SARS-CoV-2 seroprevalence in people living with HIV in South Sudan.

Objectives: The burden of SARS-CoV-2 infection in people living with HIV (PLHIV) in South Sudan is unknown. Methods: We conducted a cross-sectional seroprevalence survey of SARS-CoV-2 immunoglobulin (Ig) G antibodies and other diseases of public health importance (strongyloidiasis, toxoplasmosis) in PLHIV in South Sudan during April 1, 2020-April 30, 2022. We used a multiplex SARS-CoV-2 immunoassay to detect IgG antibodies targeting the SARS-CoV-2 spike, receptor binding domain, and nucelocapsid (N) proteins, and antigens for other pathogens (Strongyloides stercoralis and Toxoplasma gondii). Results: Among 3518 samples tested, seroprevalence of IgG antibodies to SARS-CoV-2 spike protein and receptor binding domain 591 and nucleocapsid ranged from 1.4% (95% confidence interval [CI]: 0.9-2.1%) in April-June 2020 to 53.3% (95% CI: 49.5-57.1%) in January-March 2022. The prevalence of S. stercoralis IgG ranged between 27.3% (95% CI: 23.4-31.5%) in October-December 2021 and 47.2% (95% CI: 37.8-56.8%) in July-September 2021, and, for T. gondii IgG, prevalence ranged from 15.5% (95% CI: 13.3-17.9%) in April-June 2020 to 36.2% (95% CI: 27.4-46.2%) July-September 2021. Conclusions: By early 2022, PLHIV in South Sudan had high rates of SARS-CoV-2 seropositivity. Surveillance of diseases of global health concern in PLHIV is crucial to estimate population-level exposure and inform public health responses.

Preventing HIV Among Adolescent Boys and Young Men Through PEPFAR-Supported Voluntary Medical Male Circumcision in 15 Sub-Saharan African Countries, 2018-2021.

Voluntary medical male circumcision (VMMC) is an HIV prevention intervention that has predominantly targeted adolescent and young men, aged 10-24 years. In 2020, the age eligibility for VMMC shifted from 10 to 15 years of age. This report describes the VMMC client age distribution from 2018 to 2021, at the site, national, and regional levels, among 15 countries in southern and eastern Africa. Overall, in 2018 and 2019, the highest proportion of VMMCs were performed among 10-14-year-olds (45.6% and 41.2%, respectively). In 2020 and 2021, the 15-19-year age group accounted for the highest proportion (37.2% and 50.4%, respectively) of VMMCs performed across all age groups. Similarly, in 2021 at the site level, 68.1% of VMMC sites conducted the majority of circumcisions among men aged 15-24 years. This analysis highlights that adolescent boys and young men are the primary recipients of VMMC receiving an important lifetime reduction in HIV risk.

Limited awareness of HIV Status hinders uptake of treatment among female sex workers and sexually exploited adolescents in Wau and Yambio, South Sudan.

BACKGROUND: Several factors determine uptake of HIV testing services (HTS) by female sex workers (FSW), including their knowledge of HIV and their awareness of services supporting people who are HIV-positive. HTS provided entry into the UNAIDS 90-90-90 cascade of care. We conducted a cross-sectional biobehavioural survey (BBS) to determine HIV prevalence and progress towards UNAIDS 90-90-90 cascade targets among this population in South Sudan. METHODS: Respondent-driven sampling (RDS) was used to recruit women and sexually exploited girls aged 13-18 years who exchanged sex for goods or money in the past 6 months and resided in the town for at least 1 month. Consenting participants were interviewed and tested for HIV and, if positive, they were also tested for their viral load (VL). Data were weighted in RDS Analyst and analyzed with Stata 13. RESULTS: A total of 1,284 participants were recruited. The overall HIV cascade coverages were 64.8% aware of their HIV-positive status; 91.0% of those aware of their positive status were on ART; and VL suppression among those on ART was 93.0%. CONCLUSION: Being unaware of their HIV-positive status limits, the uptake of HIV treatment among FSW in South Sudan. This underscores the importance of optimized case-finding approaches to increase HTS among FSW and sexually exploited minors.

