Diarrhoeal Diseases An abnormal

frequency and liquidity of faecal discharge"

-Hippocrates

• WHO for epidemiological reason

passing > 3 loose or watery stools in a
day
• It is one of the leading cause of the
morbidity & mortality in children <5 year
worldwide.
 Type
• Acute infectious diarrhea –
1. Non inflammatory - enterotoxin (cholera),
destruction of villus surface by virus or parasite
2. Inflammatory diarrhea - bacterial, viral,
parasitic.
• Chronic or persistent >14 days –
1.Giardia lamblia, cryptosporidium parvum &
enteroaggregative or enteropathogenic E coli.
2. Enteropathogen that infect immunocompro.
3. Damage to intestine after acute infection.
 Non infectious causes of diarrhea
• Feeding difficulty
• Malabsorption
• Endocrinopathy
• Food poison
• Neoplasm
• Mis. – milk allergy, immune deficiency,
laxative abuse, protein losing enteropathy.
 Bacterial enteropathogen
• Entero invasive E. coli, Shiga toxin
producing E. coli, Campylobactor jejuni.
Salmonella, Shigella.
• Viral – Rotavirus, Enteric adenovirus,
Norwalk agent- like virus.
• Parasitic Enteropathogen – G. lamblia,
entamoeba histolytica, Strongyloides
stercoralis.
 Average composition of diarrhea
• Sodium: 55mEq/l
• Potassium:25mEq/l
• Bicarbonate: 15mEq/l
Approach to replacement of ongoing losses
• Solution:D51/4NS + 15mEq/lbicarbonate +
25mEq/l KCL
• Replace stool ml/ml every1 -6 hour.
 Clinical assessment
• Previous WHO classification of mild moderate
and severe dehydration is modified into no
dehydration, some dehydration and severe
dehydration for clinical assessment..
Classification of dehydration
Classification

Previous

No dehydration

Mild dehydration

Moderate dehydration

Severe dehydration

Current

No dehydration

Some dehydration
%wt. loss

Severe dehydration
 Clinical Assessment
• WHO: IMCI guidelines have modified the WHO
assessment of dehydration and four signs are
now used to classify a child with dehydration.
• The sensorium
• Sunken eyes
• Thirst: whether the child drinks poorly or
eagerly
• Skin pinch: whether goes back very slowly or
slowly..
 In 1978 the editorial of Lancent
commented:

• ‘The discovery that sodium transport and

glucose transport are coupled in the small
intestine so that glucose accelerates absorption
of solute and water was potentially the most
important medical advance of the 20th century’..
 Benefit of ORT
• Following the widespread use of oral
rehydration therapy the goal of deaths due to
diarrhoea: reducing by 50% has been achieved
globally, according to World Health organization
(WHO) estimates..
 The WHO ORS
• The WHO ORS has a total osmolarity of 311
mOsmol/L which is higher than that of
plasma (i.e., 285 mOsmol/L.
• WHO-ORS formula being used in developing
countries can lead to hypernatremia as it has
higher sodium concentration than that of
solution commercially available.
 The New Hypo-osmolar ORS
• WHO and UNICEF now recommend that countries
manufacture and use the following formulation instead
of the previously recommended ORS solution with a
total osmolarity of 311 mOsm/l.

Reduced osmolarity grams/litre Reduced osmolarity mmol/litre

ORS ORS
Sodium chloride 2.6 Sodium 75
Glucose, anhydrous 13.5 Chloride 65
Potassium Chloride 1.5 Glucose, anhydrous 75
Trisodium Citrate, 2.9 Potassium 20
dihydrate Citrate 10
Total Osmolarity 245
 Rice ORS
• Out of many supers ORS, rice powder based
ORS gained popularity as a result of research
carried out in Bangladesh, Egypt, India and
Nepal and accredited rice powder's inclusion in
Super ORS.
• In Rice ORS, glucose or sucrose was replaced
by 50 gm/litre rice flour. Other electrolytes were
left intact as for standard ORS.
• The problem with Rice-ORS is that boiling is
needed to prepare it, it has a short life once
prepared and may not be suitable for babies
less than 3 months old..
 ReSoMal
• Special Rehydration Solution for Malnutrion
( ReSoMal)
• ReSoMal (low sodium and high potassium ORS)
• ReSoMal contains approximately 45 mmol Na,
40 mmol K and 3 mmol Mg/litre..
 Newer therapy and management
• New Hypo-osmolar ORS
• Zinc
• Probiotics
 Zinc

