Lecture 26: Parasitology

• Pathogen: Entamoeba histolytica (invasive protozoan). Morphologically identical species E. dispar, E. moshkovskii, E. bangladeshi are commensals only.
• Transmission: fecal-oral — contaminated water/food; oral-anal sex (MSM).
• Life cycle: ingest quadri-nucleate cyst → excystation in bowel lumen → uni-nucleate trophozoite (invasive form) → trophozoite either re-encysts (asymptomatic passer) or adheres via Gal/GalNAc-specific lectin → invades colonic mucosa → can spread to liver → abscess.

• ~34–50 million cases worldwide, 100,000 deaths/yr.
• Endemic in Central/South America, Africa, India.
• 3rd most common parasitic infection in the U.S. (immigrants, travelers, MSM).
• More severe disease in: young children, elderly, steroids/immunocompromised, pregnancy.

Workflow: for suspected liver abscess → CT/US + serology (most useful — positive in >90% convalescent). Abscess Gram stain is sterile.

• Invasive disease (colitis or liver abscess): Metronidazole (or tinidazole) — kills tissue trophozoites.
• Follow with a luminal agent to eradicate cysts: paromomycin (or diloxanide furoate, iodoquinol). Cysts do NOT respond to metronidazole — ~40–60% persist.
• Asymptomatic cyst passer: paromomycin alone.

• Pathogen: Giardia lamblia (a.k.a. G. intestinalis, G. duodenalis). Flagellated protozoan; trophozoites have a classic "falling leaf" motility with a central pear-shaped body and 2 nuclei ("smiley face").
• Transmission: fecal-oral ingestion of cysts.
• Life cycle: cyst → excystation in duodenum → trophozoites adhere to duodenal/jejunal villi via ventral sucking disk (no invasion!) → blunt villi → malabsorption → new cysts pass in stool.

• Most commonly identified intestinal parasite in the U.S. (4–7% of stools).
• Transmission: recreational fresh water (lakes, streams, untreated well water) — beavers are a classic reservoir.
• Other: day care centers, MSM sexual transmission, international travel.
• Host risk factors: IgA deficiency / CVID, hypo/achlorhydria (PPI, post-gastrectomy).

• Incubation 1–2 weeks.
• Syndromes: asymptomatic cyst passage → acute self-limited diarrhea → chronic diarrhea with malabsorption.
• Classic features: foul-smelling, greasy, non-bloody diarrhea, bloating, flatulence, crampy abdominal pain, weight loss.
• Post-giardia lactose intolerance is common (disaccharidase loss from villous blunting).

• Diagnosis:
  • Stool O&P (1 stool 60–80%; 3 stools >90%) — shedding is intermittent.
  • Stool Giardia antigen EIA (85–95% sens / 90–100% spec) — often first-line now.
• Treatment: tinidazole or metronidazole (first line); alternatives: nitazoxanide, albendazole.

• Pathogen: Cryptosporidium parvum and C. hominis (most common human species).
• Transmission: ingestion of infectious oocysts (already sporulated, infectious on excretion).
• Life cycle: oocyst → sporozoites released → invade intestinal epithelial cells but remain in a parasitophorous vacuole at the microvillus border (intracellular but extracytoplasmic) → asexual → sexual cycles → both thick-walled oocysts (environmental spread) and thin-walled oocysts (autoinfection).

• Oocysts are infectious at very low inocula and resistant to chlorine — why it causes large water-park / municipal water outbreaks.
• Classic U.S. outbreak: Milwaukee 1993 (~403,000 infected via city water supply).
• Sources: agricultural runoff, well water, pools/water parks, day care centers, person-to-person.
• Most severely affected: children and patients with depressed cellular immunity (AIDS, CD4 <100).

