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Cholera has been endemic in India and Bangladesh for the greater part of recorded history, giving this region the reputation of being the 'homeland of cholera'. The causative organism Vibrio cholerae O1 has been responsible for large epidemics and pandemics. Bangladesh and India have conducted several sequential studies of Oral Cholera Vaccine (OCV) to ascertain its safety, efficacy, effectiveness, field feasibility and acceptance in high-risk urban populations. The objective of this article is to illustrate the experience of OCV use in these endemic settings, its major challenges, and how policymakers can grant vaccine licenses as well as implement its use in the national immunization programme. The relevant aspects of the OCV studies, such as boosting the effect of vaccine, single-dose versus double-dose trials and thermal stability of the vaccine during delivery have generated strong evidence for recommendation of vaccine use in these settings. Studies have shown that a single dose is effective for children of five years of age and older age groups. The locally manufactured vaccine in India is thermostable and can be delivered in field settings without use of cold chain. The vaccine delivery is feasible and the protective efficacy (PE) of this vaccine above five years of age against cholera was 53-65%. Administration of an OCV boosting regimen elicits an immune response similar to those who received a two-dose vaccine five years back. OCV can be used as a preemptive measure in endemic settings, in natural calamities and during political instability when there is total disruption as well as collapse of safe water supply, sanitation and hygiene (WASH) facilities and other control measures. Clear identification of areas and target population (who will gain benefit from the OCVs) is required to be developed in endemic settings.

Background Case–control studies have not been examined for their utility in assessing population-level vaccine protection in individually randomized trials. Methods We used the data of a randomized, placebo-controlled trial of a cholera vaccine to compare the results of case–control analyses with those of cohort analyses. Cases of cholera were selected from the trial population followed for three years following dosing. For each case, we selected 4 age-matched controls who had not developed cholera. For each case and control, GIS was used to calculate vaccine coverage of individuals in a surrounding “virtual” cluster. Specific selection strategies were used to evaluate the vaccine protective effects. Results 66,900 out of 108,389 individuals received two doses of the assigned regimen. For direct protection among subjects in low vaccine coverage clusters, we observed 78% (95% CI: 47–91%) protection in a cohort analysis and 84% (95% CI: 60–94%) in case–control analysis after adjusting for confounding factors. Using our GIS-based approach, estimated indirect protection was 52% (95% CI: 10–74%) in cohort and 76% (95% CI: 47–89%) in case control analysis. Estimates of total and overall effectiveness were similar for cohort and case–control analyses. Conclusion The findings show that case–control analyses of individually randomized vaccine trials may be used to evaluate direct as well as population-level vaccine protection.

Background Rotavirus infections, prevalent in human populations worldwide are mostly caused by Group A viruses. Live attenuated rotavirus vaccines are highly effective in preventing severe rotavirus gastroenteritis. However, the cost of these vaccines and local availability can be a barrier for widespread adoption in public health programs in developing countries where infants suffer a heavy burden of rotavirus related morbidity and mortality. A phase I/II study was carried out with the long term aim to produce a locally licensed vaccine which is equally safe and immunogenic as compared to available licensed vaccines. Methods This study was conducted in two cohorts. In the first cohort, 20 healthy adults were administered a single dose of the rotavirus vaccine (highest antigen concentration planned for infants) or placebo and were followed up for 10 days for safety. Following demonstration of safety in adult volunteers, 100 healthy infants were recruited (cohort 2) and randomly divided into five equal study groups. They were administered three doses of either the investigational rotavirus vaccine (BRV-TV) at one of the three antigen concentrations or Rotateq or Placebo at 6–8, 10–12 and 14–16 weeks of age. All infants were followed up for safety till 28 days after the third dose. Immune response to the vaccine, in terms of seroresponse and geometric mean concentrations, was compared across the five study groups. Results Increase in anti-rotavirus serum IgA antibodies from baseline, demonstrated higher immune response for all the three antigen concentrations of BRV-TV vaccine and RotaTeq in comparison with the placebo. Sero-response rates for placebo, BRV-TV dose-levels 10 5.0 FFU, 10 5.8 FFU, 10 6.4 FFU, and Rotateq at 28 days post third dose were 11.1%, 27.8%, 41.2%, 83.3%, and 63.2% respectively using the four-fold or more criteria. The BRV-TV vaccine arm corresponding to the highest antigen concentration of 10 6.4 FFU had a higher sero-response rate compared to the active comparator arm (RotaTeq), 28 days post each vaccine dose. The safety profile was comparable across the treatment groups. Conclusions Overall, the results showed that all three doses of BRV-TV vaccine were safe, well tolerated and displayed good immunogenicity (dose–response) in healthy Indian infants.

