Systematic analysis of Kaposi's sarcoma (KS)-associated herpesvirus genomes from a KS case-control study in Cameroon: Evidence of dual infections but no association between viral sequence variation and KS risk.

In sub-Saharan Africa, Kaposi's sarcoma-associated herpesvirus (KSHV) is endemic, and Kaposi's sarcoma (KS) is a significant public health problem. Until recently, KSHV genotype analysis was performed using variable gene regions, representing a small fraction of the genome, and thus the contribution of sequence variation to viral transmission or pathogenesis are understudied. We performed near full-length KSHV genome sequence analysis on samples from 43 individuals selected from a large Cameroonian KS case-control study. KSHV genomes were obtained from 21 KS patients and 22 control participants. Phylogenetic analysis of the K1 region indicated the majority of sequences were A5 or B1 subtypes and all three K15 alleles were represented. Unique polymorphisms in the KSHV genome were observed including large gene deletions. We found evidence of multiple distinct KSHV genotypes in three individuals. Additionally, our analyses indicate that recombination is prevalent suggesting that multiple KSHV infections may not be uncommon overall. Most importantly, a detailed analysis of KSHV genomes from KS patients and control participants did not find a correlation between viral sequence variations and disease. Our study is the first to systematically compare near full-length KSHV genome sequences between KS cases and controls in the same endemic region to identify possible sequence variations associated with disease risk.

Mutual detection of Kaposi's sarcoma-associated herpesvirus and Epstein-Barr virus in blood and saliva of Cameroonians with and without Kaposi's sarcoma.

Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) are prevalent in sub-Saharan Africa, together with HIV; the consequent burden of disease is grave. The cofactors driving transmission of the two viruses and pathogenesis of associated malignancies are not well understood. We measured KSHV and EBV DNA in whole blood and saliva as well as serum antibodies levels in 175 Cameroonians with Kaposi's sarcoma and 1,002 age- and sex-matched controls with and without HIV. KSHV seroprevalence was very high (81%) in controls, while EBV seroprevalence was 100% overall. KSHV DNA was detectable in the blood of 36-46% of cases and 6-12% of controls; EBV DNA was detected in most participants (72-89%). In saliva, more cases (50-58%) than controls (25-28%) shed KSHV, regardless of HIV infection. EBV shedding was common (75-100%); more HIV+ than HIV- controls shed EBV. Cases had higher KSHV and EBV VL in blood and saliva then controls, only among HIV+ participants. KSHV and EBV VL were also higher in HIV+ than in HIV- controls. Cases (but not controls) were more likely to have detectable KSHV in blood if they also had EBV, whereas shedding of each virus in saliva was independent. While EBV VL in saliva and blood were modestly correlated, no correlation existed for KSHV. Numerous factors, several related to parasitic coinfections, were associated with detection of either virus or with VL. These findings may help better understand the interplay between the two gammaherpesviruses and generally among copathogens contributing to cancer burden in sub-Saharan Africa.

Data quality monitoring and performance metrics of a prospective, population-based observational study of maternal and newborn health in low resource settings.

BACKGROUND: To describe quantitative data quality monitoring and performance metrics adopted by the Global Network's (GN) Maternal Newborn Health Registry (MNHR), a maternal and perinatal population-based registry (MPPBR) based in low and middle income countries (LMICs). METHODS: Ongoing prospective, population-based data on all pregnancy outcomes within defined geographical locations participating in the GN have been collected since 2008. Data quality metrics were defined and are implemented at the cluster, site and the central level to ensure data quality. Quantitative performance metrics are described for data collected between 2010 and 2013. RESULTS: Delivery outcome rates over 95% illustrate that all sites are successful in following patients from pregnancy through delivery. Examples of specific performance metric reports illustrate how both the metrics and reporting process are used to identify cluster-level and site-level quality issues and illustrate how those metrics track over time. Other summary reports (e.g. the increasing proportion of measured birth weight compared to estimated and missing birth weight) illustrate how a site has improved quality over time. CONCLUSION: High quality MPPBRs such as the MNHR provide key information on pregnancy outcomes to local and international health officials where civil registration systems are lacking. The MNHR has measures in place to monitor data collection procedures and improve the quality of data collected. Sites have increasingly achieved acceptable values of performance metrics over time, indicating improvements in data quality, but the quality control program must continue to evolve to optimize the use of the MNHR to assess the impact of community interventions in research protocols in pregnancy and perinatal health. TRIAL REGISTRATION NUMBER: NCT01073475.

