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In October 2010, nine months after the massive earthquake that devastated Haiti, a second disaster began to unfold-soon to become the world's largest cholera epidemic in modern times. In a country that had never before reported cholera, the epidemic mysteriously and simultaneously appeared in river communities of central Haiti, eventually triggering nearly 800,000 cases and 9,000 deaths. What had caused the first cases of cholera in Haiti in recorded history? Who or what was the deadly agent of origin? Why did it explode in the agricultural-rich delta of the Artibonite River? When answers were few, rumors spread, causing social and political consequences of their own. Wanting insight, the Haitian government and French embassy requested epidemiological assistance from France. A few weeks into the epidemic, physician and infectious disease specialist Renaud Piarroux arrived in Haiti. InDeadly River, Ralph R. Frerichs tells the story of the epidemic, of a French disease detective determined to trace its origins so that he could help contain the spread and possibly eliminate the disease, and the political intrigue that has made that effort so difficult. The story involves political maneuvering by powerful organizations such as the United Nations and its peacekeeping troops in Haiti, as well as by the World Health Organization and the U.S. Centers for Disease Control. Frerichs explores a quest for scientific truth and dissects a scientific disagreement involving world-renowned cholera experts who find themselves embroiled in intellectual and political turmoil in a poverty-stricken country. Frerichs's narrative highlights how the world's wealthy nations, nongovernmental agencies, and international institutions respond when their interests clash with the needs of the world's most vulnerable people. The story poses big social questions and offers insights not only on how to eliminate cholera in Haiti but also how nations, NGOs, and international organizations such as the UN and CDC deal with catastrophic infectious disease epidemics. In October 2010, nine months after the massive earthquake that devastated Haiti, a second disaster began to unfold-soon to become the world's largest cholera epidemic in modern times. In a country that had never before reported cholera, the epidemic mysteriously and simultaneously appeared in river communities of central Haiti, eventually triggering nearly 800,000 cases and 9,000 deaths. What had caused the first cases of cholera in Haiti in recorded history? Who or what was the deadly agent of origin? Why did it explode in the agricultural-rich delta of the Artibonite River? When answers were few, rumors spread, causing social and political consequences of their own. Wanting insight, the Haitian government and French embassy requested epidemiological assistance from France. A few weeks into the epidemic, physician and infectious disease specialist Renaud Piarroux arrived in Haiti.InDeadly River, Ralph R. Frerichs tells the story of the epidemic-of a French disease detective determined to trace its origins so that he could help contain the spread and possibly eliminate the disease-and the political intrigue that has made that effort so difficult. The story involves political maneuvering by powerful organizations such as the United Nations and its peacekeeping troops in Haiti, as well as by the World Health Organization and the U.S. Centers for Disease Control. Frerichs explores a quest for scientific truth and dissects a scientific disagreement involving world-renowned cholera experts who find themselves embroiled in intellectual and political turmoil in a poverty-stricken country.Frerichs's narrative highlights how the world's wealthy nations, nongovernmental agencies, and international institutions respond when their interests clash with the needs of the world's most vulnerable people. The story poses big social questions and offers insights not only on how to eliminate cholera in Haiti but also how nations, NGOs, and international organizations such as the UN and CDC deal with catastrophic infectious disease epidemics.

Source of current cholera epidemic Cholera has affected human populations for centuries, and the agent responsible, Vibrio cholerae , continues to infect millions each year. Using whole genome phylogeny, it is now shown that the current seventh epidemic originated in the Bay of Bengal in the 1950s and has spread through the world in three independent waves. Vibrio cholerae is a globally important pathogen that is endemic in many areas of the world and causes 3–5 million reported cases of cholera every year. Historically, there have been seven acknowledged cholera pandemics; recent outbreaks in Zimbabwe and Haiti are included in the seventh and ongoing pandemic 1 . Only isolates in serogroup O1 (consisting of two biotypes known as ‘classical’ and ‘El Tor’) and the derivative O139 (refs 2 , 3 ) can cause epidemic cholera 2 . It is believed that the first six cholera pandemics were caused by the classical biotype, but El Tor has subsequently spread globally and replaced the classical biotype in the current pandemic 1 . Detailed molecular epidemiological mapping of cholera has been compromised by a reliance on sub-genomic regions such as mobile elements to infer relationships, making El Tor isolates associated with the seventh pandemic seem superficially diverse. To understand the underlying phylogeny of the lineage responsible for the current pandemic, we identified high-resolution markers (single nucleotide polymorphisms; SNPs) in 154 whole-genome sequences of globally and temporally representative V. cholerae isolates. Using this phylogeny, we show here that the seventh pandemic has spread from the Bay of Bengal in at least three independent but overlapping waves with a common ancestor in the 1950s, and identify several transcontinental transmission events. Additionally, we show how the acquisition of the SXT family of antibiotic resistance elements has shaped pandemic spread, and show that this family was first acquired at least ten years before its discovery in V. cholerae .

