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.

Relationship between human leukocyte antigen alleles and risk of Kaposi's sarcoma in Cameroon.

Several studies published to date report associations between human leukocyte antigen (HLA) alleles and different types of Kaposi's Sarcoma (KS). However, there is little concordance between the HLA alleles identified and the populations studied. To test whether HLA alleles associate with KS in a Cameroonian case-control study, we performed high-resolution HLA typing in KSHV seropositive individuals. Among HIV-positive individuals, carriers of HLA-B*14:01 were at a significantly higher risk of AIDS-KS (p = 0.033). For HIV-negative patients, a gene-wise comparison of allele frequencies identified the HLA-B (p = 0.008) and -DQA1 (p = 0.002) loci as possible risk factors for endemic KS. Our study provides additional understanding of genetic determinants of KS and their implications in disease pathogenesis. Further validation of these findings is needed to define the functional relevance of these associations.

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.

International prospective observational cohort study of Zika in infants and pregnancy (ZIP study): study protocol.

BACKGROUND: Until recently, Zika virus (ZIKV) infections were considered mild and self-limiting. Since 2015, they have been associated with an increase in microcephaly and other birth defects in newborns. While this association has been observed in case reports and epidemiological studies, the nature and extent of the relationship between ZIKV and adverse pregnancy and pediatric health outcomes is not well understood. With the unique opportunity to prospectively explore the full spectrum of issues related to ZIKV exposure during pregnancy, we undertook a multi-country, prospective cohort study to evaluate the association between ZIKV and pregnancy, neonatal, and infant outcomes. METHODS: At research sites in ZIKV endemic regions of Brazil (4 sites), Colombia, Guatemala, Nicaragua, Puerto Rico (2 sites), and Peru, up to 10,000 pregnant women will be recruited and consented in the first and early second trimesters of pregnancy and then followed through delivery up to 6 weeks post-partum; their infants will be followed until at least 1 year of age. Pregnant women with symptomatic ZIKV infection confirmed by presence of ZIKV RNA and/or IgM for ZIKV will also be enrolled, regardless of gestational age. Participants will be tested monthly for ZIKV infection; additional demographic, physical, laboratory and environmental data will be collected to assess the potential interaction of these variables with ZIKV infection. Delivery outcomes and detailed infant assessments, including physical and neurological outcomes, will be obtained. DISCUSSION: With the emergence of ZIKV in the Americas and its association with adverse pregnancy outcomes in this region, a much better understanding of the spectrum of clinical outcomes associated with exposure to ZIKV during pregnancy is needed. This cohort study will provide information about maternal, fetal, and infant outcomes related to ZIKV infection, including congenital ZIKV syndrome, and manifestations that are not detectable at birth but may appear during the first year of life. In addition, the flexibility of the study design has provided an opportunity to modify study parameters in real time to provide rigorous research data to answer the most critical questions about the impact of congenital ZIKV exposure. TRIAL REGISTRATION: NCT02856984 . Registered August 5, 2016. Retrospectively registered.

Correction to: International prospective observational cohort study of Zika in infants and pregnancy (ZIP study): study protocol.

Following publication of the original article [1], the author mentioned that two additional NIH staff were involved in the development of the protocol who did not receive recognition in the Acknowledgments section in their published article.

Anthropometric indices for non-pregnant women of childbearing age differ widely among four low-middle income populations.

