ERITROSIT

KONSEP DASAR INFEKSI PARASITA. PENDAHULUANTujuan BelajarMahasiswa mampu menjelaskan:Klasifikasi ParasitRespon Imun pada infeksi parasitBeberapa penyakit infeksi parasit utamaImmunopathogenesisGejala klinisPemeriksaan laboratorium dan interpretasiPenatalaksanaanB. KLASIFIKASI PARASITHelminth = cacingProtozoaArthropoda = serangga Nemathelminthes =Cacing gilig/spt benangPlatyhelminthes =Cacing pipihPhylumClassNematodaCestodaTrematodaSarcomastigophora Apicomplexa FlagellataRhizopodaCiliataCiliophora SporozoeaB. KLASIFIKASI PARASITNematodaBentuk bulat memanjangKulit luar tidak bersegmenMemiliki rongga badanJenis kelamin terpisahMetamorfosis telur larva dewasaManusia berperan sbg hospes definitifHabitat cacing dewasa bisa di usus atau jaringanDitularkan secara langsung atau melalui vektor seranggaBentuk infektif bisa berupa stadium telur atau larva

B. KLASIFIKASI PARASITTrematoda

Bentuk spt daun =pipih dorsoventralBadannya dilapisi integumenMemiliki 2 batil isap untuk melekat pada tempat hidupnya (BIM dan BIPTidak memiliki rongga badanJenis kelamin sebagian besar hermaphrodit kecuali SchistosomaMetamorfosis telur larva dewasaManusia berperan sbg hospes definitifHabitat cacing dewasa bisa di usus atau jaringanDitularkan melalui vektor invertebrataBentuk infektif bisa berupa stadium larva cercaria/metacercaria

B. KLASIFIKASI PARASITCestoda

Bentuk spt pita = pipih dorsoventralTubuhnyanya terdiri dari bagian kepala (=scolex), leher dan badan (= strobila)Scolex memiliki alat mulut berupa batil isap atau lekuk isapStrobila bersegmen-segmen disebut proglotid terdiri dari 3 kelompok (proglotid immatur, matur, dan gravid)Tidak memiliki rongga badanJenis kelamin hermaphrodit pada setiap proglotidMetamorfosis telur larva dewasaManusia berperan sbg hospes definitif Habitat cacing dewasa bisa di ususBentuk infektif berupa stadium larva melalui atau tanpa hospes perantara

B. KLASIFIKASI PARASITFlagellata

Parasit sel tunggal Terdapat stadium trofozoit dan kistaTrofozoit memiliki flagel sebagai alat gerakKista mrp stadium reproduktif kecuali TrichomonasReproduksi aseksual dengan pembelahan biner longitudinalHabitat di usus(Giardia lamblia) atau jaringan (Trichomonas vaginalis, Trypanosoma, Leishmania)B. KLASIFIKASI PARASITRhizopoda

Stadium trofozoit, protoplasma tidak dibungkus membran yang disebut pseudopodiaSebagian besar hidup di alam bebas (Fam. Amoebidae), beberapa saja yang bersifat parasit (Fam. Endamoebiadae).Amoeba hidup bebas ada yang dapat menimbulkan kelainan pada otak manusiaGenus dibedakan dari bentuk inti spt Entamoeba, Endolimax, Iodamoeba

B. KLASIFIKASI PARASITSporozoea

tidak memiliki alat gerakpada salah satu tahapan dalam siklus hidupnya memiliki bentuk seperti sporaSeluruh jenis Sporozoa hidup sebagai parasitreproduksi secara aseksual dan seksualReproduksi aseksual dilakukan dengan pembelahan biner. Reproduksi seksual dilakukan dengan pembentukan gametContoh: Toxoplasma gondii, Plasmodium

B. KLASIFIKASI PARASITCiliata

Terdapat rambut getar ( silia ) Bentuk tubuhnya oval Memiliki dua inti, yaitu makronukleus dan mikronukleus Pembelahan binerAda yang hidup bebas ada juga yang hidup parasit

Habitat di usus (Balantidium coli)

