A framework for seroepidemiologic investigations in future pandemics: insights from an evaluation of WHO's Unity Studies initiative.

BACKGROUND: The WHO Unity Studies initiative supports countries, especially low- and middle-income countries (LMICs), in conducting seroepidemiologic studies for rapidly informing responses to the COVID-19 pandemic. Ten generic study protocols were developed which standardized epidemiologic and laboratory methods. WHO provided technical support, serological assays and funding for study implementation. An external evaluation was conducted to assess (1) the usefulness of study findings in guiding response strategies, (2) management and support to conduct studies and (3) capacity built from engagement with the initiative. METHODS: The evaluation focused on the three most frequently used protocols, namely first few cases, household transmission and population-based serosurvey, 66% of 339 studies tracked by WHO. All 158 principal investigators (PIs) with contact information were invited to complete an online survey. A total of 19 PIs (randomly selected within WHO regions), 14 WHO Unity focal points at the country, regional and global levels, 12 WHO global-level stakeholders and eight external partners were invited to be interviewed. Interviews were coded in MAXQDA™, synthesized into findings and cross-verified by a second reviewer. RESULTS: Among 69 (44%) survey respondents, 61 (88%) were from LMICs. Ninety-five percent gave positive feedback on technical support, 87% reported that findings contributed to COVID-19 understanding, 65% to guiding public health and social measures, and 58% to guiding vaccination policy. Survey and interview group responses showed that the main technical barriers to using study findings were study quality, variations in study methods (challenge for meta-analysis), completeness of reporting study details and clarity of communicating findings. Untimely study findings were another barrier, caused by delays in ethical clearance, receipt of serological assays and approval to share findings. There was strong agreement that the initiative created equitable research opportunities, connected expertise and facilitated study implementation. Around 90% of respondents agreed the initiative should continue in the future. CONCLUSIONS: The Unity Studies initiative created a highly valued community of practice, contributed to study implementation and research equity, and serves as a valuable framework for future pandemics. To strengthen this platform, WHO should establish emergency-mode procedures to facilitate timeliness and continue to build capacity to rapidly conduct high-quality studies and communicate findings in a format friendly to decision-makers.

Coverage survey and lessons learned from a pre-emptive cholera vaccination campaign in urban and rural communities affected by landslides and floods in Freetown Sierra Leone.

BACKGROUND: On 14 August 2017, massive landslides and floods hit Freetown (Sierra Leone). More than 1,000 people lost their lives while approximately 6,000 people were displaced. The areas most affected included parts of the town with challenged access to basic water and sanitation facilities, with communal water sources likely contaminated by the disaster. To avert a possible cholera outbreak following this emergency, the Ministry of Health and Sanitation (MoHS), supported by the World Health Organization (WHO) and international partners, including Médecins Sans Frontières (MSF) and UNICEF, launched a two-dose pre-emptive vaccination campaign using Euvichol™, an oral cholera vaccine (OCV). METHODS: We conducted a stratified cluster survey to estimate vaccination coverage during the OCV campaign and also monitor adverse events. The study population - subsequently stratified by age group and residence area type (urban/rural) - included all individuals aged 1 year or older, living in one of the 25 communities targeted for vaccination. RESULTS: In total 3,115 households were visited, 7,189 individuals interviewed; 2,822 (39%) people in rural and 4,367 (61%) in urban areas. The two-dose vaccination coverage was 56% (95% confidence interval (CI): 51.0-61.5), 44% (95%CI: 35.2-53.0) in rural and 57% (95%CI: 51.6-62.8) in urban areas. Vaccination coverage with at least one dose was 82% (95%CI: 77.3-85.5), 61% (95%CI: 52.0-70.2) in rural and 83% (95%CI: 78.5-87.1) in urban areas. CONCLUSIONS: The Freetown OCV campaign exemplified a timely public health intervention to prevent a cholera outbreak, even if coverage was lower than expected. We hypothesised that vaccination coverage in Freetown was sufficient in providing at least short-term immunity to the population. However, long-term interventions to ensure access to safe water and sanitation are needed.

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.

Disproportionality analysis of reported drug adverse events to assess a potential safety signal for pentavalent vaccine in 2019 in El Salvador.

