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

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LECTURE 1 Introduction and Intestinal Protozoa
LECTURE 2 Malaria
LECTURE 3 Systemic Protozoa
LECTURE 4 Intestinal and Systemic Helminths
LECTURE 5 Cestodes and Trematodes

 

Strongyl_larva2_DPDx.JPG (159621 bytes) wuchereriamf-chmai.jpg (14459 bytes)
intestinal-- Strongyloides larva systemic-- microfilaria (Wuchereria)

     

Overview

Transmission and Clinical Complications

Large Intestine   transmission complications
Trichuris (threadworm) oral hemorrhagic colitis
Enterobius (pinworm) oral perianal itch
     
Small intestine    
Ascaris (round worm) oral small intestine obstruction
Strongyloides percutaneous and autoinfection duodenitis,  cutaneous larva currens,
hyperinfection in immunocompromised
Ancylostoma   & Necator  (hookworm) percutaneous iron deficiency anemia

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

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

Systemic

Worm transmission clinical picture & diagnosis
Trichinella spiralis or nativa raw pork, bear, walrus myositis, diarrhea
Dx. eosinophilia, raised CPK,  serology
Toxocara canis
(visceral larva migrans)
oral eosinophilia, hepatomegaly, fever
Dx: serology
Wuchereria bancrofti or Brugia malayi (lymphatic filariasis) mosquito vector elephantiasis, chyluria or hydrocoele
Dx: microfilaria in blood, serology, antigen capture
Onchocera volvulus
(river blindness)
black fly vector iitchiness, skin nodules, blindness
Dx: adults in skin nodules, microfilaria in skin biopsies (snips)
Loa loa (eye worm) horse fly vector Calabar swellings (3-4 days), 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-                     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

mapworm.jpg (97013 bytes)                                       

       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.

trichurisadult-chmai.jpg (9509 bytes) trichurisegg-chmai.jpg (22910 bytes)
 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

pinwor1.jpg (17764 bytes) pinwor2.jpg (13314 bytes)
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

asc_lum_adult_dpdx.jpg (31333 bytes)
adult female 20-35 cm long
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eggs ~68 mµ long
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adults from one child

AscariasisLifeCyclecdc.gif (26250 bytes)

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

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

strongadult-chmai.jpg (2830 bytes) Strongyl_larva2_DPDx.JPG (159621 bytes)
adult        filariform (invasive) larva

 Clinical
 WB00938_.GIF (1017 bytes) most asymptomatic
 WB00938_.GIF (1017 bytes) GI - peptic ulcer like symptoms, diarrhea rarely, cutaneous larvae currens (trunkal itchy dermatitis)
 WB00938_.GIF (1017 bytes)  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
WB00938_.GIF (1017 bytes) stool examination . NB: difficult to find strongyloides
WB00938_.GIF (1017 bytes) duodenal aspirate or Enterotest duodenal string test
WB00938_.GIF (1017 bytes) serology (the most sensitive)
WB00938_.GIF (1017 bytes) culture of stool (Harada-Mori or Baerman) allows "free living" strongyloides to multiply

Treatment: albendazole, ivermectin

Problems: diagnostic techniques not sensitive
                      untreated it persists for life


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

nematoHW.jpg (5946 bytes)h
mouth of Ancylostoma duodenale
hookworm-filarlarvae-chmai.jpg (7450 bytes)
filariform larva
hookworm_egg2_dpdx.jpg (24625 bytes)
egg 60 x 40 mµ  
   

Clinical  
  WB00938_.GIF (1017 bytes)   usually assymptomatic 90%
  WB00938_.GIF (1017 bytes)     heavy infections (20 - 100 worms)
  WB00938_.GIF (1017 bytes)    iron deficiency anemia
  WB00938_.GIF (1017 bytes)    malnutrition from protein loss
  WB00938_.GIF (1017 bytes)    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.

Pathology Nematodes.jpg (9724 bytes)

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.

           nema-cesta_fig4cdc.gif (55924 bytes)             


Eosinophilia

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

very high (30-80% of WBC) moderate (10-30% of WBC) low or absent (0-10% of WBC)
Trichinella hookworm Enterobius
Toxocara Strongyloides Ascaris
Fasciola Trichuris

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


trichinella_larv2_dpdx.jpg (17180 bytes) trichinella-adult-chmai.jpg (8744 bytes)
larva extracted from muscle adult from intestine wall

  Clinical
 WB00938_.GIF (1017 bytes)  Early (1-2 weeks) -      abdominal pain, diarrhea