Nationwide Measles and Rubella Outbreaks in South Sudan, 2019.

Background: South Sudan confirmed a measles outbreak in December 2018. An investigation was conducted to assess underlying causes of the outbreak. Methods: Vaccination coverage and measles surveillance data were analyzed. A suspected measles case had fever, maculopapular rash, and cough or conjunctivitis. A confirmed measles case had generalized maculopapular rash lasting >3 days, a temperature >38°C, and cough or conjunctivitis; or serologic confirmation (anti-measles immunoglobin M [IgM] antibody detection) in serum samples collected ≤30 days from rash onset. A confirmed rubella case tested measles IgM-negative and rubella IgM-positive. Results: Nationwide, 3727 suspected measles cases were reported in 2019. Seventy-five percent of all suspected measles cases were in children aged <5 years. Thirty-six percent of patients with suspected measles were admitted to the hospital, and 36 measles-related deaths were reported. Among cases, 922 (25%) were tested for measles; of these, 317 (34%) were measles IgM-positive. Among cases that tested measles IgM-negative, 149 (33%) were rubella IgM-positive. Immunization coverage for 1 dose of measles-containing vaccine (MCV) varied by state, ranging from 6% to 67%. Conclusions: Measles and rubella remain public health problems in South Sudan. To reduce measles incidence, South Sudan needs to achieve >95% coverage with 2 doses of MCV.

Genomic analysis, immunomodulation and deep phenotyping of patients with nodding syndrome.

The aetiology of nodding syndrome remains unclear, and comprehensive genotyping and phenotyping data from patients remain sparse. Our objectives were to characterize the phenotype of patients with nodding syndrome, investigate potential contributors to disease aetiology, and evaluate response to immunotherapy. This cohort study investigated members of a single-family unit from Lamwo District, Uganda. The participants for this study were selected by the Ugandan Ministry of Health as representative for nodding syndrome and with a conducive family structure for genomic analyses. Of the eight family members who participated in the study at the National Institutes of Health (NIH) Clinical Center, three had nodding syndrome. The three affected patients were extensively evaluated with metagenomic sequencing for infectious pathogens, exome sequencing, spinal fluid immune analyses, neurometabolic and toxicology testing, continuous electroencephalography and neuroimaging. Five unaffected family members underwent a subset of testing for comparison. A distinctive interictal pattern of sleep-activated bursts of generalized and multifocal epileptiform discharges and slowing was observed in two patients. Brain imaging showed two patients had mild generalized cerebral atrophy, and both patients and unaffected family members had excessive metal deposition in the basal ganglia. Trace metal biochemical evaluation was normal. CSF was non-inflammatory and one patient had CSF-restricted oligoclonal bands. Onchocerca volvulus-specific antibodies were present in all patients and skin snips were negative for active onchocerciasis. Metagenomic sequencing of serum and CSF revealed hepatitis B virus in the serum of one patient. Vitamin B6 metabolites were borderline low in all family members and CSF pyridoxine metabolites were normal. Mitochondrial DNA testing was normal. Exome sequencing did not identify potentially causal candidate gene variants. Nodding syndrome is characterized by a distinctive pattern of sleep-activated epileptiform activity. The associated growth stunting may be due to hypothalamic dysfunction. Extensive testing years after disease onset did not clarify a causal aetiology. A trial of immunomodulation (plasmapheresis in two patients and intravenous immunoglobulin in one patient) was given without short-term effect, but longer-term follow-up was not possible to fully assess any benefit of this intervention.

Use of Project ECHO in Response to COVID-19 in Countries Supported by US President's Emergency Plan for AIDS Relief.

