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SUMMARY In sub-Saharan Africa, many nomadic pastoralists have begun to settle in permanent communities as a result of long-term water, food, and civil insecurity. Little is known about the epidemiology of cholera in these emerging semi-nomadic populations. We report the results of a case-control study conducted during a cholera outbreak among semi-nomadic pastoralists in the Karamoja sub-region of northeastern Uganda in 2010. Data from 99 cases and 99 controls were analysed. In multivariate analyses, risk factors identified were: residing in the same household as another cholera case [adjusted odds ratio (aOR) 6·67, 95% confidence interval (CI) 2·83-15·70], eating roadside food (aOR 2·91, 95% CI 1·24-6·81), not disposing of children's faeces in a latrine (aOR 15·76, 95% CI 1·54-161·25), not treating drinking water with chlorine (aOR 3·86, 95% CI 1·63-9·14), female gender (aOR 2·43, 95% CI 1·09-5·43), and childhood age (10-17 years) (aOR 7·14, 95% CI 1·97-25·83). This is the first epidemiological study of cholera reported from a setting of semi-nomadic pastoralism in sub-Saharan Africa. Public health interventions among semi-nomadic pastoralists should include a two-faceted approach to cholera prevention: intensive health education programmes to address behaviours inherited from insecure nomadic lifestyles, as well as improvements in water and sanitation infrastructure. The utilization of community-based village health teams provides an important method of implementing such activities. [ABSTRACT FROM AUTHOR]

During August 2007-February 2008, the novel Bundibugyo ebolavirus species was identified during an outbreak of Ebola viral hemorrhagic fever in Bundibugyo district, western Uganda. To characterize the outbreak as a requisite for determining response, we instituted a case-series investigation. We identified 192 suspected cases, of which 42 (22%) were laboratory positive for the novel species; 74 (38%) were probable, and 77 (40%) were negative. Laboratory confirmation lagged behind outbreak verification by 3 months. Bundibugyo ebolavirus was less fatal (case-fatality rate 34%) than Ebola viruses that had caused previous outbreaks in the region, and most transmission was associated with handling of dead persons without appropriate protection (adjusted odds ratio 3.83, 95% confidence interval 1.78-8.23). Our study highlights the need for maintaining a high index of suspicion for viral hemorrhagic fevers among healthcare workers, building local capacity for laboratory confirmation of viral hemorrhagic fevers, and institutionalizing standard precautions. [ABSTRACT FROM AUTHOR]

Background: Epidemic forms of hepatitis E cause high mortality among pregnant people, with case fatality risks over 30% and adverse fetal outcomes. In 2022, the first mass reactive vaccination campaign against hepatitis E was conducted in South Sudan with the HEV239 vaccine. We aimed to assess whether vaccination against hepatitis E in pregnancy increases the risk of fetal loss in a cohort of vaccinated and unvaccinated pregnant people., Methods: In this emulated target trial, an exhaustive pregnancy census was conducted in Bentiu internally displaced persons camp after the second of three vaccination rounds. Women and girls aged 14-45 years with no current jaundice or acute illness were eligible for participation. Individuals who consented were revisited 28 days after their delivery date to document the pregnancy outcome. We used an emulated target trial framework to address biases inherent in observational studies. We matched vaccinated to unvaccinated participants on age, gestational age, and vaccination propensity score and estimated cumulative incidence functions for fetal loss in vaccinated compared to unvaccinated women in a competing risks framework using the Aalen-Johansen estimator., Findings: Between May 16 and June 30, 2022, 3421 participants were enrolled and followed up for inclusion in analysis. Among 2741 women who had a pregnancy outcome after the start of the vaccination campaign, 67 (2·4%) were vaccinated before conception, 2036 (74·3%) were vaccinated during pregnancy, and 638 (23·2%) were not vaccinated. Among the 2407 women retained in the matched analyses, the cumulative risk of fetal loss among individuals vaccinated during pregnancy was 7·2% (95% CI 5·6-8·7) compared with 6·1% (3·7-9·2) among unvaccinated individuals, implying a risk ratio of 1·2 (95% CI 0·7-1·9)., Interpretation: No evidence of increased risk of fetal loss was found among individuals vaccinated during pregnancy., Funding: Médecins Sans Frontières., Competing Interests: Declaration of interests Médecins Sans Frontières provided support in the form of salaries for ASA, VKA, PGi, PN, JD, MH, PGa, NS, MA, MR, and IC and indirectly provided salary support for Epicentre employees RCN and EG. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: We declare no competing interests.