Detection and surveillance of vaccine safety hazards is a public health staple. In the post-marketing phase, when vaccines are used in mass, it is crucial to monitor potential signals of adverse reactions that may have been missed in the pre-marketing phase. We analysed spontaneous reports of drug adverse events in El Salvador to assess a potential safety signal related to an increase in febrile seizures following the pentavalent (diphtheria, tetanus, pertussis, hepatitis B, and Haemophilus influenzae Type B) vaccine in 2019. This was a retrospective observational study of adverse event notifications in the national electronic drug safety database from 2011 to 2019. We performed standard disproportionality analysis computing Proportional Reporting Risk (PRR), Reporting Odds Ratio (ROR), Relative Reporting Ratio (RRR), Chi-squared, and Information Component (IC), comparing the pairing of febrile seizures and pentavalent vaccine to all other drugs and adverse events recorded in 2019. The occurrence of febrile seizures following pentavalent vaccination exceeded the WHO expected rate of six cases × 100 000 doses administered from April 2019, with a maximum of 9.2 in September. IC was 4.3, ORR 421.9 (95% Confidence Interval, CI: 123.8-1437.7), PRR 223.5 (95 %CI: 70.2-710.9), RRR was 19.5. The first booster presented the highest rate (14.6 per 100,000 doses) of febrile seizures, more than double than expected. Rates for 2018 remained below expected. Reports of febrile seizures following pentavalent vaccine were also on the increase globally since 2014, with highest rates in 2018 and 2019. There was a disproportion of febrile seizures notifications following pentavalent in El Salvador in 2019, suggesting the existence of a safety signal. This may be due to the change in provider. Further studies should assess the causes of the increase and compute costs and benefits of this vaccination to determine if switching to a less reactogenic vaccine formulation is indicated.

Successive epidemic waves of cholera in South Sudan between 2014 and 2017: a descriptive epidemiological study.

BACKGROUND: Between 2014 and 2017, successive cholera epidemics occurred in South Sudan within the context of civil war, population displacement, flooding, and drought. We aim to describe the spatiotemporal and molecular features of the three distinct epidemic waves and explore the role of vaccination campaigns, precipitation, and population movement in shaping cholera spread in this complex setting. METHODS: In this descriptive epidemiological study, we analysed cholera linelist data to describe the spatiotemporal progression of the epidemics. We placed whole-genome sequence data from pandemic Vibrio cholerae collected throughout these epidemics into the global phylogenetic context. Using whole-genome sequence data in combination with other molecular attributes, we characterise the relatedness of strains circulating in each wave and the region. We investigated the association of rainfall and the instantaneous basic reproduction number using distributed lag non-linear models, compared county-level attack rates between those with early and late reactive vaccination campaigns, and explored the consistency of the spatial patterns of displacement and suspected cholera case reports. FINDINGS: The 2014 (6389 cases) and 2015 (1818 cases) cholera epidemics in South Sudan remained spatially limited whereas the 2016-17 epidemic (20 438 cases) spread among settlements along the Nile river. Initial cases of each epidemic were reported in or around Juba soon after the start of the rainy season, but we found no evidence that rainfall modulated transmission during each epidemic. All isolates analysed had similar genotypic and phenotypic characteristics, closely related to sequences from Uganda and Democratic Republic of the Congo. Large-scale population movements between counties of South Sudan with cholera outbreaks were consistent with the spatial distribution of cases. 21 of 26 vaccination campaigns occurred during or after the county-level epidemic peak. Counties vaccinated on or after the peak incidence week had 2·2 times (95% CI 2·1-2·3) higher attack rates than those where vaccination occurred before the peak. INTERPRETATION: Pandemic V cholerae of the same clonal origin was isolated throughout the study period despite interepidemic periods of no reported cases. Although the complex emergency in South Sudan probably shaped some of the observed spatial and temporal patterns of cases, the full scope of transmission determinants remains unclear. Timely and well targeted use of vaccines can reduce the burden of cholera; however, rapid vaccine deployment in complex emergencies remains challenging. FUNDING: The Bill & Melinda Gates Foundation.

Lot quality assurance sampling to assess coverage and compliance following mass drug administration to eliminate lymphatic filariasis in Fiji: A methodological approach.

