RESUMO
In 2023, cholera affected approximately 1 million people and caused more than 5000 deaths globally, predominantly in low-income and conflict settings. In recent years, the number of new cholera outbreaks has grown rapidly. Further, ongoing cholera outbreaks have been exacerbated by conflict, climate change, and poor infrastructure, resulting in prolonged crises. As a result, the demand for treatment and intervention is quickly outpacing existing resource availability. Prior to improved water and sanitation systems, cholera, a disease primarily transmitted via contaminated water sources, also routinely ravaged high-income countries. Crumbling infrastructure and climate change are now putting new locations at risk - even in high-income countries. Thus, understanding the transmission and prevention of cholera is critical. Combating cholera requires multiple interventions, the two most common being behavioral education and water treatment. Two-dose oral cholera vaccination (OCV) is often used as a complement to these interventions. Due to limited supply, countries have recently switched to single-dose vaccines (OCV1). One challenge lies in understanding where to allocate OCV1 in a timely manner, especially in settings lacking well-resourced public health surveillance systems. As cholera occurs and propagates in such locations, timely, accurate, and openly accessible outbreak data are typically inaccessible for disease modeling and subsequent decision-making. In this study, we demonstrated the value of open-access data to rapidly estimate cholera transmission and vaccine effectiveness. Specifically, we obtained non-machine readable (NMR) epidemic curves for recent cholera outbreaks in two countries, Haiti and Cameroon, from figures published in situation and disease outbreak news reports. We used computational digitization techniques to derive weekly counts of cholera cases, resulting in nominal differences when compared against the reported cumulative case counts (i.e., a relative error rate of 5.67% in Haiti and 0.54% in Cameroon). Given these digitized time series, we leveraged EpiEstim-an open-source modeling platform-to derive rapid estimates of time-varying disease transmission via the effective reproduction number ( R t ). To compare OCV1 effectiveness in the two considered countries, we additionally used VaxEstim, a recent extension of EpiEstim that facilitates the estimation of vaccine effectiveness via the relation among three inputs: the basic reproduction number ( R 0 ), R t , and vaccine coverage. Here, with Haiti and Cameroon as case studies, we demonstrated the first implementation of VaxEstim in low-resource settings. Importantly, we are the first to use VaxEstim with digitized data rather than traditional epidemic surveillance data. In the initial phase of the outbreak, weekly rolling average estimates of R t were elevated in both countries: 2.60 in Haiti [95% credible interval: 2.42-2.79] and 1.90 in Cameroon [1.14-2.95]. These values are largely consistent with previous estimates of R 0 in Haiti, where average values have ranged from 1.06 to 3.72, and in Cameroon, where average values have ranged from 1.10 to 3.50. In both Haiti and Cameroon, this initial period of high transmission preceded a longer period during which R t oscillated around the critical threshold of 1. Our results derived from VaxEstim suggest that Haiti had higher OCV1 effectiveness than Cameroon (75.32% effective [54.00-86.39%] vs. 54.88% [18.94-84.90%]). These estimates of OCV1 effectiveness are generally aligned with those derived from field studies conducted in other countries. Thus, our case study reinforces the validity of VaxEstim as an alternative to costly, time-consuming field studies of OCV1 effectiveness. Indeed, prior work in South Sudan, Bangladesh, and the Democratic Republic of the Congo reported OCV1 effectiveness ranging from approximately 40% to 80%. This work underscores the value of combining NMR sources of outbreak case data with computational techniques and the utility of VaxEstim for rapid, inexpensive estimation of vaccine effectiveness in data-poor outbreak settings.
RESUMO
OBJECTIVES: The World Health Organization recommends the use of oral cholera vaccine (OCV) in cholera control efforts. Euvichol®, pre-qualified in 2015, is the leading component of the Global OCV stockpile, but data on its field effectiveness are limited. To evaluate Euvichol® vaccine effectiveness (VE), we conducted a case-control study between September 2018 to March 2020 following an OCV campaign in November 2017 in Haiti. METHODS: Cases were individuals with acute watery diarrhea. Stool samples were tested by culture and real-time polymerase chain reaction of the Vibrio cholerae ctxA gene. Cases were matched to four community controls without diarrhea by residence, enrollment time, age, and gender, and interviewed for sociodemographics, risk factors, and self-reported vaccination. Cholera cases were analyzed by conditional logistic regression in the VE study. Non-cholera diarrhea cases were analyzed in a bias-indicator study. RESULTS: We enrolled 15 cholera cases matched to 60 controls, and 63 non-cholera diarrhea cases matched to 249 controls. In the VE analysis, eight (53%) cases reported vaccination with any number of doses compared to 43 (72%) controls. Adjusted two-dose OCV VE was 69% (95% CI -71 to 94%). CONCLUSIONS: Between 10-27 months after vaccination, Euvichol® was effective and similar to Shanchol™, suggesting that it can serve as one component of multi-sectoral comprehensive cholera control.
Assuntos
Vacinas contra Cólera , Cólera , Humanos , Cólera/epidemiologia , Cólera/prevenção & controle , Estudos de Casos e Controles , Haiti/epidemiologia , Administração Oral , Vacinação , DiarreiaRESUMO
The Dominican Republic, historically non-endemic for cholera, is experiencing an ongoing cholera epidemic. We assessed the safety and immunogenicity of two doses of the killed bivalent (O1 and O139) whole-cell oral cholera vaccine (OCV) on day (D)0 and D14 in healthy participants aged ≥1 year. Immediate unsolicited systemic adverse events (AEs) were monitored up to 30 minutes and solicited systemic reactions, up to 7 days after each vaccination. Unsolicited AEs were recorded up to D14 (post-dose 1) and 30 days post-dose 2. A vibriocidal antibody assay with microtiter technique was used to measure serum antibodies to V. cholerae strains (O1 El Tor Inaba, O1 El Tor Ogawa, O139) on D0, D14 and D28. Geometric mean titers (GMTs) and seroconversion (≥4-fold increase from D0) rates were calculated. We recruited 336 participants; 112 in three age groups (1-4, 5-14 and ≥15 years). No safety concerns were observed. GMTs increased from baseline for all serotypes, with marked increases for O1 Inaba and Ogawa post-dose 1. Post-dose 2 GMTs tended to be equal or slightly lower, with ranges: O1 Inaba, 283 (95% confidence interval 191-419) to 612 (426-880); O1 Ogawa, 346 (223-536) to 754 (553-1028); and O139, 20.3 (13.5-30.6) to 43.8 (30.1-63.7). Seroconversion rates post-dose 2 for O1 Inaba and Ogawa were high (≥87%) for all age groups. OCV demonstrated an acceptable safety profile and robust immunogenicity in these participants, in-line with previous observations in epidemic and endemic settings.This study is registered on www.clinicaltrials.gov (NCT02434822).