• Immunocompetent: self-limited watery diarrhea, cramps, nausea, low-grade fever; lasts 5–10 days.
• Immunocompromised (HIV/AIDS, CD4 <50): chronic, severe, secretory diarrhea → weight loss, malabsorption, electrolyte abnormalities.
• Extraintestinal disease (AIDS): AIDS cholangiopathy (sclerosing-cholangitis-like biliary disease), pancreatitis, pneumonitis.

• Diagnosis: not seen on routine O&P. Order:
  • Modified acid-fast (Ziehl-Neelsen) stain of stool → small (~5 µm) red oocysts.
  • Cryptosporidium stool antigen / PCR.
• Treatment:
  • Immunocompetent: supportive care; nitazoxanide shortens illness.
  • AIDS: antiparasitics alone are not curative — ART to restore CD4 is the definitive treatment.

• Transmission: bite of the female sandfly (Phlebotomus Old World; Lutzomyia New World).
• Life cycle: sandfly injects promastigotes → taken up by macrophages → transform into amastigotes (no flagellum) inside phagolysosomes → replicate → infect other reticuloendothelial cells.
• Histopath buzz: amastigotes in macrophages on Giemsa = small round bodies with a rod-shaped kinetoplast next to the nucleus.

Cutaneous Leishmaniasis

• Painless non-healing ulcer at bite site with raised/rolled indurated borders.
• Weeks-to-months after exposure; often on exposed skin (face, arms).

Mucosal Leishmaniasis (Espundia)

• Erosive destruction of mucosal surfaces (nose, oropharynx, larynx) — can follow cutaneous disease years later.
• Predominantly South America (L. braziliensis).

Visceral Leishmaniasis (Kala-azar)

Severe in AIDS, transplant, and malnourished patients. May cause GI diarrhea in AIDS. Can be fatal if untreated.

• Diagnosis:
  • Cutaneous/mucosal: biopsy or scraping with Giemsa stain → amastigotes; PCR/culture.
  • Visceral: splenic aspirate (highest yield) or bone marrow aspirate; serology (rK39 rapid test); PCR.
• Treatment:
  • Visceral → liposomal amphotericin B (U.S. first line).
  • Alternatives: pentavalent antimony (stibogluconate; risk of pancreatitis, arrhythmia), miltefosine, pentamidine.
  • Selected cutaneous: fluconazole or ketoconazole.

• Pathogen: Trypanosoma cruzi.
• Vector: blood-sucking triatomine (“kissing / reduviid”) bug.
• Life cycle: bug bites face/mucous membranes and defecates at the bite; rubbing the feces into the wound introduces trypomastigotes → invade host cells → amastigotes replicate in muscle/neural tissue (heart, GI autonomic ganglia) → trypomastigotes recirculate.
• Other transmission: blood transfusion, solid organ transplant, congenital.

• Endemic: Mexico, Central and South America (most prevalent in rural poverty).
• Only 10–30% of infected patients develop chronic Chagas disease (often years to decades later).

Acute Chagas

• Romaña's sign — unilateral painless periorbital/eyelid swelling from ocular inoculation.
• Chagoma (indurated nodule at bite site), fever, lymphadenopathy, hepatosplenomegaly.
• Rarely: myocarditis, meningoencephalitis (can be fatal, especially in children).

Chronic Chagas (10–30% of infected, >10 yrs later)

• Dilated cardiomyopathy (apical aneurysm, heart block, arrhythmias, HF, sudden cardiac death). Typically right ventricle involved prominently.
• Megaesophagus — dysphagia mimicking achalasia (destruction of enteric plexus).
• Megacolon — chronic constipation, sigmoid volvulus risk.

• Diagnosis:
  • Acute: trypomastigotes on Giemsa-stained peripheral blood smear; PCR.
  • Chronic: serology (need 2 different assays for confirmation).
• Treatment: benznidazole (first-line in U.S.) or nifurtimox — most effective in acute and early chronic disease.
• Chronic cardiomyopathy / mega-syndromes managed symptomatically (pacemakers, surgery).

