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      Cholera Transmission in Ouest Department of Haiti: Dynamic Modeling and the Future of the Epidemic

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          Abstract

          In the current study, a comprehensive, data driven, mathematical model for cholera transmission in Haiti is presented. Along with the inclusion of short cycle human-to-human transmission and long cycle human-to-environment and environment-to-human transmission, this novel dynamic model incorporates both the reported cholera incidence and remote sensing data from the Ouest Department of Haiti between 2010 to 2014. The model has separate compartments for infectious individuals that include different levels of infectivity to reflect the distribution of symptomatic and asymptomatic cases in the population. The environmental compartment, which serves as a source of exposure to toxigenic V. cholerae, is also modeled separately based on the biology of causative bacterium, the shedding of V. cholerae O1 by humans into the environment, as well as the effects of precipitation and water temperature on the concentration and survival of V. cholerae in aquatic reservoirs. Although the number of reported cholera cases has declined compared to the initial outbreak in 2010, the increase in the number of susceptible population members and the presence of toxigenic V. cholerae in the environment estimated by the model indicate that without further improvements to drinking water and sanitation infrastructures, intermittent cholera outbreaks are likely to continue in Haiti.

          Author Summary

          Based on the model-fitted trend and the observed incidence, there is evidence that after an initial period of intense transmission, the cholera epidemic in Haiti stabilized during the third year of the outbreak and became endemic. The model estimates indicate that the proportion of the population susceptible to infection is increasing and that the presence of toxigenic V. cholerae in the environment remains a potential source of new infections. Given the lack of adequate improvements to drinking water and sanitation infrastructure, these conditions could facilitate ongoing, seasonal cholera epidemics in Haiti.

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          Modelling cholera epidemics: the role of waterways, human mobility and sanitation.

          We investigate the role of human mobility as a driver for long-range spreading of cholera infections, which primarily propagate through hydrologically controlled ecological corridors. Our aim is to build a spatially explicit model of a disease epidemic, which is relevant to both social and scientific issues. We present a two-layer network model that accounts for the interplay between epidemiological dynamics, hydrological transport and long-distance dissemination of the pathogen Vibrio cholerae owing to host movement, described here by means of a gravity-model approach. We test our model against epidemiological data recorded during the extensive cholera outbreak occurred in the KwaZulu-Natal province of South Africa during 2000-2001. We show that long-range human movement is fundamental in quantifying otherwise unexplained inter-catchment transport of V. cholerae, thus playing a key role in the formation of regional patterns of cholera epidemics. We also show quantitatively how heterogeneously distributed drinking water supplies and sanitation conditions may affect large-scale cholera transmission, and analyse the effects of different sanitation policies.
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            Lessons Learned during Public Health Response to Cholera Epidemic in Haiti and the Dominican Republic