The US Centers for Disease Control and Prevention, with funding from the US President's Plan for Emergency Relief, implements a virtual model for clinical mentorship, Project Extension for Community Healthcare Outcomes (ECHO), worldwide to connect multidisciplinary teams of healthcare workers (HCWs) with specialists to build capacity to respond to the HIV epidemic. The emergence of and quick evolution of the COVID-19 pandemic created the need and opportunity for the use of the Project ECHO model to help address the knowledge requirements of HCW responding to COVID-19 while maintaining HCW safety through social distancing. We describe the implementation experiences of Project ECHO in 5 Centers for Disease Control and Prevention programs as part of their COVID-19 response, in which existing platforms were used to rapidly disseminate relevant, up-to-date COVID-19-related clinical information to a large, multidisciplinary audience of stakeholders within their healthcare systems.

Protecting the gains: analysis of HIV treatment and service delivery programme data and interventions implemented in 19 African countries during COVID-19.

INTRODUCTION: The potential disruption in antiretroviral therapy (ART) services in Africa at the start of the COVID-19 pandemic raised concern for increased morbidity and mortality among people living with HIV (PLHIV). We describe HIV treatment trends before and during the pandemic and interventions implemented to mitigate COVID-19 impact among countries supported by the US Centers for Disease Control and Prevention (CDC) through the President's Emergency Plan for AIDS Relief (PEPFAR). METHODS: We analysed quantitative and qualitative data reported by 10,387 PEPFAR-CDC-supported ART sites in 19 African countries between October 2019 and March 2021. Trends in PLHIV on ART, new ART initiations and treatment interruptions were assessed. Viral load coverage (testing of eligible PLHIV) and viral suppression were calculated at select time points. Qualitative data were analysed to summarize facility- and community-based interventions implemented to mitigate COVID-19. RESULTS: The total number of PLHIV on ART increased quarterly from October 2019 (n = 7,540,592) to March 2021 (n = 8,513,572). The adult population (≥15 years) on ART increased by 14.0% (7,005,959-7,983,793), while the paediatric population (<15 years) on ART declined by 2.6% (333,178-324,441). However, the number of new ART initiations dropped between March 2020 and June 2020 by 23.4% for adults and 26.1% for children, with more rapid recovery in adults than children from September 2020 onwards. Viral load coverage increased slightly from April 2020 to March 2021 (75-78%) and viral load suppression increased from October 2019 to March 2021 (91-94%) among adults and children combined. The most reported interventions included multi-month dispensing (MMD) of ART, community service delivery expansion, and technology and virtual platforms use for client engagement and site-level monitoring. MMD of ≥3 months increased from 52% in October 2019 to 78% of PLHIV ≥ age 15 on ART in March 2021. CONCLUSIONS: With an overall increase in the number of people on ART, HIV programmes proved to be resilient, mitigating the impact of COVID-19. However, the decline in the number of children on ART warrants urgent investigation and interventions to prevent further losses experienced during the COVID-19 pandemic and future public health emergencies.

Pediatric HIV Case Identification Across 22 PEPFAR-Supported Countries During the COVID-19 Pandemic, October 2019-September 2020.

