Trypanosoma spp.HemoflagellatesFamily Trypanosomidae3 species known to be pathogenic in human are:Trypanosoma gambienseTrypanosoma rhodesienseTrypanosoma cruziCauses human sleeping sickness

Trypanosoma gambienseGeneralCauses Mid African trypanosomiasisVector: Tse Tse fly (Glossina palpalis)Final host: humansReservoir host: pig, goat, and cattleThe parasite lives in blood plasma, lymph nodes, spleen and brainTrypanosoma can also be transmitted through blood transfusions, organ transplantation, transplacentally, and in laboratory accidents

Different stages of HaemoflagellatesMorphology

Trypanosoma gambienseMorphologyBugs, Assassin bugs (or kissing bugs) Glossina (Tsetse fly)The Vector

African TrypanosomiasisTrypanosoma gambiense Life Cycle

Gambian TrypanosomiasisGeneralWest African sleeping sicknessInfection occurs through the bite of tsetse fly of Glossina palpalis and Glossina tachinoides, injecting pleomorphic trypanosomes into human blood stream by anterior inoculationInfection is characterized by three progressive stages: subcutaneous, hemolymphatic, and meningoencephalitic (chronic) stage

Gambian TrypanosomiasisClinical manifestationsSubcutaneous stage: local inflammation in the biting site (raises after about 3 wks), leads to primary chancre

Gambian TrypanosomiasisClinical manifestationsHematogeneous stage: fever, malaise, anorexia, headache, and postcervical lymphadenopathy (Winterbottoms sign)

Gambian TrypanosomiasisClinical manifestationsChronic stage: expresses 6-12 months after the first onset: increased fatigue, mental dullness to somnolence. Sleepiness progresses to coma and eventually death.

Gambian TrypanosomiasisTreatmentSuccessful treatment depends on early patient managementDrugs commonly used: pentamidine, suramin, melarsoprolPentamidine is used for early stage, admministerde by im injectionSuramin is for early stage by ivMelarsoprol is for chronic stage by iv administration

Trypanosoma rhodesienseGeneralCauses East African trypanosomiasisVector: Tse Tse fly (Glossina morsitans)Final host: humansReservoir host: antelopes (wild animal)Morphologically similar to the proceeding species

Rhodesian TrypanosomiasisClinical manifestationsEast African sleeping sicknessVectored by Glossina pallidipes, G. morsitans, and G. swynnertoniThe stages of diseases and symptomatology parallel those of prior trypanosomiasis; only the disease progresses rapidly and has shorter clinical courseThe entire course may take only 9-12 months

Rhodesian TrypanosomiasisDiagnosis and TreatmentThe diagnosis is made in the same manner as the prior oneThe drugs used in rhodesian trypanosomiasis are also the samePrognosis is poor since the clinical course is shorter

Immunoregulation:Trypanosome EliminationAntibody mediatedDestruction by Kupffer cellsSplenic macrophages minor role (cf malaria)Uptake - C3b - C3bi - direct?C mediated lysis not importantTrypanosome destroyed within minutes

ImmunoregulationNo secondary response to VSGs unless cured by chemotherapyFailure of 1ry or 2ndry response prior to deathNon specific polyclonal activationSuppresser MacrophagesFailure of Ag presentationAnti idiotype responses

Immunoregulation:Variable Surface Glycoprotein60kd (450aa) glycoprotein (CHO 7-17%) C-terminal anchored in membraneOften as a dimer (alpha helix)Densely clustered 107molecules/parasiteOnly epitopes in end third of N-terminal exposedPresented as topographical arrayT-independent antigen

Immunoregulation:VSGConstant & Variable regionsRandom rearrangement of N terminal end (2/3)Almost no homology between V VSGsExcept cystein residues S-S bondsSwitching not initiated by IRBut selected

VSG Specific IR3-4 days post infection strong IgM responseTrypanosome disappear within hoursVSG specific IgG appears - not relevantIgM response often >IgGAfter several cycles VSG abs vanishBut abs to invariant ags remain elevated

Are you suffering from sleeping sickness?

Trypanosoma cruziGeneralCauses South American trypanosomiasis or Chagas diseaseVector: Triatomine bugFinal host: humansReservoir host: pets, rodents, monkeys, armadillosLiving in two forms in human body:trypanosoma form (trypomastigote) found in peripheral blood vesselsleishmania form (amastygote) found in muscles, brain, reticuloendothelial system, and lymph nodes

Trypanosoma cruziLife Cycle

Chagas DiseaseClinical manisfestationsMost victim is child under 5 yrs oldIn 1-2 wks, the itchy bite wound leads to a local inflammatory reactionThe inflammation blocks lymphatic flow and produces an erythematous primary lession called chagoma

Chagas DiseaseClinical manisfestationsIt develops to conjunctivitis and unilateral edema o/t face and eyelids called Romanas sign

Chagas DiseaseClinical manisfestationsAcute stage appears 4-14 dys later, characterized by fever and chill, malaise, myalgia, and fatigueAbdominal rash may also occurThe most severe symptoms are seen if CNS is involved

