The Principal Investigators make up the CIDRI-Africa Steering Committee.
Honorary Professor Robert J Wilkinson: Director
Professor Valerie Mizrahi: Basic Science Platform Lead
Professor Nicola Mulder and Professor Andrew Boulle: Biomedical Data Integration Platform Co-leads
Professor Graeme Meintjes: Clinical Research Platform Lead
Professor Clifton Barry
Professor Frank Brombacher
Professor Gary Maartens
Professor Helen McIlleron
Professor Mark Nicol
Professor Thomas Scriba
Professor Carolyn Williamson
Robert J Wilkinson is a Wellcome Senior Fellow in Clinical Science held as Professor of Infectious Diseases at Imperial College London, and a senior Group Leader at The Francis Crick Institute London. He holds an Honorary professorship in Medicine in the Institute of Infectious Disease and Molecular Medicine and directs the Wellcome Centre for Infectious Diseases Research in Africa at the University of Cape Town. Wilkinson’s research interest is understanding tuberculosis and HIV-associated tuberculosis.
Esmail H, Riou C, du Bruyn E, Lai RP-J, Harley YXR, Meintjes G, Wilkinson KA, Wilkinson RJ. The immune response to Mycobacterium tuberculosis in HIV-1-coinfected persons. Annual Review of Immunology. (2018) 36(1):22.1-22.36.
Wilkinson RJ, Rohlwink U, Misra UK, van Crevel R, Mai NTH, Dooley KE, Caws M, Figaji A, Savic R, Solomons R, Thwaites GE, on behalf of the Tuberculous Meningitis International Research Consortium. Tuberculous meningitis. Nature Reviews Neurology. (2017) 13(10):581–98.
Esmail H, Lai RP, Lesosky M, Wilkinson KA, Graham CM, Coussens AK, Oni T, Warwick JM, Said-Hartley Q, Koegelenberg CF, Walzl G, Flynn JL, Young DB, Barry III CE, O’Garra A, Wilkinson RJ. Characterization of progressive HIV-associated tuberculosis using 2-deoxy-2-[18F]fluoro-D-glucose positron emission and computed tomography. Nature Medicine. (2016) 22(10):1090–3.
Valerie Mizrahi is director of the Institute of Infectious Disease and Molecular Medicine at UCT. She also leads the MRC/NHLS/UCT Molecular Mycobacteriology Research Unit, co-directs the DST/NRF Centre of Excellence for Biomedical TB Research, and was a Senior International Research Scholar of the HHMI from 2012-2017. Her research focuses on aspects of the physiology and metabolism of Mycobacterium tuberculosis of relevance to TB drug resistance, mycobacterial persistence and TB drug discovery. Valerie holds an A1 rating from the NRF. She is a Fellow of the American Academy of Microbiology, African Academy of Science and Royal Society of South Africa, an Associate Fellow of TWAS, and Member of the Academy of Science of SA. Her awards include the 2013 Christophe Mérieux Prize from the Mérieux Foundation and Institut de France; Order of the Mapungubwe (Silver) in 2007; 2017 Platinum Medal from the SAMRC, and 2000 Unesco-L’Oréal For Women in Science Award (Africa & Middle East).
Singh, V., Donini, S., Pacitto, A., Sala, C., Hartkoorn, R.C., Dhar, N., Keri, G., Ascher, D.B., Mondésert, G., Vocat, A., Lupien, A., Sommer, R., Vermet, H., Lagrange, S., Buechler, J., Warner, D.F., McKinney, J.D., Pato, J., Cole, S.T., Blundell, T.L., Rizzi, M., and Mizrahi, V. The inosine monophosphate dehydrogenase, GuaB2, is a vulnerable new bactericidal drug target for tuberculosis. ACS Infect. Dis. (2017) 3:5-17. DOI: 10.1021/acsinfecdis.6b00102. PMCID: PMC5241705.
