Trypanosoma Notes

NOTES NOTES TRYPANOSOMA GENERALLY, WHAT ARE THEY? DIAGNOSIS PATHOLOGY & CAUSES ▪ Genus of flagellated parasitic protozoa Morphology ▪ Elongated body ▪ Flagellum: forms undulated membrane along body ▪ Kinetoplast: functions as mitochondrion Transmission ▪ Through vectors ▪ Incubation period: 1–2 weeks ▪ ▪ ▪ ▪ Direct microscopy Serologic testings Laboratory findings Additional diagnostic tests may be necessary (severity, infection sitedependent) TREATMENT ▪ See individual pathogens SIGNS & SYMPTOMS ▪ See individual pathogens TRYPANOSOMA BRUCEI osms.it/trypanosoma-brucei PATHOLOGY & CAUSES ▪ Protozoan, extracellular parasite → African trypanosomiasis ▪ AKA “sleeping sickness” ▫ Neurologic alterations during meningoencephalitis stage (e.g. somnolence) Virulence factors ▪ Antigenic variation ▫ Changes variant surface glycoprotein (VSG) → immune response evasion ▪ ↑ interferon gamma → ↑ host T. brucei 578 OSMOSIS.ORG susceptibility (mechanism unknown) Morphologic forms (life-cycle) ▪ Epimastigote → procyclic trypomastigote (in tsetse fly midgut) → metacyclic trypomastigote (infectious form) Subspecies ▪ Trypanosoma brucei rhodesiense (acute, more severe disease course) ▪ Trypanosoma brucei gambiense (progressive, milder disease course) Reservoirs ▪ Domestic animals, lions, hyenas, antelopes

Chapter 104 Trypanosoma brucei Vector ▪ Male/female Glossina flies, AKA tsetse flies ▫ Ideal conditions: warm, humid climate (e.g. near river/lake); altitude < 1800m/5905ft Transmission ▪ Saliva inoculation via fly bite; vertical/ parenteral transmission very rare ▪ Endemic regions: sub-Saharan Africa; Democratic Republic of Congo (most cases) Pathogenesis ▪ Glossina bite → subcutaneous metacyclic trypomastigote inoculation → lymph vessels → bloodstream → ↑ tumor necrosis factor (TNF) alpha, interleukin 6 (IL-6), nitric oxide → ↑ capillary permeability → vasculitis → organ invasion, e.g. central nervous system (CNS) Disease stages ▪ Hemolymphatic (early) stage ▪ Meningoencephalitis (late) stage ▪ Symptom severity related to number of organisms in affected tissue (e.g. blood, CNS) RISK FACTORS ▪ Recent endemic area travel ▪ Dense vegetation near human settlement COMPLICATIONS ▪ Meningitis ▪ Myocarditis, heart failure ▪ Aspiration → bacterial pneumonia; associated with altered state of consciousness (meningoencephalitis stage) SIGNS & SYMPTOMS Hemolymphatic stage ▪ Systemic symptoms ▫ Intermittent fever, headache, malaise, weakness, pruritus, rash ▪ Trypanosomal chancre ▫ Rubbery, painful, erythematous, wellcircumscribed lesion at fly bite site approx. one week post-inoculation ▪ Lymphadenopathy ▫ Winterbottom’s sign: enlarged mobile, soft posterior cervical triangle lymph nodes ▪ Hepatosplenomegaly ▪ Dyspnea ▪ Chest pain ▪ Altered thyroid function ▪ Impotence (biologically-male), amenorrhea (biologically-female) ▪ Pain, Kerandel sign (deep hyperesthesia) Meningoencephalitis stage ▪ AKA “Sleeping sickness” ▪ Cachexia ▪ Sleep disturbances (e.g. diurnal somnolence, nocturnal insomnia) ▪ Headaches ▪ Altered state of consciousness ▪ ↓ cognitive function ▪ Personality, behavioral change ▪ Muscle spasms, ataxia, tremor, flaccid paralysis, choreiform movements ▪ Psychiatric manifestations (e.g. psychosis) DIAGNOSIS DIAGNOSTIC IMAGING MRI ▪ Cerebral ▫ May show multifocal white matter hyperintensity (indicates late-stage disease) LAB RESULTS Serologic testings ▪ Card agglutination test for trypanosomiasis (CATT) ▫ Blood + drop of reagent with trypanosomal antigen ▪ Immunofluorescence ▪ Enzyme immunoassays Cerebrospinal fluid (CSF) examination ▪ Disease staging essential ▪ ↑ leukocytes ▪ ↑ proteins ▪ IgM/Trypanosoma presence OSMOSIS.ORG 579

