Socioecological systems analysis of potential factors for cholera outbreaks and assessment of health system's readiness to detect and respond in Ilemela and Nkasi districts, Tanzania.

BACKGROUND: Cholera outbreaks are a recurrent issue in Tanzania, with Ilemela and Nkasi districts being particulary affected. The objective of this study was to conduct a socio-ecological system (SES) analysis of cholera outbreaks in these districts, identifying potential factors and assessing the preparedness for cholera prevention and control. METHODS: A cross-sectional study was carried out in Ilemela and Nkasi districts of Mwanza and Rukwa regions, respectively in Tanzania between September and October 2021. A SES framework analysis was applied to identify potential factors associated with cholera outbreaks and assess the readiness of the districts to cholera prevention and control. RESULTS: Ilemela is characterised by urban and peri-urban ecosystems while Nkasi is mainly rural. Cholera was reported to disproportionately affect people living along the shores of Lake Victoria in Ilemela and Lake Tanganyika in Nkasi, particularly fishermen and women involved infish trading. The main potential factors identified for cholera outbreaks included defecation in the shallow ends and along the edges of lakes, open defecation, bathing/swimming in contaminated waters and improper waste disposal. The preparedness of both districts for cholera prevention and response was found to be inadequate due to limited laboratory capacity, insufficient human resources, and budget constraints. CONCLUSION: People of Ilemela and Nkasi districts remain at significant risk of recurrent cholera outbreaks and the capacity of the districts to detect the disease is limited. Urgent preventive measures, such as conducting considerable community awareness campaigns on personal hygiene and environmental sanitation are needed to alleviate the disease burden and reduce future cholera outbreaks.

Cholera past and future in Nigeria: Are the Global Task Force on Cholera Control's 2030 targets achievable?

BACKGROUND: Understanding and continually assessing the achievability of global health targets is key to reducing disease burden and mortality. The Global Task Force on Cholera Control (GTFCC) Roadmap aims to reduce cholera deaths by 90% and eliminate the disease in twenty countries by 2030. The Roadmap has three axes focusing on reporting, response and coordination. Here, we assess the achievability of the GTFCC targets in Nigeria and identify where the three axes could be strengthened to reach and exceed these goals. METHODOLOGY/PRINCIPAL FINDINGS: Using cholera surveillance data from Nigeria, cholera incidence was calculated and used to model time-varying reproduction number (R). A best fit random forest model was identified using R as the outcome variable and several environmental and social covariates were considered in the model, using random forest variable importance and correlation clustering. Future scenarios were created (based on varying degrees of socioeconomic development and emissions reductions) and used to project future cholera transmission, nationally and sub-nationally to 2070. The projections suggest that significant reductions in cholera cases could be achieved by 2030, particularly in the more developed southern states, but increases in cases remain a possibility. Meeting the 2030 target, nationally, currently looks unlikely and we propose a new 2050 target focusing on reducing regional inequities, while still advocating for cholera elimination being achieved as soon as possible. CONCLUSION/SIGNIFICANCE: The 2030 targets could potentially be reached by 2030 in some parts of Nigeria, but more effort is needed to reach these targets at a national level, particularly through access and incentives to cholera testing, sanitation expansion, poverty alleviation and urban planning. The results highlight the importance of and how modelling studies can be used to inform cholera policy and the potential for this to be applied in other contexts.

Pre-emptive oral cholera vaccine (OCV) mass vaccination campaign in Cuamba District, Niassa Province, Mozambique: feasibility, vaccination coverage and delivery costs using CholTool.

