Aerosolization of viableMycobacterium tuberculosisbacilli by tuberculosis clinic attendees independent of sputum-GeneXpert status

Abstract

Rationale: Knowledge of the potential for aerosol release of Mycobacterium tuberculosis (Mtb) during disease, treatment, recovery, and asymptomatic carriage is fundamental to understanding tuberculosis (TB) transmission. Objectives: To quantify viable aerosolized Mtb from TB clinic attendees. Methods: 102 presumptive TB patients from two informal settlements in Cape Town, South Africa, were classified by laboratory, radiological, and clinical features into three mutually exclusive groups: A. Sputum GeneXpert-positive TB (n=52), B. Sputum GeneXpert-negative TB (n=20), and C. TB not diagnosed (n=30). A respiratory aerosol sampling chamber was used to collect exhaled Mtb organisms over a 15-minute period at baseline, and at 2-months and 6-months post initial presentation. Viable bacilli were enumerated based on incorporation of the fluorescent probe, DMN-trehalose. Measures and Main Results: Mtb was isolated from 92%, 90% and 93% at baseline; 87%, 74%, 71% at 2 weeks; 53%, 47% and 46% at 2 months; and 32%, 25%, 22% at 6-months for groups A, B, and C, respectively. Median Mtb counts (ranges) reduced from baseline to 6 months from 10(1-38), 5(1-31), and 9(1-38) to 3(1-28), 4(3-18), and 2(1-14) for groups A, B, and C, respectively. TB symptoms resolved in all 3 groups. Conclusions: Aerosolized Mtb was isolated from almost all TB patients at baseline and reduced during treatment. Small numbers of viable organisms remained in almost a fifth of patients completing 6-months treatment. Aerosolized Mtb may be a useful metric for modifying standard TB therapy. Aerosolized Mtb in group C may reflect exacerbation of an existing infection or transient Mtb infection not reaching a clinical threshold for TB diagnosis, consistent with recent models proposing cyclic subclinical disease states.

The Titanic question in TB control: Should we worry about the bummock?

“…The most recent challenge to domain dogma comes from Patterson et al in the current issue of the Proceedings ( 1 ). These researchers used recently developed approaches to respiratory aerosol sampling to assess Mtb respiratory tract carriage in people presenting to TB clinics outside of Cape Town, South Africa, which has one of the highest prevalences of TB in the world.…”

“…For a visual of the complexity of the experimental setup, think Tardis not sputum cup. These tools were applied to people presenting with symptoms to TB clinics, some of whom were diagnosed with TB by conventional diagnostics (GeneXpert and/or culture) and some of whom were not ( 1 ). The team found near ubiquitous aerosol carriage of viable Mtb in both cases and putative controls.…”