Contribution of malnutrition to infant and child deaths in Sub-Saharan Africa and South Asia.

Introduction: Malnutrition contributes to 45% of all childhood deaths globally, but these modelled estimates lack direct measurements in countries with high malnutrition and under-5 mortality rates. We investigated malnutrition's role in infant and child deaths in the Child Health and Mortality Prevention Surveillance (CHAMPS) network.

Methods: We analysed CHAMPS data from seven sites (Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone and South Africa) collected between 2016 and 2023.

Association of infant Rib and Alp1 surface protein N-terminal domain immunoglobulin G and invasive Group B Streptococcal disease in young infants.

Background: Vaccine development for Group B Streptococcus (GBS), a common cause of invasive disease in early-infancy and adverse pregnancy outcomes, include exploring widely-expressed GBS surface proteins as vaccine epitopes. We investigated the association between natural infant serum IgG against the RibN and Alp1N domains and risk of invasive GBS disease caused by isolates expressing these proteins.

Methods: We analyzed maternal and infant serum samples from GBS disease cases and infants born to GBS-colonized women controls.

The association between early-onset sepsis and neonatal encephalopathy.

Objective: We evaluated the association between early-onset sepsis and neonatal encephalopathy in a low-middle-income setting.

Methods: We undertook a retrospective study in newborns with gestational age ≥35 weeks and/or birth weight ≥2500 grams, diagnosed with neonatal encephalopathy. Early-onset sepsis was defined as culture-confirmed sepsis or probable sepsis.

Household Contact Tracing With Intensified Tuberculosis and Human Immunodeficiency Virus Screening in South Africa: A Cluster-Randomized Trial.

Background: Household contact tracing for tuberculosis (TB) may facilitate diagnosis and access to TB preventive treatment (TPT). We investigated whether household contact tracing and intensive TB/human immunodeficiency virus (HIV) screening would improve TB-free survival.

Methods: Household contacts of index TB patients in 2 South African provinces were randomized to home tracing and intensive HIV/TB screening or standard of care (SOC; clinic referral letters).

South African Children: A Matched Cohort Study of Neurodevelopmental Impairment in Survivors of Invasive Group B Streptococcus Disease Aged 5 to 8 Years.

Background: Invasive group B Streptococcus (iGBS) sepsis and meningitis are important causes of child mortality, but studies on neurodevelopmental impairment (NDI) after iGBS are limited. Using Griffiths Mental Development Scales-Extended Revised (GMDS-ER), we described NDI in iGBS survivors and non-iGBS children from South Africa, as part of a 5-country study.

Methods: We identified children aged 5-8 years with a history of iGBS and children with no history of iGBS between October 2019 and January 2021.

Infant serotype specific anti-capsular immunoglobulin G antibody and risk of invasive group B Streptococcal disease.

Past studies have mainly investigated the association of serotype-specific capsular IgG in the mother and risk reduction of invasive Group B Streptococcus (GBS) in their young infants. The efficiency of transplacental transfer of IgG could be affected by multiple maternal factors. Hence, investigation of infant serum GBS anti-capsular IgG and risk reduction for invasive GBS disease may be more robust and generalizable.

Quantifying long-term health and economic outcomes for survivors of group B Streptococcus invasive disease in infancy: protocol of a multi-country study in Argentina, India, Kenya, Mozambique and South Africa.

Sepsis and meningitis due to invasive group B (iGBS) disease during early infancy is a leading cause of child mortality. Recent systematic estimates of the worldwide burden of GBS suggested that there are 319,000 cases of infant iGBS disease each year, and an estimated 147,000 stillbirths and young-infant deaths, with the highest burden occurring in Sub-Saharan Africa.  The following priority data gaps were highlighted: (1) long-term outcome data after infant iGBS, including mild disability, to calculate quality-adjusted life years (QALYs) or disability-adjusted life years (DALYs) and (2) economic burden for iGBS survivors and their families.

Detection of Complex Bacilli and Nucleic Acids From Tongue Swabs in Young, Hospitalized Children.

Diagnosis of tuberculosis in pediatric patients remains challenging due to inherent difficulties associated with obtaining respiratory samples for molecular and culture-based testing. To address this, recent studies have highlighted the utility of tongue swabs to detect genomic DNA in the oral epithelia of tuberculosis infected adults. It is unknown whether tongue swabs have similar utility for diagnosis of childhood tuberculosis and if the presence of DNA in these swabs was associated with whole bacilli.

