HIV This Week

Escombe AR, Moore DA, Gilman RH, Pan W, Navincopa M, Ticona E, Martínez C, Caviedes L, Sheen P, Gonzalez A, Noakes CJ, Friedland JS, Evans CA. The Infectiousness of Tuberculosis Patients Coinfected with HIV. PLoS Med. 2008;5(9):e188. [Epub ahead of print]

The current understanding of airborne tuberculosis transmission is based on classic 1950s studies in which guinea pigs were exposed to air from a tuberculosis ward. Recently Escombe and colleagues recreated this model in Lima, Perú, and in this paper they report the use of molecular fingerprinting to investigate patient infectiousness in the current era of HIV infection and multidrug-resistant tuberculosis. All air from a mechanically ventilated negative-pressure HIV-tuberculosis 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 Mycobacterium tuberculosis. Temporal exposure patterns, drug susceptibility testing, and DNA fingerprinting of patient and animal tuberculosis strains defined infectious tuberculosis 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 tuberculosis patients. Of 292 exposed guinea pigs, 144 had evidence of tuberculosis 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 tuberculosis patients were shown by DNA fingerprinting to have caused 98% of the 125 characterised cases of secondary animal TB. 90% of tuberculosis transmission occurred from inadequately treated multi-drug resistant tuberculosis patients. Three highly infectious multi-drug resistant tuberculosis patients produced 226, 52, and 40 airborne infectious units (quanta) per hour. The study found that a small number of inadequately treated multidrug-resistant tuberculosis patients coinfected with HIV were responsible for almost all tuberculosis transmission, and some patients were highly infectious. This result highlights the importance of rapid tuberculosis drug-susceptibility testing to allow prompt initiation of effective treatment, and environmental control measures to reduce ongoing tuberculosis transmission in crowded health care settings. Tuberculosis infection control must be prioritized in order to prevent health care facilities from disseminating the drug-resistant tuberculosis that they are attempting to treat.

Editors’ note: Elegantly repeating a study from the 1950s, but using molecular tools from the 21 st century, this study found average patient infectiousness to be six times greater than that recorded in the 1950s. HIV must be playing some role. Ten of the 97 TB/HIV co-infected patients admitted to the ward were responsible for virtually all cases of TB among the guinea pigs and 6 of these 10 people had multidrug-resistant TB. Rapid testing of antibiotic susceptibility to identify people with MDR-TB for quick initiation of effective treatment should become routine. Natural or mechanical ventilation of TB wards, crowded waiting rooms, and emergency departments where patients with TB are likely to present will help prevent airborne transmission. Such environmental modifications are important everywhere and for everyone, but are critically important to reduce the risk of TB exposure for people living with HIV.

Several co-infections have been shown to impact the progression of HIV-1 infection. Walson and colleagues sought to determine if treatment of helminth co-infection in HIV-1-infected adults impacted markers of HIV-1 disease progression. To date, there have been no randomized trials to examine the effects of soil-transmitted helminth eradication on markers of HIV-1 progression. A randomized, double-blind, placebo-controlled trial of albendazole (400 mg daily for 3 days) in antiretroviral-naive HIV-1-infected adults (CD4 cell count >200 cells/microl) with soil-transmitted helminth infection was conducted at 10 sites in Kenya (Clinical Trials.gov NCT00130910). CD4 and plasma HIV-1 RNA levels at 12 weeks following randomization were compared in the trial arms using linear regression, adjusting for baseline values. Of 1551 HIV-1-infected individuals screened for helminth infection, 299 were helminth infected. Two hundred and thirty-four adults were enrolled and underwent randomization and 208 individuals were included in intent-to-treat analyses. Mean CD4 cell count was 557 cells/microl and mean plasma viral load was 4.75 log10 copies/ml at enrolment. Albendazole therapy resulted in significantly higher CD4 cell counts among individuals with Ascaris lumbricoides infection after 12 weeks of follow-up (+109 cells/microl; 95% confidence interval +38.9 to +179.0, P = 0.003) and a trend for 0.54 log10 lower HIV-1 RNA levels (P = 0.09). These effects were not seen with treatment of other species of soil-transmitted helminths. Treatment of Ascaris lumbricoides with albendazole in HIV-1-coinfected adults resulted in significantly increased CD4 cell counts during 3-month follow-up. Given the high prevalence of Ascaris lumbricoides infection worldwide, deworming may be an important potential strategy to delay HIV-1 progression.

Editors’ note: With an estimated 1.5 billion people around the world infected by Ascaris lumbricoides, predominantly in areas with high HIV disease burden, the results of this study should make us all reflect. The CD4 count improvement and RNA drop seen in this first ever randomised controlled study of the effects of eradication of soil-associated helminths on immune system activation, in a context in which average CD4 declines are 20 to 30 cells per year, could translate into significantly delayed HIV progression and potential slowing of the need for antiretroviral treatment by at least a year. Empiric deworming of all HIV-infected persons living in helminth-infected areas deserves further study.