The Infectiousness of Tuberculosis Patients Coinfected with HIV

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.

HIV and Tuberculosis: a Deadly Human Syndemic

“…Only 3 of 77 patients were responsible for over 73% of TB infections in guinea pigs, and half of all TB infections in guinea pigs were caused by one patient with laryngeal TB (91). Similarly, Escombe et al recreated the in vivo sampling model using guinea pigs housed above a mechanically ventilated HIV-TB ward in Lima, Peru (86,87). Of the nearly 100 TB-HIV-coinfected inpatients, only 10 were responsible for all characterized cases of TB infections in the guinea pigs.…”

The HIV-associated tuberculosis epidemic—when will we act?

“…68 Findings from a series of studies in Peru have provided key lessons for interventions to control infection in low-resource settings. 69,70 First, natural ventilation is a low-cost environmental measure for tuberculosis infection control. Maximum natural ventilation can be achieved with open windows and doors, enlarged or additional windows, open skylights for cross-ventilation, and rebuilding of waiting rooms in the open air.…”

“…Second, unrecognised or inadequately treated MDR tuberculosis can be a key source of nosocomial transmission, which further emphasises the importance of environmental control measures in crowded health-care settings, and the importance of rapid testing for drug susceptibility to allow eff ective treatment to be started promptly. 70 Control of tuberculosis transmission within HIV care clinics is especially important, but also extremely diffi cult, because of the high burden of undiagnosed active tuberculosis in patients entering HIV care, of whom not all will have identifi able tuberculosis-related symptoms. [52][53][54][55][56] Outbreaks can continue for long periods, aff ecting many patients from the same clinic, but might not be clearly distinguishable from background rates unless the outbreaks are due to drug-resistant tuberculosis strains causing high mortality.…”

Genomic Variability of Mycobacterium tuberculosis

“…The successful transmission of particular strains is not limited to the Beijing genotype. In a recent study, where guinea pigs were exposed to air from a HIV-tuberculosis ward, one non-Beijing strain was shown to be responsible for most of the secondary infections observed (Escombe et al, 2008). In addition to transmission capacity, it is also currently accepted that genetically different M. tuberculosis strains produce markedly different immuno-pathological events and affect disease manifestation.…”