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Background: Cough frequency, and its duration, is a lab-free bio marker that can be used in low-resource settings and has been associated with transmission and treatment response. Radiological characteristics associated with increased cough frequency may be important in understanding transmission. The relationship between cough frequency and cavitary lung disease has never been studied. Methods: We analyzed 41 human immunodeficiency virus-negative adults with culture- confirmed, drug-susceptible pulmonary tuberculosis throughout treatment. Cough recordings were based on the Cayetano Cough Monitor and sputum samples were evaluated using microscopic-observation drug susceptibility broth culture, among culture-positive samples bacillary burden was assessed by time to positivity. Computerized tomography scans were analyzed by a U.S. board-certified radiologist and an automated-computer algorithm. The algorithm evaluates cavity volume and cavitary proximity to the airway. Computerized tomography scans were taken within one month of treatment initiation. We compared small cavities (≤7-mL) versus large cavities (>7-mL) and cavities located closer to (≤10-mm) and farther (>10-mm) from the airway to cough frequency and cough cessation until treatment day 62. Results: Cough frequency during treatment was two-fold higher in pa rticipants with large cavity volumes (Rate Ratio [RR]=1.98, p=0.01) and cavities located closer to the airway (RR=2.44, p=0.001). Comparably, cough ceased three times faster in smaller cavities (adjusted hazard ratio [HR]=2.89, p=0.06) and those farther from the airway (adjusted HR=3.61, p=0.02). Similar results are found for bacillary burden and culture conversion during treatment. Conclusions: Cough frequency during treatment is greater and lasts for longer in patients with larger cavities, especially those closer to the airway

BackgroundDiagnosing 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 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.ConclusionsIn 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 registrationThis 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.