SEATTLE — In contrast to previous hypotheses, HIV-positive patients with pulmonary tuberculosis appear to have an important function in the onward transmission of Mycobacterium tuberculosis, according to findings presented at CROI 2015.
“HIV-positive patients with pulmonary tuberculosis are thought to be less likely to transmit M. tuberculosis, even accounting for sputum bacillary load, because they have a shorter duration of disease,” researchers wrote. “Whole-genome sequencing of M. tuberculosis can identify who transmits to whom, and provides a new method to test this hypothesis.”
In the study, researchers identified all TB patients in Karonga District, Malawi, and obtained information about their previous contacts with other TB patients. All available cultures from 1996 to 2010 underwent whole-genome sequencing. The researchers used a SeqTrack algorithm to reconstruct transmission networks, and they estimated the relative risk for spreading and causing disease using logistic regression analyses, with transmission evaluated using only the previous 3 years of data. In addition, the researchers used HIV status to calculate the likelihood that a TB case had contracted the disease from their named contacts with smear-confirmed TB. The researchers analyzed 1,687 high-quality sequences, representing 72% of all culture-positive cases in the district.
After excluding cases from the last 3 years, 431 of 1,346 patients with pulmonary TB were found to be a cause of transmission resulting in disease in at least one, and up to 12 additional patients. Of 588 HIV-positive patients, 30.8% transmitted TB, and of 316 HIV-negative patients, 28.6% transmitted TB. Eight percent of HIV-positive patients were on ART before TB diagnosis. The researchers found negligible difference in TB transmission between HIV-positive and HIV-negative patients (OR = 1.1; 95% CI, 0.81-1.5), and this finding persisted after adjusting for age, gender, sputum smear status and year.
In an analysis of named contacts, the researchers found that among index case-prior contact pairs, TB transmission was confirmed from 38% of 71 TB smear-positive prior contacts with HIV, and 46% of 63 TB smear-positive prior contacts without HIV (RR = 0.83, 0.55-1.2). After adjusting for closeness of contact, this finding was attenuated slightly (adjusted RR = 0.78; 95% CI, 0.54-1.1). Approximately 60% of smear-positive TB patients were HIV-positive. In the event of a hypothetical 22% reduction in TB transmission from HIV-positive patients, this population would still be responsible for 47% of transmission.
“Contrary to what is sometimes stated, HIV-positive patients appear to play an important role in onward transmission of M. tuberculosis,” the researchers wrote. “Where a high proportion of pulmonary TB patients are HIV-positive, they may be the main source of infection.” – by Jen Byrne
Glynn JR, et al. Abstract 816LB. Presented at: Conference on Retroviruses and Opportunistic Infections; Feb. 23-26, 2015; Seattle.
Disclosure: The researchers report no relevant financial disclosures.