▪ Morula/Mott cells (pathognomonic) ▫ IgM-filled plasma cells Direct microscopy ▪ Organism observation in lymph node aspiration, bone marrow, CSF, blood (thin/ thick Giemsa-stained smears) Laboratory findings ▪ Hemolytic anemia; leukocytosis; thrombocytopenia; ↑ erythrocyte sedimentation rate; hypergammaglobulinemia; hypoalbuminemia, hypocomplementemia; ↑ C-reactive protein; coagulation abnormalities Histological observation ▪ Meningoencephalitis stage (CSF sample) ▫ Morula/Mott cells in white matter (pathognomonic), edema, microhemorrhages, perivascular proliferation OTHER DIAGNOSTICS Electroencephalogram (EEG) ▪ Late stage: abnormal, slow delta waves TREATMENT MEDICATIONS ▪ Antiprotozoal medication ▫ Hemolymphatic stage: pentamidine, suramin ▫ Meningoencephalitis stage: eflornithine, eflornithine + nifurtimox, melarsoprol OTHER INTERVENTIONS ▪ Prevention ▫ Vector control, surveillance ▫ Protective clothing TRYPANOSOMA CRUZI osms.it/trypanosoma-cruzi PATHOLOGY & CAUSES ▪ Protozoan, intracellular parasite ▫ Causes American trypanosomiasis, AKA Chagas disease ▪ Morphologic forms (life cycle) ▫ Amastigote (intracellular, no flagellum) → epimastigote (in triatomine midgut) → trypomastigote (infectious form) ▪ Reservoirs ▫ Opossums, armadillos, canines ▪ Vectors ▫ Triatomine bugs (“kissing bugs”) ▫ Common species: Rhodnius prolixus, Triatoma dimidiata, Triatoma infestans ▫ Characteristics: size (2–3cm/0.79– 1.18in); obligated hematogenous; feeds at night; lives in dark, warm sites (e.g. closets, thatched roofs) 580 OSMOSIS.ORG Transmission ▪ Triatomine bite → fecal wound contamination ▪ Contaminated food/water ingestion (infection through mucous membranes) ▪ Parenteral (e.g. blood transfusion, sharing syringes) ▪ Vertical (mother → fetus) Endemic regions ▪ Rural areas of southern U.S., Latin America Pathogenesis ▪ T. cruzi trypomastigote inoculation → bloodstream → organ invasion (heart, enteric nervous system) → interstitial inflammation → tissue destruction → fibrosis Disease stages ▪ Acute phase: 8–12 weeks ▪ Indeterminate phase: decades

Chapter 104 Trypanosoma brucei ▪ Chronic phase: cardiac/gastrointestinal disease RISK FACTORS ▪ Recent endemic area travel, immunosuppression, blood transfusion, organ transplant, intravenous drug use COMPLICATIONS ▪ Heart failure, acute myocarditis, meningoencephalitis, systemic/pulmonary embolism, sudden death SIGNS & SYMPTOMS Acute phase ▪ Mostly asymptomatic ▪ Systemic: malaise, fever, anorexia, headaches ▪ Chagoma: nodular skin lesion at infection site; usually on face/extremities ▪ Romaña’s sign: unilateral eyelid edema, conjunctivitis, preauricular lymphadenitis; follows conjunctival inoculation ▪ Lymphadenopathy ▪ Hepatosplenomegaly Indeterminate phase ▪ Asymptomatic Chronic phase ▪ Cardiac manifestations: dyspnea, fatigue, palpitation, chest pain, edema, mitral/ tricuspid regurgitation murmur, splitting of S2 ▪ Gastrointestinal manifestations: megacolon (constipation, bloating, abdominal pain); megaesophagus (dysphagia, regurgitation) Congenital disease ▪ Systemic: low birthweight, anasarca, fever ▪ Petechiae ▪ Hepatosplenomegaly ▪ Neurologic abnormalities (e.g. hypotonia, tremor) DIAGNOSIS DIAGNOSTIC IMAGING ▪ Further studies: stage, clinical syndrome dependent Figure 104.1 The kissing bug, Triatoma infestans, is found in Central and South America and is a vector for Chagas disease. Chest X-ray, MRI, echocardiogram ▪ Enlarged cardiac silhouette (cardiomegaly) ▪ Pericardial effusion ▪ Valvular regurgitation ▪ Left ventricular aneurysm Barium studies ▪ Megacolon, megaesophagus LAB RESULTS ▪ Polymerase chain reaction (PCR) OSMOSIS.ORG 581

▪ Blood culture Direct microscopy ▪ Organism observation in thin/thick blood smears; for acute phase disease (high parasitemia) Serologic testing ▪ E.g. enzyme-linked immunosorbent assay (ELISA), immunofluorescence Xenodiagnosis ▪ Feed laboratory triatomes with person’s blood → examine feces weeks later Cardiac tissue microscopy ▪ Acute disease: intracellular pseudocysts (amastigotes inside myocardiocytes), interstitial inflammation ▪ Chronic disease: mural thrombi, interstitial fibrosis, myocardiocyte necrosis OTHER DIAGNOSTICS ECG ▪ Arrhythmia evidence: bundle branch/AV block TREATMENT MEDICATIONS ▪ Antitrypanosomal treatment ▪ Advanced cardiac disease: cardiac arrest prevention, ventricular fibrillation through antiarrhythmic medication OTHER INTERVENTIONS Prevention ▪ Vector control, treat parasitemia before conception 582 OSMOSIS.ORG Figure 104.2 Trypanosoma species seen on a peripheral blood smear from an individual with Chagas disease.