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Chagas disease

Etiology: - Trypanosoma cruzi Epidemiology: 1) United States, Central & South America - rarely, cases orginate in United States - one of top 5 neglected parasitic infections in the U.S. - > 300,000 Americans are infected with T cruzi [6] - 5.7 million persons infected in Latin America 2) transmitted by kissing bugs of the family Reduviidae, so named because it often bites the face 3) bug defecates at the time of biting 4) bug feces contain infective trypomastigotes that penetrate the skin as a result of scratching or rubbing or through intact mucosa 5) bug urine is also infective [11] 6) infection may be transmitted by blood transfusion 7) vertical transmission from mother to baby 8) dogs, rodents, armadillos, & other domestic & wild animals serve as reservoirs Pathology: 1) after gaining access to tissues, typomastigotes transform into dividing amastigotes 2) when the infected cell is full of amastigotes, transformation to trypomastigotes occurs, followed by cell rupture 3) trypomastigotes are released into the peripheral blood where they reach distant tissues & begin the replicative cycle again 4) cross-reactivity of Trypanosoma cruzi antigens with human protein(s) serology> - R1 & R3 epitopes of TCFL5, recognized by T- & B-cells, respectively Clinical manifestations: 1) may cause acute or chronic infection - most persons remain asymptomatic but are infected for life [8] 2) acute infection: a) generally lasts 2-3 months b) fever/chills, malaise, hepatosplenomegaly, myocarditis c) swelling of the tissue around the eye may be present if bite occurred on face (Romana's sign) d) swelling of the tissues around the bite at other sites is called a chagoma e) acute disease is more common in children under 5 f) in older individuals, infection is generally mild or asymptomatic g) vast majority of patients are asymptomatic [8] 3) chronic infection a) achalasia, megaesophagus b) megacolon c) cardiac disease - autoimmune destruction of parasympathetic innervation of heart - bundle branch block, heart block - ventricular tachycardia - segmental ventricular wall abnormalities & apical aneurysm - ventricular thrombus resulting in thromboembolism - dilated cardiomyopathy with congestive heart failure d) quiescent infections may be exacerbated by immunosuppression e) most patients remain asymptomatic but are infected for life [8] Laboratory: 1) diagnosis is made by demonstration of trypomastigotes in - peripheral blood smear [7] - buffy coat - aspirates of lymph nodes or chagomas 2) trypomastigotes a) curved with S & C shapes b) measure up to 20 um in length b) kinetoplast larger than that of T brucei 3) culture 4) xenodiagnosis in endemic areas a) examination of the gut contents of laboratory-raised rejuviid bugs that have been allowed to feed on the victim 5) serology: a) EIA, IFA & ELISA are available b) false positives may occur in patients with Leishmaniasis c) antibodies against TCFL5 (nuclear antigen) 6) see ARUP consult [5] Complications: - cardiac & gastrointestinal complications dominate - occur in 30% of infected individuals - heart failure, 45% within 10 years of onset - dilated cardiomyopathy [10] - complete heart block - ventricular arrhythmias, including sudden death [10] - stroke [10] - pulmonary embolism [10] - dysphagia from esophageal dilation - reactivation of dormant disease in immunosuppressed patients [10] images) Management: 1) treatment is unsatisfactory 2) benznidazole a) 5 mg/kg/day PO for 60 days b) delays progression to heart failure (10% vs 45&) [4] c) used for reactivation in brain (case report) [10] d) recommended as first-line therapy (only FDA-approved drug for treatment of Chagas disease) [11] 3) nifurtimox a) markedly reduces duration of symptoms, parasitemia & mortality b) 50% of infections are cured by a full course of therapy c) may be useful in exposure from laboratory accidents d) treatment should be begun as soon as possible e) 8-10 mg/kg/day for adults f) 12.5-15 mg/kg/day for adolescents g) 15-20 mg/kg/day for children ages 1-10 years h) doses given orally, divided QID i) therapy should be continued to 90-120 days j) available from CDC (707 639-3670) 4) referral to cardiologist for cardiac involvement 5) referral to gastroenterologist for GI manifestations 6) no vaccine available Notes: - known Chagas disease is a contraindication for organ domation of - heart (absolute), liver or kidney (relative)

Related

Trypanosoma cruzi (Chagas disease)

General

trypanosomiasis

References

  1. Clinical Diagnosis & Management by Laboratory Methods, 19th edition, J.B. Henry (ed), W.B. Saunders Co., Philadelphia, PA. 1996, pg 1266
  2. Stedman's Medical Dictionary 26th ed, Williams & Wilkins, Baltimore, 1995
  3. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, 1193-94
  4. Viotti R, Vigliano C, Lococo B, Bertocchi G, Petti M, Alvarez MG, Postan M, Armenti A. Long-term cardiac outcomes of treating chronic Chagas disease with benznidazole versus no treatment: a nonrandomized trial. Ann Intern Med. 2006 May 16;144(10):724-34. PMID: 16702588 - Pinto Dias JC. The treatment of Chagas disease (South American trypanosomiasis). Ann Intern Med. 2006 May 16;144(10):772-4. No abstract available. PMID: 16702594
  5. ARUP Consult: Trypanosoma cruzi - Chagas Disease The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/trypanosoma-cruzi
  6. Jones SL et al Special Section on Neglected Parasitic Infections. American Journal of Tropical Medicine and Hygiene special section on neglected parasitic infections. http://www.ajtmh.org/content/90/5.toc#SpecialSectiononNeglectedParasiticInfections - Parise ME et al Neglected Parasitic Infections in the United States: Needs and Opportunities. Am J Trop Med Hyg 2014 90(5):783-785 http://www.ajtmh.org/content/90/5/783.full - Centers for Disease Control and Prevention (CDC) Press Release. May 8, 2012 Parasitic Infections also occur in the United States. http://www.cdc.gov/media/releases/2014/p0508-npi.html
  7. Blevins SM, Greenfield RA, Bronze MS Blood smear analysis in babesiosis, ehrlichiosis, relapsing fever, malaria, and Chagas disease. Cleve Clin J Med. 2008 Jul;75(7):521-30 PMID: 18646588
  8. Rothaus C Chagas' Disease Now@NEJM. July 31, 2015 http://blogs.nejm.org/now/index.php/chagas-disease-2/2015/07/31/
  9. Gomez CA, Banaei N Trypanosoma cruzi Reactivation in the Brain. N Engl J Med 2018; 378:1824. May 10, 2018 PMID: 29742366 https://www.nejm.org/doi/full/10.1056/NEJMicm1703763
  10. Pereira Nunes MC, Beaton A, Acquatella H Chagas Cardiomyopathy: An Update of Current Clinical Knowledge and Management: A Scientific Statement From the American Heart Association. Circulation. Aug 20, 2018 PMID: 30354432 https://www.ahajournals.org/doi/10.1161/CIR.0000000000000599
  11. Rothaus C Under Our Very Eyes. NEJM REsident 360. March 4, 2020 https://resident360.nejm.org/clinical-pearls/under-our-very-eyes
  12. GARD Genetic and Rare Diseases Information Center Chagas Disease (not a rare disease) https://rarediseases.info.nih.gov/diseases/6030/chagas-disease - Centers for Disease Control and Prevention http://www.cdc.gov/ncidod/dpd/parasites/chagasdisease Division of Parasitic diseases (physicians) 770-488-7775 - Centers for Disease Control & Prevention (CDC) Parasites - American Trypanosomiasis (also known as Chagas disease) Triatomine Bug FAQs https://www.cdc.gov/parasites/chagas/gen_info/vectors/index.html