BACKGROUND: Maternal stature and body mass indices (BMI) of non-pregnant women (NPW) of child bearing age are relevant to maternal and offspring health. The objective was to compare anthropometric indices of NPW in four rural communities in low- to low-middle income countries (LMIC). METHODS: Anthropometry and maternal characteristics/household wealth questionnaires were obtained for NPW enrolled in the Women First Preconception Maternal Nutrition Trial. Body mass index (BMI, kg/m2) was calculated. Z-scores were determined using WHO reference data. RESULTS: A total of 7268 NPW participated in Equateur, DRC (n = 1741); Chimaltenango, Guatemala (n = 1695); North Karnataka, India (n = 1823); and Thatta, Sindh, Pakistan (n = 2009). Mean age was 23 y and mean parity 1.5. Median (P25-P75) height (cm) ranged from 145.5 (142.2-148.9) in Guatemala to 156.0 (152.0-160.0) in DRC. Median weight (kg) ranged from 44.7 (39.9-50.3) in India to 52.7 (46.9-59.8) in Guatemala. Median BMI ranged from 19.4 (17.6-21.9) in India to 24.9 (22.3-28.0) in Guatemala. Percent stunted (<-2SD height for age z-score) ranged from 13.9% in DRC to 80.5% in Guatemala; % underweight (BMI <18.5) ranged from 1.2% in Guatemala to 37.1% in India; % overweight/obese (OW, BMI ≥25.0) ranged from 5.7% in DRC to 49.3% in Guatemala. For all sites, indicators for higher SES and higher age were associated with BMI. Lower SES women were underweight more frequently and higher SES women were OW more frequently at all sites. Younger women tended to be underweight, while older women tended to be OW. CONCLUSIONS: Anthropometric data for NPW varied widely among low-income rural populations in four countries located on three different continents. Global comparisons of anthropometric measurements across sites using standard reference data serve to highlight major differences among populations of low-income rural NPW and assist in evaluating the rationale for and the design of optimal intervention trials. TRIAL REGISTRATION: ClinicalTrials.gov # NCT01883193 (18 June 2013, retrospectively registered).

A population-based, multifaceted strategy to implement antenatal corticosteroid treatment versus standard care for the reduction of neonatal mortality due to preterm birth in low-income and middle-income countries: the ACT cluster-randomised trial.

BACKGROUND: Antenatal corticosteroids for pregnant women at risk of preterm birth are among the most effective hospital-based interventions to reduce neonatal mortality. We aimed to assess the feasibility, effectiveness, and safety of a multifaceted intervention designed to increase the use of antenatal corticosteroids at all levels of health care in low-income and middle-income countries. METHODS: In this 18-month, cluster-randomised trial, we randomly assigned (1:1) rural and semi-urban clusters within six countries (Argentina, Guatemala, India, Kenya, Pakistan, and Zambia) to standard care or a multifaceted intervention including components to improve identification of women at risk of preterm birth and to facilitate appropriate use of antenatal corticosteroids. The primary outcome was 28-day neonatal mortality among infants less than the 5th percentile for birthweight (a proxy for preterm birth) across the clusters. Use of antenatal corticosteroids and suspected maternal infection were additional main outcomes. This trial is registered with ClinicalTrials.gov, number NCT01084096. FINDINGS: The ACT trial took place between October, 2011, and March, 2014 (start dates varied by site). 51 intervention clusters with 47,394 livebirths (2520 [5%] less than 5th percentile for birthweight) and 50 control clusters with 50,743 livebirths (2258 [4%] less than 5th percentile) completed follow-up. 1052 (45%) of 2327 women in intervention clusters who delivered less-than-5th-percentile infants received antenatal corticosteroids, compared with 215 (10%) of 2062 in control clusters (p<0·0001). Among the less-than-5th-percentile infants, 28-day neonatal mortality was 225 per 1000 livebirths for the intervention group and 232 per 1000 livebirths for the control group (relative risk [RR] 0·96, 95% CI 0·87-1·06, p=0·65) and suspected maternal infection was reported in 236 (10%) of 2361 women in the intervention group and 133 (6%) of 2094 in the control group (odds ratio [OR] 1·67, 1·33-2·09, p<0·0001). Among the whole population, 28-day neonatal mortality was 27·4 per 1000 livebirths for the intervention group and 23·9 per 1000 livebirths for the control group (RR 1·12, 1·02-1·22, p=0·0127) and suspected maternal infection was reported in 1207 (3%) of 48,219 women in the intervention group and 867 (2%) of 51,523 in the control group (OR 1·45, 1·33-1·58, p<0·0001). INTERPRETATION: Despite increased use of antenatal corticosteroids in low-birthweight infants in the intervention groups, neonatal mortality did not decrease in this group, and increased in the population overall. For every 1000 women exposed to this strategy, an excess of 3·5 neonatal deaths occurred, and the risk of maternal infection seems to have been increased. FUNDING: Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Characteristics of antiretroviral therapy-naïve patients lost-to-care in HIV clinics in Democratic Republic of Congo, Cameroon, and Burundi.