Factors associated with COVID-19 vaccine uptake and hesitancy among healthcare workers in the Democratic Republic of the Congo.

Vaccination is a critical intervention to reduce morbidity and mortality and limit strain on health systems caused by COVID-19. The slow pace of COVID-19 vaccination uptake observed in some settings raises concerns about COVID-19 vaccine hesitancy. The Democratic Republic of the Congo experienced logistical challenges and low uptake at the start of vaccine distribution, leading to one of the lowest overall COVID-19 vaccine coverage rates in the world in 2021. This study assessed the magnitude and associated factors of COVID-19 vaccine uptake among healthcare workers (HCWs) in seven provinces in DRC. We implemented a cross-sectional Knowledge, Attitudes, and Practices (KAP) questionnaire targeting HCWs, administered by trained data collectors in Haut-Katanga, Kasaï Orientale, Kinshasa, Kongo Centrale, Lualaba, North Kivu, and South Kivu provinces. Data were summarized and statistical tests were performed to assess factors associated with vaccine uptake. HCWs across the seven provinces completed the questionnaire (N = 5,102), of whom 46.3% had received at least one dose of COVID-19 vaccine. Older age, being married, being a medical doctor, being a rural resident, and having access to or having previously worked in a COVID-19 vaccination site were all strongly associated with vaccination uptake. Vaccinated individuals most frequently cited protection of themselves, their families, and their communities as motivations for being vaccinated, whereas unvaccinated individuals were most concerned about safety, effectiveness, and risk of severe side effects. The findings suggest an opinion divide between vaccine-willing and vaccine-hesitant HCWs. A multidimensional approach may be needed to increase the acceptability of the COVID-19 vaccine for HCWs. Future vaccine campaign messaging could center around the positive impact of vaccination on protecting friends, family, and the community, and also emphasize the safety and very low risk of adverse effects. These types of messages may further be useful when planning future immunization campaigns with new vaccines.

Provincial Intra-Action Review of the COVID-19 Vaccination Programme: Opportunities to Improve Vaccine Response in North Kivu, Democratic Republic of Congo.

Background: Low levels of COVID-19 vaccination coverage in many countries prompted the use of rapid assessments to characterize barriers to vaccination and identify corrective measures. The World Health Organization recommended the use of intra-action reviews (IARs) to identify best practices, gaps, and lessons learned to make real-time improvements to the COVID-19 vaccination response. Objective: The Democratic Republic of the Congo (DRC) implemented a national IAR in July 2021 that was poorly attended by the provincial health level, where vaccination activities are planned and implemented. To bridge this gap, we proposed sub-national IARs focused on COVID-19 vaccine program implementation at the provincial level. Methods: Using the WHO methodology, we organized a four-day provincial IAR workshop and invited national, provincial and health zone Ministry of Health (MoH) representatives and private and non-governmental organizations involved in the provincial COVID-19 vaccination response. Participants were divided into six groups based on their expertise, affiliation, and role within the health system to assess and identify lessons learned, challenges and the solutions within each of the six technical areas: (1) coordination, planning and monitoring; (2) service delivery; (3) risk communication and community engagement; (4) adverse effects following immunization (AEFI); (5) logistics; (6) and data management, monitoring and evaluation. Results: The first provincial COVID-19 IAR was conducted in Goma, North Kivu, from January 19-22, 2022. A total of 56 participants came from provincial and health zone offices, and non-governmental organizations. Through work group discussions, they identified best practices, challenges, and lessons learned, and made recommendations to improve implementation of vaccination activities and reach coverage targets. Activities were proposed to operationalize recommendations and address challenges to improve the provincial response. Conclusion: This provincial IAR was a useful tool for reviewing progress and areas of improvement, while evaluating aspects of the COVID-19 vaccine rollout. It provided a means to share information with vaccination partners on areas of intervention, tailored to the local context.

Lessons learned for surveillance system strengthening through capacity building and partnership engagement in post-Ebola Guinea, 2015-2019.

