Lampit (nifurtimox) / Bayer - LARVOL DELTA

LONG-TERM CARDIAC OUTCOMES OF THE LARGEST ORAL CHAGAS DISEASE OUTBREAK: A 17-YEAR FOLLOW-UP WITH EMPHASIS ON ARRHYTHMIAS (ACC 2026) - " This study followed 103 ChD cases from guava juice contamination at an urban school, treated with benznidazole or nifurtimox... This study highlights the importance of the largest epidemic of orally transmitted ChD, with presentations that deviate from the usual epidemiological characteristics, in an urban area. Despite high morbidity, the case fatality rate was low, due to early diagnosis and parasiticide treatment. The outcome was excellent at 17 years, with marked improvement in arrhythmia and the absence of HF or systolic ventricular dysfunction."

Atrial Fibrillation • Cardiovascular • Congestive Heart Failure • Heart Failure • Ventricular Tachycardia

Asymptomatic Trypanosoma cruzi Infection Identified During Blood Donation Screening. (PubMed, Cureus) - "Limited access to first-line therapy (benznidazole) necessitated treatment with nifurtimox...It also highlights the absence of standardized criteria for assessing treatment success in chronic infection. Addressing these concerns would ensure timely diagnosis, initiation of therapy, and appropriate monitoring to prevent the development of disease complications."

Journal • Developmental Disorders • Infectious Disease

Cytosolic Delivery of a Bithiophene Derivative via Polymersomes Kills Trypanosoma cruzi Amastigotes and Modulates the Inflammatory Response. (PubMed, ACS Appl Nano Mater) - "Current treatments, benznidazole and nifurtimox, have limited efficacy in this stage and are associated with significant toxicity, highlighting the need for better therapies...Importantly, Förster Resonance Energy Transfer analysis confirmed that BTAc-loaded polymersomes remain intact upon cellular uptake, escape the endosomal compartment, and release their payload directly into the cytosol, which is the intracellular niche where amastigotes persist during chronic infection. These findings underscore the potential of this nanocarrier system as an innovative approach that combines targeted antitrypanosomal therapy with enhanced immunomodulation, offering a promising strategy for the treatment of chronic Chagas disease."

Journal • Cardiomyopathy • Cardiovascular • Immunology • Infectious Disease • Inflammation

Scalable Access to N‑Acylindole Linkages: Enabling the Synthesis of Antitrypanosomal Noncanonical Cyclic Peptides for Chagas Disease. (PubMed, Angew Chem Int Ed Engl) - "The only available chemotherapeutic agents are nifurtimox and benznidazole, both of which were introduced more than half a century ago and are included in the WHO's list of essential medicines...In this study, a scalable synthetic method was developed for noncanonical cyclic peptides bearing a rare N-acylindole linkage, a structural motif not typically observed in conventional cyclic peptides. This strategy enabled the synthesis of bulbiferamide A, a potent antitrypanosomal agent reported to be effective against Chagas disease, as well as a variety of related analogues that had previously been difficult to access synthetically."

Journal • Infectious Disease

Identification of Novel Trypanosoma cruzi Cysteine Protease Inhibitors via Ligand-Based Virtual Screening of FDA-Approved Drugs with Trypanocidal Activity. (PubMed, Diseases) - "These results encourage the development of new and more potent anti-Trypanosoma cruzi agents using FDA-approved drugs as scaffolds."

FDA event • Journal

An MRC-5 cell based high-throughput, high-content imaging assay to identify hits against Trypanosoma cruzi intracellular parasites. (PubMed, SLAS Discov) - "Despite the significant burden posed by Chagas disease, especially in Latin America, only two drugs, benznidazole and nifurtimox, are currently available for treatment...Here we discuss the development, optimization, evaluation and validation of a robust and highly reproducible high-throughput, high content imaging assay in a 384-well microplate format to quantitatively assess the effects of compounds on intracellular T. cruzi amastigotes infecting MRC-5 human lung fibroblasts. The multiplexed assay design enables concurrent evaluation of compound-induced cytotoxicity on host cells within the same well, serving as an early indicator of host cell viability and compound selectivity."

Journal • Developmental Disorders

Synthesis and Biological Evaluation of Tetrahydroisoquinoline Derivatives as Trypanocidal Agents. (PubMed, ACS Omega) - "Current treatments, benznidazole and nifurtimox, are limited by their efficacy in the chronic phase, toxicity, and side effects, necessitating the search for new therapeutic agents...Notably, compound 3d and its hydrochloride salt 4d demonstrated significant antiparasitic activity with IC50 values of 10.5 and 13.7 μM, respectively. However, their low cruzain inhibition (∼15%) suggests that their mechanism of action is likely through a different biological target."

