Muki Shey

University of Cape Town | UCT · Department of Medicine

Background: Despite treatment with combination antiretroviral therapy (cART), persons living with HIV (PLWH) are at higher risk of cardiac structural abnormalities that may presage clinical heart failure, including myocardial fibrosis. This study assessed whether circulating cellular and soluble protein markers of immune activation cross-sectional...

The development of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) and its prevention using prednisone may potentially be mediated by the LTA4H genotype. We assessed this hypothesis in a clinical trial evaluating prednisone to prevent TB-IRIS. We did not find an association between LTA4H genotype and TB-IRI...

Background. Early mortality among hospitalized HIV-associated tuberculosis (TB/HIV) patients is high despite treatment. The pharmacokinetics of rifampicin, isoniazid, and pyrazinamide were investigated in hospitalized TB/HIV patients and a cohort of outpatients with TB (with or without HIV) to determine whether drug exposures differed between group...

Background Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a frequent complication of co-treatment for TB and HIV-1. We characterized Mtb-specific CD4 T cell phenotype and transcription factor profile associated with the development of TB-IRIS. Methods We examined the role of CD4 T-cell transcription factors in a m...

Background: Patients with HIV and drug-resistant tuberculosis (TB) are at high risk of death. Objectives: We investigated the association between rifampicin-resistant TB (RR-TB) and mortality in a cohort of patients who were admitted to hospital at the time of TB diagnosis. Method: Adults hospitalised at Khayelitsha Hospital and diagnosed with HI...

Background: Healthcare workers are at an increased risk of acquiring vaccine-preventable diseases and are known to be reliable sources of information for the patients and their relatives. Knowledge and attitudes of healthcare workers about vaccines are thus important determinants of their own vaccination uptake and their intention to recommend vacc...

Vaccination attitudes among healthcare workers (HCWs) predict their level of vaccination uptake and intention to recommend vaccinations to their patients. To our knowledge, no study has been conducted in South Africa to assess hesitancy toward influenza vaccines among HCWs. We adapted a questionnaire developed and validated by Betsch and colleagues...

Background Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a frequent complication of co-treatment for TB and HIV-1. We characterized Mtb-specific CD4 T cell phenotype and transcription factor profile associated with the development of TB-IRIS. Methods We examined the role of CD4 T-cell transcription factors in a m...

Background Healthcare workers are at an increased risk of acquiring vaccine-preventable diseases and are known to be reliable source of information for the patients and their relatives. Knowledge and attitudes of Healthcare workers about vaccines are thus important determinants of their own vaccination uptake and their intention to recommend vaccin...

Vaccination attitudes among healthcare workers (HCWs) is a vital factor for measuring their level of vaccination uptake and intention to recommend vaccinations to their patients. To our knowledge, no study has been conducted in South Africa to assess hesitancy to influenza vaccines among HCWs. We used questionnaire adapted from Betsch and colleague...

Background Mycobacterium tuberculosis bloodstream infection is a leading cause of death in people living with HIV and disseminated bacillary load might be a key driver of disease severity. We aimed to assess Xpert MTB/RIF Ultra (Xpert Ultra) testing of blood as a diagnostic for M tuberculosis bloodstream infection and investigate cycle threshold as...

Background Despite being highly prevalent in hospitalised patients with severe HIV-associated tuberculosis (TB) and sepsis, little is known about the mycobacteriology of Mycobacterium tuberculosis bloodstream infection (MTBBSI). We developed methods to serially measure bacillary load in blood and used these to characterise MTBBSI response to anti-T...

Background. Early mortality among hospitalized HIV-associated tuberculosis (TB/HIV) patients is high despite treatment. The pharmacokinetics of rifampicin, isoniazid, and pyrazinamide were investigated in hospitalized TB/HIV patients and a cohort of outpatients with TB (with or without HIV) to determine whether drug exposures differed between group...

Background We assessed willingness to accept vaccination against coronavirus disease 2019 (COVID-19) among healthcare workers(HCWs) at the start of South Africa’s vaccination roll-out. Research Design and Methods We conducted a cross-sectional survey among HCWs in Cape Town in March-May 2021 and assessed predictors of vaccination intentions. Resu...

Mucosal-associated invariant T (MAIT) cells are subsets of T cells abundant in human mucosal tissues and in blood. These cells are activated directly by cytokines or by vitamin B metabolites antigen presentation. MAIT cells possess antimicrobial potential against viruses and bacteria through production of cytokines and cytotoxic molecules. MAIT cel...

