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).
Adherence to chloroquine–primaquine treatment is essential for preventing Plasmodium vivax recurrence, but the 7-day primaquine regimen may be difficult to complete because of pill burden, adverse effects, early symptom improvement, and forgetfulness. We evaluated a culturally adapted educational and mobile health (mHealth) intervention to support treatment adherence in the Brazilian Amazon. We conducted a sequential exploratory mixed-methods study in Manaus and Ipixuna. In Phase 1, interviews with patients and healthcare providers identified barriers and facilitators to adherence and informed the co-design of a printed educational envelope and SMS/WhatsApp reminders. In Phase 2, 10 primary health units in Manaus were cluster-randomized to intervention or standard care. Adherence was assessed by telephone between days 7 and 12 using the 4-item Morisky Medication Adherence Scale and analyzed using modified Poisson regression with standard errors clustered by health unit. A qualitative sub-study assessed acceptability and appropriateness. Phase 1 identified pill burden, adverse effects, early symptom improvement, limited understanding of dosing instructions, and forgetfulness as key barriers, while treatment supervision and clear guidance supported adherence. In Phase 2, 274 participants were enrolled and 227 were included in the primary outcome analysis, with 117 in the intervention group and 110 in the control group. Overall adherence was 79.3
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 similar to 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.
Donovanosis is a chronic granulomatous sexually transmitted infection that may clinically mimic malignancy. We report a 64-year-old man with well-controlled HIV infection presenting with a chronic infiltrated vegetative scrotal ulcer showing progressive enlargement, exophytic growth, and hemorrhagic ulceration. Despite prolonged antimicrobial therapy with azithromycin and doxycycline, followed by adjunctive acyclovir because of suspected chronic herpes simplex coinfection, the lesion continued to progress, raising concern for squamous cell carcinoma. Initial histopathological and microbiological investigations, including cytology for Donovan bodies, were inconclusive. Repeat biopsy demonstrated pseudoepitheliomatous hyperplasia with a dense plasma cell-rich inflammatory infiltrate without cytological atypia, while periodic acid-Schiff staining identified intracellular Donovan bodies, confirming donovanosis. Doxycycline was reintroduced and maintained until complete healing after four months. This case highlights the diagnostic challenges of pseudotumoral donovanosis in patients living with HIV.
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.