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., Competing Interests: The authors have no competing interests to disclose., (Copyright: © 2024 Nesbitt et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., (© 2023 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

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., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

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., (© 2022. The Author(s).)

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.

Investment in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing in Africa over the past year has led to a major increase in the number of sequences that have been generated and used to track the pandemic on the continent, a number that now exceeds 100,000 genomes. Our results show an increase in the number of African countries that are able to sequence domestically and highlight that local sequencing enables faster turnaround times and more-regular routine surveillance. Despite limitations of low testing proportions, findings from this genomic surveillance study underscore the heterogeneous nature of the pandemic and illuminate the distinct dispersal dynamics of variants of concern-particularly Alpha, Beta, Delta, and Omicron-on the continent. Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve while the continent faces many emerging and reemerging infectious disease threats. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century.

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., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

We aimed to estimate the household secondary infection attack rate (hSAR) of SARS-CoV-2 in investigations aligned with the WHO Unity Studies Household Transmission Investigations (HHTI) protocol. We conducted a systematic review and meta-analysis according to PRISMA 2020 guidelines. We searched Medline, Embase, Web of Science, Scopus and medRxiv/bioRxiv for "Unity-aligned" First Few X cases (FFX) and HHTIs published 1 December 2019 to 26 July 2021. Standardised early results were shared by WHO Unity Studies collaborators (to 1 October 2021). We used a bespoke tool to assess investigation methodological quality. Values for hSAR and 95% confidence intervals (CIs) were extracted or calculated from crude data. Heterogeneity was assessed by visually inspecting overlap of CIs on forest plots and quantified in meta-analyses. Of 9988 records retrieved, 80 articles (64 from databases; 16 provided by Unity Studies collaborators) were retained in the systematic review; 62 were included in the primary meta-analysis. hSAR point estimates ranged from 2% to 90% (95% prediction interval: 3%-71%; I 2  = 99.7%); I 2 values remained >99% in subgroup analyses, indicating high, unexplained heterogeneity and leading to a decision not to report pooled hSAR estimates. FFX and HHTI remain critical epidemiological tools for early and ongoing characterisation of novel infectious pathogens. The large, unexplained variance in hSAR estimates emphasises the need to further support standardisation in planning, conduct and analysis, and for clear and comprehensive reporting of FFX and HHTIs in time and place, to guide evidence-based pandemic preparedness and response efforts for SARS-CoV-2, influenza and future novel respiratory viruses., (© 2022 World Health Organization; licensed by John Wiley & Sons Ltd. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

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., Competing Interests: The authors declare no competing interests., (©John Rumunu et al.)

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., Competing Interests: The authors declare no competing interests., (©John Rumunu et al.)

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., Competing Interests: The authors declare no competing interests., (©Joseph Francis Wamala et al.)

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., Competing Interests: The authors declare no competing interests., (©Otim Patrick Cossy Ramadan et al.)

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., Competing Interests: The authors declare no competing interests., (©Diba Dulacha et al.)

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., (© 2022. The Author(s).)

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.

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.

Introduction: the coronavirus disease 2019 (COVID-19) was declared a pandemic on March 11, 2020. South Sudan, a low-income and humanitarian response setting, reported its first case of COVID-19 on April 5, 2020. We describe the socio-demographic and epidemiologic characteristics of COVID-19 cases in this setting., Methods: we conducted a cross-sectional descriptive analysis of data for 1,330 confirmed COVID-19 cases from the first 60 days of the outbreak., Results: among the 1,330 confirmed cases, the mean age was 37.1 years, 77% were male, 17% were symptomatic with 95% categorized as mild, and the case fatality rate was 1.1%. Only 24.7% of cases were detected through alerts and sentinel site surveillance, with 95% of the cases reported from the capital, Juba. Epidemic doubling time averaged 9.8 days (95% confidence interval [CI] 7.7 - 13.4), with an attack rate of 11.5 per 100,000 population. Test positivity rate was 18.2%, with test rate per 100,000 population of 53 and mean test turn-around time of 9 days. The case to contact ratio was 1: 2.2., Conclusion: this 2-month initial period of COVID-19 in South Sudan demonstrated mostly young adults and men affected, with most cases reported as asymptomatic. Systems´ limitations highlighted included a small proportion of cases detected through surveillance, low testing rates, low contact elicitation, and long collection to test turn-around times limiting the country´s ability to effectively respond to the outbreak. A multi-pronged response including greater access to testing, scale-up of surveillance, contact tracing and community engagement, among other interventions are needed to improve the COVID-19 response in this setting., Competing Interests: The authors declare no competing interests., (Copyright: Joy Luba Lomole Waya et al.)