  WB00938_.GIF (1017 bytes) Midterm (2-6 weeks) - myalgia, muscle weakness, facial and periferal edema, rash; sometimes encephalitis and myocarditis

  WB00938_.GIF (1017 bytes) Long term (months) -  usually assymptomatic despite presence of trichinella "cysts"

Diagnosis
 WB00938_.GIF (1017 bytes)   clinical picture with laboratory support (eosinophilia and raised creatine phosphokinase (CK)
 WB00938_.GIF (1017 bytes)   microscopic examination of muscle biopsy
 WB00938_.GIF (1017 bytes)   serology

trichinella-musc-chmai.jpg (25165 bytes)
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_canis_eggs.jpg (15769 bytes)  Toxocara  eggs

Clinical
 WB00938_.GIF (1017 bytes)  Hepatomegaly, pneumonitis, encephalitis, fever and eosinophilia in heavy infections
 WB00938_.GIF (1017 bytes)  Retinal lesion (similar to retinoblastoma) or focal retinitis when single larva reaches retina.

Diagnosis
 WB00938_.GIF (1017 bytes)  Clinical syndrome with very high eosinophilia
 WB00938_.GIF (1017 bytes)  Serology
 WB00938_.GIF (1017 bytes)  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


Systemic nematodes

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.) and are usually difficult to remove for diagnosis. The microscopic larvae (called microfilaria) produced by 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.

 

filamapwho1.jpg (88422 bytes) Pathology Nematodes3.jpg (17052 bytes)
                               elephantiasis

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, ingested by mosquito when biting the human, 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

wuchereriamf-chmai.jpg (14459 bytes)
  microfilaria 260 µm long

Clinical
WB00938_.GIF (1017 bytes)  Asymptomatic microfilaremia
WB00938_.GIF (1017 bytes)   Lymphangitis and lymphadenitis
WB00938_.GIF (1017 bytes)   Orchitis and epididymitis
WB00938_.GIF (1017 bytes)   Elephantiasis
WB00938_.GIF (1017 bytes)   Tropical pulmonary eosinophilia
WB00938_.GIF (1017 bytes)   Chyluria

Diagnosis
WB00938_.GIF (1017 bytes)  Blood examinations (esp. Night blood) for microfilaria
WB00938_.GIF (1017 bytes)    Serology
WB00938_.GIF (1017 bytes)     Antigen capture

Treatment
WB00938_.GIF (1017 bytes)  Anti-inflammatory agents
WB00938_.GIF (1017 bytes)  Diethylcarbamazine (DEC), Ivermectin, albendizole

Prevention
WB00938_.GIF (1017 bytes)  Control of mosquitoes
WB00938_.GIF (1017 bytes)   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
WB00938_.GIF (1017 bytes)  Infective larvae transmitted to man by black flies of the genus Simulium.
WB00938_.GIF (1017 bytes)  Larvae develop to adults in subcutaneous tissue
WB00938_.GIF (1017 bytes)  Adult female produces microfilaria which wander in subcutaneous tissue, cornea, and anterior chamber of eye. Black flies acquire microfilaria on biting infected humans .
WB00938_.GIF (1017 bytes) Adult 33-50 cm x .3 mm Microfilaria 330 m x 6 m


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

Pathology Nematodes4.jpg (27422 bytes) Pathology Nematodes5.jpg (8141 bytes)
onchocerca nodule (adult curled up within) keratic precipitates and microfilaria
on inside surface of cornea

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

Treatment
WB00938_.GIF (1017 bytes)  Anti-inflammatory agents
WB00938_.GIF (1017 bytes)   Diethylcarbamazine
WB00938_.GIF (1017 bytes)  Ivermectin


Loa loa (loiasis)(Eye worm)

Biology
WB00938_.GIF (1017 bytes)  Adult worm lives in subcutaneous tissue and wanders freely
WB00938_.GIF (1017 bytes)  Microfilaria in subcutaneous tissues and blood
WB00938_.GIF (1017 bytes)  Transmitted by the bite of deer flies of the genus Chrysops
WB00938_.GIF (1017 bytes)  Adult: 55 mm x 0.5 mm Microfilaria: 280 m x 7m                      

Clinical
WB00938_.GIF (1017 bytes)  Calabar swelling (intermittant 2-3 day focal migratory angioaedema)
WB00938_.GIF (1017 bytes)   migrating worm in conjunctiva     
               
calabar.jpg (226500 bytes)
               Calabar swelling

Diagnosis
WB00938_.GIF (1017 bytes)  Excision of adult worm    
WB00938_.GIF (1017 bytes)  Blood examination for microfilariae

                                                                                                                                 

Treatment: Diethylcarbamazine, Ivermectin