INTRODUCTION: Mozambique suffers from regular floods along its principal river basins and periodic cyclones that resulted in several cholera epidemics during the last decades. Cholera outbreaks in the recent 5 years affected particularly the northern provinces of the country including Nampula and Niassa provinces. A pre-emptive oral cholera vaccine (OCV) mass vaccination campaign was conducted in Cuamba District, Niassa Province, and the feasibility, costs, and vaccination coverage assessed. METHODS: WHO prequalified OCV (Euvichol-Plus), a killed whole-cell bivalent vaccine containing Vibrio cholerae O1 (classical and El Tor) and O139, was administered in two doses with a 15-day interval during 7-31 August 2018, targeting around 180 000 people aged above 1 year in Cuamba District. Microplanning, community sensitisation, and training of local public health professionals and field enumerators were conducted. Feasibility and costs of vaccination were assessed using CholTool. Vaccination coverage and barriers were assessed through community surveys. RESULTS: The administrative coverage of the first and second rounds of the campaign were 98.9% (194 581) and 98.8% (194 325), respectively, based on the available population data that estimated total 196 652 inhabitants in the target area. The vaccination coverage survey exhibited 75.9% (±2.2%) and 68.5% (±3.3%) coverage for the first and second rounds, respectively. Overall, 60.4% (±3.4%) of the target population received full two doses of OCV. Barriers to vaccination included incompatibility between working hours and campaign time. No severe adverse events were notified. The total financial cost per dose delivered was US$0.60 without vaccine cost and US$1.98 including vaccine costs. CONCLUSION: The pre-emptive OCV mass vaccination campaign in remote setting in Mozambique was feasible with reasonable full-dose vaccination coverage to confer sufficient herd immunity for at least the next 3 to 5 years. The delivery cost estimate indicates that the OCV campaign is affordable as it is comparable with Gavi's operational support for vaccination campaigns.

Conditions to eliminate cholera in Mozambique - the pathway for the development of the national cholera plan.

Cholera disproportionately affects the most vulnerable segments of the population, particularly those who have low or no access to basic water, sanitation, and hygiene (WASH). Despite some improvements in WASH conditions, cholera still represents a persistent challenge in Mozambique, where outbreaks occur almost every year, with high case fatality rates, posing a threat to the country's economic development. The Government of Mozambique has started developing a revised National Cholera Plan (NCP), which aligns with "ending cholera-a global roadmap to 2030" launched by the Global Task Force on Cholera Control (GTFCC) in 2017. Ending cholera represents a critical step towards achieving the sustainable development goals and requires effective prevention and control interventions, ensuring that no one is left behind. The NCP must use a multi-sector approach and broad stakeholder collaboration with well-coordinated roles and functions of different partners to address major areas for cholera elimination - water and sanitation, health care services and management, epidemiology and surveillance, and health and hygiene promotion. Every cholera death is preventable. In this review, we reiterate the need for effective coordinated actions to control and eliminate cholera in Mozambique and decrease the cholera burden, enabling a healthy population over the generations.

An Assessment of Household Knowledge and Practices during a Cholera Epidemic- Dar es Salaam, Tanzania, 2016.

From August 15, 2015 to March 5, 2016, Tanzania reported 16,521 cholera cases and 251 deaths, with 4,596 cases and 44 deaths in its largest city, Dar es Salaam. To evaluate outbreak response efforts, we conducted a household survey with drinking water testing in the five most affected wards in Dar es Salaam. We interviewed 641 households 6 months after the beginning of the outbreak. Although most respondents knew that cholera causes diarrhea (90%) and would seek care if suspecting cholera (95%), only 45% were aware of the current outbreak in the area and only 5% would use oral rehydration salts (ORS) if ill. Of 200 (31%) respondents reporting no regular water treatment, 46% believed treatment was unnecessary and 18% believed treatment was too expensive. Fecal contamination was found in 45% of water samples and was associated with water availability (P = 0.047). Only 11% of samples had detectable free chlorine residual, which was associated with water availability (P = 0.025), reported current water treatment (P = 0.006), and observed free chlorine product in the household (P = 0.015). The provision of accessible, adequately chlorinated water supply, and implementation of social mobilization campaigns advocating household water treatment and use of ORS should be prioritized to address gaps in cholera prevention and treatment activities.

Economic impact of cholera in households in rural southern Malawi: a prospective study.