• Researchers in rural Bangladesh found

that zinc treatment significantly reduced
the incidence of diarrhoea and acute lower
respiratory infection, admissions to
hospital. Zinc treatment is a simple and
inexpensive intervention that can be used
within existing diarrhoeal disease control
efforts
• Zinc deficiency is highly prevalent in children in
developing countries. Inadequacy of dietary zinc
intake is exacerbated by the net loss of zinc
during diarrhoea. Zinc supplements given during
diarrhoea reduce the duration and severity of
treated episodes and, if given for 14 days during
and after diarrhoea, can reduce the incidence of
diarrhoea and acute lower respiratory infection
in the subsequent two to three months. Provision
of zinc during diarrhoea may thus be a feasible
strategy for both treatment of diarrhoea and
prevention of subsequent morbidity & mortality.
• Zinc is a micronutrient found in foods rich in
protein such as red meat, poultry, nuts and dairy
products and is essential for human growth and
protection against illness and disease. Many
people living in developing nations, such as
Bangladesh, do not have access to sufficient
amounts of zinc-rich foods. This results in zinc
deficiency that can lead to growth failure and
increased susceptibility to illness and death,
especially among young children.
 SUZY - Scaling Up Zinc treatment
for Young children with diarrhoea in
Bangladesh
• A project funded by the Bill and Melinda Gates
Foundation
• Diarrhoea remains a leading cause of morbidity and
mortality in developing countries, killing nearly 2 million
children every year. Research has shown that zinc
provides a very effective treatment for diarrhoea among
children under five years of age. Zinc treatment reduces
the severity and duration of diarrhoea as well as the
likelihood of future episodes of diarrhoea and the need
for hospitalisation. Zinc treatment can save a child’s life,
both as a treatment for diarrhoeal illness and by
preventing future infectious illnessess.
• ORS and Zinc: Treatment of diarrhoea is now
more effective
• WHO and UNICEF therefore recommend daily
20 mg zinc supplements for 10–14 days for
children with acute diarrhoea, and 10 mg per
day for infants under six months old, to curtail
the severity of the episode and prevent further
occurrences in the ensuing 2-3 months.
 Probiotics
• Probiotics are gut friendly nonpathogenic
microorganism supplement as food or in
the form of drugs that colonise the gut
and protect intestine by competing with
pathogens for attachment.
 Probiotics
• For mild diarrhoea, though, another
common piece of advice is to use dietary
supplements or foods containing
probiotics. These are believed to reach the
bowel and protect against bacteria there.
Probiotics are a familiar ingredient in some
dairy products, like yoghurt and yoghurt-
type drinks
• In the trials where the length of the case of
diarrhoea was counted, probiotics
shortened the illness by about 30 hours.

• They consist of either yeast or bacteria,

Bifidobacterium and Lactobacillus.
• Definitely indicated in the prevention of
diarrhoea following antibiotic use,
Clostridium difficile induced diarrhoea.
• Natural probiotics exist in several
foods including yogurt, certain cereals
and fermented milk. Specifically, probiotics
consist of lactic acid producing bacteria
(LAB), non-lactic acid producing bacterial
species, and non-pathogenic yeast. Some
of the commonly used microflora in
probiotics include L. acidophilus, L.
fermentum, L. paracasei
 Use of Drugs
• Many diarrhoeal episodes are self limiting
requiring only replacement of lost fluid and
electrolytes. Small proportion need IV fluid.
• Bloody diarrhoea with fever and systemic illness
is more likely to be due to Campylobacter,
Shigella or Salmonella.
• But blood in stool without systemic upset may
be due to amoebiasis..
 Stool Examination
• Characteristic of stool provide important clues
about causative organism
• Stool culture is of no value and not always
necessary, however
• During dysentery epidemics it is worth doing
culture tests to discover disease and sensitivity
pattern. In resistant cases and during
epidemics Nalidixic acid will be the first line of
drug to be used. In case of poor response
Norfloxacin, Ciprofloxacin or a 3rd generation
Cephalosporin can be used..
 Vaccine development
• Rotavirus Vaccine,
• Cholera Vaccine
• Shigelia Vaccine
• Typhoid Vaccine
• Vaccines for other Bacterial Pathogens

