Hepatitis B Virus Prevalence and Transmission in the Households of Pregnant Women in Kinshasa, Democratic Republic of Congo.

Background: The World Health Organization Africa region has high regional hepatitis B virus (HBV) prevalence, and evidence suggests more frequent horizontal HBV transmission than other regions. Context-specific epidemiological studies are needed to inform additional HBV prevention measures. Methods: In the cross-sectional Horizontal and Vertical Transmission of Hepatitis B (HOVER-HBV) study, we introduced HBV surface antigen (HBsAg) screening alongside existing HIV screening as part of routine antenatal care in high-volume maternity clinics in Kinshasa, Democratic Republic of Congo. We recruited households of pregnant women ("index mothers") who were HBsAg-positive and HBsAg-negative, defining households as index-positive and index-negative, respectively. Household members underwent HBsAg testing and an epidemiological survey. We evaluated HBsAg prevalence and potential transmission correlates. Results: We enrolled 1006 participants from 200 households (100 index-positive, 100 index-negative) across Kinshasa. HBsAg-positivity prevalence was more than twice as high in index-positive households (5.0% [95% confidence interval {CI}, 2.8%-7.1%]) as in index-negative households (1.9% [95% CI, .6%-3.2%]). HBsAg-positivity prevalence was 3.3 (95% CI, .9-11.8) times as high among direct offspring in index-positive versus index-negative households. Factors associated with HBsAg positivity included older age, marriage, and having multiple recent partners or any new sexual partners among index mothers; and older age, lower household wealth, sharing nail clippers, and using street salons among offspring in index-positive households. Conclusions: Vertical and horizontal HBV transmission within households is ongoing in Kinshasa. Factors associated with infection reveal opportunities for HBV prevention efforts, including perinatal prevention, protection during sexual contact, and sanitation of shared personal items.

Changes in hepatitis B vaccine perception in response to the COVID-19 pandemic: Development of the Shift in vaccine confidence (SVC) survey tool.

The COVID-19 pandemic has disrupted access to, adherence to, and perceptions of routine vaccinations. We developed the Shift in Vaccine Confidence (SVC) survey tool to assess the impact of the pandemic on routine vaccinations, with a focus on the HBV vaccine, in Kinshasa, Democratic Republic of Congo (DRC). This study describes the content validation steps we conducted to ensure the survey tool is meaningful to measure changes in vaccine confidence to regular immunization (HBV vaccine) due to the pandemic. Three rounds of stakeholder feedback from a DRC-based study team, content and measurement experts, and study participants allowed us to produce a measure with improved readability and clarity.

Participant perspectives to improve tenofovir adherence in the prevention of mother-to-child transmission of hepatitis B virus in Kinshasa, DRC.

Prevention of mother-to-child transmission (PMTCT) programs for hepatitis B virus (HBV) are critical to reach the World Health Organization's 2030 HBV elimination goals. Despite demonstrated feasibility utilizing HIV infrastructure, HBV PMTCT programs are not implemented in many African settings, including in the Democratic Republic of Congo (DRC). In a previous pilot of HBV PMTCT implementation in DRC's capital, Kinshasa, we observed low TDF metabolite levels at delivery among women with high-risk HBV who were given tenofovir disoproxil fumarate (TDF) antiviral therapy. As such, we conducted qualitative interviews with women who received TDF to understand facilitators and barriers of medication adherence. We used a modified Information-Motivation-Behavioral Skills model (IMB+) as a framework for thematic content analysis. We found that trust in healthcare workers, familial support, and improved awareness of the disease and treatment options were important facilitators of TDF adherence; pill size, social stigma, and low HBV knowledge were barriers to adherence. While overall acceptance of TDF was high in this pilot, improved TDF adherence is needed in order to reach efficacious levels for preventing transmission from mothers to newborns. We suggest ongoing HBV sensitization within existing maternity and HIV care infrastructure would address gaps in knowledge and stigma identified here. Additionally, given the trust women have towards maternity center staff and volunteers, scaled HBV PMTCT interventions should include specific sensitization and education for healthcare affiliates, who currently receive no HBV prevention or information in DRC. This study is timely as TDF, particularly future long-acting formulations, could be considered as an alternate rather than adjuvant to birth-dose vaccination for HBV PMTCT in sub-Saharan Africa.

