A. Classification and Organisms

1. Parastitic Organisms
   1. Protozoa - single celled eukaryotes resembling yeasts
   2. Helminths - macroscopic multicellular worms
2. Helminths
   1. Nematodes (Roundworms) - spindle shaped organisms; separate sexes
   2. Cestodes (Tapeworms) - head with segmented body; hermaphroditic sexes
   3. Trematodes (Fluke) - leaf-shaped organisms, oral and ventral suckers; hermaphrodites
3. Nematodes
   1. Enterobius vermicularis (pinworm)
   2. Trichuris trichuria (whipworm)
   3. Ascaris lumbricoides (large roundworm
   4. Necator americanus (hookworm)
   5. Ancylostoma duodenale (hookworm)
   6. Strongyloides stercoralis
   7. Onchocera volvulus (tissue nematode)
   8. Trichinella spiralis (trichinosis)
   9. Toxocara canis (visceral larva migrans)
   10. Ancyclostoma braziliense (cutaneous larva migrans)
   11. Filiarial Organisms (elephantiasis)
4. Cestodes
   1. Diphyllobothrium latum
   2. Taenia sgainata
   3. Taenia solium
   4. Hymenolepis nana
   5. Echinococcus granulosus and multilocularis (hydatid disease)
5. Trematodes
   1. Schistosomiasis: Schistosoma mansoni, S. haemoatobium, S. japonicum
   2. Tissue/Intestinal: Paragonimus (especially lung), Clonorchis, Opisthorchis, Fasciola
6. Organisms are discussed alphabetically below in more detail:
   1. Ascariasis
   2. Cestodes
   3. Cysticercosis
   4. Echinococcus (Hydatid Disease)
   5. Enterobiasis
   6. Fasciola
   7. Filariasis
   8. Hookworms
   9. Onchocerciasis
   10. Paragonimiasis
   11. Strongyloidiasis
   12. Trichuriasis
7. Near-eradication of many of these organisms is now possible with safe oral agents [9]

B. Populations at Risk

1. International students and travelers
2. Migrant laborers
3. Refugees and Immigrants [14]
   1. Universal screening of immigrants (stool analysis) may be carried out
   2. Presumptive treatment with albendazole of all immigrants, without stool analysis, is safe, cost effective, and saves lives (and money)
   3. Presumptive albendazole treatment is more cost effective than universal screening
4. Children of foreign adoptions
5. Homeless
6. Ingestion of water
7. Major Worldwide Pathogens /number (in millions) infected [1]
   1. Ascaris (common roundworm) ~1000
   2. Trichuris (whipworm) ~700
   3. Necator and Ancylostoma (hookworm) ~650
   4. Strongyloides (threadworm) ~50
   5. Toxocara (visceral and ocular larva migrans) ~40% of children
   6. Enterobius (pinworm) ~15% of children

C. Diagnosis

1. Symptoms are usually vague
2. Anorexia and nausea are common with intestinal parasites
3. Allergic symptoms such as hives may develop
4. Eosinophilia is usually mild with simple infections and may be absent
5. Parasitic Infections with High-Level Eosinophilia
   1. Strongyloidiasis
   2. Filariasis
   3. Hookworm
   4. Schistosomiasis
   5. Trichinellosis
   6. Ascaris pneumonia
   7. Toxocara (visceral larva migrans)
6. Stool examination for ova and parasites is best diagnostic test
7. Sensitivity varies with organism and lab's experience
8. Fluctuating hepatic lesions may occur with Fasciola [2]