INTRODUCTION: Cholera remains a significant contributor to diarrhoeal illness, especially in sub-Saharan Africa. Few studies have estimated the cost of illness (COI) of cholera in Malawi, a cholera-endemic country. The present study estimated the COI of cholera in Nsanje, southern Malawi, as part of the Cholera Surveillance in Malawi (CSIMA) programme following a mass cholera vaccination campaign in 2015. METHODS: Patients ≥12 months of age who were recruited as part of CSIMA were invited to participate in the COI survey. The COI tool captured household components of economic burden, including direct medical and non-medical costs, and indirect lost productivity costs. RESULTS: Between April 2016 and March 2020, 40 cholera cases were enrolled in the study, all of whom participated in the COI survey. Only two patients had any direct medical costs and five patients reported lost wages due to illness. The COI per patient was US$14.34 (in 2020), more than half of which was from direct non-medical costs from food, water, and transportation to the health centre. CONCLUSION: For the majority of Malawians who struggle to subsist on less than US$2 a day, the COI of cholera represents a significant cost burden to families. While cholera treatment is provided for free in government-run health centres, additional investments in cholera control and prevention at the community level and financial support beyond direct medical costs may be necessary to alleviate the economic burden of cholera on households in southern Malawi.

[Assessment of the humanitarian response to cholera in wash interventions.] / Evaluación de la respuesta humanitaria al cólera en las intervenciones WASH.

BACKGROUND: The humanitarian response to a cholera outbreak in a complex international crisis requires guaranteeing minimum conditions so that normalcy can be restored. Basic responses to a cholera outbreak include water and sanitation. The general objective of this systematic review was the analysis of the current evidence that addresses the effectiveness of different WASH measures to control cholera. METHODS: A review and analysis of the literature available in the main databases (PubMed, WoS and Scopus) and in a specific meta-search engine for humanitarian aid was carried out (reliefweb.int). Based on the establishment of the PICO research question "Can beneficiaries of humanitarian aid benefit from water, hygiene and sanitation interventions for cholera reduction?", the identification of keywords and databases to carry out the searches, as well as a selection process based on the established eligibility criteria: being studies in both English and Spanish where the WASH intervention was clearly defined, studies where health outcomes of cholera were presented, or data related to the function and use of the WASH intervention, was established. RESULTS: The initial search provided 17,185 documents susceptible of analysis that were screened using the search criteria, up to 22 references that were read in full text and the 11 that were finally analyzed. These were coded based on the measures set out in their protocols, on the interventions carried out in the improvement of water and its supply, the improvement of sanitation, the measures aimed at better hygiene and those that evaluated the complete WASH intervention. CONCLUSIONS: All the measures offered positive results, their effectiveness was conditioned by the education of the beneficiaries, the simplicity of the activities and the involvement of local actors.

OBJETIVO: La respuesta humanitaria ante un brote de cólera en una crisis compleja de carácter internacional requiere garantizar unas condiciones mínimas para que se pueda recuperar la normalidad. Entre las respuestas básicas a un brote de cólera están las correspondientes al agua y el saneamiento. El objetivo general de esta revisión narrativa fue el análisis de la evidencia actual que aborda la efectividad de las diferentes medidas WASH para controlar el cólera. METODOS: Se realizó una revisión y análisis de la literatura disponible en las bases de datos principales (PubMed, WoS y Scopus) y en un metabuscador específico de ayuda humanitaria (reliefweb.int). Basada en el establecimiento de la pregunta de investigación PICO: "¿Los beneficiarios de la ayuda humanitaria se pueden beneficiar de las intervenciones en agua, higiene y saneamiento para la disminución del cólera?" la identificación de las palabras clave y bases de datos para realizar las búsquedas, además de un proceso de selección basado en los criterios de elegibilidad establecidos; siendo estudios tanto en inglés como español donde la intervención WASH fue claramente definida, estudios donde se presentaran resultados de salud del cólera, o datos relacionados con la función y el uso de la intervención WASH. RESULTADOS: La búsqueda inicial proporcionó 17.185 documentos susceptibles de análisis que fueron cribados mediante los criterios de búsqueda hasta las 22 referencias que fueron leídas a texto completo y las 11 que fueron analizadas finalmente. Estas fueron codificadas en base a las medidas expuestas en sus protocolos, a las intervenciones realizadas en la mejora del agua y su suministro, la mejora del saneamiento, las medidas destinadas a una mejor higiene y aquellas que evaluaban la intervención WASH completa. CONCLUSIONES: Todas las medidas ofrecieron resultados positivos, su eficacia estuvo condicionada por la educación de los beneficiarios, la simplicidad de las actividades y la implicación de los actores locales.

