ࡱ> %'"#$a ijbjb %{]"""""""zzzz8lz:((((((,`"(((((J""((JJJ(""("(6"X"""""(JXJ""1zzJINTESTINAL PROTOZOAEntamoeba histolyticaAmebic dysentery (bloody, mucus diarrhea) and liver abscessAcute: lower abdominal discomfort, flatulence, tenesmus, constipation Chronic: low-grade symptoms - occasional diarrhea, weight loss, fatigue 90% infected = asymptomatic carriers Amebic abscess of liver (ameboma): RUQ pain, weight loss, fever, tender, enlarged liverTransmission: ingestion of cysts via fecal-oral route in contaminated food & water (also oral-anal) Lifecycle: Ingestion of cysts (4 nuclei (central dot w/ dense peripheral chromatin & chromatoidal bars=ribosomes), nonmotile, rigid cell wall, nondividing, 10-20 microns in diameter) Trophozoites (motile, phagocytic for RBCs & bacteria, disease-causing, amorphous, 1 nucleus=located eccentrically w/ evenly distributed chromatin) excyst in small intestine (1 cyst 8 trophozoites) Trophozoites invade tissues of colon Trophozoites encyst in colon OR cause pathology (liver abscess, brain abscess, flask-shaped ulcer) Cysts are passed in fecesNo animal reservoir Trophozoites invade colonic epithelium & secrete enzymes local necrosis teardrop ulcer may disseminate, esp. to right lobe of liver where it causes abscesses worldwide (tropical, poor sanitation is most common) 1-2% in USAidentification of the organism in the stool or tissues via: O & P Test: trophozoites in diarrheal stool or cysts in non-diarrheal stool; note that there will not be large numbers of polymorphonuclear leukocytes in stool (vs. shigellosis, salmonellosis, ulcerative colitis) Biopsy Distinguish between: Entamoeba dispar (nonpathogenic, morphologically identical) by PCR or monoclonal Antibodies Entamoeba hartmani: cysts have 4 nuclei, but are <10 microns Entamoeba coli: cysts are same size as E. histolytica, but have 8 nucleiMetronidazole (Flagyl) = a mixed amebicide effective against both luminal and systemic forms of the disease plus a luminal amebicide like diloxanide furoate Avoid fecal contamination of food & water Observe good personal hygiene (hand washing) purify water supplies (boiling/filtration is effective, but chlorination is not) Giardia lamblia (a flagellate protozoan)GiardiasisNonbloody, foul-smelling diarrhea abdominal discomfort which may persist for weeks to months, foul-smelling flatulence, mild to severe diarrhea, anorexia No fever In some, intestinal malabsorption and/or lactose intoleranceTransmission: ingestion of cysts via fecally contaminated food & water (oral-anal contact as well) Lifecycle: Ingestion of cysts Trophozoites excyst in duodenum (1 cyst 2 trophozoites) Trophozoites attach to gut wall (surface of villi) but do NOT invade Trophozoites cause inflammation of duodenal mucosa malabsorption of protein & fat Trophozoites encyst in small intestine Cysts are passed in fecesWorldwide, but poor sanitation is high risk becoming more prevalent in USA: campers, children in day-care centers, male homosexuals 50% infected are asymptomatic carriers who pass cysts many species act as reservoirsO & P Test: trophozoites are pear-shaped w/8 external flagella (4 pairs), 2 anterior nuclei, parallel pair of axonemes, suction disk for intestinal attachment, median bodies are curved & located below the nuclei smiling face cysts are oval, 4 nuclei, pair of axonemes Duodenal sampling using String Test (Enterotest) No serologic test is availableMetronidazole (Flagyl) = a mixed amebicide effective against both luminal and systemic forms of the disease Avoid fecal contamination of food & water Observe good personal hygiene (hand washing) purify water supplies (boiling/filtration is effective, but chlorination is not) Cryptosporidium parvum (an Apicomplexan protozoan)Cryptosporidiosis (main symptom is diarrhea)Healthy adults: mild diarrhea Infants & Immunocompromised: watery, nonbloody diarrhea causing large fluid loss, fever, dehydration, weight loss may be fatal Transmission: fecal-oral transmission of oocysts from either human or animal sources Lifecycle: Ingestion of oocysts Sporozoites excyst in small intestine (1 oocyst 4 sporozoites) Sporozoites attach to surface of and infect columnar epithelial cells of sm. & lg. intestine do NOT invade Sporozoites replicate intracellularly in a membranous sac termed a trophozoite Multiplication by sexual & asexual cycles Sexual cycle generates the oocysts that are passed out in the fecesWorldwide, but poor sanitation is high risk Animal reservoirs: cattle & sheep US outbreaks attributed to inadequate purification of drinking waterO & P Test: Acid-fast stained fecal smear (modified Kinyoun acid-fast stain) oocysts stain an intense red & the granules are black Yeasts stain green No serologic test is availableNo effective drug therapy Metronidazole (Flagyl) may be used Avoid fecal contamination of food & water Observe good personal hygiene (hand washing) purify water supplies (boiling/filtration is effective, but chlorination is not) Cyclospora cayatanensis (Cyanobacterium-Like Body (CLB))Diarrhea that may last up to 6 wksHealthy adults: mild diarrhea Infants & Immunocompromised: watery, nonbloody diarrhea causing large fluid loss, fever, dehydration, weight loss may be fatal Transmission: fecal-oral transmissionWorldwide Most commonly found in travellers and immunocompromised adults 1996 outbreak due to contaminated raspberriesO & P Test: Cysts: round, 8-10 microns in diameter, stain acid variable, fluoresce blue under UV illumination Differential must include Cryptosporidium Microsporidia (Enterocytozoon bienusi & Septata intestinalis)Microsporidiosisrare infections of intestinal tract in humans associated with severe, persistent, watery diarrhea in AIDS patientsobligate intracellular replication and spore formation spores have spiral polar filaments which upon infection, extrude