1. Female Anopheles bites (dusk–dawn) → injects sporozoites into bloodstream.
2. Sporozoites travel to liver → invade hepatocytes → mature into tissue schizonts (or persist as hypnozoites in vivax/ovale).
3. Schizont rupture releases 10,000–30,000 merozoites into blood → invade RBCs.
4. Asexual blood cycle every 48h (falciparum, vivax, ovale) or 72h (malariae) → synchronized cytokine release = paroxysms (chills → fever → sweats).
5. Some parasites form gametocytes → taken up by mosquito → sexual cycle → new sporozoites.

• General: cyclic fevers, chills, rigors, sweats, headache, hemolytic anemia, thrombocytopenia, jaundice/abnormal LFTs, splenomegaly.
• Tertian malaria (q48h): P. vivax, ovale, falciparum.
• Quartan malaria (q72h): P. malariae.
• P. falciparum typically has persistent/daily fevers (not truly cyclic).

Severe / Complicated P. falciparum (>5% parasitemia or organ dysfunction)

• Cerebral malaria (altered mental status, seizures, coma).
• Lactic acidosis.
• Hypoglycemia.
• ARDS.
• Acute kidney injury / "Blackwater fever" (massive intravascular hemolysis with hemoglobinuria).

Why is falciparum so severe? RBCs cytoadhere and sequester in microvasculature of vital organs (brain, kidney) — and falciparum can infect RBCs of all ages, producing very high parasitemia.

• Thick & thin blood smears × 3 (Giemsa) — thick for screening/parasitemia, thin for species ID.
• Rapid diagnostic tests (RDTs) detect HRP-2 or pLDH antigens.
• PCR for species confirmation / low parasitemia.

Smear Clues

• P. falciparum: small ring forms, multiple rings in one RBC, banana-shaped gametocytes, high parasitemia.
• P. vivax / ovale: enlarged RBCs with Schüffner's dots; irregularly-shaped trophozoites.
• P. malariae: band-form trophozoites.

• Chloroquine-sensitive regions: Dominican Republic, Haiti, Middle East, Central America west of Panama Canal. Everywhere else assume resistance.

• Pathogen: Babesia microti (intraerythrocytic protozoan).
• Vector: Ixodes scapularis tick (same as Lyme & Anaplasma — co-infection common).
• Geography: New England (esp. Cape Cod, Nantucket), Mid-Atlantic, upper Midwest, northern California.
• Other transmission: blood transfusion.
• Severe disease risk factors: asplenia, elderly, immunocompromised.

• Fever, chills, myalgias, fatigue.
• Hemolytic anemia, thrombocytopenia, elevated AST/ALT.
• Severe: ARDS, DIC, hemoglobinuria, AKI.
• 20% co-infection with Borrelia burgdorferi (Lyme); also with Anaplasma.

• Diagnosis: Giemsa-stained peripheral smear → intraerythrocytic ring forms; pathognomonic “Maltese cross” tetrads (4 merozoites in a cross). No RBC pigment (unlike malaria). PCR and serology available.
• Treatment:
  • Mild/moderate: atovaquone + azithromycin.
  • Severe: quinine + clindamycin; consider RBC exchange transfusion if parasitemia >10% or organ failure.

Nematodes (roundworms) are acquired by three dominant routes. Remembering the route immediately narrows diagnosis and therapy.

• Pathogen: Ascaris lumbricoides; adult worms up to 30 cm long.
• Transmission: fecal–oral ingestion of embryonated eggs from contaminated soil/produce.
• Life cycle: eggs hatch in small intestine → larvae penetrate gut wall → portal vein → liver → lungs (Loeffler pneumonitis) → coughed up and swallowed → mature into adult worms in jejunum.

• Most prevalent helminth worldwide — >1 billion infected.
• Endemic in tropics with poor sanitation; often coinfection with Trichuris & hookworm.