Intervention to Improve Diarrhea-Related Knowledge and Practices Among Informal Healthcare Providers in Slums of Kolkata.

BACKGROUND: In the densely populated slums of Kolkata, informal healthcare providers' (IHP) diarrhea-related knowledge and rationality of practices should be improved to reduce risk of adverse outcome, expenditure, and antimicrobial resistance. METHODS: A multicomponent intervention was conducted among 140 representative IHPs in the slums of 8 wards in Kolkata to assess its impact on their diarrhea-related knowledge and practice. Six intervention modules in local languages were provided (1 per month) with baseline (N = 140) and postintervention (N = 124) evaluation. RESULTS: Mean overall (61.1 to 69.3; P < .0001) and domain-specific knowledge scores for etiology/spread (5.4 to 8.1; P < .0001), management (6.4 to 7.2; P < .0001), and oral rehydration solution ([ORS] 5.7 to 6.5; P < .0001) increased significantly (at α = 0.05) after intervention and were well retained. Impact on knowledge regarding etiology/spread (adjusted odds ratio [aOR] = 5.6; P < .0001), cholera (aOR = 2.0; P = .0041), management (aOR = 3.1; P < .0001), ORS (aOR = 2.3; P = .0008), and overall (aOR = 4.3; P < .0001) were significant. Intervention worked better for IHPs who practiced for ≥10 years (aOR = 3.2; P < .0001), untrained IHPs (aOR = 4.8; P < .0001), and pharmacists (aOR = 8.3; P < .0001). Irrational practices like empirical antibiotic use for every cholera case (aOR = 0.3; P < .0001) and investigation for every diarrhea case (aOR = 0.4; P = .0003) were reduced. Rationality of testing (aOR = 4.2; P < .0001) and antibiotic use (aOR = 1.8; P = .0487) improved. CONCLUSIONS: Multicomponent educational intervention resulted in sustainable improvement in diarrhea-related knowledge and practices among IHPs in slums of Kolkata. Policy implications should be advocated along with implementation and scale-up.

Optimizing immunization schedules in endemic cholera regions: cost-effectiveness assessment of vaccination strategies for cholera control in Bangladesh.

This study is to examine the cost-effectiveness of deployment strategies of oral cholera vaccines (OCVs) in controlling cholera in Bangladesh. We developed a dynamic compartment model to simulate costs and health outcomes for 12 years for four OCVs deployment scenarios: (1) vaccination of children aged one and above with two doses of OCVs, (2) vaccination of population aged 5 and above with a single dose of OCVs, (3) vaccination of children aged 1-4 with two doses of OCVs; and (4) combined strategy of (2) and (3). We obtained all parameters from the literature and performed a cost-effectiveness analysis from both health systems and societal perspectives, in comparison with the base scenario of no vaccination.The incremental cost-effectiveness ratios (ICERs) for the four strategies from the societal perspective were $2,236, $2,250, $1,109, and $2,112 per DALY averted, respectively, with herd immunity being considered. Without herd immunity, the ICERs increased substantially for all four scenarios except for the scenario that vaccinates children aged 1-4 only. The major determinants of ICERs were the case fatality rate and the incidence of cholera, as well as the efficacy of OCVs. The projection period and frequency of administering OCVs would also affect the cost-effectiveness of OCVs. With the cut-off of 1.5 times gross domestic product per capita, the four OCVs deployment strategies are cost-effective. The combined strategy is more efficient than the strategy of vaccinating the population aged one and above with two doses of OCVs and could be considered in the resource-limited settings.

Life-Course Approach to Vaccination in Bangladesh for Meeting the Health and Health-Related Sustainable Development Goals: A Commentary.

Bangladesh is entering from low-income to lower-middle-income status in 2020, and this will be completed in the next 5 years. With gross national income growing, vaccines will need to be procured through private market for the Expanded Program on Immunization. A cost-benefit analysis is needed to evaluate vaccine demand in different socioeconomic groups in the country, to inform this procurement. Moreover, disease burden studies and awareness of importance of specific vaccines are needed as we move forward. A life-course approach to vaccination may enable whole society to realize the full potential of vaccination and address most significant threats to its success over time.

