Cough-aerosol cultures of Mycobacterium tuberculosis in the prediction of outcomes after exposure. A household contact study in Brazil

Abstract

Background: Mycobacterium tuberculosis cultures of cough-generated aerosols from patients with pulmonary tuberculosis (TB) are a quantitative method to measure infectiousness and to predict secondary outcomes in exposed contacts. However, their reproducibility has not been established.

Objective: To evaluate the predictive value of colony-forming units (CFU) of M. tuberculosis in cough aerosols on secondary infection and disease in household contacts in Brazil.

Methods: Adult sputum smear+ and culture+ pulmonary TB cases underwent a standard evaluation and were categorized according to aerosol CFU. We evaluated household contacts for infection at baseline and at 8 weeks with TST and IGRA, and secondary disease.

Results: We enrolled 48 index TB cases; 40% had negative aerosols, 27% low aerosols (<10 CFU) and 33% high aerosols (≥10 CFU). Of their 230 contacts, the proportion with a TST ≥10 mm at 8 weeks was 59%, 65% and 75%, respectively (p = 0.34). Contacts of high aerosol cases had greater IGRA readouts (median 4.6 IU/mL, IQR 0.02-10) when compared to those with low (0.8, 0.2-10) or no aerosol (0.1, 0-3.7; p = 0.08). IGRA readouts in TST converters of high aerosol cases (median 20 IU/mL, IQR 10-24) were larger than those from aerosol-negative (0.13, 0.04-3; p = o.o2). 8/9 (89%) culture+ secondary TB cases occurred in contacts of aerosol+ cases.

Conclusion: Aerosol CFU predicts quantitatively IGRA readouts among household contacts of smear positive TB cases. Our results strengthen the argument of using cough aerosols to guide targeted preventive treatment strategies, a necessary component of current TB elimination projections.

Fig 1. TST and IGRA results in 230 household contacts of TB patient according to the number of CFU of M. tuberculosis in cough-generated aerosols or AFB smear microscopy in the index TB case.

(A) Histograms represent the proportion of contacts with a TST ≥10mm at baseline (black) and those with TST conversion (grey). The solid line represents the median TST diameter (mm) for contacts with TST ≥10mm at baseline (circles) and maximum TST for those with TST conversion (triangles) for each exposure group. (B) Standard box plots of maximum IGRA readouts in contacts of smear + culture + TB cases. P = 0.08 for aerosol CFU, p = 0.26 for AFB sputum smear (C) Standard box plots of IGRA readouts in contacts with TST conversion. P = 0.02 for aerosol CFU, p = 0.33 for AFB sputum smear.

Fig 2. Proportion of household contacts with a positive (≥10mm) tTST and IGRA at study completion (8–12 weeks) by contact age group and CFU of M. tuberculosis in cough-generated aerosols in the index case: Negative (CFU = 0) or positive (CFU ≥1).

The “N” under each histogram indicates the number of contacts within each age-exposure category. The stars (*) represent the median TST or mean IGRA readout associated with each group.