Indian Pediatr 2012;49:
Prevention of Rotavirus Diarrhea in India: Is
Vaccination the Only Strategy?
Rakesh Lodha and Dheeraj Shah*
Department of Pediatrics, All India Institute of
Medical Sciences and *Department of Pediatrics, University College of
Medical Sciences and GTB Hospital, New Delhi, India.
Diarrheal diseases continue to be an important cause of morbidity and
mortality in under-fives in India despite various preventive and
standardized case management strategies . It was estimated that in
2005, 302000 children age 1- 59 months died due to diarrheal diseases
giving a mortality rate of 11.1 per 1000 live births . The WHO and
UNICEF have proposed a 7-point action plan to reduce the childhood
diarrheal morbidity and mortality . The treatment package of this
plan includes: (i) fluid replacement to prevent dehydration and (ii)
zinc treatment, while the prevention package includes (iii)
rotavirus and measles vaccinations, (iv) promotion of early and
exclusive breastfeeding and vitamin A supplementation, (v)
promotion of hand washing with soap, (vi) improved water supply
quantity and quality, including treatment and safe storage of household
water, and (vii) community-wide sanitation promotion.
The etiology of childhood diarrhea has been
determined in a few studies in India, most of which have been hospital
based. In this issue of the journal, Kahn, et al. review the
epidemiology and prevention of rotavirus gastroenteritis in India, with
main focus on the issue of introduction of a vaccine to help control
rotavirus disease . This review adds to the previous publications of
the group on the subject. A few issues need discussion to view the
results of the review in proper perspective and in an unbiased manner.
Based on the etiology studies conducted in the
country, it is estimated that approximately 40% of cases of diarrhea
among hospitalized children are due to rotavirus. Most of these studies
included in this review aimed to identify rotavirus infection only and
not all etiologic agents of childhood diarrhea . The case fatality
rates in the rotavirus and non-rotavirus diarrheas in these studies have
not been reported. So, the authors of the current review  have
extrapolated the proportion of hospitalized childhood diarrhea cases
where rotavirus infection was demonstrated to estimate the numbers of
deaths caused by rotavirus diarrhea. A recent study from Kolkata
reported that of the 493 cases positive for rotavirus, 285 (57.8%) were
co-infected with other pathogens; children had a higher co-infection
rate than adults . In such a scenario, attributing all deaths to
rotavirus where rotavirus infection was reported would be inappropriate
and would lead to an overestimation of the numbers of deaths
attributable to rotavirus diarrhea. Available data suggests that only
12% of all deaths attributed to diarrheal diseases took place in health
facility . Are the causes of death in children with diarrhea who die
at home same as those in hospitalized children? Evidence suggests that
malnutrition and systemic infection are major associates of fatal
diarrhea in hospitalized children rather than dehydration .
Arguing that rotavirus infections continue to persist
in high income settings and the proportion of diarrhea caused by
rotavirus does not vary widely between developed and developing
countries, the authors conclude that sanitation and hygiene have less of
an impact on rotavirus disease and emphasize that immunization with
rotavirus vaccines is the only specific prevention strategy . Does a
child in the developed world have the same number of episodes of
diarrhea as one does in the developing world? It is essential to know
the incidence rates of diarrhea in the developed countries, which
unfortunately the authors of the current review have chosen to ignore;
this is important for understanding the differences in the epidemiology
of childhood diarrhea in the developed and developing countries.
Available data from the WHO shows that the burden of childhood diarrheal
illness (DALY 2004) per capita was, as compared to that in high income
countries (0.0012), 11 times higher in middle income countries (0.0134)
and 51 times higher in low income countries (0.0611) . Part of the
difference is due to the high death rate in low and middle income
countries, but the difference in the per capita burden persists even
after removing the contribution of deaths. This indirectly provides
evidence of the impact of economic development, better sanitation, safe
water supply and better health systems on the diarrheal disease burden
in children, including that due to rotavirus.