            Cholera is a severe intestinal infection caused by strains of the bacteria Vibrio cholerae serogroup O1 or O139, which produce cholera toxin. Symptoms and signs can range from asymptomatic carriage to severe diarrhea, vomiting, and profound shock. Untreated cholera is fatal in ≈25% of cases, but with aggressive volume and electrolyte replacement, the number of persons who die of cholera is limited to 40 per 1,000 live births ( 4 ). Although cholera persists in Africa and southern Asia, it recently disappeared from Latin America after sustained improvements in sanitation and water purification ( 5 , 6 ). Although the country was at risk, until the recent outbreak, epidemic cholera had not been reported in Haiti since the 1800s, and Haiti, like other Caribbean nations, was unaffected during the Latin America epidemic ( 7 , 8 ). Haiti: A History of Poverty and Poor Health Haiti has extremely poor health indices. The life expectancy at birth is 61 years ( 9 ), and the estimated IMR is 64 per 1,000 live births, the highest in the Western Hemisphere. An estimated 87 of every 1,000 children born die by the age of 5 years ( 9 ), and >25% of surviving children experience chronic undernutrition or stunted growth ( 10 ). Maternal mortality rate is 630 per 100,000 live births ( 10 ). Haitians are at risk of spreading vaccine-preventable diseases, such as polio and measles, because childhood vaccination coverage is low (59%) for polio, measles-rubella, and diphtheria-tetanus-pertussis vaccines ( 9 ). Prevalence of adult HIV infection (1.9%) and tuberculosis (312 cases per 100,000 population) in the Western Hemisphere is also highest in Haiti ( 11 , 12 ), and Hispaniola, which Haiti shares with the Dominican Republic, is the only Caribbean island where malaria remains endemic ( 13 ). Only half of the Haitian population has access to health care because of poverty and a shortage of health care professionals (1 physician and 1.8 nurses per 10,000 population), and only one fourth of seriously ill persons are taken to a health facility ( 14 ). Before the earthquake hit Haiti in January 2010, only 63% of Haiti’s population had access to an improved drinking water source (e.g., water from a well or pipe), and only 17% had access to a latrine ( 15 ). Aftermath of Earthquake The earthquake of January 12, 2010, destroyed homes, schools, government buildings, and roads around Port-au-Prince; it killed 230,000 persons and injured 300,000. Two million residents sought temporary shelter, many in internally displaced person (IDP) camps, while an estimated 600,000 persons moved to undamaged locations. In response, the Haitian government developed strategies for health reform and earthquake response ( 16 , 17 ) and called on the international community for assistance. The Ministère de la Santé Publique et de la Population (MSPP) requested assistance from the Centers for Disease Control and Prevention (CDC) to strengthen reportable disease surveillance at 51 health facilities that were conducting monitoring and evaluation with support from the US President’s Emergency Plan for AIDS Relief (PEPFAR) ( 18 ) and at health clinics for IDPs ( 19 ). MSPP also asked CDC to help expand capacity at the Haiti Laboratoire National de Sante Publique to identify reportable pathogens, including V. cholerae ( 20 , 21 ), and help train Haiti’s future epidemiologic and laboratory workforce. These actions, supported through new emergency US government (USG) funds to assist Haiti after the earthquake, laid the groundwork for the rapid detection of cholera when it appeared. Cholera Outbreak On October 19, 2010, MSPP was notified of a sudden increase in patients with acute watery diarrhea and dehydration in the Artibonite and Plateau Centrale Departments. The Laboratoire National de Sante Publique tested stool cultures collected that same day and confirmed V. cholerae serogroup O1, biotype Ogawa, on October 21. The outbreak was publicly announced on October 22 ( 22 ). A joint MSPP-CDC investigation team visited 5 hospitals and interviewed 27 patients who resided in communities along the Artibonite River or who worked in nearby rice fields ( 23 ). Many patients said they drank untreated river water before they became ill, and few had defecated in a latrine. Health authorities quickly advised community members to boil or chlorinate their drinking water and to bury human waste. Because the outbreak was spreading rapidly and the initial case-fatality rate (CFR) was high, MSPP and the USG initially focused on 5 immediate priorities: 1) prevent deaths in health facilities by distributing treatment supplies and providing clinical training; 2) prevent deaths in communities by supplying oral rehydration solution (ORS) sachets to homes and urging ill persons to seek care quickly; 3) prevent disease spread by promoting point-of-use water treatment and safe storage in the home, handwashing, and proper sewage disposal; 4) conduct field investigations to define risk factors and guide prevention strategies; and 5) establish a national cholera surveillance system to monitor spread of disease. National Surveillance of Rapidly Spreading Epidemic Health officials needed daily reports (which established reportable disease surveillance systems were not able to provide) to monitor the epidemic spread and to position cholera prevention and treatment resources across the country. In the first week of the outbreak, MSPP’s director general collected daily reports by telephone from health facilities and reported results to the press. On November 1, formal national cholera surveillance began, and MSPP began posting reports on its website (www.mspp.gouv.ht). On November 5–6, Hurricane Tomas further complicated surveillance and response efforts, and many persons fled flood-prone areas. By November 19, cholera was laboratory confirmed in all 10 administrative departments and Port-au-Prince, as well as in the Dominican Republic and Florida ( 24 , 25 ) (Figure 1). Though recently affected departments in Haiti experienced high initial CFRs, by mid December, the CFR for hospitalized case-patients was decreasing in most departments, and fell to 1% in Artibonite Department ( 26 ). Reported cases decreased substantially in January, and the national CFR of hospitalized case-patients fell below 1% (Figure 2). As of July 31, 2011, a total of 419,511 cases, 222,359 hospitalized case-patients, and 5,968 deaths had been reported. Figure 1 Administrative departments of Haiti affected by the earthquake of January 12, 2010; the path of Hurricane Tomas, November 5–6, 2010; and cumulative cholera incidence by department as of December 28, 2010. Figure 2 Reported cases of cholera by day, and 14-day smoothed case-fatality rate (CFR) among hospitalized cases, by day, Haiti, October 22, 2010–July 25, 2011. UN, United Nations; CDC, Centers for Disease Control and Prevention; PAHO, Pan American Health Organization; MSPP, Ministère de la Santé Publique et de la Population. Field Investigations and Laboratory Studies To guide the public health response, officials needed to know how cholera was being transmitted, which interventions were most effective, and how well the population was protecting itself. Therefore, CDC collaborated with MSPP and other partners to conduct rapid field investigations and laboratory studies. Central early findings included the following. First, identifying