Effective treatment of chagas disease: A Synthesis of Findings from 19 Studies

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Original Abstract of the Article

Major Research Findings

Chagas disease, caused by the parasite *Trypanosoma cruzi*, affects approximately 7 million people worldwide. 14 Current treatments, primarily benznidazole (BZN) and nifurtimox (NFX), are often limited by adverse side effects and inconsistent efficacy, especially in adults with chronic Chagas disease (CCD). 14 17 Research is focusing on improving treatment outcomes through optimized dosing regimens, combination therapies, and new drug development. 14 12 16 Additionally, the development of biomarkers for monitoring treatment efficacy is crucial. 18

Treatment Summary

Treatment approaches for Chagas disease are diverse, ranging from monotherapy with medications like benznidazole, nifurtimox, fosravuconazole, posaconazole, allopurinol, and thioctic acid to combination therapies. 17 8 The success of treatment depends on factors like the type of medication, the dosage regimen, and the patient's health status. 6 Currently, benznidazole is considered the most viable option for treatment. 17 However, its side effects can be significant, leading to poor adherence to treatment. 17 Therefore, there is a continuous need for the development of new treatments with fewer side effects and shorter treatment durations. 17

Benefits and Risks

Benefit Summary

Treatment for Chagas disease offers several potential benefits, including the elimination of parasites, slowing down disease progression, and improving overall survival. 10 Additionally, it can reduce the risk of developing heart disease and other complications associated with Chagas disease. 1

Risk Summary

Treatment for Chagas disease can come with side effects. 9 Common side effects include gastrointestinal issues, skin reactions, and neurological symptoms. 17 Some medications can also cause severe side effects like liver damage and blood disorders. 9 It's crucial to have open discussions with a healthcare professional about the risks before starting treatment. 17

Comparison Between Studies

Commonalities

A common theme across multiple studies is the need for improved treatment options for Chagas disease. 17 Benznidazole continues to be recognized as an effective medication. 17 However, its side effects necessitate the development of less burdensome treatment approaches. 17

Differences

Research efforts vary in their focus, with some studies concentrating on optimizing benznidazole dosage and duration, while others explore new drug development or combination therapies. 11 8 The diverse study designs and objectives make direct comparisons of results challenging. 13

Consistency and Inconsistencies in Results

Findings on Chagas disease treatment exhibit both consistency and inconsistencies. 7 While benznidazole remains a valid treatment option, its effectiveness can vary depending on the patient and the specific parasite strain. 13 Complete parasite elimination is not always achieved, and there is a risk of re-infection. 1 Therefore, ongoing monitoring after treatment is crucial. 18

Considerations for Real-World Applications

Chagas disease, once primarily found in Latin America, is now spreading globally due to population migration and blood bank screening. 2 Research findings on Chagas disease treatment have significant implications for patients worldwide. 19 However, it's crucial to remember that treatment carries potential side effects. 9 Thorough discussions with healthcare providers regarding these risks are essential before initiating treatment. 17 Furthermore, untreated Chagas disease can lead to serious complications. 7 Therefore, early diagnosis and treatment are crucial for managing the disease effectively. 4

Limitations of Current Research

Research on Chagas disease treatment remains incomplete. 15 Particularly, studies focusing on chronic-stage treatment efficacy are limited. 3 The diverse nature of the disease, influenced by patient and parasite variations, necessitates more extensive research. 13 7

Future Research Directions

To further enhance Chagas disease treatment, research should prioritize the development of new drugs with fewer side effects and greater efficacy. 17 Developing effective biomarkers for monitoring treatment progress is another crucial area of focus. 18 Furthermore, research on preventive measures for Chagas disease is essential. 4

Conclusion

Chagas disease is a major health concern in Latin America and is spreading globally. 19 While ongoing research is improving our understanding of Chagas disease treatment, there is still a need for more effective and well-tolerated therapies. 17 Early diagnosis and treatment are vital for preventing severe complications. 7 As research continues to advance, we can hope for more promising treatment options for Chagas disease in the future. 4

Treatment List

Benznidazole, Nifurtimox, Fosravuconazole, Posaconazole, Allopurinol, Thioctic acid, E1224, Fexinidazole, Isosorbide, Nifedipine

Literature analysis of 19 papers
Positive Content
15
Neutral Content
1
Negative Content
3
Article Type
9
5
9
5
19
1.

[No association between persistence of the parasite and electrocardiographic evolution in treated patients with Chagas disease].

