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I.D. #2.22: Clinical Microbiology of Helminths

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General life cycle of human parasitic helminths
Egg -> Larval stage (one or more) -> Adult
Intermediate host - larval stage or asexual reproduction

Definitive host - adult stage or sexual reproduction

+Most helminths unable to complete life cycle in the human host

-Development of eggs / larvae in environment or intermediate host

-Geographic distribution of the parasite dependent on the above.

-Intensity of infection in humans requires repeated exposure.
General transmission of helminths
Ingestion of eggs or larvae

Penetration of intact skin by larvae

Inoculation of larvae by biting insects
Cestodes (tapeworms)
Intestinal - Taenia saginata,

Taenia solium - Pig tapeworm
Mexico, India, Philippines, Central & South America

Diphyllobothrium latum - Fish tapeworm
-Siberia, Scandanavia, Baltic, Japan, North America
-Freshwater fish


Larval - Echinococcus, Cysticercus
Nematodes (Roundworms)
Intestinal - Ascaris, Hookworm, Strongyloides, Enterobious

Tissue - Trichinella, Toxocara, Filariasis
Trematodes (flukes)
Blood - schistosomiasis

Organ - Clonorchis (liver), paragonimus (lung)
Taenia Saginata
Beef Tapeworm

Central asia, near east, africa
Microbiology of Intestinal Tapeworms (Cestodes)
Scolex
Attaches to SB mucosa
Gives rise to other segments

Proglottid
Independent segments
Contain male & female sex
Can be passed in stool
Generates eggs

Can reach 25m in length
D. latum > Taenia

Lifespan of 10-30 years

Incubation period of 1-3 m
Symptoms Diagnosis of Cestodes
Asymptomatic, mild abdominal discomfort, diarrhea.

Complications:
T. saginata proglottids are motile and can migrate out the anus, and rarely appendix, bile/pancreatic duct.

D. latum prolonged or heavy infection can result in B12 deficiency due to B12-IF disassociation and uptake.

Diagnosis:
Stool microscopy for eggs - cannot differentiate Taenia

Identification between Taenia can be made by proglottids

Eggs and proglottids may be shed intermittently
Larval Taenia Solium
Definitive host = humans
Intermediate host = humans, pigs

Human eats pork ->Taeniasis
Human eats egg -> Cysticercosis

Cysticercosis - tissue infection with larval cysts of Taenia solium.

Due to human fecal contamination. Exposure to pork not required.

Cysticercosis prevalent in Mexico, Central & S. America, SE Asia
Echinococcus Granulosis (larval tapeworm)
Definitive host = dogs
Intermediate host = humans, sheep

Human eats egg -> Echinococcosis

Echinococcosis - Hydatid disease
Tissue infection with larval cysts of E.granulosus.

Transmitted by domestic dogs in live-stock raising areas.

Prevalent in Middle East, S Europe, Africa, Latin America and SW USA.
Hydatid Disease
Hydatid cysts can be found in any organ of the body.
Liver (50-70%), Lungs (20-30%), Other (brain, heart, bone)
Can form "daughter" cysts within the primary cyst
Germinal layer gives rise to scolices hydatid sand

Symptoms:
Usually asymptomatic
Mass effect - can grow to 5-10cm and can last for decades

Complications:
Superinfection with bacteria -> pyogenic abscess
Erosion of cyst into biliary tree -> cholangitis

Cyst leakage or rupture which leads to:
Anaphylaxis from parasite antigens
Seeding of daughter cysts into surrounding tissues
Cystericercosis
Cystercerci can develop in almost any body site.

Neurocysticercosis:
-Stages: Viable -> Degenerating -> Calcified
-Viable stage can last several years due to evasion of host immune response.
-Loss of ability to control host immune response resulting in inflammation and degeneration.

