Abstract

Cough is the major determinant of tuberculosis transmission. Despite this, there is a paucity of information regarding characteristics of cough frequency throughout the day and in response to tuberculosis therapy. Here we evaluate the circadian cycle of cough, cough frequency risk factors, and the impact of appropriate treatment on cough and bacillary load. We prospectively evaluated human immunodeficiency virus-negative adults (n = 64) with a new diagnosis of culture-proven, drug-susceptible pulmonary tuberculosis immediately prior to treatment and repeatedly until treatment day 62. At each time point, participant cough was recorded (n = 670) and analyzed using the Cayetano Cough Monitor. Consecutive coughs at least 2 seconds apart were counted as separate cough episodes. Sputum samples (n = 426) were tested with microscopic-observation drug susceptibility broth culture, and in culture-positive samples (n = 252), the time to culture positivity was used to estimate bacillary load. The highest cough frequency occurred from 1 pm to 2 pm, and the lowest from 1 am to 2 am (2.4 vs 1.1 cough episodes/hour, respectively). Cough frequency was higher among participants who had higher sputum bacillary load (P < .01). Pretreatment median cough episodes/hour was 2.3 (interquartile range [IQR], 1.2-4.1), which at 14 treatment days decreased to 0.48 (IQR, 0.0-1.4) and at the end of the study decreased to 0.18 (IQR, 0.0-0.59) (both reductions P < .001). By 14 treatment days, the probability of culture conversion was 29% (95% confidence interval, 19%-41%). Coughs were most frequent during daytime. Two weeks of appropriate treatment significantly reduced cough frequency and resulted in one-third of participants achieving culture conversion. Thus, treatment by 2 weeks considerably diminishes, but does not eliminate, the potential for airborne tuberculosis transmission.

Highlights

  • Cough is the major determinant of tuberculosis transmission

  • The highest cough frequency occurred from 1 pm to 2 pm, and the lowest from 1 am to 2 am (2.4 vs 1.1 cough episodes/ hour, respectively)

  • Cough frequency was higher among participants who had higher sputum bacillary load (P < .01)

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Summary

Methods

We prospectively evaluated human immunodeficiency virus–negative adults (n = 64) with a new diagnosis of culture-proven, drug-susceptible pulmonary tuberculosis immediately prior to treatment and repeatedly until treatment day 62. The parent prospective cohort study followed adults (aged ≥18 years) with a clinically suspected diagnosis of pulmonary tuberculosis in 2 reference tertiary academic Peruvian Hospitals: Hospital Nacional Dos de Mayo and Hospital Nacional Daniel Alcides Carrión, for which a protocol detailing sample size, selection criteria, and detailed information on variables has been published [9]. Data for human immunodeficiency virus (HIV)– infected participants and those who did not have confirmed drug-susceptible pulmonary tuberculosis are being reported separately. Inclusion criteria were the subset of the parent study with sputum culture–positive tuberculosis confirmed to be susceptible to isoniazid and rifampicin (to reduce the risk of incorrect treatment confounding results) in participants confirmed to be HIV negative (due to the unknown effect of immunodeficiency on cough). Participants were asked to complete a previously published questionnaire regarding their socioeconomic status [9]

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