This page has only limited features, please log in for full access.

Unclaimed
Anna K. Coussens
Wellcome Centre for Infectious Diseases Research in Africa

Honors and Awards

The user has no records in this section


Career Timeline

The user has no records in this section.


Short Biography

The user biography is not available.
Following
Followers
Co Authors
The list of users this user is following is empty.
Following: 0 users

Feed

Preprint content
Published: 11 May 2021
Reads 0
Downloads 0

Objectives To describe the presentation and outcome of SARS-CoV2 infection in an African setting of high non-communicable co-morbidity and also HIV-1 and tuberculosis prevalence. Design Case control analysis with cases stratified by HIV-1 and tuberculosis status. Setting A single-centre observational case-control study of adults admitted to a South African hospital with proven SARS-CoV-2 infection or alternative diagnosis. Participants 104 adults with RT-PCR-proven SARS-CoV2 infection of which 55 (52.9%) were male and 31 (29.8%) HIV-1 co-infected. 40 adults (35.7% male, 30.9% HIV-1 co-infected) admitted during the same period with no RT-PCR or serological evidence of SARS-CoV2 infection and assigned alternative diagnoses. Additional in vitro data from prior studies of 72 healthy controls and 118 HIV-1 uninfected and infected persons participants enrolled to a prior study with either immune evidence of tuberculosis sensitization but no symptoms or microbiologically confirmed pulmonary tuberculosis. Results Two or more co-morbidities were present in 57.7% of 104 RT-PCR proven COVID-19 presentations, the commonest being hypertension (48%), type 2 diabetes mellitus (39%), obesity (31%) but also HIV-1 (30%) and active tuberculosis (14%). Amongst patients dually infected by tuberculosis and SARS-CoV-2, clinical features could be dominated by either SARS-CoV-2 or tuberculosis: lymphopenia was exacerbated, and some markers of inflammation (D-dimer and ferritin) elevated in singly SARS-CoV-2 infected patients were even further elevated (p < 0.05). HIV-1 and SARS-CoV2 co-infection resulted in lower absolute number and proportion of CD4 lymphocytes, with those in the lowest peripheral CD4 percentage strata exhibiting absent or lower antibody responses against SARS-CoV2. Death occurred in 30/104 (29%) of all COVID-19 patients and in 6/15 (40%) of patients with coincident SARS-CoV-2 and tuberculosis. Conclusions In this South African setting, HIV-1 and tuberculosis are common co-morbidities in patients presenting with COVID-19. In environments in which tuberculosis is common, SARS-CoV-2 and tuberculosis may co-exist with clinical presentation being typical of either disease. Clinical suspicion of exacerbation of co-existent tuberculosis accompanying SARS-CoV-2 should be high. What is already known on this topic? It has been quite widely thought that Africa has been spared the worst effects of the COVID-19 pandemic. There are very few reported case series and no case-control studies comparing COVID-19 patients admitted to hospital to those admitted for other reasons. However several studies have indicated both HIV-1 and tuberculosis co-infection that are endemic in Africa constitute risk factors for poor outcome. In addition Africa is subject to demographic transition and the prevalence of non-communicable co-morbidities such as type 2 diabetes, hypertension and cardiovascular disease is rising rapidly. No study from Africa has described the clinical impact on the presentation of COVID-19 infection. What this study adds Two or more co-morbidities were present in over half COVID-19 presentations, including HIV-1 (30%) and active tuberculosis (14%). Patients dually infected by tuberculosis and SARS-CoV-2, presented as either SARS-CoV-2 or tuberculosis. HIV-1 and SARS-CoV2 co-infection resulted in lower absolute number and proportion of CD4 lymphocytes, and those with low CD4 counts had absent or lower antibody responses against SARS-CoV2. Death occurred 29% of all COVID-19 patients and in 40% of patients with coincident SARS-CoV-2 and tuberculosis. Thus in environments in which tuberculosis is common, SARS-CoV-2 and tuberculosis may co-exist with clinical presentation being typical of either disease and clinical suspicion of exacerbation of co-existent tuberculosis accompanying SARS-CoV-2 should be high.

ACS Style

Elsa du Bruyn; Cari Stek; Remi Daroowala; Qonita Said-Hartley; Marvin Hsiao; Rene T. Goliath; Fatima Abrahams; Amanda Jackson; Sean Wasserman; Brian W Allwood; Angharad G. Davis; Rachel P-J. Lai; Anna K. Coussens; Katalin A. Wilkinson; Jantina de Vries; Nicki Tiffin; Maddalena Cerrone; Ntobeko A. B. Ntusi; Catherine Riou; Robert J. Wilkinson; Saalikha Aziz; Nonzwakazi Bangani; John Black; Marise Bremer; Wendy Burgers; Zandile Ciko; Hanif Esmail; Siamon Gordon; Yolande X. R. Harley; Francisco Lakay; Fernando-Oneissi Martinez-Estrada; Graeme Meintjes; Marc Mendelson; Tari Papavarnavas; Alize Proust; Sheena Ruzive; Georgia Schafer; Keboile Serole; Claire Whitaker; Kennedy Zvinairo. Communicable and non-communicable co-morbidities and the presentation of COVID-19 in an African setting of high HIV-1 and tuberculosis prevalence. 2021, 1 .

AMA Style

Elsa du Bruyn, Cari Stek, Remi Daroowala, Qonita Said-Hartley, Marvin Hsiao, Rene T. Goliath, Fatima Abrahams, Amanda Jackson, Sean Wasserman, Brian W Allwood, Angharad G. Davis, Rachel P-J. Lai, Anna K. Coussens, Katalin A. Wilkinson, Jantina de Vries, Nicki Tiffin, Maddalena Cerrone, Ntobeko A. B. Ntusi, Catherine Riou, Robert J. Wilkinson, Saalikha Aziz, Nonzwakazi Bangani, John Black, Marise Bremer, Wendy Burgers, Zandile Ciko, Hanif Esmail, Siamon Gordon, Yolande X. R. Harley, Francisco Lakay, Fernando-Oneissi Martinez-Estrada, Graeme Meintjes, Marc Mendelson, Tari Papavarnavas, Alize Proust, Sheena Ruzive, Georgia Schafer, Keboile Serole, Claire Whitaker, Kennedy Zvinairo. Communicable and non-communicable co-morbidities and the presentation of COVID-19 in an African setting of high HIV-1 and tuberculosis prevalence. . 2021; ():1.