D. PENYAKIT AKIBAT INFEKSI PARASITD.1. MALARIA40% of the worlds population lives in endemic areas3-500 million clinical cases per year1.5-2.7 million deaths (90% Africa)increasing problem (re-emerging disease)resurgence in some areasdrug resistance ( mortality)MALARIAAdalah penyakit infeksi disebabkan oleh parasit genus Plasmodium, ditularkan oleh nyamuk Anopheles, dengan gambaran klinis berupa demam intermitten, anemia, pembesaran limpa, atau dapat disertai berbagai kumpulan gejala oleh karena adanya komplikasi ke beberapa organ seperti otak, hati, dan ginjal.MALARIAP. falciparumP. vivaxP. malariaeP. ovalecausative agent = Plasmodium speciesprotozoan parasitemember of Apicomplexa4 species infecting humanstransmitted by anopholine mosquitoesLife Cyclesporozoites injected during mosquito feedinginvade liver cellsexoerythrocytic schizogony (merozoites)merozoites invade RBCsrepeated erythrocytic schizogony cyclesgametocytes infective for mosquitofusion of gametes in gutsporogony on gut wall in hemocoelsporozoites invade salivary glands

AnophelesTransmissionsporozoites injected with saliva enter circulationtrapped by liver (receptor-ligand)

Exoerythrocytic Schizogony

hepatocyte invasionasexual replication6-15 days1000-10,000 merozoitesno overt pathology

Hyponozoite Formssome EE forms exhibit delayed replication (ie, dormant)merozoites produced months after initial infectiononly P. vivax and P. ovale

relapse = hypnozoite

recrudescence = subpatenttErythrocytic Stageintracellular parasite undergoes trophic phaseyoung trophozoite called ring formingests host hemoglobincytostomefood vacuolehemozoin (malarial pigment)

Erythrocytic Schizogonynuclear division = begin schizont stage6-40 nucleibudding merozoites = segmentererythrocyte rupture releases merozoitesblood stage results in disease symptoms

Clinical Featurescharacterized by acute febrile attacks (malaria paroxysms)periodic episodes of fever alternating with symptom-free periodsmanifestations and severity depend on species and host statusimmunity, general health, nutritional state, geneticsrecrudescences and relapses can occur over months or yearscan develop severe complications (especially P. falciparum)

paroxysms associated with synchrony of merozoite releasebetween paroxysms temper-ature is normal and patient feels well falciparum may not exhibit classic paroxysms (continuous fever)Malaria Paroxysmtertian malariaquartan malaria

gametocyteserythrocytic schizogony48 hr in Pf, Pv, Po72 hr in PmGametocytogenesisalternative to asexual replicationinduction factors not knowndrug treatment #'simmune response #'sring gametocytePf : ~10 daysothers: ~same as schizogonysexual dimorphismmicrogametocytesmacrogametocytesno pathologyinfective stage for mosquito

Gametogenesisoccurs in mosquito gutexflagellation most obvious3X nuclear replication8 microgametes formedexposure to air induces temperature (2-3oC) pH (8-8.3)result of pCO2 gametoctye activating factor in mosquitoxanthurenic acid

Sporogony

occurs in mosquito (9-21 d)fusion of micro- and macrogametes zygote ookinete (~24 hr)ookinete transverses gut epithelium ('trans-invasion')Sporogonyookinete oocystbetween epithelium and basal laminaasexual replication sporozoitessporozoites released

Sporogonysporozoites migrate through hemocoelsporozoites 'invade' salivary glands

Invasive Stages

MerozoiteerythrocytesSporozoitesalivary glandshepatocytesOokineteepithelium

D.2. FILARIASISLymphatic Filariasis / ElephantiasisLoiasisOnchocerciasis (river blindness)para-lab by l. wafa menawi31

31para-lab by l. wafa menawi32Wuchereria bancrofti and Brugia malayi are filarial nematodesSpread by several species of night - feeding mosquitoesCauses lymphatic filariasis, also known as ElephantiasisCommonly and incorrectly referred to as ElephantitisWhat is it ?32para-lab by l. wafa menawi33Humans are the definitive host for the worms that cause lymphatic filariasisThere are no known reservoirs for W.bancrofti.B.malayi has been found in macaques, leaf monkeys, cats and civet cats

Definitive Host33para-lab by l. wafa menawi34W.bancrofti is transmitted by Culex, Aedes, and Anopheles speciesB.malayi is transmitted by Anopheles and Mansonia species.

AnophelesAedesCulex

MansoniaIntermediate Host34para-lab by l. wafa menawi35Endemic in 83 countries1.2 billion at riskMore than 120 million people infectedMore than 25 million men suffer from genital symptomsMore than 15 million people suffer from lymphoedema or elephantiasis of the legLymphatic Filariasis by the numbers35para-lab by l. wafa menawi36Adult: White and thread-like. Two rings of small papillae on the head.Female:5~10cm in lengthMale: 2.5~4cm and a curved tail with two copulatory spicules.

Morphology Ipara-lab by l. wafa menawi37Microfilaria: 177~296 m in length, a sheath with free endings. Bluntly rounded anteriorly and tapers to a point posteriorly. A nerve ring with no nuclei at anterior 1/5 of the body.