Mathematical Modeling of Endemic Cholera Transmission.

Mathematical modeling can be used to project the impact of mass vaccination on cholera transmission. Here, we discuss 2 examples for which indirect protection from mass vaccination needs to be considered. In the first, we show that nonvaccinees can be protected by mass vaccination campaigns. This additional benefit of indirect protection improves the cost-effectiveness of mass vaccination. In the second, we model the use of mass vaccination to eliminate cholera. In this case, a high population level of immunity, including contributions from infection and vaccination, is required to reach the "herd immunity" threshold needed to stop transmission and achieve elimination.

A Novel Luminescence-Based Serum Bactericidal Assay for Vibrio cholerae Reduces Assay Variation, Is Time- and Cost-Effective, and Directly Measures Continuous Titer Values.

Cholera remains a significant public health burden worldwide, and better methods for monitoring cholera incidence would enhance the effectiveness of public health interventions. The serum bactericidal assay (SBA) has been used extensively for Vibrio cholerae vaccine assessments and serosurveillance. Current SBA approaches for V. cholerae rely on colony enumeration or optical density (OD600nm) readings to measure viable bacteria following complement-mediated lysis. These methods provide titer values that are constrained to discrete dilution values and rely on bacterial outgrowth, which is time consuming and prone to variation. Detection of bacterial proteins following complement-mediated lysis presents a faster and potentially less variable alternative approach independent of bacterial outgrowth. Here, we present an SBA that measures luciferase luminescence driven by lysis-released adenylate kinase. This approach is faster and less variable than growth-dependent SBAs and directly measures continuous titer values. This novel SBA method can potentially be applied to other bacteria of interest.

Assessment of Vaccine Herd Protection: Lessons Learned From Cholera and Typhoid Vaccine Trials.

Vaccine herd protection is the extension of the defense conferred by immunization beyond the vaccinated to unvaccinated persons in a population, as well as the enhancement of the protection among the vaccinated, due to vaccination of the surrounding population. Vaccine herd protection has traditionally been inferred from observations of disease trends after inclusion of a vaccine in national immunization schedules. Rather than awaiting outcomes of widescale vaccine deployment, earlier-stage evaluation of vaccine herd protection during trials or mass vaccination projects could help inform policy decisions about potential vaccine introduction. We describe the components, influencing factors, and implications of vaccine herd protection and discuss various methods for assessing herd protection, using examples from cholera and typhoid vaccine studies.

Household Disinfection Interventions to Prevent Cholera Transmission: Facilitators, Barriers, Training, and Evidence Needs.

There are two common household disinfection interventions to prevent interhousehold transmission of cholera: household spraying, whereby a team disinfects cholera patients' households, and household disinfection kits (HDKs), whereby cleaning materials are provided to cholera patients' family members. Currently, both interventions lack evidence, and international agencies recommend HDK distribution; however, household spraying remains widely implemented. To understand this disconnect, we conducted 14 key informant interviews with international and national responders and a study in Haiti assessing HDK efficacy using two training modules including 20 household surveys and 327 surfaces samples before and after cleaning. During interviews, 80% of the international-level informants discussed evidence gaps for both interventions, and 60% preferred HDKs. Conversely, no national-level informants knew what an HDK was; therefore, they all preferred spraying. Informants discussed behavior changes, bleach perceptions, and implementation as facilitators and/or barriers to implementing both interventions. In households, training with demonstrations regarding the use of HDK led to increased reductions of Escherichia coli (P < 0.001) and Vibrio spp. (P < 0.001) on surfaces after participants cleaned the household compared with a hygiene promotion session only. These results emphasize the gap between the current international-level policy and the realities of cholera response programs, highlight the need for evidence to align household disinfection recommendations, and underscore the importance of the dissemination and training of responders and affected populations regarding methods to prevent intrahousehold cholera transmission.

The impact of improved water supply on cholera and diarrhoeal diseases in Uvira, Democratic Republic of the Congo: a protocol for a pragmatic stepped-wedge cluster randomised trial and economic evaluation.

