Community-Wide Universal Human Immunodeficiency Virus (HIV) Test and Treat Intervention Reduces Tuberculosis Transmission in Rural Uganda: A Cluster-Randomized Trial.

BACKGROUND: Human immunodeficiency virus (HIV) treatment reduces tuberculosis (TB) disease and mortality; however, the population-level impact of universal HIV-test-and-treat interventions on TB infection and transmission remain unclear. METHODS: In a sub-study nested in the SEARCH trial, a community cluster-randomized trial (NCT01864603), we assessed whether a universal HIV-test-and-treat intervention reduced population-level incident TB infection in rural Uganda. Intervention communities received annual, population-level HIV testing and patient-centered linkage. Control communities received population-level HIV testing at baseline and endline. We compared estimated incident TB infection by arms, defined by tuberculin skin test conversion in a cohort of persons aged 5 and older, adjusting for participation and predictors of infection, and accounting for clustering. RESULTS: Of the 32 trial communities, 9 were included, comprising 90 801 participants (43 127 intervention and 47 674 control). One-year cumulative incidence of TB infection was 16% in the intervention and 22% in the control; SEARCH reduced the population-level risk of incident TB infection by 27% (adjusted risk ratio = 0.73; 95% confidence interval [CI]: .57-.92, P = .005). In pre-specified analyses, the effect was largest among children aged 5-11 years and males. CONCLUSIONS: A universal HIV-test-and-treat intervention reduced incident TB infection, a marker of population-level TB transmission. Investments in community-level HIV interventions have broader population-level benefits, including TB reductions.

The Association Between Social Network Characteristics and Tuberculosis Infection Among Adults in 9 Rural Ugandan Communities.

BACKGROUND: Social network analysis can elucidate tuberculosis transmission dynamics outside the home and may inform novel network-based case-finding strategies. METHODS: We assessed the association between social network characteristics and prevalent tuberculosis infection among residents (aged ≥15 years) of 9 rural communities in Eastern Uganda. Social contacts named during a census were used to create community-specific nonhousehold social networks. We evaluated whether social network structure and characteristics of first-degree contacts (sex, human immunodeficiency virus [HIV] status, tuberculosis infection) were associated with revalent tuberculosis infection (positive tuberculin skin test [TST] result) after adjusting for individual-level risk factors (age, sex, HIV status, tuberculosis contact, wealth, occupation, and Bacillus Calmette-Guérin [BCG] vaccination) with targeted maximum likelihood estimation. RESULTS: Among 3 335 residents sampled for TST, 32% had a positive TST results and 4% reported a tuberculosis contact. The social network contained 15 328 first-degree contacts. Persons with the most network centrality (top 10%) (adjusted risk ratio, 1.3 [95% confidence interval, 1.1-1.1]) and the most (top 10%) male contacts (1.5 [1.3-1.9]) had a higher risk of prevalent tuberculosis, than those in the remaining 90%. People with ≥1 contact with HIV (adjusted risk ratio, 1.3 [95% confidence interval, 1.1-1.6]) and ≥2 contacts with tuberculosis infection were more likely to have tuberculosis themselves (2.6 [ 95% confidence interval: 2.2-2.9]). CONCLUSIONS: Social networks with higher centrality, more men, contacts with HIV, and tuberculosis infection were positively associated with tuberculosis infection. Tuberculosis transmission within measurable social networks may explain prevalent tuberculosis not associated with a household contact. Further study on network-informed tuberculosis case finding interventions is warranted.

The age-specific burden and household and school-based predictors of child and adolescent tuberculosis infection in rural Uganda.

BACKGROUND: The age-specific epidemiology of child and adolescent tuberculosis (TB) is poorly understood, especially in rural areas of East Africa. We sought to characterize the age-specific prevalence and predictors of TB infection among children and adolescents living in rural Uganda, and to explore the contribution of household TB exposure on TB infection. METHODS: From 2015-2016 we placed and read 3,121 tuberculin skin tests (TST) in children (5-11 years old) and adolescents (12-19 years old) participating in a nested household survey in 9 rural Eastern Ugandan communities. TB infection was defined as a positive TST (induration ≥10mm or ≥5mm if living with HIV). Age-specific prevalence was estimated using inverse probability weighting to adjust for incomplete measurement. Generalized estimating equations were used to assess the association between TB infection and multi-level predictors. RESULTS: The adjusted prevalence of TB infection was 8.5% (95%CI: 6.9-10.4) in children and 16.7% (95% CI:14.0-19.7) in adolescents. Nine percent of children and adolescents with a prevalent TB infection had a household TB contact. Among children, having a household TB contact was strongly associated with TB infection (aOR 5.5, 95% CI: 1.7-16.9), but the strength of this association declined among adolescents and did not meet significance (aOR 2.3, 95% CI: 0.8-7.0). The population attributable faction of TB infection due to a household TB contact was 8% for children and 4% among adolescents. Mobile children and adolescents who travel outside of their community for school had a 1.7 (95% CI 1.0-2.9) fold higher odds of TB infection than those who attended school in the community. CONCLUSION: Children and adolescents in this area of rural eastern Uganda suffer a significant burden of TB. The majority of TB infections are not explained by a known household TB contact. Our findings underscore the need for community-based TB prevention interventions, especially among mobile youth.

