Vaccination coverage and adverse events following a reactive vaccination campaign against hepatitis E in Bentiu displaced persons camp, South Sudan.

INTRODUCTION: Hepatitis E (HEV) genotypes 1 and 2 are the common cause of jaundice and acute viral hepatitis that can cause large-scale outbreaks. HEV infection is associated with adverse fetal outcomes and case fatality risks up to 31% among pregnant women. An efficacious three-dose recombinant vaccine (Hecolin) has been licensed in China since 2011 but until 2022, had not been used for outbreak response despite a 2015 WHO recommendation. The first ever mass vaccination campaign against hepatitis E in response to an outbreak was implemented in 2022 in Bentiu internally displaced persons camp in South Sudan targeting 27,000 residents 16-40 years old, including pregnant women. METHODS: We conducted a vaccination coverage survey using simple random sampling from a sampling frame of all camp shelters following the third round of vaccination. For survey participants vaccinated in the third round in October, we asked about the onset of symptoms experienced within 72 hours of vaccination. During each of the three vaccination rounds, passive surveillance of adverse events following immunisation (AEFI) was put in place at vaccination sites and health facilities in Bentiu IDP camp. RESULTS: We surveyed 1,599 individuals and found that self-reported coverage with one or more dose was 86% (95% CI 84-88%), 73% (95% CI 70-75%) with two or more doses and 58% (95% CI 55-61%) with three doses. Vaccination coverage did not differ significantly by sex or age group. We found no significant difference in coverage of at least one dose between pregnant and non-pregnant women, although coverage of at least two and three doses was 8 and 14 percentage points lower in pregnant women. The most common reasons for non-vaccination were temporary absence or unavailability, reported by 60% of unvaccinated people. Passive AEFI surveillance captured few mild AEFI, and through the survey we found that 91 (7.6%) of the 1,195 individuals reporting to have been vaccinated in October 2022 reported new symptoms starting within 72 hours after vaccination, most commonly fever, headache or fatigue. CONCLUSIONS: We found a high coverage of at least one dose of the Hecolin vaccine following three rounds of vaccination, and no severe AEFI. The vaccine was well accepted and well tolerated in the Bentiu IDP camp community and should be considered for use in future outbreak response.

Transmissibility and severity of COVID-19 in a humanitarian setting: First few X investigation of cases and contacts in Juba, South Sudan, 2020.

BACKGROUND: The first few 'X' (FFX) studies provide evidence to guide public health decision-making and resource allocation. The adapted WHO Unity FFX protocol for COVID-19 was implemented to gain an understanding of the clinical, epidemiological, virological and household transmission dynamics of the first cases of COVID-19 infection detected in Juba, South Sudan. METHODS: Laboratory-confirmed COVID-19 cases were identified through the national surveillance system, and an initial visit was conducted with eligible cases to identify all close contacts. Consenting cases and close contacts were enrolled between June 2020 and December 2020. Demographic, clinical information and biological samples were taken at enrollment and 14-21 days post-enrollment for all participants. RESULTS: Twenty-nine primary cases and 82 contacts were included in the analyses. Most primary cases (n = 23/29, 79.3%) and contacts (n = 61/82, 74.4%) were male. Many primary cases (n = 18/29, 62.1%) and contacts (n = 51/82, 62.2%) were seropositive for SARS-CoV-2 at baseline. The secondary attack rate among susceptible contacts was 12.9% (4/31; 95% CI: 4.9%-29.7%). All secondary cases and most (72%) primary cases were asymptomatic. Reported symptoms included coughing (n = 6/29, 20.7%), fever or history of fever (n = 4/29, 13.8%), headache (n = 3/29, 10.3%) and shortness of breath (n = 3/29, 10.3%). Of 38 cases, two were hospitalised (5.3%) and one died (2.6%). CONCLUSIONS: These findings were used to develop the South Sudanese Ministry of Health surveillance and contract tracing protocols, informing local COVID-19 case definitions, follow-up protocols and data management systems. This investigation demonstrates that rapid FFX implementation is critical in understanding the emerging disease and informing response priorities.