to allow penetration of the host cellGiemsa-stained: spore in feces spore in small bowel biopsyAlbendazole  UROGENITAL PROTOZOATrichomonas vaginalisTrichomoniasisWomen: watery, foul-smelling, greenish vaginal discharge accompanied by itching & burning over 50% infected are symptomatic Men: usually asymptomatic ~10% infected have urethritisTransmission: sexual contact (and hence no cyst needed) flagellated, central nucleus 4 anterior flagella, 5th recurrent flagellum, embedded in a mb Single form=mobile trophozoite (no cyst) can NOT survive outside the host No intermediate hosts does not make may basic molecules needed to maintain a living cell lacks mitochondria hydrogenosome (resemble mitochondria) and are site of action of metronidazole metronidazole is activated into its cytotoxic form in the hydrogenosomeextracellular parasite absorbs to epithelia of urogenital tract contact-dependent cytotoxicity inflammation of epithelial layer common cause of vaginitis worldwide 25-50% of US women harbor organism frequency of symptomatic disease is highest in sexually active women may affect pregnancy: premature rupture of fetal mbs, low birth weight, preterm deliverywet mount of vaginal (or prostatic) secretions, vaginal scrapings, urethral discharge, & sedimented urine pear-shaped trophozoites have a typical jerky motion no serologic testMetronidazole (Flagyl) for both partners condoms no prophylactic drug or vaccine is available BLOOD & TISSUE PROTOZOAPlasmodium (P. falciparum, P. vivax, P. malariae, P. ovale)Malaria P. falciparum & P. vivax account for >95% P. malariae ~4% P. ovale is very rare >200 million infected >1 million die each yrabrupt onset of fever & chills, HA, myalgias, arthralgias about 2 wks after mosquito bite (coincide w/ cycle between RBCs) periodic cycle of CHILLS, then FEVERS, then SWEAT (due to erythrocytic phase) develops several days after onset (note that parasites synchronize themselves) fever spike (37C to 41C) w/nausea, vomiting, & abdominal pain drenching sweats as fever breaks Splenomegaly (most) Hepatomegaly (1/3) Hemolytic Anemia (prominent) Renal damage, esp. P. falciparum GI problems Superinfections P. falciparum untreated: brain/kidney involvement may be fatal Other threee: usually self-limited P. vivax & P. ovale: Relapses may occur up to several yrs after initial illness due to hypnozoites latent in liver Recrudescence=controllable # of parasites remain latent in RBC and reactivate upon physical trauma/immunosuppressionTransmission: primarily by mosquito bites (female Anopheles); also, transplacentally, blood transfusion, IVDA Highlights of Lifecycle: Asexual cycle (schizogony schizonts) in humans (intermediate hosts) Sexual cycle (sporogony sporozoites) in mosquitoes schizogony=nuclear division without cell division P. vivax & P. ovale (48hr cycle)-benign tertian (recurs every 3rd day) P. falciparum (48hr cycle)-malignant tertian (every 3 days) P. malariae (72hr cycle)-benign quartan (every 4 days)pathogenesis mainly due to destruction of RBCs (merozoites & spleen) P. falciparum is more severe: children/elderly most @ risk Hg is degraded to provide aas for protein biosynthesis heme released Heme polymerase of plasmodium makes insoluble hemozoin (malarial pigment) Susceptibility: blacks < whites Sickle-cell trait provides protection from malaria (RBC does not support growth)Dx based on both thick (for presence of organisms) & thin (for species id) Giemsa-stained smears ring-shaped trophozoites can be seen within infected RBCs Diffs between P. falciparum & others: gametocytes are crescent-shaped, whereas others are spherical infects all RBCs higher parasitemia level (Note: P. vivax infects reticulocytes, whereas P. malariae infects mature RBCs only) produces more merozoites via asexual reproduction destroys more RBCs decrease in tissue oxygen is bigger problem sticky knobs cause adherence to & plugging-up of capillaries & vessels which may lead to life-threatening hemorrhage & necrosis (braincerebral malaria) extensive hemolysis/kidney damage hemoglobinuria dark urine = blackwater feverChloroquine for acute malaria kills merozoites does not affect hypnozoites Primaquine to prevent relapses kills hypnozoites Mefloquine or Quinine-Fansidar (sulfadoxine-pyrimethamine) combination for chloroquine-resistant strains of P. falciparumChemoprophylaxis for travellers (mefloquine OR chloroquine + Fansidar mosquito netting, window screens, protective clothing, insect repellents protection more imp. during the night drainage of stagnant waters partial immunity based on humoral antibodies that block merozoites from invading RBCs occurs in infected individuals determine what causes multi-drug resistance no vaccine Toxoplasma gondiiToxoplasmosis infects 10% of world intracellular parasite Apicomplexan, so has specialized structures @ anterior end of cell that aid in invasion (=rhoptries) Immunocompetent: most are asymptomatic/self-limiting chronic with cysts persisting for years some resemble infectious mononucleosis (heterophil negative) Congenital infection: abortion, stillbirth (1st trimester) neonatal disease w/encephalitis, chorioretinitis (blindness), & hepatosplenomegaly fever, jaundice, intracranial calcifications and hydrocephalus most infected newborns are asymptomatic though, BUT may develop chorioretinitis or mental retardation months to yrs later Immunosuppressed: life-threatening disseminated disease primarily encephalitisTransmission: contact with cat feces or ingestion of cysts in undercooked contaminated meat; also transplacental transmission Lifecycle: Domestic cat ingests cysts in raw meat (mice) Bradyzoites fromed in cat small intesttine Mucosal cells infected Male & Female gametocytes formed Gametocytes fuse to form oocysts which are then shed in cat feces Human ingests/makes contact with oocysts