Population-Based Serologic Survey of Vibrio cholerae Antibody Titers before Cholera Outbreak, Haiti, 2022.

A Vibrio cholerae O1 outbreak emerged in Haiti in October 2022 after years of cholera absence. In samples from a 2021 serosurvey, we found lower circulating antibodies against V. cholerae lipopolysaccharide in children <5 years of age and no vibriocidal antibodies, suggesting high susceptibility to cholera, especially among young children.

A population-based serological survey of Vibrio cholerae antibody titers in Ouest Department, Haiti in the year prior to the 2022 cholera outbreak.

After three years with no confirmed cholera cases in Haiti, an outbreak of Vibrio cholerae O1 emerged in October 2022. Levels of pre-existing antibodies provide an estimate of prior immunologic exposure, reveal potentially relevant immune responses, and set a baseline for future serosurveillance. We analyzed dried blood spots collected in 2021 from a population-weighted representative cross-sectional serosurvey in two communes in the Ouest Department of Haiti. We found lower levels of circulating IgG and IgA antibodies against V. cholerae lipopolysaccharide (LPS, IgG and IgA p<0.0001) in those below 5 years of age compared to those five years and older. Among a subset of patients with higher titers of antibodies, we were unable to detect any functional (vibriocidal) antibodies. In conclusion, the lack of detectable functional antibodies, and age-discordant levels of V. cholerae LPS IgG, suggest that populations in Haiti may be highly susceptible to cholera disease, especially among young children.

Case-area targeted preventive interventions to interrupt cholera transmission: Current implementation practices and lessons learned.

BACKGROUND: Cholera is a major cause of mortality and morbidity in low-resource and humanitarian settings. It is transmitted by fecal-oral route, and the infection risk is higher to those living in and near cholera cases. Rapid identification of cholera cases and implementation of measures to prevent subsequent transmission around cases may be an efficient strategy to reduce the size and scale of cholera outbreaks. METHODOLOGY/PRINCIPLE FINDINGS: We investigated implementation of cholera case-area targeted interventions (CATIs) using systematic reviews and case studies. We identified 11 peer-reviewed and eight grey literature articles documenting CATIs and completed 30 key informant interviews in case studies in Democratic Republic of Congo, Haiti, Yemen, and Zimbabwe. We documented 15 outbreaks in 12 countries where CATIs were used. The team composition and the interventions varied, with water, sanitation, and hygiene interventions implemented more commonly than those of health. Alert systems triggering interventions were diverse ranging from suspected cholera cases to culture confirmed cases. Selection of high-risk households around the case household was inconsistent and ranged from only one case to approximately 100 surrounding households with different methods of selecting them. Coordination among actors and integration between sectors were consistently reported as challenging. Delays in sharing case information impeded rapid implementation of this approach, while evaluation of the effectiveness of interventions varied. CONCLUSIONS/SIGNIFICANCE: CATIs appear effective in reducing cholera outbreaks, but there is limited and context specific evidence of their effectiveness in reducing the incidence of cholera cases and lack of guidance for their consistent implementation. We propose to 1) use uniform cholera case definitions considering a local capacity to trigger alert; 2) evaluate the effectiveness of individual or sets of interventions to interrupt cholera, and establish a set of evidence-based interventions; 3) establish criteria to select high-risk households; and 4) improve coordination and data sharing amongst actors and facilitate integration among sectors to strengthen CATI approaches in cholera outbreaks.

Achieving coordinated national immunity and cholera elimination in Haiti through vaccination: a modelling study.

BACKGROUND: Cholera was introduced into Haiti in 2010. Since then, more than 820 000 cases and nearly 10 000 deaths have been reported. Oral cholera vaccine (OCV) is safe and effective, but has not been seen as a primary tool for cholera elimination due to a limited period of protection and constrained supplies. Regionally, epidemic cholera is contained to the island of Hispaniola, and the lowest numbers of cases since the epidemic began were reported in 2019. Hence, Haiti may represent a unique opportunity to eliminate cholera with OCV. METHODS: In this modelling study, we assessed the probability of elimination, time to elimination, and percentage of cases averted with OCV campaign scenarios in Haiti through simulations from four modelling teams. For a 10-year period from January 19, 2019, to Jan 13, 2029, we compared a no vaccination scenario with five OCV campaign scenarios that differed in geographical scope, coverage, and rollout duration. Teams used weekly department-level reports of suspected cholera cases from the Haiti Ministry of Public Health and Population to calibrate the models and used common vaccine-related assumptions, but other model features were determined independently. FINDINGS: Among campaigns with the same vaccination coverage (70% fully vaccinated), the median probability of elimination after 5 years was 0-18% for no vaccination, 0-33% for 2-year campaigns focused in the two departments with the highest historical incidence, 0-72% for three-department campaigns, and 35-100% for nationwide campaigns. Two-department campaigns averted a median of 12-58% of infections, three-department campaigns averted 29-80% of infections, and national campaigns averted 58-95% of infections. Extending the national campaign to a 5-year rollout (compared to a 2-year rollout), reduced the probability of elimination to 0-95% and the proportion of cases averted to 37-86%. INTERPRETATION: Models suggest that the probability of achieving zero transmission of Vibrio cholerae in Haiti with current methods of control is low, and that bolder action is needed to promote elimination of cholera from the region. Large-scale cholera vaccination campaigns in Haiti would offer the opportunity to synchronise nationwide immunity, providing near-term population protection while improvements to water and sanitation promote long-term cholera elimination. FUNDING: Bill & Melinda Gates Foundation, Global Good Fund, Institute for Disease Modeling, Swiss National Science Foundation, and US National Institutes of Health.