Short communication-Lessons learnt during the implementation of Unity-aligned SARS-CoV-2 seroprevalence studies in Africa.

The WHO Unity Studies initiative engaged low- and middle-income countries in the implementation of standardised SARS-CoV-2 sero-epidemiological investigation protocols and timely sharing of comparable results for evidence-based action. To gain a deeper understanding of the methodological challenges faced when conducting seroprevalence studies in the African region, we conducted unstructured interviews with key study teams in five countries. We discuss the challenges identified: participant recruitment and retention, sampling, sample and data management, data analysis and presentation. Potential solutions to aid future implementation include preparedness actions such as the development of new tools, robust planning and practice.

Sustainable strategies for Ebola virus disease outbreak preparedness in Africa: a case study on lessons learnt in countries neighbouring the Democratic Republic of the Congo.

BACKGROUND: From May 2018 to September 2022, the Democratic Republic of Congo (DRC) experienced seven Ebola virus disease (EVD) outbreaks within its borders. During the 10th EVD outbreak (2018-2020), the largest experienced in the DRC and the second largest and most prolonged EVD outbreak recorded globally, a WHO risk assessment identified nine countries bordering the DRC as moderate to high risk from cross border importation. These countries implemented varying levels of Ebola virus disease preparedness interventions. This case study highlights the gains and shortfalls with the Ebola virus disease preparedness interventions within the various contexts of these countries against the background of a renewed and growing commitment for global epidemic preparedness highlighted during recent World Health Assembly events. MAIN TEXT: Several positive impacts from preparedness support to countries bordering the affected provinces in the DRC were identified, including development of sustained capacities which were leveraged upon to respond to the subsequent coronavirus disease 2019 (COVID-19) pandemic. Shortfalls such as lost opportunities for operationalizing cross-border regional preparedness collaboration and better integration of multidisciplinary perspectives, vertical approaches to response pillars such as surveillance, over dependence on external support and duplication of efforts especially in areas of capacity building were also identified. A recurrent theme that emerged from this case study is the propensity towards implementing short-term interventions during active Ebola virus disease outbreaks for preparedness rather than sustainable investment into strengthening systems for improved health security in alignment with IHR obligations, the Sustainable Development Goals and advocating global policy for addressing the larger structural determinants underscoring these outbreaks. CONCLUSIONS: Despite several international frameworks established at the global level for emergency preparedness, a shortfall exists between global policy and practice in countries at high risk of cross border transmission from persistent Ebola virus disease outbreaks in the Democratic Republic of Congo. With renewed global health commitment for country emergency preparedness resulting from the COVID-19 pandemic and cumulating in a resolution for a pandemic preparedness treaty, the time to review and address these gaps and provide recommendations for more sustainable and integrative approaches to emergency preparedness towards achieving global health security is now.

Seroincidence of Enteric Fever, Juba, South Sudan.

We applied a new serosurveillance tool to estimate typhoidal Salmonella burden using samples collected during 2020 from a population in Juba, South Sudan. By using dried blood spot testing, we found an enteric fever seroincidence rate of 30/100 person-years and cumulative incidence of 74% over a 4-year period.

Use of mobile medical teams to fill critical gaps in health service delivery in complex humanitarian settings, 2017-2020: a case study of South Sudan.

The vulnerable populations in the protracted humanitarian crisis in South Sudan are faced with constrained access to health services and frequent disease outbreaks. Here, we describe the experiences of emergency mobile medical teams (eMMT) assembled by the World Health Organization (WHO) South Sudan to respond to public health emergencies. Interventions: the eMMTs, multidisciplinary teams based at national, state and county levels, are rapidly deployed to conduct rapid assessments, outbreak investigations, and initiate public health response during acute emergencies. The eMMTs were deployed to locations affected by flooding, conflicts, famine, and disease outbreaks. We reviewed records of deployment reports, outreach and campaign registers, and analyzed the key achievements of the eMMTs for 2017 through 2020. Achievements: the eMMTs investigated disease outbreaks including cholera, measles, Rift Valley fever and coronavirus disease (COVID-19) in 13 counties, conducted mobile outreaches in emergency locations in 38 counties (320,988 consultations conducted), trained 550 healthcare workers including rapid response teams, and supported reactive measles vaccination campaigns in seven counties [148,726, (72-125%) under-5-year-old children vaccinated] and reactive oral cholera vaccination campaigns in four counties (355,790 vaccinated). The eMMT is relevant in humanitarian settings and can reduce excess morbidity and mortality and fill gaps that routine health facilities and health partners could not bridge. However, the scope of the services offered needs to be broadened to include mental and psychosocial care and a strategy for ensuring continuity of vaccination services and management of chronic conditions after the mobile outreach is instituted.

