Neonatal BCG Vaccination for Prevention of Allergy in Infants: The MIS BAIR Randomised Controlled Trial.

BACKGROUND: The beneficial off-target effects of Bacille Calmette-Guérin (BCG) vaccination potentially include protection against allergy. OBJECTIVE: In the MIS BAIR trial, we aimed to determine whether neonatal BCG vaccination reduces atopic sensitisation and clinical food allergy in infants. METHODS: In this randomised controlled trial, 1272 neonates were allocated to BCG-Denmark vaccine (0.05 mL intradermal dose) or no BCG at birth. Randomisation was stratified by recruitment site, mode of delivery and plurality of birth. The primary outcome was the incidence of atopic sensitisation determined by skin prick test at 1 year of age. Food allergy was determined by 3-monthly online questionnaires and oral food challenges. Data were analysed by intention-to-treat using binary regression. CLINICALTRIALS: gov (NCT01906853). RESULTS: Atopic sensitisation during the first year of life was 22.9% among infants in the BCG group and 18.9% in the control group (adjusted risk difference (aRD) 3.8% (95% CI -1.5 to 9.1) after multiple imputation). Clinical food allergy was similar between infants in the BCG and control groups (9.8% vs. 9.6%; aRD 0.2, 95% CI -3.4 to 3.8). An interaction was observed between the primary outcome and maternal history of BCG vaccination. No interaction was observed for the additional prespecified potential effect modifiers tested (sex, delivery mode, family history of any allergy, season of birth, hepatitis B vaccination at randomisation, BCG scar and age at BCG administration). CONCLUSIONS AND CLINICAL RELEVANCE: Neonatal BCG-Denmark vaccination does not protect against atopic sensitisation or clinical food allergy in the first year of life.

Prevalence of sexually transmitted infection in pregnancy and their association with adverse birth outcomes: a case-control study at Queen Elizabeth Central Hospital, Blantyre, Malawi.

BACKGROUND: There are limited data on the epidemiology of sexually transmitted infections (STI) and their contribution to adverse birth outcomes (ABO) in sub-Saharan Africa (SSA). We performed a case-control study to assess the prevalence of STI and their association with ABO among women attending Queen Elizabeth Central Hospital, Blantyre, Malawi. METHODS: A composite case definition for ABO included stillborn, preterm and low birthweight infants and infants admitted to neonatal intensive care unit within 24 hours of birth. Following recruitment of an infant with an ABO, the next born healthy infant was recruited as a control. Multiplex PCR for Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT) and Trichomonas vaginalis (TV) was performed on maternal vaginal swabs. HIV and syphilis status was determined on maternal and infant serum. For syphilis, we used combined treponemal/non-treponemal rapid point-of-care tests in parallel with rapid plasma reagin tests, PCR for Treponema pallidum and clinical parameters to diagnose and stage the infection. We compared STI positivity between cases and controls. RESULTS: We included 259 cases and 251 controls. Maternal prevalence of STI was 3.1%, 2.7% and 17.1% for NG, CT and TV, respectively. Maternal prevalence of untreated syphilis was 2.0% and 6.1% for early stage and late/unknown stage, respectively; prevalence of treated syphilis was 2.7%. The HIV prevalence was 16.5%. HIV infection significantly increased the odds for ABO (OR=3.31; 95% CI 1.10 to 9.91) as did NG positivity (OR=4.30; 95% CI 1.16 to 15.99). We observed higher rates of ABO among women with untreated maternal syphilis (early: OR=7.13; 95% CI 0.87 to 58.39, late/unknown stage: OR=1.43; 95% CI 0.65 to 3.15). Maternal TV and CT infections were not associated with ABO. CONCLUSION: STI prevalence among pregnant women in Malawi is comparable to other SSA countries. HIV, NG and untreated syphilis prevalence was higher among women with ABO compared with women with healthy infants.

Syphilis Prevalence Among People Living With and Without HIV in Sub-Saharan Africa: A Systematic Review and Meta-Analysis.

