Publications by authors named "Madhi S"

Objectives: To assess neurological sequelae and growth in the first 12 months of life in a cohort of congenital cytomegalovirus (cCMV) infected infants compared to cCMV uninfected infants.

Study Design: This was a prospective matched cohort study conducted in Soweto, South Africa where forty-six confirmed cCMV cases were matched on HIV-exposure, gender and gestational age (±two weeks) to 84 cCMV-uninfected controls in a 1:2 ratio. Cases and controls were followed up until 12 months of age to assess anthropometry, hearing and neurodevelopmental outcomes.

View Article and Find Full Text PDF

Background: 21 million pregnant women worldwide (18%) are estimated to carry Group B Streptococcus (GBS), which is a risk for invasive disease in newborns, pregnant women, and stillbirths. Adults ≥ 60 years or with underlying health conditions are also vulnerable to invasive GBS disease. We undertook systematic reviews on GBS organism characteristics including: capsular polysaccharide (serotype), sequence type (multi-locus sequence types (MLST)), and virulence proteins.

View Article and Find Full Text PDF

Background: Streptococcus agalactiae or group B streptococcus (GBS) is a significant cause of neonatal sepsis. Intrapartum antibiotic prophylaxis is recommended for pregnant women identified to be rectovaginally colonised between 34 and 37 weeks' gestational age to decrease the risk of invasive disease in their newborns. An effective multivalent GBS vaccine may prevent a broader scope of GBS-associated diseases, such as GBS early-onset disease, GBS late-onset disease, spontaneous abortion, stillbirth and maternal bacteraemia.

View Article and Find Full Text PDF

The potential role for serological tests in the current COVID-19 pandemic has generated very considerable recent interest across many sectors worldwide, inter alia pathologists seeking additional weapons for their armoury of diagnostic tests; epidemiologists seeking tools to gain seroprevalence data that will inform improved models of the spread of disease; research scientists seeking tools to study the natural history of COVID-19 disease; vaccine developers seeking tools to assess vaccine efficacy in clinical trials; and companies and governments seeking tools to aid return-to-work decision-making. However, much of the local debate to date has centred on questions surrounding whether regulatory approval processes are limiting access to serological tests, and has not paused to consider the intrinsically limiting impact of underlying fundamental biology and immunology on where and how different COVID-19 serological tests can usefully be deployed in the response to the current pandemic. We review, from an immunological perspective, recent experimental evidence on the time-dependency of adaptive immune responses following SARS-CoV-2 infection and the impact of this on the sensitivity and specificity of COVID-19 antibody tests made at different time points post infection.

View Article and Find Full Text PDF

Background: A key consideration for expanding recommendations for influenza vaccination is a robust assessment of immunogenicity and efficiency of transplacental antibody transfer after maternal vaccination.

Methods: We pooled data from two trials of maternal influenza vaccination to analyze vaccine immunogenicity with more power than either trial had alone. We compared hemagglutination-inhibition (HAI) titers and titer factor change for women and their infants between trial arms using t-tests; maternal and infant putative seroprotective titers (HAI ≥ 1:40) within each trial arm and maternal seroconversion between trial arms using exact tests; and transplacental antibody transfer between trial arms using t-tests.

View Article and Find Full Text PDF

Background: Routine childhood immunisation with pneumococcal conjugate vaccine (PCV) has changed the epidemiology of pneumococcal disease across age groups, providing an opportunity to reconsider PCV dosing schedules. We aimed to evaluate the post-booster dose immunogenicity of ten-valent (PCV10) and 13-valent (PCV13) PCVs between infants randomly assigned to receive a single-dose compared with a two-dose primary series.

Methods: We did an open-label, non-inferiority, randomised study in HIV-unexposed infants at a single centre in Soweto, South Africa.

View Article and Find Full Text PDF

Background: Whether digitally recorded lung sounds are associated with radiographic pneumonia or clinical outcomes among children in low-income and middle-income countries is unknown. We sought to address these knowledge gaps.

Methods: We enrolled 1 to 59monthold children hospitalized with pneumonia at eight African and Asian Pneumonia Etiology Research for Child Health sites in six countries, recorded digital stethoscope lung sounds, obtained chest radiographs, and collected clinical outcomes.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

Background: Respiratory syncytial virus (RSV) is the dominant cause of severe lower respiratory tract infection in infants, with the most severe cases concentrated among younger infants.

Methods: Healthy pregnant women, at 28 weeks 0 days through 36 weeks 0 days of gestation, with an expected delivery date near the start of the RSV season, were randomly assigned in an overall ratio of approximately 2:1 to receive a single intramuscular dose of RSV fusion (F) protein nanoparticle vaccine or placebo. Infants were followed for 180 days to assess outcomes related to lower respiratory tract infection and for 364 days to assess safety.