Epidemiological characterization of COVID-19 in displaced populations of South Sudan.

Introduction: South Sudan is facing a protracted humanitarian crisis with increasing population vulnerability. The study aimed to describe the epidemiology of COVID-19 in displaced populations in South Sudan. Methods: the study involved the internally displaced populations (IDP) in Bentiu IDP camp, South Sudan. This was a descriptive cross-sectional study involving individuals that met the COVID-19 probable and confirmed case definitions from May 2020 to November 2021. Case data were managed using Microsoft Excel databases. Results: the initial COVID-19 case in Bentiu IDP camp was reported on 2 May 2020. The overall cumulative attack rate (cases per million) was 3,230 for Bentiu IDP and 1,038 at the national level. The COVID-19 Case Fatality Ratio (CFR) among the IDPs was 19.08% among confirmed and 1.06% at the national level. There was one wave of COVID-19 transmission in the IDPs that coincided with the second COVID-19 wave in South Sudan for the period May 2020 to November 2021. Adult males aged 20-49 years were the most affected and constituted 47.1% of COVID-19 cases. Most severe cases were reported among adults 60-69 years (53%) and ≥ 70 years (80%). The risk of COVID-19 death (deaths per 10,000) increased with age and was highest in patients aged ≥ 60 years at 64.1. The commonest underlying illnesses among COVID-19 deaths was HIV-related illness, heart disease, and tuberculosis. Conclusion: COVID-19 constitutes a significant impact on internally displaced populations of South Sudan. The COVID-19 response in displaced populations and the high-risk groups therein should be optimized.

Evaluation of integrated disease surveillance and response (IDSR) and early warning and response network (EWARN) in South Sudan 2021.

Introduction: South Sudan has been implementing the Integrated Disease Surveillance and Response (IDSR) strategy since 2006, along with Early Warning and Alert Response and Network (EWARN). The IDSR/EWARN stakeholders commissioned an independent evaluation to establish performance at national, state, county, health facility, and community levels in the first half of 2021. Methods: the evaluation was conducted between June and September 2021 (during the COVID-19 pandemic) and was based on the World Health Organization (WHO) protocols for monitoring and evaluating communicable disease surveillance and response systems and the guidelines for evaluating EWARN. Results: integrated disease surveillance and response/early warning and alert response and network indicator data showed improving timeliness and completeness from the beginning of 2021 to week 16 and then a slight depression of timeliness by week 32, while completeness remained high. Event-based surveillance was active at the beginning of 2021 and in week 32. However, there was inadequate sample collection to investigate acute watery diarrhea, bloody diarrhea, and acute jaundice syndrome alerts. Respondents in all cadres had substantial experience working in IDSR/EWARN. All respondents performed the various IDSR/EWARN tasks and duties as expected, but needed more resources and training. Conclusion: while IDSR/EWARN is performing relatively well, confirmation of priority diseases by the laboratories needs to be strengthened. Health facilities need more regular supervision from the higher levels. Community health workers need more training on IDSR/EWARN. The whole IDSR/EWARN system needs more resources, particularly for communication and transport and to confirm priority diseases. Staff at all levels requested more training in IDSR/EWARN.

Integrated disease surveillance and response in humanitarian context: South Sudan experience.