Chicago/Turabian Style

Elsa du Bruyn; Cari Stek; Remi Daroowala; Qonita Said-Hartley; Marvin Hsiao; Rene T. Goliath; Fatima Abrahams; Amanda Jackson; Sean Wasserman; Brian W Allwood; Angharad G. Davis; Rachel P-J. Lai; Anna K. Coussens; Katalin A. Wilkinson; Jantina de Vries; Nicki Tiffin; Maddalena Cerrone; Ntobeko A. B. Ntusi; Catherine Riou; Robert J. Wilkinson; Saalikha Aziz; Nonzwakazi Bangani; John Black; Marise Bremer; Wendy Burgers; Zandile Ciko; Hanif Esmail; Siamon Gordon; Yolande X. R. Harley; Francisco Lakay; Fernando-Oneissi Martinez-Estrada; Graeme Meintjes; Marc Mendelson; Tari Papavarnavas; Alize Proust; Sheena Ruzive; Georgia Schafer; Keboile Serole; Claire Whitaker; Kennedy Zvinairo. 2021. "Communicable and non-communicable co-morbidities and the presentation of COVID-19 in an African setting of high HIV-1 and tuberculosis prevalence." , no. : 1.

Journal article
Published: 16 February 2021 in International Journal of Molecular Sciences
Reads 0
Downloads 0

Tuberculosis (TB) is the leading cause of death among HIV-1-infected individuals and Mycobacterium tuberculosis (Mtb) co-infection is an early precipitate to AIDS. We aimed to determine whether Mtb strains differentially modulate cellular susceptibility to HIV-1 infection (cis- and trans-infection), via surface receptor interaction by their cell envelope lipids. Total lipids from pathogenic (lineage 4 Mtb H37Rv, CDC1551 and lineage 2 Mtb HN878, EU127) and non-pathogenic (Mycobacterium bovis BCG and Mycobacterium smegmatis) Mycobacterium strains were integrated into liposomes mimicking the lipid distribution and antigen accessibility of the mycobacterial cell wall. The resulting liposomes were tested for modulating in vitro HIV-1 cis- and trans-infection of TZM-bl cells using single-cycle infectious virus particles. Mtb glycolipids did not affect HIV-1 direct infection however, trans-infection of both R5 and X4 tropic HIV-1 strains were impaired in the presence of glycolipids from M. bovis, Mtb H37Rv and Mtb EU127 strains when using Raji-DC-SIGN cells or immature and mature dendritic cells (DCs) to capture virus. SL1, PDIM and TDM lipids were identified to be involved in DC-SIGN recognition and impairment of HIV-1 trans-infection. These findings indicate that variant strains of Mtb have differential effect on HIV-1 trans-infection with the potential to influence HIV-1 disease course in co-infected individuals.

ACS Style

Marion Pouget; Anna Coussens; Alessandra Ruggiero; Anastasia Koch; Jordan Thomas; Gurdyal Besra; Robert Wilkinson; Apoorva Bhatt; Georgios Pollakis; William Paxton. Generation of Liposomes to Study the Effect of Mycobacterium Tuberculosis Lipids on HIV-1 cis- and trans-Infections. International Journal of Molecular Sciences 2021, 22, 1945 .

AMA Style

Marion Pouget, Anna Coussens, Alessandra Ruggiero, Anastasia Koch, Jordan Thomas, Gurdyal Besra, Robert Wilkinson, Apoorva Bhatt, Georgios Pollakis, William Paxton. Generation of Liposomes to Study the Effect of Mycobacterium Tuberculosis Lipids on HIV-1 cis- and trans-Infections. International Journal of Molecular Sciences. 2021; 22 (4):1945.

Chicago/Turabian Style

Marion Pouget; Anna Coussens; Alessandra Ruggiero; Anastasia Koch; Jordan Thomas; Gurdyal Besra; Robert Wilkinson; Apoorva Bhatt; Georgios Pollakis; William Paxton. 2021. "Generation of Liposomes to Study the Effect of Mycobacterium Tuberculosis Lipids on HIV-1 cis- and trans-Infections." International Journal of Molecular Sciences 22, no. 4: 1945.

Preprint content
Published: 26 November 2020
Reads 0
Downloads 0

Background The novel coronavirus, SARS-CoV-2, has increased the burden on healthcare systems already strained by a high incidence of tuberculosis (TB) as co-infection and dual presentation are occurring in syndemic settings. We aimed to understand the interaction between these diseases by profiling COVID-19 gene expression signatures on RNA-sequencing data from TB-infected individuals. Methods We performed a systematic review and patient-level meta-analysis by querying PubMed and pre-print servers to derive eligible COVID-19 gene expression signatures from human whole blood (WB), PBMCs or BALF studies. A WB influenza dataset served as a control respiratory disease signature. Three large TB RNA-seq datasets, comprising multiple cohorts from the UK and Africa and consisting of TB patients across the disease spectrum, were chosen to profile these signatures. Putative “COVID-19 risk scores” were generated for each sample in the TB datasets using the TBSignatureProfiler package. Risk was stratified by time to TB diagnosis in progressors and contacts of pulmonary and extra-pulmonary TB. An integrative analysis between TB and COVID-19 single-cell RNA-seq data was performed and a population-level meta-analysis was conducted to identify shared gene ontologies between the diseases and their relative enrichment in COVID-19 disease severity states. Results 35 COVID-19 gene signatures from nine eligible studies comprising 98 samples were profiled on TB RNA-seq data from 1181 samples from 853 individuals. 25 signatures had significantly higher COVID-19 risk in active TB (ATB) compared with latent TB infection (p <0·005), 13 of which were validated in two independent datasets.FCN1- andSPP1-expressing macrophages enriched in BALF during severe COVID-19 were identified in circulation during ATB. Shared perturbed ontologies included antigen presentation, epigenetic regulation, platelet activation, and ROS/RNS production were enriched with increasing COVID-19 severity. Finally, we demonstrate that the overlapping transcriptional responses may complicate development of blood-based diagnostic signatures of co-infection. Interpretation Our results identify shared dysregulation of immune responses in COVID-19 and TB as a dual risk posed by co-infection to COVID-19 severity and TB disease progression. These individuals should be followed up for TB in the months subsequent to SARS-CoV-2 diagnosis.

ACS Style

Dylan Sheerin; Abhimanyu Abhimanyu; Xutao Wang; William Evan Johnson; Anna Coussens. Systematic evaluation of transcriptomic disease risk and diagnostic biomarker overlap between COVID-19 and tuberculosis: a patient-level meta-analysis. 2020, 1 .

