The emergence of an epidemic of multidrug resistant (MDR) and extensively drug-resistant (XDR) TB in South Africa threatens to undermine the advances made in the antiretroviral therapy (ART) rollout for HIV. While contact investigations for household members of individuals with MDR or XDR TB holds practical appeal, the potential benefit of this strategy in the control of drug-resistant tuberculosis in a high TB prevalence setting is not known. Mathematical models evaluating the control of TB have not accounted for the realistic contact structure in respiratory transmission, precluding the evaluation of contact investigation strategies. This K01 application proposes to draw upon age-structured data on close contact rates from a South African in order to model tuberculosis transmission. Using this framework, the following specific aims are proposed: 1) To design and populate a network model of tuberculosis natural history and transmission and in a high HIV prevalence setting using empirical social contact data;2)To evaluate the effect of social contact rates and network structure on the projections of tuberculosis incidence and on the impact of enhanced case-finding and treatment success;3) To project the clinical impact and cost-effectiveness of tuberculosis screening and provision of preventive therapy for contacts of individuals with multidrug-resistant and extensively drug- resistant tuberculosis in a high HIV prevalence setting. This work will inform public health policy as well as clinical trials for development of chemoprophylaxis for MDR/XDR TB, which is a key aim of the NIAID Research Agenda for Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis. The candidate, Jason Andrews, M.D., S.M.,DTM&H is a postdoctoral fellow in infectious diseases at Massachusetts General Hospital and will benefit from the mentorship of investigators with extensive expertise in mathematical modeling, network analysis, and statistical inference. This research will be conducted in collaboration with investigators at the Desmond Tutu HIV Centre at the University of Cape Town, where extensive clinical and community-based data on HIV and TB natural history and epidemiology are available. The Candidate will gain expertise in advanced methods for mathematical modeling, network analysis and statistical inference of dynamic systems through coursework at the Harvard School of Public Health and the Applied Mathematics Department at the Harvard School of Engineering and Applied Sciences. The proposed training and research experience will provide the foundation for a career as an independent investigator.

Public Health Relevance

The rise of multidrug-resistant and extensively drug-resistant tuberculosis in high HIV prevalence settings threatens to undermine the success of the antiretroviral therapy rollout in improving life expectancy for people living with HIV. By developing models for tuberculosis transmission that incorporate the social contact structure in sub-Saharan African townships, this research will better elucidate how tuberculosis spreads and will project the impact of interventions to control drug-resistant tuberculosis.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Scientist Development Award - Research & Training (K01)
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Acquired Immunodeficiency Syndrome Research Review Committee (AIDS)
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Huebner, Robin E
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Stanford University
Internal Medicine/Medicine
Schools of Medicine
United States
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Tedijanto, Christine; Hermans, Sabine; Cobelens, Frank et al. (2018) Drivers of Seasonal Variation in Tuberculosis Incidence: Insights from a Systematic Review and Mathematical Model. Epidemiology 29:857-866
Nemes, Elisa; Rozot, Virginie; Geldenhuys, Hennie et al. (2017) Optimization and Interpretation of Serial QuantiFERON Testing to Measure Acquisition of Mycobacterium tuberculosis Infection. Am J Respir Crit Care Med 196:638-648
Andrews, Jason R; Nemes, Elisa; Tameris, Michele et al. (2017) Serial QuantiFERON testing and tuberculosis disease risk among young children: an observational cohort study. Lancet Respir Med 5:282-290
Meressa, Daniel; Hurtado, RocĂ­o M; Andrews, Jason R et al. (2015) Achieving high treatment success for multidrug-resistant TB in Africa: initiation and scale-up of MDR TB care in Ethiopia--an observational cohort study. Thorax 70:1181-8
Urrego, Juliana; Ko, Albert I; da Silva Santos Carbone, Andrea et al. (2015) The Impact of Ventilation and Early Diagnosis on Tuberculosis Transmission in Brazilian Prisons. Am J Trop Med Hyg 93:739-46
Andrews, J R; Basu, S; Dowdy, D W et al. (2015) The epidemiological advantage of preferential targeting of tuberculosis control at the poor. Int J Tuberc Lung Dis 19:375-80
Andrews, Jason R; Hatherill, Mark; Mahomed, Hassan et al. (2015) The dynamics of QuantiFERON-TB gold in-tube conversion and reversion in a cohort of South African adolescents. Am J Respir Crit Care Med 191:584-91
Wood, Robin; Morrow, Carl; Ginsberg, Samuel et al. (2014) Quantification of shared air: a social and environmental determinant of airborne disease transmission. PLoS One 9:e106622
Andrews, Jason R; Morrow, Carl; Walensky, Rochelle P et al. (2014) Integrating social contact and environmental data in evaluating tuberculosis transmission in a South African township. J Infect Dis 210:597-603