INTRODUCTION: Diarrhoeal disease remains a leading cause of mortality and morbidity worldwide. Cholera alone is estimated to cause 95,000 deaths per year, most of which occur in endemic settings with inadequate water access. Whilst a global strategy to eliminate cholera by 2030 calls for investment in improved drinking water services, there is limited rigorous evidence for the impact of improved water supply on endemic cholera transmission in low-income urban settings. Our protocol is designed to deliver a pragmatic health impact evaluation of a large-scale water supply intervention in Uvira (Democratic Republic of the Congo), a cholera transmission hotspot. METHODS/DESIGN: A stepped-wedge cluster randomised trial (SW-CRT) was designed to evaluate the impact of a large-scale drinking water supply intervention on cholera incidence among the 280,000 inhabitants of Uvira. The city was divided into 16 clusters, where new community and household taps will be installed following a randomised sequence over a transition period of up to 8 weeks in each cluster. The primary trial outcomes are the monthly incidence of "confirmed" cholera cases (patients testing positive by rapid detection kit) and of "suspected" cholera cases (patients admitted to the cholera treatment centre). Concurrent process and economic evaluations will provide further information on the context, costs, and efficiency of the intervention. DISCUSSION: In this protocol, we describe a pragmatic approach to conducting rigorous research to assess the impacts of a complex water supply intervention on severe diarrhoeal disease and cholera in an unstable, low-resource setting representative of cholera-affected areas. In particular, we discuss a series of pre-identified risks and linked mitigation strategies as well as the value of combining different data collection methods and preparation of multiple analysis scenarios to account for possible deviations from the protocol. The study described here has the potential to provide robust evidence to support more effective cholera control in challenging, high-burden settings. TRIAL REGISTRATION: This trial is registered on clinicaltrials.gov ( NCT02928341 , 10th October 2016) and has received ethics approval from the London School of Hygiene and Tropical Medicine (8913, 10603) and from the Ethics Committee from the School of Public Health, University of Kinshasa, Democratic Republic of the Congo (ESP/CE/088/2015).

RESUME (VERSION FRANçAISE): Please note this translation has been generated by the authors and has not been checked against the original, peer-reviewed English version by the Journal. Any discrepancies between the two versions should be raised with the authors. Cette traduction a été préparée par les auteurs et sa conformité avec la version anglaise revue par les pairs n'a pas été vérifiée par le journal. Toute différence entre les deux versions doit être signalée aux auteurs. INTRODUCTION: Les maladies diarrhéiques restent une cause majeure de mortalité et morbidité dans le monde. Le choléra seul cause environ 95'000 morts par an, dont la plupart dans des contextes endémiques où l'accès à l'eau est inadéquat. Tandis qu'une stratégie globale pour l'élimination du choléra d'ici à 2030 appelle des investissements dans l'amélioration des services d'approvisionnement en eau, il y a peu de données probantes et rigoureuses sur l'impact d'un approvisionnement en eau amélioré sur la transmission endémique du choléra dans les contextes urbains à faibles ressources. Notre protocole d'étude est conçu pour livrer une évaluation d'impact épidémiologique pragmatique d'une intervention d'approvisionnement en eau à large échelle à Uvira, République Démocratique du Congo, un point focal de transmission du choléra. MéTHODES/CONCEPTION: Un essai randomisé par grappes par échelons (stepped-wedge cluster randomised trial, SW-CRT) a été conçu pour évaluer l'impact d'une intervention d'approvisionnement en eau potable à large échelle sur l'incidence du choléra parmi les 280'000 habitants d'Uvira. La ville a été divisée en 16 grappes, dans lesquelles de nouvelles bornes fontaines et branchements individuels seront installés suivant une séquence randomisée sur une période allant jusqu'à 8 semaines par grappe. Le principal résultat de l'essai sera l'incidence mensuelle des cas de choléra « confirmés ¼ (patients positifs par tests de détection rapide) et des cas « suspects ¼ (patients admis au centre de traitement du choléra). Des évaluations de processus et économique menées en parallèle fourniront des informations complémentaires sur le contexte, les coûts et l'efficience de l'intervention. DISCUSSION: Dans ce protocole, nous présentons une approche pragmatique pour effectuer une recherche rigoureuse visant à évaluer les impacts d'une intervention complexe d'approvisionnement en eau sur la diarrhée sévère et le choléra dans un contexte instable et à faibles ressources, représentatif des zones affectées par le choléra. En particulier, nous considérons une série de risques pré-identifiés et les stratégies de mitigation associées ainsi que la valeur de combiner différentes méthodes de collecte de données et de préparer de multiples scénarios d'analyse pour tenir compte d'éventuelles déviations du protocole. L'étude présentée ici a le potentiel de fournir des évidences scientifiques robustes pour soutenir des stratégies de contrôle du choléra plus efficientes dans les contextes difficiles qui sont fortement affectés. ENREGISTREMENT DE L'ESSAI: Cet essai est enregistré sur clinicaltrials.gov ( NCT02928341 , 10 octobre 2016) et a reçu les approbations éthiques de la London School of Hygiene and Tropical Medicine (8913, 10603) ainsi que de l'Ecole de Santé Publique de l'Université de Kinshasa, République Démocratique du Congo (ESP/CE/088/2015).