Neurodevelopmental Impairment at 1 Year of Age in Infants With Previous Invasive Group B Streptococcal Sepsis and Meningitis.

Background: Invasive group B streptococcal (GBS) disease causes considerable morbidity and mortality in young infants, and 18% of GBS-meningitis survivors have moderate-to-severe neurodevelopmental impairment. However, there is a paucity of data regarding neurologic impairment following GBS sepsis.

Methods: A case-control study was undertaken in infants at 3 secondary-tertiary hospitals in Johannesburg, South Africa.

Intensified household contact tracing, prevention and treatment support versus enhanced standard of care for contacts of tuberculosis cases in South Africa: study protocol for a household cluster-randomised trial.

Background: Household contact tracing of index TB cases has been advocated as a key part of TB control for many years, but has not been widely implemented in many low-resource setting because of the current dearth of high quality evidence for effectiveness. Innovative strategies for earlier, more effective treatment are particularly important in contexts with hyper-endemic levels of HIV, where levels of TB infection remain extremely high.

Methods: We present the design of a household cluster-randomised controlled trial of interventions aimed at improving TB-free survival and reducing childhood prevalence of Mycobacterium tuberculosis infection among household contacts of index TB cases diagnosed in two provinces of South Africa.

Potential of Minimally Invasive Tissue Sampling for Attributing Specific Causes of Childhood Deaths in South Africa: A Pilot, Epidemiological Study.

Background: Current estimates for causes of childhood deaths are mainly premised on modeling of vital registration and limited verbal autopsy data and generally only characterize the underlying cause of death (CoD). We investigated the potential of minimally invasive tissue sampling (MITS) for ascertaining the underlying and immediate CoD in children 1 month to 14 years of age.

Methods: MITS included postmortem tissue biopsies of brain, liver, and lung for histopathology examination; microbial culture of blood, cerebrospinal fluid (CSF), liver, and lung samples; and molecular microbial testing on blood, CSF, lung, and rectal swabs.

The Association Between Breast Milk Group B Streptococcal Capsular Antibody Levels and Late-onset Disease in Young Infants.

Background: Animal-model studies have demonstrated less group B streptococcal (GBS) invasive disease and gastrointestinal colonization after enteral administration of serotype-specific capsular antibodies. There is, however, a paucity of information on the association of breast milk GBS serotype-specific capsular antibodies and risks for invasive disease in infants. The aim of this study was to explore the association between natural secretory immunoglobulin A (sIgA) capsular antibodies in breast milk and the occurrence of late-onset disease (LOD) in young infants.

The Burden of Acute Diarrheal Disease in Young Hospitalized Urban South African Children Five Years After Rotavirus Vaccine Introduction: A Retrospective Descriptive Study.

Background: Diarrheal disease is a leading cause of childhood morbidity and mortality worldwide. Multiple interventions, including rotavirus vaccination to infants since 2009, have reduced the incidence of diarrheal disease in South African children. Our study aimed to determine the burden of diarrheal disease 5 years after rotavirus vaccine introduction at a tertiary-level hospital.

Knowledge gaps among South African healthcare providers regarding the prevention of neonatal group B streptococcal disease.

Objective: To evaluate obstetric healthcare provider knowledge regarding the prevention of group B streptococcal disease in South African infants.

Methods: Questionnaires exploring knowledge, attitudes and beliefs around group B streptococcal prevention were administered to consenting doctors and maternity nurses in a tertiary academic hospital. Qualitative assessments (focus groups) were undertaken with junior doctors and nurses.

Vaccination of HIV-infected pregnant women: implications for protection of their young infants.

Background: The prevention of mother to child transmission of HIV has resulted in reduced burden of pediatric HIV-infection, but the prevalence of maternal HIV infection remains high in sub-Saharan African countries. HIV-exposed-uninfected infants have an increased risk of morbidity and mortality due to infectious diseases than HIV-unexposed infants, particularly during the first six months of life, which in part might be due to lower levels of pathogen-specific protective antibodies acquired transplacentally from their mothers. This could be mitigated by vaccinating pregnant women to boost antibody levels; although vaccine responses among HIV-infected pregnant women might differ compared to HIV-uninfected women.

Prevention of TB using rifampicin plus isoniazid reduces nevirapine concentrations in HIV-exposed infants.

