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Chagas Diseases in the traveler Andrés F. Henao Assistant Professor University of Colorado Denver Sept 28, 2016 Chagas Disease: Introduction: Discovered in 1909 by a Brazilian Physician Carlos Chagas. Paleoparasitology recovered T. cruzi in 9000 years old mummies. Charles Darwin quite possible contracted Chagas disease. Etiology/Life cycle: Vector: Transmitted to Humans and more than 150 species of domestic and wild animals by large, blood sucking reduviid bugs (Subfamily Triatominae). Epidemiology: Chagas disease infected 8 million people in Latin America by 2005 and about 20% of the population is at risk (~109 million of people). It causes 12,500 deaths annually. Epidemiology: Chagas disease is now an emerging disease associated with congenital, blood, and organ transplantation transmissions in developed countries, in which 1%–26% of immigrants are infected. In the US, approximately 300,000 individuals are estimated to be infected with T. cruzi. Clinical Infectious Diseases 2012;54(6):845–52 Traveling to areas with potential exposure: Traveling epidemiology: Rural areas in Mexico, and Central and South America —highest concentration between central Mexico and northern Argentina. Excepts the Caribbean and Uruguay. Symptomatic acquisition of acute Chagas' disease in travelers is rare, with only 5 reported cases. Sero surveys for asymptomatic infection due to travel have not been performed. Transmission risk in the Yucatán peninsula of México: Am J Trop Med Hyg 2004 ; 70 : 514 – 519 . Transmission: Vector—bites occur predominantly at night and they are painless and then become itchy. Blood Transfusion or organ transplant. Vertical (transplacental) Accidental (Laboratory). Oral: Reported in Brazil (primarily the Amazon region) since the 1960s, and in Bolivia, Colombia, and Venezuela in more recent years. Risk factors among travelers: Travelers undertaking outdoor activities such as hiking, camping, and ecotourism in endemic countries in Central and South America. Sleeping in poorly constructed houses—Huts made of mud, palm thatch, or adobe brick. Triatomines or their feces may be crushed and mixed with freshly prepared sugar cane or acai juices. In certain areas of Bolivia, the sero positivity among blood donors can be as high as 53%. Transmission scenarios among travelers: Acute infection following ingestion of contaminated food. Vector related. Sleeping in small villages with lack of netted windows and doors. Sleeping outdoor on hammocks. • J Infect Public Health. 2016 May 30. • Am J Trop Med Hyg. 2012 Dec 5; 87(6): 1038–1040. A Neglected Infection of Poverty : Chagas in the US: States with documented mammalian reservoirs * * Published human vectorassociated cases * * * > 18 infected reservoir species identified Natural course: Expert Reviews in Molecular Medicine 2010 Published by Cambridge University Press. Signs of acute infection: Asymptomatic. Fever/Chills. Lympadenopathy. Hepato-Splenomegaly. CNS involvement (rare). Unilateral palpebral swelling (Romaña sign). Clinical presentations among returning travelers: Acute Chagas disease Eye swelling, pruritus, pain. Fever, headaches, dyspnea on exertion, rash, low appetite. Am J Trop Med Hyg. 2012 Dec 5; 87(6): 1038–1040. Acute Myocarditis: Involvement of the myocardium with myocarditis during the acute infection has been constantly found through myocardial biopsies or at necropsy even if patients are asymptomatic. International journal of cardiology. 1997;60(1):49-54. Acute Chagasic myocarditis: Acute Chagas cardiac disease among travelers: Pericarditis First AV block. Pleural effusion. LV dilation. • J Infect Public Health. 