Nematodes (roundworms) Notes

NOTES NOTES NEMATODES (ROUNDWORMS) GENERALLY, WHAT ARE THEY? PATHOLOGY & CAUSES ▪ AKA roundworms ▫ Microfilariae: immature worms ▫ Microfilariae: mature worms ▪ Parasites usually enter body cutaneously ▫ Produce gastrointestinal (GI), occasionally cutaneous symptoms, disease COMPLICATIONS ▪ Loffler syndrome ▫ Transient pulmonary disease during select nematode development (Necator Americanus, Strongyloides, Ascaris Lumbricoides, Toxocara, Ancylostoma duodenale) ▫ Symptoms: irritating, nonproductive cough, substernal burning discomfort, dyspnea, wheezing, fever, blood-tinged sputum production SIGNS & SYMPTOMS ▪ GI/localized tissue symptoms, organismdependent DIAGNOSIS LAB RESULTS ▪ Eosinophilia ▪ Gammaglobulinemia abnormalities (↑/↓ depending on organism) Serology ▪ IgG levels ▪ Enzyme linked immunosorbent assays (ELISA), western blot 436 OSMOSIS.ORG TREATMENT MEDICATIONS ▪ Antihelminthic therapy ▫ Nematode location-dependent Intestinal nematodes ▪ Mebendazole/albendazole ▫ Bind tubulin colchicine-sensitive sites → inhibit microtubule assembly → inhibited glucose uptake (without human effect) → organism death Systemic nematodes ▪ Diethylcarbamazine (DEC) ▫ Piperazine derivative (uncertain mechanism of action) ▪ Ivermectin ▫ Synthetic lactone → negative-charged ion influx via glutamate-sensitive chloride channels → hyperpolarizes cells → helminth cell death ▫ Not macrofilaricidal, pregnancy contraindication

Chapter 82 Nematodes (Roundworms) ANCYLOSTOMA DUODENALE & NECATOR AMERICANUS osms.it/ancylostoma-duodenale osms.it/necator-americanus PATHOLOGY & CAUSES ▪ Infectious hookworm species Adult morphology ▪ Ancylostoma duodenale ▫ Two ventral plates on buccal capsule’s anterior margin; two large teeth fused at base (male 8–11mm, female 10–13mm long) ▪ Necator americanus ▫ Two dorsal/ventral cutting plates around buccal capsule’s anterior margin, paired subdorsal/subventral teeth (male 7–9mm, female 9–11mm long) ▪ A. duodenale, Necator americanus: most common hookworm species causing helminth gastrointestinal infection ▫ Light infection (< 100 worms) ▫ Moderate infection (100–500 worms) ▫ Heavy infection (500–1000 worms) ▪ Pathophysiology ▫ Hookworm attachment, hyaluronidase release → intestinal wall degradation, capillary laceration → anticoagulant peptides, inhibits platelet function inhibitor production → bleeding facilitation → extravasated blood ingested (approx. 0.5mL daily) ▫ Moderate–heavy infections → chronic iron-deficiency anemia; protein malnutrition Infectious form ▪ Filariform larva Life cycle ▪ Infectious form maturation ▫ Female A. duodenale lays 10,000– 30,000 eggs daily ▫ Female N. americanus lays 5,000– 10,000 eggs daily ▫ Human feces egge release → soil deposition → eggs hatch (24–48 hours—favorable conditions) → rhabditiform larvae (L1) → transformation to infectious filariform larvae (L3) in 5–10 days ▪ Human stages ▫ Filariform larvae skin penetration → passage through veins to heart, lung → pulmonary alveoli penetration, ascend bronchi to pharynx → coughed up/swallowed into small intestine → maturation → intestinal wall attachment via buccal capsule ▪ Some A. duodenale larvae undergo developmental arrest in gut tissues/muscle ▫ Await more favorable environmental conditions (hypobiotic larvae) ▪ Natural life-span ▫ A. duodenale: approx. one year ▫ N. americanus: 3–5 years Transmission ▪ Contaminated soil contact → percutaneous larval penetration ▪ Oral route ▪ Transmammary route RISK FACTORS ▪ Inadequate clean-water access ▪ Poor sanitary conditions ▪ Walking barefoot (endemic areas) COMPLICATIONS ▪ Severe iron-deficiency anemia; protein malnutrition → impaired growth, cognitive OSMOSIS.ORG 437

development (children); heart failure (adults) ▪ Pregnancy ▫ Low birth weight, maternal anemia, ↑ infant mortality SIGNS & SYMPTOMS ▪ May be asymptomatic Three phases ▪ Cutaneous phase ▫ Local pruritic dermatitis (ground itch) with papular, sometimes vesicular, focal rash at larval penetration site (usually between toes) ▪ Pulmonary phase ▫ Usually asymptomatic, may involve mild cough, pharyngeal irritation, sore throat, fever ▪ Gastrointestinal phase ▫ Midepigastric pain, appetite loss, nausea, diarrhea, vomiting Heavy infection ▪ Hypoproteinemia → weight loss, anasarca, edema ▪ Anemia → fatigue, mental dullness, dyspnea, pallor ▪ Overt gastrointestinal bleeding DIAGNOSIS DIAGNOSTIC IMAGING Abdominal X-ray ▪ Intestinal worm visualization LAB RESULTS ▪ Acute infection ▫ Eosinophelia ▪ Chronic infection ▫ Anemia ▪ Kato–Katz method (thick smear) ▪ Polymerase chain reaction (PCR) test Direct microscopy ▪ Stool specimen egg visualization 438 OSMOSIS.ORG ▫ A. duodenale, N. americanus eggs are morphologically indistinguishable OTHER DIAGNOSTICS ▪ History ▫ Contaminated-soil skin exposure; endemic-area travel; physical examination TREATMENT MEDICATIONS ▪ Anthelmintic treatment