D. Parasites with Eosinophilia - Organ Involvement (Table, Ref [34])

1. Gastrointestinal
   1. Hookworm - soil; worldwide
   2. Ascaris - unpurified water, raw fruits, vegetables; worldwide
   3. Trichuris - unpurified water, raw fruits, vegetables; tropical
   4. Anisakis - raw fish; worldwide
   5. Heterophyes - raw fish; Middle East, Asia
   6. Capillaria (C. philippinensis) - raw fish; Asia []
2. Liver
   1. Clonorchis - raw fish/seafood; Asia
   2. Opisthorchis - raw fish/seafood; Asia
   3. Schistosoma japonicum - freshwater swimming; Asia
   4. Schistosoma mansoni - freshwater swimming; Latin America, Middle East
   5. Fasciola - watercress; worldwide
   6. Toxocara ssp - dogs, soild; worldwide
3. Lung
   1. Paragnoimus - crabs and crayfish; Asia
   2. Ascaris
   3. Strongyloides - soil; tropical
   4. Brugia malayi; insect bite; Asia
   5. Wuchereria bancrofti; insect bite; Tropical
   6. Toxocara ssp.
4. Central Nervous System (CNS)
   1. Angiostrongylus - raw seafood; Asia
   2. Gnathostoma - raw fish and poultry; Asia
5. Eye
   1. Loa loa - insect bite; Africa
   2. Onchocerca - insect bite; Africa
   3. Toxocara ssp.
6. Other
   1. Bladder: Schistosoma haematobium - freshwater swimming; Middle East, Africa
   2. Muscle: Trichinella - pork; worldwide
   3. Lymphedema: Wuchereria bancrofti - insect bite; tropical

E. Ascariasis

1. Ascaris lumbricoides - roundworms (nematode)
2. Risk increased in Southeast Appalachian area
3. About One billion humans infected worldwide
4. Ingestion of eggs and adherance to small intestine where they hatch
   1. Gut penetration
   2. Tracheal migration then
   3. Swallowing to the upper GI tract
   4. Parasitize the entire human small intestine
   5. Can be acquired from pigs, but mainly from other humans
5. May be up to 35cm in length
6. Symptoms
   1. Non-specific abdominal pain, nausea, bloating and diarrhea
   2. Upper respiratory symptoms may occur - usually with eosinophilia, possible wheezing
   3. Seasonal pneumonia mainly with eosinophils may occur (Loffler's pneumonia)
   4. Small bowel obstruction
   5. Biliary obstruction with right upper quandrant pain, chronic cholangitis, fever [30]
   6. Pancreatic obstruction
7. Treatment [1,35]
   1. Single dose albendazole, mebendazole, or pyrantel show high cure rates [35]
   2. Albendazole (Albenza®) 400mg po x 1 OR
   3. Mebendazole (Vermex®) 100mg po bid x 3 days OR 500mg po x 1 OR
   4. Pyrantel pamoate (in pregnancy) 11mg/kg (to 1gm maximum) for 3 days
   5. Nitazoxanide (Alinia®) 200mg po qd x 3 days may be effective [23]
   6. Levamisole 2.5mg/kg once
8. Eradication [9]
   1. Albendazole plus diethylcarbamazine reduced roundworm prevalence from 34% to 2.3%
   2. Albendazole plus ivermectin reduced hookworm roundworm from 33.5% to 6.1%
   3. Albendazole alone reduced roundworm prevalence from 28.4% to 0.9%
   4. Lavamisole plus mebendazole reduced hookworm roundworm from 62% to 1.4%
   5. Pyrantel-oxantel reduced hookworm roundworm from 23% to 1.4%

