Benchmark assessment of orphaned and vulnerable children in areas of the Zambia Family (ZAMFAM) Project

The US Agency for International Development and US President’s Emergency Plan for AIDS Relief (PEPFAR) are supporting the Zambia Family (ZAMFAM) project to strengthen comprehensive, integrated service delivery and support to children living with, affected by, or vulnerable to HIV/AIDS (OVC) in the Lusaka, Copperbelt, Southern, and Central Provinces of Zambia. To inform that effort, Project SOAR conducted a benchmark survey among beneficiaries in the four provinces of the ZAMFAM program. The benchmark survey measured the status and conditions of OVC and their families. The findings provide a deeper understanding of the needs of OVC families and the gaps in service provision, as well as suggestions for strengthening care and support strategies for OVC in Zambia

Evaluation of ROTARIX® Booster Dose Vaccination at 9 Months for Safety and Enhanced Anti-Rotavirus Immunity in Zambian Children: A Randomised Controlled Trial

Oral rotavirus vaccines show diminished immunogenicity in low-resource settings where rotavirus burden is highest. This study assessed the safety and immune boosting effect of a third dose of oral ROTARIX® (GlaxoSmithKline) vaccine administered at 9 months of age. A total of 214 infants aged 6 to 12 weeks were randomised to receive two doses of ROTARIX® as per standard schedule with other routine vaccinations or an additional third dose of ROTARIX® administered at 9 months old concomitantly with measles/rubella vaccination. Plasma collected pre-vaccination, 1 month after first- and second-dose vaccination, at 9 months old before receipt of third ROTARIX® dose and/or measles/rubella vaccination, and at 12 months old were assayed for rotavirus-specific IgA (RV-IgA). Geometric mean RV-IgA at 12 months of age and the incidence of clinical adverse events 1 month following administration of the third dose of ROTARIX® among infants in the intervention arm were compared between infants in the two arms. We found no significant difference in RV-IgA titres at 12 months between the two arms. Our findings showed that rotavirus vaccines are immunogenic in Zambian infants but with modest vaccine seroconversion rates in low-income settings. Importantly, however, a third dose of oral ROTARIX® vaccine was shown to be safe when administered concomitantly with measles/rubella vaccine at 9 months of age in Zambia. This speaks to opportunities for enhancing rotavirus vaccine immunity within feasible schedules in the national immunization program

Comparable exposure to SARS-CoV-2 in young children and healthcare workers in Zambia

Background: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an ongoing global health crisis that has caused large scale morbidity and mortality. We aimed to determine the exposure to SARS-CoV-2 among young children and healthcare workers by measurement of anti-S1 antigen (spike protein) specific immunoglobulin G (IgG) using an in-house optimized indirect enzyme-linked immunosorbent assay (ELISA) method. Methods: Plasma samples were collected from cohorts of healthcare workers (n = 287) and young children aged from 6 weeks to 2 years old (n = 150) pre-COVID-19 pandemic between September 2018 and November 2019 and post-COVID-19 pandemic between August and December 2020 were simultaneously tested for anti-SARS-CoV-2 S1 specific IgG. The arithmetic mean of natural logarithm-transformed ELISA relative absorbance reading + (3 x standard deviation) of pre-pandemic plasma was used as the cut-off to determine SARS-CoV-2 IgG seropositivity of post-pandemic plasma, Results: There was no reactivity to SARS-CoV-2 S1 antigen detected in pre-pandemic plasma but in post pandemic plasma an 8.0% (23/287) IgG seropositivity in healthcare workers’ and 6.0% (9/150) seropositivity in children aged 2 years old was detected. Conclusions: Comparable levels of SARS-CoV-2 IgG seropositivity in healthcare workers and children suggest widespread exposure to SARS-CoV-2 in Zambia during the first wave of the pandemic. This finding has implications for continued acquisition and transmission of infection in the healthcare setting, household, and wider community