Chapter 82 Nematodes (Roundworms) ANGIOSTRONGYLUS (EOSINOPHILIC MENINGITIS) osms.it/angiostrongylus PATHOLOGY & CAUSES ▪ Parasitic nematode ▫ Causes human GI/CNS disease ▪ Angiostrongylus cantonensis ▫ Medically important species ▫ Causes angiostrongyliasis (most common eosinophilic meningitis cause) Adult morphology ▪ Three outer protective collagen layers; contains fully-developed gastrointestinal tract, simple stomal opening Hosts ▪ Primary intermediate host: snails ▪ Paratenic hosts: fish, frogs, freshwater prawns ▫ Not needed for developmental cycle ▪ Definitive hosts: wild rodents (brown, black rat) ▪ Incidental hosts: humans Life cycle ▪ Infectious form maturation ▫ Worms lay eggs in rat pulmonary artery → spread from lung capillaries to alveoli, larvae hatch → migrate up bronchi, trachea, across epiglottis → swallowed → fecal larvae passage → soil deposition → intermediate-host ingestion ▪ Human stages ▫ Intermediate host larval ingestion (contaminated water/vegetable) → CNS tropism → migration into meningeal capillaries, brain tissue → meningoencephalitis ▪ Larvae usually fail to complete life-cycle, rarely → adult form in human host Transmission ▪ Intermediate/paratenic host ingestion (raw/undercooked snails, fish, frogs), contaminated vegetables/water Pathophysiology ▪ Post-inoculation, A. cantonensis larvae exhibit neurotropism → meninges, deeper brain tissue invasion → neural-tissue mechanical, toxic byproducts damage; antigen release → meningoencephalitis ▪ Migration to mesenteric arterioles → arteritis, thrombosis, small infarctions ▫ May cause necrotic ulcers → peritonitis, fistula formation COMPLICATIONS ▪ Long-term encephalitis → permanent nerve damage, intellectual disability, permanent brain damage, death SIGNS & SYMPTOMS ▪ Incubation period: three weeks–two months ▪ Meninges invasion: meningitis picture ▫ Severe headache, photophobia, stiff neck, fatigue, fever, hyperesthesia, vomiting, paresthesias ▪ Brain parenchyma invasion: encephalitis symptoms (brain location-dependent) ▫ Cognitive impairment, slowed reactions, neuropathic pain, ascending weakness ▫ t quadriparesis, areflexia, respiratory failure, muscle atrophy, death (rare) ▪ Eye invasion: visual impairment, pain, keratitis, retinal edema OSMOSIS.ORG 439

DIAGNOSIS TREATMENT LAB RESULTS ▪ Self-limiting infection (usually) ▪ Cerebrospinal fluid (CSF) ▫ Eosinophilia ▫ ↓ glucose levels (severe meningoencephalitis) MEDICATIONS ▪ Analgesics, sedatives ▫ Treat headache, hyperesthesia ▪ Corticosteroids ▪ Antihelminthic therapy not advised ▪ Dying parasites, neurologic damage exacerbation → potential inflammatory response OTHER DIAGNOSTICS ▪ Endemic-area travel history ▪ Physical examination ▪ Clinical presentation OTHER INTERVENTIONS ▪ CSF drainage ▫ Reduces intracranial pressure, relieve headache ANISAKIS osms.it/anisakis PATHOLOGY & CAUSES ▪ Zoonotic roundworm ▫ Causes human gastrointestinal, extragastrointestinal disease ▫ Causative anisakiasis agent Adult morphology ▪ Anteriorly-located mouth surrounded by projections; length (2cm/0.8in) Infectious form ▪ L3 larvae Hosts ▪ Natural hosts: marine mammals ▪ Incidental hosts: humans Life cycle ▪ Infectious form maturation ▫ Eggs hatch into larvae (seawater) → larval crustacean ingestion → fish/ squid ingest crustaceans → muscular/ subdermal larval encystation (L3 440 OSMOSIS.ORG larvae) → marine mammals ingest fish → excystation, maturation, nematode reproduction → fecal egg release ▪ Human stages ▫ Larval ingestion (infected fish) → larvae fail maturation, cannot complete lifecycle Transmission ▪ Raw/undercooked fish ingestion Pathophysiology ▪ Infected fish larvae ingestion → larvae burrow into intestinal wall, die → dead organism → inflammatory response → possible allergic reaction, abscess, mechanical obstruction ▪ If parasites pass into large intestine ▫ Eosinophilic granulomatous response → mimic appendicitis/Crohn’s disease RISK FACTORS ▪ Raw/undercooked seafood ingestion (common in Japan)