Cysts rupture in small intestine and release forms that invade gut wall through receptor mediated process Macrophages ingest into phagosomes where Toxoplasmosis inhibits lysosome fusion with phagosome Forms differentiate into rapidly multiplying trophozoites (=tachyzoites) Tachyzoites kill macrophages & invade others CMI limits spread Parasite enters host cells in brain, muscle, liver, eyes...where they develop into pseudocysts containing dormant organisms (bradyzoites)may infect any mammal & any nucleated cell High Risk Groups: Immunosuppressed Fetus: only if mother is infected for first time during pregnancy; 35-40% transmission rate, with 10% of those infants becoming symptomatic worldwide 1% of domestic cats in USA shed Toxoplasma cystsDx is based mainly on clinical manifestations, serologic procedures (IgM), the demonstration of cysts in tissues, or inoculation of infected materials into animals Tachyzoites have been found in bronchoalveolar lavage specimens from HIV pts. Acute & congenital: immunofluorescence assay for IgM antibody is used Microscopic examination of Giemsa-stained preps shows crescent-shaped tachyzoites with dark-staining nucleiCongenital (with or without symptoms) AND Immunocom- promised: sulfadiazine & pyrimethamine combination cook meat thoroughly to kill the cysts pregnant women should avoid undercooked meat & contact with cats (they should esp. refreain from emptying cat litter boxes) cats should not be fed raw meatPneumocystis carinii (actually a fungus)Pneumonia in immunocompromised (PCP) mortality rate >80% if untreated, ~50% if treated normally a commensal first disease diagnosed in >50% of AIDS pts worldwide (up to 70% of people have been infected)sudden onset of fever, cough, dyspnea, and tachypnea is typical of Pneumocystis pneumonia (an interstitial plasma cell pneumonia) bilateral rales & rhonchi chest X-ray diffuse interstitial pneumonia more gradual onset in infantsTransmission: airborne inhalation, spread by respiratory droplets; not transmitted from person-to-person though extracellular organism found in lungs Lifecycle: cysts inhaled into alveoli inflammatory response causes frothy exudate that blocks oxygen exchange organism does not invade lung tissue pneumonia results when host defenses are reducedHigh Risk Groups: premature infants infants under 3 months malnourished children immunosuppressedsputum specimen (usually less suitable) bronchial brushing/lavage or transbronchial biopsy Giemsa-stained lung smears: look for trophozoites & intracystic bodies (opposed comma-like particles) which are diagnostic no serologic test existsTrimethoprim-sulfamethoxa-zole Pentamidine & atovaquone are alternative drugsChemoprophylaxis with trimethoprim-sulfamethoxazole for immuno-compromised Trypanosoma cruziChagas disease (American trypanosomiasis) South & Central Americaacute phase: facial edema & a nodule (chagoma=Romaas sign) near the bite site fever, malaise, lymph-adenopathy, hepato-splenomegaly resolves in ~2 months Indeterminate Stage: no evidence of parasite in blood, or disease Most remain asymptomatic, but some progress to chronic phase (years to decades later): myocarditis/cardiomyopathy cardiac arrythmia & failure may lead to death megasyndrome - heart, esophagus, colon (megacolon) meningoencephalitis in AIDS pts.Transmission: through bite of reduviid bug (Triatoma & Rhodnius); also, ingestion of parasite, blood transfusions, & organ transplants Lifecycle: infected kissing bug bites & defacates Trypomastigotes contained in feces enter host (human, cat, dog, armadillo, rat) bloodstream local replication in macrophages & consequent infiltration result in chagoma Trypomastigotes form nonflagellated, round amastigotes within host cells (esp. myocardial, glial, reticuloendothelial cells) Amastigotes differentiate into trypomastigotes which are taken up by reduviid bug when it bites host trypomastigotes multiply & differentiate into epimastigotes in insect gut epimastigotes differentiate into trypomastigotes which are then passed in insect feces when it bites another victimmost common in children <10 yrs. old amastigotes can kill cells & cause inflammation (mainly mononuclear cells) cardiac muscle most frequently affected neuronal damage causes loss of tone and subsequent megasyndrome acute: trypomastigotes in blood & amastigotes intracellularly in tissues chronic: amastigotes predominate in tissueAcute: presence of trypomastigotes in thick or thin films of patients blood amastigotes seen in stained preparation of a bone marrow aspirate or muscle biopsy culture of the organism on special medium xenodiagnosis (uninfected, lab-raised reduviid bug bites host and is then analyzed for epimastigotes in gut) serology is helpful as well Chronic: difficult because there are few trypomastigotes in blood xenodiagnosis & serologyAcute: nifurtimox (kills trypomastigotes in the blood, but is much less effective against amastigotes in tissues) Chronic: no effective therapyprotection from bite of reduviid bug improved housing insect control no prophylactic drug or vaccine is avai lableTrypanosoma gambiense & Trypanosoma rhodesiense (T. brucei species)Sleeping sickness (African trypanosomiasis) T. gambiense in Western Africa; humans only = Anthroponosis; kills humans in months to years T. rhodesiense in Eastern Africa; disease of wild animals = Zoonosis; kills humans in weeks to months Both are found in Central Africainitial lesion is an indurated skin ulcer (trypanosomal chancre) at the site of the fly bite intermittent weekly fever & lymphadenopathy (due to antigenic variation) signs of infection include: myocarditis, gamma-globulinemia, generalized immunosuppression demyelinating encephalitis initially characterized by headache, insomnia, & mood changes, followed by muscle tremors, slurred speech, & apathy