Near real-time forecasting for cholera decision making in Haiti after Hurricane Matthew.

Computational models of cholera transmission can provide objective insights into the course of an ongoing epidemic and aid decision making on allocation of health care resources. However, models are typically designed, calibrated and interpreted post-hoc. Here, we report the efforts of a team from academia, field research and humanitarian organizations to model in near real-time the Haitian cholera outbreak after Hurricane Matthew in October 2016, to assess risk and to quantitatively estimate the efficacy of a then ongoing vaccination campaign. A rainfall-driven, spatially-explicit meta-community model of cholera transmission was coupled to a data assimilation scheme for computing short-term projections of the epidemic in near real-time. The model was used to forecast cholera incidence for the months after the passage of the hurricane (October-December 2016) and to predict the impact of a planned oral cholera vaccination campaign. Our first projection, from October 29 to December 31, predicted the highest incidence in the departments of Grande Anse and Sud, accounting for about 45% of the total cases in Haiti. The projection included a second peak in cholera incidence in early December largely driven by heavy rainfall forecasts, confirming the urgency for rapid intervention. A second projection (from November 12 to December 31) used updated rainfall forecasts to estimate that 835 cases would be averted by vaccinations in Grande Anse (90% Prediction Interval [PI] 476-1284) and 995 in Sud (90% PI 508-2043). The experience gained by this modeling effort shows that state-of-the-art computational modeling and data-assimilation methods can produce informative near real-time projections of cholera incidence. Collaboration among modelers and field epidemiologists is indispensable to gain fast access to field data and to translate model results into operational recommendations for emergency management during an outbreak. Future efforts should thus draw together multi-disciplinary teams to ensure model outputs are appropriately based, interpreted and communicated.

The Impact of a One-Dose versus Two-Dose Oral Cholera Vaccine Regimen in Outbreak Settings: A Modeling Study.

BACKGROUND: In 2013, a stockpile of oral cholera vaccine (OCV) was created for use in outbreak response, but vaccine availability remains severely limited. Innovative strategies are needed to maximize the health impact and minimize the logistical barriers to using available vaccine. Here we ask under what conditions the use of one dose rather than the internationally licensed two-dose protocol may do both. METHODS AND FINDINGS: Using mathematical models we determined the minimum relative single-dose efficacy (MRSE) at which single-dose reactive campaigns are expected to be as or more effective than two-dose campaigns with the same amount of vaccine. Average one- and two-dose OCV effectiveness was estimated from published literature and compared to the MRSE. Results were applied to recent outbreaks in Haiti, Zimbabwe, and Guinea using stochastic simulations to illustrate the potential impact of one- and two-dose campaigns. At the start of an epidemic, a single dose must be 35%-56% as efficacious as two doses to avert the same number of cases with a fixed amount of vaccine (i.e., MRSE between 35% and 56%). This threshold decreases as vaccination is delayed. Short-term OCV effectiveness is estimated to be 77% (95% CI 57%-88%) for two doses and 44% (95% CI -27% to 76%) for one dose. This results in a one-dose relative efficacy estimate of 57% (interquartile range 13%-88%), which is above conservative MRSE estimates. Using our best estimates of one- and two-dose efficacy, we projected that a single-dose reactive campaign could have prevented 70,584 (95% prediction interval [PI] 55,943-86,205) cases in Zimbabwe, 78,317 (95% PI 57,435-100,150) in Port-au-Prince, Haiti, and 2,826 (95% PI 2,490-3,170) cases in Conakry, Guinea: 1.1 to 1.2 times as many as a two-dose campaign. While extensive sensitivity analyses were performed, our projections of cases averted in past epidemics are based on severely limited single-dose efficacy data and may not fully capture uncertainty due to imperfect surveillance data and uncertainty about the transmission dynamics of cholera in each setting. CONCLUSIONS: Reactive vaccination campaigns using a single dose of OCV may avert more cases and deaths than a standard two-dose campaign when vaccine supplies are limited, while at the same time reducing logistical complexity. These findings should motivate consideration of the trade-offs between one- and two-dose campaigns in resource-constrained settings, though further field efficacy data are needed and should be a priority in any one-dose campaign.

Epidemic risk from cholera introductions into Mexico.

Stemming from the 2010 cholera outbreak in Haiti, cholera transmission in Hispaniola continues with over 40,000 cases in 2013. The presence of an ongoing cholera outbreak in the region poses substantial risks to countries throughout the Americas, particularly in areas with poor infrastructure. Since September 9, 2013 nearly 200 cholera cases have been reported in Mexico, as a result of introductions from Hispaniola or Cuba. There appear to have been multiple introductions into Mexico resulting in outbreaks of 2 to over 150 people. Using publicly available data, we attempt to estimate the reproductive number (R) of cholera in Mexico, and thereby assess the potential of continued introductions to establish a sustained epidemic. We estimate R for cholera in Mexico to be between 0.8 to 1.1, depending on the number of introductions, with the confidence intervals for the most plausible estimates crossing 1. These results suggest that the efficiency of cholera transmission in some regions of Mexico is near that necessary for a large epidemic. Intensive surveillance, evaluation of water and sanitation infrastructure, and planning for rapid response are warranted steps to avoid potential large epidemics in the region.