BACKGROUND: Assessing the quality of mass drug administration (MDA) rounds is a key component of lymphatic filariasis (LF) elimination programs. Routine collection of administrative coverage is unreliable, especially when pockets with low program coverage exist. To address this gap, we used lot quality assurance sampling (LQAS) following the 10th annual LF-MDA round in Fiji to explore whether there was any area in which target coverage was not reached. We also assessed the level of drug compliance and satisfaction with the LF-MDA implementation strategy. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a cross-sectional household survey in 3 divisions of Fiji. For LQAS, we defined 19 lots in 7 medical areas of the Suva sub-division and another 12 sub-divisions in the Central, Northern, and Eastern Divisions. A sample of 16 randomly selected household members was taken un each lot. We defined our decision rule as follows: if more than 1 person in a given lot did not swallow the medication, coverage was considered inadequate, i.e. less than 80%. Of the 7 lots in Suva sub-division and 12 lots in the 3 divisions, five and two lots, respectively, were identified as having inadequate coverage. The overall program coverage estimated from 304 samples was 92%, which was higher than the reported administrative coverage of 82%. About 98% of interviewees were offered the medication and 96% swallowed it. Non-participation arose from insufficient information on how to obtain the drugs. At least 92% were satisfied with the LF-MDA implementation strategy. CONCLUSIONS: Areas of low program coverage with results discordant with the reported administrative coverage existed in both urban and rural settings. Drug compliance and satisfaction were high, even after repeated rounds. We recommend increasing efforts to deliver the service in those areas with inadequate program coverage, as well as conducting timely coverage assessment through LQAS for corrective action.

The reactive vaccination campaign against cholera emergency in camps for internally displaced persons, Borno, Nigeria, 2017: a two-stage cluster survey.

INTRODUCTION: In 2017, amidst insecurity and displacements posed by Boko Haram armed insurgency, cholera outbreak started in the Muna Garage camp for Internally Displaced Persons (IDPs) in Borno State, Nigeria. In response, the Borno Ministry of Health and partners determined to provide oral cholera vaccine (OCV) to about 1 million people in IDP camps and surrounding communities in six Local Government Areas (LGAs) including Maiduguri, Jere, Konduga, Mafa, Dikwa, and Monguno. As part of Monitoring and Evaluation, we described the coverage achieved, adverse events following immunisation (AEFI), non-vaccination reasons, vaccination decisions as well as campaign information sources. METHODS: We conducted two-stage probability cluster surveys with clusters selected without replacement according to probability-proportionate-to-population-size in the six LGAs targeted by the campaign. Individuals aged ≥1 years were the eligible study population. Data sources were household interviews with vaccine card verification and memory recall, if no card, as well as multiple choice questions with an open-ended option. RESULTS: Overall, 12 931 respondents participated in the survey. Overall, 90% (95% CI: 88 to 92) of the target population received at least one dose of OCV, range 87% (95% CI: 75 to 94) in Maiduguri to 94% (95% CI: 88 to 97) in Monguno. The weighted two-dose coverage was 73% (95% CI: 68 to 77) with a low of 68% (95% CI: 46 to 86) in Maiduguri to a high of 87% (95% CI: 74 to 95) in Dikwa. The coverage was lower during first round (76%, 95% CI: 71 to 80) than second round (87%, 95% CI: 84 to 89) and ranged from 72% (95% CI: 42 to 89) and 82% (95% CI: 82 to 91) in Maiduguri to 87% (95% CI: 75 to 95) and 94% (95% CI: 88 to 97) in Dikwa for the respective first and second rounds. Also, coverage was higher among females of age 5 to 14 and ≥15 years than males of same age groups. There were mild AEFI with the most common symptoms being fever, headache and diarrhoea occurring up to 48 hours after ingesting the vaccine. The most common actions taken after AEFI symptoms included 'did nothing' and 'self-medicated at home'. The top reason for taking vaccine was to protect from cholera while top reason for non-vaccination was travel/work. The main source of campaign information was a neighbour. An overwhelming majority (96%, 95% CI: 95% to 98%) felt the campaign team treated them with respect. While 43% (95% CI: 36% to 50%) asked no questions, 37% (95% CI: 31% to 44%) felt the team addressed all their concerns. CONCLUSION: The campaign achieved high coverage using door-to-door and fixed sites strategies amidst insecurity posed by Boko Haram. Additional studies are needed to improve how to reduce non-vaccination, especially for the first round. While OCV provides protection for a few years, additional actions will be needed to make investments in water, sanitation and hygiene infrastructure.