Background: Newborns of HIV-infected mothers are given daily doses of nevirapine to prevent HIV-1 acquisition. Infants born to mothers with TB should also receive TB preventive therapy. TB preventive regimens include isoniazid for 6 months or rifampicin plus isoniazid for 3 months (RH preventive therapy).

Temporal Changes in Invasive Group B Streptococcus Serotypes: Implications for Vaccine Development.

Introduction: There is a paucity of longitudinal data on the serotype-specific burden of invasive group B Streptococcus (GBS) disease from low-middle income countries, which could inform selection of vaccine epitopes.

Methods: From 2005 to 2014, infants less than 90 days of age with invasive GBS disease were identified through sentinel laboratory and hospital admission surveillance at Chris Hani Baragwanath Academic Hospital in Soweto, South Africa.

Results: We identified 820 cases of invasive GBS disease, including 55% among newborns <7 days age (i.

Group B Streptococcus: developing a correlate of protection for a vaccine against neonatal infections.

Purpose Of Review: Maternal vaccination to prevent invasive Group B Streptococcus (GBS) disease in infants is an important alternative strategy to intrapartum antibiotic prophylaxis. Licensure of GBS vaccines could be expedited using immunological correlates of protection.

Recent Findings: Between 2014 and 2015, we identified two studies that demonstrated an inverse association between invasive GBS disease and maternal serotype III capsular antibody levels greater than 1 μg/ml and greater than 3 μg/ml, and higher maternal antibody levels were associated with protection against serotype Ia disease.

Correlates of protection of serotype-specific capsular antibody and invasive Group B Streptococcus disease in South African infants.

Background: Vaccinating pregnant women may prevent invasive Group B Streptococcus (GBS) disease in their young infants. In a low-middle income setting, we sought to determine an association between natural maternal antibody responses and the development of invasive GBS disease.

Methods: We undertook a matched case-control study in Johannesburg, South Africa.

Integrated Source Case Investigation for Tuberculosis (TB) and HIV in the Caregivers and Household Contacts of Hospitalised Young Children Diagnosed with TB in South Africa: An Observational Study.

Background: Contact tracing, to identify source cases with untreated tuberculosis (TB), is rarely performed in high disease burden settings when the index case is a young child with TB. As TB is strongly associated with HIV infection in these settings, we used source case investigation to determine the prevalence of undiagnosed TB and HIV in the caregivers and household contacts of hospitalised young children diagnosed with TB in South Africa.

Methods: Caregivers and household contacts of 576 young children (age ≤7 years) with TB diagnosed between May 2010 and August 2012 were screened for TB and HIV.

Association between maternal Group B Streptococcus surface-protein antibody concentrations and invasive disease in their infants.

Objectives: Group B Streptococcus (GBS) surface-proteins have been shown to be immunogenic and potential vaccine candidates. We aim to determine the association between maternal IgG antibodies to select GBS surface-proteins and invasive GBS disease in their infants.

Methods: Using a matched case-control study, maternal antibody levels for GBS-immunogenic bacterial adhesin, fibrinogen-binding protein A and pilus-island (PI) PI-1, PI-2a, PI-2b were compared between infants with invasive GBS disease and well-baby controls.

Burden of invasive group B Streptococcus disease and early neurological sequelae in South African infants.

Introduction: Group B Streptococcus (GBS) is a leading cause of neonatal sepsis and meningitis. We aimed to evaluate the burden of invasive early-onset (0-6 days of life, EOD) and late-onset (7-89 days, LOD) GBS disease and subsequent neurological sequelae in infants from a setting with a high prevalence (29.5%) of HIV among pregnant women.

HIV-1 Is Associated With Lower Group B Streptococcus Capsular and Surface-Protein IgG Antibody Levels and Reduced Transplacental Antibody Transfer in Pregnant Women.

Background: Human immunodeficiency virus (HIV)-exposed infants are at increased risk of invasive Group B Streptococcus (GBS) disease; however, the reason for this increased susceptibility has not been characterized.

Methods: We compared GBS capsular and surface-protein maternal immunoglobin G antibody concentrations and cord-maternal ratios between HIV-infected and HIV-uninfected mother-newborn dyads.

Results: Median capsular antibody concentrations (µg/mL) were lower in HIV-infected than HIV-uninfected women for serotypes Ib (P = .