During 2020, an estimated 150,000 persons aged 0-14 years acquired HIV globally (1). Case identification is the first step to ensure children living with HIV are linked to life-saving treatment, achieve viral suppression, and live long, healthy lives. Successful interventions to optimize pediatric HIV testing during the COVID-19 pandemic are needed to sustain progress toward achieving Joint United Nations Programme on HIV/AIDS (UNAIDS) 95-95-95 targets.* Changes in HIV testing and diagnoses among persons aged 1-14 years (children) were assessed in 22 U.S. President's Emergency Plan for AIDS Relief (PEPFAR)-supported countries during October 1, 2019-September 30, 2020. This period corresponds to the two fiscal quarters before the COVID-19 pandemic (i.e., Q1 and Q2) and the two quarters after the pandemic began (i.e., Q3 and Q4). Testing was disaggregated by age group, testing strategy, and fiscal year quarter. During October 2019-September 2020, PEPFAR supported 4,312,343 HIV tests and identified 74,658 children living with HIV (CLHIV). The number of HIV tests performed was similar during Q1 and Q2, decreased 40.1% from Q2 to Q3, and increased 19.7% from Q3 to Q4. The number of HIV cases identified among children aged 1-14 years (cases identified) increased 7.4% from Q1 to Q2, decreased 29.4% from Q2 to Q3, and increased 3.3% from Q3 to Q4. Although testing in outpatient departments decreased 21% from Q1 to Q4, testing from other strategies increased during the same period, including mobile testing by 38%, facility-based index testing (offering an HIV test to partners and biological children of persons living with HIV) by 8%, and testing children with signs or symptoms of malnutrition within health facilities by 7%. In addition, most tests (61.3%) and cases identified (60.9%) were among children aged 5-14 years (school-aged children), highlighting the need to continue offering HIV testing to older children. These findings provide important information on the most effective strategies for identifying CLHIV during the COVID-19 pandemic. HIV testing programs should continue to use programmatic, surveillance, and financial data at both national and subnational levels to determine the optimal mix of testing strategies to minimize disruptions in pediatric case identification during the COVID-19 pandemic.

Viral load scale-up in south Sudan: Strategic implementation of tools to monitor HIV treatment success among people living with HIV.

INTRODUCTION: As access to antiretroviral therapy (ART) for people with HIV (PWH) in the Republic of South Sudan (RSS) increases, viral load (VL) suppression is critical to protect global HIV response investments. We describe VL scale-up between 2017-2020 in the RSS President's Emergency Plan for AIDS Relief (PEPFAR)-supported program. METHODS: President's Emergency Plan for AIDS Relief (PEPFAR) South Sudan developed a VL scale-up plan and tools spanning the VL cascade: pre-test, test and post-test and included assessment of clinical facility and laboratory readiness; clinical and laboratory forms and standard operating procedures for test ordering, specimen collection, processing, results return and utilization; procedures to map clients, monitor turn-around-times (TAT), and an electronic system to monitor VL performance. RESULTS: Between 2017 to 2020, VL monitoring was established in 58 facilities, with 59,600 VL samples processed, and improvements in TAT (150-28 days) and rejection rates (1.9%-0.8%). VL documentation improved for dates of ART initiation, VL test request and dispatch, and HIV regimen. Total average time from high VL to repeat VL decreased from 15.9 months to 6.4 months in 2017 and 2019, respectively. CONCLUSIONS: A concerted approach to VL scale-up has been fundamental as South Sudan strives towards UNAIDS 95-95-95 targets for PWH on ART.

Lessons Learned from Programmatic Gains in HIV Service Delivery During the COVID-19 Pandemic - 41 PEPFAR-Supported Countries, 2020.

The U.S. President's Emergency Plan for AIDS Relief (PEPFAR) supports country programs in identifying persons living with HIV infection (PLHIV), providing life-saving treatment, and reducing the spread of HIV in countries around the world (1,2). CDC used Monitoring, Evaluation, and Reporting (MER) data* to assess the extent to which COVID-19 mitigation strategies affected HIV service delivery across the HIV care continuum† globally during the first year of the COVID-19 pandemic. Indicators included the number of reported HIV-positive test results, the number of PLHIV who were receiving antiretroviral therapy (ART), and the rates of HIV viral load suppression. Percent change in performance was assessed between countries during the first 3 months of 2020, before COVID-19 mitigation efforts began (January-March 2020), and the last 3 months of the calendar year (October-December 2020). Data were reviewed for all 41 countries to assess total and country-level percent change for each indicator. Then, qualitative data were reviewed among countries in the upper quartile to assess specific strategies that contributed to programmatic gains. Overall, positive percent change was observed in PEPFAR-supported countries in HIV treatment (5%) and viral load suppression (2%) during 2020. Countries reporting the highest gains across the HIV care continuum during 2020 attributed successes to reducing or streamlining facility attendance through strategies such as enhancing index testing (offering of testing to the biologic children and partners of PLHIV)§ and community- and home-based testing; treatment delivery approaches; and improvements in data use through monitoring activities, systems, and data quality checks. Countries that reported program improvements during the first year of the COVID-19 pandemic offer important information about how lifesaving HIV treatment might be provided during a global public health crisis.

