The infectiousness of tuberculosis patients coinfected with HIV

Abstract

Background: The 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 findings: All 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.

Conclusions: A 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.

Figure 1. Pulmonary TB Patient Bed Days and TB Strain Spoligotype Pattern Compared with TB Infection in Guinea Pigs by Study Month

(A) Number of bed days in each study month resulting from pulmonary TB patients, who were either smear positive (patterned bars, “+ve”), or smear negative (white bars, “−ve”) at the time of admission. (B) Number of bed days in each study month resulting from pulmonary TB patients for whom a TB strain spoligotype pattern was available. Each block of colour corresponds to one patient, and each colour to one of the eight spoligotype patterns observed in the guinea pigs. Pale yellow represents the remaining 19 patterns observed in patients whose TB was not seen in the guinea pigs. If a patient resided on the ward for a period spanning more than one study month, that patient is included in the month where they accounted for more smear positive patient bed days. The coloured blocks containing numbers correspond to the ten identified infectious patients, numbered 1 to 10 in Table 2. (C) Percentage of animal colony skin tested each study month that were PPD positive. Each colour represents one spoligotype pattern, except for pale blue, which represents ten guinea pigs culture positive for TB but for which spoligotype patterns were unavailable. White represents animals that were PPD positive but TB culture negative. Animals culture positive for TB that were PPD false negatives or that died between skin tests were included in the subsequent month's skin test.

Figure 2. Pulmonary TB Patient Bed Days According to Sputum Smear Status and TB Drug Susceptibility

The numbers of patient bed days accounted for by patients with MDR TB, or with non-MDR TB, are shown. Results are subdivided into sputum-smear positive and culture positive (white shading); sputum-smear negative and culture positive (dark grey shading); and culture negative (black shading). Two patients are not included in this figure: one culture-positive patient with drug-susceptible TB (accounting for 6 patient days) with an unavailable smear result; and one smear-negative, culture-positive patient (accounting for 8 patient days) with no TB drug-susceptibility information. The drug-resistant category included 32 MDR TB cases and 12 isoniazid or rifampicin monoresistant cases. In non-MDR TB admissions, 34 smear-negative culture-positive and 241 culture-negative patient bed days were accounted for by patients treated empirically, without confirmation of drug-susceptibility status in our laboratory. In MDR TB admissions, 45 smear-negative culture-positive and 98 culture-negative patient days were accounted for by such patients. Comparisons between groups were made using the two-sample z-test of proportions.