F. Cestodes [1,24]

1. Majority are intestinal tapeworms
2. May come from fish, beef, pork, or dogs
3. Species
   1. Most common overall is Taenia saginata (beef tapeworm) [25]
   2. Taenia solium (pork tapeworm)
   3. Diphyllobothrium latum - fish tapeworm
   4. Most common in USA is the dwarf tapeworm, Hymenolepis nana (dwarf tapeworm)
   5. Echinococcal species cause hydatid disease
4. T. asiatica [25]
   1. In Asia, T. saginata relative is called T. asiatica
   2. In Asia, T. asiatica is found even in persons who ate pork
   3. Found in taiwan, Korea, china, Vietnam and Indonesia
5. Taenia solium / Pork Tapeworm
   1. Mainly in Central and South America
   2. Larval stage infection in humans called cysticercosis
   3. Extraneural cysticercosis is generally asymptomatic
   4. Infection of nervous system causes neurocysticercosis (and ophthalmic cysticercosis)
   5. Major cause of epileptic seizures, mainly in underdeveloped countries
   6. Cysts are rounded or oval vesicles size 2mm-2cm, usually in cerebral hemisphres
   7. Cysts can also be found in cerebellum, ventricles, brainstem, spine, other areas
   8. Serology is now best diagnostic method
   9. Eosinophils in cerebrospinal fluid suggests neurocysticercosis
   10. Computed tomographic (CT) or MRI imaging suggestive for neurocysticercosis
   11. Glucocorticoids of most benefit for neurocysticercosis
   12. Symptomatic treatment and surgery may be used
   13. Antiparasitic drugs have shown marginal benefit in neurogical disease
6. Treatment of intestinal tapeworms [3]
   1. Praziquantel (Biltricide®) - 5-10mg/kg x 1 oral is usual dose, 25mg/kg po
   2. Niclosamide (Niclocide®) - 2gm (500mg x 4 tabs) x 1 dose
   3. Nitazoxanide (Alinia®) 200mg po qd x 3 days may be effective [23]
7. Recombinant vaccines against several taeniid cestodes have shown initial efficacy [25]

G. Cysticercosis

1. Tissue infection with T. solium
2. Multiple cysts throughout body, usually asymptomatic
3. Neurocysticercosis [18,19]
   1. CNS cysts of variable size
   2. Giant subarachnoid cysts (>50mm) can occur
   3. Intracranial pressure elevation can occur
   4. May cause seizures, hydrocephalus, focal deficits [18]
4. Diagnosis by serology and imaging (CT scanning)
5. Therapeutic responses depends on extent of disease
6. Treatment
   1. Praziquantel 50mg/kg/d divided tid for 30 days OR
   2. Albendazole 15mg/kg/d in 2-3 divided doses for 8 days
   3. Neurocysticercosis (with seizures) albendazole 800mg qd + dexamethasone 6mg qd
   4. Neurocysticercosis also responds to prazquantil (similar rates as albendazole) [32]
7. Treatment of Giant Cystic Neurocysticercosis [19]
   1. Albendazole with optional praziquantel for 4 week courses
   2. Up to 4 of these 4 week courses can be given
   3. Dexamethasone is given to all patients
8. Efficacy in Neurocysticercosis [32]
   1. Either albendazole or praziquantil (cysticidal drugs)
   2. Cysticidal drugs associated with complete resolution of cystic lesions in 44%
   3. Cysticidal drugs reduced seizures better than non-cysticidal
   4. About 45% reduction in seizures with neurocysticercosis and seizures with albendazole + dexamethasone for 10 days [26]

H. Echinococcus (Hydatid Disease) [10,16]

1. Invasive cestode, often coinfecting with intestinal tapeworms
2. E. granulosus [22]
   1. Transmitted by dogs in contact with livestock, usually sheep
   2. Definitive hosts are carnivores which drop hermaphroditic eggs in their stool
   3. These eggs developed in intestines of the definitive host (usually a dog)
   4. Livestock (intermediate hosts) usually ingest parasite's eggs
   5. The chitinous shell of the parasite eggs are digested in the duodenum
   6. Embryos then enter the portal circulation and travel to visceral capillary beds
   7. From there, they develop into cystic metacestodes
   8. The intermediate host arnivores then digest the viscera of dead intermediate hosts
   9. The large tissue cysts form in the various viscera
   10. Humans can act as intermediate hosts
   11. Sites: liver (60%) > lung (25%) >> other organs (spleen, kidney, heart, others)
   12. Diagnosis: serology and imaging; usually discovered accidently on radiograph
   13. Hepatic cysts may rupture into peritoneum
   14. Ruptured cysts may cause anaphylaxis, dissemination, or both
3. E. multilocularis
   1. Transmitted by wild animals, usually foxes, wolves and mice
   2. Forms multiple cysts
   3. May be mistaken for tumors
   4. Causes alveolar echinococcosis
   5. Less susceptible than E. granulosus to currently available agents
4. E. vogeli
   1. Causes polycystic hydatid disease
   2. Restricted to Central and South America
5. E. oligarthrus - only a few reports of disease in humans
6. Treatment [10]
   1. Surgery recommended for hepatic hydatid cysts
   2. Percutaneous drainage may also be used with drug therapy
   3. Benzimidazoles mebendazole or albendazole are effective in liver cyst cases
   4. Albendazole 10mg/kg divided (usually 400mg po bid) more effective than mebendazole
   5. Albendazole can be administered indefinitely with generally good tolerance [10]
   6. Percutaneous drainage with albendazole is recommended for most patients

