Subclinical Tuberculosis in HIV-Infected Patients: Another Challenge for the Diagnosis of Tuberculosis in High-Burden Countries?

For the more than 2 decades that tuberculosis has been recognized as a major op-portunistic infection in patients with HIV infection/AIDS, the extraordinary spectrum of clinical presentations has made the diagnosis of tuberculosis very challenging. This spectrum includes both pulmonary and extrapulmonary disease, which often has atypical clinical and ra-diographic manifestations in HIV-infected patients, compared with those in HIV-negative patients [1]. The problem is compounded even more in developing countries where rates of Mycobacterium tuberculosis and HIV coinfection are high [2] and the resources and facilities for both radiographic and microbiologic diagnoses are often limited or nonexistent. For example , in many parts of the world, sputum smears for detection of acid-fast bacilli (AFB)—but not cultures—are used for the diagnosis of pulmonary tuberculosis. In resource-poor settings, diagnosis and treatment of active tuberculosis are the most important—and, sometimes, the only—components of tuberculosis-control programs (i.e., parts of the " DOTS " strategy). However, given the high incidence of tuberculosis among HIV-infected patients, where resources permit, the World Health Organization (WHO) has recommended the use of preventive therapy for HIV-infected persons who are tu-berculin positive with latent tuberculosis infection (LTBI) or are at high risk for LTBI (e.g., household contacts of patients with tuberculosis) [3]. This control strategy necessitates a distinction between the diagnosis of active tuberculosis, for which patients require multidrug therapy, and the diagnosis of LTBI, for which isoniazid alone is effective. As the use of antiret-roviral therapy increases in developing countries, and because opportunistic infection prophylaxis (including treatment of LTBI) will be offered as part of a package of care, the need for this distinction is becoming even more important [4]. The study by Mtei et al. [5] in this issue of Clinical Infectious Diseases presents a potential new challenge for the diagnosis of subtle tuberculosis in asymptomatic patients, and it may have implications with regard to treatment decisions (i.e., therapy for active disease vs. therapy for LTBI). As part of a study of an investi-gational mycobacterial vaccine for HIV-infected patients with CD4 cell counts of 1200 cells/mm 3 and no evidence of active tuberculosis, subjects in Tanzania underwent screening for tuberculosis, with an assessment for symptoms (weight loss and cough or fever), performance of tuber-culin skin tests (TSTs), chest radiography, obtainment of sputum and blood specimens for cultures for AFB, and in vitro immunologic studies. Patients with active tuberculosis were referred elsewhere for treatment with a multidrug regimen, and …