Background: Since WHO recommended introduction of at least a single dose of inactivated poliovirus vaccine (IPV) in routine immunisation schedules, there have been global IPV shortages. Fractional-dose IPV (fIPV) administration is one of the strategies to ensure IPV availability. We reviewed studies comparing the effects of fractional with full-do...

Background: MAIT cells are non-classically restricted T lymphocytes that recognize and rapidly respond to microbial metabolites or cytokines and have the capacity to kill bacteria-infected cells. Circulating MAIT cell numbers generally decrease in patients with active TB and HIV infection, but findings regarding functional changes differ. Methods:...

Tuberculous meningitis (TBM) is the most fatal form of tuberculosis and frequently occurs in children. The inflammatory process initiates secondary brain injury processes that lead to death and disability. Much remains unknown about this cerebral inflammatory process, largely because of the difficulty in studying the brain. To date, studies have ty...

Background Heart failure is a prominent cardiovascular disease manifestation sub-Sarahan Africa. Myocardial fibrosis is a central feature of heart failure that we aimed to characterize among persons living with HIV (PWH) in South Africa (SA). Methods Cardiovascular magnetic resonance (CMR) imaging was performed among PWH with viral suppression and...

We characterize the breadth, function and phenotype of innate and adaptive cellular responses in a prevention of Mycobacterium tuberculosis infection trial. Responses are measured by whole blood intracellular cytokine staining at baseline and 70 days after vaccination with H4:IC31 (subunit vaccine containing Ag85B and TB10.4), Bacille Calmette-Guer...

We characterize the breadth, function and phenotype of innate and adaptive cellular responses in a prevention of Mycobacterium tuberculosis infection trial. Responses are measured by whole blood intracellular cytokine staining at baseline and 70 days after vaccination with H4:IC31 (subunit vaccine containing Ag85B and TB10.4), Bacille Calmette-Guer...

The current standards for detecting active coronavirus disease (COVID-19) infection are molecular tests by reverse transcription polymerase chain reaction, using swabs from the lower or upper respiratory tract. Because of the expertise required and the long turnaround time for the availability of test results, faster and easier point-of-care method...

MR1-restricted T (MR1T) cells are defined by their recognition of metabolite antigens presented by the monomorphic MHC class 1-related molecule, MR1, the most highly conserved MHC class I related molecule in mammalian species. Mucosal-associated invariant T (MAIT) cells are the predominant subset of MR1T cells expressing an invariant TCR α-chain, T...

Significance Early-life immune responses have been described as suboptimal, with neonates and infants being susceptible to infections. Vγ9Vδ2 T cells are the first T lymphocytes to be generated in the human fetus. Their T cell receptor-mediated responses to in vitro stimulation and their effector functions at birth are weaker compared with those in...

The coronavirus disease (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) has become a pandemic. There is currently no vaccine or effective treatment for COVID-19. Early diagnosis and management is key to favourable outcomes. In order to prevent more widespread transmission of the virus, rapid detection and...

Background Across low-income and middle-income countries (LMICs), one in ten deaths in children younger than 5 years is attributable to diarrhoea. The substantial between-country variation in both diarrhoea incidence and mortality is attributable to interventions that protect children, prevent infection, and treat disease. Identifying subnational r...

Tuberculosis (TB), caused by the highly infectious Mycobacterium tuberculosis, remains a leading cause of death worldwide, with an estimated 1.6 million associated deaths reported in 2017. In South Africa, an estimated 322,000 (range 230,000-428,000) people were infected with TB in 2017, and a quarter of them lost their lives due to the disease. Ba...

Tuberculosis (TB), caused by the highly infectious Mycobacterium tuberculosis , remains a leading cause of death worldwide, with an estimated 1.6 million associated deaths reported in 2017. In South Africa, an estimated 322,000 (range 230,000-428,000) people were infected with TB in 2017, and a quarter of them lost their lives due to the disease. B...

Background Across low-income and middle-income countries (LMICs), one in ten deaths in children younger than 5 years is attributable to diarrhoea. The substantial between-country variation in both diarrhoea incidence and mortality is attributable to interventions that protect children, prevent infection, and treat disease. Identifying subnational r...

Introduction: HIV-associated inflammation contributes to higher CVD risk among persons living with HIV (PLWH). Heart failure (HF) is a prominent CVD manifestation in sub-Saharan Africa where HIV prevalence is high. Systolic dysfunction is a well-known complication of untreated, advanced HIV disease, but it is unknown if ongoing inflammation contrib...