The multi-sectorial emergency response to a cholera outbreak in Internally Displaced Persons camps in Borno State, Nigeria, 2017.

Introduction: In August 2017, a cholera outbreak started in Muna Garage Internally Displaced Persons camp, Borno state, Nigeria and >5000 cases occurred in six local government areas. This qualitative study evaluated perspectives about the emergency response to this outbreak. Methods: We conducted 39 key informant interviews and focus group discussions, and reviewed 21 documents with participants involved with surveillance, water, sanitation, hygiene, case management, oral cholera vaccine (OCV), communications, logistics and coordination. Qualitative data analysis used thematic techniques comprising key words in context, word repetition and key sector terms. Results: Authorities were alerted quickly, but outbreak declaration took 12 days due to a 10-day delay waiting for culture confirmation. Outbreak investigation revealed several potential transmission channels, but a leaking latrine around the index cases' house was not repaired for more than 7 days. Chlorine was initially not accepted by the community due to rumours that it would sterilise women. Key messages were in Hausa, although Kanuri was the primary local language; later this was corrected. Planning would have benefited using exercise drills to identify weaknesses, and inventory sharing to avoid stock outs. The response by the Rural Water Supply and Sanitation Agency was perceived to be slow and an increased risk from a religious festival was not recognised. Case management was provided at treatment centres, but some partners were concerned that their work was not recognised asking, 'Who gets the glory and the data?' Nearly one million people received OCV and its distribution benefited from a robust infrastructure for polio vaccination. There was initial anxiety, rumour and reluctance about OCV, attributed by many to lack of formative research prior to vaccine implementation. Coordination was slow initially, but improved with activation of an emergency operations centre (EOC) that enabled implementation of incident management system to coordinate multisectoral activities and meetings held at 16:00 hours daily. The synergy between partners and government improved when each recognised the government's leadership role. Conclusion: Despite a timely alert of the outbreak, delayed laboratory confirmation slowed initial response. Initial responses to the outbreak were not well coordinated but improved with the EOC. Understanding behaviours and community norms through rapid formative research should improve the effectiveness of the emergency response to a cholera outbreak. OCV distribution was efficient and benefited from the polio vaccine infrastructure.

Global oral cholera vaccine use, 2013-2018.

Vaccination is a key intervention to prevent and control cholera in conjunction with water, sanitation and hygiene activities. An oral cholera vaccine (OCV) stockpile was established by the World Health Organization (WHO) in 2013. We reviewed its use from July 2013 to all of 2018 in order to assess its role in cholera control. We computed information related to OCV deployments and campaigns conducted including setting, target population, timelines, delivery strategy, reported adverse events, coverage achieved, and costs. In 2013-2018, a total of 83,509,941 OCV doses have been requested by 24 countries, of which 55,409,160 were approved and 36,066,010 eventually shipped in 83 deployments, resulting in 104 vaccination campaigns in 22 countries. OCVs had in general high uptake (mean administrative coverage 1st dose campaign at 90.3%; 2nd dose campaign at 88.2%; mean survey-estimated two-dose coverage at 69.9%, at least one dose at 84.6%) No serious adverse events were reported. Campaigns were organized quickly (five days median duration). In emergency settings, the longest delay was from the occurrence of the emergency to requesting OCV (median: 26 days). The mean cost of administering one dose of vaccine was 2.98 USD. The OCV stockpile is an important public health resource. OCVs were generally well accepted by the population and their use demonstrated to be safe and feasible in all settings. OCV was an inexpensive intervention, although timing was a limiting factor for emergency use. The dynamic created by the establishment of the OCV stockpile has played a role in the increased use of the vaccine by setting in motion a virtuous cycle by which better monitoring and evaluation leads to better campaign organization, better cholera control, and more requests being generated. Further work is needed to improve timeliness of response and contextualize strategies for OCV delivery in the various settings.

An Expanded Transmission Assessment Survey to Confirm the Interruption of Lymphatic Filariasis Transmission in Wallis and Futuna.

