Shabir A Madhi

Shabir A Madhi
University of the Witwatersrand | wits · Dean Faculty of Health Sciences University of the Witwatersrand

MBBCh, FCPaeds, MMEd, PhD

About

993
Publications
148,842
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44,649
Citations
Citations since 2017
511 Research Items
31037 Citations
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Additional affiliations
January 2012 - present
University of Medicine & Dentistry of New Jersey
January 2011 - present
Stellenbosch University
January 2010 - December 2011
The University of Edinburgh

Publications

Publications (993)
Article
Full-text available
The SARS-CoV-2 Omicron (B.1.1.529) Variant of Concern (VOC) and its sub-lineages (including BA.2, BA.4, BA.5, BA.2.12.1) contain spike mutations that confer high level resistance to neutralizing antibodies induced by vaccination with ancestral spike or infection with previously circulating variants. The NVX-CoV2373 vaccine, a protein nanoparticle v...
Preprint
Full-text available
Streptococcus pneumoniae is a leading cause of pneumonia and meningitis worldwide. Many different serotypes co-circulate endemically in any one location. The extent and mechanisms of spread, and vaccine-driven changes in fitness and antimicrobial resistance (AMR), remain largely unquantified. Using geolocated genome sequences from South Africa (N=6...
Preprint
While vaccines are a well-established method of controlling the spread of infectious diseases, vaccine hesitancy jeopardizes curbing the spread of COVID-19. Through the Vaccine Information Network (VIN), this study explored barriers and motivators to COVID-19 vaccine uptake. We conducted 18 focus group discussions with male and female community mem...
Article
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Introduction Despite a growing body of research on the risks of SARS-CoV-2 infection during pregnancy, there is continued controversy given heterogeneity in the quality and design of published studies. Methods We screened ongoing studies in our sequential, prospective meta-analysis. We pooled individual participant data to estimate the absolute an...
Preprint
Full-text available
Background Vaccination of infants with pneumococcal conjugate vaccines (PCV) is recommended by the World Health Organisation. Evidence is mixed regarding the differences in immunogenicity and efficacy of the different pneumococcal vaccines. Methods In this systematic-review and network meta-analysis, we searched the Cochrane Library, Embase, Global...
Article
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Quantitative real-time PCR (qPCR) methods are now routinely used and have advanced to allow for high-throughput amplification of multiple targets in a single qPCR run. Where algorithms and comparisons are used to interpret the results of different assay-sets (primers and probe for one target), or multiple assay-sets in a run (a reaction-set), betwe...
Preprint
Full-text available
Vaccines against SARS-CoV-2 have been pivotal in overcoming the Covid-19 pandemic yet understanding the subsequent outcomes and immunological effects remain crucial, especially for at-risk groups e.g. people living with human immunodeficiency virus (HIV) (PLWH). In this study we report the longitudinal IgA and IgG antibody titers, as well as antibo...
Article
Background: In a phase 2b trial and the phase 3 MELODY trial, nirsevimab, an extended half-life, monoclonal antibody against respiratory syncytial virus (RSV), protected healthy infants born preterm or at full term against medically attended RSV lower respiratory tract infection (LRTI). In the MEDLEY phase 2-3 trial in infants at higher risk for s...
Article
Objectives: This study aimed to investigate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T-cell responses 14 days after single-dose ChAdOx1 nCoV-19 (AZD1222) vaccination in black Africans with and without HIV in South Africa, as well as determine the effect of AZD1222 vaccination on cell-mediated immune responses in people...
Article
Full-text available
Background Respiratory syncytial virus (RSV) is a major cause of infant morbidity and mortality worldwide and could be preventable by vaccination in pregnancy. Methods We conducted a randomized, placebo-controlled phase 2b trial evaluating safety, immunogenicity, and potential efficacy of a bivalent RSV prefusion F vaccine (RSVpreF) in pregnant wo...
Article
Background: SARS-CoV-2 infection in pregnant women has been associated with severe illness in the women and higher rates of premature delivery. There is, however, paucity of data on the impact of the timing of SARS-CoV-2 infection and on symptomatic or asymptomatic infections on birth outcomes. Data from low-middle income settings is also lacking....
Preprint
Full-text available
Background: Sensitive tools for detecting concurrent colonizing pneumococcal serotypes are needed for detailed evaluation of the direct and indirect impact of routine pneumococcal conjugate vaccine (PCV) immunization. Method: A high-throughput quantitative nanofluidic real-time PCR (Fluidigm) reaction-set was developed to detect and quantify 92 pne...