that progress to somnelence & coma untreated disease is usually fatal as a result of pneumoniaTransmission: through painful bite of tsetse fly (Glossina) Exhibit remarkable antigenic variation of their surface glycoproteins Lifecycle: Metacyclic trypomastigotes are injected into host when tsetse fly takes a blood meal Procyclic stage with multiplication occurs in insect midgut Migration to salivary glands Transform to epimastigotes Further multiplication yields metacyclic trypomastigotes Tsetse fly takes another blood meal and injects trypomastigotes into skin of host local multiplication w/inflammation Enter bloodstream Differentiate into blood-form trypomastigotes which multiply (and are taken up by another tsetse fly) may disseminate to LN/brainAntigenic variation allows for evasion of host humoral immune system Variant Surface Glycoprotein (VSG) 10% of parasite protein over 100 genes code, but only 1 is expressed at a time telomere-regulated effects & gene rearrangementsEarly stages: microscopic exam of blood reveals trypomastigotes aspirate of chancre or lymph nodes may reveal parasites Indications of Chronic Stage: trypanosomes in CSF, coupled with elevated protein level and pleocytosis (increased lymphocytes in CSF)Suramin - curative if given before onset of encephalitis (suramin does not cross BBB) Pentamidine as alternative CNS involvement: Suramin followed by melarsoprolprotection against fly bite, using netting & protective clothing clearing forest around villages & using insecticides no vaccineLeishmania donovaniKala-azar (visceral leishmaniasis) characteristic double peak (diurnal) of fever, hepatosplenomegaly, increase WBC count (pancytopenia) and gamma-globulin levels, & some immunosuppression intermittent weakness, weight loss , diarrhea, cough, nose bleeds, lymphadenopathy massive splenomegaly is characteristic hyperpigmentation of skin in light skinned patients (kala-azar = black-sickness) - post-kala-azar dermal lesions often remain after an apparent cure disease lasts months to years Eventually, anemia, leukopenia, & thrombocytopenia become more profound this induces weakness, infection, & GI bleeding Untreated severe disease is nearly always fatal due to 2 infection infantile form exists aroung Mediterranian SeaTransmission: through painless bite of sandfly (Phlebotomus in Old World, Lutzomyia in South America); ingestion of amastigotes in macrophages Lifecycle: female sandfly bites host to take a blood meal ingests macrophages containing amastigotes (no flagellum) Dissolution of macrophage in sandfly Amastigotes differentiate into promastigotes in the gut & multiply Migrate to sandfly pharynx Infect host with next bite Macrophages ingest promastigotes Promastigotes differentiate into amastigotes which reside in phago-lysosome of macrophage macrophages die & release amastigotes RES (liver, spleen, bone marrow) & other macrophages infectedRES most severely affected reduced BM activity & cellular destruction in spleen anemia, leukopenia, & thrombocytopenia 2 infections & bleeding attachment to macro-phage is mediated by 2 molecules on parasite: 1. gp63 (63kD-glyco-protein) 2. LPG (LipoPhospho-Glycan) AND one of several molecules on macro-phage: 1. Complement Receptor 3 2. LFA1 3. p150,95 Amastigotes are adapted to survive @ pH=4smears or culturing of white cells or bone marrow Detection of amastigotes in bone marrow, spleen, or lymph node biopsy organisms can be cultured very high IgG is indicative of infection (but not diagnostic) skin test using leishmanin (a crude homogenate of promastigotes) as antigen is available - positive in recovered pts, negative during active diseaseSodium stibogluconate -(an antimony derivative whose mech of action is unknown, but probably inhibits parasite glycolysis) Mortality rate is ~5% in treated individuals Recovery results in permanent immunityprotection from sandfly bites (netting, protective clothing, insect repellents) insecticides Leishmania tropica, Leishmania mexicana, & Leishmania braziliensisL. tropica (Old World) & L. mexicana (New World) both cause cutaneous leishmaniasis L. braziliensis (Central & South America only) causes mucocutaneous leishmaniasisCutaneous leishmaniasis: inital lesion is red papule @ bite site (usually on exposed extremity) lesion enlarges slowly (weeks to months) to form multiple satellite nodules that coalesce & ulcerate (raised edges, wet/dry crusty center) = Oriental sore, Chicleros ulcer... Immunocompetent = single lesion which usually heals in 6-12 months cellular mediated immunity Deficiency in CMI = lesions can spread to involve large areas of skin & contain enormous numbers of organisms (cf. leprosy) Mucocutaneous leishmaniasis: papule @ bite site which heals before mucocutaneous disease sets in metastatic lesions form, usually @ mucocutaneous junction of nose & mouth (mid- face) Disfiguring granulomatous, ulcerating lesions destroy nasal cartilage (but not bone) lesions slowly heal, if at all Death can occur due to 2 infection/starvation/aspiration pneumoniaTransmission: through painless bite of sandfly (Phlebotomus in Old World, Lutzomyia in South America); ingestion of amastigotes in macrophages Reservoir: forest rodents Lifecycle: (Similar to L. donovani) female sandfly bites host to take a blood meal ingests macrophages containing amastigotes (no flagellum) Dissolution of macrophage in sandfly Amastigotes differentiate into promastigotes in the gut & multiply Migrate to sandfly pharynx Infect host with next bite Macrophages ingest promastigotes Promastigotes differentiate into amastigotes which reside in phago-lysosome of macrophage macrophages die & release amastigotes along with lytic enzymestissue destruction is due to lytic products released from dying macrophages attachment to macro-phage is mediated by 2 molecules on