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., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.)

South Sudan implemented Ebola virus disease preparedness interventions aiming at preventing and rapidly containing any importation of the virus from the Democratic Republic of Congo starting from August 2018. One of these interventions was a surveillance system which included an Ebola alert management system. This study analyzed the performance of this system. A descriptive cross-sectional study of the Ebola virus disease alerts which were reported in South Sudan from August 2018 to November 2019 was conducted using both quantitative and qualitative methods. As of 30 November 2019, a total of 107 alerts had been detected in the country out of which 51 (47.7%) met the case definition and were investigated with blood samples collected for laboratory confirmation. Most (81%) of the investigated alerts were South Sudanese nationals. The alerts were identified by health workers (53.1%) at health facilities, at the community (20.4%) and by screeners at the points of entry (12.2%). Most of the investigated alerts were detected from the high-risk states of Gbudwe (46.9%), Jubek (16.3%) and Torit (10.2%). The investigated alerts commonly presented with fever, bleeding, headache and vomiting. The median timeliness for deployment of Rapid Response Team was less than one day and significantly different between the 6-month time periods (K-W = 7.7567; df = 2; p = 0.0024) from 2018 to 2019. Strengths of the alert management system included existence of a dedicated national alert hotline, case definition for alerts and rapid response teams while the weaknesses were occasional inability to access the alert toll-free hotline and lack of transport for deployment of the rapid response teams which often constrain quick response. This study demonstrates that the Ebola virus disease alert management system in South Sudan was fully functional despite the associated challenges and provides evidence to further improve Ebola preparedness in the country., Competing Interests: The authors have declared that no competing interests exist.

A fundamental, clinical, and scientific concern is how lytic bacteriophage, as well as antibiotics, impact diagnostic positivity. Cholera was chosen as a model disease to investigate this important question, because cholera outbreaks enable large enrollment, field methods are well established, and the predatory relationship between lytic bacteriophage and the etiologic agent Vibrio cholerae share commonalities across bacterial taxa. Patients with diarrheal disease were enrolled at two remote hospitals in Bangladesh. Diagnostic performance was assessed as a function of lytic bacteriophage detection and exposure to the first-line antibiotic azithromycin, detected in stool samples by mass spectrometry. Among diarrheal samples positive by nanoliter quantitative PCR (qPCR) for V. cholerae ( n  = 78/849), the odds that a rapid diagnostic test (RDT) or qPCR was positive was reduced by 89% (odds ratio [OR], 0.108; 95% confidence interval [CI], 0.002 to 0.872) and 87% (OR, 0.130; 95% CI, 0.022 to 0.649), respectively, when lytic bacteriophage were detected. The odds that an RDT or qPCR was positive was reduced by more than 99% (OR, 0.00; 95% CI, 0.00 to 0.28) and 89% (OR, 0.11; 95% CI, 0.03 to 0.44), respectively, when azithromycin was detected. Analysis of additional samples from South Sudan found similar phage effects on RDTs; antibiotics were not assayed. Cholera burden estimates may improve by accommodating for the negative effects of lytic bacteriophage and antibiotic exposure on diagnostic positivity. One accommodation is using bacteriophage detection as a proxy for pathogen detection. These findings have relevance for other diagnostic settings where bacterial pathogens are vulnerable to lytic bacteriophage predation., (Copyright © 2020 Nelson et al.)

