengue in India

Anita Chakravarti a , Rohit Arora b , Christine Luxemburger c,∗
a
Maulana Azad Medical College, Bahadur Shah Zafar Marg, New Delhi, Delhi, 10002, India
b
Sanofi Pasteur India, 54/A, Sir Mathuradas Vasanji Road, Andheri (East), Mumbai 400 093, India
c
Sanofi Pasteur, 2 av Pont Pasteur, F69367, Lyon Cedex 07, France

a r t i c l e i n f o a b s t r a c t

Article history: Dengue is the most important mosquito-borne, human viral disease in many tropical and
Received 19 May 2011 sub-tropical areas. In India the disease has been essentially described in the form of case
Received in revised form series. We reviewed the epidemiology of dengue in India to improve understanding of its
21 December 2011
evolution in the last 50 years and support the development of effective local prevention and
Accepted 23 December 2011
Available online 21 February 2012
control measures. Early outbreak reports showed a classic epidemic pattern of transmission
with sporadic outbreaks, with low to moderate numbers of cases, usually localized to urban
Keywords:
centres and neighbouring regions, but occasionally spreading and causing larger epidemics.
Dengue Trends in recent decades include: larger and more frequent outbreaks; geographic expan-
Epidemiology sion of endemic transmission; spread of the disease from urban to peri-urban and rural
Outbreaks areas; an increasing proportion of severe cases and deaths; and progression to hyperen-
India demicity, particularly in large urban areas. The global picture of dengue in India is currently
Review that of a largely endemic country. Understanding demographic differences in infection rates
Dengue virus and severity of dengue has important implications for the planning and implementation of
effective public health prevention and control measures and targeting of future vaccination
campaigns.
© 2012 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd.
All rights reserved.

1. Introduction fatal;2,3 death usually results from circulatory collapse due

Dengue emerged in the second half of the twentieth
century as a major public health concern in many tropical
and sub-tropical regions around the world. It is currently
the most important mosquito-borne, human viral disease
in terms of both the number of cases and the number of
deaths. Dengue is considered a major global threat by the
World Health Organization (WHO).1
Dengue virus (DENV) infection results in a broad spec-
trum of clinical presentations, ranging from asymptomatic
or a mild, non-specific fever, to classic dengue fever (DF),
and severe presentations such as dengue hemorrhagic
fever (DHF) or dengue shock syndrome (DSS) which is often
∗ Corresponding author. Tel.: +33 4 3737 7612.
E-mail address: christine.luxemburger@sanofipasteur.com
(C. Luxemburger).
to massive plasma leakage.2,3 There is no specific treatment
for DHF or DSS although with proper clinical diagnosis and
management fatality rates are less than 1%.1
There are four closely related DENV serotypes (DENV-
1 to DENV-4). Infection is thought to confer lifelong
immunity against variants of the same serotype but only
partial and transient (2–3 months) cross-protection against
infection by other serotypes, so one can be re-infected
sequentially with DENVs of different serotypes.1 There is
evidence that secondary heterotypic DENV infections may
carry an increased risk of developing severe forms of the
disease.4
Until recently, the burden of dengue may not have
been as widely recognized in India compared with other
Asian countries, in particular Thailand, Vietnam and the
Philippines. However, since the mid-1990s, epidemics of
dengue in India have become progressively larger and more