BACKGROUND: Syphilis is a curable sexually transmitted infection that, untreated, is associated with significant morbidity and mortality. In people living with HIV (PLWH), syphilis carries greater risks of disease progression. We estimated syphilis prevalence among PLWH in the general population in sub-Saharan Africa and compared the prevalence among PLWH and without HIV. METHODS: We searched for studies published January 1, 2011, to March 28, 2022, reporting syphilis prevalence among PLWH in sub-Saharan Africa (PROSPERO No. CRD42020167328). We excluded studies in high-risk subpopulations. We estimated pooled syphilis prevalence among PLWH using random-effects modeling and compared the prevalence with people without HIV when included in the same study. We examined influences of region, study setting, and test type in subgroup analyses. RESULTS: We identified 926 studies; 53 were included in the meta-analysis. Pooled syphilis prevalence among PLWH was 7.3% (95% confidence interval [CI], 6.3%-8.5%). Prevalence differed by region: 3.1% (95% CI, 2.2%-4.0%) in Southern, 5.5% (95% CI, 2.3%-9.3%) in West/Central, and 10.5% (95% CI, 8.0%-13.1%) in Eastern Africa. Prevalence also differed by study setting: 13.8% (95% CI, 5.7%-23.0%) in sexual and reproductive health/sexually transmitted infection care, 8.7% (95% CI, 5.0%-12.8%) in HIV care, 7.1% (95% CI, 5.8%-8.5%) in antenatal care, and 3.8% (95% CI, 2.0%-5.8%) in household/community-based settings. Syphilis prevalence was higher among PLWH than without HIV (relative risk, 3.5; 95% CI, 2.8-4.5). CONCLUSIONS: Syphilis is highly prevalent among PLWH in sub-Saharan Africa and is more common among PLWH than without HIV. Integration of syphilis screening and management into HIV care may reduce complications of HIV-syphilis coinfection among PLWH in sub-Saharan Africa.

Long-term outcomes after severe childhood malnutrition in adolescents in Malawi (LOSCM): a prospective observational cohort study.

BACKGROUND: Research on long-term outcomes of severe childhood malnutrition is scarce. Existing evidence suggests potential associations with cardiometabolic disease and impaired cognition. We aimed to assess outcomes in adolescents who were exposed to severe childhood malnutrition compared with peers not exposed to severe childhood malnutrition. METHODS: In Long-term Outcomes after Severe Childhood Malnutrition (LOCSM), we followed up adolescents who had 15 years earlier received treatment for severe childhood malnutrition at Queen Elizabeth Central Hospital in Blantyre, Malawi. Adolescents with previous severe childhood malnutrition included in LOCSM had participated in an earlier follow-up study (ChroSAM) at 7 years after treatment for severe childhood malnutrition, where they were compared to siblings and age-matched children in the community without previous severe childhood malnutrition. We measured anthropometry, body composition, strength, glucose tolerance, cognition, behaviour, and mental health during follow-up visits between Sept 9, 2021, and July 22, 2022, comparing outcomes in adolescents exposed to previous severe childhood malnutrition with unexposed siblings and adolescents from the community assessed previously (for ChroSAM) and newly recruited during current follow-up. We used a linear regression model to adjust for age, sex, disability, HIV, and socioeconomic status. This study is registered with the International Standard Randomised Controlled Trial Number Registry (ISRCTN17238083). FINDINGS: We followed up 168 previously malnourished adolescents (median age 17·1 years [IQR 16·5 to 18·0]), alongside 123 siblings (18·2 years [15·0 to 20·5]), and 89 community adolescents (17·1 years [16·3 to 18·1]). Since last measured 8 years previously, mean height-for-age Z (HAZ) scores had improved in previously malnourished adolescents (difference 0·33 [95% CI 0·20 to 0·46]) and siblings (0·32 [0·09 to 0·55]), but not in community adolescents (difference -0·01 [-0·24 to 0·23]). Previously malnourished adolescents had sustained lower HAZ scores compared with siblings (adjusted difference -0·32 [-0·58 to -0·05]) and community adolescents (-0·21 [-0·52 to 0·10]). The adjusted difference in hand-grip strength between previously malnourished adolescents and community adolescents was -2·0 kg (-4·2 to 0·3). For child behaviour checklist internalising symptom scores, the adjusted difference for previously malnourished adolescents was 2·8 (0·0 to 5·5) compared with siblings and 2·1 (-0·1 to 4·3) compared with community adolescents. No evidence of differences between previously malnourished adolescents and unexposed groups were found in any of the other variables measured. INTERPRETATION: Catch-up growth into adolescence was modest compared with the rapid improvement seen in childhood, but provides optimism for ongoing recovery of height deficits. We found little evidence of heightened non-communicable disease risk in adolescents exposed to severe childhood malnutrition, although long-term health implications need to be monitored. Further investigation of associated home and environmental factors influencing long-term outcomes is needed to tailor preventive and treatment interventions. FUNDING: The Wellcome Trust.