Preprints with The Lancet is part of SSRN´s First Look, a place where journals and other research experts identify content of interest prior to publication. These preprint papers are not peer-reviewed and are posted here as part of a 12-month trial. Authors have either opted in at submission to The Lancet family of journals to post their preprints...

Aims: Patients hospitalized at the time of human immunodeficiency virus-associated tuberculosis (HIV-TB) diagnosis have high early mortality. We hypothesized that compared to outpatients, there would be lower antituberculosis drug exposure in hospitalized HIV-TB patients, and amongst hospitalized patients exposure would be lower in patients who di...

MR1-restricted T cells (MR1Ts) are a T cell subset that recognizes and mediate host immune responses to a broad array of microbial pathogens, including Mycobacterium tuberculosis . Here, we sought to characterize development of circulating human MR1T cells, defined by MR1-5-OP-RU tetramer labelling and expression of TRAV1-2/CD26/CD161. We analyzed...

Background: Recent upsurges in yellow fever outbreaks are increasing the demand for yellow fever vaccine, while enormously straining global vaccine supply. Fractional dose yellow fever vaccination is being considered as a dose-sparing strategy to address current vaccine shortages. This systematic review and meta-analysis aimed to assess the effects...

Tuberculosis (TB), caused by the highly infectious Mycobacteriumtuberculosis , remains a leading cause of death worldwide, with an estimated 1.6 million associated deaths reported in 2017. In South Africa, an estimated 322,000 (range 230,000-428,000) people were infected with TB in 2017, and a quarter of them lost their lives due to the disease. Ba...

Introduction Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis (M.TB) and other species of the Mycobacterium tuberculosis complex. Globally, TB is ranked as the ninth leading cause of death and the leading cause of death from a single infectious agent. The bacille Calmette-Guerin (BCG) vaccine has been used globally since 1921 for...

Tuberculosis (TB), caused by the highly infectious Mycobacteriumtuberculosis , remains a leading cause of death worldwide, with an estimated 1.6 million associated deaths reported in 2017. In South Africa, an estimated 322,000 people were infected with TB in 2017, and a quarter of them lost their lives due to the disease. Bacille Calmette-Guérin (B...

Background In high-burden settings, case fatality rates are reported to be between 11% and 32% in hospitalized patients with HIV-associated tuberculosis, yet the underlying causes of mortality remain poorly characterized. Understanding causes of mortality could inform the development of novel management strategies to improve survival. We aimed to a...

Tuberculosis, caused by the highly infectious Mycobacteriumtuberculosis , remains a leading cause of death worldwide, with an estimated 1.6 million associated deaths reported in 2017. In South Africa, an estimated 322,000 people were infected with TB in 2017, and a quarter of them lost their lives due to the disease. Bacille Calmette-Guérin remains...

Tuberculosis, caused by the highly infectious Mycobacterium tuberculosis, remains a leading cause of death worldwide, with an estimated 1.6 million associated deaths reported in 2017. In South Africa, an estimated 322,000 people were infected with TB in 2017, and a quarter of them lost their lives due to the disease. Bacille Calmette-Guérin remains...

This appendix formed part of the original submission and has been peer reviewed. Supplement to: GBD 2017 SDG Collaborators. Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017. L...

Introduction WHO recommends the introduction of at least one single dose of inactivated polio vaccine (IPV) in routine immunisation schedules. Thus, there has been an increased demand and concurrent supply shortages of IPV worldwide. One of the strategies to improve access is the use of fractional instead of full doses of IPV. We aim to compare the...

Rationale HSP90B1, also known as gp96, is a chaperone for multiple Toll-like receptors (TLRs) and is necessary for TLR-mediated inflammatory responses in murine myeloid cells. The molecule is also expressed in T-cells though its specific role is unknown. We hypothesized that human HSP90B1 regulates monocyte and T-cell responses to Mycobacterium tub...

Linkage disequilibrium R2 values for relevant SNPs in the Yoruba in Ibadan (YRI) population. LD plot was generated using Ensembl (www.ensembl.org) for the YRI population from the 1000 Genomes Project phase 3. Minor allele frequencies are shown at the convergence of the vertical and horizontal cells for each individual SNP (unshaded cells). Note tha...

Genetic association data stratified by ethnicity. Genotypic frequencies and results of the Pearson’s x2 test for the dominant model are shown for selected SNPs based on self-described ethnicity. For individuals who self-identified as Black and for whom more detailed ethnicity data were available, ~93% identified as Xhosa and ~6% as Sotho. CMA = Cap...