Background: Around 2007, a nodding syndrome (NS) epidemic appeared in onchocerciasis-endemic districts of northern Uganda, where ivermectin mass distribution had never been implemented. This study evaluated the effect of community-directed treatment with ivermectin (CDTI) and ground larviciding of rivers initiated after 2009 and 2012 respectively, on the epidemiology of NS and other forms of epilepsy (OFE) in some districts of northern Uganda., Methods: In 2012, a population-based community survey of NS/epilepsy was carried out by the Ugandan Ministry of Health in Kitgum and Pader districts. In August 2017, we conducted a new survey in selected villages of these districts and compared our findings with the 2012 data. In addition, two villages in Moyo district (where CDTI was ongoing since 1993) served as comparative onchocerciasis-endemic sites in which larviciding had never been implemented. The comparison between 2012 and 2017 prevalence and cumulative incidence were done using the Fisher's and Pearson's Chi-square tests at 95% level of significance., Results: A total of 2138 individuals in 390 households were interviewed. In the selected villages of Kitgum and Pader, there was no significant decrease in prevalence of NS and OFE between 2012 and 2017. However, the cumulative incidence of all forms of epilepsy decreased from 1165 to 130 per 100 000 persons per year (P = 0.002); that of NS decreased from 490 to 43 per 100 000 persons per year (P = 0.037); and for OFE from 675 to 87 per 100 000 persons per year (P = 0.024). The median age of affected persons (NS and OFE) shifted from 13.5 (IQR: 11.0-15.0) years in 2012 to 18.0 (IQR: 15.0-20.3) years in 2017; P <  0.001. The age-standardized prevalence of OFE in Moyo in 2017 was 4.6%, similar to 4.5% in Kitgum and Pader., Conclusions: Our findings support the growing evidence of a relationship between infection by Onchocerca volvulus and some types of childhood epilepsy, and suggest that a combination of bi-annual mass distribution of ivermectin and ground larviciding of rivers is an effective strategy to prevent NS and OFE in onchocerciasis-hyperendemic areas.

Competing Interests: The authors have declared that no competing interests exist.

The correlation between cholera epidemics and climatic drivers, in particular seasonal tropical rainfall, has been studied in a variety of contexts owing to its documented relevance. Several mechanistic models of cholera transmission have included rainfall as a driver by focusing on two possible transmission pathways: either by increasing exposure to contaminated water (e.g. due to worsening sanitary conditions during water excess), or water contamination by freshly excreted bacteria (e.g. due to washout of open-air defecation sites or overflows). Our study assesses the explanatory power of these different modeling structures by formal model comparison using deterministic and stochastic models of the type susceptible-infected-recovered-bacteria (SIRB). The incorporation of rainfall effects is generalized using a nonlinear function that can increase or decrease the relative importance of the large precipitation events. Our modelling framework is tested against the daily epidemiological data collected during the 2015 cholera outbreak within the urban context of Juba, South Sudan. This epidemic is characterized by a particular intra-seasonal double peak on the incidence in apparent relation with particularly strong rainfall events. Our results show that rainfall-based models in both their deterministic and stochastic formulations outperform models that do not account for rainfall. In fact, classical SIRB models are not able to reproduce the second epidemiological peak, thus suggesting that it was rainfall-driven. Moreover we found stronger support across model types for rainfall acting on increased exposure rather than on exacerbated water contamination. Although these results are context-specific, they stress the importance of a systematic and comprehensive appraisal of transmission pathways and their environmental forcings when embarking in the modelling of epidemic cholera., (Copyright © 2018. Published by Elsevier B.V.)

In the HTML version of this Letter, the affiliations for authors Andrew S. Azman, Dhirendra Kumar and Thandavarayan Ramamurthy were inverted (the PDF and print versions of the Letter were correct); the affiliations have been corrected online.

Yemen is currently experiencing, to our knowledge, the largest cholera epidemic in recent history. The first cases were declared in September 2016, and over 1.1 million cases and 2,300 deaths have since been reported 1 . Here we investigate the phylogenetic relationships, pathogenesis and determinants of antimicrobial resistance by sequencing the genomes of Vibrio cholerae isolates from the epidemic in Yemen and recent isolates from neighbouring regions. These 116 genomic sequences were placed within the phylogenetic context of a global collection of 1,087 isolates of the seventh pandemic V. cholerae serogroups O1 and O139 biotype El Tor 2-4 . We show that the isolates from Yemen that were collected during the two epidemiological waves of the epidemic 1 -the first between 28 September 2016 and 23 April 2017 (25,839 suspected cases) and the second beginning on 24 April 2017 (more than 1 million suspected cases)-are V. cholerae serotype Ogawa isolates from a single sublineage of the seventh pandemic V. cholerae O1 El Tor (7PET) lineage. Using genomic approaches, we link the epidemic in Yemen to global radiations of pandemic V. cholerae and show that this sublineage originated from South Asia and that it caused outbreaks in East Africa before appearing in Yemen. Furthermore, we show that the isolates from Yemen are susceptible to several antibiotics that are commonly used to treat cholera and to polymyxin B, resistance to which is used as a marker of the El Tor biotype.