Chapter 82 Nematodes (Roundworms) COMPLICATIONS ▪ Small bowel obstruction ▪ Intestinal perforation ▪ Peritoneal cavity perforation (extraintestinal anisakiasis) ▪ Eosinophilic gastroenteritis/enterocolitis SIGNS & SYMPTOMS ▪ Gastric anisakiasis ▫ Acute epigastric pain, nausea, vomiting ▪ Intestinal anisakiasis ▫ Severe abdominal pain, abdominal distension, palpable abdominal mass, intestinal obstruction, bloody diarrhea ▪ Allergic reactions ▫ Urticaria, bronchoconstriction, angioedema, anaphylactic shock DIAGNOSIS DIAGNOSTIC IMAGING ▪ Parasite visualization ▫ Gastroscopic examination, emesis examination LAB RESULTS ▪ ↑ serum IgE TREATMENT SURGERY ▪ Parasite removal (endoscopically, surgically) ASCARIS LUMBRICOIDES osms.it/ascaris-lumbricoides PATHOLOGY & CAUSES ▪ Intestinal roundworm parasite ▫ Causative ascariasis agent ▪ Adult worm size: 15–30cm/5.9–11.8in ▫ Largest intestinal nematode Life cycle ▪ Female A. lumbricoides lays 200,000 eggs daily; begins egg-laying 9–11 weeks postinfection ▪ Infectious-form maturation ▫ Eggs passed in stool → soil deposition → eggs embryonate; infectious after 2–4 weeks; can survive < ten years (favorable conditions) ▪ Human stages ▫ Egg ingestion → larvae hatch → invade intestinal mucosa → portal circulation → systemic circulation → liver → lungs → larvae mature in alveoli (10–14 days) → ascend bronchial tree, pharynx, swallowed → larvae develop into adult form in small intestine ▪ Life-span: 10–24 months Pathophysiology ▪ Varies upon life-cycle stage ▫ Pulmonary phase (early): caused by larval migration into lungs → pneumonitis ▫ Intestinal phase: manifestations caused by adult-form presence → mechanical obstruction (degree worm-burdendependent) RISK FACTORS ▪ Egg-contaminated food/water ingestion (especially pig/chicken liver) ▪ Infected soil (children) ▪ Feco-oral route reinfection COMPLICATIONS ▪ Intestinal obstruction ▫ May → volvulus, ileocecal OSMOSIS.ORG 441

▪ ▪ ▪ ▪ intussusception, gangrene, intestinal perforation Children ▫ Malnutrition/malabsorption, impaired growth, cognitive development Hepatobiliary involvement ▫ Biliary colic, biliary strictures, obstructive jaundice, liver abscesses Pancreatic duct obstruction → pancreatitis Aspiration pneumonia during esophageal migration to trachea SIGNS & SYMPTOMS ▪ Often asymptomatic ▪ Pulmonary phase (Loffler syndrome): develops 4–16 days post-infection ▫ Dry cough, dyspnea, fever, wheezing, substernal discomfort, blood-tinged sputum; symptoms subside after 5–10 days ▪ Intestinal phase: develops 6–8 weeks postinfection ▫ Abdominal discomfort, anorexia, nausea, vomiting, diarrhea Barium swallow ▪ Intestinal phase ▫ Defects in filling; if worms ingest contrast, tram-track appearance demonstrated Microscopic examination ▪ Pulmonary phase ▪ Eosinophils, Charcot–Leyden crystals in sputum ▪ Intestinal phase ▪ Eggs/adult form stool visualization (KatoKatz/FLOTAC method) LAB RESULTS ▪ Pulmonary phase ▫ Peripheral eosinophilia OTHER DIAGNOSTICS ▪ Exposure/endemic-area travel history DIAGNOSIS DIAGNOSTIC IMAGING Chest X-ray ▪ Pulmonary phase ▫ May show migratory bilateral oval infiltrates, range from several mm– several cm ▪ Intestinal phase ▫ Adult Ascaris worm visualization, intestinal obstruction CT scan ▪ Pulmonary phase ▫ Multiple nodules, “ground-glass” attenuation ▪ Intestinal phase ▫ “Bull’s eye” appearance (worm crosssection) 442 OSMOSIS.ORG Figure 82.1 A barium study demonstrating ascariais. There are numerous worms in the distal part of the duodenum and the ileum.