Genetic association data for Cape Mixed Ancestry adjusted for AIMs. Cape Mixed Ancestry ethnicity genotype frequencies for select SNPs for individuals within for whom ancestry informative marker (AIMs) data were available. AIMs adjusted statistics are provided for cases versus controls under a dominant model. OR = odds ratio. 95% CI = 95% confidenc...

Sensitivity analysis of TB genetic association. Data from sensitivity analysis includes only individuals with a more stringent case or control definition. For the sensitivity analysis, a TB case was defined as individuals with ‘Definite’ and ‘Probable’ TB diagnoses, with individuals carrying a ‘Possible TB’ diagnosis excluded. Controls were defined...

rs1305392 is not associated with HSP90B1 gene expression. Gene expression was compared to expression of GAPDH in unstimulated monocytes (A), dendritic cells (B), and T-cells (C) and stratified by genotype. Median and interquartile ranges are included and sample sizes are provided in parentheses below each genotype. Results were not significant for...

Ancestry informative markers (AIMs) for cases and controls. Genotype and allele frequencies for ancestry informative markers (AIMs) are listed. Results of x2 testing for Hardy-Weinberg equilibrium are shown (HWE-p). No SNPs were in violation of HWE. Results of x2 testing using a genotypic model between cases and controls are also shown (Gen p). No...

Participant characteristics of South Africa pediatric tuberculosis genetic cohort study. CMA = Cape Mixed Ancestry. (DOCX)

Genotypic and allelic frequencies of SNPs included in this study. Results of the Pearson’s x2 test for the genotypic model are shown (p). Case = TB disease, Control = no TB disease. Chr12 Location = SNP location on chromosome 12 of the human genome using build GRCh38.p12. (DOCX)

Linkage disequilibrium R2 values for SNPs included within this study. Values were calculated using the control genotyping data from this cohort. This table can be compared to S7 Table, which provides linkage disequilibrium R2 values for the Yoruba in Ibadan population that was used to select haplotype-tagging SNPs for this study. Minor allele frequ...

Whole blood cytokine stimulation by HSP90B1 SNP. General linearized model p-values are shown for interleukin 2 (IL-2) and interferon gamma (IFN-γ) stratified by SNP genotype. (DOCX)

Intracellular cytokine staining, by select HSP90B1 SNP. General linearized model p-values are shown for CD4 positive (CD4) and CD8 positive (CD8) subsets, stratified by HSP90B1 genotype. (DOCX)

Genotype and allele frequencies from the Yoruba in Ibadan (YRI) population for SNPs that were included in our study. Data were generated from the 1000 Genomes Project phase 3 using Ensembl (www.ensembl.org). Note that for SNP rs11111854 and SNP rs2700509, the minor allele from the YRI population was the major allele in our study. (DOCX)

Background Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-leve...

Background Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-leve...

APCs such as monocytes and dendritic cells are among the first cells to recognize invading pathogens and initiate an immune response. The innate response can either eliminate the pathogen directly, or through presentation of Ags to T cells, which can help to clear the infection. Mucosal-associated invariant T (MAIT) cells are among the unconvention...

APCs such as monocytes and dendritic cells are among the first cells to recognize invading pathogens and initiate an immune response. The innate response can either eliminate the pathogen directly, or through presentation of Ags to T cells, which can help to clear the infection. Mucosal-associated invariant T (MAIT) cells are among the unconvention...

Background: An understanding of the trends in tuberculosis incidence, prevalence, and mortality is crucial to tracking of the success of tuberculosis control programmes and identification of remaining challenges. We assessed trends in the fatal and non-fatal burden of tuberculosis over the past 25 years for 195 countries and territories. Methods:...

This is the supplement for DOI: 10.1016/S1473-3099(17)30703-X

Background: Monitoring levels and trends in premature mortality is crucial to understanding how societies can address prominent sources of early death. The Global Burden of Disease 2016 Study (GBD 2016) provides a comprehensive assessment of cause-specific mortality for 264 causes in 195 locations from 1980 to 2016. This assessment includes evaluat...

Background: Strategies to reduce the risk of mother-to-child transmission of the human immunodeficiency virus (HIV) include lifelong antiretroviral therapy (ART) for HIV-positive women, exclusive breastfeeding from birth for six weeks plus nevirapine or replacement feeding plus nevirapine from birth for four to six weeks, elective Caesarean section...

Rationale: The molecular mechanisms that regulate tuberculosis susceptibility and BCG-induced immunity are mostly unknown. However, induction of the adaptive immune response is a critical step in host control of M. tuberculosis. TOLLIP is a ubiquitin-binding protein that regulates innate immune responses, including TLR signaling, which initiate ad...