Zambia Family (ZAMFAM) cohort study

To evaluate delivery of integrated psychosocial, economic strengthening, and clinical services to HIV-affected households through the Zambia Family (ZAMFAM) Project, a prospective cohort study compared socio-economic, psychosocial, and health outcomes among ZAMFAM beneficiaries with non-beneficiaries. In July to October 2017, 544 adolescents living with HIV (ALHIV) aged 5–17 years and their adult caregivers were recruited from Central (ZAMFAM implementation sites) and Eastern (non-intervention sites) Provinces. Structured interviews at baseline and one-year follow-up assessed household characteristics, socio-economic wellbeing, health service utilization, and HIV treatment outcomes

Depression-mediating pathways from household adversity to antiretroviral therapy nonadherence among children and adolescents living with HIV in Zambia: A structural equation modeling approach

Background: In Zambia, half of children and adolescents living with HIV (CALWH) on antiretroviral therapy (ART) are virologically unsuppressed. Depressive symptoms are associated with ART nonadherence but have received insufficient attention as mediating factors in the relationship between HIV self-management and household-level adversities. We aimed to quantify theorized pathways from indicators of household adversity to ART adherence, partially mediated by depressive symptoms, among CALWH in 2 Zambian provinces. Setting: In July-September 2017, we enrolled 544 CALWH aged 5-17 years and their adult caregivers into a year-long prospective cohort study. Methods: At baseline, CALWH-caregiver dyads completed an interviewer-administered questionnaire, which included validated measures of recent (past 6 months) depressive symptomatology and self-reported past-month ART adherence (never versus sometimes or often missing medication doses). We used structural equation modeling with theta parameterization to identify statistically significant (P \u3c 0.05) pathways from household adversities (past-month food insecurity and caregiver self-reported health) to depression (modeled latently), ART adherence, and poor physical health in the past 2 weeks. Results: Most CALWH (mean age: 11 years, 59% female) exhibited depressive symptomatology (81%). In our structural equation model, food insecurity significantly predicted elevated depressive symptomatology (ß = 0.128), which was associated inversely with daily ART adherence (ß = -0.249) and positively with poor physical health (ß = 0.359). Neither food insecurity nor poor caregiver health was directly associated with ART nonadherence or poor physical health. Conclusions: Using structural equation modeling, we found that depressive symptomatology fully mediated the relationship between food insecurity, ART nonadherence, and poor health among CALWH

Integrated psychosocial, economic strengthening, and clinical service-delivery to improve health and resilience of adolescents living with HIV and their caregivers: Findings from a prospective cohort study in Zambia

Background: Children and youth are profoundly impacted groups in Zambia’s HIV epidemic. To evaluate delivery of integrated psychosocial, economic strengthening, and clinical services to HIV-affected households through the Zambia Family (ZAMFAM) Project, a prospective cohort study compared socio-economic, psychosocial, and health outcomes among ZAMFAM beneficiaries to non-beneficiaries. Methods: In July–October 2017, 544 adolescents living with HIV (ALHIV) aged 5–17 years and their adult caregivers were recruited from Central (ZAMFAM implementation sites) and Eastern (non-intervention sites) Provinces. Structured interviews at baseline and one-year follow-up assessed household characteristics, socio-economic wellbeing, and health service utilization. Poisson regression with generalized estimating equations measured one-year changes in key health and socio-economic indicators, comparing ZAMFAM beneficiaries to non-beneficiaries. Results: Overall, 494 households completed two rounds of assessment (retention rate: 91%) Among ALHIV, improvements in current antiretroviral therapy use over time (Adjusted Prevalence Rate Ratio [aPRR] = 1.06, 95% Confidence Interval [95% CI]: 1.01–1.11) and reductions in non-household labor (aPRR = 0.44, 95% CI: 0.20–0.99) were significantly larger among ZAMFAM beneficiaries than non-beneficiaries. For caregivers, receiving ZAMFAM services was associated with significant reductions in HIV-related stigma (aPRR = 0.49, 95% CI: 0.28–0.88) and perceived negative community attitudes towards HIV (aPRR = 0.77, 95% CI: 0.62–0.96). Improvements in caregiver capacity to pay for unexpected (aPRR = 1.54, 95% CI: 1.17–2.04) and food-related expenses (aPRR = 1.48, 95% CI: 1.16–1.90), as well as shared decision-making authority in household spending (aPRR = 1.41, 95% CI: 1.04–1.93) and self-reported good or very good health status (aPRR = 1.46, 95% CI: 1.14–1.87), were also significantly larger among ZAMFAM beneficiaries. Conclusions: Significant improvements in caregivers’ financial capacity were observed among households receiving ZAMFAM services, with few changes in health or wellbeing among ALHIV. Integrated service-delivery approaches like ZAMFAM may yield observable socio-economic improvements in the short-term. Strengthening community-based delivery of psychosocial and health support to ALHIV is encouraged