0035-9203/$ – see front matter © 2012 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.trstmh.2011.12.007
274 A. Chakravarti et al. / Transactions of the Royal Society of Tropical Medicine and Hygiene 106 (2012) 273–282
frequent, usually starting in urban centres and quickly
spreading to neighbouring regions. India became endemic
for both DF and DHF as transmission became sustained
during the inter-epidemic periods in large parts of the
country.5,6 Moreover, recurring dengue epidemics eventu-
ally resulted in the establishment of hyperendemic areas,
typically large, densely populated cities where several or
all four DENV serotypes circulate in a sustained fashion.6
The public health importance of dengue in India is now
acknowledged, but its epidemiology has been described in
the literature primarily in the form of case series reporting
on individual outbreaks and there are few comprehensive
reviews.6–9 The purpose of this review is to provide an
overview of available data on the epidemiology of dengue
in India to improve the understanding of its evolution in
recent decades and support the development of effective
prevention and control measures.
The disease pattern of dengue in India is described using
annual numbers of reported cases and deaths and their geo-
graphic distribution, where available, together with data
on gender, age distribution, rural spread, and seasonality.
Serotype circulation data is summarized by calendar year
and state.
1.1. Literature search
Details of the literature search for papers on dengue are
shown in Box 1.
2. Discussion
2.1. Early epidemics of dengue in India
Sporadic outbreaks of DF have been reported in India
for over two centuries,2,7 but the earliest virologically con-
firmed outbreak occurred in 1956 in Vellore, Tamil Nadu.8
The first large epidemic of dengue began in 1963 in Cal-
cutta, West Bengal, from where it spread to other states,
eventually affecting most of the country.6 This was the
first dengue epidemic in India with significant numbers of
DHF cases, with up to 30% of cases showing hemorrhagic
manifestations, and resulted in 200 deaths.7–10
In the following years a number of DF outbreaks
occurred in various parts of the country, but only a few
sporadic DHF cases were reported. However, there was no
Box 1. Literature search
• A preliminary search for English language papers in Medline
database with keywords ‘dengue’ AND ‘India’ AND ‘epidemiol-
ogy’ identified 251 papers published between 1965 and 2010.
• Manuscripts describing the same epidemic from different
angles (e.g., clinical features and laboratory findings) were
grouped so as to not duplicate the number of cases.
• An additional search was done in journals published in India.
• Reference lists from these manuscripts were reviewed to iden-
tify additional manuscripts.
• Finally, data obtained from the Indian National Vector Borne
Disease Control Program (NVBDCP) and WHO sources were
reviewed and summarized.
established dengue surveillance system, and no tangible
data are available until the return of large epidemics in
the 1990s. India then experienced two major epidemics,
the first in 1993, followed in 1996 by the largest epi-
demic of DF/DHF to date. The 1996 epidemic started in
the areas around Delhi11–13 and spread rapidly across most
of the country, causing a reported 16 517 cases and 545
deaths.14,15 Delhi was the most severely affected region
with 10 252 cases and 423 deaths (respectively 62.0% and
77.6% of the overall figures);14 substantial numbers of
cases and deaths were also reported from the neighbour-
ing states of Haryana,16,17 Punjab,18–20 Rajasthan, Uttar
Pradesh21 and two southern and western states.14 The pro-
portion of severe clinical presentations, i.e., of DHF/DSS
cases, was particularly high in this epidemic resulting in
the highest case fatality rate (CFR) recorded for the whole
of India (CFR 3.3%).
2.2. Dengue surveillance system in India
The scale and severity of the 1996 DHF epidemic
prompted a series of coordinated responses at state and
national level. A passive surveillance program was set
up by the Indian government. Official disease surveil-
lance systems come under the responsibility of state
government and data is centralized by the National Vector
Borne Disease Control Program (NVBDCP). The NVBDCP
also developed guidelines for the prevention and control
of dengue and assisted state governments with their
programs, for example by standardizing methods for case
detection and vector control.5
Dengue cases were monitored through a passive
surveillance approach. Passive surveillance relies on
disease notification by health care professionals who
are required to report all suspected cases of reportable
diseases. Such systems have low sensitivity during inter-
epidemic periods, due to the low index of suspicion for
dengue. World Bank figures indicate the private sec-
tor in India covers 90% of health service costs and the
treatment of 40% of all cases of infectious disease, includ-
ing dengue. However, the private health care sector is
under-represented in the dengue surveillance program.
Public health centres in India are organized into three
levels: sub-centres at the village level, primary health
centres that serve as intermediary structures, and com-
munity health centres that are hospitals with more than
30 beds. The primary health centres and the community
health centres report the number of laboratory confirmed
dengue cases to the district medical officer who then
forwards them to the state government. Information
reported includes, age and gender, clinical manifesta-
tions, laboratory investigations (total white blood cells,
platelets and haematocrit), and IgM capture enzyme-
linked immunosorbent assay (MAC-ELISA) test result.5
However, dengue is not the subject of special attention in
the states, unlike malaria, filariasis and plague which are
given the ‘highest priority’ at the national level. Since there
are some disparities between states, the Union Health
Ministry set up in 1999, in addition to the NVBDCP, an
integrated disease surveillance program (IDSP), which
covers 110 of approximately 600 districts in total.
 A. Chakravarti et al. / Transactions of the Royal Society of Tropical Medicine and Hygiene 106 (2012) 273–282
To strengthen dengue diagnostic capacity, the Gov-
ernment of India established 137 Sentinel Surveillance
Hospitals linked to 13 Apex Referral Laboratories. Dengue
MAC-ELISA test kits, developed by the National Institute
of Virology, Pune, and as described elsewhere,22 are pro-
vided to these institutes, for case diagnosis. These hospitals
and laboratories monitor the number of confirmed and sus-
pected cases and report to the state health authorities for
implementation of measures such as vector control.
2.3. National and regional distribution of dengue in India
During the last two decades, India experienced sus-
tained, high levels of dengue transmission, with large
epidemics every 2–3 years, with the exception of the period
from 1997–2002 when numbers were relatively low (less
than 2000 cases reported on average per year) but disease
severity and CFR remained high (CFR 3.05% and 2.55% in
1997 and 1998, respectively; Figure 1). Numbers of dengue
cases rose again after 2002, with 6000–8000 cases reported
per year, reflecting sustained transmission. Case fatality
rates remained above 1% from 2003–2007 (1.08–1.69%),
falling to lower levels in 2008–2009 (CFR 0.62–0.64%). The
most striking feature of these data is the increased number
of reported cases in the last few years. This may be a result
of the newly established endemicity in many regions of
India. It may also, at least partially, be attributable to higher
sensitivity of the surveillance system due to increased
awareness among healthcare professionals of the need to
report clinically suspected dengue cases.
Analysis of nationwide data can provide useful insights
on broad disease trends but its relevance is necessarily lim-
ited, particularly in the case of a country as vast and diverse
Cases
20000
18000
16000
14000
12000
10000
8000
6000
4000
2000
0 0
1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009
Year
Figure 1. Annual numbers of dengue cases and case fatality rate (CFR) reported in India for 1991–2009.
Compiled from data published by South-East Asian Regional Office (1991–2005) and National Vector Borne Disease Control Program (NVBDCP)
(2001–2009).14,15,23,24
275
as India. Data on the numbers of dengue cases in individ-
ual states and Union Territories (UTs) of India are available
from 1997 onwards.23–25
Dengue cases and deaths were reported in 27 of the
35 states and UTs during 1997–2009 (Figure 2, Table 1).
Together, these 27 states and UTs account for >90% of the
Indian population, and display the same urban/rural dis-
tribution as India as a whole.25 Seventeen states and UTs
were responsible for >99% of all cases reported during this
period.
In the early 2000s, dengue in India progressed from
being predominantly restricted to a relatively small
number of states in the southern (Maharashtra, Kar-
nataka, Tamil Nadu and Pondicherry) and north-western
regions surrounding Delhi (Rajasthan, Haryana, Punjab
and Chandigarh) to a situation where it currently affects
large parts of the country. Dengue outbreaks have been
reported in most states and UTs, with the exception of
a few dry or mountainous regions where conditions are
unfavourable to the vector.7 A few states (Jammu and Kash-
mir, Uttarakhand, Bihar, Chhattisgarh, Orissa, Nagaland,
Madhya Pradesh, Manipur, Goa) still display an epidemic
pattern of dengue transmission, with isolated or occasional
outbreaks (Table 1). Dengue is now endemic in many states
and UTs throughout India, generally the larger or more
densely populated states, representing over 70% of the total
population.25
2.4. Disease severity
After the first large outbreak in 1963 in Calcutta, DHF
was virtually absent from India during the 1960s and 1970s,
despite the co-circulation of multiple DENV serotypes,
10
Cases 9
CFR (%)
8
7
6
5
4
3
2
1
276 A. Chakravarti et al. / Transactions of the Royal Society of Tropical Medicine and Hygiene 106 (2012) 273–282

Figure 2. Average annual number of dengue cases in the states and Union Territories of India for 1998–2001, 2002–2005 and 2006–2009.
Compiled from data published by National Vector Borne Disease Control Program (NVBDCP).15,23,24

Table 1
National and selected state-wise data on the annual number of dengue cases and deaths for the period 1997–2010

State 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

Andhra Pradesh Cases 0 0 0 5 1 61 95 230 99 197 587 313 1190 776

Deaths 0 0 0 0 0 3 5 1 2 17 2 2 11 3
Chandigarh Cases 0 0 0 0 0 15 0 0 2 182 99 167 25 221
Deaths 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Delhi Cases 273 333 168 180 322 45 2882 606 1023 3366 548 1312 1153 6259
Deaths 1 5 2 2 3 2 35 3 9 65 1 2 3 8
Goa Cases 0 0 0 0 1 0 12 3 1 1 36 43 277 242
Deaths 0 0 0 0 0 0 2 0 0 0 0 0 5 0
Gujarat Cases 5 0 92 29 69 40 249 117 454 545 570 1065 2461 2568
Deaths 0 0 0 0 0 0 9 4 11 5 2 2 2 0
Haryana Cases 54 14 3 2 260 3 95 25 183 838 365 1137 125 866
Deaths 0 0 0 0 5 0 4 0 1 4 11 9 1 20
Karnataka Cases 262 115 39 196 220 428 1226 291 587 109 230 339 1764 2285
Deaths 4 3 0 0 0 1 7 2 17 7 0 3 8 7
Kerala Cases 0 6 0 0 41 219 3546 686 1028 981 603 733 1425 2597
Deaths 0 0 0 0 0 2 68 8 8 4 11 3 6 17
Madhya Pradesh Cases NR NR NR NR NR NR NR NR NR 16 51 3 1467 175
Deaths NR NR NR NR NR NR NR NR NR NR 2 0 5 1
Maharashtra Cases 249 193 59 66 54 370 772 856 349 736 614 743 2255 1489
Deaths 5 5 12 3 2 18 45 22 56 25 21 22 20 5
Manipur Cases NR NR NR NR NR NR NR NR NR 0 51 0 NR 7
Deaths NR NR NR NR NR NR NR NR NR 0 1 0 NR 0
Pondicherry Cases 0 0 0 0 0 0 6 0 0 0 274 35 66 96
Deaths 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Punjab Cases 23 0 419 91 49 27 848 52 251 1166 28 4349 245 4012
Deaths 3 0 1 1 0 2 13 0 2 6 0 21 1 15
Rajasthan Cases 18 2 1 0 1452 325 685 207 370 1805 540 682 1389 1823
Deaths 1 0 0 0 35 5 11 5 5 26 10 4 18 9
Tamil Nadu Cases 264 33 135 81 816 392 1600 1027 1142 477 707 530 1072 2051
Deaths 21 5 2 1 8 0 8 0 8 2 2 3 7 8
Uttar Pradesh Cases 29 0 28 0 21 0 738 8 121 639 132 51 168 960
Deaths 1 0 0 0 0 0 8 0 4 14 2 2 2 8
West Bengal Cases NR NR NR NR 0 0 0 32 6375 1230 95 1038 399 805
Deaths NR NR NR NR 0 0 0 0 34 8 4 7 0 1
National Total Cases 1177 707 944 650 3306 1926 12 754 4153 11 985 12 317 5534 12 561 15 535 28292
Deaths 36 18 17 7 53 33 215 45 157 184 69 80 96 110