parasite: 1. gp63 (63kD-glyco-protein) 2. LPG (LipoPhospho-Glycan) AND one of several molecules on macro-phage: 1. Complement Receptor 3 2. LFA1 3. p150,95 Amastigotes are adapted to survive @ pH=4presence of amastigotes in skin lesion smear leishmanin skin test becomes positive when the skin ulcer appearsSodium stibogluconate -(an antimony derivative whose mech of action is unknown, but probably inhibits parasite glycolysis) Results are frequently unsatisfactoryprotection from sandfly bites (netting, protective clothing, insect repellents) insecticides CESTODES (Tapeworms)Taenia solium (Pork tapeworm)Taeniasis (ingestion of larvae) & Cysticercosis (T. solium larvae upon ingestion of eggs) scolex of T. solium has 4 suckers and circle of hooks (a scolex is a rounded head which has suckers, hooks, or sucking grooves for attachment gravid proglottids of T. solium have 5-10 (<12) primary uterine branches (proglottids are segments which make up body of tapeworm; distal proglottids are gravid & produce eggs which are excreted in feces & transmitted)most pts w/adult tapeworms are asymptomatic (but anorexia & diarrhea can occur) Cysticercosis in brain causes headache, vomiting, & seizures Cysticercosis in eyes can appear as uveitis or retinitis, or the larvae can be visualized floating in the vitreous worldwide, but endemic in Mexico, Latin America, Spain, Portugal, Africa, India, SE Asia, China (Rarely in USA)Taeniasis: ingestion of raw, cured, or undercooked pork containing the larvae (=cysticerci) [a cysticercus consists of a pea-sized fluid-filled bladder w/ a single inverted scolex] in sm. intestine, larvae ingested from eating raw pork attach to gut wall and take ~3 months to grow into adult worms (up to 5m) gravid proglottids detach daily, are passed in feces, & accidentally eaten by pigs (=intermediate hosts) Human is definitive host Cysticercosis: (far more dangerous) Ingestion of eggs in food or water that has been fecally contaminated (human source always) Eggs hatch in small intestine embryos (oncospheres) burrow through wall into blood vessel disseminate to many organs (esp. brain & eyes & muscle & subcutaneous tissue) where they encyst to form cysticerci human is intermediate hostadult tapeworm attached to intestinal wall causes little damage cysticerci can become very large, esp. in brain, where they manifest as a space-occupying lesion subcutaneous: stationary masses (cf. lipomas) Ocular: aqueous or vitreous humor vision problems CNS: 1. parenchymal cysts seizures or mass effect 2. Meningeal involvement meningitis or hydrocephalus 3. Intraventricular cysts hydrocephalus 4. Spinal variety of symptoms living cysticerci do not cause inflammation when cysticerci die they may provoke inflammation & eventually calcifyID of gravid proglottids w/5-10 primary uterine branches in stool (differentiate between T. saginata whose gravid proglottids contain 15-20 primary uterine branches) Dx of cysticercosis = clinical picture + cyst seen in x-ray/CT scan/MRI + CSF serologyNiclosamide for intestinal worms (uncouples ox phos immobilization expulsion) Praziquantel for cysticercosis (increases parasite cell mb permeability to calcium antibody-mediated leukocyte killing) Albendazole as alternative to praziquantelcooking pork adequately prevent pigs from ingesting human feces treat all pts. (even when asymptomatic) to prevent autoinfection leading to cysticercosis observe proper hygiene (hand washing, etc. to prevent contamination of food w/eggs) Taenia saginata (Beef tapeworm)Taeniasis (ingestion of larvae) (Note that T. saginata larvae do not cause cysticercosis in humans) scolex of T. saginata has 4 muscular suckers but NO HOOKLETS gravid proglottids of T. solium have 15-20 (>12) primary uterine branchesmost pts w/adult tapeworms are asymptomatic (but anorexia & diarrhea can occur) In some, proglottids appear in stools & may even protrude from anus (=most distressing) worldwide, but endemic in Africa, S. America, eastern Europe (Rarely in USA)Taeniasis: ingestion of raw or undercooked beef containing the larvae (=cysticerci) in sm. intestine, larvae ingested from eating raw pork attach to gut wall and take ~3 months to grow into a single adult worm (up to 10m) gravid proglottids detach daily, are passed in feces, & accidentally eaten by cattle (=intermediate hosts) *Human is definitive host embryos (oncospheres) emerge from eggs in cows intestine & burrow into blood vessel, where they are carried to skeletal muscle in muscle develop into cysticerci (=larvae) which can then be ingested by humanadult tapeworm attached to intestinal wall causes little damageID of gravid proglottids w/15-20 primary uterine branches in stool (differentiate between T. solium whose gravid proglottids contain 5-10 primary uterine branches) Dx of cysticercosis = clinical picture + cyst seen in x-ray/CT scan/MRI + CSF serologyNiclosamide for intestinal worms (uncouples ox phos immobilization expulsion)cooking beef adequately prevent cattle from ingesting human feces by disposing of waste properly Echinococcus granulosus (Dog tapeworm)Unilocular Hydatid Cyst Disease (caused by larva) ONLY 3 proglottids (=one of smallest tapeworms) Each protoscolex has the potential to become an adult worm many are asymptomatic hydatic cysts develop slowly Liver cysts may cause hepatic dysfunction/pain when they reach a critical size Lung cysts can erode into a bronchus bloody sputum, but are usually asymptomatic Cerebral cysts can cause headache and focal neurologic signs rupture of the cyst can cause fatal anaphylactic shock hydatic cysts can become secondarily infected w/ bacteria older cysts may calcifydog = definitive host sheep = intermediate host humans = dead-end intermediate hosts Lifecycle: 1000s of worms in dogs intestines liberate 1000s of eggs in dog feces & thereby