A Controlled Study of Tuberculosis Diagnosis in HIV-Infected and Uninfected Children in Peru.

BACKGROUND: Diagnosing tuberculosis in children is challenging because specimens are difficult to obtain and contain low tuberculosis concentrations, especially with HIV-coinfection. Few studies included well-controls so test specificities are poorly defined. We studied tuberculosis diagnosis in 525 children with and without HIV-infection. METHODS AND FINDINGS: 'Cases' were children with suspected pulmonary tuberculosis (n = 209 HIV-negative; n = 81 HIV-positive) and asymptomatic 'well-control' children (n = 200 HIV-negative; n = 35 HIV-positive). Specimens (n = 2422) were gastric aspirates, nasopharyngeal aspirates and stools analyzed by a total of 9688 tests. All specimens were tested with an in-house hemi-nested IS6110 PCR that took <24 hours. False-positive PCR in well-controls were more frequent in HIV-infection (P≤0.01): 17% (6/35) HIV-positive well-controls versus 5.5% (11/200) HIV-negative well-controls; caused by 6.7% (7/104) versus 1.8% (11/599) of their specimens, respectively. 6.7% (116/1719) specimens from 25% (72/290) cases were PCR-positive, similar (P>0.2) for HIV-positive versus HIV-negative cases. All specimens were also tested with auramine acid-fast microscopy, microscopic-observation drug-susceptibility (MODS) liquid culture, and Lowenstein-Jensen solid culture that took ≤6 weeks and had 100% specificity (all 2112 tests on 704 specimens from 235 well-controls were negative). Microscopy-positivity was rare (0.21%, 5/2422 specimens) and all microscopy-positive specimens were culture-positive. Culture-positivity was less frequent (P≤0.01) in HIV-infection: 1.2% (1/81) HIV-positive cases versus 11% (22/209) HIV-negative cases; caused by 0.42% (2/481) versus 4.7% (58/1235) of their specimens, respectively. CONCLUSIONS: In HIV-positive children with suspected tuberculosis, diagnostic yield was so low that 1458 microscopy and culture tests were done per case confirmed and even in children with culture-proven tuberculosis most tests and specimens were false-negative; whereas PCR was so prone to false-positives that PCR-positivity was as likely in specimens from well-controls as suspected-tuberculosis cases. This demonstrates the importance of control participants in diagnostic test evaluation and that even extensive laboratory testing only rarely contributed to the care of children with suspected TB. TRIAL REGISTRATION: This study did not meet Peruvian and some other international criteria for a clinical trial but was registered with the ClinicalTrials.gov registry: ClinicalTrials.gov NCT00054769.

Surveillance for early silicosis in high altitude miners using pulse oximetry.

Two cross-sectional studies in a high altitude region of Perú evaluated the role of pulse oximetry for detection of silicosis in high-altitude miners. In study one, exercise pulse oximetry and chest radiographs were used to evaluate 343 silica-exposed miners and 141 unexposed subjects for evidence of silicosis. Study 2 investigated the association between exercise oxygen saturation and silicosis in 32 non-silicotic and 65 silicotic miners. In study one, age (Odds Ratio [OR] 1.10, 95% Cofidence Interval (CI) 1.07-1.12) and resting oxygen saturation (OR 0.95, 95%CI 0.90-0.99) were associated with silicosis. In study two, years of mining employment (OR 1.14, 95%CI 1.05-1.23) and exercise oxygen saturation at 30% maximum heart rate (OR 0.86, 95%CI 0.75-0.99) were associated with silicosis. Hypoxemia at rest and with exercise is associated with silicosis in high altitude miners. Pulse oximetry should be further investigated as a screening tool for silicosis at high altitudes.