Vaccine is an important and cost effective weapon

in the fight against diarrhoeal disease
 Rotavirus Vaccine
• Rotavirus is the leading cause of severe
diarrhoea among infant & children. Each year
> 500.000 children die in developing countries.
Another two million are hospitalized.
• The development of rotavirus vaccine has
received priority in research activities. The
Rotavirus Vaccine Program is a collaboration
between PATH, the World Health Organization
and the U.S. Centers for Disease Control and
Prevention, and is funded by the Global Alliance
for Vaccines and Immunization
• Rotarix is a human, live attenuated rotavirus
vaccine containing a rotavirus strain of G1P[8]
specificity
 Cholera vaccine
• Traditional parenteral whole-cell (WC) cholera vaccine has never
been recommended by the World Health Organization (WHO)
because of its low protective efficacy and its high reactogenicity.
• Currently available oral cholera vaccines (OCV) are safe and offer
good protection (over 70%) for an acceptable period of time (at least
one year).
• The use of OCV is considered as an additional public health tool to
usually recommended cholera control measures such as provision
of safe water and adequate sanitation.
• OCV use is recommended for populations to limit the risk of:
– occurrence of cholera outbreaks in displaced populations in endemic
areas,
– spread and incidence of cholera during an outbreak.
• Live attenuated single-dose cholera vaccine CVD 103-
HgR, Orochol-E®, contains a live attenuated strain
derived from reference strain 569B (classical, O1, Inaba)
presented in a single dose.
– Protective efficacy was reached 8 days after administration of
the vaccine in a volunteer's challenge study.
– Therefore, use of the single dose OCV may be possible
once an outbreak has started.
• Killed WC B subunit cholera vaccine (WC/rBS),
Dukoral®, derived from mixtures of WC killed strains.
They are given in two doses, 10-14 days apart.
– Protective efficacy is reached 10 days after the second dose.
– The two-dose OCV is currently not indicated for use once an
outbreak has started.
 Shigella vaccine
• Shigallosis, especially that due to shigella
dysenteriae type I (Shiga bacillus), remains an
important cause of dysentery epidemics and
morbity and mortality.
 Pediatric Shigella Vaccine Safe,
Immunogenic
• Aug. 25, 2003 — An experimental Shigella
conjugate vaccine is safe and immunogenic in
one- to four-year-old children, according to the
results of a preliminary trial published in the
August issue of the Pediatric Infectious Disease
Journal. This age group is at greatest risk for
shigellosis.
• To form conjugates, the investigators bound the O-
specific polysaccharides of S. sonnei and S. flexneri 2a,
the two most common shigellae from patients in Israel, to
medically useful carrier proteins. Eighty healthy one- to
four-year-old children were randomized to receive two
0.5-mL intramuscular injections, given six weeks apart,
of either S. sonnei-CRM9 or S. flexneri 2a-rEPAsucc.
• Low-grade fever (37.8-39.0 ° C) lasting 24 to 48 hours
occurred after the first injection of S. flexneri 2a-
rEPAsucc in two of 40 children, after the second injection
of S. flexneri 2a-rEPAsucc in four of 40 children, and
after the second injection of S. sonnei-CRM9 in two of 38
children. All children had normal liver function test after
vaccination.
• IgG anti-lipopolysaccharide (LPS) antibodies rose at least four-fold
in 92.1% of S. sonnei- CRM9 vaccinees and in 85% of S. flexneri
2a-rEPAsucc vaccinnees after the second injection (P < .0001). Both
conjugates elicited type-specific booster responses. Two years after
vaccination, the geometric mean concentrations of both IgG anti-
LPS antibodies were significantly higher than preimmunization
levels. IgG anti-diphtheria antibodies rose at least four-fold in 65.8%,
and IgG anti-ETA rose at least four-fold in 77.5%.
• "These experimental Shigella conjugate vaccines were safe and
immunogenic in one- to four-year-old children, the authors write. "On
the basis of these data, an efficacy trial for prevention of shigellosis
in Israel is planned.
 Typhoid vaccine
• There is now an oral typhoid vaccine and
a single-dose injectable vaccine that
produces fewer side effects than the older
two-dose injectable vaccine. Both
vaccines are equally effective and offer
65% to 75% protection against the
disease.
• The oral vaccine (Vivotif) contains a live but weakened
strain of the Salmonella bacteria that causes typhoid
fever. The vaccine consists of four capsules that are
taken every other day over a one-week period. The
capsule protects the vaccine against stomach acid so it
remains active when it reaches the intestine where the
immunity develops. The oral vaccine can be given either
as a first-time dose or as a booster dose. The protection
should last about 5 years, at which time another booster
dose would be needed if traveling again. The oral
vaccine is not recommended for children under 6 years
old.
• The single-dose injectable vaccine (Typhim Vi)
containing capsular polysaccharide antigen
became available in February, 1995. The
protection offerred by this vaccine is effective
starting 2 weeks after injection and should last
for 2 years. Subsequent booster doses are
recommended at 2-year intervals. This vaccine
can be used in children as young as 2 years old.
Side effects, while greater than those of the oral
vaccine, are much less than those experienced
with the old 2-dose injectable vaccine.
 Antiemetics
• Vomiting is not a disease and usually
stops by itself once dehydration is
corrected.
• Rotavirus diarrhoea starts with vomiting–
vomiting stops by self and diarrhoea
follows. Small and frequent doses of
ORS and other feeds should be given if
the patient is vomiting.
• For cause of vomiting outside GI tract
should also be sought..