Lecture 4.    Nematodes (Roundworm): Intestinal and Systemic         J. D. MacLean                                                

Overview

                      Clinical Complications

Large intestine

Trichuris (threadworm)           oral hemorrhagic colitis

Enterobius (pinworm)             oral perianal itch

Small intestine

Ascaris lumbricoides (round worm)     oral small intestine obstruction(hookworm)

                                                            iron deficiency anemia

Strongyloides stercoralis       duodenitis

                                              cutaneous larva currens

                                              hyperinfection in immunocompromised

Diagnosis: stool examination for larvae (strongyloides) or eggs (the rest)

Treatment: albendizole or ivermectin (strongyloides) or mebendazole (the rest)

Systemic

Trichinella spiralis or nativa raw pork, bear,walrus

                                                myositis, diarrhea

                                                trichinosis diagnosis: eosinophilia, raised CPK, serology

Toxocara canis oral eosinophilia, hepatomegaly,

(visceral larva migrans) dx: serology

Wuchereria bancrofti mosquito vector adults block lymphatics;

(lymphatic filariasis) elephantiasis, chyluria or hydrocoele

dx: microfilaria in blood

Onchocera volvulus black fly vector itchiness, skin nodules,

(river blindness) blindness

dx: adults in skin nodules, microfilaria in skin biopsies (snips)

Loa loa horse fly vector Kalabar swellings (short

(eye worm) lived), eye worm

dx: microfilaria in blood

Diagnosis: blood or tissue examination for microfilaria; serology for Trichinella and Toxocara

Treatment: Wuchereria, Onchocerca, Loa- ivermectin, diethylcarbamazine

Trichinosis, Toxocara- thiabendizole, albendizole

Introduction

The helminths (from the Greek meaning worm) are higher, multicellular forms of parasite with specialized organs. There are two basic groups

Nematodes - roundworms

Platyhelminths - flatworms - cestodes (tapeworm)

- trematodes (fluke)

Nematodes

Characteristics - round in cross section

- bilaterally symmetrical

- variable size - 1 mm to 1 meter

- organs - digestive, nervous, excretory, cuticle, muscle, sexual

- develops by molting (shedding cuticle)

- separate sexes

- reproduction and development: egg egg fertilization embryo in egg larva 4 molts adult

Categories

Bowel nematodes - with adults in bowel

Ascaris lumbricoides

Trichuris trichiura

Ancylostoma duodenale and Necator americanus

nterobius vermicularis

Strongyloides stercoralis

Tissue nematodes - adults or larval stage in tissue

Trichinella spiralis

Toxocara canis (visceral larva migrans)

Filaria - Wuchereria bancrofti

Brugia malayi

Onchocerca volvulus

Loa loa

etc.

Trichuris trichiura (Whipworm)

Epidemiology:- about 350 million infected, in some areas 90-100% of population

- restricted to warm climate by necessity for egg to embryonate on moist warm soil for 10-14 days before becoming infective

- spread: fecal - oral (esp. via foods and hands)

Biology: - life cycle: people infected by swallowing embryonated egg egg hatches in small intestine attaches to colonic epithelium and matures to egg laying in 3 months.

- organism: adult female, approx. 45 mm

                                                    eggs approx. 52 mu long

Clinical - clinical: 99% assymptomatic

heavy load gives diarrhea dysentery anemia

rectal prolapse

Diagnosis: - examine stool (standard techniques) - pathognomonic egg

Treatment: - mebendizole, albendizole

Problems: - lack of cost effective control methods in LDC (least developed countries)

Enterobius vermicularis (Pinworm)

Epidemiology :-very common in all geographic areas - 20%+ in Toronto's children

- spread: fecal - oral; eggs can survive days to weeks in environment

Biology: - infected by swallowing egg which hatches after contact with stomach and matures to adult which then resides in lumen of caecum (from egg to adult maturation in 15-43 days) . Female migrates onto perianal skin to lay eggs at night.

- organism: adult female approx. 10 mm long; egg approx. 55 µm long

Clinical: most asymptomatic

<10% anal pruritus; rarely vaginitis

Diagnosis: less then 10% found in stools, i.e. not a useful examination;

best is pinworm swab - cellophane tape swab, or sticky paddle

Treatment: mebendizole

Problems: insensitivity of pinworm swabs (intermittent deposition of eggs) : eradication of infection from a family.

Ascaris lumbricoides (Roundworm)

Epidemiology: About 650 million infected worldwide mainly tropics. Transmission by faecal- oral; egg very resistant, can survive years

Biology: egg ingested, hatches in duodenum; larvae penetrate intestine wall, enter blood vessels and embolize through liver to lungs. They then migrate into airspaces, up trachea and are swallowed, taking up permanent adult residence in the small intestine - 2 months from egg to mature adult

Organism: adult female 20-35 cm long; egg approx. 68 mu long

Clinical: related to number of worms; small numbers asymptomatic

- large numbers of larva transiting lung -- Loefflers pneumonitis

- large numbers of adults in intestine -- obstruction, pains

- at times adults migrate into bile duct, up esophagus, through surgical anastomoses of intestine

- cause malnutrition if in large numbers

Diagnosis: stool examination

Treatment: mebendizole

Strongyloides stercoralis

Epidemiology: The only important helminth that can complete its life cycle in the human host and hence increase its numbers. Special problem in immunocompromized because of this. Mainly a tropical parasite because requires warm moist soil for transmission.