AMA Style

Dylan Sheerin, Abhimanyu Abhimanyu, Xutao Wang, William Evan Johnson, Anna Coussens. Systematic evaluation of transcriptomic disease risk and diagnostic biomarker overlap between COVID-19 and tuberculosis: a patient-level meta-analysis. . 2020; ():1.

Chicago/Turabian Style

Dylan Sheerin; Abhimanyu Abhimanyu; Xutao Wang; William Evan Johnson; Anna Coussens. 2020. "Systematic evaluation of transcriptomic disease risk and diagnostic biomarker overlap between COVID-19 and tuberculosis: a patient-level meta-analysis." , no. : 1.

Comment
Published: 10 February 2020 in The Lancet Respiratory Medicine
Reads 0
Downloads 0
ACS Style

Matthew Quaife; Rein M G J Houben; Brian Allwood; Ted Cohen; Anna Coussens; Anthony D Harries; Sanne van Kampen; Florian M Marx; Sedona Sweeney; Robert S Wallis; Nicolas A Menzies. Post-tuberculosis mortality and morbidity: valuing the hidden epidemic. The Lancet Respiratory Medicine 2020, 8, 332 -333.

AMA Style

Matthew Quaife, Rein M G J Houben, Brian Allwood, Ted Cohen, Anna Coussens, Anthony D Harries, Sanne van Kampen, Florian M Marx, Sedona Sweeney, Robert S Wallis, Nicolas A Menzies. Post-tuberculosis mortality and morbidity: valuing the hidden epidemic. The Lancet Respiratory Medicine. 2020; 8 (4):332-333.

Chicago/Turabian Style

Matthew Quaife; Rein M G J Houben; Brian Allwood; Ted Cohen; Anna Coussens; Anthony D Harries; Sanne van Kampen; Florian M Marx; Sedona Sweeney; Robert S Wallis; Nicolas A Menzies. 2020. "Post-tuberculosis mortality and morbidity: valuing the hidden epidemic." The Lancet Respiratory Medicine 8, no. 4: 332-333.

Review
Published: 01 February 2020 in Future Virology
Reads 0
Downloads 0

Accelerated tuberculosis and AIDS progression seen in HIV-1 and Mycobacterium tuberculosis ( Mtb)-coinfected individuals indicates the important interaction between these syndemic pathogens. The immunological interaction between HIV-1 and Mtb has been largely defined by how the virus exacerbates tuberculosis disease pathogenesis. Understanding of the mechanisms by which pre-existing or subsequent Mtb infection may favor the replication, persistence and progression of HIV, is less characterized. We present a rationale for the critical consideration of ‘latent’ Mtb infection in HIV-1 prevention and cure strategies. In support of this position, we review evidence of the effect of Mtb infection on HIV-1 acquisition, replication and persistence. We propose that ‘latent’ Mtb infection may have considerable impact on HIV-1 pathogenesis and the continuing HIV-1 epidemic in sub-Saharan Africa.

ACS Style

Robyn Waters; Mthawelanga Ndengane; Melissa-Rose Abrahams; Collin R Diedrich; Robert J Wilkinson; Anna K Coussens. TheMtb-HIV syndemic interaction: why treatingM. tuberculosisinfection may be crucial for HIV-1 eradication. Future Virology 2020, 15, 101 -126.

AMA Style

Robyn Waters, Mthawelanga Ndengane, Melissa-Rose Abrahams, Collin R Diedrich, Robert J Wilkinson, Anna K Coussens. TheMtb-HIV syndemic interaction: why treatingM. tuberculosisinfection may be crucial for HIV-1 eradication. Future Virology. 2020; 15 (2):101-126.

Chicago/Turabian Style

Robyn Waters; Mthawelanga Ndengane; Melissa-Rose Abrahams; Collin R Diedrich; Robert J Wilkinson; Anna K Coussens. 2020. "TheMtb-HIV syndemic interaction: why treatingM. tuberculosisinfection may be crucial for HIV-1 eradication." Future Virology 15, no. 2: 101-126.

Research article
Published: 27 December 2018 in PLOS ONE
Reads 0
Downloads 0

HIV-1 co-infection is a leading cause of susceptibility to tuberculosis (TB), with the risk of TB being increased at all stages of HIV-1 infection. Antiretroviral treatment (ART) is the most effective way to reduce the risk of TB in HIV-1 co-infected people. Studying protective, ART-induced, immune restoration in HIV-1 infected individuals sensitised by Mycobacterium tuberculosis (Mtb) can thus help identify mechanisms of protection against TB. In order to understand ART-mediated prevention of TB in HIV-1 infected adults, we investigated the expression of 30 genes in whole blood from HIV-1 infected patients during the first 6 months of ART-induced immune reconstitution. The 30 selected genes were previously described to be differentially expressed between sorted Mtb specific central and effector memory CD4 T cells. HIV-1 infected persons sensitised by Mtb were recruited in Khayelitsha, South Africa, when initiating ART. RNA was extracted from whole blood at initiation and 1, 3 and 6 months of ART. qRT-PCR was used to determine gene expression and three reference ‘housekeeping’ genes were used to calculate the fold change in the expression of each gene relative to day 0 of ART. Results were assessed longitudinally. We observed a decrease in the expression of a number of genes at 6 months of ART, reflecting a decrease in immune activation. However, following correction for multiple comparisons and increasing CD4 counts, only the decrease in CD27 gene expression remained statistically significant. While not statistically significant, a number of genes also showed increased expression at various timepoints, illustrating the broad regeneration of the T cell pool in HIV-1 infected adults on ART. Our findings generate hypotheses underlying ART- induced protective immune reconstitution and may pave the way for future studies to evaluate ART mediated prevention of TB in HIV-1 infected persons.

ACS Style

Nishtha Jhilmeet; David M. Lowe; Catherine Riou; Thomas Scriba; Anna Coussens; Rene Goliath; Robert Wilkinson; Katalin Andrea Wilkinson. The effect of antiretroviral treatment on selected genes in whole blood from HIV-infected adults sensitised by Mycobacterium tuberculosis. PLOS ONE 2018, 13, e0209516 .

AMA Style

Nishtha Jhilmeet, David M. Lowe, Catherine Riou, Thomas Scriba, Anna Coussens, Rene Goliath, Robert Wilkinson, Katalin Andrea Wilkinson. The effect of antiretroviral treatment on selected genes in whole blood from HIV-infected adults sensitised by Mycobacterium tuberculosis. PLOS ONE. 2018; 13 (12):e0209516.