The 2014-2016 Ebola outbreak in Guinea revealed systematic weaknesses in the existing disease surveillance system, which contributed to delayed detection, underreporting of cases, widespread transmission in Guinea and cross-border transmission to neighboring Sierra Leone and Liberia, leading to the largest Ebola epidemic ever recorded. Efforts to understand the epidemic's scale and distribution were hindered by problems with data completeness, accuracy, and reliability. In 2017, recognizing the importance and usefulness of surveillance data in making evidence-based decisions for the control of epidemic-prone diseases, the Guinean Ministry of Health (MoH) included surveillance strengthening as a priority activity in their post-Ebola transition plan and requested the support of partners to attain its objectives. The U.S. Centers for Disease Control and Prevention (US CDC) and four of its implementing partners-International Medical Corps, the International Organization for Migration, RTI International, and the World Health Organization-worked in collaboration with the Government of Guinea to strengthen the country's surveillance capacity, in alignment with the Global Health Security Agenda and International Health Regulations 2005 objectives for surveillance and reporting. This paper describes the main surveillance activities supported by US CDC and its partners between 2015 and 2019 and provides information on the strategies used and the impact of activities. It also discusses lessons learned for building sustainable capacity and infrastructure for disease surveillance and reporting in similar resource-limited settings.

Implementation of DHIS2 for Disease Surveillance in Guinea: 2015-2020.

A robust epidemic-prone disease surveillance system is a critical component of public health infrastructure and supports compliance with the International Health Regulations (IHR). One digital health platform that has been implemented in numerous low- and middle-income countries is the District Health Information System Version 2 (DHIS2). In 2015, in the wake of the Ebola epidemic, the Ministry of Health in Guinea established a strategic plan to strengthen its surveillance system, including adoption of DHIS2 as a health information system that could also capture surveillance data. In 2017, the DHIS2 platform for disease surveillance was piloted in two regions, with the aim of ensuring the timely availability of quality surveillance data for better prevention, detection, and response to epidemic-prone diseases. The success of the pilot prompted the national roll-out of DHIS2 for weekly aggregate disease surveillance starting in January 2018. In 2019, the country started to also use the DHIS2 Tracker to capture individual cases of epidemic-prone diseases. As of February 2020, for aggregate data, the national average timeliness of reporting was 72.2%, and average completeness 98.5%; however, the proportion of individual case reports filed was overall low and varied widely between diseases. While substantial progress has been made in implementation of DHIS2 in Guinea for use in surveillance of epidemic-prone diseases, much remains to be done to ensure long-term sustainability of the system. This paper describes the implementation and outcomes of DHIS2 as a digital health platform for disease surveillance in Guinea between 2015 and early 2020, highlighting lessons learned and recommendations related to the processes of planning and adoption, pilot testing in two regions, and scale up to national level.

Contextual, Social and Epidemiological Characteristics of the Ebola Virus Disease Outbreak in Likati Health Zone, Democratic Republic of the Congo, 2017.

While the clinical, laboratory and epidemiological investigation results of the Ebola outbreak in Likati Health Zone, Democratic Republic of the Congo (DRC) in May 2017 have been previously reported, we provide novel commentary on the contextual, social, and epidemiological characteristics of the epidemic. As first responders with the outbreak Surveillance Team, we explain the procedures that led to a successful epidemiological investigation and ultimately a rapid end to the epidemic. We discuss the role that several factors played in the trajectory of the epidemic, including traditional healers, insufficient knowledge of epidemiological case definitions, a lack of community-based surveillance systems and tools, and remote geography. We also demonstrate how a collaborative Rapid Response Team and implementation of community-based surveillance methods helped counter contextual challenges during the Likati epidemic and aid in identifying and reporting suspected cases and contacts in remote and rural settings. Understanding these factors can hinder or help in the rapid detection, notification, and response to future epidemics in the DRC.

Lessons Learned from Reinforcing Epidemiologic Surveillance During the 2017 Ebola Outbreak in the Likati District, Democratic Republic of the Congo.