Treatment-adjusted prevalence to assess HIV testing programmes.

Scale-up of human immunodeficiency virus (HIV) testing and antiretroviral therapy (ART) for people living with HIV has been increasing in sub-Saharan Africa. As a result, areas with high HIV prevalence are finding a declining proportion of people testing positive in their national testing programmes. In eastern and southern Africa, where there are settings with adult HIV prevalence of 12% and above, the positivity from national HIV testing services has dropped to below 5%. Identifying those in need of ART is therefore becoming more costly for national HIV programmes. Annual target-setting assumes that national testing positivity rates approximate that of population prevalence. This assumption has generated an increased focus on testing approaches which achieve higher rates of HIV positivity. This trend is a departure from the provider-initiated testing and counselling strategy used early in the global HIV response. We discuss a new indicator, treatment-adjusted prevalence, that countries can use as a practical benchmark for estimating the expected adult positivity in a testing programme when accounting for both national HIV prevalence and ART coverage. The indicator is calculated by removing those people receiving ART from the numerator and denominator of HIV prevalence. Treatment-adjusted prevalence can be readily estimated from existing programme data and population estimates, and in 2019, was added to the World Health Organization guidelines for HIV testing and strategic information. Using country examples from Kenya, Malawi, South Sudan and Zimbabwe we illustrate how to apply this indicator and we discuss the potential public health implications of its use from the national to facility level.

Le dépistage du virus de l'immunodéficience humaine (VIH) et le traitement antirétroviral (TAR) pour les personnes vivant avec le VIH ont connu un véritable essor en Afrique subsaharienne. Par conséquent, les régions touchées par une forte prévalence du VIH détectent un pourcentage moins élevé de personnes testées positives dans leurs programmes de dépistage nationaux. En Afrique orientale et australe, là où certains endroits affichent une prévalence du VIH chez l'adulte égale ou supérieure à 12%, le taux de positivité des services de dépistage nationaux est passé sous la barre des 5%. Identifier les personnes nécessitant un TAR devient donc plus coûteux pour les programmes nationaux consacrés au VIH. Pour définir les objectifs annuels, on part du principe que les taux de positivité nationaux se rapprochent du taux de prévalence au sein de la population. Cette supposition a orienté les démarches vers des méthodes de dépistage permettant d'obtenir des taux de positivité plus élevés; une tendance qui s'écarte de la stratégie des services de dépistage et de conseil à l'initiative des prestataires, utilisée à l'aube de la lutte mondiale contre le VIH. Dans le présent document, nous nous intéressons à un nouvel indicateur, la prévalence ajustée sur le traitement. Cet indicateur peut servir de référence concrète pour les pays qui souhaitent évaluer le taux de positivité attendu chez l'adulte dans un programme de dépistage, en tenant compte de la prévalence du VIH au niveau national ainsi que de la portée du TAR. Le calcul consiste à enlever les personnes recevant un TAR du numérateur et du dénominateur de la prévalence du VIH. La prévalence ajustée sur le traitement peut aisément être déterminée en fonction des données de programme et estimations de population existantes. En 2019, elle a également été ajoutée aux lignes directrices de l'Organisation mondiale de la Santé pour l'information stratégique et le dépistage du VIH. En nous inspirant d'exemples issus du Kenya, du Malawi, du Soudan du Sud et du Zimbabwe, nous expliquons comment employer cet indicateur et abordons les potentielles implications liées à son utilisation en matière de santé publique, en partant du niveau national jusqu'aux établissements.

