Performance of QuantiFERON-TB Gold Plus for detection of latent tuberculosis infection in pregnant women living in a tuberculosis- and HIV-endemic setting.

We evaluated the performance of QuantiFERON-TB Gold Plus (QFT-Plus), which includes two Mycobacterium tuberculosis antigen formulations (TB1 and TB2), for detection of latent tuberculosis infection during pregnancy. Eight-hundred-twenty-nine Ethiopian pregnant women (5.9% HIV-positive) were tested with QFT-Plus, with bacteriological sputum analysis performed for women with clinically suspected tuberculosis and HIV-positive women irrespective of clinical presentation. QFT-Plus read-out was categorized according to the conventional cut-off (0.35 IU/ml) for both antigen formulations. In addition, we analysed the distribution of QFT-Plus results within a borderline zone (0.20-0.70 IU/ml), and interferon-γ response in relation to HIV infection and gestational age. Two-hundred-seventy-seven women (33%) were QFT-Plus-positive (HIV-positive 16/49 [33%]; HIV-negative 261/780 [33%]). There was a strong agreement between the two antigen formulations (κ = 0.92), with discordant results in 29 cases (3.5%). Whereas discordant QFT-Plus results were rare in pregnancy, several results with both TB1 and TB2 within the borderline range were observed (11/49 [22%] vs. 43/780 [5.5%] in HIV-positive and HIV-negative women, respectively; p<0.0001). HIV-positive women had lower absolute interferon-γ levels (TB1: 0.47 vs. 2.16 IU/ml; p<0.001, TB2: 0.49 vs. 2.24 IU/ml, p<0.001, considering results ≥0.20 IU/ml) compared to HIV-negative women. QFT-Plus-positive women who submitted samples at later stages of pregnancy had lower mitogen- (p<0.001) but higher TB-antigen-specific (p = 0.031 for TB1, p = 0.061 for TB2) interferon-γ response. Considering their lower capacity to produce TB-specific interferon-γ, a lower cut-off level for defining QFT-Plus-positivity may be considered in HIV-positive pregnant women.

Outcome of tuberculosis treatment in HIV-positive adults diagnosed through active versus passive case-finding.

BACKGROUND: The World Health Organization strongly recommends regular screening for tuberculosis (TB) in HIV-positive individuals. OBJECTIVE: To compare the outcome of anti-tuberculosis treatment (ATT) in HIV-positive adults diagnosed with TB through active case-finding (ACF) or passive case-finding (PCF). DESIGN: Antiretroviral therapy (ART)-naïve adults diagnosed with TB were included from two prospective cohort studies conducted in Ethiopia between September 2010 and March 2013. The PCF cohort was based at out-patient TB clinics, whereas participants in the ACF cohort were actively screened for TB by bacteriological sputum testing (smear microscopy, Xpert MTB/RIF assay, and liquid culture) without pre-selection on the basis of symptoms and signs. Outcomes of ATT were compared between participants in the two cohorts; characteristics at diagnosis and predictors of adverse outcomes were analysed. RESULTS: Among 439 TB/HIV co-infected participants, 307 and 132 belonged to PCF and ACF cohorts, respectively. Compared with the ACF participants, hemoptysis, conjunctival pallor, bedridden status, and low mid upper-arm circumference (MUAC) were significantly more common in participants identified through PCF. Sputum smear-positivity rates among pulmonary TB cases were 44.2% and 21.1% in the PCF and ACF cohorts, respectively (p<0.001). Treatment success was ascertained in 247 (80.5%) of the participants in the PCF cohort and 102 (77.2%) of the participants in the ACF cohorts (p=0.223). Low MUAC (p=0.001) independently predicted mortality in the participants in both cohorts. CONCLUSION: Although patients identified through ACF had less advanced TB disease, ATT outcome was similar to the patients identified through PCF. To achieve a better outcome, case management in ACF strategy should be strengthened through enhanced patient-centred counselling and adherence support.

Intensified tuberculosis case-finding in HIV-positive adults managed at Ethiopian health centers: diagnostic yield of Xpert MTB/RIF compared with smear microscopy and liquid culture.

BACKGROUND: Detection 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. METHODS: Participants 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. RESULTS: TB 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/mm(3), this increased to 82.9% in those with CD4 cell counts ≤100 cells/mm(3). Compared with Xpert-positive TB patients, Xpert-negative cases had less advanced HIV and TB disease characteristics. CONCLUSIONS: Previously 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.