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==Overview==
==Overview==
[[Benznidazole]] and [[nifurtimox]] are the only antimicrobial therapies with proven efficacy against ''T. cruzi'' infection. Neither drug is FDA-approved, but can be obtained under investigational protocol. Either benznidazole or nifurtimox may be used to manage congenital infection, acute infection, and chronic infection (only among young patients < 50-55 years) including those with early cardiomyopathy.
[[Benznidazole]] and [[nifurtimox]] are the only [[antimicrobial]] [[therapies]] with proven efficacy against ''T. cruzi'' infection. Neither drug is [[FDA]]-approved, but can be obtained under investigational protocol. Either [[benznidazole]] or [[nifurtimox]] may be used to manage [[congenital]] infection, [[acute]] [[infection]], and [[chronic]] [[infection]] (only among young patients < 50-55 years) including those with early [[cardiomyopathy]].


==Medical Therapy==
==Medical Therapy==
*[[Benznidazole]] and [[nifurtimox]] are the only 2 antimicrobial agents that have demonstrated to be effective against ''T. cruzi'' infection.
*[[Benznidazole]] and [[nifurtimox]] are the only 2 [[antimicrobial]] agents that have demonstrated to be effective against ''T. cruzi'' [[infection]].
*Neither benznidazole nor nifurtimox is FDA-approved in the treatment of ''T. cruzi'', but are often used as investigational protocols.
*Neither [[benznidazole]] nor [[nifurtimox]] is FDA-approved in the treatment of ''T. cruzi'', but are often used as investigational protocols.


===Acute Chagas Disease===
===Acute Chagas Disease===
*Both benznizadole and nifurtimox are effective against acute ''T. cruzi'' infections with a cure rate that ranges from 80% to 90%.<ref name="pmid26222561">{{cite journal| author=Bern C| title=Chagas' Disease. | journal=N Engl J Med | year= 2015 | volume= 373 | issue= 5 | pages= 456-66 | pmid=26222561 | doi=10.1056/NEJMra1410150 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26222561  }} </ref>
*Both benznizadole and [[nifurtimox]] are effective against acute ''T. cruzi'' [[infections]] with a [[cure]] rate that ranges from 80% to 90%.<ref name="pmid26222561">{{cite journal| author=Bern C| title=Chagas' Disease. | journal=N Engl J Med | year= 2015 | volume= 373 | issue= 5 | pages= 456-66 | pmid=26222561 | doi=10.1056/NEJMra1410150 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26222561  }} </ref>


===Chronic Chagas Disease===
===Chronic Chagas Disease===
*While it was thought that chronic Chagas disease cannot be managed by pharmacotherapy, new evidence from randomized and non-randomized trials demonstrated that young patients (age < 50-55 years of age) with chronic Chagas disease, including those with early cardiomyopathy, may be managed using long-term antitrypanosomal antimicrobial therapy.<ref name="pmid8937280">{{cite journal| author=de Andrade AL, Zicker F, de Oliveira RM, Almeida Silva S, Luquetti A, Travassos LR et al.| title=Randomised trial of efficacy of benznidazole in treatment of early Trypanosoma cruzi infection. | journal=Lancet | year= 1996 | volume= 348 | issue= 9039 | pages= 1407-13 | pmid=8937280 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8937280  }} </ref><ref name="pmid9790423">{{cite journal| author=Sosa Estani S, Segura EL, Ruiz AM, Velazquez E, Porcel BM, Yampotis C| title=Efficacy of chemotherapy with benznidazole in children in the indeterminate phase of Chagas' disease. | journal=Am J Trop Med Hyg | year= 1998 | volume= 59 | issue= 4 | pages= 526-9 | pmid=9790423 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9790423  }} </ref>
*While it was thought that [[chronic]] Chagas disease cannot be managed by [[pharmacotherapy]], new evidence from randomized and non-randomized trials demonstrated that young patients (age < 50-55 years of age) with [[chronic]] Chagas disease, including those with early [[cardiomyopathy]], may be managed using long-term antitrypanosomal [[antimicrobial]] [[therapy]].<ref name="pmid8937280">{{cite journal| author=de Andrade AL, Zicker F, de Oliveira RM, Almeida Silva S, Luquetti A, Travassos LR et al.| title=Randomised trial of efficacy of benznidazole in treatment of early Trypanosoma cruzi infection. | journal=Lancet | year= 1996 | volume= 348 | issue= 9039 | pages= 1407-13 | pmid=8937280 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8937280  }} </ref><ref name="pmid9790423">{{cite journal| author=Sosa Estani S, Segura EL, Ruiz AM, Velazquez E, Porcel BM, Yampotis C| title=Efficacy of chemotherapy with benznidazole in children in the indeterminate phase of Chagas' disease. | journal=Am J Trop Med Hyg | year= 1998 | volume= 59 | issue= 4 | pages= 526-9 | pmid=9790423 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9790423  }} </ref>


*Seroconversion (seropositivity to seronegativity) may only occur several years following the beginning of antimicrobial therapy.<ref name="pmid26222561">{{cite journal| author=Bern C| title=Chagas' Disease. | journal=N Engl J Med | year= 2015 | volume= 373 | issue= 5 | pages= 456-66 | pmid=26222561 | doi=10.1056/NEJMra1410150 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26222561  }} </ref>
*Seroconversion (seropositivity to seronegativity) may only occur several years following the beginning of antimicrobial therapy.<ref name="pmid26222561">{{cite journal| author=Bern C| title=Chagas' Disease. | journal=N Engl J Med | year= 2015 | volume= 373 | issue= 5 | pages= 456-66 | pmid=26222561 | doi=10.1056/NEJMra1410150 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26222561  }} </ref>


