Shorter Drug Regimens Boost Tuberculosis Preventive Treatment Completion Among Brazilian Children

Tuberculosis remains one of the world’s most stubborn infectious disease challenges, and while much of the public conversation focuses on treating active cases, a quieter battle unfolds in clinics every day: convincing children and adolescents who carry dormant Mycobacterium tuberculosis bacteria to complete months of preventive medication before the infection ever has a chance to flare into disease. A new retrospective cohort study from Brazil, published in BMC Infectious Diseases, has now mined one of the largest national datasets of its kind to answer a deceptively simple question — which children actually finish their tuberculosis preventive treatment, and what factors tip the scales toward success or abandonment?

The research team, led by João Paulo Cola and Thiago Nascimento do Prado and spanning institutions including the State Department of Health of Espírito Santo, the Federal University of Espírito Santo, the Federal University of Rio de Janeiro, and the Oswaldo Cruz Institute, analyzed notifications recorded in Brazil’s national tuberculosis database between 2018 and 2023. Their focus was a cohort of children and young adolescents aged 0 to 15 years who had been prescribed tuberculosis preventive treatment, commonly abbreviated TPT. Out of 31,121 notified cases, 24,903 carried complete outcome information — a substantial analytical sample that allowed the investigators to model completion patterns with statistical rigor using a robust variance Poisson regression approach, reporting relative risks with 95 percent confidence intervals.

The headline finding is both encouraging and sobering. Completion rates were modestly higher among children aged 5 to 9 years, with a relative risk of 1.02 (95 percent CI 1.01–1.04), and among adolescents aged 10 to 15, with a relative risk of 1.03 (95 percent CI 1.02–1.05). Children of white skin color showed slightly higher completion (RR 1.02; 95 percent CI 1.01–1.03), as did those vaccinated with BCG (RR 1.05; 95 percent CI 1.02–1.08) and those using immunosuppressive therapy (RR 1.07; 95 percent CI 1.03–1.19). But the strongest signals belonged to the treatment regimens themselves: shorter courses of four months of rifampicin (RR 1.10; 95 percent CI 1.08–1.12) and three months of isoniazid plus rifapentine (RR 1.13; 95 percent CI 1.12–1.15) were associated with meaningfully better completion than the traditional long-course alternatives.

To appreciate why these numbers matter, it helps to understand the pharmacological landscape of preventive therapy. For decades, the global standard for treating latent tuberculosis infection has been six to nine months of daily isoniazid — regimens designated 6H and 9H in the study’s nomenclature, involving 180 to 270 doses taken over six to twelve months. Adherence to such prolonged schedules is notoriously difficult for anyone, let alone a toddler or a teenager juggling school, family dynamics, and the general impatience of youth. Each additional month of daily pills multiplies the opportunities for missed doses, side effects, caregiver fatigue, and eventual dropout. The alternative regimens examined in this study flip that equation: 4R consists of 120 doses of rifampicin taken over four to six months, while 3HP — the regimen combining rifapentine with isoniazid — requires only 12 weekly doses administered over 12 to 15 weeks. The 3HP scheme, in particular, represents a paradigm shift, compressing what was once nearly a year of daily compliance into roughly three months of weekly visits.

The Brazilian health system context amplifies the significance of these findings. Brazil’s Unified Health System, known locally as SUS, provides tuberculosis care free of charge across a vast and geographically diverse country, and the national surveillance infrastructure — including the Information System for Notification of People on Tuberculosis Preventive Treatment, or IL-TB — captures granular data on who is prescribed preventive therapy and how their courses conclude. This study leveraged that infrastructure to assemble one of the most comprehensive pictures to date of pediatric preventive treatment in a high-burden, middle-income setting. The cohort period, 2018 to 2023, also straddles an important policy transition: the gradual introduction of shorter regimens, including 3HP, into Brazilian clinical practice following World Health Organization recommendations.

Notably, the association between 3HP and completion held even after the researchers adjusted for demographic and clinical confounders in their multivariate model. A relative risk of 1.13 may sound incremental, but when applied across tens of thousands of treatment courses, it translates into thousands of additional children who finish therapy and thereby gain durable protection against future active disease. The 4-month rifampicin regimen showed a similar magnitude of benefit at RR 1.10. These effect sizes are consistent with the broader international literature, which has repeatedly demonstrated that shorter preventive regimens outperform longer ones on adherence, though direct comparisons across health systems are complicated by differences in drug availability, cost, and clinical guidelines.