Author: ZulantayInés, ArribadaArturo, HonoresPatricia, SánchezGittith, SolariAldo, OrtizSylvia, OsunaAntonio, RodríguezJorge, AptWerner

Chagas disease persistence

There is no association between the persistence of the parasite in treated patients with Chagas disease and the evolution of electrocardiographic tracings.

English AbstractA summary of a research paper/publication written in English for a wider audience.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : Spanish

2.

Evaluation and treatment of chagas disease in the United States: a systematic review.

Author: BernCaryn, MontgomerySusan P, HerwaldtBarbara L, RassiAnis, Marin-NetoJose Antonio, DantasRoberto O, MaguireJames H, AcquatellaHarry, MorilloCarlos, KirchhoffLouis V, GilmanRobert H, ReyesPedro A, SalvatellaRoberto, MooreAnne C

Chagas disease treatment
Adverse effects

This review provides practical recommendations for the evaluation, management, and etiologic treatment of Chagas disease in the United States.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

3.

[Efficacy of nifurtimox for the treatment of chronic Chagas disease].

Author: Fuentes BRodrigo, Maturana AMario, de la Cruz MRolando

Inconclusive outcome

Nifurtimox treatment for chronic asymptomatic Trypanosoma cruzi infection showed mixed results, indicating a need for further studies to determine its efficacy.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : Spanish

4.

Chagas disease. What is known and what should be improved: a systemic review.

Author: CouraJosé Rodrigues, Borges-PereiraJosé

Treatment of Chagas disease

This review summarizes the current understanding and areas needing improvement in the fight against Chagas disease, a serious illness caused by a parasite called Trypanosoma cruzi. The review covers topics like the disease's development, current and potential treatments, diagnostic testing, regional variations in prevalence, the role of insects (triatomines) in spreading the disease, and the importance of controlling the disease in endemic areas like the Amazon and Gran Chaco regions. The authors emphasize the need for continued efforts to control Chagas disease globally.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

5.

Improved completion rates and characterization of drug reactions with an intensive Chagas disease treatment program in rural Bolivia.

Author: TornheimJeffrey A, Lozano BeltranDaniel F, GilmanRobert H, CastellonMario, Solano MercadoMarco A, SullcaWalter, TorricoFaustino, BernCaryn

Improved treatment completion
Reduced ADEs
Dermatologic ADEs

Intensive management of Chagas disease patients receiving benznidazole treatment improved completion rates and identified more adverse drug events (ADEs), but did not reduce the incidence of moderate or severe ADEs.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

6.

Course of Chronic Trypanosoma cruzi Infection after Treatment Based on Parasitological and Serological Tests: A Systematic Review of Follow-Up Studies.

Author: SguasseroYanina, CuestaCristina B, RobertsKaren N, HicksElizabeth, ComandéDaniel, CiapponiAgustín, Sosa-EstaniSergio

Chagas disease treatment

Chagas disease is caused by a parasite called Trypanosoma cruzi and is common in Latin America. A negative result on at least two blood tests is used to determine if a person has been cured of the chronic stage of the disease. However, treatment outcomes can vary, and if the parasite is still detected, it indicates that treatment has failed.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

7.

Should trypanocidal therapy be used to treat patients in the chronic phase of Chagas disease?

Author: PopoffFederico, IzcovichAriel

Chagas' disease prevention
Treatment uncertainty

This review examined the evidence on whether treating Chagas' disease in its chronic stage with antiparasitic drugs improves survival or reduces complications. While some studies were included, the quality of the evidence was very low, making it unclear whether these treatments are beneficial.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.

Language : English

8.

Treatment of adult chronic indeterminate Chagas disease with benznidazole and three E1224 dosing regimens: a proof-of-concept, randomised, placebo-controlled trial.

Author: TorricoFaustino, GasconJoaquim, OrtizLourdes, Alonso-VegaCristina, PinazoMaría-Jesús, SchijmanAlejandro, AlmeidaIgor C, AlvesFabiana, Strub-WourgaftNathalie, RibeiroIsabela,

Benznidazole for Chagas disease
E1224 for Chagas disease
Benznidazole liver enzyme increase
E1224 transient effect

Benznidazole was more effective than E1224 in achieving sustained parasitological response in adult patients with chronic indeterminate Chagas disease.

Clinical Trial, Phase IIA Phase II trial is a trial that further evaluates the efficacy and safety of a new drug or treatment, whose safety has been confirmed to some extent in a Phase I trial, in a small number of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

9.

Safety Profile of Benznidazole in the Treatment of Chronic Chagas Disease: Experience of a Referral Centre and Systematic Literature Review with Meta-Analysis.

