Background-Tuberculosis is a common complication and leading cause of death in HIV infection. Antiretroviral therapy (ART) lowers the risk of tuberculosis, but may not be sufficient to control HIV-related tuberculosis. Isoniazid preventive therapy (IPT) reduces tuberculosis incidence significantly, but is not widely used.

Betina Durovni and colleagues evaluated whether implementation of Xpert MTB/RIF increased the notification rate of laboratory-confirmed pulmonary tuberculosis and reduced the time to tuberculosis treatment initiation in 14 Brazilian primary care laboratories. Please see later in the article for the Editors' Summary

The importance of high-incidence "hotspots" to population-level tuberculosis (TB) incidence remains poorly understood. TB incidence varies widely across countries, but within smaller geographic areas (e.g., cities), TB transmission may be more homogeneous than other infectious diseases. We constructed a steady-state compartmental model of TB in Rio de Janeiro, replicating nine epidemiological variables (e.g., TB incidence) within 1% of their observed values. We estimated the proportion of TB transmission originating from a high-incidence hotspot (6.0% of the city's population, 16.5% of TB incidence) and the relative impact of TB control measures targeting the hotspot vs. the general community. If each case of active TB in the hotspot caused 0.5 secondary transmissions in the general community for each within-hotspot transmission, the 6.0% of people living in the hotspot accounted for 35.3% of city-wide TB transmission. Reducing the TB transmission rate (i.e., number of secondary infections per infectious case) in the hotspot to that in the general community reduced city-wide TB incidence by 9.8% in year 5, and 29.7% in year 50-an effect similar to halving time to diagnosis for the remaining 94% of the community. The importance of the hotspot to city-wide TB control depended strongly on the extent of TB transmission from the hotspot to the general community. High-incidence hotspots may play an important role in propagating TB epidemics. Achieving TB control targets in a hotspot containing 6% of a city's population can have similar impact on citywide TB incidence as achieving the same targets throughout the remaining community.infectious disease transmission | theoretical models | urban population | epidemiology | communicable disease control T uberculosis (TB) remains a leading infectious cause of morbidity and mortality, with over 8.8 million cases and 1.4 million deaths annually worldwide (1). TB is known to cluster in hyperendemic "hotspots" often characterized by crowding (2), poverty (3), HIV infection (4), and other social determinants (5). However, compared with other infectious diseases [e.g., sexually transmitted diseases (6) and vector-borne diseases (7)], where 20% of the population may generate 80% of transmission (7), TB transmission appears relatively more homogeneous. As a result, though spatial targeting is often advocated as an efficient method for achieving control of diseases such as malaria (8), the degree to which hotspots contribute to community-wide transmission of TB remains uncertain. The concept of geographically defined hotspots driving TB transmission has biological plausibility. Preventing TB cases in high-transmission areas (e.g., crowded urban slums, poorly ventilated hospitals) may avert many more secondary transmissions than similar efforts in low-transmission areas. Similarly, cases in high-transmission areas are more likely to represent recent infection (which is more amenable to intervention) than reactivation of latent disease (9). Prior explorations of heterogeneity in TB tra...

Summary Background Preventive therapy for tuberculosis among HIV-infected patients is effective but has not been widely implemented in moderate/high-burden settings. Objectives To determine the impact of widespread use of isoniazid preventive therapy on rates of tuberculosis and death in HIV-infected individuals in Brazil. Design Stepped wedge, cluster randomized trial Participants Patients actively enrolled in 29 HIV clinics in Rio de Janeiro, Brazil Control period Standard of care Intervention period Staff training in tuberculosis screening, performance of tuberculin skin tests and use of isoniazid preventive therapy. Randomization Clinics were randomly allocated a date to begin the intervention period with two clinics beginning the intervention every 2 months starting September 1 2005. Main outcome measures Tuberculosis incidence alone or combined with death in the control versus intervention periods through August 31 2009. Results Among 17,413 patients in the THRio cohort, 12,816 were eligible for the intervention. Overall, there were 475 tuberculosis cases and 838 deaths. The intervention increased the rate of patients receiving skin tests from 19/100 person-years to 59/100 person-years, and from 36/100 person-years to 144/100 person-years for those eligible for isoniazid preventive therapy. In the control period, 221 tuberculosis cases were diagnosed (1·31/100 person-years) compared to 254 (1·10/100 person-years) in the intervention (unadjusted hazard ratio (HR)=0·87;95%CI:0·69–1·10). Rates of tuberculosis incidence or death were 3·64 and 3·04/100 person-years, respectively (HR=0·76; 95%CI:0·66–0·87). When adjusted for age, sex, entry CD4 count and use of antiretroviral therapy, the HR for tuberculosis was 0·73 (95%CI:0·54–0·99) and for tuberculosis or death was 0·69 (95%CI:0·57–0·83). Among 12,196 patients remaining in care (secondary analyses, 399 tuberculosis cases and 656 deaths), the adjusted HR of tuberculosis alone and combined with death were 0·42 (95%CI:0·29–0·60) and 0·45 (95%CI:0·35–0·56), respectively, Conclusions Operational training aimed at increasing tuberculosis screening, provision of tuberculin skin tests and use of isoniazid preventive therapy in Brazilian HIV clinics significantly reduced incident tuberculosis and death. Thus, scale-up of preventive therapy for HIV-infected patients in moderate tuberculosis incident settings is achievable and should be strongly considered in Brazil and elsewhere. Trial registration This trial is registered at clinicaltrials.gov (NCT00107887) Funding Bill & Melinda Gates Foundation; National Institutes of Health