Journal • Infectious Disease

Trypanocidal Activity of Dual Redox-Active Quinones: Trypanosoma cruzi Mitochondrion as a Target Organelle In Vitro and Anti-Inflammatory Properties In Vivo. (PubMed, Pathogens) - "Chagas disease is caused by the protozoan Trypanosoma cruzi, and its current treatment is limited to the use of two nitroderivatives, benznidazole (Bz) and nifurtimox; however, their toxicity often leads to discontinuation, justifying the search for new therapeutic options...In vivo, this compound presented moderate trypanocidal and promising anti-inflammatory activity. Its combination with Bz could enhance current therapeutic protocols and should be better explored in the future."

Journal • Preclinical • Cardiovascular • Infectious Disease • Inflammation

Physician Knowledge of Chagas Disease in a Non-Endemic Country: A Nationwide Cross-Sectional Survey. (PubMed, Trop Med Int Health) - "Physicians showed moderate knowledge of Chagas disease, with important gaps in diagnosis and treatment. Targeted, large-scale educational initiatives supported by institutions are urgently needed to strengthen awareness and clinical preparedness in non-endemic settings with significant Latin American migrant populations."

Journal • Infectious Disease

The epidemiology and clinical features of HIV and Trypanosoma cruzi (Chagas disease) co-infection: A systematic review and individual patient data analysis. (PubMed, PLoS Negl Trop Dis) - "T. cruzi reactivation mainly affects those with untreated HIV and lower CD4 counts. CNS reactivation is the most common clinical picture and confers high mortality. Prompt recognition of reactivation and immediate initiation of trypanocidal therapy (with benznidazole or nifurtimox) is recommended. Increased education and better awareness of the risks of co-infection are needed, as is systematic screening of individuals at-risk."

Journal • Cardiovascular • CNS Disorders • Human Immunodeficiency Virus • Infectious Disease • Inflammation • CD4

Inhibitory Activity of LDT10 and LDT119, New Saturated Cardanols, Against Trypanosoma cruzi. (PubMed, Pharmaceuticals (Basel)) - "Background/Objectives: Chagas disease, caused by Trypanosoma cruzi, remains a major neglected tropical disease with limited therapeutic options restricted to benznidazole and nifurtimox, both associated with significant toxicity and reduced efficacy during chronic infection... LDT10 and LDT119 exhibited potent and selective in vitro activity against all developmental stages of T. cruzi, with low micromolar to submicromolar IC50/LD50 values, minimal mammalian cytotoxicity, and extensive morphological and ultrastructural damage consistent with disruption of phospholipid biosynthesis pathways. Combined with favorable in silico pharmacokinetic predictions, these CNSL-derived phospholipid analogs represent promising candidates for future Chagas disease chemotherapy and warrant further in vivo evaluation."

Journal • CNS Disorders • Depression • Infectious Disease • Psychiatry

Therapeutic Potential of 3D-Printed Nifurtimox for Chagas Disease: Effects on Survival, Parasitemia Control and Immune Modulation. (PubMed, Trop Med Int Health) - "3D nifurtimox represents a promising new version of nifurtimox capable of being used in low doses with comparable or superior effects to benznidazole (100 mg/kg) and can be considered a promising tool for anti-T. cruzi therapies."

Journal • Immune Modulation • Immunology • Infectious Disease • Inflammation • CCL2 • IL10 • IL6

Kinetics of Biomarkers for Therapeutic Assessment in Swiss Mice Infected with a Virulent Trypanosoma cruzi Strain. (PubMed, Pathogens) - "This variability complicates the evaluation and comparison of new therapeutic compounds against existing drugs, namely benznidazole and nifurtimox...To complete the report, a necropsy evaluation was performed at the end of the acute, fatal infection, and it is presented here. This study fulfills a long-standing recommendation from diverse drug discovery groups for the creation of a definitive reference model to standardize preclinical testing for anti-Chagasic agents."

Journal • Preclinical • Hematological Disorders • Infectious Disease

Ruthenium Complexes Containing Thiobenzamide Act as Potent and Selective Anti-Trypanosoma cruzi Agents through Apoptotic Cell Death. (PubMed, ACS Infect Dis) - "Chagas disease remains a significant global health concern, with current therapies limited to benznidazole and nifurtimox, which have adverse effects and show reduced efficacy in the chronic phase...In a murine model, FOR0212A (20 mg/kg) reduced parasitemia by 50.2% during the acute phase without any toxicity. These findings identify FOR0212A as a promising therapeutic candidate for Chagas disease, acting via oxidative stress and apoptosis-like mechanisms in T. cruzi."

Journal

Application of Data-Centric Supervised Machine Learning to Predict Phenotypic Activity Against Clinically Relevant Stages of Trypanosoma cruzi. (PubMed, Pharmaceutics) - "The therapeutic arsenal against T. cruzi is so far limited to only two approved drugs, benznidazole and nifurtimox, that have considerable side effects and limited efficacy in the chronic stage of the disease... We have built portable meta-classifiers capable of identifying small molecules with trypanocidal activity against amastigotes, the clinically most relevant stage of T. cruzi. The predictive ability of this meta-classifier was experimentally validated."