Association between domesticated animal ownership and Plasmodium falciparum parasite prevalence in the Democratic Republic of the Congo: a national cross-sectional study.

BACKGROUND: Domesticated animal ownership is an understudied aspect of the human environment that influences mosquito biting behaviour and malaria transmission, and is a key part of national economies and livelihoods in malaria-endemic regions. In this study, we aimed to understand differences in Plasmodium falciparum prevalence by ownership status of common domesticated animals in DR Congo, where 12% of the world's malaria cases occur and anthropophilic Anopheles gambiae vectors predominate. METHODS: In this cross-sectional study, we used survey data from individuals aged 15-59 years in the most recent (2013-14) DR Congo Demographic and Health Survey and previously performed Plasmodium quantitative real-time PCR (qPCR) to estimate P falciparum prevalence differences by household ownership of cattle; chickens; donkeys, horses, or mules; ducks; goats; sheep; and pigs. We used directed acyclic graphs to consider confounding by age, gender, wealth, modern housing, treated bednet use, agricultural land ownership, province, and rural location. FINDINGS: Of 17 701 participants who had qPCR results and covariate data, 8917 (50·4%) of whom owned a domesticated animal, we observed large differences in malaria prevalence across types of animals owned in both crude and adjusted models. Household chicken ownership was associated with 3·9 (95% CI 0·6 to 7·1) more P falciparum infections per 100 people, whereas cattle ownership was associated with 9·6 (-15·8 to -3·5) fewer P falciparum infections per 100 people, even after accounting for bednet use, wealth, and housing structure. INTERPRETATION: Our finding of a protective association conferred by cattle ownership suggests that zooprophylaxis interventions might have a role in DR Congo, possibly by drawing An gambiae feeding away from humans. Studies of animal husbandry practices and associated mosquito behaviours could reveal opportunities for new malaria interventions. FUNDING: The National Institutes of Health and the Bill & Melinda Gates Foundation. TRANSLATIONS: For the French and Lingala translations of the abstract see Supplementary Materials section.

Hepatitis B virus prevalence and transmission in the households of pregnant women in Kinshasa, Democratic Republic of Congo.

Background: Despite routine infant vaccination and blood donor screening, the Democratic Republic of Congo (DRC) has high hepatitis B virus (HBV) prevalence compared to the United States and Europe. Through the cross-sectional Horizontal and Vertical Transmission of Hepatitis B (HOVER-HBV) study, we characterized household prevalence in DRC's capital, Kinshasa, to inform additional prevention efforts. Methods: We introduced HBV surface antigen (HBsAg) screening alongside existing HIV screening as part of routine antenatal care (ANC) in high-volume maternity clinics in Kinshasa. We recruited households of pregnant women who were HBsAg-positive and HBsAg-negative, defining households as "exposed" and "unexposed," respectively. Household members underwent HBsAg testing and an epidemiological survey. We evaluated HBsAg prevalence and potential transmission correlates. Results: We enrolled 1,006 participants from 200 households (100 exposed, 100 unexposed) across Kinshasa. HBsAg prevalence was more than twice as high in exposed households (5.0%; 95% CI: 2.8%-7.1%) as in unexposed households (1.9%; 0.6%-3.2%). Exposed direct offspring had 3.3 (0.9, 11.8) times the prevalence of unexposed direct offspring. Factors associated with HBsAg-positivity included older age, marriage, and having multiple recent partners or any new sexual partners among index mothers; and older age, lower household wealth, sharing nail clippers, and using street salons among exposed offspring. Conclusions: Vertical and horizontal HBV transmission within households is ongoing in Kinshasa. Factors associated with infection reveal opportunities for HBV prevention efforts, including perinatal prevention, protection during sexual contact, and sanitation of shared personal items.

