Lecture 4.    Nematodes (Roundworm): Intestinal

Overview

intestinal-- Strongyloides larva	systemic-- microfilaria (Wuchereria)

  Transmission and Clinical Complications

Diagnosis: stool examination for larvae (strongyloides) or eggs (the rest)
Treatment: albendizole or ivermectin (strongyloides) or mebendazole (the rest)

Systemic

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

Treatment:  Wuchereria, Onchocerca, Loa-  ivermectin, diethylcarbamazine, albendizole              
                      Trichinosis, Toxocara-  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
                                            Trichuris trichiura
                                   Ancylostoma duodenale and Necator americanus
                                   Enterobius vermicularis
                                   Strongyloides stercoralis
                                   Enterobius vermicularis

       Tissue nematodes - adults or larval stage in tissue
                          Trichinella spiralis, native etc
                      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 for10-14 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.

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 acid 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

	pinworm egg 50-60 µm
pinworm adult     8-13 mm

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, albendazole, pyrantel pamoate

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

Ascaris lumbricoides (Roundworm)

Epidemiology
-About 650 million infected worldwide mainly tropics. Transmission is 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

adult female 20-35 cm long

eggs ~68 mµ long

adults from one child

Adult worms1 live in the lumen of the small intestine. A female may produce up to 240,000 eggs
per day, which are passed with the feces 2. Fertile eggs embryonate and become infective after
18 days to several weeks 3, depending on the environmental conditions (optimum: moist, warm,
shaded soil). After infective eggs are swallowed 4, the larvae hatch 5, invade the intestinal
mucosa, and are carried via the portal, then systemic circulation to the lungs 6 . The larvae
mature further in the lungs (10 to 14 days), penetrate the alveolar walls, ascend the bronchial tree
to the throat, and are swallowed 7. Upon reaching the small intestine, they develop into adult
worms 1. Between 2 and 3 months are required from ingestion of the infective eggs to oviposition
by the adult female. Adult worms can live 1 to 2 years.      (CDC 1999)

Clinical
- related to number of worms; small numbers asymptomatic
- large numbers of adults in intestine -- obstruction, pains
- at times adults migrate into bile duct, up esophagus or through surgical anastomoses of   intestine
- cause malnutrition if in large numbers

Diagnosis: stool examination for eggs
Treatment: mebendizole, albendazole

Strongyloides stercoralis (Threadworm)

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

adult	filariform (invasive) larva

 Clinical
  most asymptomatic
  GI - peptic ulcer like symptoms, diarrhea rarely, cutaneous larvae currens (trunkal itchy 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 (the most sensitive)
culture of stool (Harada-Mori or Baerman) allows "free living" strongyloides to multiply
  agar plate tracking

Treatment: albendazole, ivermectin

Problems: diagnostic techniques not sensitive
                      untreated it persists for life

Ancylostoma duodenale and Necator americanus

(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

h mouth of Ancylostoma duodenale	filariform larva
	egg 60 x 40 mµ

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, albendazole

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

Cutaneous Larva Migrans

Ancylostoma caninum, Ancylostoma braziliensis etc.

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 (without a concentration technique) 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:
i.  zinc sulfate solution flotation - eggs float to top of solution
ii.  formal ethyl acetate sedimentation

4. Culture: Harada Mori or Baerman culture or charcoal 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

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 (not cardiac), remaining viable and quiet for many years. Adult female is 5 mm.long

larva extracted from muscle	adult from intestine wall

  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 creatine phosphokinase (CK)
    microscopic examination of muscle biopsy
    serology

larva in muscle cell at biopsy

Treatment: steroids and mebendizole or albendazole

Problems: education of meat consumer
                     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 especially in liver.

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

                                                          Toxocara  eggs

Clinical
   Hepatomegaly, pneumonitis, encephalitis, fever and eosinophilia in heavy infections
   Retinal lesion (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  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).

5. Bayliascaris procyonis: Raccoon nematode in North America producing a visceral larva migrans like Toxocaris (above) but with severe encephalitis