Introduction: decades of instability continue to impact the implementation of the Integrated Disease Surveillance and Response (IDSR) strategy. The study reviewed the progress and outcomes of rolling out IDSR in South Sudan. Methods: this descriptive cross-sectional study used epidemiological data for 2019, 2020, and other program data to assess indicators for the five surveillance components including surveillance priorities, core and support functions, and surveillance system structure and quality. Results: South Sudan expanded the priority disease scope from 26 to 59 to align with national and regional epidemiological trends and the International Health Regulations (IHR) 2005. Completing the countrywide rollout of electronic Early Warning Alert and Response (EWARS) reporting has improved both the timeliness and completeness of weekly reporting to 78% and 90%, respectively, by week 39 of 2020 in comparison to a baseline of 54% on both timeliness and completeness of reporting in 2019. The National Public Health Laboratory confirmatory testing capacities have been expanded to include cholera, measles, HIV, tuberculosis (TB), influenza, Ebola, yellow fever, and Severe Acute Respiratory Syndrome 2 (SARS-COV-2). Rapid response teams have been established to respond to epidemics and pandemics. Conclusion: since 2006, South Sudan has registered progress towards using indicator and event-based surveillance and continues to strengthen IHR (2005) capacities. Following the adoption of third edition IDSR guidelines, the current emphasis entails maintaining earlier gains and strengthening community and event-based surveillance, formalizing cross-sectoral one-health engagement, optimal EWARS and District Health Information Systems (DHIS2) use, and strengthening cross-border surveillance. It is also critical that optimal government, and donors' resources are dedicated to supporting health system strengthening and disease surveillance.

Analysis of the 2017-2018 Rift valley fever outbreak in Yirol East County, South Sudan: a one health perspective.

Introduction: the emergence and re-emergence of zoonotic diseases have threatened both human and animal health globally since their identification in the 20th century. Rift Valley fever (RVF) virus is a recurrent zoonotic disease in South Sudan, with the earliest RVF cases confirmed in 2007 in Kapoeta North County, Eastern Equatoria state. Methods: we analyzed national RVF outbreak data to describe the epidemiological pattern of the RVF outbreak in Yirol East county in Lakes State. The line list of cases (confirmed, probable, suspected, and non-cases) was used to describe the pattern and risk factors associated with the outbreak. The animal and human blood samples were tested using Enzyme-Linked Immunosorbent Assay (ELISA) (Immunoglobulin IgG and IgM) and Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR). Qualitative data were collected from weekly RVF situation reports, and national guidelines and policies. Results: between December 2017 and December 2018, 58 suspected human RVF cases were reported. The cases were reclassified based on laboratory and investigations results, such that as of 16th December 2018, there were a total of six (10.3%) laboratory-confirmed, three (5.2%) probable, one (1.7%) suspected, and 48 (82.8%) non-cases were reported. A total of four deaths were reported during the outbreak (case fatality rate (CFR) 6.8% (4/58). A total of 28 samples were collected from animals; of these, six tested positives for RVF (positivity rate of 32.1% (9/28). The outbreak was announced in March 2018, after four months of the first reported suspected RVF case. Several factors were attributed to the delayed notification and outbreak announcement such as lack of multi-sectorial coordination at the state and county level, multi-sectoral coordination at national level mostly attended by public health experts from human health, inadequate animal health surveillance, poor coordination between livestock disease surveillance and public health surveillance, limited in-country laboratory diagnostic capacity, the laboratory results for the animal health took longer than expected, and lack of a national One Health approach strategy. Conclusion: the outbreak demonstrated gaps to investigate and respond to zoonotic disease outbreaks in South Sudan.

The COVID-19 pandemic in the African continent.

In December 2019, a new coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and associated disease, coronavirus disease 2019 (COVID-19), was identified in China. This virus spread quickly and in March, 2020, it was declared a pandemic. Scientists predicted the worst scenario to occur in Africa since it was the least developed of the continents in terms of human development index, lagged behind others in achievement of the United Nations sustainable development goals (SDGs), has inadequate resources for provision of social services, and has many fragile states. In addition, there were relatively few research reporting findings on COVID-19 in Africa. On the contrary, the more developed countries reported higher disease incidences and mortality rates. However, for Africa, the earlier predictions and modelling into COVID-19 incidence and mortality did not fit into the reality. Therefore, the main objective of this forum is to bring together infectious diseases and public health experts to give an overview of COVID-19 in Africa and share their thoughts and opinions on why Africa behaved the way it did. Furthermore, the experts highlight what needs to be done to support Africa to consolidate the status quo and overcome the negative effects of COVID-19 so as to accelerate attainment of the SDGs.

