Implementation and Operational Research: Declining Tuberculosis Incidence Among People Receiving HIV Care and Treatment Services in East Africa, 2007-2012.

BACKGROUND: Antiretroviral therapy (ART) reduces the risk of Tuberculosis (TB) among people living with HIV (PLWH). With ART scale-up in sub-Saharan Africa over the past decade, incidence of TB among PLWH engaged in HIV care is predicted to decline. METHODS: We conducted a retrospective analysis of routine clinical data from 168,330 PLWH receiving care at 35 facilities in Kenya, Tanzania, and Uganda during 2003-2012, participating in the East African region of the International Epidemiologic Databases to Evaluate AIDS. Temporal trends in facility-based annual TB incidence rates (per 100,000 person years) among PLWH and country-specific standardized TB incidence ratios using annual population-level TB incidence data from the World Health Organization were computed between 2007 and 2012. We examined patient-level and facility-level factors associated with incident TB using multivariable Cox models. RESULTS: Overall, TB incidence rates among PLWH in care declined 5-fold between 2007 and 2012 from 5960 to 985 per 100,000 person years [P = 0.0003] (Kenya: 7552 to 1115 [P = 0.0007]; Tanzania: 7153 to 635 [P = 0.0025]; Uganda: 3204 to 242 [P = 0.018]). Standardized TB incidence ratios significantly decreased in the 3 countries, indicating a narrowing gap between incidence rates among PLWH and the general population. We observed lower hazards of incident TB among PLWH on ART and/or isoniazid preventive therapy and receiving care in facilities offering TB treatment onsite. CONCLUSIONS: Annual TB incidence rates among PLWH significantly declined during ART scale-up but remained higher than the general population. Increasing access to ART and isoniazid preventive therapy and co-location of HIV and TB treatment may further reduce TB incidence among PLWH.

Comparing interferon-gamma release assays to tuberculin skin test in Thai children with tuberculosis exposure.

BACKGROUND: Data on the performance of interferon-gamma release assays (IGRAs), QuantiFERON TB Gold In-tube (QFNGIT) and T-Spot.TB, in diagnosing tuberculosis (TB) are limited in Southeast Asia. This study aims to compare the performances of the two IGRAs and TST in Thai children with recent TB exposure. METHODS: This multicenter, prospective study enrolled children with recent exposure to active TB adults. Children were investigated for active TB. TST was performed and blood collected for T-Spot.TB and QFNGIT. RESULTS: 158 children were enrolled (87% TB-exposed and 13% active TB, mean age 7.2 years). Only 3 children had HIV infection. 66.7% had TST≥10 mm, while 38.6% had TST≥15 mm. 32.5% had positive QFNGIT; 29.9% had positive T-Spot.TB. QFNGIT and T-Spot.TB positivity was higher among children with active TB compared with TB-exposed children. No indeterminate IGRA results were detected. No statistically significant differences between the performances of the IGRAs and TST at the two cut-offs with increasing TB exposure were detected. Concordance for positive IGRAs and TST ranged from 42-46% for TST≥10 mm and 62-67% for TST≥15 mm. On multivariable analyses, exposure to household primary/secondary caregiver with TB was associated with positive QFNGIT. Higher TB contact score and active TB were associated with positive T-Spot.TB. CONCLUSIONS: Both QFNGIT and T-Spot.TB performed well in our Thai pediatric study population. No differences in the performances between tests with increasing TB exposure were found. Due to accessibility and low cost, using TST may more ideal than IGRAs in diagnosing latent and active TB in healthy children in Thailand and other similar settings.

Powassan meningoencephalitis, New York, New York, USA.

Disease caused by Powassan virus (POWV), a tick-borne flavivirus, ranges from asymptomatic to severe neurologic compromise and death. Two cases of POWV meningoencephalitis in New York, USA, highlight diagnostic techniques, neurologic outcomes, and the effect of POWV on communities to which it is endemic.

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.