I. Enterobiasis

1. Enterobius vermicularis - Pinworm (nematode)
   1. Small intestinal parasite, resides in ileo-cecal ergion
   2. Lays eggs in anal canal and peritoneum
2. Susceptible persons
   1. Most common helminth in North America
   2. Up to 80% of school aged children in USA
3. Symptoms
   1. Anal pruritis
   2. Irritability and sleeplessness
   3. Vulvovaginitis is uncommon
4. Diagnosis
   1. Examination of perianal skin is better than stool tests
   2. Clear celophane tape is applied to unwashed perianal skin in morning
   3. Under microscope, eggs are colorless and measure 50-60µm on one side
5. Treatment [3]
   1. Pyrantel pamoate (Antiminth®) 11mg/kg x 1 (preganancy okay); repeat after 2 weeks OR
   2. Mebendazole (Vermex®) 100mg x 1 (children >2 years and adults); repeat in 2 weeks OR
   3. Albendazole 400mg po x 1; repeat in two weeks
   4. Entire family should be treated and all bedding cleared

J. Fasciola [2]

1. F. hepatica or F. gigantica
2. Rare in North America
3. Usually acquired by eating freshwater plants
4. Symptoms in ~85% of persons
   1. Fever
   2. Abdominal pain
   3. Headache
   4. Itch or urticaria
5. Hepatic lesions are common and fluctuate as organisms mature
6. Chronic biliary stage occurs in 2-4 months
   1. Biliary pain (colic)
   2. Fatigue
7. Diagnosis
   1. Clinical suspicion
   2. History of watercress ingestion
   3. Eosinophilia
   4. Hypodense multiple lesions on computerized tomographic scan of liver
   5. Stool analysis often not helpful, including culture
   6. Serologic assay positive
8. Triclabendazole (compassionate use from Novartis) is effective

K. Filariasis

1. Eight major mosquito-borne nematodes cause filarial infections:
   1. Wuchereria bancrofti
   2. Brugia malayi
   3. Loa loa
   4. Onchocerca volvulus (river blindness, see below)
   5. Mansonella: M. perstans, M. streptocerca
   6. Mainly transmitted by mosquitos
2. Lymphatic Filariasis [6,29]
   1. Usually caused by Wuchereria bancrofti and less often by Brugia malayi
   2. Threadlike-worms, lie coiled in lymphatic vessels (lifespan ~10 years)
   3. About 40 million people worldwide are infected
   4. Symptoms: obstructive lymphatics with occasional massive lymphedema (elephantiasis)
   5. Microfilaria found in the bloodstream
   6. May present with hematuria due to pyelolymphatic fistula [27]
   7. Ivermectin is very effective in single doses
   8. Combination of ivermectin with albendazole single dose extremely effective
   9. Caution when using azoles in heavily infected individuals (may cause anaphylaxis)
   10. Annual single dose diethylcarbamazine with ivermectin can reduce serious human infections by ~50% and reduce mosquito carriage by up to 98% [11]
   11. Four annual treatments with diethylcarbamazine ± ivermectin reduces carrier rates ~90% and incidence of hydrocele and leg edema by 70-85% [21]
   12. Most of these agent have activity against microfilariae, not adult macrofilariae
   13. Doxycycline 200mg po qd x 8 weeks had good activity against adult worms (macrofilariae) as well as microfilariae and is well tolerated [28]
3. Eradication Potential [31]
   1. Eradication of lymphatic filariasis may now be possible
   2. Mass drug administrations across large communities have been effective
   3. Diethylcarbamazine and albendazole once yearly for 5 years greatly reduces prevalence
   4. In meta-analyses, prevalence reduced from 16.7% to 5.3% with diethylcarbamazine plus albendazole or from 12.6% to 4.6% with ivermectin plus albendzole [9]
   5. Mass drug administration greatly reduces transmission, prevalence
4. Loaiasis
   1. Caused by Loa loa (eyeworm)
   2. Filarial disease of West Africa
   3. Intense tearing pain and "fear" (subconjunctival migration)
   4. Fever, itching, hives and pain when worms migrate through skin
   5. Constant marked eosinophilia
   6. Diethylcarbamazine has some efficacy