Symptoms:
Seizures
-Inflammation from degenerating cysts
-Most common symptom from NCC
Mass effect from giant cysts - localized neurologic deficits
Hydrocephalus - cysts in the ventricles blocking CSF circulation
Dx of Neurocysticercosis
Imaging on MRI/CT demonstrating scolex

Imaging + Serology + Epidemiologic criteria
-Household contact with T.solium infection
-Comes from, lives, frequent travel to endemic region
Dx of Hydatid Disease
Combination of imaging and serology
Serologic testing

-False positive - due to other tapeworm

-False negative - dependent on site of infection

Cyst aspiration or biopsy may be complicated by anaphylaxis or secondary spread.
Treatment of Neurocysticercosis
Seizures - anti epileptic

Anti-helminthic therapy is controversial
-Can precipitate/worsen inflammation
-Inidicated for symptomatic patients with many cysts in conjunction with corticosteroids.
Treatment for Hydatid Disease
Indication: symptomatic, large (>10cm), high chance of rupture, superinfected, mass effect.

Open surgery

PAIR (puncture, aspiration, injection, re-aspiration)

Anti-helminthic with or without above procedure.
Intestinal Roundworms (nematodes)
Adult worms live in the GI tract (SB and/or colon).

Acquisition of infection:
Ingestion of eggs:
Ascaris
Enterobius, Trichuris

Penetration of skin by larva:
Strongyloides, Hookworm

Development:
Solely within GI tract:
Enterobius, Trichuris

Transpulmonary migration phase:
Ascaris, Strongyloides, Hookworm
Enterobius Vermicularis
Pinworm - lifespan 1 month

Prevalent worldwide
U.S. - most common helminth
Children & institutionalized

Female migrates to perianal region to lay eggs.

Symptoms:
Perineal & perianal itching

Diagnosis:
Tape perianal region in the AM.
Trichuris Trichiura
Whipworm - lifespan 1 year

Tropical & subtropical regions
U.S. - SE, poor rural regions
Children may have heavy burden.

Thin whip-like portion of parasite embedded in colonic crypts.

Symptoms: (Heavy infection)
Tenesmus, rectal prolapse

Diagnosis:
ID of egg in stool or worm seen in prolapsed mucosa, colonoscopy.

In soil
Ascaris Lumbricoides
Most common helminthic infection
Lifespan 1-2 years

Tropical & subtropical regions
U.S. - SE, "night soil"
Children may have heavy burden.

Symptoms:
Löffler syndrome: fever, cough, dyspnea, eosinophilia, pulmonary infiltrate.

Malnutrition, bowel / duct obstruction.

Diagnosis:
ID of egg in stool, or seen on imaging

Adult is about 15-35 cm
Hookworm
Ancylostoma duodenale
Middle East, N Africa, S Europe

Necator americanus
Americas, SE Asia, Australia

Lifespan 1-5 years
2nd most common helminth

Symptoms:
Löffler syndrome (mild)
Abdominal pain, diarrhea, eosinophilia
Fe deficiency anemia, malnutrition

Diagnosis:
ID of egg in stool.

Sucks blood from exposed capillaries
Strongyloides Stercoralis
Tropics and subtropics:
SE Asia, Latin America, SE USA, sub-Saharan Africa

Parasitic cycle
Filariform larvae - infective

Adult lives in the mucosa.

Eggs deposited inside villi
and hatch inside the gut.

Rhabditiform larvae passed
in stool.

Autoinfection:
R larvae -> F larvae in gut
F larvae can penetrate gut
Leads to indefinite infection
Regulated by host CMI

Free-living cycle
Occurs in the soil.
Strongyloides Stercoralis Presentation
Symptoms:

Acute infection:
Localized pruritic, erythematous, papular rash at site of larval penetration

Pulmonary symptoms with eosinophilia, abdominal pain with diarrhea

Chronic infection:
Asymptomatic, fluctuating eosinophilia, recurrent rash - buttocks, perineum

Hyperinfection:
Due to increased generation of filariform larvae from impaired CMI.

Risks: corticosteroid use, other immunosuppressive drugs, hematologic malignancy, severe malnutrition, HTLV-1 infection, rarely HIV.

Increased larvae in intestines and lungs: GI ulcerations/hemorrhage, pneumonitis and hemoptysis. Can have secondary bacterial infections.

Disseminated disease: involve organs outside of autoinfection cycle
Diagnosis of Strongyloides Stercoralis
Acute infection:
Biopsy of rash, sputum microscopy
Takes 1 month from initial infection before finding rhabditiform larvae in stool.

