Trypanosomiasis Sleeping Sickness David Humber

Trypanosomes of Vertebrates T.corvi Corvids T.cruzi Humans, rodents, marsupials T.brucei sp Man, ungulates T.lewisi Rodents T.musculis Rodents T.microti Voles T.dionisii Bats T.equiperdum Equids Bone Marrow Heart muscle, autonomic ganglia Blood Lymphoid tissue Heart muscle Genitals SpeciesHostSite

African Sleeping Sickness Ngana South American Sleeping Sickness Chagas Disease

South American Sleeping Sickness Carlos Chagas 1907 Chagas Disease Transmitted by faeces of Assassin Bugs

The Parasite b Motile extracellular EpimastigoteTrypomastigoteSpindle-shapedFlagellated b Non-motile intracellular Amastigote Pseudocysts Ovoid Aflagellate

The Vector Reduvid Bugs Triatome >100 species Confused taxonomy Obligate Haematophagus Nymphs/Adults/Males & Females

Main Vectors b Triatome infestans b Rhodmius prolixix

Non Vector Transmission Triatome bugs 80% Blood transfusion 20,000 cases/year Congenital transmission 10% chance - 3% of cases

Animal Reservoirs Wide range >125 species across 24 families Infection rates 1-100% Acute/Intermediate/chronic But often different pathology

Animal Reservoirs b Domestic Dog **Dog ** CatCat Guinea PigsGuinea Pigs b Sylvatic Rodents ** Opossum Bats Armadillos Primates Not found in Birds/Reptiles/Amphibians

The Life Cycle b b Mammal Trypomastigote Amastigote Trypomastigote b Triatome Bug Trypomastigote –metacyclic Epimastigote

Clinical Features b Acute Phase Chagoma 2-3 weeks - usually on faceChagoma 2-3 weeks - usually on face b Indeterminate Phase Largely asymptomaticLargely asymptomatic b Chronic Phase years often asymptomatic10-20 years often asymptomatic Myocarditis - megasyndromesMyocarditis - megasyndromes

Diagnosis b Direct microscopy of blood Acute phase (100%)Acute phase (100%) Chronic phase (<1%)Chronic phase (<1%) b Xenodiagnosis Chronic phase (40%)Chronic phase (40%) b Serology b Electrocardiography b Radiology

Epidemiology 100 million at risk million infected >45,000 deaths/year Risk of infection directly related to socioeconomic class

Chemotherapy b Nifurtimox b Benznidazol b Gentian violet 24hrs pre treatment of blood24hrs pre treatment of blood b Pacemaker! b Eat carefully!

Control b Vector control Organochloride insecticidesOrganochloride insecticides b Transfusion screening Crystal violet 24hrsCrystal violet 24hrs b Improved health care & housing Chemotherapy & Vaccination

Natural Resistance Amphibians and birds ressistant Birds - Ab independant C activation Lysis of blood stream Tryps No lysis by fresh mammalian serum No natural resistance in humans

Immunology IgG Abs important in chronic phase Role of T cytotoxic & NK unclear Passive Ag coating Autoantibodies important in pathogenesis Poly clonal activation Immunosupression

Vaccination Animal models Vaccine candidates ?

Progress Since 1907 “The control of American Trypanosomiasis offers several practical difficulties, all of them economical. Some day we will not lack the necessary energy to face it in a decisive manner.” Carlos Chagas