HIV-associated tuberculosis: diagnostic and treatment challenges.

Tuberculosis (TB) and the human immunodeficiency virus (HIV) are, individually, two of the world's greatest ongoing public health threats. In combination, the two diseases can be even more devastating. HIV significantly increases an individual's chances of reactivation of latent TB infection and progression to active TB disease. HIV's associated immunosuppression makes it more difficult to diagnose active TB due to a higher likelihood of atypical and extrapulmonary presentation and poorer performance of standard diagnostic tools. TB is the major cause of death in individuals infected with HIV, and the combination of both illnesses creates unique treatment challenges for providers due to interactions between antituberculous and antiretroviral medications, overlapping drug toxicities, and the immune reconstitution inflammatory syndrome. Magnifying these challenges even further is the fact that much of the burden of TB/HIV coinfection exists in some of the world's most resource-limited settings. Concerted efforts are needed to identify rapid and accurate diagnostic tools for active TB disease and latent TB infection (LTBI) that are practical and inexpensive and that perform well in individuals with HIV infection. Also needed are effective and feasible strategies to optimize management of both conditions in the coinfected patient.

Sensitivity analysis and potential uses of a novel gamma interferon release assay for diagnosis of tuberculosis.

Sputum smears for acid-fast bacilli (AFB) are the primary methods for diagnosis of tuberculosis (TB) in many countries. The tuberculin skin test (TST) is the primary method for diagnosis of latent TB infection (LTBI) worldwide. The poor sensitivity of the former and the poor specificity of the latter warrant the development of new tests and strategies to enhance diagnostic capabilities. We evaluated the sensitivity of an "in-tube" gamma interferon release assay (IGRA) using TB-specific antigens in comparison to the TST and the sputum smear for AFB in TB cases in South Africa. The sensitivity of the IGRA for TB was considered a surrogate of sensitivity in LTBI. Among 154 patients with a positive culture for Mycobacterium tuberculosis, the sensitivity of the IGRA for the diagnosis of TB varied by clinical subgroup from 64% to 82%, that of the TST varied from 85% to 94%, and that of two sputum smears for AFB varied from 35% to 53%. The sensitivity of the IGRA in human immunodeficiency virus (HIV)-infected TB cases was 81%. HIV-infected TB patients were significantly more likely to have indeterminate IGRA results and produced quantitatively less gamma interferon in response to TB-specific antigens than HIV-negative TB patients. The overall sensitivity of the TST in all TB cases was higher than that of the IGRA (90% versus 76%, respectively). The combined sensitivities of the TST plus IGRA and TST plus a single sputum smear were 96% and 93%, respectively. The TST combined with IGRA or with a single sputum smear may have a role in excluding the diagnosis of TB in some settings.

Comparison of altitude effect on Mycobacterium tuberculosis infection between rural and urban communities in Peru.

The mechanism of high altitude effect on tuberculosis (TB) infection has not been fully established. We previously reported a lower positive tuberculin skin test (TST) prevalence in high altitude villages compared with sea level communities in Peru. In this study, four additional communities were tested to assess whether decreased TB transmission was also in urban environments at high altitude. TST results from 3,629 individuals in nine communities were analyzed using generalized estimating equations to account for community clustering. Positive TST prevalence was not significantly different between the urban highland and the urban non-highland communities after adjusting for age, household contacts with a TST-positive person or a TB case, and presence of a Bacillus Calmette-Guérin vaccination scar. The effect of population concentration and increased contact with active TB overwhelmed the protective effect of altitude in urban highlands. Highland cities require the same preventive efforts against TB as non-highland communities.