Chagas DiseaseClinical manisfestationsThe symptoms of chronic stage are dependent on the organ system affected and the extend of cellular damageCardiomegaly, dyspnea, and aphasia may occur due to the involvement of heart, lung, and CNS

Chagas DiseaseTreatment and PreventionDrugs of choice:NifurtimoxNifrofurazonePreventive action is the combination of disease and vector control

TrypanosomaLaboratory diagnosis :Microscopic examination : blood, lymphnode fluid, CNS fluid, biopsy of chancreConcentration techniques and serial examinations are frequently needed. Serologic testing , normally is used for screening purposes only

Leishmania spp.GeneralClass ZoomastigophoreaOrder KinetoplastidaFamily Trypanosomidae3 species known to be pathogenic in humans are:Leishmania donovaniLeishmania tropicaLeishmania braziliensis

Leishmania donovaniGeneralCauses leishmaniasis visceral, Kala-azar disease, black water feverFinal host: humansHabitat is humans reticuloendothelial cellsVector: Phlebotomus fly (sandfly)Reservoir host: canine

Sand flyThe Vector

Leishmania donovaniMorphologyDuring the life cycle, Leishmania has two stages: Leishmania stage (amastigote) found in humans and canines RE cellsLeptomonas (promastigote) stage found in vectors intestineAmstigote is rounded or ovoid, measured 2-4 microns, contains kinetoplast, blepharoplast, and rizoplast

Leishmania donovaniMorphologyPromastigotes

Leishmania donovaniLife Cycle

Leishmaniasis Cutaneous Leishmaniasis Mucocutaneous Leishmaniasis Visceral Leishmaniasis

LeishmaniasisEtiologic agentsCutaneous leishmaniasis:Oriental sore : is caused by Leishmania tropica complexDistributed in India and Middle East countriesVectored by Phlebotomus sandfly

Bay sore is caused by Leishmania mexicana complexExtends from southern Texas, Mexico, Central and South America Vectored by Lutzomyia sandfly

Mucocutaneous leishmaniasisCaused by Leishmania braziliensis complexVisceral leishmaniasisCaused by Leishmania donovani complex

Cutaneous LeishmaniasisClinical manifestations The clinical manifestations of both cutaneous leishmaniasis are similarIncubation period vary from several wks to three yrs

Cutaneous LeishmaniasisClinical manifestations The first sign is small red papule at the initial site of the insect biteFormation of crateriform lessionGenerally heal spontaneously, but may leave serious scarsContact spread of infection is possible

Cutaneous LeishmaniasisDiagnosis Specimen of choice is taken by aspiration or biopsy from the active lessionFinding amastigote form in microscopic examinationMontenegro (leishmanin) skin testSerologic test

Cutaneous LeishmaniasisTreatment and PreventionDrug of choice: sodium stibogluconate (antimony sodium gluconate: Pentostam), im for 10 daysAlternate choice: meglumine antimonate (Glucantime), amphotericin B, and ketoconazolePrevention lies in vector and reservoir control, as well as the other vector transmitted infections

Mucoutaneous LeishmaniasisGeneralEtiologic agents: Leishmania braziliensis complex

Vectored by Lutzomyia and Psychodopygus sandflies

Mucoutaneous LeishmaniasisClinical manifestationsIt tends to invade the mucous membrane of the mouth and nasopharynx by hematogenous or lymphatic transmissionPrimary lession develop in the same manner as oriental sore

Mucoutaneous LeishmaniasisClinical manifestationsClinical progression may take years, results in ulcers that erode soft tissue o/t face and palate

Mucoutaneous LeishmaniasisClinical manifestationsLeishmanioma

Mucoutaneous LeishmaniasisDiagnosis and TreatmentDiagnosis, treatment and preventive action is similar to cutaneous leishmaniasis

Visceral LeishmaniasisGeneralAlso known as kala azar or dum-dum feverThe most severe leishmania infectionCausative agents: Leishmannia donovani complex, parasitized the reticuloendothelial cells Distributed troughout India, Pakistan, Thailand, parts of Africa, and ChinaVectored by Phlebotomus and Lutzomyia sandfly

Visceral LeishmaniasisClinical manifestationsVariable incubation period, 3 wks to 2 yrsInfected macrophages migrate by lymphatic and hematogenous spread to distant lymphoid tissueProdromal symptoms include headache, malaise, fever, and weight lossThe fever may occurs periodically, mimicking malaria

Visceral LeishmaniasisClinical manifestationsPhysical examination: hepatosplenomegaly and lymphadenopathyHyperpigmentation o/t forehead and hands (kala azar) may be observedPrognosis of untreated cases is poor

Visceral LeishmaniasisDiagnosisTissue biopsy from spleen and liver demonstrating amastigote with Giemsa stainingSerologic examinationMontenegro skin test

Visceral LeishmaniasisTreatment and PreventionDrugs of choice: Pentostam and pentamidine isothionate (Lomidine)Alternate choice: amphotericin BCombination of allupurinol and Pentostam is effective Preventive actions include managing the vector and reservoir host

THANK YOU