Compiled from data published by National Vector Borne Disease Control Program (NVBDCP). Data from all regions which reported less than 50 cases in
any given year (Bihar, Orissa, Jammu & Kashmir, Dadra & Nagar Haveli, Sikkim, Uttrakhand, Nagaland, Chhattisgarh) were removed.
NR: Not reported.
 A. Chakravarti et al. / Transactions of the Royal Society of Tropical Medicine and Hygiene 106 (2012) 273–282
considered as a risk factor for DHF.26 A similar situation
has been described for neighbouring countries such as Sri
Lanka where, prior to 1989 all four serotypes circulated
and many cases of DF but few cases of DHF occurred.9 This
picture in India and elsewhere in the Indian subcontinent
differs to that of epidemic DHF described for Southeast Asia
for the same period, following a first epidemic in Manila,
the Philippines, in 1953.6,26 In India, from the mid to late
1980s and early 1990s small numbers of DHF cases and
deaths were reported culminating in the large epidemic
of 1996.27,28 This pattern of a gradual increase from small
numbers of sporadic DHF cases occurring for several years,
leading to a major epidemic is typical of every region
where epidemic DHF has become established.3
Following the re-emergence of DHF in India in 1996, two
other large epidemics with substantial numbers of deaths
occurred in 2003 and 2006. Delhi became hyperendemic for
dengue throughout this period29–32 with a large proportion
of the total numbers of cases and deaths occurring in this
region every year since 2003. There was an overall trend
for progressively lower mortality since 1996, with CFRs
remaining below 1% for the first time in the last two years.
This is a common feature in many regions where, follow-
ing a series of large epidemics, increased awareness of the
disease resulted in better case diagnosis and management.1
2.5. Outbreak reports
A large number of studies have been published on
dengue outbreaks in India since 1961 (Table 2). The vast
majority of these reports are relatively small case series
usually from one or a few neighbouring hospitals. They nev-
ertheless provide useful information on variables such as
age, gender, and urban/rural distribution of cases, as well as
on the seasonality of outbreaks and trends in the circulation
of DENV serotypes.
2.6. Age distribution
Most authors reported dengue in India to be pre-
dominantly a disease of young adults. Studies in Delhi,
spanning the period 1999–2006 showed a consistent
pattern with the peak number of confirmed cases
occurring in 21–30 year-olds, generally followed by adoles-
cents (11–20 year-old group).29,30,55,62,69–71 Young adults
were also predominantly affected during epidemics in
Chandigarh,51,59 in Haryana,16,17 Maharashtra,44 Punjab20
and Uttar Pradesh.21,63
In a study of the 1996 epidemic in Delhi, Dar and col-
laborators report the highest numbers of cases in the 5–12
year-old group.11 Similar results were observed in West
Bengal in 1990 and in 2005,10,27 in Tamil Nadu in 1998
and 2003,54,61 in Madhya Pradesh in 2001 and 2003,65,74
in Uttar Pradesh in 2003–200660 and in Pondicherry in
2003–2004.66
Patient age is a risk factor for severe dengue disease.
DHF is considered to affect primarily children under 15
years of age (although adults can also be affected) and is
an important cause of paediatric hospitalization.1,2 In the
first DHF epidemic in Calcutta in 1963, clinical severity was
277
more pronounced in younger age groups.7 In most of the
studies reviewed here, however, the results for age strat-
ification do not differentiate between DF and DHF cases.
In those that did, some found higher numbers of severe
cases among younger patients whilst others found young
adults to be more severely affected. Age, however, is not the
only factor. Pre-existing dengue immunity at the individual
and population levels resulting from past outbreaks, and
dengue viruses’ varying epidemic and pathogenic capacity
are also thought to play a role.2 It is therefore possible that
the contrasting observations cited above can be explained
by differing disease dynamics and epidemiological his-
tory across regions in a large and diverse country such as
India.
2.7. Gender distribution
Males outnumbered females in the majority of the
reports of dengue outbreaks in India, and in a few stud-
ies, all from Delhi, the male to female ratio was as high as
3–5:1.13,45,62,69,72 The significance of this finding in unclear.
A number of other studies reported no difference in the
gender distribution of dengue cases, and in two stud-
ies females were more commonly affected than males:
in one the difference is no longer seen when restricted
to confirmed cases61 and in the other the numbers are
small.11 This gender difference in dengue cases in India
may be explained by bias in case ascertainment: most of
the studies were hospital-based and the reported gender
differences may simply reflect social and cultural bias in
healthcare-seeking behaviour.75 Consistent with this, the
differences in gender distribution reported when the over-
all number of dengue cases is considered are no longer
present when severe outcomes (severe cases and CFR) are
considered.12
2.8. Seasonality
The seasonal character of dengue epidemics in India
has been documented by ecological studies.64 Outbreaks
of DF and DHF generally occur during the warm and humid
conditions of the rainy season which favour abundant
mosquito growth. In a study of the influence of climatic fac-
tors on the pattern of dengue infections, carried out in Delhi
during 2003, the interaction between rainfall, tempera-
ture and relative humidity was found to be associated with
the distribution of serologically confirmed dengue cases,
which peaked at the end of the monsoon season during the
months of October and November.64 A similar seasonal pat-
tern with the highest numbers of dengue cases occurring
during the post-monsoon period was observed across the
studies reviewed.
A small number of studies report dengue outbreaks dur-
ing the dry summer months: in Rajasthan, Chouhan et al.
report an outbreak occurring during April and May 1985;43
in Maharashtra, outbreaks of dengue occurred from May
to June 1987 and from March to May 1989.47 A thorough
understanding of the relationships between climate, vector
density and incidence of dengue disease is key to the imple-
mentation of effective preventive and control strategies.64
278 A. Chakravarti et al. / Transactions of the Royal Society of Tropical Medicine and Hygiene 106 (2012) 273–282

Table 2
Data on circulating serotypes, seasonality, sex ratio and age of cases from reports of dengue outbreaks in India

Ref Outbreak year Peak period State/UT Dengue serotype Male/Female Age
(confirmed cases)
1 2 3 4