untreated drinking water as the primary source for cholera reinforced the need to provide water purification tablets and to teach the population how to use them. Although most of the population had heard messages about treating their drinking water, many lacked the means to do so. In addition, in Artibonite Department, those with cholera-like illness died at home, after reaching hospitals, and after discharge home, which suggests that persons were unaware of how quickly cholera kills and that the overwhelmed health care system needed more capacity and training to deliver lifesaving care. Also, water and seafood from the harbors at St. Marc and Port-au-Prince were contaminated with V. cholerae, which affirmed the need to cook food thoroughly and advise shipmasters to exchange ballast water at sea to avoid contaminating other harbors. The epidemic strain was resistant to many antimicrobial agents but susceptible to azithromycin and doxycycline. Guidelines were rapidly disseminated to ensure effective antimicrobial drug treatment. Cholera affected inmates at the national penitentiary in Port-au-Prince in early November, causing ≈100 cases and 12 deaths in the first 4 days. The problem abated after the institution’s drinking water was disinfected and inmates were given prophylactic doxycycline. Finally, investigators found that epidemic V. cholerae isolates all shared the same molecular markers, which suggests that a point introduction had occurred. The epidemic strain differed from Latin American epidemic strains and closely resembled a strain that first emerged in Orissa, India, in 2007 and spread throughout southern Asia and parts of Africa ( 27 ). These hybrid Orissa strains have the biochemical features of an El Tor biotype but the toxin of a classical biotype; the later biotype causes more severe illness and produces more durable immunity ( 28 , 29 ). A representative isolate was placed in the American Type Culture Collection, and 3 gene sequences were placed in GenBank ( 23 ). Training Clinical Caregivers and Community Health Workers CDC developed training materials (in French and Creole) on cholera treatment and on November 15–16 held a training-of-trainers workshop in Port-au-Prince for locally employed clinical training staff working at PEPFAR sites across all 10 departments. These materials were also posted on the CDC website (www.cdc.gov/haiticholera/traning). The training-of-trainers graduates subsequently led training sessions in their respective departments; 521 persons were trained by early December. During the initial response ≈10,000 community health workers (CHWs), supported through the Haitian government and other organizations, staffed local first aid clinics, taught health education classes, and led prevention activities in their communities. Training materials for CHWs developed by CDC were distributed at departmental training sessions, shared with other nongovernmental organization (NGO) agencies, and used in a follow-up session for CHWs held on March 1–3, 2011 (see pages 2162–5). The CHW materials discussed treating drinking water by using several water disinfection products; how to triage persons coming to a primary clinic with diarrhea and vomiting; making and using ORS; and disinfecting homes, clothing, and cadavers with chlorine bleach solutions. Materials were posted on the CDC website as well. Working with Partners to Increase Capacity for Cholera Treatment Supply logistics were daunting as cholera spread rapidly across Haiti. Sudden, unexpected surges in cases could easily deplete local stocks of intravenous rehydration fluids and ORS sachets, and resupplying them could be slow. The national supply chain, called Program on Essential Medicine and Supplies, was managed by MSPP, with technical assistance from the Pan American Health Organization, and received shipments of donated materials and distributed them to clinics. Early in November the USG provided essential cholera treatment supplies through the US Agency for International Development’s Office of Foreign Disaster Assistance (OFDA) to the national warehouse and IDP camps. CDC staff also distributed limited supplies to places with acute needs. To complement efforts by MSPP and aid organizations to establish preventive and treatment services, OFDA provided emergency funding to NGO partners with clinical capacity. When surveillance and modeling suggested that the spread of cholera across Haiti could outpace the public health response, the USG reached out to additional partners to expand cholera preventive services and treatment capacity. PEPFAR clinicians were authorized to assist with clinical management of cholera patients and participated in clinical training across the country. In December, CDC received additional USG emergency funds and awarded MSPP and 6 additional PEPFAR partners $14 million to further expand cholera treatment and prevention efforts through 4,000 CHWs and workers at 500 community oral rehydration points. Funds were also used to expand cholera treatment sites at 55 health facilities. In addition, CDC established the distribution of essential cholera supplies to PEPFAR partners through an existing HIV commodities supply chain management system. Improvements in Water, Sanitation, and Hygiene To increase access to treated water and raise awareness of ways to prevent cholera, a consortium of involved NGOs and agencies, called the water, sanitation, and hygiene cluster, met weekly. Led by Haiti’s National Department of Drinking Water and Sanitation and the United Nation’s Children’s Fund, the members of this cluster targeted all piped water supplies for chlorination, and began distributing water purifying tablets for use in homes throughout Haiti. CDC helped the National Department of Drinking Water and Sanitation monitor these early efforts with qualitative and quantitative assessments of knowledge, attitudes, and practices. Emergency measures, especially enhanced chlorination of central water supplies, were expanded in the IDP camps because of the perceived high risk. OFDA and CDC provided water storage vessels, soap, and large quantities of emergency water treatment supplies for households and piped water systems. Distributing water purifying tablet supplies to difficult-to-reach locations remained a challenge. Educating the Public Beginning October 22, MSPP broadcast mass media messages, displayed banners, and sent text messages encouraging the population to boil drinking water and seek care quickly if they became ill. Early investigations affirmed the public’s need for 5 basic messages:1) drink only treated water; 2) cook food thoroughly (especially seafood); 3) wash hands; 4) seek care immediately for diarrheal illness; 4) and give ORS to anyone with diarrhea. In mid November, focus group studies in Artibonite indicated that residents were confused about how cholera was spreading and how to best prevent it, but they understood the need to treat diarrheal illness with ORS, how to prepare ORS, and how to disinfect water with water purification tablets ( 30 ). Posters provided graphic messages for those who could not read (Figure 3). On November 14, Haitian President René Préval led a 4-hour televised public conference to promote prevention, stressing home water treatment and handwashing, and comedian Tonton Bichat showed how to mix ORS. Figure 3 Educational poster (in