This community-based, cross-sectional study will test a simple low-cost diagnostic modality for rapid diagnosis of pulmonary tuberculosis (TB). We shall test whether saline-induced sputum improves the diagnostic yield of smear positive TB in HIV-infected and HIV-uninfected adolescents and adults. It will be tested at our established research site near Cape Town, South Africa, where clinical and epidemiological studies are being conducted in preparation for trials of novel TB vaccines. We have successfully used this technique to investigate over 1,800 children in a Phase IV BCG vaccine trial.
Specific aims : To determine whether induced sputum improves rapid microbiological diagnosis of pulmonary TB in: (a) HIV-infected people, and (b), in all people with suspected tuberculosis, regardless of HIV status. We shall enroll 600 patients presenting to community health services with suspected TB. Two routine sputum collections, one induced sputum collection with saline nebulization, and an HIV test will be performed. Direct smear sputum microscopy and mycobacterial culture will be performed in an accredited laboratory. HIV test results will be used to stratify participants for evaluation of the primary outcome, positive direct smear microscopy, and the secondary outcome, positive culture of Mycobacterium tuberculosis. These outcomes will be analyzed as the difference in diagnostic yield (proportion of culture-proven TB cases) detected by direct smear microscopy of one, or two, routine sputum collections, compared to a single induced sputum. TB accounted for 10% of all deaths in this region in 2004. Rapid diagnosis of pulmonary TB is especially critical in HIV-infected individuals, since delay in therapy may be fatal. Paradoxically, diagnosis is more difficult in HIV-infected people with pauci-bacillary disease. Previous studies have demonstrated diagnostic benefit of induced sputum among individuals with negative routine sputum smear microscopy. This study will allow objective assessment of the impact of induced sputum on TB case detection among HIV-infected and HIV-uninfected persons, by calculating the gain in diagnostic yield that might be achieved by a regional TB control program in a high-prevalence developing country. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI075603-02
Application #
7470119
Study Section
Special Emphasis Panel (ZAI1-GSM-M (M1))
Program Officer
Jacobs, Gail G
Project Start
2007-08-01
Project End
2011-07-31
Budget Start
2008-08-01
Budget End
2009-07-31
Support Year
2
Fiscal Year
2008
Total Cost
$79,461
Indirect Cost
Name
University of Cape Town
Department
Type
DUNS #
568227214
City
Rondebosch
State
Country
South Africa
Zip Code
7700
Geldenhuys, H D; Whitelaw, A; Tameris, M D et al. (2014) A controlled trial of sputum induction and routine collection methods for TB diagnosis in a South African community. Eur J Clin Microbiol Infect Dis 33:2259-66
Gonzalez-Angulo, Yulieth; Geldenhuys, Hennie; Van As, Danelle et al. (2013) Knowledge and acceptability of patient-specific infection control measures for pulmonary tuberculosis. Am J Infect Control 41:717-22
Gonzalez-Angulo, Y; Wiysonge, C S; Geldenhuys, H et al. (2012) Sputum induction for the diagnosis of pulmonary tuberculosis: a systematic review and meta-analysis. Eur J Clin Microbiol Infect Dis 31:1619-30
Geldenhuys, H D; Kleynhans, W; Buckerfield, N et al. (2012) Safety and tolerability of sputum induction in adolescents and adults with suspected pulmonary tuberculosis. Eur J Clin Microbiol Infect Dis 31:529-37
Hatherill, M; Hawkridge, T; Zar, H J et al. (2009) Induced sputum or gastric lavage for community-based diagnosis of childhood pulmonary tuberculosis? Arch Dis Child 94:195-201