33 1961 Sept–Nov Tamil Nadu ++ NR NR

1962 Aug–Oct Tamil Nadu ++ + NR NR
1963 Aug–Oct Tamil Nadu + ++ + NR NR
34 1965 Oct Tamil Nadu + NR NR
35 1966 July–Nov Tamil Nadu ++ NR NR
36 1967 NR Delhi + NR NR
37 1968 July–Nov Tamil Nadu + ++ + ++ NR NR
38 1969 Sept–Nov Rajasthan ++ ++ 1.2:1 NR
36 1970 NR Delhi ++ ++ NR NR
39 1970–1971 NR Karnataka + + NR NR
40 1974 Aug–Oct Kerala + NR Majority <16 y.o.
41 1975 Aug–Dec Maharashtra ++ NR NR
36 1982 Aug–Oct Delhi ++ + NR NR
42 1983 July–Aug West Bengal + NR Mostly young adults
43 1985 Apr–May Rajasthan + ++ 2.6:1 Mostly infants, children and young adults
44 1988 May–Jun Maharashtra + ++ ∼1:1 Majority 21–50 y.o.; Peak 31–50 y.o.
28 1988 Sept–Oct Delhi ++ 1.8:1 Peak 6–10 y.o. (pediatric study)
45 1988 Sep–Oct Delhi ++ 5:1 NR
46 1988–1989 NR Gujarat ++ NR NR
47 1989 Mar–May Maharashtra + ++ M>F All age groups
27 1990 Sept–Dec West Bengal ++ 2:1 Majority 0–15 y.o. (77.5%); Peak 0–5 y.o.
48 1992 Jun–Jul Madyha Pradesh ∼2:1 Mostly adults
49 1993 July–Nov Karnataka + NR NR
50 1993 Sept–Nov Kashmir + 1:1 Majority 5–17 y.o. (92.7%)
11 1996 Aug–Nov Delhi + ++ 0.8:1 Peak 5–12 y.o.(40.7%)
12 1996 Sept–Nov Delhi ++ ∼1:1 Peak 8 y.o.; 9% infants (pediatric study)
13 1996 Aug Delhi 3.1:1 Mean age 26.3 y.o. (adult study)
16 1996 Aug Haryana + NR Majority >19 y.o. (51%)
18 1996 Sept–Dec Punjab ∼1:1 Peak 11–20 y.o.(32.8%); 0–10 y.o. 22.4%
20 1996 Oct–Nov Punjab 2.5:1 Mean age 32.2 y.o.
21 1996 Oct–Dec Uttar Pradesh + 1.9:1 Majority 11–30 y.o.; Peak 21–30 y.o. (30%)
51 1996 NR Punjab/Haryana 2.3:1 Peak 21–30 y.o. (29.3%); 0–10 y.o. 17.6%
17 1996 Jul–Aug Haryana ++ 1.2:1 NR
19 1996–1997 Oct–Dec Punjab 2:1 Peak 21–40 y.o.
52 1997 Sept–Dec Delhi ++ NR NR
53 1997–1998 Sept–Nov Delhi + 3:1 Mean age 26 y.o.
54 1998 Jan–Mar Tamil Nadu 2.3:1 Majority <10 y.o. (80%)
13 1996 July–Nov Delhi M>F Majority >14 y.o. (69.5%)
51 1999 NR Punjab/Haryana 2.3:1 Peak 21–30 y.o. (29.3%); 0–10 y.o. 17.6%
55 1999–2001 Sept–Nov Delhi M>F Peak 21–30 y.o. (37.6%); 11–20 y.o. 27.1%
56 2000 Sept–Nov Andhra Pradesh ++ NR Peak >15 y.o.
57 2001 Sept–Nov Madyha Pradesh ++ 2.6:1 Majority <15 y.o.; Peak 6–15 y.o. (43.2%)
58 2001 Oct–Dec Tamil Nadu + + ∼1:1 Peak 6–15 y.o. (51%) (pediatric study)
59 2002 Sept–Dec Punjab/Haryana ++ 2:1 Majority <15 y.o.; Peak 15–29 y.o.
31 2002–2005 NR Delhi + ++ ++ + NR NR
60 2003–2005 Oct–Dec Uttar Pradesh 2.5:1 Mean age 5.6 y.o
61 2003 July Tamil Nadu + 1.5:1 Majority 6–15 y.o.
61 2003 Sept–Dec Delhi 3:1 Peak 20–29 y.o. (40%); no cases <12 y.o.
29 2003 Sept–Nov Delhi + + + + 2.1:1 Majority <30 y.o; Peak 21–30 y.o. (34.2%)
63 2003 Sept–Dec Uttar Pradesh 2.1:1 Peak 21–40 y.o. (45%) (adult study)
64 2003 Oct–Nov Delhi NR Majority adults; 76.9% >12 y.o.
65 2003 Oct–Nov Madhya Pradesh/Delhi + 1.28:1 Majority children; 89% <15 y.o.
30 2003 Sept–Nov Delhi + + + + 2.3:1 Majority >10 y.o.; Peak 21–30 y.o.
66 2003–2004 Oct–Feb Pondicherry ++ NR Majority 1–15 y.o.
67 2004 Sept–Oct Delhi ++ 2.6:1 Majority >25 y.o. (52.5%)
30 2004 Sept–Nov Delhi + 1.7:1 Majority >10 y.o.; Peak 21–30 y.o.
2005 Sept–Nov Delhi + ++ 1.9:1 Majority >10 y.o.; Peak 21–30 y.o.
68 2005 Sept–Nov Delhi ++ ++ NR NR
2005 Aug–Sept Maharashtra ++ + NR NR
10 2005 Aug–Nov West Bengal 1.65:1 Peak 0–16 y.o. (44.6%)
69 2006 Oct. Delhi 3:1 Peak 21–30 y.o (35.5%); 11–20 y.o. 25.6%
70 2006 Aug–Nov Delhi ++ + ++ + 1.52:1 Peak 20–30 y.o.(35.4%); 12–20 y.o. 20.8%
71 2006 Sept–Nov Delhi ++ 2.1:1 Peak 21–30 y.o. (35.6%); 11–20 y.o. 32.8%
Adult/pediatric ratio 4.1:1
72 2006 Aug–Nov Delhi 4.3:1 Mean age 28 y.o.
73 2002–2007 Jun–Dec Karnataka 1.7:1 Majority 15–44 y.o. (56.4%)

+ 5 samples or fewer or unspecified number of samples, ++ predominant serotype(s)/more than 5 samples;