2016 May 30. • Am J Trop Med Hyg. 2012 Dec 5; 87(6): 1038–1040. Natural history: Lancet; Vol 375 April 17, 2010. Chronic Chagas Disease: Conduction system abnormalities. Cardiomegaly with heart failure. Apical aneurysms and systemic/pulmonary thromboembolism. Sudden death. Lancet; Vol 375 April 17, 2010. Cardiac changes stages: Lancet 2010; 375: 1388–402. Continue: Mega-esophagus Megacolon Lancet; Vol 375 April 17, 2010. Diagnosis: N Engl J Med 2011;364:2527-34. Difficulties in diagnosis: Observation of the parasites in blood (only useful in the acute phase). Xenodiagnosis. Only 30 to 60% of untreated patients with chronic T. cruzi infection have positive results. Inoculation of the patient's blood into a susceptible laboratory animal. Culture methods are not clinically useful because parasites may not be seen for several weeks. Continue: PCR: Because the circulating parasite load is low in the chronic phase, PCR sensitivity in untreated patients is not high Serologies: Testing for anti–T. cruzi IgM AB is not useful because tests for this antibody isotype are not well-standardized. No single assay has sufficient sensitivity and specificity to be relied on alone. Two tests based on different antigens, techniques: (e.g., enzyme-linked immunosorbent assay [ELISA], immunofluorescence antibody assay, and immunoblot assay). Lab abnormalities in the returning traveler: Mild anemia, atypical lymphocytes. Mildly elevated liver enzymes. EKG with low QRS voltage. Echocardiogram diastolic left ventricular dysfunction, dilated left atrium, thickened pericardium and pericardial effusion. Differential Diagnosis: Acute infection: Acute HIV, malaria, Viral infections—Zika, dengue, CHIKV), leptospira, etc. Chronic: Other forms of dilated Cardiomyopathy. Achalasia of the esophagus. Hirschsprung’s disease of the colon. Chagas-HIV co-infection: Reactivation of Chagas’ disease occurred in 15-35% in co-infected untreated HIV patients. Chagas’ disease serology can be inconclusive and, occasionally, non-reactive in untreated HIV patients. Clinical reactivation generally occurs in persons with CD4+T cell counts <200 cells/mm3 and most commonly involves the CNS. Trans R Soc Trop Med Hyg. 2010 Jul;104(7):447-52. Clin Infect Dis. 2007 Nov 1;45(9):1208-13. General treatment: Nifurtimox and Benznidazole. The drugs have variable efficacy, must be taken for extended periods, and patients may experience significant side effects. Parasitological cure is believed to occur in 60-85% of persons with acute infection. Continue: Benznidazole: 5 to 7 mg/kg per day orally in two divided doses for 60 days. Nifurtimox: 8 to 10 mg/kg per day orally in three or four divided doses for 90 to 120 days N Engl J Med 2011;364:2527-34. Indications for anti-trypanosomal therapy: Acute, congenital or reactivation in the immunosuppressed patient. All children 18 years or younger with chronic T. cruzi infection. Chronic infection up to 50-55 years of age including those with evidence of early Chagas heart disease (e.g. ECG abnormalities or LV dysfunction without heart failure). But not in those with advanced Chagas cardiomyopathy. SHOULD NEVER BE OFFERED in pregnancy or marked liver or renal dysfunction. Benznidazole for Chronic Chagas’ Disease: Results at 1 year by PCR detection and in patients with mostly on indeterminate cardiac forms (60%). Treatment on chronic infection in adults-I: Ann Intern Med. 2006;144:724-734 Treatment on chronic infection in adults-II: Despite the evidence that therapy reduced parasite-related outcomes, the low quality and inconsistency of the data for patientimportant outcomes must be treated with caution. Cochrane Database Syst Rev. 2014 May 27;5:CD003463 Treatment in adults-III: Effectiveness of Benznidazole therapy: Monitoring response to therapy: Reduction on the titers or negative seroconversion. Quantitative PCR. Xenodiagnosis after treatment. Progression on cardiac disease. N Engl J Med 2015;373:456-66. Prognosis: Lancet; Vol 375 April 17, 2010. Prevention while traveling-I: Do not sleep in natives' hut or outdoor hammocks. Search for hidden insects— under the mattress, behind pictures, in drawers, or dark corners of the room. Carry repellents and insecticides. Spray the walls around your bed, especially where there are cracks. Use bed nets. If camping—stay away from palm trees, stones or wood piles. Prevention while traveling-II: Unless a life-threatening emergency exists, blood transfusions that have not been assuredly screened for Chagas' disease should be avoided. Travelers should avoid freshly prepared fruit and cane juices from unsanitary sources. Thank you Questions?