Historically, the human prevalence of Wuchereria bancrofti infection in Wallis and Futuna (WAF) was among the highest in the Pacific and mass drug administration (MDA) against lymphatic filariasis (LF) either with diethylcarbamazine citrate (DEC) or the combination of DEC and albendazole had been implemented for decades. To determine whether LF antigen prevalence in WAF was lower than 1%, the infection threshold for elimination in an area where Aedes spp. are the principal vectors, we conducted the WHO-recommended transmission assessment survey in 2012. We present the results of a school-based survey, which targeted 1,014 students in all 13 elementary schools in WAF. From a fingerprick, the circulating filarial antigen (CFA) positivity was checked for grade 2-5 students using BinaxNOW filariasis test (immunochromatographic test). Of 935 children tested, three were positive for CFA in two schools. At the territory level, this was below the critical cutoff of nine cases, if the whole territory was considered as a single evaluation unit. The prevalence of CFA in WAF is less than 1%, reaching the goal for LF elimination set by the WHO. We were able to recommend stopping LF MDA and move to post-MDA surveillance to detect any recrudescence. This survey successfully paved the way for WAF to be validated as achieving LF elimination as a public health problem by 2020.

Delayed second dose of oral cholera vaccine administered before high-risk period for cholera transmission: Cholera control strategy in Lusaka, 2016.

BACKGROUND: In April 2016, an emergency vaccination campaign using one dose of Oral Cholera Vaccine (OCV) was organized in response to a cholera outbreak that started in Lusaka in February 2016. In December 2016, a second round of vaccination was conducted, with the objective of increasing the duration of protection, before the high-risk period for cholera transmission. We assessed vaccination coverage for the first and second rounds of the OCV campaign. METHODS: Vaccination coverage was estimated after each round from a sample selected from targeted-areas for vaccination using a cross-sectional survey in to establish the vaccination status of the individuals recruited. The study population included all individuals older than 12 months residing in the areas targeted for vaccination. We interviewed 505 randomly selected individuals after the first round and 442 after the second round. Vaccination status was ascertained either by vaccination card or verbal reporting. Households were selected using spatial random sampling. RESULTS: The vaccination coverage with two doses was 58.1% (25/43; 95%CI: 42.1-72.9) in children 1-5 years old, 59.5% (69/116; 95%CI: 49.9-68.5) in children 5-15 years old and 19.9% (56/281; 95%CI: 15.4-25.1) in adults above 15 years old. The overall dropout rate was 10.9% (95%CI: 8.1-14.1). Overall, 69.9% (n = 309/442; 95%CI: 65.4-74.1) reported to have received at least one OCV dose. CONCLUSIONS: The areas at highest risk of suffering cholera outbreaks were targeted for vaccination obtaining relatively high vaccine coverage after each round. However, the long delay between doses in areas subject to considerable population movement resulted in many individuals receiving only one OCV dose. Additional vaccination campaigns may be required to sustain protection over time in case of persistence of risk. Further evidence is needed to establish a maximum optimal interval time of a delayed second dose and variations in different settings.

Effectiveness of oral cholera vaccine in preventing cholera among fishermen in Lake Chilwa, Malawi: A case-control study.

BACKGROUND: In response to a cholera outbreak among mobile, difficult-to-reach fishermen on Lake Chilwa, Malawi in 2016, a novel vaccine distribution strategy exploited the proven vaccine thermostability. Fishermen, while taking the first vaccine dose under supervision, received the second dose in a sealed bag, and were told to drink it two weeks later. This study assessed short-term vaccine protection of this strategy. METHODS: Patients with diarrhoea admitted to health facilities around lake were interviewed and a stool sample collected for PCR testing. Vaccine effectiveness was assessed in a case-control test-negative design by comparing cases (PCR-positive for V. cholerae O1) and controls (patients with diarrhoea but PCR-negative) and with the screening method that compared the proportions of vaccinated among cholera cases versus the general fishermen population. RESULTS: Of 145 study participants, 120 were fishermen living on the lake. Vaccine effectiveness at three-months was 90.0% [95%CI:38.8;98.4] among fishermen and 83.3% [95%CI: 20.8; 96.5] among all participants in the case-control test-negative design, and 97.5% [95%CI: 90.9;99.3] with the screening method. CONCLUSION: This strategy was effective in providing short-term protection in fishermen against cholera. Further research is needed to determine the adding value of the second dose and to identify the optimal vaccination strategies for different contexts.

Oral cholera vaccination in hard-to-reach communities, Lake Chilwa, Malawi.

