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==Treatment==
==Treatment==
[[Chagas disease medical therapy|Medical therapy]] | [[Chagas disease surgery|Surgical options]] | [[Chagas disease primary prevention|Primary prevention]]  | [[Chagas disease secondary prevention|Secondary prevention]] | [[Chagas disease cost-effectiveness of therapy|Financial costs]] | [[Chagas disease future or investigational therapies|Future therapies]]
[[Chagas disease medical therapy|Medical therapy]] | [[Chagas disease surgery|Surgical options]] | [[Chagas disease primary prevention|Primary prevention]]  | [[Chagas disease secondary prevention|Secondary prevention]] | [[Chagas disease cost-effectiveness of therapy|Financial costs]] | [[Chagas disease future or investigational therapies|Future therapies]]
==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 (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.
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.
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.<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>
*[[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>
==Prevention==
==Prevention==
[[Image:Triatoma infestans.jpg|thumb|Vector insect ''[[Triatoma infestans]]'' (Kissing Bug)]]
[[Image:Triatoma infestans.jpg|thumb|Vector insect ''[[Triatoma infestans]]'' (Kissing Bug)]]

Revision as of 15:20, 27 January 2012

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Chagas disease
Photomicrograph of Giemsa-stained Trypanosoma cruzi crithidia (CDC)
ICD-10 B57
ICD-9 086
DiseasesDB 13415
MedlinePlus 001372
MeSH D014355

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

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Prevention

Vector insect Triatoma infestans (Kissing Bug)

A reasonably effective vaccine was developed in Ribeirão Preto in the 1970s, using cellular and subcellular fractions of the parasite, but it was found economically unfeasible. More recently, the potential of DNA vaccines for immunotherapy of acute and chronic Chagas' disease is being tested by several research groups.

Prevention is centered on fighting the vector (Triatoma) by using sprays and paints containing insecticides (synthetic pyrethroids), and improving housing and sanitary conditions in the rural area. For urban dwellers, spending vacations and camping out in the wilderness or sleeping at hostels or mud houses in endemic areas can be dangerous, a mosquito net is recommended. If the traveller intends to travel to the area of prevalence, he/she should get information on endemic rural areas for Chagas' disease in traveller advisories, such as the CDC.

In most countries where Chagas' disease is endemic, testing of blood donors is already mandatory, since this can be an important route of transmission. The United States FDA has recently licensed a test for antibodies against T. cruzi for use on blood donors but has not yet mandated its use. The AABB recommends that past recipients of blood components from donors found to be infected be notified and themselves tested. In the past, donated blood was mixed with 0,25 g/L of gentian violet successfully to kill the parasites. Early detection and treatment of new cases, including mother-to-baby cases, will also help reduce the burden of disease.

With all these measures, some landmarks were achieved in the fight against Chagas' disease in Latin America: a reduction by 72% of the incidence of human infection in children and young adults in the countries of the Initiative of the Southern Cone, and at least two countries (Uruguay, in 1997, and Chile, in 1999), were certified free of vectorial and transfusional transmission. In Brazil, with the largest population at risk, 10 out of the 12 endemic states were also certified free.

Some stepstones of vector control:

  • A yeast trap has been tested for monitoring infestations of certain species of the bugs:"Performance of yeast-baited traps with Triatoma sordida, Triatoma brasiliensis, Triatoma pseudomaculata, and Panstrongylus megistus in laboratory assays."[1]
  • Promising results were gained with the treatment of vector habitats with the fungus Beauveria bassiana, (which is also in discussion for malaria- prevention):"Activity of oil-formulated Beauveria bassiana against Triatoma sordida in peridomestic areas in Central Brazil."[2]
  • Targeting the symbionts of Triatominae through paratransgenesis.[3]

See also

Notes

  1. ↑ Pires HH, Lazzari CR, Diotaiuti L, Lorenzo MG. "Performance of yeast-baited traps with Triatoma sordida, Triatoma brasiliensis, Triatoma pseudomaculata, and Panstrongylus megistus in laboratory assays." Rev Panam Salud Publica. 2000 Jun;7(6):384-8. PMID 10949899
  2. ↑ Luz C, Rocha LF, Nery GV, Magalhaes BP, Tigano MS. "Activity of oil-formulated Beauveria bassiana against Triatoma sordida in peridomestic areas in Central Brazil." Mem Inst Oswaldo Cruz. 2004 Mar;99(2):211-8. PMID 15250478 Online.
  3. ↑ "PubMed Search on Triatominae symbiosis".

References

  • CDC, Division of Parasitic Diseases. Chagas Disease Fact Sheet. (23 September 2004). Accessed 24 September 2006.
  • Dumonteil E, Escobedo-Ortegon J, Reyes-Rodriguez N, Arjona-Torres A, Ramirez-Sierra M (2004). "Immunotherapy of Trypanosoma cruzi infection with DNA vaccines in mice". Infect Immun. 72 (1): 46–53. PMID 14688079.
  • CDC, Division of Parasitic Diseases.Chagas Disease(23 October 2007). Accessed 16 August 2007.
  • CDC, Division of Parasitic Diseases.Chagas Disease Epidemiology.(23 October 2007). Accessed 16 August 2007.
  • CDC, Division of Parasitic Diseases. Treatment(23 October 2007). Accessed 16 August 2007.

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