Kana, B. D., Gordhan, B.G., Downing, K.J., Sung. N., Vostroktunova, G., Machowski, E.E., Tsenova, G., Young, M., Kaprelyants, A., Kaplan, G., and Mizrahi, V. The resuscitation-promoting factors of Mycobacterium tuberculosis are required for virulence and resuscitation from dormancy but are collectively dispensable for growth in vitro. Mol. Microbiol. (2008) 67:672-684.
Boshoff, H.I.M., Reed, M.B., Barry, C.E., III*, and Mizrahi, V*. DnaE2 polymerase contributes to in vivo survival and the emergence of drug resistance in Mycobacterium tuberculosis. Cell. (2003) 113:183-193.
Professor Mulder heads the Computational Biology Division at the University of Cape Town, and leads H3ABioNet, a large Pan African Bioinformatics Network of ~30 institutions in 17 African countries. H3ABioNet aims to develop bioinformatics capacity to enable genomic data analysis on the continent by developing and providing access to skills and computing infrastructure for data analysis. Prior to her position at UCT, she worked for 9 years at the European Bioinformatics Institute (EBI) in Cambridge, as a Team Leader for bioinformatics resources. At UCT her research focuses on genetic determinants of susceptibility to disease, African genome variation, microbiomes, microbial genomics and infectious diseases from both the host and pathogen perspectives. Her group also provides bioinformatics services for the local researchers, through which they develop visualization and analysis tools for high-throughput biology. Her team has also been involved in the development of new and improved algorithms for the analysis of complex African genetic data as well as for downstream analysis and interpretation of GWAS data. Professor Mulder is actively involved in training and education as well as curriculum development in bioinformatics and genomic medicine.
Issarow CM, Mulder N, Wood R. Environmental and social factors impacting on epidemic and endemic tuberculosis: a modelling analysis. Royal Society Open Science. (2018) 5(1):170726.
Choudhury A, Ramsay M, Hazelhurst S, Aron S, Bardien S, Botha G, Chimusa ER, Christoffels A, Gamieldien J, Sefid-Dashti MJ, Joubert F, Meintjes A, Mulder N, Ramesar R, Rees J, Scholtz K, Sengupta D, Soodyall H, Venter P, Warnich L, Pepper MS. Whole-genome sequencing for an enhanced understanding of genetic variation among South Africans. Nature Communications. (2017) 8(1):2062.
Mulder N, Adebamowo CA, Adebamowo SN, Adebayo O, Adeleye O, Alibi M, Baichoo S, Benkahla A, Fadlelmola FM, Ghazal H, Ghedira K, Matimba A, Moussa A, Mungloo-Dilmohamud Z, Owolabi MO, Radouani F, Rotimi CN, Stein DJ, Souiai O. Genomic research data generation, analysis and sharing – challenges in the African setting. Data Science Journal. (2017) 16:49.
Andrew Boulle is a Public Health Specialist with the Western Cape Department of Health and Professor in Public Health Medicine at the University of Cape Town. He co-leads the data integration platform for CIDRI-Africa, focussing on clinical and population health questions which can be addressed through routine clinical and administrative data, and data platform innovations for the linkage of routine data with clinical research and experimental data.
Within government he oversees the development of a consolidated environment for person-level health data, which also functions as an information exchange for selected clinical information systems. He leads the African Health Information Exchange (AHIE) project, which develops interoperability solutions in support of services for HIV and TB and other priority health conditions.
A dominant focus of his academic work has been on HIV cohort epidemiology. He is the principal investigator of the Khayelitsha HIV cohort and part of the IeDEA-SA data centre.
Osler M, Hilderbrand K, Goemaere E, Ford N, Smith M, Meintjes G, Kruger J, Govender NP, Boulle A. The continuing burden of advanced HIV disease over 10 years of increasing antiretroviral therapy coverage in South Africa. Clinical Infectious Diseases. (2018) 66(suppl_2):S118-S25.