Chicago/Turabian Style

Nishtha Jhilmeet; David M. Lowe; Catherine Riou; Thomas Scriba; Anna Coussens; Rene Goliath; Robert Wilkinson; Katalin Andrea Wilkinson. 2018. "The effect of antiretroviral treatment on selected genes in whole blood from HIV-infected adults sensitised by Mycobacterium tuberculosis." PLOS ONE 13, no. 12: e0209516.

Review article
Published: 13 December 2018 in Frontiers in Immunology
Reads 0
Downloads 0

In high burden settings, the risk of infection with Mycobacterium tuberculosis increases throughout childhood due to cumulative exposure. However, the risk of progressing from tuberculosis (TB) infection to disease varies by age. Young children (<5 years) have high risk of disease progression following infection. The risk falls in primary school children (5 to <10 years), but rises again during puberty. TB disease phenotype also varies by age: generally, young children have intrathoracic lymph node disease or disseminated disease, while adolescents (10 to <20 years) have adult-type pulmonary disease. TB risk also exhibits a gender difference: compared to adolescent boys, adolescent girls have an earlier rise in disease progression risk and higher TB incidence until early adulthood. Understanding why primary school children, during what we term the “Wonder Years,” have low TB risk has implications for vaccine development, therapeutic interventions, and diagnostics. To understand why this group is at low risk, we need a better comprehension of why younger children and adolescents have higher risks, and why risk varies by gender. Immunological response to M. tuberculosis is central to these issues. Host response at key stages in the immunopathological interaction with M. tuberculosis influences risk and disease phenotype. Cell numbers and function change dramatically with age and sexual maturation. Young children have poorly functioning innate cells and a Th2 skew. During the “Wonder Years,” there is a lymphocyte predominance and a Th1 skew. During puberty, neutrophils become more central to host response, and CD4+ T cells increase in number. Sex hormones (dehydroepiandrosterone, adiponectin, leptin, oestradiol, progesterone, and testosterone) profoundly affect immunity. Compared to girls, boys have a stronger Th1 profile and increased numbers of CD8+ T cells and NK cells. Girls are more Th2-skewed and elicit more enhanced inflammatory responses. Non-immunological factors (including exposure intensity, behavior, and co-infections) may impact disease. However, given the consistent patterns seen across time and geography, these factors likely are less central. Strategies to protect children and adolescents from TB may need to differ by age and sex. Further work is required to better understand the contribution of age and sex to M. tuberculosis immunity.

ACS Style

James A. Seddon; Silvia Chiang; Hanif Esmail; Anna Coussens. The Wonder Years: What Can Primary School Children Teach Us About Immunity to Mycobacterium tuberculosis? Frontiers in Immunology 2018, 9, 2946 .

AMA Style

James A. Seddon, Silvia Chiang, Hanif Esmail, Anna Coussens. The Wonder Years: What Can Primary School Children Teach Us About Immunity to Mycobacterium tuberculosis? Frontiers in Immunology. 2018; 9 ():2946.

Chicago/Turabian Style

James A. Seddon; Silvia Chiang; Hanif Esmail; Anna Coussens. 2018. "The Wonder Years: What Can Primary School Children Teach Us About Immunity to Mycobacterium tuberculosis?" Frontiers in Immunology 9, no. : 2946.

Review article
Published: 14 November 2018 in Frontiers in Immunology
Reads 0
Downloads 0

Certain individuals are able to resist Mycobacterium tuberculosis infection despite persistent and intense exposure. These persons do not exhibit adaptive immune priming as measured by tuberculin skin test (TST) and interferon-γ (IFN-γ) release assay (IGRA) responses, nor do they develop active tuberculosis (TB). Genetic investigation of individuals who are able to resist M. tuberculosis infection shows there are likely a combination of genetic variants that contribute to the phenotype. The contribution of the innate immune system and the exact cells involved in this phenotype remain incompletely elucidated. Neutrophils are prominent candidates for possible involvement as primers for microbial clearance. Significant variability is observed in neutrophil gene expression and DNA methylation. Furthermore, inter-individual variability is seen between the mycobactericidal capacities of donor neutrophils. Clearance of M. tuberculosis infection is favored by the mycobactericidal activity of neutrophils, apoptosis, effective clearance of cells by macrophages, and resolution of inflammation. In this review we will discuss the different mechanisms neutrophils utilize to clear M. tuberculosis infection. We discuss the duality between neutrophils' ability to clear infection and how increasing numbers of neutrophils contribute to active TB severity and mortality. Further investigation into the potential role of neutrophils in innate immune-mediated M. tuberculosis infection resistance is warranted since it may reveal clinically important activities for prevention as well as vaccine and treatment development.

ACS Style

Elouise E. Kroon; Anna K. Coussens; Craig Kinnear; Marianna Orlova; Marlo Möller; Allison Seeger; Robert Wilkinson; Eileen G. Hoal; Erwin Schurr. Neutrophils: Innate Effectors of TB Resistance? Frontiers in Immunology 2018, 9, 2637 .

AMA Style

Elouise E. Kroon, Anna K. Coussens, Craig Kinnear, Marianna Orlova, Marlo Möller, Allison Seeger, Robert Wilkinson, Eileen G. Hoal, Erwin Schurr. Neutrophils: Innate Effectors of TB Resistance? Frontiers in Immunology. 2018; 9 ():2637.

Chicago/Turabian Style

Elouise E. Kroon; Anna K. Coussens; Craig Kinnear; Marianna Orlova; Marlo Möller; Allison Seeger; Robert Wilkinson; Eileen G. Hoal; Erwin Schurr. 2018. "Neutrophils: Innate Effectors of TB Resistance?" Frontiers in Immunology 9, no. : 2637.

Review
Published: 01 November 2018 in Current Opinion in HIV and AIDS
Reads 0
Downloads 0

Tuberculosis is the leading infectious cause of death worldwide, and HIV-1 the best recognized risk factor for active TB. This review focuses on immune complex formation; the interplay of type I and II interferon signaling; and T-cell activation in HIV–TB pathogenesis. Circulating immune complexes and complement, and Fcγ signaling in whole blood act as early markers of TB disease in HIV-1-infected persons. HIV-1 is associated with a type I interferon response in whole blood, reducing the specificity of TB biomarkers dependent on type I and II interferon genes. Type I and type II interferons are implicated in both protection and TB disease, a protective outcome may depend on modulating these pathways. Whilst M. tuberculosis-specific CD4 T cells are preferentially depleted during HIV-1 infection, activation markers on M. tuberculosis-specific CD4 T cells, in particular HLA-DR, reflect immune activation and have promise as biomarkers of M. tuberculosis disease activity in individuals with HIV-1. TB pathogenesis in HIV-1 involves a complex interaction of underlying activation of both the innate and adaptive immune systems. Further research is required to understand whether biomarkers of activation could be used to predict or quantify TB disease in the context of HIV-1 infection.