NR: not reported.
 A. Chakravarti et al. / Transactions of the Royal Society of Tropical Medicine and Hygiene 106 (2012) 273–282
2.9. Urban/rural distribution
Historically dengue was considered an urban dis-
ease. Rapid urban growth in developing countries in the
mid-twentieth century resulted in widespread precarious
housing, deficient water supply and wastewater man-
agement systems. These circumstances created the ideal
conditions for the proliferation and spread of the vector
and the virus.2,76
Outbreaks of DF/DHF have typically occurred in
large cities: Delhi,12,28,30,31,36,45,52,53,55,62,64,67,70,71
Chandigarh,51,59 Pondicherry,66 Bangalore and Mangalore
in Karnataka,39,49 Gwalior in Madhya Pradesh,57,65,74
Amalner in Maharashtra,41 Ludhiana in Punjab,18–20 Jalore
and Ajmer in Rajasthan,38,43 Vellore and Chennai in Tamil
Nadu,33,35,37,58,77 Lucknow in Uttar Pradesh21,60,63,78 and
Calcutta in West Bengal.10,27,42 While this is still the case,
the disease is progressively spreading to rural settings. The
first outbreak reported from a typically rural area occurred
in northern India (Haryana) in 1996.16,17 Other rural
districts with reported dengue activity include Tamil Nadu
and Maharashtra.44,47,61 Entomological investigations
during outbreaks in Gujarat in 1988 and 1989 showed
widespread distribution of Aedes aegypti in both rural
and urban areas.46 From 2003–2005 in Lucknow region,
Uttar Pradesh, the rates of serologically confirmed cases
indicated that dengue transmission was occurring both in
rural (53.4%) and urban (44.1%) areas.63
The spread of dengue from urban to rural areas is
thought to be related to socio-economic and human
ecological changes, such as increased transport con-
tact, mobility and spread of peri-urbanization, although
improved reporting may also contribute.75 These changes
resulted in the invasion of rural areas by A. aegypti
mosquitoes. What was primarily an urban problem has
now become a widespread health concern in India.
2.10. Serotype prevalence
The first DENV isolated from human sera in India, in
Calcutta in 1945, was a serotype 1 virus.8 There were no
further DENV isolations until 1956, when DENV-2 was
identified.8 DENV-4 was isolated in 196037 and DENV-3 in
1965.33,34
The four DENV serotypes circulated in India during the
1960s, occasionally with isolation of multiple serotypes
in some epidemics. For example, DENV-1, DENV-2 and
DENV-4 were isolated during a DF outbreak in Vellore
in 196333 and all four serotypes were isolated during
another outbreak in the same city in 1968.37 DENV-1
has been identified in various parts of India at regular
intervals. Recently, there has been a rise in DENV-1, which
accounted for approximately 30% of the all cases reported
during the 2006 DF epidemic, co-circulating with the
predominant DENV-3.70 DENV-1 and DENV-4 have not
been associated with any major outbreak in the country.
DENV-2 emerged as the predominant serotype from the
early 1970s to 2000, during which time it was responsible
for the large epidemics of DF in 199349,50 and of DF/DHF in
1996.11,12,16,17,21 DENV-3 which had not been isolated in
India since 199027 reappeared in 2001 in a small outbreak
279
in Tamil Nadu.58 It subsequently became the main serotype
in the large outbreak of DF in 2003.29,30,61,65,66 During the
following years, DENV-3 became the dominant serotype
and was responsible for the epidemic of 2006 in Delhi.70,71
All four DENV serotypes were found to co-circulate in
Delhi for the first time in 2003, which thus became a
hyperendemic region for dengue.29–32,68 Co-circulation of
multiple DENV serotypes has resulted in concurrent infec-
tion in some patients with more than one serotype.70
Epidemiological and experimental observations suggest
that secondary heterotypic DENV infections may increase
the risk of severe forms of dengue.4 This provides a plau-
sible explanation for the increased frequency and spread
of DHF in Southeast Asia in the 1960s and 1970s: the
emergence of epidemic DHF would have resulted from the
introduction of novel serotypes to dengue endemic regions
due to population movements or growing international
travel.76 Further support is provided by the observation
that the emergence of epidemics of DHF is often associ-
ated with hyperendemicity—the co-circulation of multiple
of serotypes.76 However, some studies have failed to find
a significant association between secondary heterotypic
DENV infection, or co-circulation of different serotypes, and
DHF/DSS.75,79
Data on serotype prevalence in India shows a mixed
picture regarding a possible association between hyper-
endemicity and DHF. DENV-1, 2 and 4 were isolated in
Tamil Nadu in 1963 during the first large DF/DHF epidemic
in India, and all four serotypes were isolated in Delhi in
2003 and again in 2006, two recent outbreaks with sub-
stantial numbers of DF/DHF cases and deaths. The return
of DENV-3 coincided with the recrudescence of dengue
activity in India in the last ten years, supporting the idea
that increases in dengue activity may be connected with
changes in predominant serotypes. In contrast during the
1996 epidemic, the largest DHF epidemic in India to date,
most studies found only one serotype (DENV-2).
2.11. Genotypes in India
Human viruses of dengue serotypes 1, 2 and 3 are
each classified into five genotypes related to their geo-
graphic origin, while serotype 4 viruses are classified into
four genotypes. Epidemiological analysis suggests that dif-
ferent genotypes differ in their epidemic potential and
virulence.80–82
Of the five genotypes (I to V) of DENV-1 (previously
known as the Asian, Thai, Sylvatic/Malaysian, South Pacific,
and American/African genotypes, respectively) isolates col-
lected in India since 1956 are of genotypes I, III or V,
with genotype III viruses identified in isolates from Vellore
(1956, 1962–1964), Rajasthan (1971), Gwalior (2002 and
2004) and New Delhi (1970, 1982, 2001, 2003, 2005–2007),
suggesting the persistent circulation of this genotype in
India since 1956.83–86 Genotype V was identified in a study
of DENV-1 strains in New Delhi in 2007–2008 (Chakravarti,
unpublished data). Genotype I has been identified in New
Delhi isolates only (1997–1998).86
The five genotypes of DENV-2 are labeled Asian,
Cosmopolitan (previously known as genetic type IV), Amer-
ican (previously known as genetic type V), Southeast
280 A. Chakravarti et al. / Transactions of the Royal Society of Tropical Medicine and Hygiene 106 (2012) 273–282