Chronic infection (Uncomplicated):
Repeated stool exam. Single stool specimen 30% sensitivity.
Duodenal aspirate, small bowel biopsy.
Serologic testing 90-95% sensitive. May have false positives.

Hyperinfection / Disseminated (Complicated):
Readily diagnosed from stool samples, sputum samples, other tissues in disseminated disease (lymph nodes, liver, brain).
Peripheral eosinophilia often absent in disseminated disease
Strongyloides Filariform larvae
Strongyloides Filariform Larvae
Tissue Nematodes
Many have evolved mechanisms of evading the host immune response allowing prolonged survival.

Acquisition of infection:
Ingestion
-Trichinella
-Toxocara
-Dracunculus

Biting insects
Filaria
-Wuchereria / Brugia
-Onchocerca
-Loa
Trichinella Spiralis (badass because you eat bear)
Trichinosis / Trichinellosis

Worldwide distribution
Infects wide variety of carnivores/omnivores.

Eating undercooked pork, bear, walrus.
Larva invades SB -> adult (viviparous) -> larvae enter bloodstream.
Adult lives 30d, can produce 1500 larvae.

Symptoms: (dependent on inoculum size)
Enteric phase - abdominal pain, diarrhea
Systemic phase - fever, severe myalgias, periorbital edema, myocarditis -> CHF.

Diagnosis - serology, muscle biopsy.
Toxocara Canis (dogs)/cat (cats)
Toxocariasis

Worldwide distribution. Primarily children.
Eggs hardy.

Risks include: sandbox, pica, contaminated public playgrounds.

In definitive host - Ascaris-like lifecycle.
Transplacental transmission in animals.

Symptoms:
Visceral Larva Migrans
Can be asymptomatic to fulminating; covert.
Fever, eosinophilia, HSM, seizures, asthma.

Ocular Larva Migrans
Larva trapped in sub-retinal space.

Diagnosis:
Usually presumptive, serology.
Dracunculus Medinensis
Guinea worm

Tropical Africa. Ponds & wells where crustacean lives.

Larvae enter abdominal cavity and retroperitoneal space.

Mature into adults, male dies after copulation. Female migrates to connective tissue.
Female dies after discharging all her larvae.

Symptoms:
None until female adult ready to discharge (8-10m later).
Lymphatic Filariasis
Wuchereria bancrofti
Tropics - Africa, Asia, S. America

Brugia malayi / Brugia timori
Tropics - South and SE Asia

Adults -> Lymphatics (5-20 yrs)
Microfilariae -> Blood (1 yr)

Infection begins in childhood but clinical disease in adults.

Symptoms:
Acute lymphangitis - 20 bacterial infxn.

Chronic lymphedema:
hydrocele, elephantiasis, chyluria

Diagnosis:
Peripheral blood smear at night.
Filaria transmitted by flies
loa loa - west and central africa

Symptoms:
Calabar swelling - localized immune reaction to migrating adult worm.
"Eye worm" - migration of adult worm in subconjunctival region.
Microfilaremia asymptomatic, eosinophilia less common in indigenous population.
Dx - peripheral blood smear at noon


Onchocerca volvulus
Africa, C and S africa

Symptoms:
"River blindness" - microfilariae in the cornea resulting in keratitis and scarring.
Dermatitis which can lead to loss of elasticity, thickening, & depigmentation.
Adult worms in nodules are asymptomatic

diagnosis: skin snip
Schistosomiasis
~ 200 million infected worldwide.
Distribution based on the snail.

Adult lives in venous circulation.
Adult lifespan 3-5yrs, up to 30yrs.
Produce hundreds of eggs/day.

Vesical venules:
S. haematobium - Africa & Middle East

Mesenteric venules:
S. mansoni - Africa & S. America

S. japonicum - Far East & SE Asia

S. mekongi - SE Asia

S. intercalatum - Central & West Africa
Acute Schistosomiasis
Katayama Fever
Tourists and travellers (previously uninfected).
-Not seen in indigenous population probably
due to in-utero sensitization

Occurs 2-8 wks after infection (time of initial egg deposition).
-Eggs usually not found in stool or urine until late in this disease.

Systemic hypersensitivity reaction.
-Severity dependent on burden of infection/exposure with cercariae.