Author: Crespillo-AndújarClara, Venanzi-RulloEmmanuele, López-VélezRogelio, Monge-MailloBegoña, NormanFrancesca, López-PolínAna, Pérez-MolinaJosé A

Adverse reactions
Treatment discontinuations

Benznidazole, a treatment for Chagas disease, had a high incidence of adverse reactions (ARs) and treatment discontinuations (TDs), particularly in adults. The most common ARs were skin reactions, gastrointestinal complaints, and neurological symptoms.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

10.

Isosorbide and nifedipine for Chagas' megaesophagus: A systematic review and meta-analysis.

Author: Borges MigliavacaCelina, SteinCinara, ColpaniVerônica, René Pinto de Sousa MiguelSandro, Nascimento CruzLuciane, Oliveira DantasRoberto, FalavignaMaicon

Symptom improvement
Headache

Both isosorbide and nifedipine can effectively reduce esophageal symptoms in patients with Chagas' megaesophagus. Isosorbide appears to be more effective, while nifedipine has a better tolerability profile.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

11.

Efficacy and safety assessment of different dosage of benznidazol for the treatment of Chagas disease in chronic phase in adults (MULTIBENZ study): study protocol for a multicenter randomized Phase II non-inferiority clinical trial.

Author: Molina-MorantD, FernándezM L, Bosch-NicolauP, SulleiroE, BangherM, SalvadorF, Sanchez-MontalvaA, RibeiroA L P, de PaulaA M B, EloiS, Correa-OliveiraR, VillarJ C, Sosa-EstaniS, MolinaI

CD treatment

Chagas disease (CD) is a serious infection that affects many people worldwide. While benznidazole (BNZ) is the main drug used for treatment, its effectiveness is limited, especially in adults. The current recommended dosage is based on studies that weren't rigorously designed, and the optimal dose of BNZ hasn't been thoroughly tested in clinical trials.

Clinical Trial, Phase IIA Phase II trial is a trial that further evaluates the efficacy and safety of a new drug or treatment, whose safety has been confirmed to some extent in a Phase I trial, in a small number of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

12.

New regimens of benznidazole monotherapy and in combination with fosravuconazole for treatment of Chagas disease (BENDITA): a phase 2, double-blind, randomised trial.

Author: TorricoFaustino, GascónJoaquim, BarreiraFabiana, BlumBethania, AlmeidaIgor C, Alonso-VegaCristina, BarbozaTayná, BilbeGraeme, CorreiaErika, GarciaWilson, OrtizLourdes, ParradoRudy, RamirezJuan Carlos, RibeiroIsabela, Strub-WourgaftNathalie, VaillantMichel, Sosa-EstaniSergio,

New benznidazole regimens for Chagas disease

This study evaluated the efficacy and safety of new benznidazole monotherapy regimens and combinations with fosravuconazole for treating Chagas disease, considering the limitations of current treatment options.

Clinical Trial, Phase IIA Phase II trial is a trial that further evaluates the efficacy and safety of a new drug or treatment, whose safety has been confirmed to some extent in a Phase I trial, in a small number of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

13.

Genetic polymorphism of Trypanosoma cruzi bloodstream populations in adult chronic indeterminate Chagas disease patients from the E1224 clinical trial.

Author: RamírezJuan Carlos, AcevedoGonzalo Raúl, TorresCarolina, ParradoRudy, De La BarraAnabelle, VillarroelSandro, GarcíaLineth, GasconJoaquim, OrtizLourdes, TorricoFaustino, RibeiroIsabela, SchijmanAlejandro Gabriel

Improved treatment outcomes

The study analyzed the genetic diversity of Trypanosoma cruzi populations in chronic Chagas disease (CD) patients participating in the E1224 clinical trial, investigating its role in response to trypanocidal treatment.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

14.

New chemotherapy regimens and biomarkers for Chagas disease: the rationale and design of the TESEO study, an open-label, randomised, prospective, phase-2 clinical trial in the Plurinational State of Bolivia.

Author: Alonso-VegaCristina, UrbinaJulio A, SanzSergi, PinazoMaría-Jesús, PintoJimy José, GonzalezVirginia R, RojasGimena, OrtizLourdes, GarciaWilson, LozanoDaniel, SoyDolors, MaldonadoRosa A, NagarkattiRana, DebrabantAlain, SchijmanAlejandro, ThomasM Carmen, LópezManuel Carlos, MichaelKatja, RibeiroIsabela, GasconJoaquim, TorricoFaustino, AlmeidaIgor C

BZN/NFX dosing
CD treatment
Adverse events

Chagas disease (CD) affects millions worldwide. While the main medications for CD (benznidazole and nifurtimox) work well in children and during the early stages, they are less effective in adults with chronic CD. These drugs also have significant side effects. Research suggests that giving these medications less often, but for a longer period, might be just as effective and cause fewer side effects.