Chapter 82 Nematodes (Roundworms) TREATMENT MEDICATIONS ▪ Anthelmintic treatment ▫ Only effective in intestinal phase ▫ Pregnancy: pyrantel pamoate SURGERY ▪ Complete intestinal obstruction, volvulus, intussusception, appendicitis, perforation cases OTHER INTERVENTIONS ▪ Endoscopic retrograde cholangiopancreatography (ERCP) ▫ Hepatobiliary-involvement cases Figure 82.2 Ascaris worms emerging from the two free ends of the small intestine during an operation to remove a length of ischemic bowel. Figure 82.3 Small bowel packed with Ascaris lumbricoides worms. The bowel is distended so greatly that the visceral peritoneum on the antimesenteric border is split. OSMOSIS.ORG 443

ENTEROBIUS VERMICULARIS (PINWORM) osms.it/enterobius-vermicularis PATHOLOGY & CAUSES ▪ Small roundworm ▫ May infect human colon, rectum ▫ Causative enterobiasis agent Life cycle ▪ Female E. vermicularis lays > 10,000 eggs daily ▪ Perianal fold egg deposition → autoinfection by scratching; contaminated hand, mouth contact → eggs hatch into larvae (small intestine) → adult-form maturation (cecum, appendix) ▪ Life-span: 2–3 months Transmission ▪ Scratching perianal area (autoinfection) → hand–mouth contact ▪ Contaminated hands (person–person) ▪ Contaminated surface contact ▪ Eggs may become airborne, inhaled ▪ High worm burden → abdominal pain, nausea, vomiting DIAGNOSIS OTHER DIAGNOSTICS ▪ Pinworm paddle/Scotch tape test ▫ Adhesive clear plastic paddle pressed against perianal areas → placed onto glass slide; reveals eggs upon microscopic examination TREATMENT MEDICATIONS ▪ Anthelmintic treatment RISK FACTORS ▪ Crowded living conditions ▪ Children 5–10 years old COMPLICATIONS ▪ Persistent perianal-area scratching, skin tearing → bacterial dermatitis, folliculitis ▪ Adult worms migrate to extraintestinal sites; cause vulvovaginitis, salpingitis, oophoritis, cervical granuloma, peritoneal inflammation SIGNS & SYMPTOMS ▪ Mostly asymptomatic ▪ Perianal itching (pruritus ani) occurs nocturnally 444 OSMOSIS.ORG Figure 82.4 Pinworm found incidentally in an appendectomy specimen.

Chapter 82 Nematodes (Roundworms) GUINEA WORM (DRACUNCULIASIS) osms.it/guinea-worm PATHOLOGY & CAUSES ▪ Water-borne nematode disease ▫ Characterization: rash, GI illness with subcutaneous worm visualization Life cycle/transmission ▪ Infected water → human copepod ingestion → GI, subcutaneous migration, sexual reproduction → pruritus, percutaneous larval eruption upon water-immersion → copepod larval consumption → two molting processes → pathogenic larvae in copepods Pathogenesis ▪ GI symptoms ▫ Ingested copepod death in GI system → larval migration into stomach, intestinal wall → entry into abdominal, retroperitoneal space ▪ Cutaneous symptoms ▫ Larval sexual reproduction → female survival, skin migration → limb waterimmersion → eruption RISK FACTORS ▪ Rural Eastern-Africa residence/travel ▪ Cutaneous symptoms ▫ Painful papule (2–7cm/0.8–2.8in) → enlarges, ↑ pain → worm emerges through ulceration DIAGNOSIS DIAGNOSTIC IMAGING X-ray ▪ Calcified dead worm in subcutaneous tissue ▫ If worm does not emerge through skin OTHER DIAGNOSTICS ▪ Endemic-area travel/residence history ▪ Physical examination ▫ Systemic → cutaneous symptom development TREATMENT OTHER INTERVENTIONS ▪ Worm extraction; careful extraction protocol ▫ Multiple days (centimeters at a time); keeps worm intact, prevents local pruritic, edematous reaction COMPLICATIONS ▪ Ectopic site migration → abscess development ▫ Lung, eye, pericardium, spinal cord ▪ Broken worm → intensely painful, edematous local, subcutaneous reaction SIGNS & SYMPTOMS ▪ Systemic symptoms initially ▫ Fever, urticaria, pruritus, dizziness, nausea/vomiting, diarrhea Figure 82.5 A match stick being used to extract a guinea worm from an ulcer on the leg. OSMOSIS.ORG 445

Prevention ▪ Community surveillance, transmission methods education ▪ Safe water precautions ▫ Nylon filters for water filtration, insecticides in drinking water courses, water source covering (prevents infected body-part immersion) ▪ Occlusive dressings applied to papules LOA LOA (EYE WORM) osms.it/loa-loa PATHOLOGY & CAUSES ▪ Vector-borne filarial nematode endemic in Africa ▫ Characterization: transient swelling episodes, subconjunctival adult worm migration ▪ AKA African eye worm ▪ Allergic reaction ▪ Subconjunctival infiltration ▫ Associated with conjunctivitis, eyelid swelling Life cycle/transmission ▪ Vector ▫ Chrysops (biting deer fly; AKA tabanid fly) ▫ Breed in rainforest canopies, lay eggs in muddy swamps; bite humans during daytime ▪ Tabanid fly human bite → filarial larvae transmission → three month maturation process → microfilarial production → bloodstream release ( ↑ release during daytime) → tabanid blood meal (infected individual) → filarial maturation in tabanid fly RISK FACTORS ▪ Endemic-area residence/travel ▫ Eastern, Central Africa 446 OSMOSIS.ORG COMPLICATIONS ▪ Onchocerciasis co-infection ▪ Encephalitis (coincident headache, insomnia, coma may result) ▪ Cardiomyopathy (endomyocardial fibrosis) ▪ Nephropathy ▪ Arthritis ▪ Lymphadenitis ▪ Calabar swelling → entrapment neuropathy SIGNS & SYMPTOMS Allergic reactions ▪ Calabar swellings ▫ 5–20cm/2–7.9in non-erythematous lesions ▫ Transient, local subcutaneous swelling; face, extremities most common; localized pain, itching prior to swelling episodes ▫ Urticaria, pruritus, asthma Subconjunctival eye infection ▪ Commonly non-painful infiltration of eye subconjunctival area; conjunctivitis may occur (with eyelid swelling) ▪ Worm may be visible