Wuchereria bancroftiBrugia malayiMorphology IIpara-lab by l. wafa menawi38B.malayi microfilariae are slightly smaller than those of W.bancrofti.Microfilariae are sheathed, and about 200 to 275 m.Not much is known about the adult worms, as they are not often recoveredOne distinctive feature of B.malayi is that the microfilarial nuclei extends to the tip of the tail

Morphology - B.malayi38para-lab by l. wafa menawi39The morphological differences between two microfilaria W.bancrofti B. malayi

Size 244~296 m 177~230 m Cephalic space Shorter LongerNuclei Equal sized Unequal sized clearly coalescing countable uncountableTerminal nucleus No Twopara-lab by l. wafa menawi40Host: Mosqutoes (intermediate host) Human (final host)Location: Lymphatics and lymph nodesInfective stage: Infective larvaeTransmission stage: MicrofilariaeDiagnostic stage: MicrofilariaeCharacteristic of life cyclepara-lab by l. wafa menawi41Life cycle

para-lab by l. wafa menawi42Wuchereria Life Cycle

42para-lab by l. wafa menawi43

43para-lab by l. wafa menawi44 Phenomen which the number of microfilariae in peripherial blood is very low density during daytime, but increase from evening to midnight and reach the greatest density at 10p.m to 2 a.m.May be related to cerebral activity and vasoactivity of pulmonary vessels. Nocturnal periodicitypara-lab by l. wafa menawi45 Larva deposited by mosquito biteTravel through dermis to lymphatic vesselsGrowth (approx 9 months) to mature worms(20-100mm long)Worms live 5-7 years (occasionally up to15 years)Mate->Microfilariae (1st stage larva)Females->release up to 10,000 microfilariae/day into bloodstreamMicrofilarie taken up by mosquito biteDevelop into 2nd and 3rd stage larva over 10-14 days inside mosquito vectorpara-lab by l. wafa menawi46Network of vessels that collect fluid that leaks out of the blood into tissues (lymph)Redirects lymph back into the blood stream

Lymphatic System46para-lab by l. wafa menawi47Initially asymptomaticSymptoms develop with increasing numbers of wormsLess than 1/3 of infected individuals have acute symptomsClinical Course is 3 phases:Asymptomatic MicrofilaremiaAcute Adenolymphangitis (ADL)Chronic/Irreversible lymphedemaSuperimposed upon repeated episodes of ADLClinical Course4747para-lab by l. wafa menawi48Presents with sudden onset of fever and painful lymphadenopathy Retrograde LymphangitisInflammation spreads distally away from lymph node group Immune mediated response to dying wormsMost common areas: Inguinal nodes and Lower extremitiesAcute ADL4848para-lab by l. wafa menawi49Inflammation spontaneously resolve after 4-7 days but can recur frequentlyRecurrences usually 1-4 times/year with increasing severity of lymphedemaSecondary bacterial infections in edematous(elephantatic) areasFilarial fever (fever w/o lymphangitis)Tropical Pulmonary EosinophiliaHyperresponsiveness to microfilariae trapped in lungsNocturnal Wheezing

para-lab by l. wafa menawi50LymphedemaMostly LE and inguinal, but can affect UE and breastInitially pitting edema, with gradual hardening of tissues hyperpigmentation & hyperkeratosisGenitaliaHydrocelesChronic Manifestations5050para-lab by l. wafa menawi51Renal involvement Chylurialymph discharge into urineLoss of fat and protein hypoproteinemia & anemiaHematuria, proteinuria from ?immune complex nephritisSecondary bacterial/fungal infections

Chronic Manifestationspara-lab by l. wafa menawi52

Elephantiasis: accumulation of lymph in extremeties, fibrosis, and thickening of skin.

para-lab by l. wafa menawi53Debilitates millions of humans by scarring eyes & causing permanent blindnessAffects people along rivers in West & Central Africa (native) & South America (introduced via slavery)Caused by Onchocerca volvulusAdult females are up to 500mm long & males up to 40mm longAdults live up to 14 yearsRestricted to humans (no known animal reservoirs)Transmitted by black flies (Simuliidae)Larvae live in fast-flowing water

Onchocerciasis (river blindness)para-lab by l. wafa menawi54Black flies ingest microfilariae from bloodMove from gut to flight muscles & mature into infective larvae (L3)L3 larvae migrate to head & enter humans via bite wound; mature into adults (2-4 months)Adults accumulate in subcutaneous nodules (1cm diameter) which dont cause much damageMating in nodules produces microfilariaeLive under skin causing rashes & wrinklesCause blindness when invade eyes tissues & die there