Women in the sexually active age group are far more likely to get Zika than men (+90% increase); sexual transmission is the most probable cause. Women in the 15-65 years age group are also 30% more likely to be reported with dengue than men, which is probably due to women being more careful with their health.

Objective The TB/HIV in Rio (THRio) study was launched in September 2005 to assess the impact of integrated tuberculosis (TB) and HIV treatment strategies in 29 HIV clinics in Rio de Janeiro, Brazil. Design THRio is a cluster-randomized trial (CRT) to determine whether routine screening for and treatment of latent TB in HIV clinic patients with access to antiretroviral therapy will reduce TB incidence at the clinic level. THRio is part of the Consortium to Respond Effectively to AIDS/TB Epidemic that is implementing research studies to assess the impact of bold, new public health paradigms for controlling the AIDS/TB epidemic. Methods Twenty-nine public primary HIV clinics were randomly assigned a date to begin implementing TB screening procedures and provision of isoniazid preventive therapy (IPT) for TB/HIV coinfected patients. Final analysis of the CRT is expected in 2011. Results Starting at date of tuberculin skin test (TST)/IPT implementation at each clinic through August 2010, 1670 HIV-infected patients initiated IPT, of which 215 are still receiving treatment. Of the remaining 1455 patients, 1230 (85%) completed therapy and only 20 (1.2%) patients initiating IPT reported adverse reactions leading to discontinuation of therapy. IPT completion was higher among HIV-infected patients receiving HAART (87%) than those not yet receiving HAART (79%, P < 0.01). Times to TST and IPT have markedly decreased postintervention, but remain considerably long. The richness of the THRio database has resulted in several analyses of this expansive cohort of HIV-infected patients that are reviewed here. Conclusions The national implementation of TST and IPT for HIV-positive patients in Brazil has been invigorated partly due to THRio’s baseline results. Expanded use of IPT in HIV patients in Rio de Janeiro is achievable with high adherence and low adverse events, although this effort requires a package of activities including training, advocacy and reorganization of services.

Studies with cluster-randomized order of intervention introduction can provide useful information on intervention effects. Their design and analysis are more complicated than for individually randomized parallel design trials. The methods we describe represent practical approaches to the challenges raised in the course of designing this study.

Loss to follow-up is a major source of bias in cohorts of patients with human immunodeficiency virus (HIV) and could lead to underestimation of mortality. The authors developed a hierarchical deterministic linkage algorithm to be used primarily with cohorts of HIV-infected persons to recover vital status information for patients lost to follow-up. Data from patients known to be deceased in 2 cohorts in Rio de Janeiro, Brazil, and data from the Rio de Janeiro State mortality database for 1999–2006 were used to validate the algorithm. A fully automated procedure yielded a sensitivity of 92.9% and specificity of 100% when no information was missing. When the automated procedure was combined with clerical review, in a scenario of 5% death prevalence and 20% missing mothers’ names, sensitivity reached 96.5% and specificity 100%. In a practical application, the algorithm significantly increased death rates and decreased the rate of loss to follow-up in the cohorts. The finding that 23.9% of matched records did not give HIV or acquired immunodeficiency syndrome as the cause of death reinforces the need to search all-cause mortality databases and alerts for possible underestimation of death rates. These results indicate that the algorithm is accurate enough to recover vital status information on patients lost to follow-up in cohort studies.