HIV Testing and Treatment with the Use of a Community Health Approach in Rural Africa.

BACKGROUND: Universal antiretroviral therapy (ART) with annual population testing and a multidisease, patient-centered strategy could reduce new human immunodeficiency virus (HIV) infections and improve community health. METHODS: We randomly assigned 32 rural communities in Uganda and Kenya to baseline HIV and multidisease testing and national guideline-restricted ART (control group) or to baseline testing plus annual testing, eligibility for universal ART, and patient-centered care (intervention group). The primary end point was the cumulative incidence of HIV infection at 3 years. Secondary end points included viral suppression, death, tuberculosis, hypertension control, and the change in the annual incidence of HIV infection (which was evaluated in the intervention group only). RESULTS: A total of 150,395 persons were included in the analyses. Population-level viral suppression among 15,399 HIV-infected persons was 42% at baseline and was higher in the intervention group than in the control group at 3 years (79% vs. 68%; relative prevalence, 1.15; 95% confidence interval [CI], 1.11 to 1.20). The annual incidence of HIV infection in the intervention group decreased by 32% over 3 years (from 0.43 to 0.31 cases per 100 person-years; relative rate, 0.68; 95% CI, 0.56 to 0.84). However, the 3-year cumulative incidence (704 incident HIV infections) did not differ significantly between the intervention group and the control group (0.77% and 0.81%, respectively; relative risk, 0.95; 95% CI, 0.77 to 1.17). Among HIV-infected persons, the risk of death by year 3 was 3% in the intervention group and 4% in the control group (0.99 vs. 1.29 deaths per 100 person-years; relative risk, 0.77; 95% CI, 0.64 to 0.93). The risk of HIV-associated tuberculosis or death by year 3 among HIV-infected persons was 4% in the intervention group and 5% in the control group (1.19 vs. 1.50 events per 100 person-years; relative risk, 0.79; 95% CI, 0.67 to 0.94). At 3 years, 47% of adults with hypertension in the intervention group and 37% in the control group had hypertension control (relative prevalence, 1.26; 95% CI, 1.15 to 1.39). CONCLUSIONS: Universal HIV treatment did not result in a significantly lower incidence of HIV infection than standard care, probably owing to the availability of comprehensive baseline HIV testing and the rapid expansion of ART eligibility in the control group. (Funded by the National Institutes of Health and others; SEARCH ClinicalTrials.gov number, NCT01864603.).

Implementation and Operational Research: Population-Based Active Tuberculosis Case Finding During Large-Scale Mobile HIV Testing Campaigns in Rural Uganda.

BACKGROUND: Active tuberculosis (TB) screening outside clinics and in communities may reduce undiagnosed TB. METHODS: To determine the yield of TB screening during community-based HIV testing campaigns (CHC) in 7 rural Ugandan communities within an ongoing cluster-randomized trial of universal HIV testing and treatment (SEARCH, NCT:01864603), we offered sputum microscopy to participants with prolonged cough (>2 weeks). We determined the number of persons needed to screen to identify one TB case, and the number of cases identified that linked to clinic and completed TB treatment. RESULTS: Of 36,785 adults enumerated in 7 communities, 27,214 (74%) attended CHCs, and HIV testing uptake was >99%, with 941 (3.5%) HIV-infected adults identified. Five thousand seven hundred eighty-six adults (21%) reported cough and 2876 (11%) reported cough >2 weeks. Staff obtained sputum in 1099/2876 (38%) participants with prolonged cough and identified 10 adults with AFB-positive sputum; 9 new diagnoses and 1 known case already under treatment. The number needed to screen to identify one new TB case was 3024 adults overall: 320 adults with prolonged cough and 80 HIV-infected adults with prolonged cough. All 9 newly diagnosed AFB+ participants were linked to TB care within 2 weeks and were initiated TB treatment. CONCLUSIONS: In a rural Ugandan setting, TB screening as an adjunct to large-scale mobile HIV testing campaigns provides an opportunity to increase TB case detection.