Population-level effect of cholera vaccine on displaced populations, South Sudan, 2014.
In April 2014, two months after vaccine deployment, South Sudan confirmed the first case of cholera in the country since 2009; [approximately equal to] 4 weeks later, officials declared a cholera outbreak. Over 5 months, 6,269 suspected cholera cases were reported, including 156 deaths. Most cases occurred outside vaccinated camps, often in communities or camps surrounding vaccinated populations.
Several studies have demonstrated the individual-level (direct) effects of oral cholera vaccination (2-4), but few have estimated the overall population-level effect (a combination of direct and indirect effects), which is critical to determining costs and benefits. To estimate the overall effect, the observed epidemic in vaccinated areas must be compared with a counterfactual epidemic that is modeled or based on an observed suitable control population.
We used detailed epidemiologic data from the 2014 vaccination campaigns and the subsequent cholera outbreak in South Sudan to determine how vaccine use may have altered the epidemic course in vaccinated areas. We compared epidemics in 2 areas that included vaccinated and unvaccinated populations: 1) PoC sites (vaccinated) and the community (unvaccinated) in Juba; and 2) Malakal PoC (vaccinated) and Wau Shilluk IDP (unvaccinated), 2 similar camps separated by a river.
The South Sudan Ministry of Health and World Health Organization implemented a clinic-based cholera surveillance system that captured basic patient data, laboratory results (if available), and outcomes. A suspected cholera case-patient was defined as anyone with acute watery diarrhea (diagnosed by a clinician); suspected cases were considered confirmed if the patient had a culture-positive fecal sample. Our analyses include all suspected cases.
We considered 5 populations in our comparisons, 3 in Juba County and 2 in Malakal County. In Juba, displaced persons were largely confined to 2 camps: 1) Tongping PoC camp (population 14,015) near the center of Juba; and 2) the UN House PoC camp (population 17,627) on the outskirts the city. We assumed all camp occupants were at risk for cholera and that, in the Juba community, only those residents without access to improved sanitation were at risk (5,6) (online Technical Appendix, http://wwwnc.cdc.gov/ EID/article/22/6/15-1592-Techapp1.pdf).
Two-dose vaccine coverage among those eligible for vaccination (based on age and pregnancy status) was 93% in Tongping PoC and 95% at UN House; the remaining Juba population was not vaccinated (1). In Malakal, we compared an informal unvaccinated IDP settlement, Wau Shilluk (population 39,000; online Technical Appendix), with an official PoC site, Malakal PoC camp (population 17,000; online Technical Appendix). Two-dose vaccine coverage in Malakal was 92.2% based on a coverage survey using systematic random sampling (1).
We estimated the time-varying reproductive number of cholera within each location (online Technical Appendix) (7). We assumed that the median generation time for cholera followed a gamma distribution with a median of 5 days and that all infectious cases were clinically apparent. We calculated 95% CIs by using a multiple imputation and bootstrapping routine, in which we first stochastically imputed missing or inconsistent symptom onset times and then resampled observations with replacement (online Technical Appendix).
The cholera attack rate in the Juba community was 53.4 cases/10,000 persons at risk (i.e., 2,229 cases/387,512 persons at risk), compared with 49.9 cases/10,000 persons at risk in the Juba camps (i.e., 158 cases/31,642 persons at risk). Although the overall attack rates were similar, the age distribution in camps differed markedly from those in the community. In the community, the risk for cholera among children <5 and those >5 years of age was nearly identical (risk ratio [RR] 1.0), but in the camps, the risk was substantially higher among children <5 years of age (Table; Figure 1). These age-specific differences in attack rates between camps and the community did not appear to be explained by population structure, age-specific vaccination coverage, or circulation of another diarrheal pathogen in the camps (online Technical Appendix); the differences point toward possible lower vaccine effectiveness among young children. The response mounted to oral vaccines is weaker in children than adults (8), although considerable uncertainty remains regarding the response to the oral cholera vaccine.
The difference in the estimated cumulative cholera attack rates between the unvaccinated Wau Shilluk IDP camp (236.4 cases/10,000 persons at risk) and the vaccinated Malakal PoC camp (38.8 cases/10,000 persons at risk) was even more striking (incidence rate ratio 6.1) (Table). Age-specific population figures were unavailable for Wau Shilluk.
Although differences in attack rates suggest a likely reduction in cholera risk in vaccinated areas and the possibility of age-dependent vaccine protection, these estimates are uncertain and should be cautiously interpreted. An alternative approach to understanding the effect of vaccination is to compare observed cholera transmission dynamics within vaccinated and unvaccinated populations.
The epidemic curves within vaccinated camps in Juba had no distinct peak and suggest a series of cholera introductions with little to no onward transmission (Figure 2). We estimated that the daily reproductive number ([R.sub.t]; i.e., average number of secondary cases from a case becoming symptomatic on day t; online Technical Appendix) in vaccinated camps was [less than or equal to] 1 for most of the epidemic. Each vaccinated camp had only 2 days on which the 95% CI of [R.sub.t] was above unity. This finding contrasts with our estimates in unvaccinated areas, where despite conditions that may have been less suitable for transmission, [R.sub.t] remained >1 for a sufficient and significantly longer time for an epidemic to progress (p<0.0001; Table; online Technical Appendix).
