Chagas disease. (American trypanosomiasis)

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1 Chagas disease (American trypanosomiasis)

2 Epidemiology 7 to 8 million people worldwide are infected Endemic in Latin America and South America USA, Canada, Europe

3 Epidemiology

4 Transmission Trypanosoma Cruzi Faeces (Triatomine Bugs) Blood transfusion Organ transplants Vertical transmission

5

6

7 Trypomastigotes circulating in blood do not replicate Difference to Trypanosoma brucei Trypomastigotes Epimastigotes Amastigotes

8 Carlos Chagas 1879 in Oliveira in Rio de Janeiro Trypanosoma Cruzi Mentor Oswaldo Cruz and

9 Acute phase Lasts two months Often oligosymptomatic First sign chagoma Fever for several weeks

10 Romana sign Orbital unilateral oedema Accompanied by local lymphadenopathies

11 Headache Dyspnoe Myalgia Abdominal pain Cough Diarrhoea

12 Hepatomegaly Splenomegaly Myocarditis (heart failure) Meningoencephalitis If untreated - life-long persistence

13 Chronic phase Asymptomatic form Cardiac form Arrhythmia, cardiomyopathy, secondary thromboembolism, sudden death Digestive lesions Megacolon, megaesophagus, Ileus

14

15 Pathogenesis Infected macrophages, neutrophils cardiomyocytes, neurons induce immune reaction Cytokine and chemokine release IFN-γ, TNF-α, IL-1β ROS (reactive oxygen species) formed by blood leukocytes, splenocytes, vascular and heart tissue Fabiana S. Machado,Herbert B. Tanowitz et al Pathogenesis of Chagas Cardiomyopathy: Role of Inflammation and Oxidative Stress. J Am Heart Assoc. 2013;2:e000539; originally published October 23, 2013;

16 ROS NADPH oxidase transfers an electron to molecular oxygen forming the superoxide ion O 2 Superoxide Ion is converted by superoxide dismutase to H 2 O 2 ROS hyperactivation leads to decrease of NAD + induce inflammatory, hypertrophic gene expression and cell death K Murphy. Janeway s Immunobiology. 8th ed. New York: Garland Science 2012,pp

17 Diagnosis Acute phase Blood smear Blood concentration technique (Microhaematocrit) Stained preparations

18 Diagnosis Chronic phase Serologic tests ELISA Immunochromatography Haemoculture Xenodiagnosis PCR

19 Treatment Urgent treatment in acute phase and reactivation (immunosuppression) Nearly 100% eradication Benznidazole Nifurtimox Contra-indications Pregnancy Renal or hepatic failure (Nifurtimox: psychiatric and neurological diseases)

20 Benznidazole Activated by nitroreductase Inhibits protein- and RNA-synthesis Side effects Allergic dermatitis Peripheral neuropathy Anorexia and weight loss insomnia

21 Nifurtimox Activated form reacts with molecular oxygen, producing active oxygen species Damage to DNA - mutagenic Side effects Anorexia Polyneuropathy Nausea Headache/vertigo

22 Prevention No vaccine Insecticide spraying House improvement Bed nets

23

24

25 Thank you for your attention!

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