BackgroundDetection of active tuberculosis (TB) before antiretroviral therapy (ART) initiation is important, but optimal diagnostic methods for use in resource-limited settings are lacking. We assessed the prevalence of TB, evaluated the diagnostic yield of Xpert MTB/RIF in comparison with smear microscopy and culture, and the impact of Xpert results on clinical management in HIV-positive adults eligible for ART at health centers in a region of Ethiopia.MethodsParticipants were prospectively recruited and followed up at 5 health centers. Trained nurses collected data on socio-demographic characteristics, medical history and symptoms, and performed physical examination. Two paired morning sputum samples were obtained, and lymph node aspirates in case of lymphadenopathy. Diagnostic yield of Xpert MTB/RIF in sputum was compared with smear microscopy and liquid culture.ResultsTB was diagnosed in 145/812 participants (17.9%), with bacteriological confirmation in 137 (16.9%). Among bacteriologically confirmed cases, 31 were smear-positive (22.6%), 96 were Xpert-positive (70.1%), and 123 were culture-positive (89.8%). Xpert MTB/RIF increased the TB detection rate by 64 cases (47.4%) compared with smear microscopy. The overall sensitivity of Xpert MTB/RIF was 66.4%, and was not significantly lower when testing one compared with two samples. While Xpert MTB/RIF was 46.7% sensitive among patients with CD4 cell counts >200 cells/mm3, this increased to 82.9% in those with CD4 cell counts ≤100 cells/mm3. Compared with Xpert-positive TB patients, Xpert-negative cases had less advanced HIV and TB disease characteristics.ConclusionsPreviously undiagnosed TB is common among HIV-positive individuals managed in Ethiopian health centers. Xpert MTB/RIF increased TB case detection, especially in patients with advanced immunosuppression. An algorithm based on the use of a single morning sputum sample for individuals with negative sputum smear microscopy could be considered for intensified case finding in patients eligible for ART. However, technical and cost-effectiveness issues relevant for low-income countries warrant further study.

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Among HIV-infected, antiretroviral therapy (ART)–naive adults with positive World Health Organization tuberculosis (TB) symptom screening, clinical scoring could categorize patients for the risk of TB. This strategy would reduce the proportion of patients requiring TB testing before starting ART.

BackgroundThe clinical correlations and significance of subnormal CD4 levels in HIV-negative patients with TB are unclear. We have determined CD4 cell levels longitudinally during anti-tuberculosis treatment (ATT) in patients, with and without HIV co-infection, and their associations with clinical variables.MethodAdults diagnosed with TB (maximum duration of ATT for 2 weeks, and with no history of antiretroviral therapy (ART) in HIV-positive subjects) were included consecutively in eight out-patient clinics in Ethiopia. Healthy individuals were recruited for comparison at one of the study health centers. Data on patient characteristics and physical findings were collected by trained nurses following a structured questionnaire at inclusion and on follow-up visits at 2 and 6 months. In parallel, peripheral blood CD4 cell levels were determined. The evolution of CD4 cell levels during ATT was assessed, and the association between clinical characteristics and low CD4 cell levels at baseline was investigated using regression analysis.ResultsIn total, 1116 TB patients were included (307 HIV-infected). Among 809 HIV-negative patients, 200 (25%) had subnormal CD4 cell counts (<500 cells/mm3), with <350 cells/mm3 in 82 (10%) individuals. CD4 cell levels increased significantly during the course of ATT in both HIV+ and HIV- TB-patients, but did not reach the levels in healthy subjects (median 896 cells/mm3). Sputum smear status, signs of wasting (low mid upper arm circumference (MUAC)), and bedridden state were significantly associated with low CD4 cell counts.ConclusionA high proportion of Ethiopian TB patients have subnormal CD4 cell counts before starting treatment. Low CD4 cell levels are associated with smear positive disease and signs of wasting. The continuous increase of CD4 cell counts during the course of ATT suggest a reversible impact of active TB on CD4 cell homeostasis, which may be considered in interpretation of CD4 cell counts in HIV/TB co-infected subjects.