Antiretroviral therapy (ART)-naïve patients are vulnerable to becoming lost-to-care (LTC) because they are not monitored as often as patients on treatment. We examined data from 19,461 HIV positive adults at 10 HIV clinics in Democratic Republic of Congo (DRC), Cameroon, and Burundi participating in the Phase 1 International epidemiologic Databases to Evaluate AIDS Central Africa (IeDEA-CA) study. Patients were LTC if they were ART-naïve and did not return within 7 months of the end of data collection. Logistic regression was used to obtain odds ratios (ORs) and 95% confidence intervals (CIs) for risk factors associated with LTC. Of 5353 ART-naïve patients, 4420 (83%) were LTC and 933 (17%) were in-care. The odds of being LTC were greatest among patients from DRC (OR = 2.16, CI: 1.64-2.84, p < .0001), males (OR = 1.39, CI: 1.15-1.69, p = .0009), and ages 18-49 (OR = 1.45, CI: 1.16-1.82, p = .001). The odds of being LTC were least among patients with a WHO Clinical Stage of 1 or 2 (OR = 0.65, CI: 0.55-0.77, p < .0001) and in a perceived concordant relationship (OR = 0.61, CI: 0.43-0.87, p < .0001). LTC patients were more likely to have characteristics associated with higher risk for HIV transmission and progression. Many entered care at advanced stages and were less likely to know their partner's serostatus. Greater efforts to retain ART-naïve patients may increase earlier initiation of ART.

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.

Patient outcomes in Lubumbashi, Democratic Republic of Congo after a disruption in HIV care due to decreased global fund appropriations.

This study examines care seeking behaviors, clinical outcomes, and satisfaction with care of HIV-positive adults in Lubumbashi, DRC, one year after a disruption in care due to decreased global fund appropriations. We describe outcomes before and after the disruption. We compared characteristics of those who completed the survey and those who did not using the Wald F test. Most patients sought care after the disruption and continued antiretroviral therapy (ART), though use of cotrimoxizole prophylaxis declined. Though there was little change in WHO clinical stage at the new site of care, the majority of participants lost weight, adherence decreased, support group participation dropped, and satisfaction with care worsened. Patients were more likely to participate in the study if they were taking ART. This study highlights the importance of provider-patient communication during a transfer and the vulnerability of pre-ART patients to becoming lost to follow-up.

Preconception maternal nutrition: a multi-site randomized controlled trial.

BACKGROUND: Research directed to optimizing maternal nutrition commencing prior to conception remains very limited, despite suggestive evidence of its importance in addition to ensuring an optimal nutrition environment in the periconceptional period and throughout the first trimester of pregnancy. METHODS/STUDY DESIGN: This is an individually randomized controlled trial of the impact on birth length (primary outcome) of the time at which a maternal nutrition intervention is commenced: Arm 1: ≥ 3 mo preconception vs. Arm 2: 12-14 wk gestation vs. Arm 3: none.192 (derived from 480) randomized mothers and living offspring in each arm in each of four research sites (Guatemala, India, Pakistan, Democratic Republic of the Congo). The intervention is a daily 20 g lipid-based (118 kcal) multi-micronutient (MMN) supplement. Women randomized to receive this intervention with body mass index (BMI) <20 or whose gestational weight gain is low will receive an additional 300 kcal/d as a balanced energy-protein supplement. Researchers will visit homes biweekly to deliver intervention and monitor compliance, pregnancy status and morbidity; ensure prenatal and delivery care; and promote breast feeding. The primary outcome is birth length. Secondary outcomes include: fetal length at 12 and 34 wk; incidence of low birth weight (LBW); neonatal/infant anthropometry 0-6 mo of age; infectious disease morbidity; maternal, fetal, newborn, and infant epigenetics; maternal and infant nutritional status; maternal and infant microbiome; gut inflammatory biomarkers and bioactive and nutritive compounds in breast milk. The primary analysis will compare birth Length-for-Age Z-score (LAZ) among trial arms (independently for each site, estimated effect size: 0.35). Additional statistical analyses will examine the secondary outcomes and a pooled analysis of data from all sites. DISCUSSION: Positive results of this trial will support a paradigm shift in attention to nutrition of all females of child-bearing age. TRIAL REGISTRATION: ClinicalTrials.gov NCT01883193.

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.

A multicountry randomized controlled trial of comprehensive maternal nutrition supplementation initiated before conception: the Women First trial.