contaminate environment (grass, etc.) eggs ingested by sheep (or humans) oncosphere embryos emerge in sm. intestine and migrate to liver (and sometimes then to lungs, bones, & brain) here, embryos develop into large fluid filled hydatid cysts inner germinal layer of hydatid cysts generates many protoscoleces within brood capsules liver containing hydatic cysts of slaughtered sheep (=entrails) are eaten by dogs and cycle continuesE. granulosus usually forms ONE large fluid-filled cyst (unilocular) that contains 1000s of individual scoleces + many daughter cysts individual scoleces @ bottom = hydatid sand cyst = space-occupying lesion cyst fluid contains parasite antigens, which can sensitize the host anaphylaxis if cyst ruptures Distribution: primarily in sheep-raising areas (S. America, Africa, Mediterranean area, Middle East, Central Asia, Australia, CA, AZ, NM, UT, Alaska, Can.ID of cysts via ultrasound, CT, MRI hydatic sand @ surgery is diagnostic Microscopic exam showing brood capsules containing many protoscoleces Serologic tests (indirect hemagglutination test) are useful, but may be falsely negative (15% of liver cysts & 50% of lung cysts have negative serology)Surgical removal of cyst using extreme care not to rupture cyst hypertonic saline should be injected into cyst to kill organisms & prevent accidental dissemination Albendazole is being evaluated for the prevention of spread of cysts following surgeryDo not feed entrails of slaughtered sheep to dogs! TREMATODES (Flukes)Schistosoma (S. mansoni, S. japonicum, S. haematobium) - Blood FlukesSchistosomiasis S. mansoni & S. japonicum affect gastrointestinal system (adults live in mesenteric veins) S. haematobium affects urinary tract (adults live in urinary bladder) Adults exist as separate sexes, but live attached to each other (female resides in a groove in the male = the schist) 200 million infected & 200 thousand death/yr (2nd to malaria) 2-30 yrs. is prime age for infection in endemic areasmost are asymptomatic chronic infections may become symptomatic Acute Phase (shortly after cercarial penetration): itching, dermatitis fever, chills, diarrhea, lymph-adenopathy, hepatosplenomegaly 2-3 wks later Intense eosinophilia in response to migrating larvae Resolves spontaneously Chronic: S. mansoni/S. japonicum = GI hemorrhage, hepatomegaly, massive splenomegaly; death by exsanguination of esophageal varices; chronic salmonella infections, cirrhosis, neurological problems S. haematobium = hematuria; superimposed bacterial UTIs, calcified bladder, carcinoma of bladder Swimmers Itch: due to penetration of the skin by cercariae of nonhuman schistosomes (bird-infective schistosomes), which are incapable of replicating in humans frequent problem of US lakesLifecycle/Transmission: Free-swimming, fork-tailed cercariae penetrate skin of humans (=definitive hosts) Cercariae differentiate to larvae (schistosomula) and enter the blood Schistosomula are carried via veins to arterial circulation (Superior Mesenteric artery portal system liver) Become adult flukes in liver S. mansoni & S. japonicum migrate against portal flow to reside in mesenteric venules, whereas S. haematobium adults reach the bladder veins through the venous plexus between the rectum & bladder Female adult lays fertilized eggs Eggs penetrate vascular endothelium to enter lumen (gut or bladder) Eggs are excreted (Feces or urine) Eggs hatch in fresh water and become ciliated larvae (miracidia) Miracidia penetrate snails (=intermediate hosts) Cercariae are formed in snails and then released to fresh water where they are able to penetrate human skineggs in liver, spleen, or wall of gut are responsible for most pathology Liver: eggs secrete antigens intense immune response granulomas impaired circulation fibrosis, hepatomegaly, & portal HTN splenomegaly hepatocytes undamaged function tests = normal Intestines: proteolytic enzymes & inflammatory response Bladder: granulomas fibrosus carcinoma of bladder Immune Response: Ab dependent, CD4+ mediated (IL-4, IL-10) IgE-dep macrophages IgE & IgG-dep eosinophils IgE-dep platelets/mast cells only schistosomula are susceptible to immune attack Schistosomes evade host defenses surface coated w/host antigens (C3 receptor, IgG receptor, maybe TNF-alpha receptor) SDIF (schistosome-derived inhibitory factor) strongly inhibits lymphocyte proliferationS. mansoni & S. japonicum: eggs in stool, blood in stool, rectal biopsy S. haematobium: eggs in urine, blood in urine, bladder biopsy Distinguish by egg morphology: S. mansoni eggs have a prominent lateral spine S. japonicum eggs have a very small lateral spine S. haematobium eggs have a terminal spine Distribution: S. mansoni: Africa, Middle East, Latin America (+Puerto Rico) S. haematobium: Africa, Middle East S. japonicum: Orient only (Phillipines, Thailand, Laos, Cambodia, China); water buffalo, pigs as reservoirsPraziquantel (all 3 species) prognosis is grave in cases of long duration & in malnourished children/people often exposed to cercariaProper disposal of human waste eradication of snail host avoid swimming in endemic areas INTESTINAL NEMATODES (Roundworms)Enterobius vermicularis (Pinworm)Enterobiasis (or Pinworm infection) adult female is 1cm in length w/pointed tail (hence the name pinworm)majority = asymptomatic perianal pruritis (most prominent symptom) scratching predisposes to 2 bacterial infection sometimes vaginal pruritis no evidence that it causes appendicitisTransmission/Lifecycle (humans only): ingestion of eggs or inhalation and eventual swallowing of eggs eggs hatch in small intestine larvae differentiate into adults and migrate to colon, cecum, & appendix Adult male & female live & mate in colon At night, female migrates & releases 1000s of fertilized eggs on the perianal skin & into environment eggs develop into