Cholera outbreaks in sub-Saharan Africa during 2010-2019: a descriptive analysis.

BACKGROUND: Cholera remains a public health threat but is inequitably distributed across sub-Saharan Africa. Lack of standardized reporting and inconsistent outbreak definitions limit our understanding of cholera outbreak epidemiology. METHODS: From a database of cholera incidence and mortality, we extracted data from sub-Saharan Africa and reconstructed outbreaks of suspected cholera starting in January 2010 to December 2019 based on location-specific average weekly incidence rate thresholds. We then described the distribution of key outbreak metrics. RESULTS: We identified 999 suspected cholera outbreaks in 744 regions across 25 sub-Saharan African countries. The outbreak periods accounted for 1.8 billion person-months (2% of the total during this period) from January 2010 to January 2020. Among 692 outbreaks reported from second-level administrative units (e.g., districts), the median attack rate was 0.8 per 1000 people (interquartile range (IQR), 0.3-2.4 per 1000), the median epidemic duration was 13 weeks (IQR, 8-19), and the median early outbreak reproductive number was 1.8 (range, 1.1-3.5). Larger attack rates were associated with longer times to outbreak peak, longer epidemic durations, and lower case fatality risks. CONCLUSIONS: This study provides a baseline from which the progress toward cholera control and essential statistics to inform outbreak management in sub-Saharan Africa can be monitored.

SARS-CoV-2 Variants, South Sudan, January-March 2021.

As the coronavirus pandemic continues, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequence data are required to inform vaccine efforts. We provide SARS-CoV-2 sequence data from South Sudan and document the dominance of SARS-CoV-2 lineage B.1.525 (Eta variant) during the country's second wave of infection.

Rabies post-exposure healthcare-seeking behaviors and perceptions: Results from a knowledge, attitudes, and practices survey, Uganda, 2013.

BACKGROUND: Rabies is a viral disease of animals and people causing fatal encephalomyelitis if left untreated. Although effective pre- and post-exposure vaccines exist, they are not widely available in many endemic countries within Africa. Since many individuals in these countries remain at risk of infection, post-exposure healthcare-seeking behaviors are crucial in preventing infection and warrant examination. METHODOLOGY: A rabies knowledge, attitudes, and practices survey was conducted at 24 geographically diverse sites in Uganda during 2013 to capture information on knowledge concerning the disease, response to potential exposure events, and vaccination practices. Characteristics of the surveyed population and of the canine-bite victim sub-population were described. Post-exposure healthcare-seeking behaviors of canine-bite victims were examined and compared to the related healthcare-seeking attitudes of non-bite victim respondents. Wealth scores were calculated for each household, rabies knowledge was scored for each non-bitten survey respondent, and rabies exposure risk was scored for each bite victim. Logistic regression was used to determine the independent associations between different variables and healthcare-seeking behaviors among canine-bite victims as well as attitudes of non-bitten study respondents. RESULTS: A total of 798 households were interviewed, capturing 100 canine-bite victims and a bite incidence of 2.3 per 100 person-years. Over half of bite victims actively sought medical treatment (56%), though very few received rabies post-exposure prophylaxis (3%). Bite victims who did not know or report the closest location where PEP could be received were less likely to seek medical care (p = 0.05). Respondents who did not report having been bitten by a dog with higher knowledge scores were more likely to respond that they would both seek medical care (p = 0.00) and receive PEP (p = 0.06) after a potential rabies exposure event. CONCLUSIONS: There was varying discordance between what respondents who did not report having been bitten by a dog said they would do if bitten by a dog when compared to the behaviors exhibited by canine-bite victims captured in the KAP survey. Bite victims seldom elected to wash their wound or receive PEP. Having lower rabies knowledge was a barrier to theoretically seeking care and receiving PEP among not bitten respondents, indicating a need for effective and robust educational programs in the country.