Sexual debut and risk behaviors among orphaned and vulnerable children in Zambia: Which protective deficits shape HIV risk?

Orphaned and vulnerable children (OVC) are not only affected by, but also rendered at-risk of, HIV due to overlapping deficits in protective assets, from school to household financial security. Drawing from a protective deficit framework, this study examines correlates of sexual risk—including multiple sexual partnerships, unprotected sex, and age at sexual debut—among OVC aged 13–17 years in Zambia. In May-October 2016, a two-stage stratified random sampling design was used to recruit OVC and their adult caregivers (N = 2,034) in four provinces. OVC-caregiver dyads completed a structured interview addressing household characteristics, protective assets (i.e. finances, schooling, and nutrition), and general health and wellbeing. Associations of factors derived from the multi-component protective deficits framework were examined using multivariable ordered logistic regression, comparing sexually inexperienced OVC to those with a sexual debut and reporting ≥ 1 sexual behavior(s). A sub-analysis of older (ages 15–17) OVC identified correlates of early (before age 15) and later (at or after age 15) sexual debut using multinomial logistic regression. Among 735 OVC aged 13–17, 14% reported a sexual debut, among whom 14% and 22% reported 2+ past-year partners and non-condom last sex, respectively. Older age (Adjusted Odds Ratio [aOR] = 2.08, 95% Confidence Interval [CI] 1.32–3.27), male sex (aOR = 1.90, CI 1.22–2.96), not having a birth certificate (aOR = 2.05, CI 1.03–4.09), out-of-school status (aOR = 2.63, CI 1.66–4.16), and non-household labor (aOR = 1.84, CI 1.01–3.38) were significantly associated with higher sexual risk. Male sex was the only factor significantly associated with early sexual debut in multivariable analysis. Sexual risk-reduction strategies require age- and sex-specific differentiation and should be prioritized for OVC in financially distressed households

Sexual and reproductive health knowledge, attitudes and service uptake barriers among Zambian in-school adolescents: A mixed methods study

The provision of comprehensive sexuality education (CSE) accords opportunities for scientifically accurate information about sexual and reproductive health (SRH). We used a mixed-methods study to characterise adolescent SRH knowledge, attitudes and service utilisation experiences in the context of CSE implementation in Zambia. In-school young people aged 12–24 years (N = 1,612) in the North-Western Province were randomly surveyed. A 29-item index was constructed to measure alignment of knowledge, attitudes and values (KAV) with the CSE curriculum. Logistic regression, stratifying by sexual debut status, modelled associations of past-year HIV counselling and testing and family planning service access, respectively, with CSE-KAV index scores. Focus group discussions further explored perceptions of and experiences accessing SRH services. Despite moderate SRH knowledge and acceptability of SRH services, fewer than half of sexually experienced young people reported accessing SRH services. Among sexually experienced youth, neither HIV testing nor family planning service utilisation in the previous year were associated with higher CSE-KAV index scores. Salient barriers to SRH service uptake included limited perceived benefits, unsupportive household and community environments, and negative interactions with health providers. To increase accessibility and uptake of youth SRH services, linking school-based CSE to SRH services is recommended

Impact of antibiotics on gut microbiome composition and resistome in the first years of life in low- to middle-income countries: A systematic review.