• Pulmonary phase (larval migration): Loeffler syndrome — cough, wheeze, transient pulmonary infiltrates with eosinophilia.
• Intestinal phase: abdominal pain, malnutrition.
• Heavy burden: bowel obstruction (classic pediatric vignette), biliary/pancreatic duct obstruction, cholangitis, pancreatitis.

• Diagnosis: stool O&P — characteristic knobby/mammillated eggs.
• Treatment: albendazole or mebendazole (single dose).

• Pathogen: Trichuris trichiura.
• Transmission: fecal–oral ingestion of embryonated eggs. No tissue/lung migration.
• Life cycle: adults embed into the cecum/colon mucosa.

• Light infection: usually asymptomatic.
• Heavy pediatric burden: chronic bloody diarrhea, anemia, and rectal prolapse (classic board clue).

• Diagnosis: football-shaped eggs with bipolar plugs on stool O&P.
• Treatment: albendazole or mebendazole × 3 days.

• Pathogens: Ancylostoma duodenale and Necator americanus.
• Transmission: filariform larva penetrates intact skin (often bare foot) on warm, moist soil.
• Life cycle: skin → blood → lungs → coughed up & swallowed → adult worms attach to small-intestinal mucosa and suck blood.

• “Ground itch” at site of skin entry.
• Chronic blood loss → iron-deficiency microcytic anemia (cardinal feature); in pregnancy/children may cause failure to thrive.

• Diagnosis: stool O&P (ovoid, thin-shelled eggs).
• Treatment: albendazole or mebendazole; iron replacement.

• Pathogen: Enterobius vermicularis.
• Transmission: fecal–oral via ingested eggs; autoinfection from scratching.
• Life cycle: gravid female migrates to perianal skin at night to lay eggs → intense pruritus ani → scratching spreads eggs.

• Most common helminthic infection in the United States.
• Especially common in school-age children; spreads rapidly within households.

• Nocturnal perianal itching is the hallmark; may be asymptomatic.
• Occasional vulvovaginitis or secondary bacterial infection from scratching.

• Diagnosis: Scotch-tape test → flattened, D-shaped eggs.
• Treatment: albendazole or pyrantel pamoate; repeat in 2 weeks; treat entire household.

• Pathogen: Strongyloides stercoralis.
• Transmission: filariform larva penetrates skin → lungs → gut.
• Unique feature — autoinfection: larvae can transform into the infectious filariform form within the host and re-penetrate the gut wall or perianal skin, sustaining infection for decades.

• Chronic infection: often subclinical; intermittent abdominal pain, diarrhea, urticaria, and larva currens (serpiginous migratory rash).
• Hyperinfection / disseminated disease: in immunocompromised hosts (corticosteroids, organ transplant, HTLV-1). Presents with gram-negative bacteremia/meningitis (from bowel translocation), ARDS, and high mortality.

• Diagnosis: stool agar plate culture or serology — O&P is insensitive (intermittent shedding). Suspect in any immigrant/refugee with unexplained eosinophilia.
• Treatment: ivermectin (first line). Screen before chronic steroids or transplant.

• Pathogens: Toxocara canis and T. cati.
• Transmission: ingestion of eggs from dog/cat feces (pica — toddlers eating dirt or sandbox exposure).
• Life cycle: larvae migrate systemically; humans are a dead-end host (no adult worms).

• Visceral larva migrans: hepatosplenomegaly, fever, eosinophilia, pulmonary infiltrates.
• Ocular larva migrans: unilateral retinal granuloma mistaken for retinoblastoma → vision loss.

• Diagnosis: serology (ELISA).
• Treatment: albendazole ± corticosteroids for ocular disease.

• Pathogen: Trichinella spiralis.
• Transmission: ingestion of encysted larvae in undercooked pork, bear, or wild game.
• Life cycle: larvae released in gut → enter circulation → encyst in striated muscle.