La ampliación de las pruebas de detección del virus de la inmunodeficiencia humana (VIH) y del tratamiento antirretrovírico (TAR) para las personas infectadas por el VIH ha aumentado en el África subsahariana. En consecuencia, el porcentaje de personas que dan positivo en las pruebas de detección del VIH en los programas nacionales está disminuyendo en las zonas con alta prevalencia del virus. En África meridional y oriental, donde hay entornos con una prevalencia del VIH en adultos del 12 % o superior, la tasa de positividad de los servicios nacionales de pruebas de detección del VIH ha descendido a menos del 5 %. Por lo tanto, la identificación de las personas que necesitan TAR es cada vez más costosa para los programas nacionales de VIH. El establecimiento de objetivos anuales supone que las tasas de positividad de las pruebas nacionales se aproximan a las de la prevalencia de la población. Esta suposición ha generado una mayor atención a los enfoques de las pruebas que logran tasas más altas de positividad del VIH. Esta tendencia se aleja de la estrategia del asesoramiento y las pruebas que iniciaron los proveedores y que se utilizó al principio de la respuesta mundial al VIH. Se analiza un nuevo indicador, la prevalencia ajustada según el tratamiento, que los países pueden emplear como punto de referencia práctico para estimar la tasa de positividad esperada en adultos en un programa de pruebas de detección cuando se tiene en cuenta tanto la prevalencia nacional del VIH como la cobertura del TAR. El indicador se calcula eliminando del numerador y el denominador de la prevalencia del VIH a las personas que reciben TAR. La prevalencia ajustada según el tratamiento se puede estimar con facilidad a partir de los datos de los programas existentes y de las estimaciones de población, además, en 2019, se incluyó en las directrices de la Organización Mundial de la Salud para las pruebas de detección del VIH y en la información estratégica. A través de ejemplos de países como Kenia, Malaui, Sudán meridional y Zimbabue, se demuestra cómo aplicar este indicador y se discuten las posibles implicaciones para la salud pública de su uso desde el nivel nacional hasta el de los centros.

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.

Impact of Policy and Funding Decisions on COVID-19 Surveillance Operations and Case Reports - South Sudan, April 2020-February 2021.

Early models predicted substantial COVID-19-associated morbidity and mortality across Africa (1-3). However, as of March 2021, countries in Africa are among those with the lowest reported incidence of COVID-19 worldwide (4). Whether this reflects effective mitigation, outbreak response, or demographic characteristics, (5) or indicates limitations in disease surveillance capacity is unclear (6). As countries implemented changes in funding, national policies, and testing strategies in response to the COVID-19 pandemic, surveillance capacity might have been adversely affected. This study assessed whether changes in surveillance operations affected reporting in South Sudan; testing and case numbers reported during April 6, 2020-February 21, 2021, were analyzed relative to the timing of funding, policy, and strategy changes.* South Sudan, with a population of approximately 11 million, began COVID-19 surveillance in February 2020 and reported 6,931 cases through February 21, 2021. Surveillance data analyzed were from point of entry screening, testing of symptomatic persons who contacted an alert hotline, contact tracing, sentinel surveillance, and outbound travel screening. After travel restrictions were relaxed in early May 2020, international land and air travel resumed and mandatory requirements for negative pretravel test results were initiated. The percentage of all testing accounted for by travel screening increased >300%, from 21.1% to 91.0% during the analysis period, despite yielding the lowest percentage of positive tests among all sources. Although testing of symptomatic persons and contact tracing yielded the highest percentage of COVID-19 cases, the percentage of all testing from these sources decreased 88%, from 52.6% to 6.3% after support for these activities was reduced. Collectively, testing increased over the project period, but shifted toward sources least likely to yield positive results, possibly resulting in underreporting of cases. Policy, funding, and strategy decisions related to the COVID-19 pandemic response, such as those implemented in South Sudan, are important issues to consider when interpreting the epidemiology of COVID-19 outbreaks.

Lessons learned from implementation of a national hotline for Ebola virus disease emergency preparedness in South Sudan.

