Incidence of tuberculous infection in a TB-endemic city.

Current metrics for TB transmission include TB notifications, disease mortality, and prevalence surveys. These metrics are helpful to national TB programs to assess the burden of disease, but they do not directly measure incident infection in the community.To estimate incidence of Mycobacterium tuberculosis infection in Kampala, Uganda, we performed a prospective cohort study between 2014 and 2017 which enrolled of 1,275 adult residents without signs of tuberculous infection (tuberculin skin test [TST] <5 mm and no signs of TB disease) and followed them for conversion of TST at 1 year.During follow-up, 194 participants converted the TST and 158 converted by one year. The incidence density of TST conversion was 13.2 conversions/100 person-year (95% CI 11.6-15.1), which corresponds to an annual cumulative incidence of tuberculous infection of 12.4% (95% CI 10.7-14.3). Cumulative incidence was greater among older participants and among men. Among participants who reported prior exposure to TB cases, the cumulative risk was highest among those reporting exposure during follow-up.The high annual incidence of infection suggests that residents of Kampala have adequate contact for infection with undetected, infectious cases of TB as they go about their daily lives..

In utero and peripartum antiretroviral exposure as predictor of cognition in 6- to 10-year-old HIV-exposed Ugandan children - a prospective cohort study.

OBJECTIVES: To quantify association between in utero/peripartum antiretroviral (IPA) exposure and cognition, i.e. executive function (EF) and socioemotional adjustment (SEA), in school-aged Ugandan children who were perinatally HIV-infected (CPHIV, n = 100) and children who were HIV-exposed but uninfected (CHEU, n = 101). METHODS: Children were enrolled at age 6-10 years and followed for 12 months from March 2017 to December 2018. Caregiver-reported child EF and SEA competencies were assessed using validated questionnaires at baseline, 6 and 12 months. IPA type - combination antiretroviral therapy (cART), intrapartum single-dose nevirapine ± zidovudine (sdNVP ± ZDV), nevirapine + zidovudine + lamivudine (sdNVP + ZDV + 3TC) - or no IPA (reference) was verified via medical records. IPA-related standardized mean differences (SMDs) with corresponding 95% confidence intervals (CIs) in cognitive competencies were estimated from regression models with adjustment for caregiver sociodemographic and contextual factors. Models were fitted separately for CPHIV and CHEU. RESULTS: Among CPHIV children, cART (SMD = -0.82, 95% CI: -1.37 to -0.28) and sdNVP ± ZDV (SMD = -0.41, 95% CI: -0.81 to -0.00) vs. no IPA predicted lower executive dysfunction over 12 months. Intrapartum sdNVP + ZDV + 3TC vs. no IPA predicted executive dysfunction (SMD = 0.80, 95% CI: 0.30-1.31), SEA problems (SMD = 0.63-0.76, 95% CI: 0.00-1.24) and lower adaptive skills (SMD = -0.36, 95% CI: -0.75-0.02) over 12 months among CHEU. Further adjustment for contextual factors attenuated associations, although most remained of moderate clinical importance (|SMD| > 0.33). CONCLUSIONS: Among CPHIV children, cART and sdNVP ± ZDV IPA exposure predicted, on average, lower executive dysfunction 6-10 years later. However, peripartum sdNVP + ZDV + 3TC predicted executive and SEA dysfunction among CHEU 6-10 years later. These data underscore the need for more research into long-term effects of in utero ART to inform development of appropriate interventions so as to mitigate cognitive sequelae.

Performance of the QuantiFERON®-TB Gold In-Tube assay in tuberculin skin test converters: a prospective cohort study.

OBJECTIVE: To investigate diagnostic agreement of the QuantiFERON®-TB Gold In-Tube (QFT-GIT) test in adult tuberculin skin test (TST) converters in a high tuberculosis (TB) burden setting. SETTING AND DESIGN: We performed a case-cohort study from 2014 to 2016 in Uganda among residents who were not infected with Mycobacterium tuberculosis. Participants were followed up for 1 year, when they were retested to determine TST conversion. All TST converters and a random sample of participants from baseline were offered QFT-GIT testing. RESULTS: Of 368 enrolled participants, 61 (17%) converted their TST by 1 year. Among 61 converters, 42 were tested using QFT-GIT, 64% of whom were QFT-GIT-positive. Of 307 participants with a persistent negative TST, 48 were tested using QFT-GIT, 83% of whom were QFT-negative. Overall concordance of TST and QFT-GIT was moderate (κ = 0.48, 95%CI 0.30-0.66). Converters with a conversion of 15 mm had a higher proportion of concordant QFT-GIT results (79%) than converters with increments of 10-14.9 mm (52%). CONCLUSION: Concordance between TST and QFT-GIT was moderate among TST converters in this urban African population. These findings call for improved tests that more accurately measure conversion to tuberculous infection.

Quality of life among perinatally HIV-affected and HIV-unaffected school-aged and adolescent Ugandan children: a multi-dimensional assessment of wellbeing in the post-HAART era.

OBJECTIVE: To examine quality of life (QOL) in perinatally HIV-infected (PHIV) or HIV-exposed uninfected (PHEU) vs. healthy HIV-unexposed uninfected (HUU) children during school-age/adolescence. METHODS: PHIV infection was diagnosed via DNA PCR. Current HIV status was confirmed by HIV rapid diagnostic test. Three HIV groups were defined: PHIV, PHEU, and HUU. QOL was assessed with proxy and self-report versions of the PedsQL™ 4.0 instrument at 6-18 years of age. QOL scores ranged from zero (least QOL) to 100 (highest QOL) in the following dimensions: combined QOL inventory (CQOLI), multi-dimensional vigor (MDV), general wellbeing (GWB), present functioning, and general cognitive functioning (CF). Multivariable linear regression models estimated HIV-related percent differences (ß) in QOL scores and 95% confidence intervals (CI). FINDINGS: Compared to HUU CQOLI deficits ranged from 6.5 to 9.2% (95% CI -15.4, -1.6), GWB deficit ranged from 6.5 to 10.5% (95% CI -16.0, -1.3), MDV deficit ranged from 6.8 to 11.6% (95% CI -14.5, 0.9), and CF deficit ranged from 9.7 to 13.1% for PHIV children. QOL deficits of similar magnitude and direction in most domains were observed for PHIV compared to PHEU. However, self-reported indicators of GWB (ß = -3.5; 95% CI -9.0, 2.0) and present functioning (ß = 4.0; 95% CI -4.6, 12.5) were similar for PHIV compared to PHEU. QOL scores were generally similar for PHEU compared to HUU. CONCLUSION: PHEU and HUU had similar QOL profile but PHIV predicted sustained deficits in multiple QOL domains. PHIV and PHEU children were similar with respect to general wellbeing and present functioning. Psychosocial and scholastic interventions in combination with HIV care are likely to improve QOL in PHIV.