Symptoms: fever, malaise, myalgias, abd pain, diarrhea.

PE: hepatosplenomegaly and lymphadenopathy.

Labs: eosinophilia, pulmonary infiltrates on imaging.
Usually self-limited, resolves in 2-10 wks.
Chronic Schistosomiasis
Pathology due to immune reaction against the eggs:
Eggs secrete proteolytic enzymes through pores in the shell
Immune response results in granuloma formation and fibrosis
Severity of disease dependent on duration & intensity of infection as well as individual immune responses.

Urinary (S. haematobium)
Hematuria due to small bladder ulcerations.

Eventually leads to fibrosis and calcification of the bladder -> urine reflux and obstruction -> hydroureter / hydronephrosis -> CRF

Complications:
Secondary bacterial urinary tract infections

Associated with increased risk of bladder cancer (Squamous Cell)

Chronic Salmonella bacteriuria (attach to the tegument of schistosomes)
Hepatic Schistosomiasis
S. mansoni & S. japonicum
Eggs trapped in presinusoidal space -> preserved liver function

Early inflammatory: hepatosplenomegaly

Late fibrotic: occurs many years later, Symmer's pipestem fibrosis -> portal hypertension and esophageal varices
Intestinal Schistosomiasis
Intermittent abdominal pain and diarrhea ± blood

Large bowel mucosal inflammation, ulceration, pseudopolyposis
Ectopic Schistosomiasis
Lungs -> pulmonary hypertension
CNS -> transverse myelitis, seizures
Genitals -> infertility
Dx of Schistosomiasis
- Identification of ova in stool or urine, requires repeated sampling

- Biopsy of rectum (all species) or bladder (S. haematobium)

- Serologic testing (ensitivity 99% S. mansoni, 95% S. haematobium)
Liver fluke
Clonorchis sinensis - East Asia

Opisthorchis viverrini - SE Asia
Undercooked freshwater fish.

Adults lives within the biliary tree.
Lifespan up to 30 years.

Symptoms:
Chronic infection - RUQ abd pain, cholangitis, cholecystitis, liver abscess, pigment stones.

Associated with increased risk for cholangiocarcinoma.

Diagnosis:
Eggs in stool. US & ERCP -> adult.
Lung Fluke
Paragonimus species
East & SE Asia, Africa, America

Freshwater crabs and crayfish.

Adults live in lungs.
Lifespan up to 20 years.

Symptoms:
Abdominal pain - initial migratory phase.
Chronic cough, chest pain. Eosinophilic pleural effusion.

Diagnosis:
Eggs in sputum or stool. Egg or adult in lung biopsy tissue. Serology.
Anit Helminthic Therapy
Albendazole
Binds to helminthic b-tubulin preventing microtubule assembly, and inhibits glucose uptake.

Intestinal roundworms:
Enterobius, Ascaris, Hookworm, Trichuris
Less effective against Strongyloides

Tissue roundworms:
Trichinella, Toxocara

Larval tapeworms:
Echinococcus, Cysticercosis
Praziquantel
Damages the helminthic integument increasing permeability to Ca ions resulting in paralysis.
Damaged integument also exposes parasite antigens (eg actin) facilitating host immune attack.

Intestinal tapeworms:
Taenia, Diphyllobothrium

Trematodes:
Schistosoma, Clonorchis / Opisthorchis, Paragonimus
Diethylcarbamazine (DEC)
Decreases helminthic muscle activity -> paralysis

Alters helminthic surface membrane facilitating host immune attack.

Filaria:
-Kills microfilaria - Wuchereria, Brugia, Loa, Onchocerca
-Does NOT kill adults.
-Do not use for Onchocerca -> severe Mazzotti reaction including eye.
-Does not reverse severe lymphatic damage of elephantiasis.
---Chronic lymphatic damage due to secondary bacterial infections
Ivermectin
Activates the opening of gated chloride channels found only in nematodes resulting in paralysis.

Filaria:
Kills microfilaria - Wuchereria, Brugia, Loa, Onchocerca

First line agent for Onchocerca

Does NOT kill adults.

Intestinal roundworms:
First line agent for Strongyloides
Summary