Date Published: September 16, 2008
Publisher: Public Library of Science
Author(s): A. Roderick Escombe, David A. J Moore, Robert H Gilman, William Pan, Marcos Navincopa, Eduardo Ticona, Carlos Martínez, Luz Caviedes, Patricia Sheen, Armando Gonzalez, Catherine J Noakes, Jon S Friedland, Carlton A Evans, Peter Wilson
Abstract: BackgroundThe current understanding of airborne tuberculosis (TB) transmission is based on classic 1950s studies in which guinea pigs were exposed to air from a tuberculosis ward. Recently we recreated this model in Lima, Perú, and in this paper we report the use of molecular fingerprinting to investigate patient infectiousness in the current era of HIV infection and multidrug-resistant (MDR) TB.Methods and FindingsAll air from a mechanically ventilated negative-pressure HIV-TB ward was exhausted over guinea pigs housed in an airborne transmission study facility on the roof. Animals had monthly tuberculin skin tests, and positive reactors were removed for autopsy and organ culture for M. tuberculosis. Temporal exposure patterns, drug susceptibility testing, and DNA fingerprinting of patient and animal TB strains defined infectious TB patients. Relative patient infectiousness was calculated using the Wells-Riley model of airborne infection. Over 505 study days there were 118 ward admissions of 97 HIV-positive pulmonary TB patients. Of 292 exposed guinea pigs, 144 had evidence of TB disease; a further 30 were tuberculin skin test positive only. There was marked variability in patient infectiousness; only 8.5% of 118 ward admissions by TB patients were shown by DNA fingerprinting to have caused 98% of the 125 characterised cases of secondary animal TB. 90% of TB transmission occurred from inadequately treated MDR TB patients. Three highly infectious MDR TB patients produced 226, 52, and 40 airborne infectious units (quanta) per hour.ConclusionsA small number of inadequately treated MDR TB patients coinfected with HIV were responsible for almost all TB transmission, and some patients were highly infectious. This result highlights the importance of rapid TB drug-susceptibility testing to allow prompt initiation of effective treatment, and environmental control measures to reduce ongoing TB transmission in crowded health care settings. TB infection control must be prioritized in order to prevent health care facilities from disseminating the drug-resistant TB that they are attempting to treat.
Partial Text: Seminal experiments demonstrating airborne tuberculosis (TB) transmission by droplet nuclei were performed by Riley and coworkers in the 1950s–1960s [1,2]. Guinea pigs acquired TB by breathing exhaust air from a TB ward. The studies demonstrated TB transmission from a minority of patients, marked variability in patient infectiousness, and reduced infectiousness following initiation of effective chemotherapy [1–3]. These classic studies were recently recreated in Lima, Perú, in the modern era of HIV infection and multidrug-resistant (MDR) TB, and again showed striking variability in patient infectiousness .
This study provides novel characterization of the heterogeneity and determinants of infectiousness of HIV-positive TB patients by applying molecular strain characterization to track airborne TB transmission to guinea pigs. This research has for the first time (to our knowledge) demonstrated that amongst HIV-positive patients TB infectiousness is extremely variable, that a few HIV-positive patients were highly infectious, and that inadequately treated MDR TB patients accounted for the great majority of TB transmission. In contrast to seminal studies of TB transmission using a similar guinea-pig method of detection half a century ago, this study was conducted in a real-life busy ward in a low-resource setting with unselected patients, composed of a heterogeneous mix of new and established diagnoses of drug-susceptible and drug-resistant TB, with varying treatment regimens. These results therefore have important implications for TB infection control, especially in the era of increasingly integrated TB and HIV care and the emergence of XDR TB strains.