Chapter 82 Nematodes (Roundworms) DIAGNOSIS LAB RESULTS ▪ ▪ ▪ ▪ Hypergammaglobulinemia ↑ IgE level Worm’s presence (blood smear) Serology ▫ IgG antibodies against L. loa antigens OTHER DIAGNOSTICS ▪ History, physical examination ▫ Worm detection in subcutaneous tissue, conjunctiva ▫ Onchocerciasis co-infection contraindicated (DEC provokes severe inflammatory skin, eye response; Mazzotti reaction) ▫ Eradication may require multiple treatment rounds ▪ Albendazole ▫ Sterilizes mature worms without microfilarial activity ▪ Antihistamine/corticosteroids ▫ Limits post-treatment immune reactions (e.g. Calabar swelling) SURGERY ▪ Large worm removal TREATMENT MEDICATIONS ▪ Diethylcarbamazine (DEC) ▫ Active against L. loa microfilariae, microfilariae (adult worms) OTHER INTERVENTIONS Prevention ▪ Weekly DEC prophylaxis ▪ Only considered for long-term endemicarea exposure ONCHOCERCA VOLVULUS (RIVER BLINDNESS) osms.it/onchocerca-volvulus PATHOLOGY & CAUSES ▪ Filarial nematode transmitted by blackflies ▪ Leading preventable blindness cause in sub-Saharan Africa Life cycle/transmission ▪ Simulium blackfly human bite → larvae skin deposited → adult parasite maturation (microfilariae) → subcutaneous/deeper intramuscular tissue migration → fibrous capsule/nodule development → reproduction → microfilarial (immature worm) production, subcutaneous tissue migration → human blackfly bite → microfilarial development into infective larvae (in blackfly) Ocular onchocerciasis ▪ Common manifestation: West African savanna ▪ Commonly affects anterior eye chamber ▫ Iridocyclitis, glaucoma, uveitis ▪ Posterior chamber may also be affected ▫ Onchochorioretinits, optic atrophy ▪ Ocular involvement degree correlates with symbiotic Wolbachia bacteria quantity Onchocercal skin disease ▪ AKA Leopard/lizard/elephant skin (especially when depigmentation present); common manifestation in African forest areas ▪ Classified by chronicity ▫ Acute/chronic papular onchodermatitis OSMOSIS.ORG 447

▪ Lichenified onchodermatitis (AKA sowda/ black/dark); epidermal atrophy, elastic fiber breakdown may occur PATHOLOGY Subcutaneous involvement ▪ Onchocercoma ▪ Dermal O. volvulus → inflammatory response (prostaglandin E2, transforming growth factor-beta-mediated) → nodule formation (onchocercoma); nodules predominate in bony prominence areas, peak inflammatory response occurs upon subcutaneous male O. volvulus death Ocular involvement ▪ Anterior chamber disease ▫ O. volvulus infiltration → immune response, O. volvulus death → Wolbachia release → innate immune response → corneal damage ▪ Posterior chamber disease ▫ O. volvulus infiltration → immune response → cross-reactivity of O. volvulus antigen with retinal pigment epithelial protein → persistent immunologic response → inflammatory limbus, iris, choroid damage RISK FACTORS ▪ West Africa, Eastern South America travel/ residence ▫ Especially savanna, forest SIGNS & SYMPTOMS Cutaneous ▪ Pruritus ▪ Nodule development (lymphadenopathy may develop, persist depending on infection duration) ▪ Focal darkening/depigmentation ▪ Epidermal atrophy, hyperpigmentation, hyperkeratosis may be present Ocular ▪ Punctate keratitis → fluffy corneal opacities → eosinophilic infiltrate → sclerosing keratitis → corneal opacification; 448 OSMOSIS.ORG progressive (eventually irreversible) vision deficit DIAGNOSIS DIAGNOSTIC IMAGING Ultrasound ▪ Deep ochoceroma detection LAB RESULTS ▪ Eosinophilia ▪ Hypergammaglobulinemia ▪ PCR assay ▫ O. volvulus OTHER DIAGNOSTICS ▪ Rheumatologic/dermatologic onchocercoma evaluation Skin snips ▪ Corneoscleral punch biopsy (ocular involvement)/ disposable razor blade for epidermal sample (cutaneous disease) ▪ 2+ snips taken in areas likely to harbor highest microfilariae concentration ▪ Positive only within 9–15 months postinfection (mature microfilariae produce microfilariae) Patch test ▪ Topical DEC application → local skin reaction assessment ▪ Akin to Mazzotti reaction Fundoscopic and corneal evaluation ▪ Slit-lamp examination reveals wriggling microfilariae ▪ Individuals sit forward for two minutes prior to examination (↑ microfilarial visualization likelihood on chamber examination) TREATMENT MEDICATIONS ▪ Ivermectin, doxycycline ▫ Ivermectin: kills immature worms only, adult worm repopulate months after treatment