We show that cholera vaccination campaigns likely played a key role in curtailing cholera transmission in vaccinated areas within South Sudan. The age-specific transmission patterns within the vaccinated camps in Juba suggest that vaccinated young children were less protected in the camps, although further investigation is needed to explore this and other possible explanations, including age-specific differences in care-seeking behavior between populations.
Our study had several limitations. Analyses were based on suspected cases, which were defined by using a sensitive, but less specific, case definition; thus, many included cases were likely to be false positives. Our estimates of cholera attack rates depended on estimates of the population at risk in each area. We used the most reliable and up-to-date sources from agencies with an operational presence on the ground; however, the sizes of the dynamic community and camp populations used in the analyses were uncertain, and this uncertainty was not accounted for in the models. Last, we estimated the time-varying reproductive number of cholera by assuming a fixed generation time throughout the epidemic, which may not reflect reality due to the possibility of differences in care-seeking behavior and differential contraction of generation intervals between populations with an increasing prevalence of cholera (9).
Our findings provide evidence of the population-level effects of oral cholera vaccine. More work is needed to quantify this effect across multiple settings in reactive and preemptive deployments of the vaccine. High-quality surveillance and capacity to confirm suspect cases can greatly improve the possibility of making future estimates.
We acknowledge the work of all the public health workers involved in these vaccination campaigns and the larger cholera response, including members of the South Sudan National Cholera Task Force.
The work of A.S.A., D.A.S., J.L., and F.J.L. was supported by the Bill and Melinda Gates Foundation (OPP1089243 and the DOVE [Delivering Oral Vaccine Effectively] project, OPP153556).
Dr. Azman is a research associate in the Epidemiology Department at Johns Hopkins University Bloomberg School of Public Health. His research interests include infectious disease dynamics and vaccine study design, with a particular focus on cholera and hepatitis E.
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Address for correspondence: Andrew S. Azman, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe St, Rm E6003, Baltimore, MD 21205, USA; email: email@example.com
Andrew S. Azman, John Rumunu, Abdinasir Abubakar, Haley West, Iza Ciglenecki, Trina Helderman, Joseph Francis Wamala, Olimpia de la Rosa Vazquez, William Perea, David A. Sack, Dominique Legros, Stephen Martin, Justin Lessler, Francisco J. Luquero
Author affiliations: Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA (A.S. Azman, D.A. Sack, J. Lessler, F.J. Luquero); Ministry of Health, Juba, South Sudan (J. Rumunu); World Health Organization, Juba (A. Abubakar, J.F. Wamala); International Organization for Migration, Juba (H. West); Medecins Sans Frontieres, Geneva, Switzerland (I. Ciglenecki); Medair, Ecublens, Switzerland (T Helderman); Medecins Sans Frontieres, Barcelona, Spain (O. de la Rosa Vazquez); World Health Organization, Geneva (W. Perea, D. Legros, S. Martin); Epicentre, Paris, France (F.J. Luquero)
Table. Effect of oral cholera vaccine by location, South Sudan, 2014 * Location Variable Jubaf Tongping Setting type Community PoC Camp Population vaccinated No Yes Population at risk 387,512 14,015 No. cases/10,000 persons 53.4 51.3 No. cases/10,000 children 56.0 186.5 <5 y of age Risk ratio, children <5 y 1.0 3.6 compared with those [greater than or equal to] 5 y of age No. days with [R.sub.t] 16 ([double dagger]) 2 ([double dagger]) >1 Maximum [R.sub.t] 2.4 1.5 Location Variable UN House Wau Shilluk ([dagger]) Setting type PoC Camp IDP camp Population vaccinated Yes No Population at risk 17,627 39,000 No. cases/10,000 persons 48.8 236.4 No. cases/10,000 children 146.5 -- <5 y of age Risk ratio, children <5 y 3.0 -- compared with those [greater than or equal to] 5 y of age No. days with [R.sub.t] 2 ([double dagger]) 14 ([double dagger]) >1 Maximum [R.sub.t] 1.5 2.2 Location Variable Malakal Setting type PoC camp Population vaccinated Yes Population at risk 17,000 No. cases/10,000 persons 38.8 No. cases/10,000 children -- <5 y of age Risk ratio, children <5 y -- compared with those [greater than or equal to] 5 y of age No. days with [R.sub.t] 2 ([double dagger]) >1 Maximum [R.sub.t] 1.9 * IDP, internally displaced person; PoC, protection of civilian; [R.sub.t], reproductive number; UN, United Nations; --, no age-specific population data available. ([dagger]) Reference population. ([double dagger]) Significant difference (p<0.0001) in number of days with [R.sub.t] >1, compared with reference population.
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|Author:||Azman, Andrew S.; Rumunu, John; Abubakar, Abdinasir; West, Haley; Ciglenecki, Iza; Helderman, Trina;|
|Publication:||Emerging Infectious Diseases|
|Date:||Jun 1, 2016|
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