Seroepidemiology of SARS-CoV-2 in a cohort of pregnant women and their infants in Uganda and Malawi.

BACKGROUND: Data on SARS-CoV-2 infection in pregnancy and infancy has accumulated throughout the course of the pandemic, though evidence regarding asymptomatic SARS-CoV-2 infection and adverse birth outcomes are scarce. Limited information is available from countries in sub-Saharan Africa (SSA). The pregnant woman and infant COVID in Africa study (PeriCOVID Africa) is a South-South-North partnership involving hospitals and health centres in five countries: Malawi, Uganda, Mozambique, The Gambia, and Kenya. The study leveraged data from three ongoing prospective cohort studies: Preparing for Group B Streptococcal Vaccines (GBS PREPARE), SARS-CoV-2 infection and COVID-19 in women and their infants in Kampala and Mukono (COMAC) and Pregnancy Care Integrating Translational Science Everywhere (PRECISE). In this paper we describe the seroepidemiology of SARS-CoV-2 infection in pregnant women enrolled in sites in Uganda and Malawi, and the impact of SARS-CoV-2 infection on pregnancy and infant outcomes. OUTCOME: Seroprevalence of SARS-CoV-2 antibodies in maternal blood, reported as the proportion of seropositive women by study site and wave of COVID-19 within each country. METHODS: The PeriCOVID study was a prospective mother-infant cohort study that recruited pregnant women at any gestation antenatally or on the day of delivery. Maternal and cord blood samples were tested for SARS-CoV-2 antibodies using Wantai and Euroimmune ELISA. In periCOVID Uganda and Malawi nose and throat swabs for SARS-Cov-2 RT-PCR were obtained. RESULTS: In total, 1379 women were enrolled, giving birth to 1387 infants. Overall, 63% of pregnant women had a SARS-CoV-2 positive serology. Over subsequent waves (delta and omicron), in the absence of vaccination, seropositivity rose from 20% to over 80%. The placental transfer GMR was 1.7, indicating active placental transfer of anti-spike IgG. There was no association between SARS-CoV-2 antibody positivity and adverse pregnancy or infancy outcomes.

The prevalence of gestational syphilis in Malawi between 2014 and 2022: spatiotemporal modeling of population-level factors.

Background: Mother-to-child transmission of syphilis remains high especially in the WHO AFRO region with a prevalence of 1.62%, resulting in a congenital syphilis rate of 1,119 per 100,000 live births. Elimination efforts can be supported by an understanding of the spatial and temporal changes in disease over time, which can identify priority areas for targeted interventions aimed at reducing transmission. Methods: We collated routine surveillance data from health facilities and covariate data from demographic and health surveys conducted in Malawi between 2014 and 2022. We fitted a Bayesian hierarchical mixed model with spatial and temporally structured random effects to model the district-level monthly counts of maternal syphilis notifications as a function of individual- and district-level predictors. We then generated district-level spatiotemporally explicit risk profiles to estimate the effect of individual- and district-level covariates on maternal syphilis notifications and to identify hotspot areas. Results: Overall, the national prevalence of maternal syphilis increased from 0.28% (95% CI: 0.27-0.29%) in 2014 to peaking in 2021 at 1.92% (95% CI: 1.89-1.96%). Between 2020 and 2022, there was a decline in prevalence, with the most significant decline seen in Zomba District (1.40, 95% CI: 1.12-1.66%). In regression models, a one percentage point increase in district-level antenatal HIV prevalence was associated with increased maternal syphilis (prevalence ratio [PR]: 1.15, 95% credible interval [CrI]: 1.10-1.21). There was also an increased prevalence of maternal syphilis associated with an increased district-level mean number of sex partners (PR: 1.05, 95% CrI: 0.80-1.37). The number of districts with a high prevalence of maternal syphilis also increased between 2014 and 2022, especially in the southern region, where most had a high probability (approaching 100%) of having high maternal syphilis (defined as relative risk >1 compared to the standard population of women aged 15-49 years) in 2022. Conclusion: Maternal syphilis prevalence in Malawi shows an increasing upward trend, with an estimated six times relative increase between 2014 and 2022 (0.28% to 1.73%) and strong associations with higher district-level HIV prevalence. Controlling syphilis depends on reaching vulnerable populations at the sub-national level, which may be disproportionately affected. Our findings support the move to integrate the elimination of mother-to-child transmission (EMTCT) of syphilis programs with existing prevention of mother-to-child transmission (PMTCT) of HIV programs.