Journal

The efficacy and safety of benznidazole in adults with seropositive indeterminate form, Trypanosoma cruzi infection: a systematic review and meta-analysis. (PubMed, BMC Infect Dis) - No abstract available

Journal • Retrospective data • Review • Infectious Disease

Efficacy of sulfonamides targeting malic enzyme in an animal model of Chagas disease. (PubMed, Front Pharmacol) - "Benznidazole and nifurtimox are the only approved treatments, but their limited efficacy and adverse effects highlight the urgent need for new therapies...These findings demonstrate the potential of this sulfonamide scaffold while also underscoring metabolic instability and limited systemic exposure as major challenges. Future optimization efforts will focus on structural modifications and formulation strategies to enhance pharmacokinetics and therapeutic efficacy."

Journal • Preclinical

Callunene, mitophagy, and flagellum removal in trypanosomatids. (PubMed, Int J Parasitol) - "Notably, callunene's in vitro efficacy against T. brucei was comparable to that of nifurtimox, although its cytotoxicity toward human cells may limit direct therapeutic application...Moreover, callunene alters acidocalcisome abundance, further connecting its role to regulation of mitochondrial physiology. Given its effects on mitochondria and ability to interact with NIPSNAP, callunene represents a promising chemical probe for studying mitophagy, a poorly understood process in trypanosomatids, and may provide new insights into mitochondrial biology of these parasites."

Journal • Infectious Disease • NIPSNAP1

Mechanisms of resistance of Trypanosoma cruzi to benznidazole and nifurtimox: Molecular implications and multifaceted impact. (PubMed, Acta Trop) - "Therapeutic failure transforms patients into persistent reservoirs, which perpetuates the chain of parasite transmission. The concern that resistance established in laboratory models may translate into clinical settings, coupled with the resulting increase in morbidity and mortality and the socioeconomic burden, underscores the urgent need to develop new drugs designed to evade these mechanisms of reduced susceptibility."

Journal • Review • Infectious Disease

Inhibition of calreticulin by protein nanoparticles carrying antisense oligonucleotides reduce gene expression and infection of Trypanosoma cruzi trypomastigotes on mammalian cells. (PubMed, Nanomedicine (Lond)) - "At least two drugs directed against the parasite (Benznidazole and Nifurtimox) have low effectiveness in treating Chronic Chagasic patients...Decreased parasite survival, altered parasite morphology, increased complement susceptibility, produced metabolic alteration, and substantially reduced mammal cell infection were also observed. The results indicate that protein nanoparticles carrying antisense oligonucleotides are a promising strategy directed against T. cruzi."

CALR • Journal • Infectious Disease • CALR

Novel cosolvent systems for nifurtimox: improving solubility, trypanocidal efficacy, and stability. (PubMed, Ther Deliv) - "Cosolvent-based delivery systems enhance the solubility of nifurtimox while maintaining adequate trypanocidal activity against Trypanosoma cruzi and demonstrating acceptable stability and safety profiles. Thus, these formulations represent a promising strategy to improve the therapeutic effectiveness of nifurtimox."

Journal • Hematological Disorders

Comparative transcriptomics of naturally susceptible and resistant Trypanosoma cruzi strains in response to Benznidazole. (PubMed, Int J Parasitol Drugs Drug Resist) - "Chagas disease (CD), caused by the protozoan Trypanosoma cruzi, remains a major public health challenge due to limited treatment options, Benznidazole and Nifurtimox; which are associated with adverse effects and variable efficacy...These findings expand our current understanding of intrinsic Benznidazole resistance in T. cruzi, moving beyond purely experimental models. Specifically, they highlight novel metabolic and redox pathways that could serve as therapeutic targets effective against diverse T. cruzi strains and Discrete Typing Units (DTUs)."

Journal

Novel cationic gold(I) compounds with 5-nitrofuryl containing thiosemicarbazone ligands exhibit activity against Trypanosoma cruzi. (PubMed, J Inorg Biochem) - "Two of these complexes were more active than their respective thiosemicarbazone ligands and exhibited antiparasitic activity comparable to that of Nifurtimox...In addition, DNA competitive binding with ethidium bromide, evaluated by fluorescence measurements, demonstrated that the compounds interact with this biomolecule. Overall, these three active gold(I) complexes can be considered promising hits for the development of prospective agents against T. cruzi."

Journal

Trypanocidal Treatment for Chronic Chagas Disease: Past, Present, and Future. (PubMed, Rev Soc Bras Med Trop) - "The etiological treatment is based on the use of benznidazole and nifurtimox, both of which were developed over five decades ago...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."

Journal • Review

Virtual Screening of FDA-Approved Drugs on Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH) to Obtain New Trypanocidal Agents. (PubMed, Med Chem) - "Seven FDA-approved drugs are candidates for further studies leading to the development of potential new treatments for Chagas disease."

FDA event • Journal • Oncology • GAPDH