L. Hookworms [5]

1. Caused by Necator americanus (New World) and Ancylostoma duodenale (Old World)
   1. Both types native through tropical Eastern hemisphere
   2. Necator found in southeastern USA and South America
   3. Estimated 740 million cases in rural tropics and subtropics (mainly in impoverished areas)
   4. Most cases in Asia (China greatest) followed by sub-Saharan Africa
   5. Parasitize the upper hhhhhhhhhuman small intestine
2. Life Cycle
   1. Juveniles develop in soil from eggs in feces
   2. Juveniles become dormant, than enter moist, sandy soil
   3. Molt into infective, filariform larvae (called "third-stage" larvae)
   4. Larvae can penetrtae skin (usually through bare feet)
   5. Larvae migrate to lungs, then coughed up and swallowed
   6. Migrate to small intestine
3. Symptoms
   1. Pruritic rash on feet, also called "ground itch"
   2. Iron deficiency anemia and malnutrition (particularly in children; stunts growth)
   3. Geophagia - desire to eat dirt (with iron deficiency anemia, pica)
   4. Protein malnutrition; hypoalbuminemia also due to malabsorption
   5. Chronic Fatigue
   6. Skin invasion by zoonotic Ancylostoma braziliense causes cutaneous larva migrans (CLM)
   7. CLM is self-limited, with 1-5cm serpinginous 1-2mm wide eruptions under skin
4. Treatment
   1. Mebendazole (Vermox®) 100mg bid x 3 days OR 500mg po x 1 (preferred) OR
   2. Albendazole 400mg po x 1 OR
   3. Pyrantel 11mg/kg po (up to 1gm) qd for 3 days
   4. Praziquantel may be combined with mebendazole
   5. Mebendazole - safe in second and third trimesters of pregnancy and clearly reduces anemia, numbers of stillbirths, and perinatal deaths in infected patients [15]
   6. Mebendazole should be avoided in the first trimester (some increase in birth defects)
   7. Albendazole more effective than mebendzole and pyrantel []
   8. Nitazoxanide (Alinia®) 200mg po qd x 3 days may be effective [23]
   9. Levamisole 2.5mg/kg once; repeat after days for heavy infection
   10. Iron supplementation as needed
5. Eradication
   1. Albendazole plus diethylcarbamazine reduced hookworm prevalence from 10.3% to 1.9%
   2. Albendazole plus ivermectin reduced hookworm prevalence from 7.8% to 0%
   3. Albendazole alone reduced hookworm prevalence from 8.1% to 1.3%