Preprint
Full-text available
How human genetic variation contributes to vaccine immunogenicity and effectiveness is unclear, particularly in infants from Africa. We undertook genome-wide association analyses of eight vaccine antibody responses in 2,499 infants from three African countries and identified significant associations across the human leukocyte antigen (HLA) locus fo...
Preprint
Full-text available
Introduction The detection of respiratory syncytial virus (RSV) in upper airway samples does not necessarily infer causality of illness. Calculating the attributable fraction (AF) of RSV in clinical syndromes could refine disease burden estimates. Methods Using unconditional logistic regression models, we estimated the AF of RSV-associated influenz...
Article
Objective Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection during pregnancy has been associated with poor pregnancy outcomes. There is, however, not much information on the impact of the timing of SARS-CoV-2 infection on pregnancy outcomes, and studies from low-middle income settings are also scarce. Study Design We conducted...
Article
Using hospital surveillance data, we estimated hMPV hospitalization incidence by age and HIV-exposure status. hMPV-associated hospitalization incidence was highest in <1-year children. Incidence rate ratios of HIV-exposed over unexposed children were 1.5 (95%CI 0.9-2.4) for <6-month children, 1.4 (95%CI 0.7-2.4) for 6-11-month children and 0.9 (95%...
Article
Full-text available
Importance Although child mortality trends have decreased worldwide, deaths among children younger than 5 years of age remain high and disproportionately circumscribed to sub-Saharan Africa and Southern Asia. Tailored and innovative approaches are needed to increase access, coverage, and quality of child health care services to reduce mortality, bu...
Article
Full-text available
Influenza vaccination of pregnant women reduces influenza-associated illness in the women and their infants, but effectiveness estimates against influenza-associated hospitalization are limited and are lacking from settings with high maternal HIV-infection prevalence. We assessed the effect of maternal vaccination in HIV-uninfected women and women...
Article
Full-text available
Host genetic factors are known to modify the susceptibility, severity, and outcomes of COVID-19 and vary across populations. However, continental Africans are yet to be adequately represented in such studies despite the importance of genetic factors in understanding Africa’s response to the pandemic. We describe the development of a research resour...
Article
Full-text available
Background COVID-19 vaccine rollout is lagging in Africa, where there has been a high rate of SARS-CoV-2 infection. We aimed to evaluate the effect of SARS-CoV-2 infection before vaccination with the ChAdOx-nCoV19 (AZD1222) vaccine on antibody responses through to 180 days. Methods We did an unmasked post-hoc immunogenicity analysis after the firs...
Preprint
Full-text available
The SARS-CoV-2 Omicron (B.1.1.529) Variant of Concern (VOC) and its sub-lineages (including BA.2, BA.4, BA.5, BA.2.12.1) contain spike mutations that confer high level resistance to neutralizing antibodies. The NVX-CoV2373 vaccine, a protein nanoparticle vaccine, has value in countries with constrained cold-chain requirements. Here we report neutra...
Article
Full-text available
HIV-exposed uninfected infants (HEU) are highly vulnerable to infections in the first 6 months of life, and this vulnerability decreases to the age of 24 months. Because the microbiome plays a critical role in the education of the infant immune system, which protects them against infections, we characterized the gut microbiomes of HEU and HIV-unexp...
Poster
Full-text available
Severe social challenges have arisen in the wake of the COVID-19 pandemic in manifestations of victim-blaming, dehumanization, othering, and stigmatization. During both past and present pandemics, people have equally scapegoated 'the other' for causing and spreading diseases such as smallpox, the third bubonic plague, the 1918 influenza, and, more...
Article
Full-text available
Unprecedented in scale, immense COVID-19 immunization programs have been rolled out globally. This article explores aspects of hypothetical vaccine acceptability in Soweto, South Africa, shortly before such vaccines became available. Whereas hypothetical acceptance was normative, this has not translated into uptake today, which remains concerningly...
Article
(N Engl J Med. 2022;386:837–846. doi: 10.1056/NEJMoa2110275) Infants experience medically attended illness and hospitalization at elevated rates from respiratory syncytial virus (RSV) infection. As a monoclonal antibody with an extended half-life, Nirsevimab (N) is an emerging treatment that binds to the RSV fusion protein and has enhanced inhibito...