Boulle A, Schomaker M, May MT, Hogg RS, Shepherd BE, Monge S, et al. Mortality in patients with HIV-1 infection starting antiretroviral therapy in South Africa, Europe, or North America: a collaborative analysis of prospective studies. PLoS Medicine. (2014) 11(9):e1001718.
Boulle A, Van Cutsem G, Cohen K, Hilderbrand K, Mathee S, Abrahams M, et al. Outcomes of nevirapine- and efavirenz-based antiretroviral therapy when coadministered with rifampicin-based antitubercular therapy. JAMA. (2008) 300(5):530-9.
Graeme Meintjes is a Professor of Medicine, Wellcome Fellow and SARChI Chair of Poverty-related Infections at the University of Cape Town. He is an Infectious Diseases Physician who undertakes consultant clinical work at Khayelitsha and Groote Schuur Hospitals. His research focuses on the clinical conditions affecting patients with advanced HIV disease including disseminated HIV-associated tuberculosis, the tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) and cryptococcal meningitis. His group also investigates drug-resistant tuberculosis. He has been the PI or local PI of several clinical trials and conducts observational cohort studies that address questions related to disease pathogenesis. Recently, he was PI of the EDCTP-funded PredART trial that demonstrated that prednisone was effective and safe for the prevention of TB-IRIS in patients at high-risk starting ART. He has contributed to the development of management guidelines for HIV, TB and cryptococcal meningitis at a provincial and national level and World Health Organization Guideline Development Groups.
Boulware DR, Meya DB, Muzoora C, Rolfes MA, Huppler Hullsiek K, Musubire A, Taseera K, Nabeta HW, Schutz C, Williams DA, Rajasingham R, Rhein J, Thienemann F, Lo MW, Nielsen K, Bergemann TL, Kambugu A, Manabe YC, Janoff EN, Bohjanen PR, Meintjes G, for the COAT Trial Team. Timing of antiretroviral therapy after diagnosis of cryptococcal meningitis. New England Journal of Medicine. (2014) 370(26):2487–98.
Kaplan SR, Oosthuizen C, Stinson K, Little F, Euvrard J, Schomaker M, Osler M, Hilderbrand K, Boulle A, Meintjes G. Contemporary disengagement from antiretroviral therapy in Khayelitsha, South Africa: a cohort study. PLOS Medicine. (2017) 14(11):e1002407.
Janssen S, Schutz C, Ward A, Nemes E, Wilkinson KA, Scriven J, Huson MA, Aben N, Maartens G, Burton R, Wilkinson RJ, Grobusch MP, Van der Poll T, Meintjes G. Mortality in severe Human Immunodeficiency Virus-tuberculosis associates with innate immune activation and dysfunction of monocytes. Clinical Infectious Diseases. (2017) 65(1):73–82.
Professor Brombacher moved to South Africa from Germany in 1998 to join UCT, where he established an extramural South African Medical Research Council Unit in 2000. In 2005, he became a UCT “Fellow for Life” and South African Research Chair and Coordinator at the International Centre for Genetic Engineering and Biotechnology (Cape Town component). He is A-rated by the NRF.
His group’s main research focus is the understanding of host protective immune responses in human diseases. The group investigates important regulatory mechanisms—including pattern recognition receptors and cytokine network and cellular crosstalk during innate immunity—which may lead to subsequent adaptive immunity or failure thereof. Their strategy is centred on a “gain of knowledge by loss of function” approach based on deficient mouse models generated by gene targeting in embryonic stem cells. The group works on experimental mouse models for TB, leishmaniasis, and trypanosomiasis, as well as helminth infections and schistosomiasis, and have additional interests in allergic conditions such as asthma and food-related allergies.
Professor Brombacher studied Biology at the Alberts-Ludwigs University Freiburg, Germany, and completed his PhD in Molecular Immunology at the Max Planck Institute in 1989.
