Tuberculosis is the major infectious cause of mortality among AIDS patients in the developing world, and HIV infection has been shown to increase mortality from tuberculosis five-fold in parts of Subsaharan Africa. Increasingly, HI V-infected children in developing countries are becoming infected with Mycobacterium tuberculosis (Mtb) and dying at an early age, presenting new dilemmas that differ from those facing adults with HIV-Mtb coinfection. The diagnosis of pediatric TB is complicated by inefficient and expensive methods to recover Mtb and vague diagnostic criteria. This project will evaluate novel approaches to the diagnosis of AIDS-related pediatric TB in a hyperendemic setting using 1) rapid, cost-effective Mtb culture and susceptibility methods based on direct microscopic observation techniques and 2) alternative non-invasive specimens such as nasopharyngeal aspirates (NPA) and stool to detect Mtb. An optional component will assess improved rapid detection of Mtb by a semi-nested polymerase chain reaction assay (N2 PCR), a technique appropriate for regional reference laboratories in developing countries. Our preliminary data show a high correlation between culture results and N2 PCR results in adults (sputum PCR) and children (stool and NPA PCR) with tuberculosis, and mean time to detection of Mtb by our microscopic observation method was 9 days (at a fraction of the cost of rapid methods used in the U.S.). This is a collaborative effort between PRISMA, a Peruvian private voluntary organization, two U.S. universities (Tulane and Johns Hopkins), and a Peruvian university (Cayetano Heredia). Two hundred-sixty children with pulmonary disease meeting clinical criteria for TB disease (including at least 100 HIV-infected) from the Hospital del Nino, Lima, Peru, and 260 age-matched controls from both high- and low-risk communities will be enrolled. Mtb will be detected in gastric aspirates (cases only), NPAs, and stool by new and traditional culture methods and by N2 PCR. Children with a positive N2 PCR but without clinical evidence of TB requiring antituberculous therapy will be followed longitudinally. These new diagnostic methods have tremendous potential to improve and simplify the diagnosis of pediatric tuberculosis in low-income countries with limited laboratory resources.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI049139-03
Application #
6619408
Study Section
AIDS and Related Research 8 (AARR)
Program Officer
Near, Karen A
Project Start
2001-09-30
Project End
2005-05-31
Budget Start
2003-06-01
Budget End
2004-05-31
Support Year
3
Fiscal Year
2003
Total Cost
$226,675
Indirect Cost
Name
Tulane University
Department
Internal Medicine/Medicine
Type
Schools of Public Health
DUNS #
053785812
City
New Orleans
State
LA
Country
United States
Zip Code
70118
Oberhelman, Richard A; Soto-Castellares, Giselle; Gilman, Robert H et al. (2015) A Controlled Study of Tuberculosis Diagnosis in HIV-Infected and Uninfected Children in Peru. PLoS One 10:e0120915
Rath, Barbara A; von Kleist, Max; Castillo, Maria E et al. (2013) Antiviral resistance and correlates of virologic failure in the first cohort of HIV-infected children gaining access to structured antiretroviral therapy in Lima, Peru: a cross-sectional analysis. BMC Infect Dis 13:1
Paz-Soldán, Valerie A; Alban, Rebecca E; Jones, Christy D et al. (2013) The provision of and need for social support among adult and pediatric patients with tuberculosis in Lima, Peru: a qualitative study. BMC Health Serv Res 13:290
Oberhelman, Richard A; Soto-Castellares, Giselle; Gilman, Robert H et al. (2010) Diagnostic approaches for paediatric tuberculosis by use of different specimen types, culture methods, and PCR: a prospective case-control study. Lancet Infect Dis 10:612-20
Carrión, A G; Laguna-Torres, V A; Soto-Castellares, G et al. (2009) Molecular characterization of the human immunodeficiency virus type 1 among children in Lima, Peru. AIDS Res Hum Retroviruses 25:833-5
Wolf, Hilary; Mendez, Melissa; Gilman, Robert H et al. (2008) Diagnosis of pediatric pulmonary tuberculosis by stool PCR. Am J Trop Med Hyg 79:893-8
Ramirez-Cardich, Maria E; Kawai, Vivian; Oberhelman, Richard A et al. (2006) Clinical correlates of tuberculosis co-infection in HIV-infected children hospitalized in Peru. Int J Infect Dis 10:278-81
Oberhelman, Richard A; Soto-Castellares, Giselle; Caviedes, Luz et al. (2006) Improved recovery of Mycobacterium tuberculosis from children using the microscopic observation drug susceptibility method. Pediatrics 118:e100-6
Montenegro, Sonia H; Gilman, Robert H; Sheen, Patricia et al. (2003) Improved detection of Mycobacterium tuberculosis in Peruvian children by use of a heminested IS6110 polymerase chain reaction assay. Clin Infect Dis 36:16-23