The Detection of Airborne Transmission of Tuberculosis from HIV-Infected Patients, Using an In Vivo Air Sampling Model

Abstract

Background Nosocomial transmission of tuberculosis remains an important public health problem. We created an in vivo air sampling model to study airborne transmission of tuberculosis from patients coinfected with human immunodeficiency virus (HIV) and to evaluate environmental control measures. Methods An animal facility was built above a mechanically ventilated HIV-tuberculosis ward in Lima, Peru. A mean of 92 guinea pigs were continuously exposed to all ward exhaust air for 16 months. Animals had tuberculin skin tests performed at monthly intervals, and those with positive reactions were removed for autopsy and culture for tuberculosis. Results Over 505 consecutive days, there were 118 ward admissions by 97 patients with pulmonary tuberculosis, with a median duration of hospitalization of 11 days. All patients were infected with HIV and constituted a heterogeneous group with both new and existing diagnoses of tuberculosis. There was a wide variation in monthly rates of guinea pigs developing positive tuberculin test results (0%–53%). Of 292 animals exposed to ward air, 159 developed positive tuberculin skin test results, of which 129 had laboratory confirmation of tuberculosis. The HIV-positive patients with pulmonary tuberculosis produced a mean of 8.2 infectious quanta per hour, compared with 1.25 for HIV-negative patients with tuberculosis in similar studies from the 1950s. The mean monthly patient infectiousness varied greatly, from production of 0–44 infectious quanta per hour, as did the theoretical risk for a health care worker to acquire tuberculosis by breathing ward air. Conclusions HIV-positive patients with tuberculosis varied greatly in their infectiousness, and some were highly infectious. Use of environmental control strategies for nosocomial tuberculosis is therefore a priority, especially in areas with a high prevalence of both tuberculosis and HIV infection.

Differential Virulence and Disease Progression following Mycobacterium tuberculosis Complex Infection of the Common Marmoset (Callithrix jacchus)

“…Mice infected with most Beijing lineage strains have reduced survival, higher bacterial loads, greater volumes of lung disease, and, in some studies, lower production of gamma interferon (IFN-␥) compared to non-Beijing strains (29,(47)(48)(49). Guinea pigs are highly susceptible to experimental M. tuberculosis infection but can restrict the growth of M. tuberculosis under some exposure conditions (50)(51)(52). However, like mice, they are also highly susceptible to Beijing strains, with rapid and extensive primary lesion necrosis in the lung and extrapulmonary lesion necrosis, as well as higher bacterial burdens, compared to non-Beijing strains (32,53).…”

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.…”

“…In addition, of the 125 TB-infected guinea pigs for which TB drug susceptibility and spoligotype results were available, 98% were matched to the drug susceptibility and spoligotype patterns of TB from one single HIV-infected patient. TB infectiousness varies widely between different TB-HIVcoinfected patients and is correlated with proven determinants of TB transmission, such as sputum smear positivity, lung cavi- tation, laryngeal TB, cough frequency, and sputum volume and consistency (86,87,92,165,206). HIV can affect TB transmission dynamics by altering the traditional determinants of TB transmission.…”

Variability of Airborne Transmission of Mycobacterium tuberculosis: Implications for Control of Tuberculosis in the HIV Era

“…A World Health Organization Global Task Force on XDR tuberculosis recommended several interventions, including accelerated implementation of infection-control measures to reduce transmission and strategies that promote prevention and control of XDR tuberculosis [2]. In this context, the article by Escombe et al [3] in this issue of Clinical Infectious Diseases could not be more relevant.…”