Clinical Trial, Phase IIA Phase II trial is a trial that further evaluates the efficacy and safety of a new drug or treatment, whose safety has been confirmed to some extent in a Phase I trial, in a small number of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.

Language : English

15.

Use of benznidazole to treat chronic Chagas disease: An updated systematic review with a meta-analysis.

Author: Crespillo-AndújarClara, ComecheBelén, HamerDavidson H, Arevalo-RodriguezIngrid, Alvarez-DíazNoelia, ZamoraJavier, Pérez-MolinaJosé A

Seroreversion in children

This meta-analysis evaluated the effectiveness of benznidazole for chronic Chagas disease (CCD). 17 studies with 6,640 patients were included. Benznidazole showed a beneficial effect on seroreversion in children, but efficacy in adults remains uncertain. More data is needed to assess the clinical efficacy of benznidazole for CCD in both children and adults.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

16.

A Phase 2, Randomized, Multicenter, Placebo-Controlled, Proof-of-Concept Trial of Oral Fexinidazole in Adults With Chronic Indeterminate Chagas Disease.

Author: TorricoFaustino, GascónJoaquim, OrtizLourdes, PintoJimy, RojasGimena, PalaciosAlejandro, BarreiraFabiana, BlumBethania, SchijmanAlejandro Gabriel, VaillantMichel, Strub-WourgaftNathalie, PinazoMaria-Jesus, BilbeGraeme, RibeiroIsabela

Parasite clearance
Liver enzyme elevation
Neutropenia

Fexinidazole, a nitroimidazole drug, showed potential for effective treatment of Chagas disease (CD) in a dose-finding, proof-of-concept study. Sustained parasitological clearance from end of treatment to 12 months follow-up varied between 66.7% and 100.0%, depending on the dosage and duration of treatment. Further evaluation is needed to establish fexinidazole's minimum effective dosage and risk-benefit relationship.

Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Clinical Trial, Phase IIA Phase II trial is a trial that further evaluates the efficacy and safety of a new drug or treatment, whose safety has been confirmed to some extent in a Phase I trial, in a small number of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

17.

Monotherapy and combination chemotherapy for Chagas disease treatment: a systematic review of clinical efficacy and safety based on randomized controlled trials.

Author: Santana NogueiraSilas, Cardoso SantosEliziária, Oliveira SilvaRoberta, Vilela GonçalvesReggiani, LimaGraziela Domingues Almeida, Dias NovaesRômulo

ChD treatment
Adverse reactions

This review examined research on treating Chagas disease, a parasitic infection. The review found that the medication benznidazole (BNZ) is the most effective treatment, with higher success rates when taken for longer periods (up to 60 days). However, treatment with BNZ can cause side effects, leading to discontinuation in some cases. The review suggests that shorter treatment regimens, lower doses, and combinations of BNZ with other medications may be promising approaches to improve treatment outcomes and reduce side effects.

Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

18.

ELISA F29 -A therapeutic efficacy biomarker in Chagas disease: Evaluation in pediatric patients treated with nifurtimox and followed for 4 years post-treatment.

Author: RiveroRocio, EstevaMónica Inés, HuangErya, ColmegnaLeylen, AltchehJaime, GrossmannUlrike, RuizAndrés Mariano,

Improved treatment

Nifurtimox treatment for Chagas disease reduces the levels of the T. cruzi calcium-binding flagellar protein F29 in children, as measured by an ELISA technique.

Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Clinical Trial, Phase IIIA Phase III trial is a trial that further rigorously verifies the efficacy and safety of a new drug or treatment, whose efficacy and safety have been confirmed in a Phase II trial, in a large number of patients, and evaluates whether it is superior to existing treatments.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

19.

The economic burden of Chagas disease: A systematic review.

Author: AndradeMônica Viegas, NoronhaKenya Valéria Micaela de Souza, de SouzaAline, Motta-SantosAndré Soares, BragaPaulo Estevão Franco, BracarenseHenrique, de MirandaMaria Carolina Corrêa, NascimentoBruno Ramos, MolinaIsrael, Martins-MeloFrancisco Rogerlândio, PerelPablo, GeissbühlerYvonne, QuijanoMonica, MachadoIsis Eloah, RibeiroAntônio Luiz Pinho

CD treatment

Chagas disease (CD) affects millions globally, but its economic impact is poorly understood. This study aims to assess the costs associated with treating CD in both regions where the disease is common and in areas where it's less prevalent.

Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

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