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==Medical Therapy==
==Medical Therapy==
===Acute Pharmacotherapy===
*[[Benznidazole]] and [[nifurtimox]] are the only 2 antimicrobial agents that have demonstrated to be effective against ''T. cruzi'' infection.
Medication for Chagas' disease is usually only effective when given during the [[Acute (medical)|acute]] stage of infection. The drugs of choice are azole or nitroderivatives such as [[benznidazole]]<ref>Garcia S, Ramos CO, Senra JF, ''et al.'' "Treatment with benznidazole during the chronic phase of experimental Chagas disease decreases cardiac alterations." Antimicrob Agents Chemother. 2005 Apr;49(4):1521–8. PMID 15793134 [http://aac.asm.org/cgi/content/abstract/49/4/1521 Online]</ref> or [[nifurtimox]] (under an Investigational New Drug protocol from the [[Centers for Disease Control and Prevention|CDC]] Drug Service), but resistance to these drugs has already been reported.<ref>Buckner FS, Wilson AJ, White TC, Van Voorhis WC. "Induction of resistance to azole drugs in Trypanosoma cruzi." Antimicrob Agents Chemother. 1998 Dec;42(12):3245–50. PMID 9835521 [http://aac.asm.org/cgi/content/abstract/42/12/3245 Online]</ref> Furthermore, these agents are very toxic and have many [[adverse effect (medicine)|adverse effects]], and cannot be taken without medical supervision. The antifungal agent [[Amphotericin B]] has been proposed as a second-line drug, but cost and this drug's relatively high toxicity have limited its use. Moreover, 10-year study of chronic administration of drugs in Brazil has revealed that current chemotherapy does not totally remove [[parasitemia]].<ref>Lauria-Pires L, Braga MS, Vexenat AC, ''et al.'' "Progressive chronic Chagas heart disease ten years after treatment with anti-Trypanosoma cruzi nitroderivatives." Am J Trop Med Hyg. 2000 Sep-Oct;63(3-4):111-8. PMID 11388500 [http://www.ajtmh.org/cgi/reprint/63/3/111.pdf PDF Full text]</ref> Thus, the decision about whether to use [[antiparasitic]] therapy should be individualized in consultation with an expert.
*Neither benznidazole nor nifurtimox is FDA-approved in the treatment of ''T. cruzi'', but are often used as investigational protocols.


In the [[chronic (medicine)|chronic]] stage, treatment involves managing the clinical manifestations of the disease, e.g., drugs and [[heart pacemaker]] for [[chronic heart failure]] and [[heart arryhthmia]]s; [[surgery]] for megaintestine, etc., but the disease per se is not curable in this phase. Chronic heart disease caused by Chagas' disease is now a common reason for [[heart transplantation]] surgery. Until recently, however, Chagas' disease was considered a [[contraindication]] for the procedure, since the heart damage could recur as the parasite was expected to seize the opportunity provided by the [[immunosuppression]] that follows surgery. The research that changed the indication of the transplant procedure for Chagas' disease patients was conducted by Dr. [[Adib Jatene]]'s group at the Heart Institute of the University of São Paulo, in São Paulo, Brazil.<ref>Bocchi EA, Bellotti G, Mocelin AO, Uip D, ''et al.'' "Heart transplantation for chronic Chagas' heart disease." Ann Thorac Surg. 1996 Jun;61(6):1727–33. PMID 8651775[http://ats.ctsnetjournals.org/cgi/content/abstract/61/6/1727 Online]</ref> The research noted that survival rates in Chagas' patients can be significantly improved by using lower dosages of the immunosuppressant drug [[cyclosporin]]. Recently, direct [[stem cell therapy]] of the heart muscle using [[bone marrow]] cell transplantation has been shown to dramatically reduce risks of heart failure in Chagas patients.<ref>Vilas-Boas F, Feitosa GS, Soares MB, Mota A, ''et al.'' "[Early results of bone marrow cell transplantation to the myocardium of patients with heart failure due to Chagas disease]." Arq Bras Cardiol. 2006 Aug;87(2):159-66. PMID 16951834 [http://publicacoes.cardiol.br/abc/2004/8202/8202010i.pdf PDF Full text.] [http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0066-782X2004000200010&tlng=en&lng=en&nrm=iso Also available here.]</ref> Patients have also been shown to benefit from the strict prevention of reinfection, though the reason for this is not yet clearly understood.
===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>


Some examples for the struggle for advances:
===Chronic Chagas Disease===
*Use of oxidosqualene cyclase inhibitors and [[cysteine protease]] inhibitors has been found to cure experimental infections in animals.<ref>Engel JC, Doyle PS, Hsieh I, McKerrow JH. "Cysteine protease inhibitors cure an experimental Trypanosoma cruzi infection." J Exp Med. 1998 August 17;188(4):725-34. PMID 9705954[http://www.jem.org/cgi/content/abstract/188/4/725 Online.]</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>
*[[Dermaseptin]]s from frog species ''Phyllomedusa oreades'' and ''P. distincta''. Anti-''Trypanosoma cruzi ''activity without [[cytotoxicity]] to mammalian cells.<ref>PMID 12379643</ref>
*Design of inhibitors to enzymes involved in [[trypanothione]] metabolism, which is unique to the kinetoplastid group of parasites.<ref>Fairlamb AH, Cerami A. "Metabolism and functions of trypanothione in the Kinetoplastida." Annu Rev Microbiol. 1992;46:695–729. PMID 1444271</ref>
*The sesquiterpene lactone dehydroleucodine (DhL) affects the growth of cultured epimastigotes of ''Trypanosoma cruzi''<ref>Brengio SD, Belmonte SA, Guerreiro E, ''et al.'' "The sesquiterpene lactone dehydroleucodine (DhL) affects the growth of cultured epimastigotes of Trypanosoma cruzi." J Parasitol. 2000 Apr;86(2):407-12. PMID 10780563</ref>
* The [[genome]] of Trypanosoma cruzi has been sequenced.<ref>El-Sayed NM, Myler PJ, Bartholomeu DC, ''et al.'' (2005). "The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease". Science 309 (5733): 409-15. PMID 16020725</ref> Proteins that are produced by the disease but not by humans have been identified as possible drug targets to defeat the disease.<ref>El-Sayed, ''et al.'', 2005</ref>


===Antimicrobial Regimen===
*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===
*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==
:* '''Chagas disease'''<ref>{{Cite web | title =  Parasites - American Trypanosomiasis (also known as Chagas Disease) | url = http://www.cdc.gov/parasites/chagas/health_professionals/tx.html }}</ref>
:* '''Chagas disease'''<ref>{{Cite web | title =  Parasites - American Trypanosomiasis (also known as Chagas Disease) | url = http://www.cdc.gov/parasites/chagas/health_professionals/tx.html }}</ref>
::* 1. Preferred regimen(1):
::* 1. Preferred regimen(1):

Revision as of 01:03, 6 August 2015

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

There are two approaches to therapy, both of which can be life saving. They include antiparasitic treatment to kill the parasite and symptomatic treatment to manage the symptoms and signs of infection.

Medical Therapy

  • 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.

Acute Chagas Disease

  • Both benznizadole and nifurtimox are effective against acute T. cruzi infections with a cure rate that ranges from 80% to 90%.[1]

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.

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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