Combining the official cholera line list data and outbreak investigation reports from the ministries of health in Uganda and South Sudan with molecular analysis of Vibrio cholerae strains revealed the interrelatedness of the epidemics in both countries in 2014. These results highlight the need for collaboration to control cross-border outbreaks.

Displaced persons living in camps are at an increased risk of diarrheal diseases. Subclinical carriage of pathogens may contribute to the spread of disease, especially for microbes that require a low infectious dose. Multiplex real-time polymerase chain reaction was performed to detect a panel of 20 bacterial, viral, and protozoal targets, and we report a high prevalence of enteropathogen carriage, including Shigella spp. or enteroinvasive Escherichia coli in 14%, among a sample of 88 asymptomatic individuals in an internally displaced persons camp in South Sudan. Further studies are needed to determine the contribution of such carriage to the spread of disease.

In sub-Saharan Africa, little is known about the epidemiology of pandemic-prone influenza viruses in urban settings. Using data from a prospective sentinel surveillance network, we characterized the emergence, epidemiology, and transmission dynamics of 2009 pandemic A/H1N1 influenza (H1N1pdm09) in Kampala, Uganda. After virus introduction via international air travel from England in June 2009, we estimated the basic reproductive number in Kampala to be 1.06-1.13, corresponding to attack rates of 12-22%. We subsequently identified 613 cases of influenza in Kampala from 2009 to 2015, of which 191 (31.2%) were infected with H1N1pdm09. Patients infected with H1N1pdm09 were more likely to be older adult (ages 35-64) males with illness onset during rainy season months. Urban settings in sub-Saharan Africa are vulnerable to importation and intense transmission of pandemic-prone influenza viruses. Enhanced surveillance and influenza pandemic preparedness in these settings is needed.

Introduction: In June 2015, a cholera outbreak was declared in Juba, South Sudan. In addition to standard outbreak control measures, oral cholera vaccine (OCV) was proposed. As sufficient doses to cover the at-risk population were unavailable, a campaign using half the standard dosing regimen (one-dose) targeted high-risk neighborhoods and groups including neighbors of suspected cases. Here we report the operational details of this first public health use of a single-dose regimen of OCV and illustrate the feasibility of conducting highly targeted vaccination campaigns in an urban area., Methodology/principal Findings: Neighborhoods of the city were prioritized for vaccination based on cumulative attack rates, active transmission and local knowledge of known cholera risk factors. OCV was offered to all persons older than 12 months at 20 fixed sites and to select groups, including neighbors of cholera cases after the main campaign ('case-triggered' interventions), through mobile teams. Vaccination coverage was estimated by multi-stage surveys using spatial sampling techniques. 162,377 individuals received a single-dose of OCV in the targeted neighborhoods. In these neighborhoods vaccine coverage was 68.8% (95% Confidence Interval (CI), 64.0-73.7) and was highest among children ages 5-14 years (90.0%, 95% CI 85.7-94.3), with adult men being less likely to be vaccinated than adult women (Relative Risk 0.81, 95% CI: 0.68-0.96). In the case-triggered interventions, each lasting 1-2 days, coverage varied (range: 30-87%) with an average of 51.0% (95% CI 41.7-60.3)., Conclusions/significance: Vaccine supply constraints and the complex realities where cholera outbreaks occur may warrant the use of flexible alternative vaccination strategies, including highly-targeted vaccination campaigns and single-dose regimens. We showed that such campaigns are feasible. Additional work is needed to understand how and when to use different strategies to best protect populations against epidemic cholera.

