BackgroundShort-course tuberculosis preventive therapy with isoniazid and rifapentine (HP) is widely recommended, but the acceptability and safety of one month of daily HP (1HP) compared to three months of weekly HP (3HP) is uncertain. We compared treatment with these two regimens in people with a positive latent tuberculosis infection test and without HIV infection. We hypothesized that 1HP would have greater treatment completion and fewer targeted safety events than 3HP.Methods and findingsWe conducted a Phase 4 randomized trial of 1HP versus 3HP in adolescents and adults without HIV infection with recent tuberculosis exposure and a positive latent tuberculosis infection test in two sites in Brazil. The primary outcomes were successful completion of >90% of medication as ascertained by self-report, pill counts, and pharmacologic monitoring, and safety. Treatment safety was defined as occurrence of Grade >2 targeted events or discontinuation of treatment for side effects. We randomized 500 individuals to 1HP (249) and 3HP (251); 193 males and 307 females, with a median age of 39 years. Treatment completion was 89.6% for 1HP recipients versus 84.1% for 3HP recipients (site-adjusted risk difference 5.2%, [95% CI: [-0.1%, 11.2%], p = 0.10). Targeted >Grade 2 adverse safety events or treatment discontinuation occurred in 16.1% of 1HP recipients and 10.4% of 3HP recipients (site-adjusted risk difference 6.1%, [95%CI: [-0.04%, 12.3%], p = 0.05). The proportions who discontinued treatment for any side effect were 7.2% for 1HP and 4.4% for 3HP. The risk difference for the primary safety outcome adjusted for site and baseline demographic and clinical covariates was 3.4% (95% CI [-2.3,9.1%], p = 0.24). The trial was not designed to ascertain efficacy.ConclusionBoth 1HP and 3HP had high rates of treatment success. Participants assigned to 1HP had more targeted safety events, mostly low-grade. Neither regimen was superior to the other. These results will inform global guidelines for tuberculosis preventive therapy. NCT04703075 (clinicaltrials.gov).
Background Adherence to the complete chloroquine–primaquine regimen is important for achieving a radical cure of Plasmodium vivax malaria. However, the 7- or 14-day treatment course and its associated challenges may hinder consistent medication use in endemic areas. This study aimed to assess a combined educational and mHealth intervention to support adherence to P. vivax treatment in the Brazilian Amazon. Methods We conducted a sequential exploratory mixed-methods study in two municipalities of the Brazilian Amazon. In Phase 1, semi-structured interviews were conducted with patients and healthcare providers (HCPs) to explore perceptions, barriers, and facilitators related to P. vivax treatment adherence. These findings informed the co-design of a culturally adapted adherence support intervention, consisting of a printed educational envelope and SMS and/or WhatsApp messages delivered throughout treatment. In Phase 2, a cluster-randomized trial was conducted in 10 health units in Manaus, comparing the intervention (educational envelope plus messages) with standard care. Adherence was assessed between days 7 and 12 using the Morisky Medication Adherence Scale. A qualitative sub-study was conducted to assess the acceptability and appropriateness of the intervention. Results In Phase 1, qualitative findings identified key determinants of adherence, including the role of directly observed therapy, barriers related to pill burden and side effects, and the potential of digital reminders. These findings informed the development of a combined adherence support intervention, consisting of a printed educational envelope (validated by 16 HCPs) and a set of SMS and/or WhatsApp messages. In Phase 2, 227 participants were enrolled across 10 health units, with 117 in the intervention group and 110 in the control group. Overall adherence was 79%, with no substantial difference observed between the intervention and control groups (81% vs 77%). The qualitative sub-study indicated high acceptability of the intervention. The educational envelope supported medication organization, while cell phone message reminders helped reduce forgetfulness. Conclusions Although no significant improvement in adherence was observed, the intervention was feasible, well accepted, and contextually appropriate. Low-cost, culturally adapted tools may complement directly observed therapy in urban Amazonian settings and be adapted for remote areas with limited connectivity to support malaria elimination in Brazil.