Transmission: skin contact with invasive larvae in soil.

Biology: larvae passed into soil in human feces where mature in several days to skin invasive (filariform) larvae. Can exist for months in soil "free living" by completing life cycle without contact with human host man. Larvae penetrate skin, move via blood vessels to lung, invade airspace, move up bronchi, are swallowed, and then penetrate small intestinal mucosa where they mature to adults in submucosa. They deposit eggs in submucosa and these hatch and migrate into intestinal lumen. Small numbers of larvae get into blood vessels and circulate again to produce more adults (internal autoinfective cycle) or invade perianal skin and enter blood vessels to eventually produce new adults (external autoinfective cycle).

Organism: female adult - 2.7 mm long, rhabditiform larvae approx. 0.38 mm, filariform larvae approx. 0.6 mm long

Clinical: - most asymptomatic

- GI - peptic ulcer like symptoms, diarrhea rarely, cutaneous larvae currens (buttock dermatitis)

- hyperinfection (disseminated strongyloides) in immunocompromised; spread of larvae to peritoneum, lung, CNS with contamination of those organs with gram negative bacteria; transmural small intestine spread of larvae and bacteria with necrosis of intestine

Diagnosis: stool examination . NB: difficult to find strongyloides

duodenal aspirate or Enterotest duodenal string test

serology

culture of stool (Harada-Mori or Baerman) allows "free living" strongyloides to multiply

Treatment: albendazole, ivermectin

Problems: diagnostic techniques not sensitive

Ancylostoma duodenale and Necator mericanus

(Hookworm)

Epidemiology: transmission by contact of skin with soil contaminated with larvae.

Biology: eggs in feces hatch and mature as larvae in warm moist soil; develops into to infective (filariform) larvae in 7 days. Filariform larvae penetrate skin of host (e.g. bare feet), circulate to lungs where they penetrate alveoli, move up bronchi and are swallowed. Then, as adults, they attach by mouth to small intestinal mucosa and suck blood. (Necator 0.03 ml/day, Ancylostoma 0.15 ml/day). Prepatent period (time from skin penetration to egg production) is 4-5 weeks. Adults can live 5-15 years.

Organism: Adult female 12 mm long (A.d) ova approx. 60 mu long

Adult female 10 mm long (N.a) ova approx. 65 mu long

Clinical: Usually assymptomatic 90%

Heavy infections (20 - 100 worms)                                  

- iron deficiency anemia

- malnutrition from protein loss

- rarely itch at skin entry site

Diagnosis: Stool examination for ova

Treatment: mebendizole

Problems: Lack of cost effective LDC (least developed country) control

Cutaneous Larva Migrans

Ancylostoma caninum

Ancylostoma braziliensis

Non-human (dog, cat etc) hookworms that penetrate human skin (as does human hookworm) but cannot go further. Migrate and produce serpiginous itchy traits in subcutaneous tissue.

Treatment: albendizole, ivermectin.

Laboratory procedures for diagnosing intestinal helminths

Stool ova and parasite (O & P) examination

1. Direct microscopic examination: not very sensitive

2. Kato technique: uses glycerin mixed with stool which "clears" (makes transparent) fecal debris making eggs visable. Can be used for counting eggs/gram feces.

3. Concentration techniques: zinc sulfate solution - eggs float to top of solution

formal ethyl acetate

4. Culture: Harada Mori or Baerman culture - only strongyloides

will multiply in an incubated stool specimen - increases numbers of larvae and sensitivity of microscopy.

Eosinophilia

Increased blood eosinophil counts are normal host response to helminth infection; not seen in protozoan infections

very high moderate low or absent

% of total WBC count (30 - 80%) (10 - 30%) (0 - 10%)

Trichinella hookworm Ascaris

Toxocara Strongyloides Trichuris

Enterobius

Trichinella spiralis, nativa (Trichinosis, Trichinellosis)

Epidemiology:

Common in geographic areas where undercooked pork is eaten, in the Arctic where raw walrus is eaten and among bear hunters in North America; 5-15% of North American population infected at some time.This is a zoonosis infecting most carnivorous mammals; especially pigs, bear, walrus, and rats. Man infected by eating Trichinella infected uncooked meat.