AbstractLarge protracted outbreaks of hepatitis E virus (HEV) have been documented in displaced populations in Africa over the past decade though data are limited outside these exceptional settings. Serological studies can provide insights useful for improving surveillance and disease control. We conducted an age-stratified serological survey using samples previously collected for another research study from 206 residents of an internally displaced person camp in Juba, South Sudan. We tested serum for anti-HEV antibodies (IgM and IgG) and estimated the prevalence of recent and historical exposure to the virus. Using data on individuals' serostatus, camp arrival date, and state of origin, we used catalytic transmission models to estimate the relative risk of HEV infection in the camp compared with that in the participants' home states. The age-adjusted seroprevalence of anti-HEV IgG was 71% (95% confidence interval = 63-78), and 4% had evidence of recent exposure (IgM). We estimated HEV exposure rates to be more than 2-fold (hazard ratio = 2.3, 95% credible interval = 0.3-5.8) higher in the camp than in the participants' home states, although this difference was not statistically significant. HEV transmission may be higher than previously appreciated, even in the absence of reported cases. Improved surveillance in similar settings is needed to understand the burden of disease and minimize epidemic impact through early detection and response.

Shortages of vaccines for epidemic diseases, such as cholera, meningitis, and yellow fever, have become common over the past decade, hampering efforts to control outbreaks through mass reactive vaccination campaigns. Additionally, various epidemiological, political, and logistical challenges, which are poorly documented in the literature, often lead to delays in reactive campaigns, ultimately reducing the effect of vaccination. In June 2015, a cholera outbreak occurred in Juba, South Sudan, and because of the global shortage of oral cholera vaccine, authorities were unable to secure sufficient doses to vaccinate the entire at-risk population-approximately 1 million people. In this Personal View, we document the first public health use of a reduced, single-dose regimen of oral cholera vaccine, and show the details of the decision-making process and timeline. We also make recommendations to help improve reactive vaccination campaigns against cholera, and discuss the importance of new and flexible context-specific dose regimens and vaccination strategies., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Cholera rapid diagnostic tests (RDT) could play a central role in outbreak detection and surveillance in low-resource settings, but their modest performance has hindered their broad adoption. The addition of an enrichment step may improve test specificity. We describe the results of a prospective diagnostic evaluation of the Crystal VC RDT (Span Diagnostics, India) with enrichment step and of culture, each compared to polymerase chain reaction (PCR), during a cholera outbreak in South Sudan. RDTs were performed on alkaline peptone water inoculated with stool and incubated for 4-6 hours at ambient temperature. Cholera culture was performed from wet filter paper inoculated with stool. Molecular detection of Vibrio cholerae O1 by PCR was done from dry Whatman 903 filter papers inoculated with stool, and from wet filter paper supernatant. In August and September 2015, 101 consecutive suspected cholera cases were enrolled, of which 36 were confirmed by PCR. The enriched RDT had 86.1% (95% CI: 70.5-95.3) sensitivity and 100% (95% CI: 94.4-100) specificity compared to PCR as the reference standard. The sensitivity of culture versus PCR was 83.3% (95% CI: 67.2-93.6) for culture performed on site and 72.2% (95% CI: 54.8-85.8) at the international reference laboratory, where samples were tested after an average delay of two months after sample collection, and specificity was 98.5% (95% CI: 91.7-100) and 100% (95% CI: 94.5-100), respectively. The RDT with enrichment showed performance comparable to that of culture and could be a sustainable alternative to culture confirmation where laboratory capacity is limited., Competing Interests: The authors have declared that no competing interests exist.

Rationale: Little is known about the epidemiology of severe acute respiratory infection (SARI) or influenza in sub-Saharan Africa. Characterization of influenza transmission dynamics and risk factors for severe disease and mortality is critical to inform prevention and mitigation strategies., Objectives: To characterize the epidemiology and transmission dynamics of influenza and risk factors for influenza-associated severe respiratory infection in Uganda., Methods: Clinicians at 12 sentinel surveillance sites prospectively collected clinical data and upper respiratory tract samples from consecutive patients who met criteria for SARI and influenza-like illness (ILI). Samples were tested for influenza A and B viruses using real-time reverse transcription-polymerase chain reaction. Spatial and spatiotemporal cluster modeling was performed to identify loci of increased influenza transmission. Morbidity and mortality were assessed through chart review in a defined subset of patients. Univariable and multivariable analyses were used to identify risk factors for severe respiratory infection, prolonged hospitalization, and in-hospital mortality., Measurements and Main Results: From October 2010 to June 2015, 9,978 patients met case definitions for SARI and ILI and had samples tested for influenza A and B. Of the 9,978 patient samples tested, 1,113 (11.2%) were positive for influenza. Among 6,057 patients with ILI, 778 samples (12.8%) were positive, and among 3,921 patients with SARI, 335 samples (8.5%) were positive. Significant clustering of influenza cases was observed in urban and periurban areas and during rainy seasons. Among 1,405 cases of SARI with available outcome data, in-hospital mortality was 1.6%. Infection with the 2009 pandemic A/H1N1 subtype and prolonged time to presentation were independently associated with SARI among influenza cases., Conclusions: Influenza is associated with a substantial proportion of acute respiratory infection in Uganda. As influenza vaccination programs are developed in East Africa, timing campaigns to confer protection during rainy seasons should be considered, particularly among high-risk urban populations.