Hurdayal R, Ndlovu HH, Revaz-Breton M, Parihar SP, Nono JK, Govender M, Brombacher F. IL-4-producing B cells regulate T helper cell dichotomy in type 1- and type 2-controlled diseases. Proc Natl Acad Sci USA. (2017) 114: E8430-E8439.
Hoving JC, Cutler AJ, Leeto M, Horsnell WG, Dewals BG, Nieuwenhuizen NE, Brombacher F. Interleukin 13-mediated colitis in the absence of IL-4Ra signalling. Gut. (2017) 66: 2037-2039.
Parihar SP, Ozturk M, Marakalala MJ, Loots DT, Hurdayal R, Beukes D, Van Reenen M, Zak DE, Mbandi SK, Darboe F, Penn-Nicholson A, Hanekom WA, Leitges M, Scriba TJ, Guler R, Brombacher F. Protein kinase C-delta (PKCd), a marker of inflammation and tuberculosis disease progression in humans, is important for optimal macrophage killing effector functions and survival in mice. Mucosal Immunol. (2017) Aug 23. doi: 10.1038/mi.2017.68.
Oetjen LK, Mack MR, Feng J, Whelan TM, Niu H, Guo CJ, Chen S, Trier AM, Xu AZ, Tripathi SV, Luo J, Gao X, Yang L, Hamilton SL, Wang PL, Brestoff JR, Council ML, Brasington R, Schaffer A, Brombacher F, Hsieh CS, Gereau RW 4th, Miller MJ, Chen ZF, Hu H, Davidson S, Liu Q, Kim BS. Sensory Neurons Co-opt Classical Immune Signaling Pathways to Mediate Chronic Itch. Cell. (2017) Aug 26. [Epub ahead of print].
White AJ, Baik S, Parnell SM, Holland AM, Brombacher F, Jenkinson WE, Anderson G. A type 2 cytokine axis for thymus emigration. J Exp Med. (2017) 214:2205-16.
Fischer K, HH Ruiz, K Jhun, B Finan, DJ Oberlin, V van der Heide, A V Kalinovich, N Petrovic, Y Wolf, C Clemmensen, A C Shin, S Divanovic, F Brombacher, E Glasmacher, S Keipert, M Jastroch, J Nagler, K-W Schramm, D Medrikova, G Collden, S C Woods, S Herzig, D Homan, S Jung, J Nedergaard, B Cannon, MH Tschöp, T D Müller & C Buettner. Alternatively activated macrophages do not synthesize catecholamines or contribute to adipose tissue adaptive thermogenesis. Nature Medicine. (2017) 23:623-30.
Gary Maartens is head of the Division of Clinical Pharmacology and a chief specialist physician (internist) at Groote Schuur hospital, where he does clinical service in internal medicine and infectious diseases. His main research interests are in therapeutic aspects of HIV-associated tuberculosis, drug-resistant tuberculosis, and antiretroviral therapy in resource-limited settings. He has published over 200 peer reviewed articles, including invited seminars on both tuberculosis and HIV for the Lancet. In 2015 he was awarded a gold medal for outstanding contributions to medical research by the Medical Research Council of South Africa. He was the founding president for the College of Clinical Pharmacologists. He has been involved in international guideline development for the management of HIV and tuberculosis for the World Health Organization and the Centers for Disease Control and Prevention. He serves on the Tuberculosis Transformative Science Group of the AIDS Clinical Trials Group, National Institutes of Health.
Griesel R, Stewart A, van der Plas H, Sikhondze W, Rangaka MX, Nicol MP, Kengne AP, Mendelson M, Maartens G. Optimizing tuberculosis diagnosis in Human Immunodeficiency Virus–infected inpatients meeting the criteria of Seriously Ill in the World Health Organization algorithm. Clinical Infectious Diseases. (in press) https://doi.org/10.1093/cid/cix988
Dheda K, Barry CE, Maartens G. Tuberculosis. The Lancet. (2016) 387(10024):1211–26.