On May 12, 2017, the Democratic Republic of Congo (DRC) publicly declared an outbreak of Ebola virus disease (EVD) in the Likati District of the Bas-Uélé Province, 46 days after the index case became symptomatic. The delayed EVD case detection and reporting highlights the importance of establishing real-time surveillance, consistent with the Global Health Security Agenda. We describe lessons learned from implementing improved EVD case detection and reporting strategies at the outbreak epicenter and make recommendations for future response efforts. The strategies included daily coordination meetings to enhance effective and efficient outbreak response activities, assessment and adaptation of case definitions and reporting tools, establishment of a community alert system using context-appropriate technology, training facility and community health workers on adapted case definitions and reporting procedures, development of context-specific plans for outbreak data management, and strengthened operational support for communications and information-sharing networks. Post-outbreak, surveillance officials should preemptively plan for the next outbreak by developing emergency response plans, evaluating the case definitions and reporting tools used, retraining on revised case definitions, and developing responsive strategies for overcoming telecommunications and technology challenges. The ongoing EVD outbreak in the North Kivu and Ituri provinces of DRC, currently the second largest EVD outbreak in history, demonstrates that documentation of successful context-specific strategies and tools are needed to combat the next outbreak. The lessons learned from the rapid containment of the EVD outbreak in Likati can be applied to the DRC and other rural low-resource settings to ensure readiness for future zoonotic disease outbreaks.

Assessing the Surveillance System for Priority Zoonotic Diseases in the Democratic Republic of the Congo, 2017.

High-functioning communicable disease surveillance systems are critical for public health preparedness. Countries that cannot quickly detect and contain diseases are a risk to the global community. The ability of all countries to comply with the International Health Regulations is paramount for global health security. Zoonotic diseases can be particularly dangerous for humans. We conducted a surveillance system assessment of institutional and individual capacity in Kinshasa and Haut Katanga provinces in the Democratic Republic of the Congo for nationally identified priority zoonotic diseases (eg, viral hemorrhagic fever [VHF], yellow fever, rabies, monkeypox, and influenza monitored through acute respiratory infections). Data were collected from 79 health workers responsible for disease surveillance at 2 provincial health offices, 9 health zone offices, 9 general reference hospitals, and 18 health centers and communities. A set of questionnaires was used to assess health worker training in disease surveillance methods; knowledge of case definitions; availability of materials and tools to support timely case detection, reporting, and data interpretation; timeliness and completeness of reporting; and supervision from health authorities. We found that health workers either had not been recently or ever trained in surveillance methods and that their knowledge of case definitions was low. Timeliness and completeness of weekly notification of epidemic-prone diseases was generally well performed, but the lack of available standardized reporting forms and archive of completed forms affected the quality of data collected. Lessons learned from our assessment can be used for targeted strengthening efforts to improve global health security.

Repeat 24-hour recalls and locally developed food composition databases: a feasible method to estimate dietary adequacy in a multi-site preconception maternal nutrition RCT.

Background: Our aim was to utilize a feasible quantitative methodology to estimate the dietary adequacy of >900 first-trimester pregnant women in poor rural areas of the Democratic Republic of the Congo, Guatemala, India and Pakistan. This paper outlines the dietary methods used. Methods: Local nutritionists were trained at the sites by the lead study nutritionist and received ongoing mentoring throughout the study. Training topics focused on the standardized conduct of repeat multiple-pass 24-hr dietary recalls, including interview techniques, estimation of portion sizes, and construction of a unique site-specific food composition database (FCDB). Each FCDB was based on 13 food groups and included values for moisture, energy, 20 nutrients (i.e. macro- and micronutrients), and phytate (an anti-nutrient). Nutrient values for individual foods or beverages were taken from recently developed FAO-supported regional food composition tables or the USDA national nutrient database. Appropriate adjustments for differences in moisture and application of nutrient retention and yield factors after cooking were applied, as needed. Generic recipes for mixed dishes consumed by the study population were compiled at each site, followed by calculation of a median recipe per 100 g. Each recipe's nutrient values were included in the FCDB. Final site FCDB checks were planned according to FAO/INFOODS guidelines. Discussion: This dietary strategy provides the opportunity to assess estimated mean group usual energy and nutrient intakes and estimated prevalence of the population 'at risk' of inadequate intakes in first-trimester pregnant women living in four low- and middle-income countries. While challenges and limitations exist, this methodology demonstrates the practical application of a quantitative dietary strategy for a large international multi-site nutrition trial, providing within- and between-site comparisons. Moreover, it provides an excellent opportunity for local capacity building and each site FCDB can be easily modified for additional research activities conducted in other populations living in the same area.