Asian/American, and Sylvatic.87–91 The Asian genotype is Reports of individual outbreaks reviewed here, although
further divided into Asian genotype I (including viruses useful in terms of describing the overall pattern and evo-
from Malaysia and Thailand) and II (viruses from Viet- lution of dengue in India over the past few decades, did
nam, China, Taiwan, Sri Lanka and the Philippines). In India, not allow detailed analysis. Most of the studies consisted
DENV-2 viruses isolated in 1956, 1957, 1963, 1964, 1967, of small case series, often involving hospitalized patients
1971 and 1980 were of the American genotype, while who had been referred to tertiary centres. The methods
viruses isolated in Gwalior in 2001–2002 and in various for case selection and ascertainment were not consistently
places in 1974, 1983, 1990-97, 2004 and 2005 belong to described and dengue case definitions evolved over time
the Cosmopolitan genotype.57,92 Two subgroups of Cos- resulting in lack of comparability between studies. These
mopolitan genotype viruses have been circulating in India, limitations may contribute to variability in the results,
one of which includes the Indian 1974 isolate and shares which prevented the full examination of some of the epi-
ancestry with DENV-2 viruses circulating in the Indian demiological trends of dengue in India.
Ocean islands (Seychelles SC/SEY42/1977 and Sri Lanka
SL/SL206/1990) and West Africa, while the other includes
3. Conclusions
Indian isolates from 1983–1991 and display phylogenetic
proximity with Sri Lankan (LK/271235/1990) and Ugandan
In recent years the epidemiology of dengue infection
(UG/CAMR11/1993) isolates.92
in India has evolved rapidly. Regular and gradually larger
Of the five genotypes of DENV-3 (I to V) genotype
outbreaks have been observed, accompanied by a tendency
III is predominant in India, and was identified between
for the disease to spread from urban to rural areas resulting
2003 and 2008 in Delhi, Gwalior, and Hyderabad.81–95
in an expansion in geographic range. Outbreaks of dengue
These isolates diverge from global DENV-3 genotype III
have been reported throughout India with the exception of
isolates and form a distinct Indian lineage closely related
a few areas where conditions do not support the propaga-
to the Guatemala-98, Puerto Rico-00 and Martinique-01
tion of the vector. Dengue endemicity has been established
isolates.95 The 2003 GWL-60 isolate from Gwalior is
in large areas throughout India.
phylogenetically different to other DENV-3 genotype
Disease patterns are also evolving in recent epidemics.
III isolates and is closer to 1996–2000 isolates from Sri
Circulation of multiple DENV serotypes is increasing, par-
Lanka, Martinique, Nicaragua, Mexico and Guatemala.95
ticularly in large urban areas such as Delhi which is now
Circulation of a DENV-3 genotype V strain that is closely
hyperendemic, and which accounts for a substantial pro-
related to the strains circulating in Asia (Philippine-56,
portion of the reported cases and deaths. Dengue is not
China-2000 and Japan-1973) has also been identified in
always perceived as a serious public health problem in
New Delhi in 2007 (Chakravarti, unpublished data).
India, yet the country is currently largely endemic and sub-
Sequence analysis of E-NS1 gene of DENV-4 shows that
jected to the unpredictable occurrence of outbreaks.
this serotype exhibits greater degree of sequence con-
Laboratory-based active surveillance systems are
servation compared with the other serotypes (92%) with
needed to complement the current passive surveillance
96–100% conservation at the level of E protein amino acids
and control programs. Regular sentinel surveillance and
sequence.96 The four genotypes are genotype I from South-
sample surveys during interepidemic periods are also
east Asia, genotype II from Southeast Asia and the Americas,
necessary to detect and monitor sudden increases in the
genotype III from Thailand, and Sylvatic genotype from
numbers of dengue cases or changes in the predominant
Malaysia.97 In India DENV-4 genotype I has been isolated
serotypes which usually precede major outbreaks. New
in Hyderabad in 2007, Pune in 2009–2010 and New Delhi
molecular diagnostic techniques, such as RT-PCR, are
in 2007 and 2009.97,98 The south Indian (Pune and Hyder-
particularly useful in this context31,99 their speed and
abad) DENV-4 genotype I strain is phylogenetically closer
sensitivity enabling the rapid detection of increased viral
to the India-1996 (isolated in Japan) and Srilanka-1978
circulation or changes in predominant serotypes.
isolates.97,98 Two lineages have been identified among
Finally, thoughtfully designed and well conducted,
the North Indian (New Delhi) DENV-4 genotype I strains.
large, population-based studies are needed to fill the
North Indian DENV-4 strains (isolated in 2007) are closely
knowledge gaps and identify the key determinants of the
related to Thailand-1963 while New Delhi 2009, Hyderabad
incidence of DF and identify the vulnerable population
2007, Pune 2009-10 isolates are closer to India-1996 and
groups at increased risk for severe forms of the disease.
Srilanka-1978.
Understanding the role of the demographic factors in infec-
tion rates and disease severity has important implications
2.12. Limitations
in planning and implementing effective public health pre-
vention and control measures, including future dengue
The national and regional data on dengue epidemiology,
immunization programs.
which forms the basis of this review, were derived from
the national dengue surveillance system in India. Passive
surveillance systems are likely to underestimate the true Authors’ contributions: CL oversaw the initial litera-
extent of DENV transmission due in large part to the often ture search and review; AC and RA identified additional
mild, non-specific presentation of the disease.12,54,75 More- literature and data published in India. All authors con-
over, the published data do not discriminate between DF tributed to the conception and writing of this manuscript
and DHF cases, hampering the accurate assessment of the and approved the final version. CL is guarantor of the
true burden of dengue in India. paper.
 A. Chakravarti et al. / Transactions of the Royal Society of Tropical Medicine and Hygiene 106 (2012) 273–282
Acknowledgements: We thank C. Okais at Sanofi Pas-
teur for her contribution to the literature search. This
manuscript was prepared with the assistance of a
professional medical writer, E Seleiro.
Funding: This work was funded by Sanofi Pasteur.
Competing interests: RA and CL are employed by Sanofi
Pasteur, manufacturer of an investigational dengue vaccine
candidate.
Ethical approval: Not required.
References
1. World Health Organization. dengue guidelines for diagnosis,
treatment, prevention and control. 2009. http://whqlibdoc.who.
int/publications/2009/9789241547871 eng.pdf [accessed 16 May
2011].
2. Gubler DJ. Dengue and dengue hemorrhagic fever. Clin Microbiol Rev
1998;11:480–96.
3. Gubler DJ. Epidemic dengue/dengue haemorrhagic fever: a global
public health problem in the 21st century. Dengue Bull 1997;21:1–15.
4. Halstead SB. Dengue. Lancet 2007;370:1644–52.
5. National Vector Borne Disease Control Programme. Guidelines
for Clinical Management of Dengue Fever, Dengue Hemorrhagic
Fever and Dengue Shock Syndrome. http://www.nvbdcp.gov.
in/Doc/Clinical%20Guidelines.pdf [accessed 18 May 2010].
6. Chaturvedi UC, Nagar R. Dengue and dengue haemorrhagic fever:
Indian perspective. J Biosci 2008;33:429–41.
7. Lall R, Dhanda V. Dengue haemorrhagic fever and the dengue shock
syndrome in India. Natl Med J India 1996;9:20–3.
8. Rao CV. Dengue fever in India. Indian J Pediatr 1987;54:11–4.
