In 2011, there were 8.7 million new cases of active tuberculosis worldwide. Recent advances in diagnostics, drugs, and vaccines and enhanced implementation of interventions are helping to improve the prospects for global tuberculosis control. The latest review in our Current Concepts series covers the diagnosis and treatment of latent, active, and drug-resistant tuberculosis and also reviews new drugs and vaccines.
Despite the availability of a cheap and effective cure, tuberculosis remains responsible for millions of active tuberculosis cases and deaths worldwide, disproportionately affecting the poorest in both high-income and developing countries. Recent advances in new diagnostics, drugs, and vaccines and enhanced implementation of existing interventions now provide optimism for improved clinical care and prospects for global tuberculosis control.
• What are the clinical manifestations of tuberculosis?
The classical clinical features of pulmonary tuberculosis include chronic cough, sputum production, appetite loss, weight loss, fever, night sweats, and hemoptysis. Extrapulmonary tuberculosis (EPTB) occurs in 10 to 42% of cases, depending on ethnic background, host, M. tuberculosis strain genotype, and immune status. EPTB can affect any organ in the body, has varied and protean clinical manifestations, and requires a high index of clinical suspicion.
• How does coinfection with HIV affect the risk for and presentation of tuberculosis?
The risk of active tuberculosis disease increases soon after infection with HIV and the manifestations of pulmonary tuberculosis at this stage are similar to those in HIV-negative persons. At CD4 counts <200 per cubic millimeter, the presentation of tuberculosis may be atypical, with subtle infiltrates, pleural effusions, hilar lymphadenopathy, and other forms of EPTB in as many as 50% of patients. At CD4 counts <75 per cubic millimeter, pulmonary findings may be absent and disseminated tuberculosis is more frequent, presenting as a non-specific chronic febrile illness with widespread organ involvement, mycobacteremia, and high early mortality. Cases may be mistakenly diagnosed as other infectious diseases, and are often only identified by autopsy. Asymptomatic, smear-negative, culture-positive, chest X-ray negative, subclinical tuberculosis is a common feature of HIV-associated tuberculosis and may represent 10% of cases in endemic regions.
Morning Report Questions
Q: What tests are available for diagnosing active tuberculosis?
A: Sputum microscopy and culture in liquid media with subsequent drug susceptibility testing (DST) are current recommended standard tuberculosis diagnostics. Solid culture media are more cost-effective in resource poor countries. Interferon gamma release assays an tuberculin skin tests have no role in the diagnosis of active tuberculosis disease. Nucleic acid amplification tests (NAATs), imaging, and histopathological examination of biopsies supplement these evaluations. The new molecular diagnostic test Xpert MTB/RIF assay detects M. tuberculosis complex rapidly in 2 hours with assay sensitivity much higher than smear microscopy. In HIV-patients it yields up to a 45% increase in tuberculosis case detection compared with smear microscopy.
Q: How does tuberculosis coinfection affect the treatment of HIV?
A: Tuberculosis leads to CD4+ cell activation and accelerated progression of HIV disease with attendant high mortality. Early initiation of antiretroviral therapy (ART) results in reduction of mortality and AIDS-defining conditions; short-term mortality risk without ART is high for those with very low CD4+ cell counts. WHO recommends that ART be started within the first eight weeks of initiating tuberculosis treatment, and that those with CD4+ counts <50 cells should receive ART within the first two weeks. One exception is tuberculosis meningitis where earlier ART initiation does not improve outcomes and results in more adverse events. Immune reconstitution inflammatory syndrome (IRIS) occurs in at least 5 to 10% of HIV-infected patients starting ART during tuberculosis treatment. This includes both “unmasking IRIS” (new active tuberculosis detected after ART initiation) and “paradoxical IRIS” (clinical worsening during tuberculosis treatment after ART initiation). IRIS is more common with lower CD4+ cell counts and at earlier ART initiation during tuberculosis treatment, with rates approaching 50% among patients with CD4+ cell count <50 and ART initiation within 4 weeks of beginning tuberculosis treatment.