Abstract Rationale Non-sputum biomarkers to monitor tuberculosis treatment and predict poor outcomes are lacking. Objectives To evaluate host-blood transcriptomic signatures for treatment monitoring and prognosis of death, treatment failure, and recurrence in adults with pulmonary tuberculosis. Methods Adults with culture-confirmed, drug-susceptible pulmonary tuberculosis were enrolled at 5 Brazilian sites. Whole-blood PAXgene samples were collected at baseline, month 2 (M2), and end of treatment (EoT). Treatment failure was defined as sputum culture positivity at month 5 or later. Participants were followed for 24 months from treatment initiation for clinical or microbiological tuberculosis recurrence. Unfavorable outcomes were matched ∼1:3 to recurrence-free cure. Twenty-two published blood transcriptomic signatures were measured by microfluidic RT-qPCR and benchmarked against the WHO Target Product Profile (TPP) criteria. Measurements and Main results We matched 263 participants with recurrence-free cure to 33 with treatment failure, 24 who died (tuberculosis/unknown cause), and 9 with recurrence. Signature scores generally declined from baseline to EoT. Multiple signatures measured at baseline and M2 predicted recurrence (AUC range 0.71-0.91), with waning performance when measured at EoT (AUC range 0.42-0.89). Against the WHO TPP, 2/22 signatures met minimum criteria at baseline, 13/22 at M2, and none at EoT. Prediction of treatment failure was poor across timepoints (AUC < 0.70). In contrast, several signatures measured at baseline predicted death during treatment or follow-up (AUC ≥ 0.80). Conclusions Blood transcriptomic signatures tracked treatment response and predicted recurrence and death, meeting WHO TPP benchmarks at baseline and M2. These findings support prospective, biomarker-guided trials to individualize tuberculosis therapy—shortening regimens for early responders and intensifying care for high-risk patients.
ABSTRACT American tegumentary leishmaniasis (ATL) remains a significant public health problem in the Americas, with the Amazon region standing out in Brazil for its high number of cases. This article aimed to present advances in the understanding of epidemiology, diagnosis, treatment and control of ATL in the state of Amazonas over the past decades. This study is a narrative review of scientific studies published in the literature between 2011 and 2025, retrieved from databases such as PubMed and SciELO, as well as public data from the Notifiable Diseases Information System (SINAN), official reports from the Ministry of Health and technical notes from the Amazonas Health Surveillance Foundation. The evolution of disease incidence is reported, highlighting the predominance of Leishmania (Viannia) guyanensis and the environmental factors associated with the increase in cases, such as deforestation and unplanned urbanization. Advances in diagnostic strategies include the expanded use of molecular techniques and the strengthening of the primary healthcare network. Regarding therapy, clinical trials with drugs such as pentamidine, miltefosine, tamoxifen and itraconazole have demonstrated their efficacy in treatment. The review also includes socio-environmental, genetic and experimental studies that have contributed to a better understanding of the disease. It emphasizes the need to establish a priority agenda that includes the use of telemedicine and the institutionalization of collaborative research for therapeutic innovation, integration between research and healthcare services and strategies adapted to the Amazonian context. Regional scientific advances can support more effective control policies and reduce the burden of ATL in this highly endemic setting.
The burden of lower respiratory tract infections (LRTIs) caused by Mycobacterium tuberculosis (MTB) among children and adolescents is often underestimated due to challenges in obtaining lower respiratory tract samples, nonspecific signs and symptoms, the paucibacillary nature of tuberculosis (TB), and the low yield of microbiological tests. Xpert MTB/RIF Ultra in induced sputum (IS) samples is the most promising test for improving microbiologic diagnosis of pulmonary tuberculosis (PTB) in young children. We describe the TBPed Brazil study, a multicenter, cross-sectional study in participants aged 6 months to 15 years. We designed a two-arm study: a hospital-based arm with patients hospitalized with LRTI and an outpatient-based arm with children and adolescents referred to TB-specialized clinics. The main aim in the hospital-based arm is to determine the prevalence of PTB. In the outpatient-based arm, the main objective is to determine the accuracy of Xpert MTB/RIF Ultra in IS samples compared to liquid culture. We evaluate in both arms: tuberculosis infection (TBI) prevalence, the accuracy of tongue swabs compared to liquid culture and clinical diagnosis, the risk factors associated with PTB or TBI; the accuracy of the Brazilian Ministry of Health scoring system for the diagnosis of PTB. In the hospital-based arm, we also evaluate the prevalence of viral and/or bacterial pathogens associated with LRTI. The sample size is 1,848 participants (1,118 hospitalized and 730 outpatients). Enrollment began in December 2021 and is expected to conclude in 2026, involving 27 study sites across Brazil. This is the first prospective nationwide investigation into the prevalence of PTB and TBI, as well as diagnostic accuracy across different methods, in children and adolescents in a large country with a significant TB burden. Study results will provide critical data on epidemiological, clinical, and diagnostic approaches to MTB and other respiratory pathogens in children in Brazil, guiding future studies and public health policies.