Biology

Encysted larvae in meat, when eaten, excyst (hatch) and penetrate into small intestine submucosa where they mature to adults in 1-2 weeks producing larvae which penetrate blood vessels and diseminate to all muscles. There, they cause inflammation and encyst in muscle cells, remaining viable for many years. Adult female is 5 mm.long

Clinical: Early (1-2 weeks) - abdominal pain, diarrhea

Midterm (2-6 weeks) - myalgia, muscle weakness, facial and periferal edema, rash; sometimes encephalitis and myocarditis

Long term (months) - usually assymptomatic despite presence of trichinella cysts

Diagnosis: - clinical picture with laboratory support (eosinophilia and raised CPK)

- muscle biopsy with trichinoscopy

- serology

Treatment: steroids and mebendizole

Problems: education of meat consumers

lack of good drugs

Toxocara Canis (Visceral Larva Migrans)

Epidemiology: This is a zoonotic roundworm with the dog as reservoir. Uncommon human infection but consequences serious. Transmission is dog fecal (dog)-oral (human) .

Dog feces especially in sandboxes and parks where children play. Eggs in soil viable and infective for several months.

Biology: Adult has cycle in dog the same as Ascaris in man. Man an accidental "dead end" host. Eggs ingested by man/child, hatch after stomach passage and larvae migrate through small intestinal wall into vasculature and then to liver and lungs and beyond. Do not mature to adults but cause local inflammation.

Organism: In man larvae are 0. 5 mm long; egg in dog feces, looks like a round Ascaris egg.

Clinical: - Hepatomegaly, pneumonitis, encephalitis, fever and eosinophilia in heavy infections

- Retinal mass (similar to retinoblastoma) or focal retinitis when single larva reaches retina.

Diagnosis: - Clinical syndrome with very high eosinophilia

- Serology

- Nothing in stools

Treatment: Steroids and thiabendizole or albendizole

Problems: - Control of dog and cat feces in parks and sandboxes

- Diagnosis difficult because of nonspecificity of symptoms

Other Nematodes

1. Anisakis sp: Salt water fish (cod, herring etc) roundworm that when ingested produces a nematode inflammatory mass in stomach of raw fish consumer or eosinophilic gastritis (mainly Japan, Holland).

2. Angiostrongylus cantonensis: nematode of amphibians producing eosinophilic meningitis (mainly SE Asia).

3. Gnathostoma spinigerum: nematode of cat producing migratory local subcutaneous swelling, and at times encephalomyelitis (mainly SE Asia).

4. Capillaria philippinensis: small intestine nematode producing diarrhea and malabsorption (Philippines).

Filariases

Overview

This is a group of thread-like roundworms that are acquired via an insect (intermediate host) vector. The adults live in various tissues (lymphatics, subcutaneous etc.) Ansd are usually difficult to remove for diagnosis. The microscopic larvae (called microfilaria) of the adult female are very motile, circulating in blood or subcutaneously and because they are produced in such large numbers, are much easy to find. Disease can be produced by either the adults or the microfilaria or both, depending on the species.

Wuchereria bancrofti and Brugia malayi (lymphatic filariasis)

Epidemiology:

Cause lymphatic filariasis occasionally terminating in elephantiasis. 250 million humans affected; widely distributed throughout tropical and subtropical countries. Transmitted to humans by mosquitoes.

Organism: Adults live in afferent lymphatic vessels

Microfilariae born to female adult worms circulate in the blood. W. bancrofti microfilariae circulate preferentially from 10:00 p.m. to 2 a.m. - this corresponds to peak activity of vector mosquitoes.

Microfilaria develops to a 3rd stage juvenile larva in mosquito, and it is transmitted to new host at the time of feeding. Larva then matures to adult in the lymphatics; maturation to adult requires several months.

Adult 50 mm x 150 m

Clinical

Asymptomatic microfilaremia

Lymphangitis and lymphadenitis

Orchitis and epididymitis

Elephantiasis

Tropical eosinophilia

Chylurea

Diagnosis:

Blood examinations (esp. Night blood) for microfilaria

Serology

Treatment: Anti-inflammatory agents

Diethylcarbamazine (DEC), Ivermectin, albendizole

Prevention: Control of mosquitoes

Insect repellants

Onchocerca volvulus (onchocerciasis) (River blindness)

Epidemiology: 20 million affected. Predominantly Africa and South and Central America, most commonly along rivers, the breeding site of the black fly vector.

Biology: Infective larvae transmitted to man by black flies of the genus Simulium.

Larvae develop to adults in subcutaneous tissue

Adult female produces microfilaria which wander in subcutaneous tissue, cornea, and anterior chamber of eye. Black flies acquire microfilaria on biting infected humans

Adult 33-50 cm x .3 mm Microfilaria 330 m x 6 m

Clinical : Skin nodules, onchocercal dermatitis, hanging groin, blindness

Diagnosis: Skin snip (small biopsy and incubation for microfilaria)

Treatment: Anti-inflammatory agents

Diethylcarbamazine

Ivermectin

Loa loa (loiasis)(Eye worm)

Biology: Adult worm lives in subcutaneous tissue and wanders freely

Microfilaria in subcutaneous tissues and blood

Transmitted by the bite of deer flies of the genus Chrysops

Adult: 55 mm x 0.5 mm Microfilaria: 280 m x 7m

Clinical: Calabar swelling, migrating worm in conjunctiva

Diagnosis: Excision of adult worm

Blood for microfilariae

Treatment: Diethylcarbamazine, Ivermectin