9. Raheel U, Faheem M, Riaz MN, Kanwal N, Javed F, Zaidi NS, Qadri I.
Dengue fever in the Indian subcontinent: an overview. J Infect Dev
Ctries 2011;5:239–47.
10. Hati AK. Studies on dengue and dengue haemorrhagic fever (DHF) in
West Bengal State, India. J Commun Dis 2006;38:124–9.
11. Dar L, Broor S, Sengupta S, Xess I, Seth P. The first major out-
break of dengue hemorrhagic fever in Delhi, India. Emerg Infect Dis
1999;5:589–90.
12. Kabra SK, Jain Y, Pandey RM, et al. Dengue haemorrhagic fever in
children in the 1996 Delhi epidemic. Trans R Soc Trop Med Hyg
1999;93:294–8.
13. Sharma S, Sharma SK, Mohan A, et al. Clinical profile of dengue haem-
orrhagic fever in adults during 1996 - outbreak in Delhi, India. Dengue
Bull 1998;22:20–7.
14. World Health Organization, Regional Office for South-East Asia.
Trend of Dengue case and CFR in SEAR Countries. http://www.
searo.who.int/en/Section10/Section332/Section2277.htm [accessed
16 May 2011].
15. World Health Organization, Regional Office for South-East
Asia. Dengue cases and deaths reported from SEARO countries.
http://www.searo.who.int/LinkFiles/Dengue dengue updated tables
06.pdf [accessed 16 May 2011].
16. Jamaluddain M, Saxena VK. First outbreak of Dengue fever in a typ-
ical rural area of Haryana state in northern India. J Commun Dis
1997;29:169–70.
17. Kumar A, Sharma SK, Padbidri VS, Thakare JP, Jain DC, Datta KK. An
outbreak of dengue fever in rural areas of northern India. J Commun
Dis 2001;33:274–81.
18. Gill KS, Bora D, Bhardwaj M, Bandyopadhyay S, Kumar K, Katyal R.
Dengue outbreak in Ludhiana (Punjab), India, 1996. Dengue Bull
1997;21:47–51.
19. Ram S, Khurana S, Kaushal V, Gupta R, Khurana SB. Incidence of dengue
fever in relation to climatic factors in Ludhiana, Punjab. Indian J Med
Res 1998;108:128–33.
20. Kaur H, Prabhakar H, Mathew P, Marshalla R, Arya M. Dengue haemor-
rhagic fever outbreak in October-November 1996 in Ludhiana, Punjab,
India. Indian J Med Res 1997;106:1–3.
21. Agarwal R, Kapoor S, Nagar R, et al. A clinical study of the patients with
dengue hemorrhagic fever during the epidemic of 1996 at Lucknow,
India. Southeast Asian J Trop Med Public Health 1999;30:735–40.
22. Sathish N, Manayani DJ, Shankar V, Abraham M, Nithyanandam G,
Sridharan G. Comparison of IgM capture ELISA with a commercial
281
rapid immunochromatographic card test & IgM microwell ELISA
for the detection of antibodies to dengue viruses. Indian J Med Res
2002;15:31–6.
23. National Vector Borne Disease Control Programme. Dengue Cases and
Deaths in the Country since 2007. http://www.nvbdcp.gov.in/den-
cd.html [accessed 16 May 2011].
24. Central Bureau of Health Intelligence. Public Health Statistics
2003, Dengue Cases and Deaths since 1997 http://cbhidghs.nic.in/
writereaddata/linkimages/10076703637330.pdf [accessed 16 May
2011].
25. Office of the Registrar General and Census Commissioner, India.
Census Reference Tables, A-Series Tables: General Population Tables.
http://censusindia.gov.in/Tables Published/Tables published.html
[accessed 16 May 2011].
26. Rigau-Pérez JG, Clark GG, Gubler DJ, Reiter P, Sanders EJ, Vorndam AV.
Dengue and dengue haemorrhagic fever. Lancet 1998;352:971–7.
27. Bhattacharjee N, Mukherjee KK, Chakravarti SK, et al. Dengue haem-
orrhagic fever (DHF) outbreak in Calcutta–1990. J Commun Dis
1993;25:10–4.
28. Srivastava VK, Suri S, Bhasin A, Srivastava L, Bharadwaj M. An epidemic
of dengue haemorrhagic fever and dengue shock syndrome in Delhi:
a clinical study. Ann Trop Paediatr 1990;10:329–34.
29. Gupta E, Dar L, Narang P, Srivastava VK, Broor S. Serodiagnosis of
dengue during an outbreak at a tertiary care hospital in Delhi. Indian
J Med Res 2005;121:36–8.
30. Gupta E, Dar L, Kapoor G, Broor S. The changing epidemiology of
dengue in Delhi, India. Virol J 2006;3:92.
31. Chakravarti A, Kumaria R, Kar P, Batra VV, Verma V. Improved Detec-
tion of Dengue Virus Serotypes from Serum Samples-Evaluation
of Single-Tube Multiplex RT-PCR with Cell Culture. Dengue Bull
2006;30:133–40.
32. Kumaria R. Correlation of disease spectrum among four Dengue
serotypes: a five years hospital based study from India. Braz J Infect
Dis 2010;14:141–6.
33. Carey DE, Myers RM, Reuben R, Rodrigues FM. Studies on dengue in
Vellore, South India. Am J Trop Med Hyg 1966;15:580–7.
34. Myers RM, Carey DE, Banerjee K, Reuben R, Ramamurti DV. Recovery
of dengue type 3 virus from human serum and Aedes aegypti in South
India. Indian J Med Res 1968;56:781–7.
35. Myers RM, Carey DE, DeRanitz CM, Reuben R, Bennet B.
Virological investigations of the 1966 outbreak of Dengue
type 3 in Vellore, Southern India. Indian J Med Res 1969;57:
1392–401.
36. Rao CV, Bagchi SK, Pinto BD, et al. The 1982 epidemic of dengue fever
in Delhi. Indian J Med Res 1985;82:271–5.
37. Myers RM, Varkey MJ, Reuben R, Jesudass ES. Dengue outbreak in Vel-
lore, southern India, in 1968, with isolation of four dengue types from
man and mosquitoes. Indian J Med Res 1970;58:24–30.
38. Ghosh SN, Pavri KM, Singh KR, et al. Investigations on the outbreak of
dengue fever in Ajmer City, Rajasthan State in 1969. Part I. Epidemio-
logical, clinical and virological study of the epidemic. Indian J Med Res
1974;62:511–22.
39. George S, Soman RS. Studies on dengue in Bangalore city: isolation of
virus from man and mosquitoes. Indian J Med Res 1975;63:396–401.
40. Sreenivasan MA, Rodrigues FM, Venkateshan CN, Jayaram Panikar CK.
Isolation of dengue virus from Trichur district (Kerala State). Indian J
Med Res 1979;69:538–41.
41. Rao GL, Khasnis CG, Rodrigues FM, et al. Investigation of the 1975
dengue epidemic in Amalner town of Maharashtra. Indian J Med Res
1981;74:156–63.
42. Mukherjee KK, Chakravarti SK, Dey PN, Dey S, Chakraborty MS. Out-
break of febrile illness due to dengue virus type 3 in Calcutta during
1983. Trans R Soc Trop Med Hyg 1987;81:1008–10.
43. Chouhan GS, Rodrigues FM, Shaikh BH, et al. Clinical & virological
study of dengue fever outbreak in Jalore city, Rajasthan 1985. Indian J
Med Res 1990;91:414–8.
44. Mehendale SM, Risbud AR, Rao JA, Banerjee K. Outbreak of dengue
fever in rural areas of Parbhani district of Maharashtra (India). Indian
J Med Res 1991;93:6–11.
45. Acharya SK, Buch P, Irshad M, Gandhi BM, Joshi YK, Tandon BN. Out-
break of Dengue fever in Delhi. Lancet 1988;2:1485–6.
46. Mahadev PV, Kollali VV, Rawal ML, et al. Dengue in Gujarat state, India
during 1988 & 1989. Indian J Med Res 1993;97:135–44.
47. Risbud AR, Mehendale SM, Joshi GD, Banerjee K. Recurrent outbreaks
of dengue fever in rural areas of Maharashtra (an experience from
Parbhani district). Indian J Virol 1991;7:120–7.
48. Mahadev PV, Prasad SR, Ilkal MA, Mavale MS, Bedekar SS, Banerjee K.
Activity of dengue-2 virus and prevalence of Aedes aegypti in the Chir-
imiri colliery area, Madhya Pradesh, India. Southeast Asian J Trop Med
Public Health 1997;28:126–37.
282 A. Chakravarti et al. / Transactions of the Royal Society of Tropical Medicine and Hygiene 106 (2012) 273–282
49. Padbidri VS, Adhikari P, Thakare JP, et al. The 1993 epidemic of dengue
fever in Mangalore, Karnataka state, India. Southeast Asian J Trop Med
Public Health 1995;26:699–704.
50. Padbidri VS, Thakare JP, Risbud AR, et al. An outbreak of dengue hem-
orrhagic fever in Jammu. Indian J Virol 1996;12:83–7.
51. Ratho RK, Mishra B, Kumar S, Verma V. Dengue Fever/Dengue
Haemorrhagic Fever in Chandigarh (North India). Dengue Bull
2006;30:278–80.
52. Vajpayee M, Mohankumar K, Wali JP, Dar L, Seth P, Broor S. Dengue
virus infection during post-epidemic period in Delhi, India. Southeast
Asian J Trop Med Public Health 1999;30:507–10.
53. Kurukumbi M, Wali JP, Broor S, et al. Seroepidemiology and active
surveillance of dengue fever/dengue haemorrhagic fever in Delhi.