ACS Style

Elsa Du Bruyn; Nashied Peton; Hanif Esmail; Patrick J. Howlett; Anna Coussens; Robert Wilkinson. Recent progress in understanding immune activation in the pathogenesis in HIV–tuberculosis co-infection. Current Opinion in HIV and AIDS 2018, 13, 455 -461.

AMA Style

Elsa Du Bruyn, Nashied Peton, Hanif Esmail, Patrick J. Howlett, Anna Coussens, Robert Wilkinson. Recent progress in understanding immune activation in the pathogenesis in HIV–tuberculosis co-infection. Current Opinion in HIV and AIDS. 2018; 13 (6):455-461.

Chicago/Turabian Style

Elsa Du Bruyn; Nashied Peton; Hanif Esmail; Patrick J. Howlett; Anna Coussens; Robert Wilkinson. 2018. "Recent progress in understanding immune activation in the pathogenesis in HIV–tuberculosis co-infection." Current Opinion in HIV and AIDS 13, no. 6: 455-461.

Journal article
Published: 26 September 2018 in Clinical Infectious Diseases
Reads 0
Downloads 0

Background The risk of individuals infected with human immunodeficiency virus (HIV)-1 developing tuberculosis (TB) is high, while both prognostic and diagnostic tools remain insensitive. The potential for plasma biomarkers to predict which HIV-1–infected individuals are likely to progress to active disease is unknown. Methods Thirteen analytes were measured from QuantiFERON Gold in-tube (QFT) plasma samples in 421 HIV-1–infected persons recruited within the screening and enrollment phases of a randomized, controlled trial of isoniazid preventive therapy. Blood for QFT was obtained pre-randomization. Individuals were classified into prevalent TB, incident TB, and control groups. Comparisons between groups, supervised learning methods, and weighted correlation network analyses were applied utilizing the unstimulated and background-corrected plasma analyte concentrations. Results Unstimulated samples showed higher analyte concentrations in the prevalent and incident TB groups compared to the control group. The largest differences were seen for C-X-C motif chemokine 10 (CXCL10), interleukin-2 (IL-2), IL-1α, transforming growth factor-α (TGF-α). A predictive model analysis using unstimulated analytes discriminated best between the control and prevalent TB groups (area under the curve [AUC] = 0.9), reasonably well between the incident and prevalent TB groups (AUC > 0.8), and poorly between the control and incident TB groups. Unstimulated IL-2 and IFN-γ were ranked at or near the top for all comparisons, except the comparison between the control vs incident TB groups. Models using background-adjusted values performed poorly. Conclusions Single plasma biomarkers are unlikely to distinguish between disease states in HIV-1 co-infected individuals, and combinations of biomarkers are required. The ability to detect prevalent TB is potentially important, as no blood test hitherto has been suggested as having the utility to detect prevalent TB amongst HIV-1 co-infected persons.

ACS Style

Maia Lesosky; Molebogeng X Rangaka; Cara Pienaar; Anna K Coussens; Rene Goliath; Shaheed Mathee; Judith Mwansa-Kambafwile; Gary Maartens; Robert Wilkinson; Katalin Andrea Wilkinson. Plasma Biomarkers to Detect Prevalent or Predict Progressive Tuberculosis Associated With Human Immunodeficiency Virus–1. Clinical Infectious Diseases 2018, 69, 295 -305.

AMA Style

Maia Lesosky, Molebogeng X Rangaka, Cara Pienaar, Anna K Coussens, Rene Goliath, Shaheed Mathee, Judith Mwansa-Kambafwile, Gary Maartens, Robert Wilkinson, Katalin Andrea Wilkinson. Plasma Biomarkers to Detect Prevalent or Predict Progressive Tuberculosis Associated With Human Immunodeficiency Virus–1. Clinical Infectious Diseases. 2018; 69 (2):295-305.

Chicago/Turabian Style

Maia Lesosky; Molebogeng X Rangaka; Cara Pienaar; Anna K Coussens; Rene Goliath; Shaheed Mathee; Judith Mwansa-Kambafwile; Gary Maartens; Robert Wilkinson; Katalin Andrea Wilkinson. 2018. "Plasma Biomarkers to Detect Prevalent or Predict Progressive Tuberculosis Associated With Human Immunodeficiency Virus–1." Clinical Infectious Diseases 69, no. 2: 295-305.

Original research article
Published: 03 August 2018 in Frontiers in Cellular and Infection Microbiology
Reads 0
Downloads 0

An emerging realization of infectious disease is that pathogens can cause a high incidence of genetic instability within the host as a result of infection-induced DNA lesions. These often lead to classical hallmarks of cancer, one of which is the ability to evade apoptosis despite the presence of numerous genetic mutations that should be otherwise lethal. The Human Immunodeficiency Virus type 1 (HIV-1) is one such pathogen as it induces apoptosis in CD4+ T cells but is largely non-cytopathic in macrophages. As a consequence there is long-term dissemination of the pathogen specifically by these infected yet surviving host cells. Apoptosis is triggered by double-strand breaks (DSBs), such as those induced by integrating retroviruses like HIV-1, and is coordinated by the p53-regulated long noncoding RNA lincRNA-p21. As is typical for a long noncoding RNA, lincRNA-p21 mediates its activities in a complex with one of its two protein binding partners, namely HuR and hnRNP-K. In this work, we monitor the cellular response to infection to determine how HIV-1 induces DSBs in macrophages yet evades apoptosis in these cells. We show that the virus does so by securing the pro-survival MAP2K1/ERK2 cascade early upon entry, in a gp120-dependent manner, to orchestrate a complex dysregulation of lincRNA-p21. By sequestering the lincRNA-p21 partner HuR in the nucleus, HIV-1 enables lincRNA-p21 degradation. Simultaneously, the virus permits transcription of pro-survival genes by sequestering lincRNA-p21's other protein partner hnRNP-K in the cytoplasm via the MAP2K1/ERK2 pathway. Of particular note, this MAP2K1/ERK2 pro-survival cascade is switched off during T cell maturation and is thus unavailable for similar viral manipulation in mature CD4+ T cells. We show that the introduction of MAP2K1, ERK2, or HDM2 inhibitors in HIV-infected macrophages results in apoptosis, providing strong evidence that the viral-mediated apoptotic block can be released, specifically by restoring the nuclear interaction of lincRNA-p21 and its apoptosis protein partner hnRNP-K. Together, these results reveal a unique example of pathogenic control over mammalian apoptosis and DNA damage via a host long noncoding RNA, and present MAP2K1/ERK2 inhibitors as a novel therapeutic intervention strategy for HIV-1 infection in macrophages.