Seroprevalence of Severe Acute Respiratory Syndrome Coronavirus 2 IgG in Juba, South Sudan, 20201.

Relatively few coronavirus disease cases and deaths have been reported from sub-Saharan Africa, although the extent of its spread remains unclear. During August 10-September 11, 2020, we recruited 2,214 participants for a representative household-based cross-sectional serosurvey in Juba, South Sudan. We found 22.3% of participants had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor binding domain IgG titers above prepandemic levels. After accounting for waning antibody levels, age, and sex, we estimated that 38.3% (95% credible interval 31.8%-46.5%) of the population had been infected with SARS-CoV-2. At this rate, for each PCR-confirmed SARS-CoV-2 infection reported by the Ministry of Health, 103 (95% credible interval 86-126) infections would have been unreported, meaning SARS-CoV-2 has likely spread extensively within Juba. We also found differences in background reactivity in Juba compared with Boston, Massachusetts, USA, where the immunoassay was validated. Our findings underscore the need to validate serologic tests in sub-Saharan Africa populations.

Seroprevalence of anti-SARS-CoV-2 IgG antibodies in Juba, South Sudan: a population-based study.

BACKGROUND: Relatively few COVID-19 cases and deaths have been reported through much of sub-Saharan Africa, including South Sudan, although the extent of SARS-CoV-2 spread remains unclear due to weak surveillance systems and few population-representative serosurveys. METHODS: We conducted a representative household-based cross-sectional serosurvey in Juba, South Sudan. We quantified IgG antibody responses to SARS-CoV-2 spike protein receptor-binding domain and estimated seroprevalence using a Bayesian regression model accounting for test performance. RESULTS: We recruited 2,214 participants from August 10 to September 11, 2020 and 22.3% had anti-SARS-CoV-2 IgG titers above levels in pre-pandemic samples. After accounting for waning antibody levels, age, and sex, we estimated that 38.5% (32.1 - 46.8) of the population had been infected with SARS-CoV-2. For each RT-PCR confirmed COVID-19 case, 104 (87-126) infections were unreported. Background antibody reactivity was higher in pre-pandemic samples from Juba compared to Boston, where the serological test was validated. The estimated proportion of the population infected ranged from 30.1% to 60.6% depending on assumptions about test performance and prevalence of clinically severe infections. CONCLUSIONS: SARS-CoV-2 has spread extensively within Juba. Validation of serological tests in sub-Saharan African populations is critical to improve our ability to use serosurveillance to understand and mitigate transmission.

COVID-19 case management strategies: what are the options for Africa?

The ongoing coronavirus disease 2019 (COVID-19) pandemic has put a strain on health systems globally. Although Africa is the least affected region to date, it has the weakest health systems and an exponential rise in cases as has been observed in other regions, is bound to overwhelm its health systems. Early detection and isolation of suspected and confirmed COVID-19 cases are pivotal to the prevention and control of the pandemic. The World Health Organization (WHO) recommends that all laboratory-confirmed cases should be isolated and treated in a health care facility; however, where this is not possible due to the health system capacity, patients can be isolated in re-purposed facilities or at home. An already very apparent future challenge for Africa is facility-based isolation of COVID-19 cases, given the already limited health infrastructure and health workforce, and the risk of nosocomial transmission. Use of repurposed facilities requires additional resources, including health workers. Home isolation, on the other hand, would be a challenge given the poor housing, overcrowding, inadequate access to water and sanitation, and stigma related to infectious disease that is prevalent in many African societies. Conflict settings on the continent pose an additional challenge to the prevention and control of COVID-19 with the resultant population displacements in overcrowded camps where access to social services is limited. These unique cultural, social, economic and developmental differences on the continent, call for a tailored approach to COVID-19 case management strategies. This article proposes three broad case management strategies based on the transmission scenarios defined by WHO, and the criteria and package of care for each option, for consideration by policy makers and governments in African countries. Moving forward, African countries should generate local evidence to guide the development of realistic home-grown strategies, protocol and equipment for the management of COVID-19 cases on the continent .

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.