Rangaka MX, Wilkinson RJ, Boulle A, Glynn JR, Fielding K, van Cutsem G, Wilkinson KA, Goliath R, Mathee S, Goemaere E, Maartens G. Isoniazid plus antiretroviral therapy to prevent tuberculosis: a randomised double-blind, placebo-controlled trial. The Lancet. (2014) 384(9944):682–90.
Based in the Division of Clinical Pharmacology at the University of Cape Town, Prof Helen McIlleron (MBChB, PhD) has lead and collaborated on multiple PK and PK/PD studies of anti-TB drugs and antiretrovirals in adults and children with focus on TB/HIV co-infection and special populations. I strongly believe in the development of investigator driven research for these diseases with the application of analytical tools facilitating research to optimize treatment in the relevant populations.
Bienczak A, Denti P, Cook A, Wiesner L, Mulenga V, Kityo C, Kekitiinwa A, Gibb DM, Burger D, Walker AS, McIlleron H. Plasma efavirenz exposure, sex, and age predict virological response in HIV-infected African children. Journal of Acquired Immune Deficiency Syndromes (1999). (2016) 73(2):161–8.
McIlleron H, Hundt H, Smythe W, Bekker A, Winckler J, van der Laan L, Smith P, Zar HJ, Hesseling AC, Maartens G, Wiesner L, van Rie A. Bioavailability of two licensed paediatric rifampicin suspensions: implications for quality control programmes. The International Journal of Tuberculosis and Lung Disease. (2016) 20(7):915–9.
Chigutsa E, Pasipanodya JG, Visser ME, van Helden PD, Smith PJ, Sirgel FA, Gumbo T, McIlleron H. Impact of nonlinear interactions of pharmacokinetics and MICs on sputum bacillary kill rates as a marker of sterilizing effect in tuberculosis. Antimicrobial Agents and Chemotherapy. (2015) 59(1):38–45.
Mark Nicol is a medical microbiologist who holds the Wernher and Beit Chair of Medical Microbiology at the University of Cape Town and the National Health Laboratory Service (NHLS) of South Africa. He studied medicine and medical microbiology at the University of the Witwatersrand and completed his PhD in childhood tuberculosis in Cape Town. His research interests are in the pathogenesis and diagnosis of respiratory infection in children, evaluation and implementation of novel diagnostic tests for tuberculosis, the cascade of care for patients with drug-resistant tuberculosis and the human microbiome.
Professor Scriba is an immunologist and heads a team of clinical immunologists, post-doctoral fellows and postgraduate students at UCT where he is a Member of the Institute of Infectious Disease and Molecular Medicine; he is also Deputy Director (Immunology) at the South African Tuberculosis Vaccine Initiative (SATVI). SATVI’s mission is the development of new and effective prevention strategies against TB, including vaccination and biomarker-targeted treatment approaches. His particular interests focus on immunopathology of mycobacterial infection and TB disease, correlates of risk of M. tuberculosis infection and TB disease, immunological development in childhood, and novel TB vaccine development. He has been co-investigator on more than 15 phase I/II/IIb clinical trials of novel TB vaccines, and has led the design and immunological analyses of vaccine-induced T cell responses for most of these. In the last 5 years he has also been leading studies of correlates of risk of TB in different cohorts.
Penn-Nicholson A, Tameris M, Smit E, Day TA, Musvosvi M, Jayashankar L, Vergara J, Mabwe S, Bilek N, Geldenhuys H, Luabeya AK-K, Ellis R, Ginsberg AM, Hanekom WA, Reed SG, Coler RN, Scriba TJ, Hatherill M. Safety and immunogenicity of the novel tuberculosis vaccine ID93 + GLA-SE in BCG-vaccinated healthy adults in South Africa: a randomised, double-blind, placebo-controlled phase 1 trial. The Lancet Respiratory Medicine. (2018) 6(4):287–98.