BackgroundInappropriate antimicrobial usage is a key driver of antimicrobial resistance (AMR). Low- and middle-income countries (LMICs) are disproportionately burdened by AMR and young children are especially vulnerable to infections with AMR-bearing pathogens. The impact of antibiotics on the microbiome, selection, persistence, and horizontal spread of AMR genes is insufficiently characterized and understood in children in LMICs. This systematic review aims to collate and evaluate the available literature describing the impact of antibiotics on the infant gut microbiome and resistome in LMICs.Methods and findingsIn this systematic review, we searched the online databases MEDLINE (1946 to 28 January 2023), EMBASE (1947 to 28 January 2023), SCOPUS (1945 to 29 January 2023), WHO Global Index Medicus (searched up to 29 January 2023), and SciELO (searched up to 29 January 2023). A total of 4,369 articles were retrieved across the databases. Duplicates were removed resulting in 2,748 unique articles. Screening by title and abstract excluded 2,666 articles, 92 articles were assessed based on the full text, and 10 studies met the eligibility criteria that included human studies conducted in LMICs among children below the age of 2 that reported gut microbiome composition and/or resistome composition (AMR genes) following antibiotic usage. The included studies were all randomized control trials (RCTs) and were assessed for risk of bias using the Cochrane risk-of-bias for randomized studies tool. Overall, antibiotics reduced gut microbiome diversity and increased antibiotic-specific resistance gene abundance in antibiotic treatment groups as compared to the placebo. The most widely tested antibiotic was azithromycin that decreased the diversity of the gut microbiome and significantly increased macrolide resistance as early as 5 days posttreatment. A major limitation of this study was paucity of available studies that cover this subject area. Specifically, the range of antibiotics assessed did not include the most commonly used antibiotics in LMIC populations.ConclusionIn this study, we observed that antibiotics significantly reduce the diversity and alter the composition of the infant gut microbiome in LMICs, while concomitantly selecting for resistance genes whose persistence can last for months following treatment. Considerable heterogeneity in study methodology, timing and duration of sampling, and sequencing methodology in currently available research limit insights into antibiotic impacts on the microbiome and resistome in children in LMICs. More research is urgently needed to fill this gap in order to better understand whether antibiotic-driven reductions in microbiome diversity and selection of AMR genes place LMIC children at risk for adverse health outcomes, including infections with AMR-bearing pathogens

Maternal and Infant Histo-Blood Group Antigen (HBGA) Profiles and Their Influence on Oral Rotavirus Vaccine (Rotarix^TM) Immunogenicity among Infants in Zambia

Live-attenuated, oral rotavirus vaccines have significantly reduced rotavirus-associated diarrhoea morbidity and infant mortality. However, vaccine immunogenicity is diminished in low-income countries. We investigated whether maternal and infant intrinsic susceptibility to rotavirus infection via histo-blood group antigen (HBGA) profiles influenced rotavirus (ROTARIX®) vaccine-induced responses in Zambia. We studied 135 mother–infant pairs under a rotavirus vaccine clinical trial, with infants aged 6 to 12 weeks at pre-vaccination up to 12 months old. We determined maternal and infant ABO/H, Lewis, and secretor HBGA phenotypes, and infant FUT2 HBGA genotypes. Vaccine immunogenicity was measured as anti-rotavirus IgA antibody titres. Overall, 34 (31.3%) children were seroconverted at 14 weeks, and no statistically significant difference in seroconversion was observed across the various HBGA profiles in early infant life. We also observed a statistically significant difference in rotavirus-IgA titres across infant HBGA profiles at 12 months, though no statistically significant difference was observed between the study arms. There was no association between maternal HBGA profiles and infant vaccine immunogenicity. Overall, infant HBGAs were associated with RV vaccine immunogenicity at 12 months as opposed to in early infant life. Further investigation into the low efficacy of ROTARIX® and appropriate intervention is key to unlocking the full vaccine benefits for U5 children