Background: Reported benefits of maternal nutrition supplements commenced during pregnancy in low-resource populations have typically been quite limited. Objectives: This study tested the effects on newborn size, especially length, of commencing nutrition supplements for women in low-resource populations ≥3 mo before conception (Arm 1), compared with the same supplement commenced late in the first trimester of pregnancy (Arm 2) or not at all (control Arm 3). Methods: Women First was a 3-arm individualized randomized controlled trial (RCT). The intervention was a lipid-based micronutrient supplement; a protein-energy supplement was also provided if maternal body mass index (kg/m2) was <20 or gestational weight gain was less than recommendations. Study sites were in rural locations of the Democratic Republic of the Congo (DRC), Guatemala, India, and Pakistan. The primary outcome was length-for-age z score (LAZ), with all anthropometry obtained <48 h post delivery. Because gestational ages were unavailable in DRC, outcomes were determined for all 4 sites from WHO newborn standards (non-gestational-age-adjusted, NGAA) as well as INTERGROWTH-21st fetal standards (3 sites, gestational age-adjusted, GAA). Results: A total of 7387 nonpregnant women were randomly assigned, yielding 2451 births with NGAA primary outcomes and 1465 with GAA outcomes. Mean LAZ and other outcomes did not differ between Arm 1 and Arm 2 using either NGAA or GAA. Mean LAZ (NGAA) for Arm 1 was greater than for Arm 3 (effect size: +0.19; 95% CI: 0.08, 0.30, P = 0.0008). For GAA outcomes, rates of stunting and small-for-gestational-age were lower in Arm 1 than in Arm 3 (RR: 0.69; 95% CI: 0.49, 0.98, P = 0.0361 and RR: 0.78; 95% CI: 0.70, 0.88, P < 0.001, respectively). Rates of preterm birth did not differ among arms. Conclusions: In low-resource populations, benefits on fetal growth-related birth outcomes were derived from nutrition supplements commenced before conception or late in the first trimester. This trial was registered at clinicaltrials.gov as NCT01883193.

HIV care and treatment clinic performance following President's Emergency Plan for AIDS Relief-funded infrastructure improvement in Tanzania.

Purpose: To assess how the infrastructure improvements supported by the US Centers for Disease Control and Prevention (CDC) and the United States President's Emergency Plan for AIDS Relief (PEPFAR) contributed to facility-level quarterly and annual new patient enrolment in HIV care and treatment and antiretroviral therapy (ART) uptake and retention in care. Methods: Aggregate quarterly and annual facility-based HIV care and treatment data from the CDC-managed PEPFAR Reporting Online and Management Information System database collected between 2005 and 2012 were analysed for the 11 rural and 32 urban facilities that met the eligibility criteria. Infrastructure improvements, including both renovations and new construction, occurred on different dates for the facilities; therefore, data were adjusted such that pre- and post-infrastructure improvements were aligned and date-time was ignored. The analysis calculated the mean (95% confidence interval) number of patients per facility who were (1) newly enrolled in HIV care, (2) patients initiated on ART, (3) patients retained in care, defined as alive and on ART, and (4) reasons for attrition, defined as transferred out, lost to follow-up, deceased or stopped ART. Results: The overall mean number of adult patients newly enrolled in HIV care clinics per quarter declined from 187.7 (151.4-223.9) to 135.2 (117.4-152.9) after infrastructure improvements but was not statistically significant (p = 0.20). However, the mean number of patients who were alive and remained on ART increased from 193.2 (145.3-241.1) to 273.2 (219.0-327.3) after improvements in both rural and urban facilities, although not significantly (p = 0.59). A similar picture was observed for overall paediatric enrolment and retention in care. Health facility-specific case studies show variations in new patient enrolment and retention in care between health facilities depending on the catchment area, population HIV prevalence and coverage of ART facilities. Regarding attrition, the mean number of adult patients lost to follow-up changed from 76.6 (20.8-132.3) to 139.4 (79.6-199.1) (p = 0.65) among rural facilities, while the mean number of children lost to follow-up increased significantly from 3.4 (0.5-6.3) to 8.7 (5.0-12.3) (p = 0.02) after improvements. Conclusion: Patient retention in care improved in HIV care and treatment facilities with infrastructure improvements. However, the overall number of patients newly enrolled and initiated on ART declined and attrition increased in facilities after improvements.

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.