Chapter 82 Nematodes (Roundworms) ▫ Doxycycline: kills Wolbachia (symbiotic bacteria needed for O. volvulus fertility) for 24 months; block reproduction OTHER INTERVENTIONS Prevention ▪ Protective clothing, insect repellent (especially when blackflies most active— morning/evening) STRONGYLOIDES STERCORALIS osms.it/strongyloides-stercoralis PATHOLOGY & CAUSES ▪ Filarial disease endemic in tropical areas with characteristic pulmonary infection route, complications include septic shock in immunocompromised individuals ▪ Mild GI, cutaneous, pulmonary inflammation, disease ▫ Dermatitis, urticaria, duodenitis, enterocolitis, pneumonitis ▫ May persist for years Life cycle ▪ Larvae live in fecally-contaminated ground soil → enter human host through broken skin → hematologic spread → pulmonary alveolar sac infiltration, penetration → ascend tracheobronchial tree → swallowed → larval maturation in duodenum, jejunum → larval reproduction, fecal excretion ▪ Autoinfection (single-host life-cycle completion) may occur via larval perianal skin entry PATHOLOGY ▪ Larvae contaminate skin through breakage → lung migration → inflammation infiltrate → intestinal wall migration → maturation, replication → larval intestinal mucosa penetration → autoinfection RISK FACTORS ▪ Constipation, diverticula, steroid-use, ↓ bowel motility → ↑ autoinfection likelihood ▪ Hypogammaglobulinemia ▪ Anti-tumor necrosis factor receptor therapy ▪ Organ transplantation, immune suppression COMPLICATIONS ▪ Hyperinfection (uncontrolled autoinfection → high worm-burden disease) ▫ Immunocompromised individuals ▫ Hematologic parasite spread includes CNS, heart, liver, lungs, endocrine glands ▫ May manifest as septic shock SIGNS & SYMPTOMS ▪ Immunocompetent individuals ▫ Bloating, diarrhea ▪ Cutaneous ▫ Edema, petechiae, serpiginous/urticarial tracking ▪ Gastrointestinal ▫ Anorexia, nausea, vomiting, epigastric pain (duodenal ulceration cases), malabsorption (chronic enterocolitis) ▪ Pulmonary ▫ Dry cough, throat irritation, dyspnea, wheezing, hemoptysis OSMOSIS.ORG 449

DIAGNOSIS DIAGNOSTIC IMAGING Chest X-ray ▪ Pulmonary disease ▫ Foci of hemorrhage, pneumonitis, pulmonary edema LAB RESULTS Organism identification ▪ Stool examination ▫ Low sensitivity due to intermittent larval release ▫ Repeat testing ↑ finding’s reliability ▪ ELISA ▫ Immunocompetent individuals TREATMENT MEDICATIONS ▪ Ivermectin ▪ Albendazole ▫ May combine with ivermectin in hyperinfection/disseminated disease states OTHER INTERVENTIONS Prevention ▪ Proper shoe wearing ▫ Prevents broken-skin exposure ▪ Serologic evaluation ▫ Solid organ transplant donors OTHER DIAGNOSTICS ▪ Endemic-area travel history Endoscopy ▪ Histopathological (biopsy-driven) diagnosis ▫ Stomach, duodenum, colon evaluation of mucosa appearance Figure 82.6 A duodenal biopsy containing an entire Strongyloides worm, likely an adult female. 450 OSMOSIS.ORG

Chapter 82 Nematodes (Roundworms) TOXOCARA CANIS (VISCERAL LARVA MIGRANS) osms.it/toxocara-canis PATHOLOGY & CAUSES ▪ Human roundworm disease: dog, cat, pig vectors characterized by cutaneous/ocular disease ▫ Dogs: toxocara canis ▫ Cats: toxocara cati ▫ Pigs: Ascaris suum Life cycle/transmission ▪ Definitive hosts: cats, dogs, pigs ▪ Accidental hosts: humans ▪ Egg-laden stool → soil contamination → definitive host ingestion → GI tract reproduction → larval gut wall penetration → pulmonary migration, penetration → ascend tracheobronchial tree → swallowed → small intestine worm maturation → reproduction, egg excretion in stool ▪ Paratenic host: non-canine, small mammals; egg ingestion → larval gut wall penetration → tissue migration → cyst formation → human paratenic host ingestion → infection Disease ▪ Ocular involvement: inflammatory granuloma of posterior pole, diffuse endophthalmitis, solitary peripheral retinal granuloma RISK FACTORS ▪ Raw liver/undercooked meat ingestion (e.g. rabbit, chicken, cattle, pork) ▪ Children ▫ Playground, sandbox use COMPLICATIONS ▪ Hepatitis ▪ Pneumonitis ▪ Cardiac ▫ Pericarditis, myocarditis ▪ CNS involvement ▫ Myelitis, meningoencephalitis, seizure, cerebral vasculitis ▪ Ocular ▫ Retinal detachment, blindness SIGNS & SYMPTOMS ▪ Visceral larva migrans ▫ Pruritic urticaria, fever, anorexia, malaise, irritability ▪ Ocular larva migrans ▫ Unilateral vision impairment, uveitis, papillitis, endophthalmitis ▪ Hepatomegaly ▪ Respiratory distress DIAGNOSIS DIAGNOSTIC IMAGING Chest X-ray ▪ Bilateral peribronchial infiltrates CT scan ▪ Chest: multifocal subpleural nodules, “ground-glass” opacities, ill-defined margins ▪ Abdomen: multiple ill-defined lesions in liver parenchyma Ultrasound ▪ Abdomen: may also identify lesions LAB RESULTS ▪ Leukocytosis ▪ Hypogammaglobulinemia (↑ IgG, IgE) ▪ ELISA OSMOSIS.ORG 451

