Chagas disease medical therapy
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
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Overview
Treatment
There are two approaches to therapy, both of which can be life saving:
- antiparasitic treatment, to kill the parasite; and
- symptomatic treatment, to manage the symptoms and signs of infection.
Medication for Chagas' disease is usually only effective when given during the acute stage of infection. The drugs of choice are azole or nitroderivatives such as benznidazole[1] or nifurtimox (under an Investigational New Drug protocol from the CDC Drug Service), but resistance to these drugs has already been reported.[2] Furthermore, these agents are very toxic and have many 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.[3] Thus, the decision about whether to use antiparasitic therapy should be individualized in consultation with an expert.
In the chronic stage, treatment involves managing the clinical manifestations of the disease, e.g., drugs and heart pacemaker for chronic heart failure and heart arryhthmias; 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.[4] 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.[5] Patients have also been shown to benefit from the strict prevention of reinfection, though the reason for this is not yet clearly understood.
Some examples for the struggle for advances:
- Use of oxidosqualene cyclase inhibitors and cysteine protease inhibitors has been found to cure experimental infections in animals.[6]
- Dermaseptins from frog species Phyllomedusa oreades and P. distincta. Anti-Trypanosoma cruzi activity without cytotoxicity to mammalian cells.[7]
- Design of inhibitors to enzymes involved in trypanothione metabolism, which is unique to the kinetoplastid group of parasites.[8]
- The sesquiterpene lactone dehydroleucodine (DhL) affects the growth of cultured epimastigotes of Trypanosoma cruzi[9]
- The genome of Trypanosoma cruzi has been sequenced.[10] Proteins that are produced by the disease but not by humans have been identified as possible drug targets to defeat the disease.[11]
References
- ↑ 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 Online
- ↑ 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 Online
- ↑ 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 PDF Full text
- ↑ 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 8651775Online
- ↑ 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 PDF Full text. Also available here.
- ↑ 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 9705954Online.
- ↑ PMID 12379643
- ↑ Fairlamb AH, Cerami A. "Metabolism and functions of trypanothione in the Kinetoplastida." Annu Rev Microbiol. 1992;46:695–729. PMID 1444271
- ↑ 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
- ↑ 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
- ↑ El-Sayed, et al., 2005