• GI prodrome (diarrhea) in the first week.
• Classic triad: periorbital edema + myositis (muscle pain) + eosinophilia, often with fever.
• Severe cases: myocarditis, encephalitis.

• Diagnosis: serology and/or muscle biopsy showing encysted larvae; elevated CK.
• Treatment: albendazole; steroids for severe myositis or CNS involvement.

Cestodes (tapeworms) are acquired by ingesting larval cysts (cysticerci / metacestodes) in undercooked meat or fish, or by accidentally ingesting tapeworm eggs from contaminated food/water/dog feces. The clinical picture depends on whether the human serves as the definitive host (adult worm in gut) or the intermediate host (larval cyst in tissue).

• Pathogen: Taenia solium.
• Two very different pictures:
  1. Taeniasis: ingest larval cyst (cysticercus) in undercooked pork → adult worm in intestine → usually mild GI symptoms.
  2. Cysticercosis / neurocysticercosis: ingest eggs (fecal–oral from a human carrier) → larvae migrate to muscle, eye, or brain → form cysts.

• Endemic in Latin America, sub-Saharan Africa, Asia.
• Seen in immigrants and travelers to endemic regions.

• Intestinal taeniasis: mild abdominal symptoms; proglottids in stool.
• Neurocysticercosis: new-onset seizures in adults from endemic regions — signature exam clue.
• Imaging: multiple small cystic lesions with calcified scolex on CT/MRI.

• Diagnosis: stool O&P for intestinal disease; CT/MRI + serology for cysticercosis.
• Treatment:
  • Intestinal taeniasis: praziquantel.
  • Neurocysticercosis: albendazole + corticosteroids (blunt inflammation from dying cysts) + anti-epileptics. Avoid treating purely inactive / calcified lesions.

• Pathogen: Taenia saginata.
• Transmission: ingestion of cysticerci in undercooked beef.
• Humans are only the definitive host — cysticercosis does not occur with T. saginata.

• Mild abdominal discomfort.
• Patients may notice motile proglottids in stool or underwear.

• Diagnosis: proglottids / eggs on stool O&P.
• Treatment: praziquantel.

• Pathogen: Diphyllobothrium latum; adult worms can exceed 10 meters.
• Transmission: ingestion of larvae in raw/undercooked freshwater fish (sushi, sashimi, ceviche, smoked fish).

• Often asymptomatic; mild abdominal symptoms.
• Worm competitively absorbs vitamin B₁₂ → megaloblastic anemia and occasional neurologic symptoms in chronic infection.

• Diagnosis: operculated eggs on stool O&P.
• Treatment: praziquantel + B₁₂ replacement.

• Pathogen: Echinococcus granulosus.
• Life cycle: dogs are definitive hosts; sheep are usual intermediate hosts. Humans accidentally ingest eggs from dog feces.
• Larvae migrate to the liver and form slow-growing hydatid cysts.

• Sheep-herding regions: Middle East, Mediterranean, South America, Central Asia.

• Large hepatic cyst with daughter cysts (“eggshell calcification” on CT).
• Rupture → release of antigenic fluid → anaphylaxis.
• May also involve lung, bone, brain.

• Diagnosis: imaging (CT/US) + serology.
• Treatment: albendazole pre/post-procedure + PAIR (Puncture, Aspiration, Injection of scolicidal agent, Re-aspiration) or surgical cystectomy. Do not simply aspirate without scolicide — spillage causes dissemination and anaphylaxis.

• Pathogens: S. mansoni, S. japonicum, S. haematobium.
• Life cycle: freshwater snail intermediate host releases cercariae → penetrate human skin during wading/swimming → mature into adult worms in venous plexuses (mesenteric or vesical).

• Diagnosis: eggs on stool O&P (mansoni/japonicum) or urine (haematobium). S. mansoni has a lateral spine; S. haematobium has a terminal spine.
• Treatment: praziquantel for all species.