Article
In pregnant women antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein cross the placenta and can be detected in cord-blood at the time of delivery. We measured SARS-CoV-2 full-length anti-spike IgG in blood samples collected from women living with HIV (WLWHIV) and without HIV when presenting for labour, and...
Preprint
Full-text available
Unprecedented in scale, immense COVID-19 immunization programmes have been rolled out globally. This article explores aspects of hypothetical vaccine acceptability in Soweto, South Af-rica, shortly before such vaccines became available. Whereas hypothetical acceptance was norma-tive, this has not translated into uptake today, which remains concerni...
Article
Full-text available
Background Serotype 24F is one of the emerging pneumococcal serotypes after the introduction of pneumococcal conjugate vaccine (PCV). We aimed to identify lineages driving the increase of serotype 24F in France and place these findings into a global context. Methods Whole-genome sequencing was performed on a collection of serotype 24F pneumococci...
Article
Full-text available
Objective This sequential, prospective meta-analysis (sPMA) sought to identify risk factors among pregnant and postpartum women with COVID-19 for adverse outcomes related to: disease severity, maternal morbidities, neonatal mortality and morbidity, adverse birth outcomes. Data sources We prospectively invited study investigators to join the sPMA v...
Article
Full-text available
IntroductionThe high burden of stillbirths and neonatal deaths is driving global initiatives to improve birth outcomes. Discerning stillbirths from neonatal deaths can be difficult in some settings, yet this distinction is critical for understanding causes of perinatal deaths and improving resuscitation practices for live born babies.Methods We eva...
Preprint
In this South African phase 1/2b study, we demonstrated vaccine efficacy (VE) of two doses of AZD1222 for asymptomatic and symptomatic SARS-CoV-2 infection: 90.6% against wild-type and 77.1% against the Delta variant ≥9 months after vaccination. VE against infection with the Beta variant, which preceded circulation of Delta, was 6.7%. Clinical tri...
Preprint
The SARS-CoV-2 Omicron (B.1.1.529) Variant of Concern (VOC) and its sub-lineages (including BA.2, BA.4/5, BA.2.12.1) contain spike mutations that confer high level resistance to neutralizing antibodies. The NVX-CoV2373 vaccine, a protein nanoparticle vaccine, has value in countries with constrained cold-chain requirements. Here we report neutralizi...
Preprint
Background The B.1.1.529 (Omicron BA.1) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global resurgence of coronavirus disease 2019 (Covid-19). The contribution of BA.1 infection to population immunity and its effect on subsequent resurgence of B.1.1.529 sub-lineages warrant investigation. Methods We conducted an...
Article
Background : A potential explanation for the fact that the high rate of infection of SARS-CoV-2 in South Africa did not translate into high rates of severe illness and death may be the presence of cross-reactive immunity induced by common cold coronaviruses (CCoV). Methods : We used SARS-CoV-2 peptide pools and whole virus antigen to stimulate peri...
Article
Full-text available
Introduction The provision of kangaroo mother care (KMC) involving continuous skin-to-skin care (SSC) is an important intervention in neonatal care, which is recommended even when women are infected with severe acute respiratory syndrome coronavirus (SARS-CoV-2). We report on a nosocomial outbreak of SARS-CoV-2 infections in a KMC ward. Methods Co...
Article
Worldwide, childhood mortality has declined significantly, with improvements in hygiene and vaccinations against common childhood illnesses, yet newborn mortality remains high. Group B Streptococcus (GBS) disease significantly contributes to newborn mortality and is the leading cause of meningitis in infants. Many years of research have demonstrate...
Article
Full-text available
Streptococcus pneumoniae is a major human pathogen responsible for over 317000 deaths in children <5 years of age with the burden of the disease being highest in low- and middle-income countries including South Africa. Following the introduction of the 7-valent and 13-valent pneumococcal conjugate vaccine (PCV) in South Africa in 2009 and 2011, res...
Article
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Original article: https://doi.org/10.17159/sajs.2022/13323 The following terminology was erroneously reported: “non-white race” should be “people of colour”, or “black African, coloured and people of Indian descent”.
Article
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Background The true burden of lower respiratory tract infections (LRTIs) due to respiratory syncytial virus (RSV) remains unclear. This study aimed to provide more robust, multinational data on RSV-LRTI incidence and burden in the first 2 years of life. Methods This prospective, observational cohort study was conducted in Argentina, Bangladesh, Ca...