Substantial gains in the control of diarrheal
diseases in the industrialized countries were made before introduction
of rotavirus vaccines. Even in India there are significant differences
in the mortality rates due to diarrhea in children 1- 59 months age
among various states: these vary from 0.3 (95 % CI: 0.0- 1.6) in Kerala
to 17.8 (95 % CI 15.9-19.8) per 1000 live births in Bihar . The rates
are 2.5 times higher in the lower-income Indian states compared with
higher-income states (14.8 vs 5.8). This suggests that reduction
in the mortality rates due to diarrheal illnesses can be achieved even
in the absence of rotavirus vaccines; most of this may be due to better
sanitation, water supply and better health systems.
There are systematic reviews supporting the important
role of good sanitation, hand washing and safe water supply in reducing
the morbidity due to diarrheal diseases . In such a scenario,
excessively greater weightage assigned to the use of rotavirus vaccine
for prevention of rotavirus diarrhea by the authors of the review
appears unjustified. The authors have inappropriately dismissed the
importance of other strategies for prevention of rotavirus diarrhea
without providing strong scientific evidence. Improving sanitation,
ensuring supply of safe drinking water, promoting good hygiene and hand
washing are likely to have substantial gains not just for childhood
diarrheal diseases but also for reducing the burden of enteric diseases
in all age groups; the disease burden in older children and adults in
India is also substantial. Fischer Walker et al. have provided
evidence for the impact of a multi-pronged strategy including the WASH
(water, sanitation and hygiene) interventions for diarrhea prevention
using the Lives Saved Tool analysis .
The rotavirus serotypes prevalent in the country
appear to be different from that in the west. In a multi-center study
enrolling 4243 children with diarrhea (39% tested positive for
rotavirus), the most common types of strains were G2P(4) (25.7% of
strains), G1P(8) (22.1%), and G9P(8) (8.5%) . The authors of the
study observed that 22.1% of the strains identified in this study would
be covered by Rotarix (GSK Biologicals) and 47.9% by RotaTeq (Merck)
. While there is some evidence to suggest that there may be
cross-protection, the same has not been shown in India.
There have been no trials in Indian children
evaluating efficacy of the two available vaccines against rotavirus
diarrhea; the efficacy data from other countries may not be applicable
to the country. One study evaluated the immunogenicity of Rotarix
vaccine . In this study, it was observed that 27% of the 8-week old
infants were initially seropositive; the seroconversion rate observed
one month post-dose 2 in the Rotarix group was 58.3% (95% CI: 48.7;
67.4) . In another study evaluating the immunogenicity of Rotateq
vaccine it was observed that 20% of 6- 12 week old infants had serum
anti rotavirus IgA ³20
IU/mL at baseline . 83% infants demonstrated seroconversion
(increase in the anti rotavirus IgA titers by a factor of 3 or more from
baseline to approximately 6 months) in the per protocol analysis .
The percentage of patients who demonstrated 3 fold increase in G1
neutralizing antibody titre was 38.2%, for G2, G3, G4 and P1 were 14.7%,
30.4%, 37.2% and 30.4% respectively. The low rate of seroconversion
against G2 may be of concern as this is an important serotype in Indian
scenario. It is surprising that these two vaccines have been approved
for marketing in India by the regulators despite insufficient
immunogenicity and absent efficacy data in Indian children. In such a
scenario, there is need for efficacy data for the existing and newer
rotavirus vaccines in Indian children; this is particularly important to
address the issue of adding the vaccine to the UIP.
While all Indian children should benefit from the
available, safe and efficacious vaccines, the decisions to incorporate
new vaccines in national schedule will need discussions with policy
makers where various issues other than the safety and efficacy will also
be important. The current estimate of disease burden itself shows major
gaps. Cost of the vaccine is important; however, with various options
available, the same can be worked around. One also has to assess the
capacity of the health systems to determine if the intervention will be
delivered effectively. The overall immunization rates are still
inadequate. Particularly important for rotavirus vaccination is the time
of administration of the doses; for Rotateq vaccine, immunization should
not be initiated beyond 12 weeks of age. In such a scenario, will the
health care system be able to deliver the rotavirus vaccine to children
efficiently, particularly to those who need it the most? The prevention
of rotavirus diarrhea in children can be best achieved with a
multi-pronged strategy; introduction of the rotavirus vaccine at some
stage may be one of them, provided there is sufficient and reliable
efficacy and effectiveness data from the country.
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