Serological surveillance can improve how we monitor cholera in high-burden areas where clinical surveillance is limited. However, vaccination can produce immune responses similar to infection, leading to overestimates in seroincidence. This study extends seroincidence estimation techniques using machine learning models to partially vaccinated populations. We analyzed antibody dynamics from vaccinated and infected individuals to develop methods that reduce the misclassification of vaccinated individuals as recently infected. These methods enable reliable seroincidence estimates in areas with recent vaccination campaigns, providing a step toward better epidemiologic monitoring in the context of global cholera control initiatives. Studies in other populations are needed to further validate our results and understand their generalizability.

Official projections of the cholera epidemic in Haiti have not incorporated existing disease trends or patterns of transmission, and proposed interventions have been debated without comparative estimates of their effect. We used a mathematical model of the epidemic to provide projections of future morbidity and mortality, and to produce comparative estimates of the effects of proposed interventions. We designed mathematical models of cholera transmission based on existing models and fitted them to incidence data reported in Haiti for each province from Oct 31, 2010, to Jan 24, 2011. We then simulated future epidemic trajectories from March 1 to Nov 30, 2011, to estimate the effect of clean water, vaccination, and enhanced antibiotic distribution programmes. We project 779 000 cases of cholera in Haiti (95% CI 599 000–914 000) and 11 100 deaths (7300–17 400) between March 1 and Nov 30, 2011. We expect that a 1% per week reduction in consumption of contaminated water would avert 105 000 cases (88 000–116 000) and 1500 deaths (1100–2300). We predict that the vaccination of 10% of the population, from March 1, will avert 63 000 cases (48 000–78 000) and 900 deaths (600–1500). The proposed extension of the use of antibiotics to all patients with severe dehydration and half of patients with moderate dehydration is expected to avert 9000 cases (8000–10 000) and 1300 deaths (900–2000). A decline in cholera prevalence in early 2011 is part of the natural course of the epidemic, and should not be interpreted as indicative of successful intervention. Substantially more cases of cholera are expected than official estimates used for resource allocation. Combined, clean water provision, vaccination, and expanded access to antibiotics might avert thousands of deaths. National Institutes of Health.

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. 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. 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.

In October 2010, a virulent South Asian strain of El Tor cholera began to spread in Haiti. Interventions have included treatment of cases and improved sanitation. Use of cholera vaccines would likely have further reduced morbidity and mortality, but such vaccines are in short supply and little is known about effective vaccination strategies for epidemic cholera. We use a mathematical cholera transmission model to assess different vaccination strategies. With limited vaccine quantities, concentrating vaccine in high-risk areas is always most efficient. We show that targeting one million doses of vaccine to areas with high exposure to Vibrio cholerae, enough for two doses for 5% of the population, would reduce the number of cases by 11%. The same strategy with enough vaccine for 30% of the population with modest hygienic improvement could reduce cases by 55% and save 3,320 lives. For epidemic cholera, we recommend a large mobile stockpile of enough vaccine to cover 30% of a country's population to be reactively targeted to populations at high risk of exposure.

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. 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. 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.

Mathematical models can provide key insights into the course of an ongoing epidemic, potentially aiding real-time emergency management in allocating health care resources and by anticipating the impact of alternative interventions. We study the ex post reliability of predictions of the 2010–2011 Haiti cholera outbreak from four independent modeling studies that appeared almost simultaneously during the unfolding epidemic. We consider the impact of different approaches to the modeling of spatial spread of Vibrio cholerae and mechanisms of cholera transmission, accounting for the dynamics of susceptible and infected individuals within different local human communities. To explain resurgences of the epidemic, we go on to include waning immunity and a mechanism explicitly accounting for rainfall as a driver of enhanced disease transmission. The formal comparative analysis is carried out via the Akaike information criterion (AIC) to measure the added information provided by each process modeled, discounting for the added parameters. A generalized model for Haitian epidemic cholera and the related uncertainty is thus proposed and applied to the year-long dataset of reported cases now available. The model allows us to draw predictions on longer-term epidemic cholera in Haiti from multiseason Monte Carlo runs, carried out up to January 2014 by using suitable rainfall fields forecasts. Lessons learned and open issues are discussed and placed in perspective. We conclude that, despite differences in methods that can be tested through model-guided field validation, mathematical modeling of large-scale outbreaks emerges as an essential component of future cholera epidemic control.

Cholera was identified in Haiti on October 1, 2022, after no confirmed cases had occurred for more than 3 years. Sequencing of the strain indicates a close relationship to the pathogen from the 2010 Haiti outbreak.