Background The test-negative design (TND) has emerged as a simple method for evaluating vaccine effectiveness (VE). Its utility for evaluating oral cholera vaccine (OCV) effectiveness is unknown. We examined this method's validity in assessing OCV effectiveness by comparing the results of TND analyses with those of conventional cohort analyses. Methods Randomized controlled trials of OCV were conducted in Matlab (Bangladesh) and Kolkata (India), and an observational cohort design was used in Zanzibar (Tanzania). For all three studies, VE using the TND was estimated from the odds ratio (OR) relating vaccination status to fecal test status ( Vibrio cholerae O1 positive or negative) among diarrheal patients enrolled during surveillance (VE = (1 − OR)×100%). In cohort analyses of these studies, we employed the Cox proportional hazard model for estimating VE (=1 − hazard ratio)×100%). Results OCV effectiveness estimates obtained using the TND (Matlab: 51%, 95% CI:37–62%; Kolkata: 67%, 95% CI:57–75%) were similar to the cohort analyses of these RCTs (Matlab: 52%, 95% CI:43–60% and Kolkata: 66%, 95% CI:55–74%). The TND VE estimate for the Zanzibar data was 94% (95% CI:84–98%) compared with 82% (95% CI:58–93%) in the cohort analysis. After adjusting for residual confounding in the cohort analysis of the Zanzibar study, using a bias indicator condition, we observed almost no difference in the two estimates. Conclusion Our findings suggest that the TND is a valid approach for evaluating OCV effectiveness in routine vaccination programs.

The burden of typhoid fever remains high in impoverished settings, and increasing antibiotic resistance is making treatment costly. One strategy for reducing the typhoid morbidity and mortality is vaccination with the Vi polysaccharide vaccine. We use a wealth of new economic and epidemiological data to evaluate the cost-effectiveness of Vi vaccination against typhoid in sites in four Asian cities: Kolkata (India), Karachi (Pakistan), North Jakarta (Indonesia), and Hue (Vietnam). We report results from both a societal as well as a public sector financial perspective. Baseline disease burden estimates in the four areas are: 750 cases per year in two Kolkata neighborhoods (pop 185,000); 84 cases per year in the city of Hue (pop 280,000); 298 cases per year in two sub-districts in North Jakarta (pop 161,000), and 538 cases per year in three squatter settlements in Karachi (pop 102,000). We estimate that a vaccination program targeting all children (2–14.9) would prevent 456, 158, and 258 typhoid cases (and 4.6, 1.6, and 2.6 deaths), and avert 126, 44, and 72 disability-adjusted life years (DALYs) over 3 years in Kolkata, North Jakarta and Karachi, respectively. The net social costs would be US$160 and US$549, per DALY averted in Kolkata and North Jakarta, respectively. These programs, along with a similar program in Karachi, would be considered “very cost-effective” (e.g. costs per DALY averted less than per capita gross national income (GNI)) under a wide range of assumptions. Community-based vaccination programs that also target adults in Kolkata and Jakarta are less cost-effective because incidence is lower in adults than children, but are also likely to be “very cost-effective”. A program targeting school-aged children in Hue, Vietnam would prevent 21 cases, avert 6 DALYs, and not be cost-effective (US$3779 per DALY averted) because of the low typhoid incidence there.

A mass typhoid Vi vaccination campaign was carried out among approximately 60,000 slum residents of Kolkata, India. This study evaluated the impact of the campaign on spatial patterns of typhoid fever. Eighty contiguous residential groups of households in the study area were randomized to receive either a single dose of the Vi polysaccharide vaccine or a single dose of the inactivated hepatitis A vaccine as the control agent. Persons aged two years and older were eligible to receive the vaccine. Vaccine protection against typhoid fever was monitored for two years after vaccination at both outpatient and inpatient facilities serving the study population. Geographic analytic and mapping tools were used in the analysis. Spatial randomness of the disease was observed during the pre-vaccination period, which turned into a significant pattern after vaccination. The high-risk areas for typhoid were observed in the area dominated by the control clusters, and the low-risk areas were in the area dominated by the Vi clusters. Furthermore, the control clusters surrounded by the Vi clusters were low risk for typhoid fever. The results demonstrated the ability of mass vaccination to change the spatial patterns of disease through the creation of spatial barriers to transmission of the disease. Understanding and mapping the disease risk could be useful for designing a community-based vaccination strategy to control disease.

Immune responses after one and two doses of the reformulated killed oral cholera vaccine were measured in a double-blind, randomized, placebo-controlled trial of 77 adults aged 18-40 years and 77 children aged 1-17 years residing in Kolkata, India. 65% of adults and 87% of children and 46% of adults and 82% of children exhibited aor =4-fold rise in serum Vibrio cholerae O1 vibriocidal antibody titers from baseline following dose 1 and 2, respectively. Responses to V. cholerae O139 were less pronounced but followed a similar pattern. We demonstrate that in a cholera-endemic area, the vaccine elicited vibriocidal responses after a single-dose of the vaccine.