Attributes of drinking water, sanitation, and hygiene associated with microbiological water quality of stored drinking water in rural schools in Mozambique and Uganda.

Contaminated drinking water causes morbidity and mortality worldwide, especially in low- and middle-income countries. Drinking water quality has been studied extensively in household settings, but little research is available on drinking water quality in schools. School settings are of particular importance, because children are more susceptible than adults to a variety of diseases from contaminated drinking water. Many school water, sanitation and hygiene (WaSH) interventions have been studied for their efficacy to reduce diarrheal disease incidence, but few have evaluated drinking water quality, which reflects an important exposure pathway between WaSH services and health outcomes. Using school surveys developed from internationally established WaSH indicators and field microbiological water quality tests, we studied 374 rural schools in Mozambique and Uganda to understand the association between specific WaSH services and drinking water microbiological contamination, specifically testing most probable number (MPN) of Escherichia coli, an indicator of fecal contamination, per 100 mL. In Mozambique and Uganda, 71% and 83% respectively of rural schools had low risk drinking water quality (<1 E. coli/100 mL); thirteen percent and seven percent had very high-risk water quality (≥100 E. coli/100 mL). When accounting for all WaSH services studied, schools that used an improved-type water source had 0.22 times less E. coli in stored drinking water in Mozambique (95% CI: 0.07, 0.65) and 0.12 times less E. coli in Uganda (95% CI: 0.02, 0.80). In Mozambique, use of a water source within 30 minutes for travel and collection and the presence of water and soap/ash for handwashing were also significantly associated with less E. coli in drinking water. The findings of this study provide public health practitioners with implementable WaSH services to improve school drinking water quality, which has implications for the health, learning environment, and cognitive development of school children in rural Mozambique and Uganda.

Rapid analysis of local data to inform off-label tocilizumab use early in the COVID-19 pandemic.

The interleukin-6 receptor antagonist tocilizumab became widely used early in the coronavirus disease 2019 (COVID-19) pandemic based on small observational studies that suggested clinical benefit in COVID-19 patients with a hyperinflammatory state. To inform our local treatment algorithms in the absence of randomized clinical trial results, we performed a rapid analysis of the first 11 hospitalized COVID-19 patients treated with tocilizumab at our academic medical center. We report their early clinical outcomes and describe the process by which we assembled a team of diverse trainees and stakeholders to extract, analyze, and disseminate data during a time of clinical uncertainty.

Arresting vertical transmission of hepatitis B virus (AVERT-HBV) in pregnant women and their neonates in the Democratic Republic of the Congo: a feasibility study.