ACS Style

Samantha Barichievy; Jerolen Naidoo; Mikaël Boullé; Janine Scholefield; Suraj Prakash Parihar; Anna Coussens; Frank Brombacher; Alex Sigal; Musa M. Mhlanga. Viral Apoptosis Evasion via the MAPK Pathway by Use of a Host Long Noncoding RNA. Frontiers in Cellular and Infection Microbiology 2018, 8, 263 .

AMA Style

Samantha Barichievy, Jerolen Naidoo, Mikaël Boullé, Janine Scholefield, Suraj Prakash Parihar, Anna Coussens, Frank Brombacher, Alex Sigal, Musa M. Mhlanga. Viral Apoptosis Evasion via the MAPK Pathway by Use of a Host Long Noncoding RNA. Frontiers in Cellular and Infection Microbiology. 2018; 8 ():263.

Chicago/Turabian Style

Samantha Barichievy; Jerolen Naidoo; Mikaël Boullé; Janine Scholefield; Suraj Prakash Parihar; Anna Coussens; Frank Brombacher; Alex Sigal; Musa M. Mhlanga. 2018. "Viral Apoptosis Evasion via the MAPK Pathway by Use of a Host Long Noncoding RNA." Frontiers in Cellular and Infection Microbiology 8, no. : 263.

Journal article
Published: 16 January 2018 in Proceedings of the National Academy of Sciences
Reads 0
Downloads 0

The transition between latent and active tuberculosis (TB) occurs before symptom onset. Better understanding of the early events in subclinical disease will facilitate the development of diagnostics and interventions that improve TB control. This is particularly relevant in the context of HIV-1 coinfection where progression of TB is more likely. In a recent study using [18F]-fluoro-2-deoxy-d-glucose positron emission/computed tomography (FDG-PET/CT) on 35 asymptomatic, HIV-1–infected adults, we identified 10 participants with radiographic evidence of subclinical disease, significantly more likely to progress than the 25 participants without. To gain insight into the biological events in early disease, we performed blood-based whole genome transcriptomic analysis on these participants and 15 active patients with TB. We found transcripts representing the classical complement pathway and Fcγ receptor 1 overabundant from subclinical stages of disease. Levels of circulating immune (antibody/antigen) complexes also increased in subclinical disease and were highly correlated with C1q transcript abundance. To validate our findings, we analyzed transcriptomic data from a publicly available dataset where samples were available in the 2 y before TB disease presentation. Transcripts representing the classical complement pathway and Fcγ receptor 1 were also differentially expressed in the 12 mo before disease presentation. Our results indicate that levels of antibody/antigen complexes increase early in disease, associated with increased gene expression of C1q and Fcγ receptors that bind them. Understanding the role this plays in disease progression may facilitate development of interventions that prevent this, leading to a more favorable outcome and may also be important to diagnostic development.

ACS Style

Hanif Esmail; Rachel P. Lai; Maia Lesosky; Katalin Wilkinson; Christine M. Graham; Stuart Horswell; Anna K. Coussens; Clifton E. Barry; Anne O’Garra; Robert Wilkinson. Complement pathway gene activation and rising circulating immune complexes characterize early disease in HIV-associated tuberculosis. Proceedings of the National Academy of Sciences 2018, 115, E964 -E973.

AMA Style

Hanif Esmail, Rachel P. Lai, Maia Lesosky, Katalin Wilkinson, Christine M. Graham, Stuart Horswell, Anna K. Coussens, Clifton E. Barry, Anne O’Garra, Robert Wilkinson. Complement pathway gene activation and rising circulating immune complexes characterize early disease in HIV-associated tuberculosis. Proceedings of the National Academy of Sciences. 2018; 115 (5):E964-E973.

Chicago/Turabian Style

Hanif Esmail; Rachel P. Lai; Maia Lesosky; Katalin Wilkinson; Christine M. Graham; Stuart Horswell; Anna K. Coussens; Clifton E. Barry; Anne O’Garra; Robert Wilkinson. 2018. "Complement pathway gene activation and rising circulating immune complexes characterize early disease in HIV-associated tuberculosis." Proceedings of the National Academy of Sciences 115, no. 5: E964-E973.

Preprint
Published: 21 June 2017
Reads 0
Downloads 0

SUMMARYAn emerging realisation of infectious disease is the high incidence of genetic instability resulting from pathogen-induced DNA lesions, often leading to classical hallmarks of cancer such as evasion of apoptosis. The Human Immunodeficiency Virus type 1 (HIV-1) induces apoptosis in CD4+ T cells but is largely non-cytopathic in macrophages, thereby leading to long-term dissemination of the pathogen specifically by these host cells. Apoptosis is triggered by double-strand breaks (DSBs), such as those induced by integrating retroviruses, and is coordinated by the p53-regulated long noncoding RNA lincRNA-p21, in a complex with its protein binding partners HuR and hnRNP-K. Here, we monitor the cellular response to infection to determine how HIV-1 induces DSBs in macrophages yet evades apoptosis in these cells. We show that the virus does so by securing the pro-survival MAP2K1/ERK2 cascade early upon entry, in a gp120-dependent manner, to orchestrate a complex dysregulation of lincRNA-p21. By sequestering HuR in the nucleus, HIV-1 enables lincRNA-p21 degradation. Simultaneously, the virus permits transcription of pro-survival genes by sequestering hnRNP-K in the cytoplasm via the MAP2K1/ERK2 pathway. Notably, this pro-survival cascade is unavailable for similar viral manipulation in CD4+ T cells. The introduction of MAP2K1, ERK2 or HDM2 inhibitors in HIV-infected macrophages results in apoptosis providing strong evidence that the viral-mediated apoptotic block can be released, specifically by restoring the nuclear interaction of lincRNA-p21 and hnRNP-K. These results reveal pathogenic control of apoptosis and DNA damage via a host long noncoding RNA, and present MAP2K1/ERK2 inhibitors as a novel therapeutic intervention strategy for HIV-1 infection in macrophages.

ACS Style

Samantha Barichievy; Jerolen Naidoo; Mikael Boulle; Janine Scholefield; Suraj P. Parihar; Anna K. Coussens; Frank Brombacher; Alex Sigal; Musa M. Mhlanga. Viral apoptosis evasion via the MAPK pathway by use of a host long noncoding RNA. 2017, 153130 .