OBJECTIVE: To evaluate vaccination coverage, identify reasons for non-vaccination and assess satisfaction with two innovative strategies for distributing second doses in an oral cholera vaccine campaign in 2016 in Lake Chilwa, Malawi, in response to a cholera outbreak. METHODS: We performed a two-stage cluster survey. The population interviewed was divided in three strata according to the second-dose vaccine distribution strategy: (i) a standard strategy in 1477 individuals (68 clusters of 5 households) on the lake shores; (ii) a simplified cold-chain strategy in 1153 individuals (59 clusters of 5 households) on islands in the lake; and (iii) an out-of-cold-chain strategy in 295 fishermen (46 clusters of 5 to 15 fishermen) in floating homes, called zimboweras. FINDING: Vaccination coverage with at least one dose was 79.5% (1153/1451) on the lake shores, 99.3% (1098/1106) on the islands and 84.7% (200/236) on zimboweras. Coverage with two doses was 53.0% (769/1451), 91.1% (1010/1106) and 78.8% (186/236), in the three strata, respectively. The most common reason for non-vaccination was absence from home during the campaign. Most interviewees liked the novel distribution strategies. CONCLUSION: Vaccination coverage on the shores of Lake Chilwa was moderately high and the innovative distribution strategies tailored to people living on the lake provided adequate coverage, even among hard-to-reach communities. Community engagement and simplified delivery procedures were critical for success. Off-label, out-of-cold-chain administration of oral cholera vaccine should be considered as an effective strategy for achieving high coverage in hard-to-reach communities. Nevertheless, coverage and effectiveness must be monitored over the short and long term.

Oral cholera vaccine coverage during a preventive door-to-door mass vaccination campaign in Nampula, Mozambique.

BACKGROUND: In addition to improving water, sanitation and hygiene (WASH) measures and optimal case management, the introduction of Oral cholera vaccine (OCV) is a complementary strategy for cholera prevention and control for vulnerable population groups. In October 2016, the Mozambique Ministry of Health implemented a mass vaccination campaign using a two-dose regimen of the Shanchol™ OCV in six high-risk neighborhoods of Nampula city, in Northern Mozambique. Overall 193,403 people were targeted by the campaign, which used a door-to-door strategy. During campaign follow-up, a population survey was conducted to assess: (1) OCV coverage; (2) frequency of adverse events following immunization; (3) vaccine acceptability and (4) reasons for non-vaccination. METHODOLOGY/PRINCIPAL FINDINGS: In the absence of a household listing and clear administrative neighborhood delimitations, we used geospatial technology to select households from satellite images and used the support of community leaders. One person per household was randomly selected for interview. In total, 636 individuals were enrolled in the survey. The overall vaccination coverage with at least one dose (including card and oral reporting) was 69.5% (95%CI: 51.2-88.2) and the two-dose coverage was 51.2% (95%CI: 37.9-64.3). The campaign was well accepted. Among the 185 non-vaccinated individuals, 83 (44.6%) did not take the vaccine because they were absent when the vaccination team visited their houses. Among the 451 vaccinated individuals, 47 (10%) reported minor and non-specific complaints, and 78 (17.3%) mentioned they did not receive any information before the campaign. CONCLUSIONS/SIGNIFICANCE: In spite of overall coverage being slightly lower than expected, the use of a mobile door-to-door strategy remains a viable option even in densely-populated urban settings. Our results suggest that campaigns can be successfully implemented and well accepted in Mozambique in non-emergency contexts in order to prevent cholera outbreaks. These findings are encouraging and complement the previous Mozambican experience related to OCV.

Oral cholera vaccine in cholera prevention and control, Malawi.

PROBLEM: With limited global supplies of oral cholera vaccine, countries need to identify priority areas for vaccination while longer-term solutions, such as water and sanitation infrastructure, are being developed. APPROACH: In 2017, Malawi integrated oral cholera vaccine into its national cholera control plan. The process started with a desk review and analysis of previous surveillance and risk factor data. At a consultative meeting, researchers, national health and water officials and representatives from nongovernmental and international organizations reviewed the data and local epidemiological knowledge to determine priority districts for oral cholera vaccination. The final stage was preparation of an application to the global oral cholera vaccine stockpile for non-emergency use. LOCAL SETTING: Malawi collects annual data on cholera and most districts have reported cases at least once since the 1970s. RELEVANT CHANGES: The government's application for 3.2 million doses of vaccine to be provided over 20 months in 12 districts was accepted in April 2017. By April 2018, over 1 million doses had been administered in five districts. Continuing surveillance in districts showed that cholera outbreaks were notably absent in vaccinated high-risk areas, despite a national outbreak in 2017-2018. LESSONS LEARNT: Augmenting advanced mapping techniques with local information helped us extend priority areas beyond those identified as high-risk based on cholera incidence reported at the district level. Involvement of the water, sanitation and hygiene sectors is key to ensuring that short-term gains from cholera vaccine are backed by longer-term progress in reducing cholera transmission.

