The effect of ART on rates and transmission of TB

Bekker, Linda-Gail

Abstract

Mycobacterium tuberculosis is the commonest pathogen leading to fatal opportunistic disease in sub-Saharan Africa. South Africa is one of 5 countries with HIV-positive TB > 300 cases/100,000This proposal aims at demonstrating the benefits of antiretroviral therapy on TB in the community of Masiphumelele. Because the major cause of morbidity and mortality in HIV-1 infected adults and children is TB, safeguarding the household from the disease is a public health priority Project hypothesis: The introduction of ART in HIV-positive members of a community will have an impact on the TB morbidity and mortality in both HIV negative and positive members. Masiphumelele, a well circumscribed community of 10,000 in Cape Town where 600 adults, 100 children and 60 neonates will be treated with ART (Project 1 and 2 of this CIPRA). In addition it is our hypothesis that ART will change transmission patterns of tuberculosis in this community.
Specific Aims : 1. To measure the impact of community-based antiretroviral therapy (ART) on active tuberculosis case rates, TB hospitalization rates and tuberculosis death rates, of the community residents, both HIV infected and un-infected. 2. To measure the impact of ART on the proportion of active TB in HIV infected individuals due to reactivation of latent infection versus reinfection. 3. To measure the impact of ART on transmission patterns of TB within the community. Is there a reduction of cluster sizes of M. tuberculosis? 4. To measure the contribution of HIV infected individuals to the transmission of TB. 5. To type the strains of M. tuberculosis cultured from the community using restriction length polymorphism (RFLP) to determine if the introduction of ART will change the transmission patterns of tuberculosis qualitatively as well as quantitatively in this community. 6. To use a geographic information system (GIS) and RFLP database for the Masiphumelele village, identifying TB transmission locations. 7. To measure the ongoing transmission of TB using annual tuberculin skin tests (TST) in cohorts of local school children and correlate it with the successful use of ART by. the reduction in AIDS related deaths, opportunistic infections and hospitalizations.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Allergy and Infectious Diseases (NIAID)
• Type: Research Program--Cooperative Agreements (U19)
• Project #: 1U19AI053217-01
• Application #: 6594377
• Study Section: Special Emphasis Panel (ZAI1)
• Project Start: 2002-06-01
• Project End: 2007-05-31
• Support Year: 1
• Fiscal Year: 2002

Institution

• Name: University of Witwaterstrand
• City: Johannesburg
• Country: South Africa

Publications

Nwosu, Emmanuel C; Robertson, Frances C; Holmes, Martha J et al. (2018) Altered brain morphometry in 7-year old HIV-infected children on early ART. Metab Brain Dis 33:523-535

Toich, Jadrana T F; Taylor, Paul A; Holmes, Martha J et al. (2017) Functional Connectivity Alterations between Networks and Associations with Infant Immune Health within Networks in HIV Infected Children on Early Treatment: A Study at 7 Years. Front Hum Neurosci 11:635

Jankiewicz, Marcin; Holmes, Martha J; Taylor, Paul A et al. (2017) White Matter Abnormalities in Children with HIV Infection and Exposure. Front Neuroanat 11:88

Lewis, Joanna; Payne, Helen; Walker, A Sarah et al. (2017) Thymic Output and CD4 T-Cell Reconstitution in HIV-Infected Children on Early and Interrupted Antiretroviral Treatment: Evidence from the Children with HIV Early Antiretroviral Therapy Trial. Front Immunol 8:1162

Innes, Steve; van Toorn, Ronald; Otwombe, Kennedy et al. (2017) Late-Onset Hiv Encephalopathy In Children With Long-Standing Virologic Suppression Followed By Slow Spontaneous Recovery Despite no Change In Antiretroviral Therapy: 4 Case Reports. Pediatr Infect Dis J 36:e264-e267

Mbugua, Kenneth K; Holmes, Martha J; Cotton, Mark F et al. (2016) HIV-associated CD4+/CD8+ depletion in infancy is associated with neurometabolic reductions in the basal ganglia at age 5 years despite early antiretroviral therapy. AIDS 30:1353-62

Ackermann, C; Andronikou, S; Saleh, M G et al. (2016) Early Antiretroviral Therapy in HIV-Infected Children Is Associated with Diffuse White Matter Structural Abnormality and Corpus Callosum Sparing. AJNR Am J Neuroradiol 37:2363-2369

van Zyl, Gert U; Bedison, Margaret A; van Rensburg, Anita Janse et al. (2015) Early Antiretroviral Therapy in South African Children Reduces HIV-1-Infected Cells and Cell-Associated HIV-1 RNA in Blood Mononuclear Cells. J Infect Dis 212:39-43

Madhi, Shabir A; Izu, Alane; Nunes, Marta C et al. (2015) Longitudinal study on Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus nasopharyngeal colonization in HIV-infected and -uninfected infants vaccinated with pneumococcal conjugate vaccine. Vaccine 33:2662-9

Alhamud, A; Taylor, Paul A; Laughton, Barbara et al. (2015) Motion artifact reduction in pediatric diffusion tensor imaging using fast prospective correction. J Magn Reson Imaging 41:1353-64