View Article and Find Full Text PDF
Article Synopsis
  • Respiratory syncytial virus (RSV) is a major cause of lower respiratory infections in infants, prompting the development of nirsevimab, a monoclonal antibody that offers protection for an entire RSV season with a single dose.
  • A clinical trial involved 1,453 preterm infants who were randomly assigned to receive nirsevimab or a placebo, assessing the drug's effectiveness in preventing RSV-related respiratory infections and hospitalizations over 150 days.
  • Results showed that nirsevimab significantly reduced the incidence of RSV infections (70.1% lower) and hospitalizations (78.4% lower) compared to placebo, with no major safety concerns reported between the two groups.
View Article and Find Full Text PDF

Background: An improved understanding of childhood pneumonia etiology is required to inform prevention and treatment strategies. Lung aspiration is the gold standard specimen for pneumonia diagnostics. We report findings from analyses of lung and pleural aspirates collected in the Pneumonia Etiology Research for Child Health (PERCH) study.

View Article and Find Full Text PDF

Immunization during pregnancy has been recommended in an increasing number of countries. The aim of this strategy is to protect pregnant women and infants from severe infectious disease, morbidity and mortality and is currently limited to tetanus, inactivated influenza, and pertussis-containing vaccines. There have been recent advancements in the development of vaccines designed primarily for use in pregnant women (respiratory syncytial virus and group B vaccines).

View Article and Find Full Text PDF

Background: Colonisation with Streptococcus pneumoniae can lead to invasive pneumococcal disease and pneumonia. Pneumococcal acquisition and prevalence of colonisation are high in children. In older adults, a population susceptible to pneumococcal disease, colonisation prevalence is reported to be lower, but studies are heterogeneous.

View Article and Find Full Text PDF

Background: Sub-Saharan Africa and south Asia contributed 81% of 5·9 million under-5 deaths and 77% of 2·6 million stillbirths worldwide in 2015. Vital registration and verbal autopsy data are mainstays for the estimation of leading causes of death, but both are non-specific and focus on a single underlying cause. We aimed to provide granular data on the contributory causes of death in stillborn fetuses and in deceased neonates and children younger than 5 years, to inform child mortality prevention efforts.

View Article and Find Full Text PDF

Background: Maternal influenza immunisation can reduce morbidity and mortality associated with influenza infection in pregnant women and young infants. We aimed to determine the vaccine efficacy of maternal influenza immunisation against maternal and infant PCR-confirmed influenza, duration of protection, and the effect of gestational age at vaccination on vaccine efficacy, birth outcomes, and infant growth up to 6 months of age.

Methods: We did a pooled analysis of three randomised controlled trials done in Nepal (2011-2014), Mali (2011-2014), and South Africa (2011-2013).

View Article and Find Full Text PDF

Background: Infections in children treated for cancer contribute to morbidity and mortality. There is a paucity of studies on the incidence, etiology, risk factors and outcome of bacterial infections in African children treated for cancer. The aim of the study was to delineate the epidemiology of infectious morbidity and mortality in children with cancer.

View Article and Find Full Text PDF
Article Synopsis
  • Late in pregnancy, women transfer antibodies to their babies, specifically human leukocyte antigens (HLA), but there's limited data about how these antibodies interact and their significance in pregnancy and newborns.!* -
  • Using advanced Luminex technology, researchers found that a significant percentage of mothers and infants had HLA antibodies, indicating a strong connection between maternal and infant immune responses.!* -
  • The study suggests there's selective transfer of HLA antibodies from mother to infant, which could influence how infants develop their own immune responses and could provide insights into immune tolerance in newborns.!*
View Article and Find Full Text PDF

This analysis includes pooled data from 2 placebo-controlled maternal influenza immunization trials, with a separate analysis on a meningococcal conjugate vaccine-controlled maternal influenza immunization trial. Maternal influenza immunization was not associated with infant or maternal all-cause mortality in placebo-controlled trials. In the meningococcal conjugate vaccine-controlled trial, there were fewer deaths during low or any influenza circulation weeks among infants whose mothers received meningococcal conjugate vaccine.

View Article and Find Full Text PDF

Knowledge of pneumococcal lineages, their geographic distribution and antibiotic resistance patterns, can give insights into global pneumococcal disease. We provide interactive bioinformatic outputs to explore such topics, aiming to increase dissemination of genomic insights to the wider community, without the need for specialist training. We prepared 12 country-specific phylogenetic snapshots, and international phylogenetic snapshots of 73 common Global Pneumococcal Sequence Clusters (GPSCs) previously defined using PopPUNK, and present them in Microreact.

View Article and Find Full Text PDF

Respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) during early childhood may be associated with subsequent pulmonary sequelae, including recurrent wheezing and asthma. We undertook a systematic review to investigate the pulmonary function sequelae following RSV LRTI in the first 3 years of life. The systematic review protocol was registered on PROSPERO (CRD42018087168).

View Article and Find Full Text PDF
Article Synopsis
  • - The study evaluated the immunogenicity and safety of a single dose of inactivated hepatitis-A virus (HAV) vaccine and live attenuated varicella zoster virus (VZV) vaccine in South African children, including both HIV-exposed uninfected (HEU) and HIV-unexposed children.
  • - After vaccination, 91.8% of HIV-unexposed and 82.9% of HEU children tested positive for hepatitis-A antibodies, while VZV antibody responses were similar, but seroconversion rates were lower than previous studies at only 44%.
  • - Adverse events were reported at similar frequencies between the groups, although HEU children experienced more systemic adverse effects after VZ
View Article and Find Full Text PDF