Cholera epidemic in Yemen, 2016-18: an analysis of surveillance data.

BACKGROUND: In war-torn Yemen, reports of confirmed cholera started in late September, 2016. The disease continues to plague Yemen today in what has become the largest documented cholera epidemic of modern times. We aimed to describe the key epidemiological features of this epidemic, including the drivers of cholera transmission during the outbreak. METHODS: The Yemen Health Authorities set up a national cholera surveillance system to collect information on suspected cholera cases presenting at health facilities. Individual variables included symptom onset date, age, severity of dehydration, and rapid diagnostic test result. Suspected cholera cases were confirmed by culture, and a subset of samples had additional phenotypic and genotypic analysis. We first conducted descriptive analyses at national and governorate levels. We divided the epidemic into three time periods: the first wave (Sept 28, 2016, to April 23, 2017), the increasing phase of the second wave (April 24, 2017, to July 2, 2017), and the decreasing phase of the second wave (July 3, 2017, to March 12, 2018). We reconstructed the changes in cholera transmission over time by estimating the instantaneous reproduction number, Rt. Finally, we estimated the association between rainfall and the daily cholera incidence during the increasing phase of the second epidemic wave by fitting a spatiotemporal regression model. FINDINGS: From Sept 28, 2016, to March 12, 2018, 1 103 683 suspected cholera cases (attack rate 3·69%) and 2385 deaths (case fatality risk 0·22%) were reported countrywide. The epidemic consisted of two distinct waves with a surge in transmission in May, 2017, corresponding to a median Rt of more than 2 in 13 of 23 governorates. Microbiological analyses suggested that the same Vibrio cholerae O1 Ogawa strain circulated in both waves. We found a positive, non-linear, association between weekly rainfall and suspected cholera incidence in the following 10 days; the relative risk of cholera after a weekly rainfall of 25 mm was 1·42 (95% CI 1·31-1·55) compared with a week without rain. INTERPRETATION: Our analysis suggests that the small first cholera epidemic wave seeded cholera across Yemen during the dry season. When the rains returned in April, 2017, they triggered widespread cholera transmission that led to the large second wave. These results suggest that cholera could resurge during the ongoing 2018 rainy season if transmission remains active. Therefore, health authorities and partners should immediately enhance current control efforts to mitigate the risk of a new cholera epidemic wave in Yemen. FUNDING: Health Authorities of Yemen, WHO, and Médecins Sans Frontières.

Implementation research: reactive mass vaccination with single-dose oral cholera vaccine, Zambia.

OBJECTIVE: To describe the implementation and feasibility of an innovative mass vaccination strategy - based on single-dose oral cholera vaccine - to curb a cholera epidemic in a large urban setting. METHOD: In April 2016, in the early stages of a cholera outbreak in Lusaka, Zambia, the health ministry collaborated with Médecins Sans Frontières and the World Health Organization in organizing a mass vaccination campaign, based on single-dose oral cholera vaccine. Over a period of 17 days, partners mobilized 1700 health ministry staff and community volunteers for community sensitization, social mobilization and vaccination activities in 10 townships. On each day, doses of vaccine were delivered to vaccination sites and administrative coverage was estimated. FINDINGS: Overall, vaccination teams administered 424 100 doses of vaccine to an estimated target population of 578 043, resulting in an estimated administrative coverage of 73.4%. After the campaign, few cholera cases were reported and there was no evidence of the disease spreading within the vaccinated areas. The total cost of the campaign - 2.31 United States dollars (US$) per dose - included the relatively low cost of local delivery - US$ 0.41 per dose. CONCLUSION: We found that an early and large-scale targeted reactive campaign using a single-dose oral vaccine, organized in response to a cholera epidemic within a large city, to be feasible and appeared effective. While cholera vaccines remain in short supply, the maximization of the number of vaccines in response to a cholera epidemic, by the use of just one dose per member of an at-risk community, should be considered.