Haitian Creole) used by the Haitian Ministère de la Santé Publique et de la Population (MSPP) to graphically present the ways of preventing cholera. DINEPA, Direction Nationale de l’Eau Potable et d’ Assainessement; UNICEF, United Nations Children’s Fund; ACF, Action Contre la Faim. Cholera Epidemic in Dominican Republic Compared with Haiti’s experience, the epidemic has been less severe in Dominican Republic. Though the countries share the island, conditions in Dominican Republic are better than in Haiti: the IMR is one third that of Haiti, gross domestic product per capita is 5× greater, and 86% of the population has access to improved sanitation. Within 48 hours of the report of cholera in Haiti, the Ministry of Health in the Dominican Republic and CDC established the capacity for diagnosing cholera at the national laboratory; the first cholera case was confirmed on October 31. Dominican officials quickly planned for cholera treatment centers in at least 70 hospitals, trained staff in primary care clinics and prison dispensaries, and stocked medical supplies sufficient to treat 20,000 cases. By December, 75% of doctors had received training in the management of cholera. Chlorination levels and water quality were monitored in municipal water systems across the country. The border with Haiti was not closed, and no major trade disruptions occurred. Sanitation improvements were instituted in border markets, schools, institutions, and mass gatherings. Public education in the first 3 months included dissemination of 4,300 mass media messages, nearly 3 million flyers, 50,000 classroom booklets for teachers, and a volunteer effort to visit 1 million homes. A survey of the knowledge, attitudes, and practices of residents of Santo Domingo showed that 89% had received cholera prevention messages. Transmission was limited, but sustained, in mid December and continued at low levels through the spring. One large outbreak affected guests at a wedding in January 2011, including some visitors from Venezuela and the United States (see pages 2172–4). From October 21, 2010, through July 30, 2011, a total of 14,598 suspected cases of cholera were reported; 256 persons died (of these, cases in 92 patients were laboratory confirmed) ( 31 ). Uncertainties and Challenges of Cholera in the Caribbean Cholera may increase seasonally in Haiti each year (during the rainy season) as it did in 2011. The lack of a history of cholera in the Caribbean makes prediction a challenge because cholera seasonality varies from place to place. Other unknown factors are what proportion of the population has now been immunized by natural infection and how long this immunity might last. In a setting in which the population has poor access to clean water and sanitation, endemic transmission could persist for years if the epidemic strain finds long-term reservoirs in brackish coastal waters. Antimicrobial drug resistance may emerge in toxigenic V. cholerae O1, making continued monitoring of antimicrobial drug susceptibility essential. Whether the epidemic will spread beyond Hispaniola is also uncertain. With the highest IMR in the Western Hemisphere (reflecting major gaps in sanitation and health care), Haiti is uniquely susceptible. Other countries in the Caribbean region have an IMR less than half that of Haiti (Guatemala is next with an IMR of 33), which suggests less risk for sustained transmission. If shipmasters leaving Haitian ports would exchange their ships’ ballast water at sea, they could help prevent the transfer of epidemic cholera from harbor to harbor. The origin of cholera in Haiti also raises questions. It has been suggested that United Nations peacekeeping troops from Nepal may have introduced cholera into Haiti ( 32 ). Genetic comparison of the Haitian epidemic strain with other strains from around the world suggests that it resembles strains seen in southern Asia and African ( 23 ) and strains from Nepal ( 33 ). Although knowing how cholera was introduced into Haiti would not help dampen its spread throughout Hispaniola, the knowledge might help foster disease monitoring and sanitation policies that would prevent such introductions elsewhere ( 34 ). A continuing challenge facing Haiti is how to manage cholera treatment with limited resources. Cholera training for doctors and nurses should be added to clinical curricula. By increasing use of ORS and expanding the antimicrobial drug treatment of hospitalized patients, intravenous fluid needs might be decreased, without posing an undue risk for antimicrobial drug resistance. Focusing on supply chain logistics is critical to ensuring the maintenence of tenuous buffer stocks of supplies. Residents of IDP camps have been largely spared from the outbreak because of safer water supplies and improved sanitation in the camps, but preserving that protection as persons move on to homes without piped water or sewage systems will be a challenge. Encouraging and empowering residents to disinfect drinking water in their homes, schools, and clinics by using chlorine products has been effective in many African and Latin American countries and is a practical interim solution for Haiti ( 35 ). The role of oral cholera vaccine in the immediate postepidemic period continues to be evaluated ( 36 , 37 ). Both the global cholera vaccine supply and Haitian vaccine cold chain are currently insufficient to mount national vaccination campaigns on Hispaniola. A limited vaccination pilot study could increase our global understanding of the costs, benefits, and practical applicability of using oral cholera vaccine in such circumstances. Lessons Learned The existing PEPFAR program that provided support for clinical care delivery and public health infrastructure was a powerful framework that sustained the national cholera response in Haiti. Through additional USG funding for PEPFAR partners, an expanded cadre of Haitian clinicians and CHWs received cholera training, resulting in expanded access to cholera treatment throughout Haiti. In addition, the postearthquake enhancement of diagnostic laboratory testing capacity for reportable diseases enabled health officials to quickly confirm the cholera outbreak and monitor antimicrobial drug susceptibility of the bacterial strains. The Haitian epidemic shows that as long as cholera exists anywhere in the world, many who drink untreated water and live in areas of poor sanitation are at risk. The epidemic also shows how cholera can emerge where it is least expected. Despite heightened efforts to detect acute watery diarrhea among persons in urban IDP camps, cholera appeared first in rural Haiti, just as in Mexico in the 1990s, where it first emerged unexpectedly in a remote mountainous region ( 8 ). Therefore, the ability to detect and confirm cholera needs to be broadly available. The Haitian experience also shows the continued success of the rehydration treatment strategies first developed in Bangladesh and refined over the past 40 years. With training and adequate supplies and treatment facilities, hospitalized case-fatality ratios of $6 billion to Haiti for relief. A long-term plan to build safe drinking water and sewerage systems is well within the range of the resources pledged.
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              Vaccination strategies for epidemic cholera in Haiti with implications for the developing world.

