Nifurtimox 120mg tablets

BackgroundMaternal-foetal transmission of Chagas disease (CD) affects newborns worldwide. Although Benznidazole and Nifurtimox therapies are the standard treatments, their use during pregnancy is contra-indicated. The effectiveness of trypanocidal medications in preventing congenital Chagas Disease (cCD) in the offsprings of women diagnosed with CD was highly suggested by other studies.MethodsWe performed a systematic review and meta-analysis of studies evaluating the effectiveness of treatment for CD in women of childbearing age and reporting frequencies of cCD in their children. PubMed, Scopus, Web of Science, Cochrane Library, and LILACS databases were systematically searched. Statistical analysis was performed using Rstudio 4.2 using DerSimonian and Laird random-effects models. Heterogeneity was examined with the Cochran Q test and I2 statistics. A p-value of ResultsSix studies were included, comprising 744 children, of whom 286 (38.4%) were born from women previously treated with Benznidazole or Nifurtimox, trypanocidal agents. The primary outcome of the proportion of children who were seropositive for cCD, confirmed by serology, was signigicantly lower among women who were previously treated with no congenital transmission registered (OR 0.05; 95% Cl 0.01-0.27; p = 0.000432; I2 = 0%). In women previously treated with trypanocidal drugs, the pooled prevalence of cCD was 0.0% (95% Cl 0-0.91%; I2 = 0%), our meta-analysis confirms the excellent effectiveness of this treatment. The prevalence of adverse events in women previously treated with antitrypanocidal therapies was 14.01% (95% CI 1.87-26.14%; I2 = 80%), Benznidazole had a higher incidence of side effects than Nifurtimox (76% vs 24%).ConclusionThe use of trypanocidal therapy in women at reproductive age with CD is an effective strategy for the prevention of cCD, with a complete elimination of congenital transmission of Trypanosoma cruzi in treated vs untreated infected women.

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This article reviews the trypanocidal therapy for chronic Chagas disease, emphasizing its indications, efficacy, limitations, and future perspectives. The etiological treatment is based on the use of benznidazole and nifurtimox, both of which were developed over five decades ago. These drugs are most effective in the acute phase, but are also recommended for children, adolescents, and adults aged <50 years without severe organ damage, and women of childbearing age to prevent congenital transmission. Adherence to treatment is limited by adverse drug reactions, which affect approximately half of the patients, leading to treatment discontinuation in approximately 30% of cases. The cure criteria included parasitological, serological, and clinical responses that required long-term follow-up. Clinical trials and systematic reviews have shown heterogeneous results that are influenced by age, clinical stage, and geographical region. Recent public policies supported by non-governmental organizations and academic networks have expanded access to diagnosis and treatment, although structural and informational barriers persist. New therapeutic strategies include shortened benznidazole regimens, drug repositioning, and combination therapies aimed at reducing adverse drug reactions and improving efficacy. Novel molecules with distinct mechanisms and vaccines with therapeutic and preventive potentials are under investigation. Despite these advances, the challenge remains in translating these innovations into concrete benefits for affected populations, particularly in the most vulnerable regions.

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Abstract Background Sleeping sickness is an infectious disease transmitted mainly by the Trypanosoma Brucei, with the tsetse fly as a vector. The condition has two stages: The hemolymphatic and the meningo-encephalitic stage. The second stage is caused mainly by the Trypanosoma Brucei Gambiense. The treatment of the second stage has changed from melarsoprol, eflornithine, to now nifurtimox-eflornithine (NECT). This systematic review will focus on the efficacy and the toxicity of the medication. Methods We use PRISMA and MOOSE protocol for this review. On figure 1, we detail the methodology used for the extraction of information from the systematic review. To assess the study's bias, we used Cochrane Collaboration’s tool for risk assessment of the clinical trials and the Robins I tool for the observational studies. Results We collected four clinical trials and two observational studies after an extensive search. Three clinical trials showed that NECT was non-inferior to eflornithine with the following cure rates (NECT VS eflornithine): 1) 96.3% vs. 94.1% ; 2) 90.9% vs. 88.9%; 3) 91.6% vs. 96.5%. An additional clinical trial revealed that the proportion of patient discharge from the hospital was 98.4% (619/629); 95% CI [97.1%; 99.1%]). The two observational studies discussed the pharmacovigilance of the drug and toxicity related to NECT. In one study, patients treated with NECT, 589 (86%) experienced at least one adverse effect (AE) during treatment, and 70 (10.2%) experience serious AE. On average, children experienced fewer AEs than adults. In the other study at least one AE was described in 1043 patients (60.1%), and Serious AE was reported in 19 patients (1.1% of treated), leading to nine deaths (case fatality rate of 0.5%). The major limitations of the studies were the lack of blinding because most of them were open-label. Also, there was heterogenicity in the definition of the outcomes in the observational studies. PRISMA Flow Chart Conclusion NECT is not inferior to eflornithine, and the proportion of patients discharged from the hospital alive showed favorable results. The observational studies revealed a high frequency of AE. However, NECT is more convenient and safe than Eflornithine and Melarsoprol. Disclosures All Authors: No reported disclosures