AMA Style

Samantha Barichievy, Jerolen Naidoo, Mikael Boulle, Janine Scholefield, Suraj P. Parihar, Anna K. Coussens, Frank Brombacher, Alex Sigal, Musa M. Mhlanga. Viral apoptosis evasion via the MAPK pathway by use of a host long noncoding RNA. . 2017; ():153130.

Chicago/Turabian Style

Samantha Barichievy; Jerolen Naidoo; Mikael Boulle; Janine Scholefield; Suraj P. Parihar; Anna K. Coussens; Frank Brombacher; Alex Sigal; Musa M. Mhlanga. 2017. "Viral apoptosis evasion via the MAPK pathway by use of a host long noncoding RNA." , no. : 153130.

Journal article
Published: 01 June 2017 in The International Journal of Tuberculosis and Lung Disease
Reads 0
Downloads 0

We speculate that vitamin D-mediated signalling of pro-inflammatory innate immune cells, along with high antigenic load, may mediate paradoxical reactions in anti-tuberculosis treatment.

ACS Style

D. A. Barr; A. K. Coussens; S. Irvine; N. D. Ritchie; K. Herbert; B. Choo-Kang; D. Raeside; D. J. Bell; R. A. Seaton. Paradoxical upgrading reaction in extra-pulmonary tuberculosis: association with vitamin D therapy. The International Journal of Tuberculosis and Lung Disease 2017, 21, 677 -683.

AMA Style

D. A. Barr, A. K. Coussens, S. Irvine, N. D. Ritchie, K. Herbert, B. Choo-Kang, D. Raeside, D. J. Bell, R. A. Seaton. Paradoxical upgrading reaction in extra-pulmonary tuberculosis: association with vitamin D therapy. The International Journal of Tuberculosis and Lung Disease. 2017; 21 (6):677-683.

Chicago/Turabian Style

D. A. Barr; A. K. Coussens; S. Irvine; N. D. Ritchie; K. Herbert; B. Choo-Kang; D. Raeside; D. J. Bell; R. A. Seaton. 2017. "Paradoxical upgrading reaction in extra-pulmonary tuberculosis: association with vitamin D therapy." The International Journal of Tuberculosis and Lung Disease 21, no. 6: 677-683.

Observational study
Published: 05 May 2017 in Clinical Infectious Diseases
Reads 0
Downloads 0

Extensive immunopathology occurs in human immunodeficiency virus (HIV)/tuberculosis (TB) coinfection, but the underlying molecular mechanisms are not well-defined. Excessive matrix metalloproteinase (MMP) activity is emerging as a key process but has not been systematically studied in HIV-associated TB. We performed a cross-sectional study of matrix turnover in HIV type 1 (HIV-1)–infected and –uninfected TB patients and controls, and a prospective cohort study of HIV-1–infected TB patients at risk of TB immune reconstitution inflammatory syndrome (TB-IRIS), in Cape Town, South Africa. Sputum and plasma MMP concentrations were quantified by Luminex, plasma procollagen III N-terminal propeptide (PIIINP) by enzyme-linked immunosorbent assay, and urinary lipoarabinomannan (LAM) by Alere Determine TB LAM assay. Peripheral blood mononuclear cells from healthy donors were cultured with Mycobacterium tuberculosis and extracellular matrix in a 3D model of TB granuloma formation. MMP activity differed between HIV-1–infected and –uninfected TB patients and corresponded with specific TB clinical phenotypes. HIV-1–infected TB patients had reduced pulmonary MMP concentrations, associated with reduced cavitation, but increased plasma PIIINP, compared to HIV-1–uninfected TB patients. Elevated extrapulmonary extracellular matrix turnover was associated with TB-IRIS, both before and during TB-IRIS onset. The predominant collagenase was MMP-8, which was likely neutrophil derived and M. tuberculosis–antigen driven. Mycobacterium tuberculosis–induced matrix degradation was suppressed by the MMP inhibitor doxycycline in vitro. MMP activity in TB differs by HIV-1 status and compartment, and releases matrix degradation products. Matrix turnover in HIV-1–infected patients is increased before and during TB-IRIS, informing novel diagnostic strategies. MMP inhibition is a potential host-directed therapy strategy for prevention and treatment of TB-IRIS.

ACS Style

Naomi F Walker; Katalin A Wilkinson; Graeme Meintjes; Liku B Tezera; Rene Goliath; Janique M Peyper; Rebecca Tadokera; Charles Opondo; Anna K Coussens; Robert J Wilkinson; Jon S Friedland; Paul T Elkington. Matrix Degradation in Human Immunodeficiency Virus Type 1–Associated Tuberculosis and Tuberculosis Immune Reconstitution Inflammatory Syndrome: A Prospective Observational Study. Clinical Infectious Diseases 2017, 65, 121 -132.

AMA Style

Naomi F Walker, Katalin A Wilkinson, Graeme Meintjes, Liku B Tezera, Rene Goliath, Janique M Peyper, Rebecca Tadokera, Charles Opondo, Anna K Coussens, Robert J Wilkinson, Jon S Friedland, Paul T Elkington. Matrix Degradation in Human Immunodeficiency Virus Type 1–Associated Tuberculosis and Tuberculosis Immune Reconstitution Inflammatory Syndrome: A Prospective Observational Study. Clinical Infectious Diseases. 2017; 65 (1):121-132.

Chicago/Turabian Style

Naomi F Walker; Katalin A Wilkinson; Graeme Meintjes; Liku B Tezera; Rene Goliath; Janique M Peyper; Rebecca Tadokera; Charles Opondo; Anna K Coussens; Robert J Wilkinson; Jon S Friedland; Paul T Elkington. 2017. "Matrix Degradation in Human Immunodeficiency Virus Type 1–Associated Tuberculosis and Tuberculosis Immune Reconstitution Inflammatory Syndrome: A Prospective Observational Study." Clinical Infectious Diseases 65, no. 1: 121-132.

Journal article
Published: 01 May 2017 in International Journal of Infectious Diseases
Reads 0
Downloads 0
ACS Style

Anna K. Coussens; Paul H. Mason; Tolu Oni. Socio-political prescriptions for latent tuberculosis infection are required to prevent reactivation of tuberculosis. International Journal of Infectious Diseases 2017, 58, 115 -116.

AMA Style

Anna K. Coussens, Paul H. Mason, Tolu Oni. Socio-political prescriptions for latent tuberculosis infection are required to prevent reactivation of tuberculosis. International Journal of Infectious Diseases. 2017; 58 ():115-116.