▫ IgG antibodies against Toxocara excretory/secretory antigens ▫ Does not differentiate Toxocara canis from cati OTHER DIAGNOSTICS ▪ Endemic-area travel history ▪ Physical examination TREATMENT MEDICATIONS ▪ Moderate → severe symptoms ▫ Albendazole ▪ Severe inflammatory disease (myocarditis, pneumonitis, CNS involvement) ▫ Prednisone ▪ Ocular larva migrans ▫ Corticosteroids, albendazole OTHER INTERVENTIONS Prevention ▪ Hand hygiene practice ▪ Pet feces disposal, deworming ▪ Undercooked meat (especially liver) consumption risk education TRICHINELLA SPIRALIS osms.it/trichinella-spiralis PATHOLOGY & CAUSES → female worm release larvae → striated muscle encystation ▪ Roundworm infection (prevalent worldwide) ▫ Raw/undercooked meat with encysted organism consumption ▪ Trichinella: nine species, twelve genotypes ▫ Animal intermediate host-specific ▫ T. spiralis: most common worldwide; variety of carnivorous, omnivorous animals Disease ▪ Severity correlates with multiple factors ▫ Number of ingested larvae directly correlates with ingested meat cooking temperature ▫ Trichinella species ▫ Incubation period (shorter correlates with ↑ disease severity) ▪ Gastrointestinal involvement ▫ Maturing larvae burrow in intestinal mucosa ▫ Diarrheal illness, nausea, vomiting ▪ Muscular involvement ▫ Adult worm dissemination into skeletal muscle ▫ Symptom resolution occurs with complete worm encystment ▫ Mild subclinical fatigue, post-exercise weakness persists months–years Life cycle/transmission ▪ Domestic cycle: involves pigs, rodents ▪ Sylvatic cycle: broad animal range ▫ Bear, moose, wild boar most common human infection sources ▪ Trichinella larvae/mature worm ingestion by intermediate host → GI tract maturation → larvae release, migrate from female worms to striated muscles → encyst → intermediate host consumption (inadequate cooking temperature) → larval ingestion → larvae release in stomach (upon gastric acid, pepsin exposure) → small bowel mucosa invasion → adult worm maturation 452 OSMOSIS.ORG RISK FACTORS ▪ Undercooked/raw meat consumption

Chapter 82 Nematodes (Roundworms) COMPLICATIONS ▪ Myositis, myocarditis ▫ Eosinophil-enriched inflammatory response → life-threatening arrhythmia development ▪ Encephalitis, pneumonia ▫ Direct larval parenchyma infiltration, respiratory muscle disease SIGNS & SYMPTOMS ▪ Gastrointestinal ▫ Nausea/vomiting, abdominal pain, diarrhea ▪ Muscular ▫ Most severe symptoms ▫ Pain (activity-dependent; ↑ muscle use/ strain correlates with ↑ ↑ pain) ▫ Tenderness, swelling, weakness ▪ Other ▫ High fever, periorbital edema, chemosis, visual disturbance ▫ Retinal hemorrhage on fundoscopic examination DIAGNOSIS DIAGNOSTIC IMAGING CT scan/MRI ▪ In severe neurologic-involvement cases ▪ Multifocal cerebral cortex, white matter lesions LAB RESULTS ▪ Serology ▫ ELISA, western blot, immunofluorescence assays ▫ Antibodies only detectable after 2-3 weeks of disease ▫ Eosinophilia ▫ Leukocytosis ▫ ↑ Muscle enzymes, ↑ creatinine kinase, ↑ lactate dehydrogenase ▪ Muscle biopsy ▫ Near tendinous insertion → highest yield obtained Figure 82.7 A muscle biopsy containing a Trchinella spp. larva. TREATMENT MEDICATIONS ▪ Mild disease ▫ Self-resolving ▫ Analgesia, antipyretics ▪ Systemic symptoms ▫ Antiparasitic therapy (assists larval burrowing into intestinal mucosa treatment) ▫ Corticosteroids OTHER INTERVENTIONS Prevention ▪ Postexposure prophylaxis in suspected cases ▫ Mebendazole within six days of exposure ▪ Undercooked/raw meat consumption risk education, safe cooking practices OSMOSIS.ORG 453