===Congenital Chagas Disease===
===Congenital Chagas Disease===
*Similar to acute Chagas disease, both benznizadole and nifurtimox are effective against acute ''T. cruzi'' infections. When managed early, the cure rate of congenital Chagas disease ranges from 80% to 90%.<ref name="pmid26222561">{{cite journal| author=Bern C| title=Chagas' Disease. | journal=N Engl J Med | year= 2015 | volume= 373 | issue= 5 | pages= 456-66 | pmid=26222561 | doi=10.1056/NEJMra1410150 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26222561  }} </ref>
*Similar to acute Chagas disease, both [[benznizadole]] and [[nifurtimox]] are effective against acute ''T. cruzi'' infections. When managed early, the cure rate of [[congenital]] Chagas disease ranges from 80% to 90%.<ref name="pmid26222561">{{cite journal| author=Bern C| title=Chagas' Disease. | journal=N Engl J Med | year= 2015 | volume= 373 | issue= 5 | pages= 456-66 | pmid=26222561 | doi=10.1056/NEJMra1410150 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26222561  }} </ref>


==Antimicrobial Regimen==
==Antimicrobial Regimen==
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== Chagas heart disease ==
== Chagas heart disease ==


*In the past three decades, a consensus has emerged that parasite persistence is crucial to the development and progression of Chagas cardiomyopathy. It was believed that Antiparasitic treatment in the chronic phase of Chagas disease could prevent complications related to the disease. However, according to the results of the benefit trial, benznidazole seems to have no benefit for arresting disease progression in patients with chronic Chagas cardiomyopathy.  
*In the past three decades, a consensus has emerged that parasite persistence is crucial to the development and progression of Chagas [[cardiomyopathy]]. It was believed that [[Antiparasitic]] treatment in the [[chronic]] phase of Chagas disease could prevent [[complications]] related to the [[disease]]. However, according to the results of the benefit trial, [[benznidazole]] seems to have no benefit for arresting [[disease]] progression in patients with [[chronic]] Chagas [[cardiomyopathy]].


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Revision as of 22:01, 14 February 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Yazan Daaboul, M.D.

Overview

Benznidazole and nifurtimox are the only antimicrobial therapies with proven efficacy against T. cruzi infection. Neither drug is FDA-approved, but can be obtained under investigational protocol. Either benznidazole or nifurtimox may be used to manage congenital infection, acute infection, and chronic infection (only among young patients < 50-55 years) including those with early cardiomyopathy.

Medical Therapy

Acute Chagas Disease

Chronic Chagas Disease

  • While it was thought that chronic Chagas disease cannot be managed by pharmacotherapy, new evidence from randomized and non-randomized trials demonstrated that young patients (age < 50-55 years of age) with chronic Chagas disease, including those with early cardiomyopathy, may be managed using long-term antitrypanosomal antimicrobial therapy.[2][3]
  • Seroconversion (seropositivity to seronegativity) may only occur several years following the beginning of antimicrobial therapy.[1]

Congenital Chagas Disease

  • Similar to acute Chagas disease, both benznizadole and nifurtimox are effective against acute T. cruzi infections. When managed early, the cure rate of congenital Chagas disease ranges from 80% to 90%.[1]

Antimicrobial Regimen

  • Chagas disease[4]
  • 1. Preferred regimen(1):
  • Patients of age < 12 years- Benznidazole 5-7.5 mg/kg/ day PO bid for 60 days
  • Patients of age 12 years or older- Benznidazole 5-7 mg/kg/day PO bid for 60 days
  • 2. Preferred regimen(2):
  • Patients of age ≤ 10 years- Nifurtimox 15-20 mg/kg/day PO tid/ qid for 90 days
  • Patients of age 11-16 years- Nifurtimox 12.5-15 mg/kg/day PO tid/ qid for 90 days
  • Patients of age 17 years or older- Nifurtimox 8-10 mg/kg/day PO tid/ qid for 90 days
  • Note: In the United States, Nifurtimox and Benznidazole are not FDA approved and are available only from CDC under investigational protocols.

Chagas heart disease


References

  1. 1.0 1.1 1.2 Bern C (2015). "Chagas' Disease". N Engl J Med. 373 (5): 456–66. doi:10.1056/NEJMra1410150. PMID 26222561.
  2. de Andrade AL, Zicker F, de Oliveira RM, Almeida Silva S, Luquetti A, Travassos LR; et al. (1996). "Randomised trial of efficacy of benznidazole in treatment of early Trypanosoma cruzi infection". Lancet. 348 (9039): 1407–13. PMID 8937280.
  3. Sosa Estani S, Segura EL, Ruiz AM, Velazquez E, Porcel BM, Yampotis C (1998). "Efficacy of chemotherapy with benznidazole in children in the indeterminate phase of Chagas' disease". Am J Trop Med Hyg. 59 (4): 526–9. PMID 9790423.
  4. "Parasites - American Trypanosomiasis (also known as Chagas Disease)".

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