Indian J Med Sci 2001;55:149–56.
54. Singh J, Balakrishnan N, Bhardwaj M, et al. Silent spread of dengue
and dengue haemorrhagic fever to Coimbatore and Erode districts in
Tamil Nadu, India, 1998: need for effective surveillance to monitor
and control the disease. Epidemiol Infect 2000;125:195–200.
55. Chakravarti A, Kumaria R, Berry N, Sharma VK. Serodiagnosis of
dengue infection by rapid immunochromatography test in a hospital
setting in Delhi, India, 1999-2001. Dengue Bull 2002;26:107–12.
56. Rajendran G, Amalraj D, Das LK, Ravi R, Das PK. Epidemiological
and entomological investigation of dengue fever in Sulurpet, Andhra
Pradesh, India. Dengue Bull 2006;30:93–8.
57. Dash PK, Parida MM, Saxena P, et al. Emergence and continued circu-
lation of dengue-2 (genotype IV) virus strains in northern India. J Med
Virol 2004;74:314–22.
58. Kabilan L, Balasubramanian S, Keshava SM, Satyanarayana K. The 2001
dengue epidemic in Chennai. Indian J Pediatr 2005;72:919–23.
59. Ratho RK, Mishra B, Kaur J, Kakkar N, Sharma K. An outbreak of
dengue fever in periurban slums of Chandigarh, India, with spe-
cial reference to entomological and climatic factors. Indian J Med Sci
2005;59:518–26.
60. Tripathi P, Kumar R, Tripathi S, Tambe JJ, Venkatesh V. Descriptive
epidemiology of dengue transmission in Uttar Pradesh. Indian Pediatr
2008;45:315–8.
61. Paramasivan R, Thenmozhi V, Hiriyan J, Dhananjeyan K, Tyagi B, Dash
AP. Serological and entomological investigations of an outbreak of
dengue fever in certain rural areas of Kanyakumari district, Tamil
Nadu. Indian J Med Res 2006;123:697–701.
62. Singh NP, Jhamb R, Agarwal SK, et al. The 2003 outbreak of Dengue
fever in Delhi, India. Southeast Asian J Trop Med Public Health
2005;36:1174–8.
63. Kishore J, Singh J, Dhole TN, Ayyagari A. Clinical and serological study
of first large epidemic of dengue in and around Lucknow, India, in
2003. Dengue Bull 2006;30:72–9.
64. Chakravarti A, Kumaria R. Eco-epidemiological analysis of dengue
infection during an outbreak of dengue fever, India. Virol J 2005;2:32.
65. Dash PK, Saxena P, Abhyankar A, Bhargava R, Jana AM. Emergence
of dengue virus type-3 in northern India. Southeast Asian J Trop Med
Public Health 2005;36:370–7.
66. Hoti SL, Soundravally R, Rajendran G, Das LK, Ravi PK, Das PK.
Dengue and dengue haemorrhagic fever outbreak in Pondicherry,
South India, during 2003-2004: emergence of DENV-3. Dengue Bull
2006;30:42–50.
67. Dash PK, Parida MM, Saxena P, et al. Reemergence of dengue virus
type-3 (subtype-III) in India: implications for increased incidence of
DHF & DSS. Virol J 2006;3:55.
68. Saxena P, Parida MM, Dash PK, et al. Co-circulation of dengue virus
serotypes in Delhi, India, 2005: implication for increased DHF/DSS.
Dengue Bull 2006;30:283–7.
69. Pandey A, Diddi K, Dar L, et al. The evolution of dengue over a decade
in Delhi, India. J Clin Virol 2007;40:87–8.
70. Bharaj P, Chahar HS, Pandey A, et al. Concurrent infections by all four
dengue virus serotypes during an outbreak of dengue in 2006 in Delhi,
India. Virol J 2008;5:1.
71. Rai S, Chakravarti A, Matlani M, et al. Clinico-laboratory findings of
patients during dengue outbreak from a tertiary care hospital in Delhi.
Trop Doct 2008;38:175–7.
72. Sinha N, Gupta N, Jhamb R, Gulati S, Kulkarni AV. The 2006 dengue
outbreak in Delhi, India. J Commun Dis 2008;40:243–8.
73. Kumar A, Pandit VR, Shetty S, Pattanshetty S, Krish SN, Roy S. A pro-
file of dengue cases admitted to a tertiary care hospital in Karnataka,
southern India. Trop Doct 2010;40:45–6.
74. Parida MM, Dash PK, Upadhyay C, Saxena P, Jana AM. Serological &
virological investigation of an outbreak of dengue fever in Gwalior,
India. Indian J Med Res 2002;116:248–54.
75. Guha-Sapir D, Schimmer B. Dengue fever: new paradigms for a chang-
ing epidemiology. Emerg Themes Epidemiol 2005;2:1.
76. Ooi EE, Gubler DJ. Dengue in Southeast Asia: epidemiological char-
acteristics and strategic challenges in disease prevention. Cad Saude
Publica 2009;25(Suppl 1):S115–24.
77. Kabilan L, Velayutham T, Sundaram B, et al. Field-and laboratory-
based active dengue surveillance in Chennai, Tamil Nadu, India:
observations before and during the 2001 dengue epidemic. Am J Inf
Control 2004;32:391–6.
78. Chandrakanta RK, Garima JA, Jain A, Nagar R. Changing clinical
manifestations of dengue infection in north India. Dengue Bull
2008;32:118–25.
79. Rosen L. Comments on the epidemiology, pathogenesis and control of
dengue. Med Trop (Mars) 1999;59:495–8.
80. Chaudhry S, Swaminathan S, Khanna N. Viral genetics as a basis of
dengue pathogenesis. Dengue Bull 2006;30:121–32.
81. Lanciotti RS, Lewis JG, Gubler DJ, Trent DW. Molecular evolution and
epidemiology of dengue-3 viruses. J Gen Virol 1994;75:65–75.
82. Messer WB, Gubler D, Harris E, Sivananthan K, de Silva AM. Emergence
and global spread of a dengue serotype 3, subtype III virus. Emerg Infect
Dis 2003;9:800–9.
83. Goncalvez AP, Escalante AA, Pujol FH, et al. Diversity and evolution of
the envelope gene of dengue virus type 1. Virology 2002;303:110–9.
84. Rico-Hesse R. Microevolution and virulence of dengue viruses. Adv
Virus Res 2003;59:315–41.
85. Patil JA, Cherian S, Walimbe AM, et al. Evolutionary dynamics of the
American African genotypes of dengue type 1 virus in India (1962-
2005). Infect Gent Evol 2011;11:1443–8.
86. Kukreti H, Dash PK, Parida MM, et al. Phylogenetic studies reveal
existence of multiple lineages of a single genotype of DENV-1
(genotype III) in India during 1956-2007. Virol J 2009;6:1.
87. Lewis JA, Chang GJ, Lanciotti RS, Kinney RM, Mayer LW, Trent
DW. Phylogenetic relationships of dengue-2 viruses. Virology
1993;197:216–24.
88. Rico-Hesse R, Harrison LM, Salas RA, et al. Origins of dengue type
2 viruses associated with increased pathogenicity in the Americas.
Virology 1997;230:244–51.
89. Twiddy SS, Farrar JJ, Chau NV, et al. Phylogenetic relationships and
differential selection pressures among genotypes of dengue-2 Virus.
Virology 2002;298:63–72.
90. Vasilakis N, Tesh RB, Weaver SC. Sylvatic dengue virus type 2 activity
in humans, Nigeria, 1966. Emerg Infect Dis 2008;14:502–4.
91. Wang E, Ni H, Xu R, et al. Evolutionary relationships of
endemic/epidemic and sylvatic dengue viruses. J Virol
2000;74:3227–34.
92. Kumar SRP, Patil JA, Cecilia D, et al. Evolution, dispersal and
replacement of American genotype dengue type 2 viruses in India
(1956-2005): selection pressure and molecular clock analyses. J Gen
Virol 2010;91:707–20.
93. Wittke V, Robb TE, Thu HM, et al. Extinction and rapid emergence
of strains of dengue 3 virus during an interepidemic period. Virology
2002;301:148–56.
94. Sharma S, Dash PK, Agarwal S, Shukla J, Parida MM, Rao PVL.
Comparative complete genome analysis of dengue virus type 3 cir-
culating in India between 2003 and 2008. J Gen Virol 2011;92:
1595–600.
95. Kukreti H, Mittal V, Chaudhary A, et al. Continued persistence of
a single genotype of dengue virus type-3 (DENV-3) in Delhi, India
since its re-emergence over the last decade. J Microbiol Immunol Infect
2010;43:53–61.
96. Lanciotti RS, Gubler DJ, Trent DW. Molecular evolution and phylogeny
of dengue-4 viruses. J Gen Virol 1997;78:2279–84.
97. Dash PK, Sharma S, Srivastava A, et al. Emergence of dengue virus type
4 (genotype I) in India. Epidemiol Infect 2011;139:857–61.
98. Cecilia D, Kakade MB, Bhagat AB, et al. Detection of dengue-4 virus in
Pune, western India after an absence of 30 years - its association with
two severe cases. Virol J 2011;8:46.
99. Kumaria R, Chakravarti A. Molecular detection and serotypic char-
acterization of dengue viruses by single-tube multiplex reverse
transcriptase-polymerase chain reaction. Diagn Microbiol Infect Dis
2005;52:311–6.