Chicago/Turabian Style

Anna K. Coussens; Paul H. Mason; Tolu Oni. 2017. "Socio-political prescriptions for latent tuberculosis infection are required to prevent reactivation of tuberculosis." International Journal of Infectious Diseases 58, no. : 115-116.

Review
Published: 24 February 2017 in Microbiology Spectrum
Reads 0
Downloads 0

Immunology is a central theme when it comes to tuberculosis (TB). The outcome of human infection with Mycobacterium tuberculosis is dependent on the ability of the immune response to clear or contain the infection. In cases where this fails, the bacterium replicates, disseminates within the host, and elicits a pathologic inflammatory response, and disease ensues. Clinical presentation of TB disease is remarkably heterogeneous, and the disease phenotype is largely dependent on host immune status. Onward transmission of M. tuberculosis to new susceptible hosts is thought to depend on an excessive inflammatory response causing a breakdown of the lung matrix and formation of lung cavities. But this varies in cases of underlying immunological dysfunction: for example, HIV-1 infection is associated with less cavitation, while diabetes mellitus comorbidity is associated with increased cavitation and risk of transmission. In compliance with the central theme of immunology in tuberculosis, we rely on detection of an adaptive immune response, in the form of interferon-gamma release assays or tuberculin skin tests, to diagnose infection with M. tuberculosis . Here we review the immunology of TB in the human host, focusing on cellular and humoral adaptive immunity as well as key features of innate immune responses and the underlying immunological dysfunction which associates with human TB risk factors. Our review is restricted to human immunology, and we highlight distinctions from the immunological dogma originating from animal models of TB, which pervade the field.

ACS Style

Thomas J. Scriba; Anna Coussens; Helen A. Fletcher. Human Immunology of Tuberculosis. Microbiology Spectrum 2017, 5, 1 .

AMA Style

Thomas J. Scriba, Anna Coussens, Helen A. Fletcher. Human Immunology of Tuberculosis. Microbiology Spectrum. 2017; 5 (1):1.

Chicago/Turabian Style

Thomas J. Scriba; Anna Coussens; Helen A. Fletcher. 2017. "Human Immunology of Tuberculosis." Microbiology Spectrum 5, no. 1: 1.

Review
Published: 01 January 2017 in Photochemical & Photobiological Sciences
Reads 0
Downloads 0

Individual components of solar radiation, UVA, UVB and heat generation, are linked to their downstream immune functions, inducing vitamin D production, demonstrating a great degree of overlap between various components.

ACS Style

Abhimanyu Abhimanyu; Anna K. Coussens. The role of UV radiation and vitamin D in the seasonality and outcomes of infectious disease. Photochemical & Photobiological Sciences 2017, 16, 314 -338.

AMA Style

Abhimanyu Abhimanyu, Anna K. Coussens. The role of UV radiation and vitamin D in the seasonality and outcomes of infectious disease. Photochemical & Photobiological Sciences. 2017; 16 (3):314-338.

Chicago/Turabian Style

Abhimanyu Abhimanyu; Anna K. Coussens. 2017. "The role of UV radiation and vitamin D in the seasonality and outcomes of infectious disease." Photochemical & Photobiological Sciences 16, no. 3: 314-338.

Correspondence
Published: 31 October 2016 in European Respiratory Journal
Reads 0
Downloads 0

Albert et al . [1] advocate for a multipronged approach in rolling out new diagnostic technology for tuberculosis (TB), stating “diagnostic tests alone, if not implemented with a comprehensive package of accompanying tools and within the context of a strengthened health system, may fail to demonstrate the expected benefit”. This is a lesson learned from those who have walked this path before us; one should not be too complacent to ignore basic strategies in the face of escalating technological advances in our field. Without societal, lifestyle and dietary innovations, new technologies will be ineffectual in stopping tuberculosis

ACS Style

Paul H. Mason; Tolu Oni; Maarten M.J.W. Van Herpen; Anna K. Coussens. Tuberculosis prevention must integrate technological and basic care innovation. European Respiratory Journal 2016, 48, 1529 -1531.

AMA Style

Paul H. Mason, Tolu Oni, Maarten M.J.W. Van Herpen, Anna K. Coussens. Tuberculosis prevention must integrate technological and basic care innovation. European Respiratory Journal. 2016; 48 (5):1529-1531.

Chicago/Turabian Style

Paul H. Mason; Tolu Oni; Maarten M.J.W. Van Herpen; Anna K. Coussens. 2016. "Tuberculosis prevention must integrate technological and basic care innovation." European Respiratory Journal 48, no. 5: 1529-1531.

Review
Published: 18 October 2016 in International Journal of Environmental Research and Public Health
Reads 0
Downloads 0

In this review, reports were retrieved in which vitamin D status, as assessed by serum 25-hydroxyvitamin D [25(OH)D] levels, was measured in South African population groups with varied skin colours and ethnicities. Healthy children and adults were generally vitamin D-sufficient [25(OH)D level >50 nmol/L] but the majority of those aged above 65 years were deficient. A major role for exposure to solar ultraviolet radiation (UVR) in determining 25(OH)D levels was apparent, with the dietary contribution being minor. Limited data exist regarding the impact of recent changes in lifestyles on vitamin D status, such as urbanisation. With regard to disease susceptibility, 11 of 22 relevant publications indicated association between low 25(OH)D levels and disease, with deficiency most notably found in individuals with tuberculosis and HIV-1. Information on the relationship between vitamin D receptor variants and ethnicity, disease or treatment response in the South African population groups demonstrated complex interactions between genetics, epigenetics and the environment. Whether vitamin D plays an important role in protection against the range of diseases that currently constitute a large burden on the health services in South Africa requires further investigation. Only then can accurate advice be given about personal sun exposure or dietary vitamin D supplementation.

ACS Style

Mary Norval; Anna K. Coussens; Robert Wilkinson; Liza Bornman; Robyn M. Lucas; Caradee Y. Wright. Vitamin D Status and Its Consequences for Health in South Africa. International Journal of Environmental Research and Public Health 2016, 13, 1019 .

AMA Style

Mary Norval, Anna K. Coussens, Robert Wilkinson, Liza Bornman, Robyn M. Lucas, Caradee Y. Wright. Vitamin D Status and Its Consequences for Health in South Africa. International Journal of Environmental Research and Public Health. 2016; 13 (10):1019.

Chicago/Turabian Style

Mary Norval; Anna K. Coussens; Robert Wilkinson; Liza Bornman; Robyn M. Lucas; Caradee Y. Wright. 2016. "Vitamin D Status and Its Consequences for Health in South Africa." International Journal of Environmental Research and Public Health 13, no. 10: 1019.