BACKGROUND: The world's second largest Ebola outbreak occurred in the Democratic Republic of Congo from 2018 to 2020. At the time, risk of cross-border spread into South Sudan was very high. Thus, the South Sudan Ministry of Health scaled up Ebola preparedness activities in August 2018, including implementation of a 24-h, toll-free Ebola virus disease (EVD) hotline. The primary purpose was the hotline was to receive EVD alerts and the secondary goal was to provide evidence-based EVD messages to the public. METHODS: To assess whether the hotline augmented Ebola preparedness activities in a protracted humanitarian emergency context, we reviewed 22 weeks of call logs from January to June 2019. Counts and percentages were calculated for all available data. RESULTS: The hotline received 2114 calls during the analysis period, and an additional 1835 missed calls were documented. Callers used the hotline throughout 24-h of the day and were most often men and individuals living in Jubek state, where the national capital is located. The leading reasons for calling were to learn more about EVD (68%) or to report clinical signs or symptoms (16%). Common EVD-related questions included EVD signs and symptoms, transmission, and prevention. Only one call was documented as an EVD alert, and there was no documentation of reported symptoms or whether the person met the EVD case definition. CONCLUSIONS: Basic surveillance information was not collected from callers. To trigger effective outbreak investigation from hotline calls, the hotline should capture who is reporting and from where, symptoms and travel history, and whether this information should be further investigated. Electronic data capture will enhance data quality and availability of information for review. Additionally, the magnitude of missed calls presents a major challenge. When calls are answered, there is potential to provide health communication, so risk communication needs should be considered. However, prior to hotline implementation, governments should critically assess whether their hotline would yield actionable data and if other data sources for surveillance or community concerns are available.

Implementation of tuberculosis preventive treatment among people living with HIV, South Sudan.

OBJECTIVE: To describe an intervention to scale up tuberculosis preventive treatment for people living with human immunodeficiency virus (HIV) in South Sudan, 2017-2020. METHODS: Staff of the health ministry and United States President's Emergency Plan for AIDS Relief designed an intervention targeting the estimated 30 400 people living with HIV on antiretroviral therapy across South Sudan. The intervention comprised: (i) developing sensitization and operational guidance for clinicians to put tuberculosis preventive treatment delivery into clinical practice; (ii) disseminating monitoring and evaluation tools to document scale-up; (iii) implementing a programmatic pilot of tuberculosis preventive treatment; and (iv) identifying a mechanism for procurement and delivery of isoniazid to facilities dispensing tuberculosis preventive treatment. Staff aggregated routine programme data from facility registers on the numbers of people living with HIV who started on tuberculosis preventive treatment across all clinical sites providing this treatment during July 2019-March 2020. FINDINGS: Tuberculosis preventive treatment was implemented in 13 HIV treatment sites during July-October 2019, then in 26 sites during November 2019-March 2020. During July 2019-March 2020, 6503 people living with HIV started tuberculosis preventive treatment. CONCLUSION: Lessons for other low-resource settings may include supplementing national guidelines with health ministry directives, clinician guidance and training, and an implementation pilot. A cadre of field supervisors can rapidly disseminate a standardized approach to implementation and monitoring of tuberculosis preventive treatment, and this approach can be used to strengthen other tuberculosis-HIV services. Procuring a reliable and steady supply of tuberculosis preventive treatment medication is crucial.

Analyses of the performance of the Ebola virus disease alert management system in South Sudan: August 2018 to November 2019.

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.

Case Definitions Used During the First 6 Months of the 10th Ebola Virus Disease Outbreak in the Democratic Republic of the Congo - Four Neighboring Countries, August 2018-February 2019.

