HIV-positive individuals with multidrug-resistant tuberculosis (MDR-TB) can be highly infectious, according to a study published in the September edition of PLoS Medicine. Investigators used a classic experiment to understand the transmission of airborne tuberculosis that involves exposing guinea pigs to air from a TB ward. The study, which was conducted in Lima, Peru, showed that just 9% of HIV-positive patients with TB were the source of 98% of the TB infections observed in the guinea pigs.
The investigators were able to use DNA fingerprinting to show that most of these infections originated in a small number of patients with MDR-TB.
These findings have important implications for infection control in facilities treating HIV-positive patients with TB, argue the investigators, and they emphasise that such patients should be isolated, be rapidly diagnosed and promptly given appropriate treatment.
In the 1950s, tests that involved exposing guinea pigs to air expelled from a TB ward demonstrated the airborne transmission of the infection. The tests also showed that only a minority of TB patients transmitted the infection, and that the risk of transmission occurring differed between individuals. Treatment with anti-TB drugs was shown by the research to reduce the risk of transmission.
Investigators repeated this experiment to find out the factors associated with TB transmission amongst a group of HIV-positive patients with the infection, many of whom had MDR-TB.
The study took place at the TB-HIV ward at Hospital Nacional Dos de Mayo, Lima, Peru. A total of 292 guinea pigs were exposed to air expelled from the ward for a total of 505 days.
A total of 161 patients had 181 admissions to the ward. Most of these admissions (67%) involved pulmonary TB. None of the patients were taking antiretroviral therapy.
TB with resistance to one drug was diagnosed in twelve patients, with 24% having a confirmed diagnosis of MDR-TB and a further 21 patients presumptive MDR-TB after failure to respond to standard first-line therapy. Only 38% had confirmed fully drug-susceptible TB.
A total of 159 guinea pigs had positive PPD skin tests, with a total of 135 having positive TB cultures.
It was possible to conduct drug susceptibility tests on 125 of these guinea pigs, and 121 (97%) were found to be infected with MDR-TB. It was also possible to match the strain of TB in 122 of the guinea pigs with those in patients. A total of ten patients had infectious TB, six of whom had MDR-TB. Of the three patients with drug susceptible TB, two had spent time on the ward untreated, and the third had stopped treatment. There were also two other patients with MDR-TB who infected guinea pigs, but it was not possible to type their TB.
Statistical analysis was performed which showed that TB transmission from patients to guinea pigs was significantly associated with infection with MDR-TB (p = 0.02). Patients with smear-positive TB were also more likely to transmit TB, but not significantly so).
Next the investigators calculated the probability of TB transmission according to certain patient characteristics. The probability of infectiousness was 3% for a patient with drug susceptible smear-negative TB. This increased to 18% for patients with either smear-positive TB or MDR-TB, and was 59% for patients with both smear-positive and MDR-TB.
“This research has for the first time…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”, write the investigators.
They believe that their findings have “important implications for TB infection control, especially in the era of increasingly integrated TB and HIV care and the emergence of XDR-TB.”
Rapid diagnosis, isolation and prompt treatment with appropriate drugs are essential to control the spread of MDR-TB in healthcare facilities, argue they authors. They add that the design of such facilities should incorporate systems of natural ventilation that increase airflow and reduce the risk of TB transmission.
Escombe A R et al. The infectiousness of tuberculosis patients coinfected with HIV. PLoS Medicine 5 (9): e188.