Mycobacterium tuberculosis is the commonest pathogen leading to fatal opportunistic disease in sub-SaharanAfrica. This proposal aims at demonstrating the benefits of antiretroviral therapy on TB in the community ofMasiphumelele. 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 priorityCountries in Africa are experiencing rapid increases in tuberculosis (TB), and other respiratory diseases,which is attributable to an explosive HIV-1 epidemic, ineffective TB control programs and difficulties in theaccurate diagnosis and management of infections o). HIV-1 fuels the TB epidemic in two ways: 1) HIV-1 is themost powerful risk factor for reactivation of latent TB infection to active disease, and 2) HIV-1 infected personswho become newly infected or re-infected with Mycobacterium tuberculosis progress much more rapidly to activeTB.This study is of crucial importance because:South Africa is one of 5 countries with HIV-positive TB > 300 cases/100,0000)There are 1600 new HIV infections daily in South Africa, 3.6 million already infected.TB control programs including DOTS have not been able to contain incident active TB.The increase of TB in HIV negative individuals relates to the increasing HIV (2).Tuberculosis consumes resources and shifts them from the HIV uninfected population.Introduction of ART may be more feasible if we demonstrate an impact of ART on TB incidence.Our group is uniquely qualified to conduct this research because:Dr Linda-Gaii Bekker has a long standing record of clinical, epidemiological and basic science research, oftuberculosis. (3.4)We have a well established TB program based on the WHO guidelines including DOTS, managed at a primaryhealth care level, with tuberculosis reference labs, and diagnostic laboratory resources ).Our Masiphumelele site has an effective notification and surveillance systemWe have established international research links with TB and HIV researchers:Prof. Gilla Kaplan, (Rockefeller university),Prof. Barry Kreiswirth( Public Health Research Laboratory, NY, who will provide the training andsupport required by this project to transfer the RFLP technology to Cape Town.John McKinney (Rockefeller University)Prof. Alan Aderem (Institute of Systems Biology, Seattle)Prof. Michael Tovey (Pasteur Institute, Paris)

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI053217-07
Application #
7679031
Study Section
Special Emphasis Panel (NSS)
Project Start
2008-09-01
Project End
2010-08-31
Budget Start
2008-09-01
Budget End
2009-08-31
Support Year
7
Fiscal Year
2008
Total Cost
$521,956
Indirect Cost
Name
Wits Health Consortium (Pty), Ltd
Department
Type
DUNS #
639391218
City
Johannesburg
State
Country
South Africa
Zip Code
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

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