M. Onchocerciasis [12,29]

1. River Blindness
   1. Caused by skin filaria Onchocerca vovulus
   2. Carried by black river flies (Simulium)
2. Mainly in tropical and Western Africa; some Yemen and Latin America
3. Symptoms and Signs
   1. Subcutaneous nodules
   2. Thickened pruritic skin and punctate keratitis
   3. Classical "leopard-skin" appearance of skin: hypopigmentation on dark-skinned persons
   4. Progressive blindness
4. Acute and chronic inflammatory reactions, mainly hypersensitivity type
5. Diagnosis
   1. Microfilariae in thin skin sample OR
   2. Slit lamp exam of cornea
6. Treatment
   1. Ivermectin 200µg/kg/day is main therapy but daily adminstration difficult
   2. Treatment with 400µg/kg initially, then 400-800µg/kg q 3 months very effective [20]
   3. Intermittent suppressive therapy with ivermectin 150µg/kg q6 months is highly effective
   4. Intermittent ivermectin use not associated with development of resistance [33]
   5. Doxycycline 100mg qd x 6 weeks preceding ivermectin is also effective
   6. In patients with very high parasite loads, ivermectin can induce hypotension

N. Paragonimiasis [7]

1. Food-borne parasitic infection
2. Endemic in Asia, Africa, Americas
3. Humans infected when eatining raw or partially cooked crab or crayfish
4. Symptoms of infection usually occur within a few months of ingestion
5. Can live in human host for up to 20 years
6. Symptoms and Signs
   1. Lung is major target organ
   2. Patients usually present with cough and dyspnea
   3. Night sweats, weight loss, hemoptysis, pleuritic chest pain
   4. Ectopic infections in subcutaneous tissues and brain can lead to symptoms
   5. Brain involvement usually with headache; seizures may occur
7. Evaluation
   1. Chest radiographs with infiltrates, pleural effusions and thickening
   2. Eosinophilia - may be marked (up to 25%)
   3. Diagnosis by finding organism in sputum, gastric washings, pleural fluid, feces
8. Pulmonary disease rarely fatal, but cerebral disease can be fatal
9. Treatment with praziquantel x 2 days

O. Strongyloidiasis

1. Strongyloides stercoralis (nematode)
2. Prevalence increased in immigrants and in southern USA
3. Route of Infection: Host skin penetration by filariform larvae
4. Signs and Symptoms
   1. Asymptomatic in most immunocompetent persons
   2. Diarrhea, nausea, cramping and anorexia may occur
   3. Fatal dissemination may occur in immunocompromised hosts
5. Diagnosis
   1. Ova and Parasite examination not sensitive
   2. May require duodenal aspiration
   3. Serology may be helpful (available from Centers for Disease Control)
6. Treatment [1]
   1. Thiabendazole 50mg/g/d in 2 doses x 2 days
   2. AND/OR Praziquantel (anti-mobility agent) 40mg/kg/d in 2 doses
   3. OR Ivermectin 200µg/kg/d x 1-2 days
   4. Longer courses in disseminated disease, with therapy for for bacterial sepsis

P. Trichuriasis

1. Trichuris trichiura - whipworm (nematode)
2. Often found with Ascaris infection
3. Common in Southern USA, foreign immigrants (usually children), and migrant workers
4. Life Cycle
   1. Eggs require 3 weeks in soil for development
   2. Ingested eggs progress to jejunum and hatch into larvae, burrow into wall
   3. The larvae remain in wall for one week then progress to colon
   4. Adults are 3-5 cm
   5. Parasitize the colon, especially the cecum
5. Symptoms and Signs
   1. Usually asymptomatic
   2. Colitis, typically with mild chronic bloody diarrhea
   3. Proctitis, rectal prolapse, anorexia
   4. Growth impairment
6. Treatment [1,13]
   1. Multiple doses are required; single doses of antihelminthics are not satisfactory [35]
   2. Mebendazole 100mg po bid x 3 days OR 500mg x 1 OR
   3. Albendazole 400mg po x 1 or qd x 3 days OR
   4. Nitazoxanide (Alinia®) 200mg po qd x 3 days may be effective [23]
   5. Family screening for asymptomatic infection
7. Eradication [9]
   1. Albendazole plus diethylcarbamazine reduced whipworm prevalence from 55% to 43%
   2. Albendazole plus ivermectin reduced whipworm prevalence from 42.7% to 8.9%
   3. Albendazole alone reduced whipworm prevalence from 52% to 32%

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