Background: Oral cholera vaccines represent a new effective tool to fight cholera and are licensed as two-dose regimens with 2-4 weeks between doses. Evidence from previous studies suggests that a single dose of oral cholera vaccine might provide substantial direct protection against cholera. During a cholera outbreak in May, 2015, in Juba, South Sudan, the Ministry of Health, Médecins Sans Frontières, and partners engaged in the first field deployment of a single dose of oral cholera vaccine to enhance the outbreak response. We did a vaccine effectiveness study in conjunction with this large public health intervention., Methods: We did a case-cohort study, combining information on the vaccination status and disease outcomes from a random cohort recruited from throughout the city of Juba with that from all the cases detected. Eligible cases were those aged 1 year or older on the first day of the vaccination campaign who sought care for diarrhoea at all three cholera treatment centres and seven rehydration posts throughout Juba. Confirmed cases were suspected cases who tested positive to PCR for Vibrio cholerae O1. We estimated the short-term protection (direct and indirect) conferred by one dose of cholera vaccine (Shanchol, Shantha Biotechnics, Hyderabad, India)., Findings: Between Aug 9, 2015, and Sept 29, 2015, we enrolled 87 individuals with suspected cholera, and an 898-person cohort from throughout Juba. Of the 87 individuals with suspected cholera, 34 were classified as cholera positive, 52 as cholera negative, and one had indeterminate results. Of the 858 cohort members who completed a follow-up visit, none developed clinical cholera during follow-up. The unadjusted single-dose vaccine effectiveness was 80·2% (95% CI 61·5-100·0) and after adjusting for potential confounders was 87·3% (70·2-100·0)., Interpretation: One dose of Shanchol was effective in preventing medically attended cholera in this study. These results support the use of a single-dose strategy in outbreaks in similar epidemiological settings., Funding: Médecins Sans Frontières., (Copyright © 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.)

Despite recent large-scale cholera outbreaks, little is known about the immunogenicity of oral cholera vaccines (OCV) in African populations, particularly among those at highest cholera risk. During a 2015 preemptive OCV campaign among internally displaced persons in South Sudan, a year after a large cholera outbreak, we enrolled 37 young children (1-5 years old), 67 older children (6-17 years old) and 101 adults (≥18 years old), who received two doses of OCV (Shanchol) spaced approximately 3 weeks apart. Cholera-specific antibody responses were determined at days 0, 21 and 35 post-immunization. High baseline vibriocidal titers (>80) were observed in 21% of the participants, suggesting recent cholera exposure or vaccination. Among those with titers ≤80, 90% young children, 73% older children and 72% adults seroconverted (≥4 fold titer rise) after the 1 st OCV dose; with no additional seroconversion after the 2 nd dose. Post-vaccination immunological endpoints did not differ across age groups. Our results indicate Shanchol was immunogenic in this vulnerable population and that a single dose alone may be sufficient to achieve similar short-term immunological responses to the currently licensed two-dose regimen. While we found no evidence of differential response by age, further immunologic and epidemiologic studies are needed.

Following mass population displacements in South Sudan, preventive cholera vaccination campaigns were conducted in displaced persons camps before a 2014 cholera outbreak. We compare cholera transmission in vaccinated and unvaccinated areas and show vaccination likely halted transmission within vaccinated areas, illustrating the potential for oral cholera vaccine to stop cholera transmission in vulnerable populations.