On August 1, 2018, the Democratic Republic of the Congo (DRC) declared its 10th Ebola virus disease (Ebola) outbreak in an area with a high volume of cross-border population movement to and from neighboring countries. The World Health Organization (WHO) designated Rwanda, South Sudan, and Uganda as the highest priority countries for Ebola preparedness because of the high risk for cross-border spread from DRC (1). Countries might base their disease case definitions on global standards; however, historical context and perceived risk often affect why countries modify and adapt definitions over time, moving toward or away from regional harmonization. Discordance in case definitions among countries might reduce the effectiveness of cross-border initiatives during outbreaks with high risk for regional spread. CDC worked with the ministries of health (MOHs) in DRC, Rwanda, South Sudan, and Uganda to collect MOH-approved Ebola case definitions used during the first 6 months of the outbreak to assess concordance (i.e., commonality in category case definitions) among countries. Changes in MOH-approved Ebola case definitions were analyzed, referencing the WHO standard case definition, and concordance among the four countries for Ebola case categories (i.e., community alert, suspected, probable, confirmed, and case contact) was assessed at three dates (2). The number of country-level revisions ranged from two to four, with all countries revising Ebola definitions by February 2019 after a December 2018 peak in incidence in DRC. Case definition complexity increased over time; all countries included more criteria per category than the WHO standard definition did, except for the "case contact" and "confirmed" categories. Low case definition concordance and lack of awareness of regional differences by national-level health officials could reduce effectiveness of cross-border communication and collaboration. Working toward regional harmonization or considering systematic approaches to addressing country-level differences might increase efficiency in cross-border information sharing.

The first sixty days of COVID-19 in a humanitarian response setting: a descriptive epidemiological analysis of the outbreak in South Sudan.

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.

Scaling Up Testing for Human Immunodeficiency Virus Infection Among Contacts of Index Patients - 20 Countries, 2016-2018.

In 2017, the Joint United Nations Programme on HIV/AIDS (UNAIDS) estimated that worldwide, 36.9 million persons were living with human immunodeficiency virus (HIV) infection, the virus infection that causes acquired immunodeficiency syndrome (AIDS). Among persons with HIV infection, approximately 75% were aware of their HIV status, leaving 9.4 million persons with undiagnosed infection (1). Index testing, also known as partner notification or contact tracing, is an effective case-finding strategy that targets the exposed contacts of HIV-positive persons for HIV testing services. This report summarizes data from HIV tests using index testing in 20 countries supported by CDC through the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) during October 1, 2016-March 31, 2018. During this 18-month period, 1,700,998 HIV tests with 99,201 (5.8%) positive results were reported using index testing. The positivity rate for index testing was 9.8% among persons aged ≥15 years and 1.5% among persons aged <15 years. During the reporting period, HIV positivity increased 64% among persons aged ≥15 years (from 7.6% to 12.5%) and 67% among persons aged <15 years (from 1.2% to 2.0%). Expanding index testing services could help increase the number of persons with HIV infection who know their status, are initiated onto antiretroviral treatment, and consequently reduce the number of persons who can transmit the virus.

Nodding syndrome may be an autoimmune reaction to the parasitic worm Onchocerca volvulus.

Nodding syndrome is an epileptic disorder of unknown etiology that occurs in children in East Africa. There is an epidemiological association with Onchocerca volvulus, the parasitic worm that causes onchocerciasis (river blindness), but there is limited evidence that the parasite itself is neuroinvasive. We hypothesized that nodding syndrome may be an autoimmune-mediated disease. Using protein chip methodology, we detected autoantibodies to leiomodin-1 more abundantly in patients with nodding syndrome compared to unaffected controls from the same village. Leiomodin-1 autoantibodies were found in both the sera and cerebrospinal fluid of patients with nodding syndrome. Leiomodin-1 was found to be expressed in mature and developing human neurons in vitro and was localized in mouse brain to the CA3 region of the hippocampus, Purkinje cells in the cerebellum, and cortical neurons, structures that also appear to be affected in patients with nodding syndrome. Antibodies targeting leiomodin-1 were neurotoxic in vitro, and leiomodin-1 antibodies purified from patients with nodding syndrome were cross-reactive with O. volvulus antigens. This study provides initial evidence supporting the hypothesis that nodding syndrome is an autoimmune epileptic disorder caused by molecular mimicry with O. volvulus antigens and suggests that patients may benefit from immunomodulatory therapies.