larvae & become infectious within 6 hours reinfection can occur if they are carried to the mouth by fingers Worldwide most common helminth in USA <12yrs is most common group infected (ie. school children)Scotch tape technique to recover eggs from perianal skin Eggs are NOT found in stools small, whitish adult worms may be found in stools or near the anus of diapered childrenMebendazole OR Pyrantel pamoate (kill adult worms in colon, but not the eggs) Reinfection is very common Should treat twice (2 wks apart)NoneAscaris lumbricoides (Giant roundworm)Ascariasis very common - up to 1 billion infected (esp. in tropics) worldwide, esp. where sanitation is poor & human excreta are used as fertilizers in USA, southern states mostly affectedmost = asymptomatic Lung: inflammation w/an eosinophilic exudate transient pulmonary infiltrates & eosinophilia (Loefflers syndrome) ascaris pneumonia w/fever, cough, & eosinophilia can occur w/heavy larval burden GI: malnutrition w/heavy worm burden (esp. children) abdominal pain, diarrhea, intestinal obstruction Other: invasion of bile ducts may produce liver abscesses, cholangitis, bile duct obstruction, & pancreatitis worms may be vomited or migrate out nasopharynxTransmission/Lifecycle: humans are infected by eating embryonated eggs from fecally contaminated food or beverages, or from fomites or dirty fingers eggs hatch in small intestine larvae migrate through gut wall bloodstream lungs enter alveoli pass up the bronchi & trachea swallowed become adults within small intestine live in lumen, do NOT attach to wall, & derive sustenance from ingested food adults grow to 25cm or more (largest intestinal nematodes) 1000s of eggs laid/day (up to 200,000) passed in feces eggs form embryos in warm, moist soil humans ingest embryonated eggsmajor damage due to larval migration (rather than adult worm in intestine)detection of eggs in stool egg is oval with an irregular surface (bumpy outer coat, brownish in color) occasionally pt. sees adult worms in the stoolsMebendazole and Pyrantel pamoate are both effectiveproper disposal of feces can prevent ascariasis Ancylostoma duodenale & Necator americanus (Hookworms)Hookworm infection Ancylostoma = Old World hookworm Necator = New World hookworm Adult worms measure 1cm in lengthsymptoms proportional to worm burden loss of blood accounts for major damage (up to 0.1 - 0.3mL per worm per day) microcytic anemia weakness & pallor (esp. malnourished, iron deficient) Ground itch = pruritic papule or vesicle, can occur at larval site of entry on skin transient pulmonary infiltrates & eosinophilia (Loefflers syndrome) during larval migration through lung pneumoniaTransmission/Lifecycle: humans infected when larvae in moist soil penetrate the skin (usually feet or legs); A. duodenale may also be acquired by ingestion of larvae enter bloodstream lungs alveoli bronchi & trachea swallowed develop into adults in small intestine attach to wall w/ either cutting plates (Necator) OR pairs of teeth (Ancylostoma) feed on blood from capillaries of intestinal villi 1000s of eggs/day passed in feces eggs develop first into noninfectious, feeding (rhabditiform) larvae & then into third-stage, infectious, nonfeeding (filariform) larvae filariform larvae penetrate skinworm makes an anticoagulant worldwide, esp. tropical areas (warm, moist, poor sanitation) 1/4 worlds population thought to be infected in USA, Necator is endemic in soutern statesDetection of eggs in stool (eggs of two are indistinguishable) differentiate from Strongyloides larvae occult blood frequent in stools eosinophilia is typicalMebendazole and Pyrantel pamoate are both effectivedispose of sewage properly wear shoes Strongyloides stercoralis (Small Roundworm)Strongyloidiasis up to 100 million infections adult females are 2-3mm in lengthmost are aymptomatic (esp. low worm burden) adult female worms in wall of sm. intestine inflammation watery diarrhea Autoinfection: penetrating larvae may cause sufficient damage to the intestinal mucosa that sepsis due to enteric bacteria can occur Hyperinfection: large numbers of larvae transform into infective stages & invade intestine severe, possibly bloody diarrhea Lung: larvae may produce pneuminitis, cough, wheezing, transient pulmonary infiltrates & marked eosinophilia (Loefflers syndrome) similar to that caused by Ascaris Ground itch can occur @ site of larval penetration of the skin (as w/ hookworm) Disseminated strongyloidiasis / Hyperinfection in malnourished, debilitated, immunosuppressedTransmission/Lifecycle: (2 distinct lifecycles - human & soil) Infectious filariform larvae penetrate unbroken skin (usually feet) of human when direct contact is made w/ soil containing infective larvae Migrate to lungs alveoli bronchi & trachea swallowed small intestine in small intestine, larvae molt into adults adult females enter mucosa of duodenum & jejunum & produce eggs (without aid of fertilization by the male) eggs hatch within mucosa rhabditiform larvae (noninfective) rhabditiform larvae are passed in feces some larvae molt to form filarial larvae (infective), which penetrate the intestinal wall directly without leaving the host & migrate to the lungs (autoinfection) - esp. in immunosuppressed (AIDS, etc.) - may be fatal larvae passed in feces enter soil & can pass through entire life cycle (=free-living cycle) with filarial larvae being infectious to humansworldwide, but primarily in tropics - warm, humid environ-ments where sanitation is poor & soil is contaminated w/ human feces (SE Asia) in USA: endemic to SE statesLarvae in stool (Baermann technique, Harada-Mori technique) String test (EnteroTest) Eosinophilia may be striking Serology not helpful (cannot distinguish between current & past infections)Thiabendazole (interferes w/ synthesis of microtubules and decreases