Experiencia piloto con esquema rifapentina-isoniazida semanal por 3 meses para tratamiento de la infección tuberculosa latente en el Programa Nacional de Tuberculosis de Chile / Pilot experience with weekly rifapentine-isoniazid treatment for 3 months for latent tuberculosis infection at the Tuberculosis National Program of Chile

INTRODUCCIÓN: La prevención de la tuberculosis activa en los grupos de riesgo es clave para el control y eliminación de la tuberculosis. El tratamiento de la infección tuberculosa latente (TITL) con rifapentina e isoniazida en dosis semanales por 12 semanas es más corto que con otros esquemas, tiene menor hepatotoxicidad, mejor adherencia y es costo-efectivo. El OBJETIVO del estudio es evaluar la factibilidad de implementar este esquema a nivel programático en Chile. MÉTODOS: Se hizo una intervención piloto en territorios seleccionados entre mayo de 2018 y marzo de 2019. En esos territorios se reemplazó el esquema normado de TITL con isoniazida 6 meses por el esquema rifapentina-isoniazida 12 semanas. Además, se amplió la población objetivo, incluyendo a contactos mayores de 14 años. El tratamiento consistió en la administración conjunta de isoniazida y rifapentina por vía oral con frecuencia semanal, por 12 semanas, de forma supervisada por personal de salud. RESULTADOS: Ingresaron 238 pacientes al piloto, de los cuales 53% fueron mujeres y 54,2% fueron mayores de 14 años. Del total de pacientes, 203 (85,3%) completaron el tratamiento, 22 (9,2%) lo abandonaron, 8 (3,4%) presentaron reacciones adversas y 5 tuvieron otros motivos de egreso. CONCLUSIÓN: Tanto el TITL con rifapentinaisoniazida por 3 meses en dosis semanales supervisadas, como la incorporación de contactos adultos a TITL, son factibles de implementar a nivel programático en Chile.

INTRODUCTION: Prevention of active tuberculosis in risk groups is crucial in tuberculosis control and elimination. Treatment of latent tuberculosis (TITL) with rifapentine and isoniazid in weekly doses for 12 weeks is shorter than other pharmacological treatments, with less liver toxicity, better patient compliance and it is cost-effective. The OBJECTIVE of this study is to evaluate the feasibility to implement this treatment at a programmatic level in Chile. METHODS: A pilot intervention was conducted in selected territories between May 2018 and March 2019. Within these territories, the regulated treatment with isoniazid 6 months was replaced by the 12 weeks treatment with weekly rifapentine-isoniazide. Additionally, the target population was expanded to include contacts over 14 years old, currently not included in the national guidelines. Treatment consisted in oral administration of rifapentine and isoniazide together once a week for 12 weeks, under supervision of trained health workers. RESULTS: From 238 patients entered to the protocol, 53% of them were women and 54.2% were older than 14 years-old. Out of the total number of patients, 203 (85.3%) completed treatment, 22 (9.2%) abandoned, 8 (3.4%) had adverse drug reactions, and 5 ended treatment for different causes. CONCLUSION: Both TITL with rifapentine-isoniazide in 12 supervised weekly doses, and the inclusion of adult contacts in TITL, are feasible to implement at a programmatic level in Chile.

Rifapentine for latent tuberculosis infection treatment in the general population and human immunodeficiency virus-positive patients: summary of evidence

AbstractLatent tuberculosis infection (LTBI) and human immunodeficiency virus (HIV)-coinfection are challenges in the control of tuberculosis transmission. We aimed to assess and summarize evidence available in the literature regarding the treatment of LTBI in both the general and HIV-positive population, in order to support decision making by the Brazilian Tuberculosis Control Program for LTBI chemoprophylaxis. We searched MEDLINE, Cochrane Library, Centre for Reviews and Dissemination, Embase, LILACS, SciELO, Trip database, National Guideline Clearinghouse, and the Brazilian Theses Repository to identify systematic reviews, randomized clinical trials, clinical guidelines, evidence-based synopses, reports of health technology assessment agencies, and theses that investigated rifapentine and isoniazid combination compared to isoniazid monotherapy. We assessed the quality of evidence from randomized clinical trials using the Jadad Scale and recommendations from other evidence sources using the Grading of Recommendations, Assessment, Development, and Evaluations approach. The available evidence suggests that there are no differences between rifapentine + isoniazid short-course treatment and the standard 6-month isoniazid therapy in reducing active tuberculosis incidence or death. Adherence was better with directly observed rifapentine therapy compared to self-administered isoniazid. The quality of evidence obtained was moderate, and on the basis of this evidence, rifapentine is recommended by one guideline. Available evidence assessment considering the perspective of higher adherence rates, lower costs, and local peculiarity context might support rifapentine use for LTBI in the general or HIV-positive populations. Since novel trials are ongoing, further studies should include patients on antiretroviral therapy.

Search for newer antileprosy drugs.

In 1991 World Health Organization proclaimed the goal of global elimination of leprosy as a public health problem by year 2000 by implementing multidrug therapy (MDT). Since then the prevalence rate has declined by 85%. However, during the same period the incidence rate of leprosy has remained constant or even has been increasing. This suggests that it will take a long time for the eradication of leprosy and that without in-vitro cultivation of M. leprae, eradication of leprosy is not likely to be achieved. While in-vitro cultivation is a long-term goal, as an immediate measure, there is an urgent need for the development of newer drugs and newer multidrug therapy regimens. Using the in-vitro system for screening potential antileprosy drugs and also using the mouse foot-pad system we have evaluated several compounds in four classes of drugs--dihydrofolate reductase inhibitors, fluoroquinolones, rifampicin analogues and phenazines--and identified at least two compounds that appear to be more potent than dapsone, rifampicin and clofazimine. Newer combinations of rifampicin analogues and fluoroquinolones have also been identified that seem to be better than the combination of rifampicin and ofloxacin.

Comparative in vitro activities of rifamycin analogues against Mycobacterium leprae.

Comparative activities of various rifamycin analogues against leprosy were studied by evaluating their effects on in vitro growth of Mycobacterium leprae in DH medium as described earlier. Among the seven analogues studied, KRM-1648 was found to be the most potent in inhibiting the growth of rifampicin-sensitive strains of M. leprae, MIC being 0.05 microgram/ml. This was followed by KRM-2312 and T9 (MIC of each being 0.1 microgram/ml) and rifabutin (MIC, 0.2 microgram/ml). Rifampicin, along with KRM-1657 and KRM-1668, were least effective, with MIC for each being 0.4 microgram/ml. The effects of each at their respective MICs were bactericidal. The results were similar for rifampicin-resistant strains of M. leprae, but the MICs were higher than those obtained with rifampicin-sensitive strains of M. leprae. Thus, even though rifampicin has been the first-line drug in the treatment of leprosy, the results in present studies suggest that other rifamycin analogues are available that are more potent than rifampicin against both rifampicin-sensitive as well as rifampicin-restraint strains of M. leprae.