Article
Background Tuberculosis is a major public health problem worldwide. Immunisation with Mycobacterium bovis BCG vaccine is partially effective in infants, reducing the incidence of miliary and tuberculosis meningitis, but is less effective against pulmonary tuberculosis. We aimed to compare safety and immunogenicity of VPM1002—a recombinant BCG vacci...
Article
Full-text available
Older age, male sex, and non-white race have been reported to be risk factors for COVID-19 mortality. Few studies have explored how these intersecting factors contribute to COVID-19 outcomes. This study aimed to compare demographic characteristics and trends in SARS-CoV-2 admissions and the health care they received. Hospital admission data were co...
Article
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Background Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory infection in young children. We previously estimated that in 2015, 33·1 million episodes of RSV-associated acute lower respiratory infection occurred in children aged 0-60 months, resulting in a total of 118 200 deaths worldwide. Since then, several com...
Article
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Background There is a paucity of data on COVID-19 vaccines in people living with HIV-1, who could be at increased risk of severe illness and death from COVID-19. We evaluated the safety and immunogenicity of a Matrix-M adjuvanted recombinant spike protein nanoparticle COVID-19 vaccine (NVX-CoV2373; Novavax) in HIV-negative people and people living...
Article
Coronavirus disease 2019 (COVID-19) which is caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been associated with severe illness in pregnant women. Furthermore, COVID-19 during pregnancy is associated with adverse foetal outcomes, including preterm labour. Pregnant women were largely excluded from initial clinical tri...
Article
Full-text available
Background: Diagnosis of pneumonia remains challenging. Digitally recorded and remote human classified lung sounds may offer benefits beyond conventional auscultation, but it is unclear whether classifications differ between the two approaches. We evaluated concordance between digital and conventional auscultation. Methods: We collected digitall...
Article
Full-text available
Global genomic surveillance of SARS-CoV-2 has identified variants associated with increased transmissibility, neutralization resistance and disease severity. Here we report the emergence of the PANGO lineage C.1.2, detected at low prevalence in South Africa and eleven other countries. The initial C.1.2 detection is associated with a high substituti...
Article
Transplacental hMPV-neutralizing antibody transfer was reduced from mothers living with HIV-1. However, a comparison of antibody titers at birth between hMPV hospitalization cases at <6 months and matched controls suggested that reduced maternal antibody might not be the primary cause of the previously reported elevated hMPV risk in HIV-1-exposed i...
Article
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Introduction Existing risk assessment tools to identify children at risk of hospitalised pneumonia-related mortality have shown suboptimal discriminatory value during external validation. Our objective was to derive and validate a novel risk assessment tool to identify children aged 2–59 months at risk of hospitalised pneumonia-related mortality ac...
Article
Full-text available
Influenza virus hemagglutinin (HA) stalk-specific antibodies have been shown to potently induce Fc-mediated effector functions which are important in protection from disease. In placebo-controlled maternal influenza (MatFlu) vaccination trials of pregnant women living with or without HIV, reduced risk of influenza illness was associated with high H...
Article
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Background Data are limited regarding long-term consequences of invasive GBS (iGBS) disease in early infancy, especially from low- and middle-income countries (LMIC) where most cases occur. We aimed to estimate risk of neurodevelopmental impairment (NDI) in children with a history of iGBS disease. Methods A multi-country matched cohort study was u...
Article
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Background Group B streptococcus (GBS) colonisation during pregnancy can lead to invasive GBS disease (iGBS) in infants, including meningitis or sepsis, with a high mortality risk. Other outcomes include stillbirths, maternal infections, and prematurity. There are data gaps, notably regarding neurodevelopmental impairment (NDI), especially after iG...
Article
Full-text available
Effective risk communication is essential for outbreak mitigation, as recently highlighted during the coronavirus disease 2019 (COVID-19) pandemic. Hand hygiene is one of the proposed public health interventions to protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) acquisition and transmission along with social distancing,...
Article
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Background Binding and neutralising anti-Spike antibodies play a key role in immune defence against SARS-CoV-2 infection. Since it is known that antibodies wane with time and new immune-evasive variants are emerging, we aimed to assess the dynamics of anti-Spike antibodies in an African adult population with prior SARS-CoV-2 infection and to determ...