Scriba TJ, Penn-Nicholson A, Shankar S, Hraha T, Thompson EG, Sterling D, Nemes E, Darboe F, Suliman S, Amon LM, Mahomed H, Erasmus M, Whatney W, Johnson JL, Boom WH, Hatherill M, Valvo J, De Groote MA, Ochsner UA, Aderem A, Hanekom WA, Zak DE, other members of the ACS cohort study team. Sequential inflammatory processes define human progression from M. tuberculosis infection to tuberculosis disease. PLOS Pathogens. (2017) 13(11):e1006687.
Zak DE, Penn-Nicholson A, Scriba TJ, Thompson E, Suliman S, Amon LM, Mahomed H, Erasmus M, Whatney W, Hussey GD, Abrahams D, Kafaar F, Hawkridge T, Verver S, Hughes EJ, Ota M, Sutherland J, Howe R, Dockrell HM, Boom WH, Thiel B, Ottenhoff THM, Mayanja-Kizza H, Crampin AC, Downing K, Hatherill M, Valvo J, Shankar S, Parida SK, Kaufmann SHE, Walzl G, Aderem A, Hanekom WA. A blood RNA signature for tuberculosis disease risk: a prospective cohort study. The Lancet. (2016) 387(10035):2312–22.
Carolyn Williamson is Head of Division of Medical Virology; Member of the Institute of Infectious Disease and Molecular Medicine (IDM); Member of the Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa); and a Research Associate of the Centre for AIDS Research in South Africa (CAPRISA).
Carolyn Williamson’s research is focused on HIV-1 basic and translational research aimed at informing vaccines discovery, biomedical interventions, and a cure. She is interested in understanding mechanisms of transmission, B and T cell epitopes, immunogen design, and elucidating mechanisms of protection through the characterising HIV-1 breakthrough infections in HIV vaccine, microcode and passive immunization trials. She is also involved in research characterising latent reservoirs in HIV-1 infected women. Carolyn has published over 150 peer review articles and has extensive experience in mentoring Honours, MSc and PhD candidates, as well as early career investigators. Carolyn participates in numerous multi-centre national and international studies including the Centre for AIDS Programme for Research in South Africa (CAPRISA), Collaboration for AIDS Vaccine Discovery (CAVD), the HIV Vaccine Trials Network (HVTN), and the Medical Research Council (MRC) Strategic Health Innovation Partnerships (SHIP).
Selhorst P, Masson L, Ismail SD, Samsunder N, Garrett N, Mansoor LE, Abdool Karim Q, Abdool Karim SS, Passmore J-AS, Williamson C. Cervicovaginal inflammation facilitates acquisition of less infectious HIV variants. Clinical Infectious Diseases. (2017) 64(1):79–82.
Rademeyer C, Korber B, Seaman MS, Giorgi EE, Thebus R, Robles A, Sheward DJ, Wagh K, Garrity J, Carey BR, Gao H, Greene KM, Tang H, Bandawe GP, Marais JC, Diphoko TE, Hraber P, Tumba N, Moore PL, Gray GE, Kublin J, McElrath MJ, Vermeulen M, Middelkoop K, Bekker L-G, Hoelscher M, Maboko L, Makhema J, Robb ML, Abdool Karim S, Abdool Karim Q, Kim JH, Hahn BH, Gao F, Swanstrom R, Morris L, Montefiori DC, Williamson C. Features of recently transmitted HIV-1 clade C viruses that impact antibody recognition: implications for active and passive immunization. PLOS Pathogens. (2016) 12(7):e1005742.
Bhiman JN, Anthony C, Doria-Rose NA, Karimanzira O, Schramm CA, Khoza T, Kitchin D, Botha G, Gorman J, Garrett NJ, Abdool Karim SS, Shapiro L, Williamson C, Kwong PD, Mascola JR, Morris L, Moore PL. Viral variants that initiate and drive maturation of V1V2-directed HIV-1 broadly neutralizing antibodies. Nature Medicine. (2015) 21(11):1332–6.