Abstract licence: CC BY 4.0

IntroductionChagas disease (CD) remains a major cause of cardiac and digestive morbidity and premature death in the Americas. Although benznidazole (BZN) and nifurtimox (NFX) are the only two available trypanocidal agents worldwide, direct comparisons between these two drugs in Brazilian adults are lacking. Therapeutic efficacy in chronically infected adults remains unclear as parasitological response is variable and serological negativisation is not frequent within short-term follow-up. Furthermore, the genetic diversity of Trypanosoma cruzi may influence treatment response and has been largely overlooked in clinical studies. The BENBRASIL trial aims to compare the efficacy and safety of BZN versus NFX in adults with chronic CD and to explore geographical variation in response to standard BZN treatment.Methods and analysisThe BENBRASIL trial is a multicentre, randomised, double-blind, double-dummy phase II superiority trial conducted in Brazil alongside a prospective observational cohort.A total of 150 adults with chronic indeterminate or mild cardiac forms of CD will be randomly allocated in a 1:1 ratio to receive standard BZN dose or NFX for 8 weeks in a double-blind, double-dummy placebo-controlled design and will be followed for 12 months. The primary endpoint is therapeutic efficacy defined as sustained parasitological response in PCR for parasitic DNA results for 12 months follow-up. Treatment failure will be defined as one confirmed PCR positivity, treatment discontinuation due to toxicity or death related to CD. Secondary outcomes include drug tolerability (including graded adverse events), treatment adherence and serological titres. The sample size (75 participants per arm) was calculated to provide approximately 80-85% power to detect a 25% absolute difference in sustained PCR negativity between groups at a two-sided α of 0.05. Additionally, a prospective observational cohort will enrol 300 additional participants receiving standard treatment of BZN to evaluate the effectiveness and safety of BZN across five epidemiological and geographical regions of Brazil representing distinct parasite genetic backgrounds. It aims to explore geographical variation in parasitological response within different discrete typing units using mixed-effects regression models adjusted for baseline covariates. The primary analysis will follow the intention-to-treat principle. For the primary endpoint, missing outcome data will be conservatively classified as treatment failure, with sensitivity analyses using multiple imputations. Recruitment began in March 2024.Ethics and disseminationThe protocol has been approved by Brazil's National Research Ethics Committee and the institutional review boards of all participating centres. Written informed consent will be obtained from all participants. An independent Data Safety Monitoring Board will oversee safety outcomes. Study findings will be disseminated through peer-reviewed publications, scientific conferences and communication with national health authorities. Results may guide clinical practice and regulatory policies, strengthening therapeutic options for CD.Trial registration numberReBEC U1111-1287-7587. Date of registration: 06/07/2023 (https://ensaiosclinicos.gov.br/rg/RBR-973pt5n).

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When testing poorly tolerated or long-term treatments, including a run-in phase enhances clinical trial efficiency and internal validity by selecting more adherent participants. This report describes the adherence and tolerance of Colombian participants in EQUITY (a randomized, concealed, parallel-group, placebo-controlled trial testing nifurtimox and benznidazole among Trypanosoma cruzi-seropositive adults without cardiomyopathy). Our design included a 10-day, single-blind, placebo run-in phase. On completion, willing participants reporting good adherence (≥80%) and tolerance were randomized to any five 120-day, blinded treatments: four with either active medication, each given as 120-day half dose or 60-day full dose (followed/preceded by a randomly allocated 60-day placebo treatment), or a 120-day placebo. Side effects were compared after the run-in (day 0) between excluded and enrolled participants, and between those randomized to active medications or placebo 20 days after starting each treatment period (days 20/80). Those excluded (44/351, 12.5%) more often reported gastrointestinal (15.9/4.6%), nonspecific (13.7/4.2%), and musculoskeletal symptoms (9.1/1.6%) than those randomized. Participants given nifurtimox (n = 84) or benznidazole (n = 86) versus placebo (n = 126) on day 20 reported more nonspecific (15.5/10.5/4.8%, respectively) or cutaneous side effects (6.0/12.8/3.2%). When starting active treatments (transition OFF-ON, n = 171 and n = 61 in first and second 60-day treatment periods), more participants reported emerging-worsening than receding-ending side effects (49/13 and 15/5, respectively). Despite inducing a nocebo effect, the run-in phase highlighted more closely related side effects, strengthening causal inference and informing adherence and tolerance to conventional trypanocides.

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