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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
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