One of the more intriguing findings concerns the youngest children. Those under 5 years of age did not show the modest completion advantage observed in older age bands — and this matters enormously from a public health standpoint, because children under 5 who are household contacts of infectious tuberculosis cases face the highest risks of rapid progression from infection to severe, disseminated disease such as tuberculous meningitis. Pediatric guidelines therefore prioritize this age group for preventive treatment, often without requiring confirmation of infection through a tuberculin skin test or interferon gamma release assay. Yet the very factors that make young children a priority — their dependence on caregivers for every dose, the challenges of administering medications formulated for adults, and the frequency of intercurrent childhood illnesses that interrupt treatment — also make them the most vulnerable to incomplete courses. The study’s authors conclude that targeted strategies to improve adherence among children younger than 5 years may be essential to enhancing overall completion in Brazil.

The associations with BCG vaccination status and skin color deserve careful interpretation. The finding that BCG-vaccinated children showed higher completion (RR 1.05) likely reflects underlying differences in healthcare access and surveillance rather than any direct pharmacological effect of the vaccine on adherence. Similarly, the modest completion advantage among children recorded as having white skin color (RR 1.02) echoes well-documented patterns of health inequity in Brazil, where structural factors — including socioeconomic status, geographic proximity to clinics, and the quality of patient-provider interactions — shape treatment trajectories long before a prescription is written. The researchers were careful to characterize these associations as modest, and the confidence intervals, while statistically significant, indicate effects that are real but small in absolute terms. The clinical and policy implications therefore hinge less on any single demographic factor and more on the systemic levers — regimen choice above all — that can be pulled at scale.

The finding that children on immunosuppressive therapy showed higher completion (RR 1.07; 95 percent CI 1.03–1.19) is also worth unpacking. These are children whose underlying conditions — perhaps autoimmune diseases, oncologic diagnoses, or pre-transplant preparation — require medications that dampen the immune system, dramatically raising the stakes of untreated latent tuberculosis infection, which can reactivate catastrophically under immunosuppression. In such cases, families and clinicians alike have powerful, immediate motivations to see preventive therapy through to completion, and the data suggest that this heightened vigilance translates into measurable adherence gains. It is a reminder that perceived risk is one of the strongest drivers of health behavior, and that communicating the seriousness of latent infection to families of otherwise healthy children remains an ongoing challenge.

As the world pursues the End TB Strategy’s goals of drastic reductions in tuberculosis incidence and mortality, the study’s message is clear: the tools to prevent disease in children already exist, and the frontier now lies in delivery. Shorter regimens like 3HP and 4-month rifampicin offer a pharmacological shortcut to adherence, but their impact will be realized only if health systems can reliably identify eligible children, initiate treatment promptly after exposure, and support families through the full course. Brazil’s experience, documented across more than 31,000 pediatric notifications over six years, provides both a warning — that the youngest and most vulnerable remain the hardest to reach with complete preventive courses — and a roadmap, showing that regimen simplification is among the most effective levers available. For a disease that has coexisted with humanity for millennia, the quiet arithmetic of pill counts and completed courses may prove as consequential as any laboratory breakthrough.

Subject of Research: Completion of tuberculosis preventive treatment among children and adolescents aged 0 to 15 years in Brazil

Article Title: Completion of tuberculosis preventive treatment in children and adolescents aged 0 to 15 in Brazil: analysis of a retrospective cohort

Article References: Cola, J. P., da Conceição Costa, L., de Souza, F. M., Caetano, C. L., dos Santos, G. S., Sales, C. M. M., Carvalho, A. C. C., Maciel, E. L. N., & do Prado, T. N. (2026). Completion of tuberculosis preventive treatment in children and adolescents aged 0 to 15 in Brazil: analysis of a retrospective cohort. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14204-7

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14204-7

Keywords: tuberculosis, preventive treatment, children, adolescents, Brazil, 3HP regimen, isoniazid, rifapentine, rifampicin, treatment adherence, public health, BMC Infectious Diseases