              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.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                plos
                plosntds
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, CA USA )
                1935-2727
                1935-2735
                October 2015
                21 October 2015
                : 9
                : 10
                : e0004153
                Affiliations
                [1 ]Department of Biostatistics, College of Public Health and Health Professions and College of Medicine, University of Florida, Gainesville, Florida, United States of America
                [2 ]Emerging Pathogens Institute, University of Florida, Gainesville, Florida, United States of America
                [3 ]Department of Environmental and Global Health, College of Public Health and Health Professions, University of Florida, Gainesville, Florida, United States of America
                [4 ]Department of Medicine, College of Medicine, University of Florida, Gainesville, Florida, United States of America
                University of Minnesota, UNITED STATES
                Author notes

                The authors have declared that no competing interests exist.

                Conceived and designed the experiments: AK TAW YY AA JGM IML. Performed the experiments: AK TAW YY AA JGM IML. Analyzed the data: AK TAW YY AA JGM IML. Contributed reagents/materials/analysis tools: AK TAW YY AA JGM IML. Wrote the paper: AK TAW YY AA JGM IML. Worked on the literature review, performed the data analysis and corresponding estimation, outputs and graphs: AK TAW. Participated in discussions and interpretation of the results: AK TAW YY AA JGM IML.

                Article
                PNTD-D-15-00480
                10.1371/journal.pntd.0004153
                4619523
                26488620
                ce752fec-255d-4379-9226-c82e3ec89aaa
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 24 March 2015
                : 19 September 2015
                Page count
                Figures: 4, Tables: 0, Pages: 12
                Funding
                This work was funded by NIH grants R01 AI097405 and U54 314 GM111274. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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