glucose uptake; severe toxicity though)Proper disposal of sewage wear shoes! TISSUE NEMATODES (Roundworms)Wuchereria bancrofti and Brugia malayi (thin thread-like worms)Filariasis Brugia malayi causes filariasis in Malaysia 80 million infected, 900 million @ riskSpectrum of disease dependent on worm burden early = asymptomatic microfilariae do not cause symptoms later filarial fevers, tropical pulmonary eosinophilia, lymphangitis, cellulitis, back/headaches adult worms die in lymph nodes inflammation, fibrosis, and calcification around dead adult obstruction of lymphatic vessels edema of legs & genitalia Elephantiasis in pts. who have been repeatedly infected over a long period Lymph glands can develop hydrocaele rupture Chyluria (milky white urine)Transmission/Lifecycle: Female mosquito (esp. Anopheles, Aedes, Culex) deposits infective larvae (L3 larva) on human skin while biting larvae penetrate skin enter lymph node in 3-6 months, larvae mature to adults that produce microfilariae (L1 stage larva) microfilariae circulate in blood (esp. @ night=nocturnal periodicity) & are ingested by biting mosquitoes within mosquito, microfilariae produce infective larvae that are transferred with the next bite (L2 larva in muscle, L3 larva in salivary gland) humans = only definitive host adult worms live in lymph nodes for 5-8 yrs.humid tropics follows distribution of mosquitoesthick blood smears taken from the pt @ night reveal the microfilariae Microfilaria are sheathed in both Brugia & Wuchereria, but can be distinguished by nuclei in the tail: Brugia - 2 Wuchereria - 0 Diethylcarbamazine may help in dx by providing a provocative challenge which induces microfilaria to migrate from deep vessels to peripheral vesselsDiethylcarba-mazine (micro-filariae only) - [alters surface mbs paralysis & increased susceptibility to host defenses] No drug therapy for adult worm is availableMosquito control w/ insecticides, protective clothing, netting, repellentsOnchocerca volvulusOnchocerciasis Millions affected in Central Africa (nodules on lower body) & Central America (nodules on upper body) infection rates >80% in endemic areas male=5cm female=up to 50cmInflammation in subcutaneous tissue death of microfilaria in subcutaneous tissue itching (pruritis), rashes, & pigmentation changes edema of surrounding area fibrosis around dead cells thickening of skin & loss of elasticity onchocercal dermatitis & hanging groin microfilariae in eyes can lead to blindness (river blindness, because blackflies develop in rivers & people who live along those rivers are affected)Transmission/Lifecycle: Female blackfly (Simulium) deposits infective larvae on human skin while biting larvae enter wound migrate into subcutaneous tissue differentiate into adults and live as a pair within dermal (subcutaneous) nodules (for 10-15yrs) female produces microfilariae which are not sheathed microfilariae migrate through subcutaneous tissue concentrate in eyes microfilariae ingested by another blackfly infective larvae develop from microfilariae in blackfly Humans = only definitive hostdisease is due to a cellular immune response to the death of microfilaria major cause of blindnessbiopsy of affected skin reveals microfilariae in these skin snips examination of blood is NOT useful microfilariae do NOT circulate in bloodIvermectin (microfilariae only) - [stimulates the Cl- channel GABA receptor complex to cause muscle paralysis] sterilizes females for 6 months Suramin kills adult, but is very toxic - used for eye involvement Skin nodules removed surgically, but normally not curativeControl of blackfly w/ insecticides Ivermectin prevents the disease Do not give diethylcarbamazin - it would increase pathology of diseaseLoa loa (African eye worm)Loiasis Only in tropical Central & West Africa (habitat of deerfly) adults = 3-7cmCalabar swellings = transient (2-3 days), localized, erythematous, subcutaneous edema Adult worm crawling across the conjunctiva of the eye (harmless, but disconcerting)Transmission/Lifecycle: Deerfly (mango fly - Chrysops) deposits infective larvae on human skin while biting larvae enter bite wound wander in body develop into adults females release microfilariae microfilariae enter blood (esp. during the day) microfilariae taken up by deerfly differentiate into infective larvae in deerflyno inflammatory response to the microfilariae or adults, but a hypersensitivity rxn is responsible for Calabar swellingsvisualization of sheathed microfilariae in blood smearDiethylcarba-mazine eliminates microfilariae & may kill the adults Worms in eyes may be removed surgicallyControl deerfly with insecticidesDracunculus medinensis (Guinea Worm)Dracunculiasis large areas of tropical Africa, India, & Pakistaninflammation, blistering, & ulceration of the skin (usually lower extremities) inflamed papule/nodule burns & itches (=very painful) may become secondarily infectedTransmission/Lifecycle: Humans are infected when tiny crustaceans (copepods) containing infective larvae are swallowed in drinking water larvae are released in the small intestine migrate into body develop into adults (1 meter long!) meter-long female lives in a nodule at lower extremities of leg & produces motile larvae (also responsible for skin pathology) nodule erupts release of L1 larvae into environment (fresh water) copepods eat larvae larvae molt to form infective larvae (L3 stage) in copepod humans eat copepodsadult female produces a substance that causes clinical symptomsusually see the head of the worm in the skin ulcerTime-honored tx consists of gradually extracting the worm by winding it up on a stick over a period of days Niridazole or metronidazole makes the worm easier to extractFiltering or boiling drinking water P A R A S I T E S DISEASECLINICAL 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