BACKGROUND: Hepatitis B virus (HBV) remains endemic throughout sub-Saharan Africa despite the widespread availability of effective childhood vaccines. In the Democratic Republic of the Congo, HBV treatment and birth-dose vaccination programmes are not established. We, therefore, aimed to evaluate the feasibility and acceptability of adding HBV testing and treatment of pregnant women as well as the birth-dose vaccination of HBV-exposed infants to the HIV prevention of mother-to-child transmission programme infrastructure in the Democratic Republic of the Congo. METHODS: We did a feasibility study in two maternity centres in Kinshasa: Binza and Kingasani. Using the already established HIV prevention of mother-to-child transmission programme at these two maternity centres, we screened pregnant women for HBV infection at routine prenatal care registration. Those who tested positive and had a gestational age of 24 weeks or less were included in this study. Eligible pregnant women with a high viral load (≥200 000 IU/mL or HBeAg positivity, or both) were considered as having HBV of high risk of mother-to-child transmission and initiated on oral tenofovir disoproxil fumarate (300 mg/day) between 28 weeks and 32 weeks of gestation and continued through 12 weeks post partum. All HBV-exposed infants received a birth-dose of monovalent HBV vaccine (Euvax-B Pediatric: Sanofi Pasteur, Seoul, South Korea; 0·5 mL) within 24 h of life. All women were followed up for 24 weeks post partum, when they completed an exit questionnaire that assessed the acceptability of study procedures. The primary outcomes were the feasibility of screening pregnant women to identify those at high risk for HBV mother-to-child transmission and to provide them with antiviral prophylaxis, the feasibility of administrating the birth-dose vaccine to exposed infants, and the acceptability of this prevention programme. This study is registered with ClinicalTrials.gov, NCT03567382. FINDINGS: Between Sept 24, 2018, and Feb 22, 2019, 4016 women were approached and screened. Of these pregnant women, 109 (2·7%) were positive for HBsAg. Of the 109 women, 91 (83%) met the eligibility criteria for participation. However, only data from 90 women-excluding one woman who had a false pregnancy-were included in the study analysis. The median overall age of the enrolled women was 31 years (IQR 25-34) and the median overall gestational age was 19 weeks (15-22). Ten (11%) of 91 women evaluated had high-risk HBV infection. Nine (90%) of the ten pregnant women with high-risk HBV infection received tenofovir disoproxil fumarate and one (10%) refused therapy and withdrew from the study; five (56%) of the nine women achieved viral suppression (ie, <200 000 IU/mL) on tenofovir disoproxil fumarate therapy by the time of delivery and the remaining four (44%) had decreased viral loads from enrolment to delivery. A total of 88 infants were born to the 90 enrolled women. Of the 88 infants, 60 (68%) received a birth-dose vaccine; of these, 46 (77%) received a timely birth-dose vaccine. No cases of HBV mother-to-child transmission were observed. No serious adverse events associated with tenofovir disoproxil fumarate nor with the birth-dose vaccine were reported. Only one (11%) of nine women reported dizziness during the course of tenofovir disoproxil fumarate therapy. The study procedures were considered highly acceptable (>80%) among mothers. INTERPRETATION: Adding HBV screening and treatment of pregnant women and infant birth-dose vaccination to existing HIV prevention of mother-to-child transmission platforms is feasible in countries such as the Democratic Republic of the Congo. Birth-dose vaccination against HBV infection integrated within the current Expanded Programme on Immunisation and HIV prevention of mother-to-child transmission programme could accelerate progress toward HBV elimination in Africa. FUNDING: Gillings Innovation Laboratory award and the National Institutes of Health. TRANSLATIONS: For the French and Lingala translations of the abstract see Supplementary Materials section.

Analysis of false-negative rapid diagnostic tests for symptomatic malaria in the Democratic Republic of the Congo.

The majority of Plasmodium falciparum malaria diagnoses in Africa are made using rapid diagnostic tests (RDTs) that detect histidine-rich protein 2. Increasing reports of false-negative RDT results due to parasites with deletions of the pfhrp2 and/or pfhrp3 genes (pfhrp2/3) raise concern about existing malaria diagnostic strategies. We previously identified pfhrp2-negative parasites among asymptomatic children in the Democratic Republic of the Congo (DRC), but their impact on diagnosis of symptomatic malaria is unknown. We performed a cross-sectional study of false-negative RDTs in symptomatic subjects in 2017. Parasites were characterized by microscopy; RDT; pfhrp2/3 genotyping and species-specific PCR assays; a bead-based immunoassay for Plasmodium antigens; and/or whole-genome sequencing. Among 3627 symptomatic subjects, 427 (11.8%) had RDT-/microscopy + results. Parasites from eight (0.2%) samples were initially classified as putative pfhrp2/3 deletions by PCR, but antigen testing and whole-genome sequencing confirmed the presence of intact genes. 56.8% of subjects had PCR-confirmed malaria. Non-falciparum co-infection with P. falciparum was common (13.2%). Agreement between PCR and HRP2-based RDTs was satisfactory (Cohen's kappa = 0.66) and superior to microscopy (0.33). Symptomatic malaria due to pfhrp2/3-deleted P. falciparum was not observed. Ongoing HRP2-based RDT use is appropriate for the detection of falciparum malaria in the DRC.