TRICHURIS TRICHIURA (WHIPWORM) osms.it/trichuris-trichiura PATHOLOGY & CAUSES ▪ Human intestinal parasite (AKA whipworm) ▪ T. Trichiura causative trichuriasis agent Morphology ▪ Adult ▫ 4 cm/1.6 in in length; made of anterior whip-like esophageal portion, posterior intestine/reproductive organ portion ▪ Egg ▫ Prolate spheroids, polar plugs at each end Life cycle ▪ Female T. Trichiura lays 3000–20,000 eggs daily 60–70 days post-infection ▪ Infectious form maturation ▫ Unembryonated egg passage in stool → soil deposition → eggs embryonate, become infectious in 15–30 days ▪ Human stages ▫ Egg ingestion → eggs hatch into larvae in small intestine → larvae mature into adult worms, embed in cecum, ascending colon ▪ Life-span: 1-3 years RISK FACTORS ▪ Poor hygiene, sanitary conditions; inadequate human fecal disposal; uncooked/contaminated vegetable ingestion 454 OSMOSIS.ORG COMPLICATIONS ▪ Heavy infection → rectal prolapse ▫ Inflammation, edema caused by high embedded worm quantity in rectum (usually small children) ▪ Persistent blood loss → iron-deficiency anemia ▪ Children ▫ Impaired growth, cognitive development SIGNS & SYMPTOMS ▪ Mostly asymptomatic ▪ Heavier infection ▫ Abdominal pain, distension, diarrhea, fecal blood/mucus, nocturnal stooling, tenesmus DIAGNOSIS OTHER DIAGNOSTICS ▪ Kato–Katz thick-smear technique ▫ Eggs in stool visualization TREATMENT MEDICATIONS ▪ Antihelminthic treatment

Chapter 82 Nematodes (Roundworms) WUCHERERIA BANCROFTI (LYMPHATIC FILARIASIS) osms.it/wuchereria-bancrofti PATHOLOGY & CAUSES ▪ Mosquito-borne nematode infection ▫ Characterization: lymphatic, subcutaneous involvement → disfigurement, disability ▪ Mosquito species vector geographicspecific (e.g. Culex, Aedes) Life cycle/transmission ▪ Filarial larvae introduction into human skin during mosquito bloodmeal → lymphatic spread → maturation into adult worm → reproduction, microfilarial hematologic release (commonly nocturnal release) → further transmission after infected individual’s mosquito bite Disease ▪ Adenolymphangitis, tropical pulmonary eosinophilia, hydrocele, chronic lymphatic disease ▪ Chyluria ▫ Intestinal lymphatic discharge into pelvis ▫ May → nutritional deficiency (including anemia, hypoproteinemia) SIGNS & SYMPTOMS ▪ Fever, hydrocele Lymphatic disease ▪ Acute adenolymphangitis ▪ Painful lymphadenopathy, retrograde lymphangitis; self-resolving (4–7 days), may recur multiple times per year ▪ Dilation ▪ Lymphangiectasia ▪ Lymphedema ▫ Pitting edema → non-pitting edema → limb hardening ▫ Hyperpigmentation, hyperkeratosis may occur late in disease Pathogenesis ▪ Filarial antigens → TH2-type immune response → cytokine production (IL-5, IgE) ▪ Adult worm → mechanical lymphatic disruption → lymphangiectasia, lymphatic dilation ▪ Endosymbiotic bacteria Wolbachia → immune response potentiation DIAGNOSTIC IMAGING RISK FACTORS LAB RESULTS ▪ Sub-Saharan africa, Southeast Africa, India, Pacific island travel/residence COMPLICATIONS ▪ Lymphedema (AKA elephantiasis) ▫ Chronic lymphatic vessel inflammation → limb swelling DIAGNOSIS Ultrasound ▪ Lymphatic dilation, lymphangiectasia, adult worms may be visualized ▪ Circulating filarial antigen assays ▫ ELISA: Og4C3 antigen detection ▫ ↑ IgG4 levels indicate active infection ▪ Blood smear ▫ Nocturnal blood draw important to ↑ microfilariae concentration OSMOSIS.ORG 455

OTHER DIAGNOSTICS ▪ Physical examination ▫ Wriggling adult filariae in lymphatic vessels TREATMENT MEDICATIONS ▪ DEC ▫ Contraindication: onchocerciasis, severe Loa Loa infection, pregnancy ▫ Doxycycline may be added as combination agent for direct larvicidal activity ▫ ↓ lymphedema effectiveness ▫ Proper skin care, topical antimicrobial administration (antifungal, antibacterial agents), extremity elevation, exercise may ↓ edema over time SURGERY ▪ Hydrocele complications 456 OSMOSIS.ORG Figure 82.8 A histological section of a lymph node which contains a filarial worm. The normal lymph node architecture has been replaced with an inflammatory infiltrate composed largely of eosinophils. OTHER INTERVENTIONS Prevention ▪ Mass drug administration programs ▪ Insecticide-treated bed nets ▪ Repellant, protective clothing in mosquitoendemic regions

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