Article
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Background Group B Streptococcus (GBS) infections are a major cause of invasive disease (IGbsD) in young infants and cause miscarriage and stillbirths. Immunization of pregnant women against GBS in addition to intrapartum antibiotic prophylaxis could prevent disease. Establishing accurate serological markers of protection against IGbsD could enable...
Article
Full-text available
Vitamin D regulates the master iron hormone hepcidin, and iron in turn alters vitamin D metabolism. Although vitamin D and iron deficiency are highly prevalent globally, little is known about their interactions in Africa. To evaluate associations between vitamin D and iron status we measured markers of iron status, inflammation, malaria parasitemia...
Article
Background: Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection and hospitalization in infants. Nirsevimab is a monoclonal antibody to the RSV fusion protein that has an extended half-life. The efficacy and safety of nirsevimab in healthy late-preterm and term infants are uncertain. Methods: We randomly assign...
Article
Full-text available
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 pr...
Article
Purpose: Current quantitative real-time Polymerase Chain Reaction (qPCR) methods are unable to distinguish serotypes 6A from 6B, 18C from 18A/B and 22F from 22A. We established a nanofluidic real-time PCR (Fluidigm) to distinguish between these individual serotypes by including Dual Priming Oligonucleotide (DPO) primers, a Locked Nucleic Acid (LNA)...
Article
Full-text available
Background Globally, mortality in children younger than 5 years has been decreasing over the past few decades, but high under-5 mortality persists across regions of sub-Saharan Africa and southern Asia. Interventions—such as improved quality of clinical and antenatal care, better access to emergency obstetrical procedures, better triage and risk st...
Article
Background: The B.1.1.529 (omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified on November 25, 2021, in Gauteng province, South Africa. Data regarding the seroprevalence of SARS-CoV-2 IgG in Gauteng before the fourth wave of coronavirus disease 2019 (Covid-19), in which the omicron variant was domi...
Poster
Full-text available
SARS-CoV2 antibody testing is an important auxillary test especially for retrospective diagnosis or in patients with long COVID-19 or multisystem inflammatory syndrome of childhood. Epidemiological serology studies may also assist public health planning. Access to formal laboratory testing is not universal in many low-and middle-income (LMIC) count...
Poster
Access to SARS-CoV-2 polymerase chain reaction (PCR) testing is a bottleneck globally, especially in low- and middle-income countries (LMICs). Reliable point-of- care (POC) diagnostics for coronavirus disease 2019 (COVID-19) are cheaper and easier to scale-up than PCR especially in LMICs, and will facilitate interruption of transmission. We report...
Preprint
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We investigated Omicron infections among healthcare workers (HCW) presenting with symptoms of SARS-CoV-2 infection and evaluated the protective effect of vaccination or prior infection. Between 24 th November and 31 st December 2021, HCW in Johannesburg, South Africa, were tested for SARS-CoV-2 infection by Nucleic Acid Amplification Test (NAAT). B...
Article
Currently, no formal mechanisms or systematic approaches exist to inform developers of new vaccines of the evidence anticipated to facilitate global policy recommendations, before a vaccine candidate approaches regulatory approval at the end of pre-licensure efficacy studies. Consequently, significant delays may result in vaccine introduction and u...
Article
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Comparisons of histopathological features and microbiological findings between decedents with respiratory symptoms due to SARS-CoV-2 infection or other causes, in settings with high prevalence of HIV and Mycobacterium tuberculosis (MTB) infections have not been reported. Deaths associated with a positive ante-mortem SARS-CoV-2 PCR test and/or respi...
Article
The rapid development of COVID-19 vaccines was the result of decades of research to establish flexible vaccine platforms and understand pathogens with pandemic potential, as well as several novel changes to the vaccine discovery and development processes that partnered industry and governments. And while vaccines offer the potential to drastically...
Article
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Background Streptococcus agalactiae or Group B Streptococcus (GBS) is an encapsulated gram-positive bacterial pathobiont that commonly colonizes the lower gastrointestinal tract and reproductive tract of human hosts. This bacterium can infect the gravid reproductive tract and cause invasive infections of pregnant patients and neonates. Upon coloniz...
Article
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Purpose: The diagnosis of tubercular uveitis (TBU) is difficult. The lack of a diagnostic gold standard has contributed to challenges in determining the true prevalence and clinical predictors of TBU. We aimed to determine the proportion of TBU cases in adults with uveitis and to examine clinical features associated with TBU. Methods: A prospect...