NodulesDamaged eye tissuesOnchocerciasis (river blindness)para-lab by l. wafa menawi55

para-lab by l. wafa menawi56Early stages of eye damage can be reversed by drug treatmentParasiticide ivermectin is most popularTransfer of worms affected by feeding behaviour of fliesWaggle mouth parts during biting to increase wound size & create pool of blood (pool feeders)Main vector = Simulium damnosumComplex of >40 sibling species in West & East AfricaNot all sibling species transmit wormsInsecticide applications used to control larvae in rivers

Onchocerciasis (river blindness)para-lab by l. wafa menawi57Caused by infection with Loa loa Adult worms move under human skinObserved beneath skin or passing through conjunctiva of eyes (eye worms)Worms = 2 races (attack humans or arboreal primates)Transmitted by horse flies (Tabanidae) in genus ChrysopsDay-feeding & forest-dwellingRare case of Tabanidae = biological vectorsDisease endemic to rain forest regions of West & Central AfricaGenerally mild & painless (chronic) with 10-15 year incubation periodMay cause swellings of skin (Calabar swelling)

Microfilariae in human bloodAdult in human eyeLoiasispara-lab by l. wafa menawi58

para-lab by l. wafa menawi59The standard method for diagnosing active infection is the identification of microfilariae by microscopic examinationHowever, microfilariae circulate nocturnally, making blood collection an issue

Diagnosis59para-lab by l. wafa menawi60A card test for parasite antigens requring only a small amount of blood has been developedDoes not require laboratory equipmentBlood drawn by finger stickUrinalysis, CBC and Comprehensive Chemistries Foot Biopsy: Normal Skin with areas of chronic inflammationDiagnosispara-lab by l. wafa menawi61Microfilariae are seen in blood smears and are DIAGNOSTIC

para-lab by l. wafa menawi62

Blood Smear - Microfilaria Note wavy microfilarial worm in the thick part of blood film. Dark blue structures are nucleiTail end tapering (no nuclei)Sheath covering worm.para-lab by l. wafa menawi63

Blood Smear - Microfilaria Note wavy microfilarial worm in the thick part of blood film. Head end of the worm rounded (no nuclei)(Sheath is not clearly seen)para-lab by l. wafa menawi64

Blood Smear - Microfilaria Note wavy microfilarial worm in the thick part of blood film. Dark blue structures are nucleiTail end - tapering sheath (no nuclei)para-lab by l. wafa menawi65

Hydrocele fluid cell block. Note wavy microfilarial worms. Inflammatory cells lymphocytes.Hemorrhagic fluid sedimentpara-lab by l. wafa menawi66

Hydrocele fluid cell block. Note wavy microfilarial worms. Inflammatory cells lymphocytes.RBCpara-lab by l. wafa menawi67

Hydrocele fluid cell block. Note wavy microfilarial worms. Inflammatory cells lymphocytes.RBCpara-lab by l. wafa menawi68

Hydrocele fluid cell block. Inflammatory cells lymphocytes.RBC Microfilaria. para-lab by l. wafa menawi69As with malaria, the most effective method of controlling the spread of W.bancrofti and B.malayi is to avoid mosquito bitesThe CDC recommends that anyone in at-risk areas:Sleep under a bed netWear long sleeves and trousersWear insect repellent on exposed skin, especially at nightControl69para-lab by l. wafa menawi70Covering water-storage containers and improving waste-water and solid-waste treatment systems can help by reducing the amount of standing water in which mosquitoes can lay eggs.Killing eggs (oviciding) and killing or disrupting larva (larviciding) in bodies of stagnant water can further reduce mosquito populations.Vector control70para-lab by l. wafa menawi71Treatment of filariasis involves two components:Getting rid of the microfilariae in people's blood Maintaining careful hygiene in infected persons to reduce the incidence and severity of secondary (e.g., bacterial) infections. Treatment71para-lab by l. wafa menawi72Anti-filariasis medicines commonly used include:Diethylcarbamazine (DEC) reduces microfilariae concentrations kills adult worms Albendazole kills adult wormsIvermectin kills the microfilariae produced by adult worms Drugs, Drugs, Drugs!72para-lab by l. wafa menawi73The disease is usually treated with single-dose regimens of a combination of two drugs, one targeting microfilariae and one targeting adult worms (i.e.,either diethylcarbamazine and albenadazole, or ivermectin and albendazoleIn some areas, DEC laced table salt is used as a prophylacticAnd more drugs!73