Effectiveness of a killed whole-cell oral cholera vaccine in Bangladesh: further follow-up of a cluster-randomised trial.

BACKGROUND: Killed whole-cell oral cholera vaccines (OCVs) are widely used for prevention of cholera in developing countries. However, few studies have evaluated the protection conferred by internationally recommended OCVs for durations beyond 2 years of follow-up. METHODS: In this study, we followed up the participants of a cluster-randomised controlled trial for 2 years after the end of the original trial. Originally, we had randomised 90 geographical clusters in Dhaka slums in Bangladesh in equal numbers (1:1:1) to a two-dose regimen of OCV alone (targeted to people aged 1 year or older), a two-dose regimen of OCV plus a water-sanitation-hygiene (WASH) intervention, or no intervention. There was no masking of group assignment. The WASH intervention conferred little additional protection to OCV and was discontinued at 2 years of follow-up. Surveillance for severe cholera was continued for 4 years. Because of the short duration and effect of the WASH intervention, we combined the two OCV intervention groups. The primary outcomes were OCV overall protection (protection of all members of the intervention clusters) and total protection (protection of individuals who got vaccinated in the intervention clusters) against severe cholera, which we assessed by multivariable survival models appropriate for cluster-randomised trials. This trial is registered on ClinicalTrials.gov, NCT01339845. FINDINGS: The study was done between April 17, 2011, and Nov 1, 2015. 268 896 participants were present at the time of the first dose, with 188 206 in the intervention group and 80 690 in the control group. OCV coverage of the two groups receiving OCV was 66% (123 659 of 187 214 participants). During 4 years of follow-up, 441 first episodes of severe cholera were detected (243 episodes in the vaccinated groups and as 198 episodes in the unvaccinated group). Overall OCV protection was 36% (95% CI 19 to 49%) and total OCV protection was 46% (95% CI 32 to 58). Cumulative total vaccine protection was notably lower for people vaccinated before the age of 5 years (24%; -30 to 56) than for people vaccinated at age 5 years or older (49%; 35 to 60), although the differences in protection for the two age groups were not significant (p=0·3308). Total vaccine protection dropped notably (p=0·0115) after 3 years in children vaccinated at 1-4 years of age. INTERPRETATION: These findings provide further evidence of long-term effectiveness of killed whole-cell OCV, and therefore further support for the use of killed whole-cell OCVs to control endemic cholera, but indicate that protection is shorter-lived in children vaccinated before the age of 5 years than in people vaccinated at the age of 5 years or older. FUNDING: Bill & Melinda Gates Foundation. TRANSLATION: For the Bengali translation of the abstract see Supplementary Materials section.

The past and present of pandemic management: health diplomacy, international epidemiological surveillance, and COVID-19.

The establishment of international sanitary institutions, which took place in the context of rivalry among the great European powers and their colonial expansion in Asia, allowed for the development of administrative systems of international epidemiological surveillance as a response to the cholera epidemics at the end of the nineteenth century. In this note, I reflect on how a historical analysis of the inception of international epidemiological surveillance and pandemic management helps us to understand what is happening in the COVID-19 pandemic today.