Volume 7. Tissue Dwelling Nematodes
Co- Authors: M. Arcari
1, A. Baxendine 1 and C. E. Bennett2
Intersep Ltd 2.
University of Southampton
7. Unusual tissues dwelling
Tissue Dwelling Nematodes
species of nematodes are known to indirectly infect man causing an array of
symptoms and diseases. Many of the larvae of these parasites cause serious
zoonosis in man. These parasites are known to infect many intermediate hosts
during their life cycle with a variety of animals being the definitive host,
whilst man is normally an accidental definitive host.
Angiostrongylus cantonensis was first described in 1945
in Taiwan from a boy with suspected meningitis. Since then it has been
recognised throughout the Pacific areas with sporadic cases reported in other
parts of the world including Central America and Cuba It is associated with
eosinophilic meningitis. The species A.
cantonensis and A. costaricensis
have now been reclassified into the genus Parastrongylus
(Peters & Gilles, 1995)
Angiostrongylus cantonensis is also known as the rat
nematodes where the main cause of eosinophilic meningitis is infection with
the larvae of this nematode. Man and rats become infected by eating infected
molluscs of the giant land snail (intermediate hosts) or food which is
contaminated by the snails’ bodies.
The definitive host of A. cantonensis is the rat. Adult worms reside in the pulmonary
arteries. (Diag. 1) The eggs are
released, carried to the lungs in the bloodstream, they break through the
pulmonary tract and are then swallowed. The
eggs hatch in the intestine and the 1st stage larvae are passed in
the stools. The 1st stage larvae in the rats faeces are eaten by
the intermediate hosts, from the various genera, Achatina, Cipangopaludina and Bradybaena
and also various slugs. (Fig. 1)The
larvae develop within these intemediate hosts to the 3rd stage
larvae. These, infected molluscs are then eaten by rats where the larvae can
complete the cycle.
Human infection occurs by the ingestion of infective larvae in the slugs, snails or on vegetation. The larvae migrate to the brain and cannot continue their growth cycle. It is the death of the larvae which invokes the inflammatory response in the meninges resulting in eosinophilic meningitis.
cycle of the rat nematode Angiostrongylus
cantonensis, which is known to infect humans and is the main cause of
Angiostrongylus cantonensis is a long slender worm
measuring between 17 and 25 mm long by 0.26 to 0.34 mm wide. (Fig. 2)
Figure 1. The 1st stage
larvae of Angiostrongylus cantonensis. The
larvae are found in the faeces of rats. (x 160)
(Peters & Gilles, 1995)
Figure 2. The adult worms of Angiostrongylus
cantonensis. They measure between 17 – 25mm long and reside in the
pulmonary arteries and arterioles of the definitive hosts. (x 3.5) (Peters
& Gilles, 1995)
The incubation period is usually about 20 days but can be
up to 47 days. Infection in man is usually self-limiting but can result in
fatalities. The main symptom is
severe headache but other symptoms include convulsions, vomiting, facial
paralyses, parasthesia, neck stiffness and fever.
It is accompanied by moderate eosinophilia in the CSF i.e. the cell
count is 100 – 2000/mm3.
Blood eosinophilia is also common. Eye involvement is accompanied
by visual impairment, ocular pain, keratitis and retinal oedema.
Living worms have been reported and are removed surgically.
diagnosis can be made on the basis of the patients symptoms i.e. fever,
meningitis, ocular involvement and severe headache. Eosinophilia in CSF and peripheral blood is also suggestive.
Larvae or young adults can be recovered in the CSF. ELISA can also
Angiostrongylus costaricensis was first described in 1971.
Human infections are most common in Costa Rica but have been reported
in Mexico, Central and South America.
The life cycle is similar to A.
cantonensis, (Diag. 1) with the human being an accidental host by
consumption of snails and salad vegetables which have become contaminated by
infective larvae that have been shed by slugs in their mucus. Unlike A.
cantonensis, the larvae of A.
costaricensus penetrates the intestinal wall and results in inflammatory
lesions of the bowel wall. Here the life cycle ends.
eggs are 90mm,
oval, thin shelled and can be embryonated. The adult female measures 42 x
300mm and the males measure 22 x 140mm. (Fig.
3 & 4)
showing the caudal end of the male adult worm, Angiostrongylus costaricensis, showing clearly the copulatory bursa.
showing the adult Angiostrongylus
costaricensis worms in the natural host of a rat. The worms normally
localise within the mesenteric arteries, especially those of the ileocaecal
region of the natural definitive host. (www.cdfound.to.it)
The most common symptoms are
pain and tenderness with fever, vomiting and diarrhoea.
A tumour-like mass is often palpable and can mimic malignancy.
The symptoms of abdominal pain, vomiting and diarrhoea, and anorexia,
are often mistaken for those of appendicitis. Worms can be found in the
regional lymph nodes and mesenteric arteries.
They can also be found in the spermatic arteries causing testicular
obstruction and necrosis. Occasionally the larvae and the ova reach the liver and
mimic visceral larvae migrans.
Eosinophilia is also present.
Anisakiasis is a collective
name for infections belonging to the genera of nematodes, Anisakis, Phokanema, Tarranova and Contracaecum. The adult worms from the many species belonging to
this family, Anisakidae, occur in
various sea mammals, seals, dolphins, porpoises
and whales, the larvae can cause a serious zoonosis, anisakiasis, in man. Anisakiasis
was first reported in the Netherlands in 1960 and since then cases have been
reported from Japan, North America, Canada, Chile and the United Kingdom with
the increase in popularity of ‘sushi’.
Two species of nematode have
been especially implicated worldwide in causing human anisakiasis, Anisakis
simplex and Pseudoterranova
osculatum. The larvae of P.
osculatum can be distinguished from A.
simplex by the possession of a caecum.
These nematodes are parasites
in a large number of marine animals including seals, sea-lions, whales and
dolphins. It is in these mammals that the adult worm is found. Eggs are passed out in the faeces of these mammals they
embryonate and hatch to liberate the first stage larvae into the sea water.
These larvae then become ingested by crustaceans and moult to become L2
and L3 larvae. If fish and squid eat the infected
crustaceans, the third stage larvae become liberated and penetrate the
intestine or muscles of that host. These larvae and encyst. Over 100 species of fish can act as
intermediate hosts. The marine
mammals ingest the fish and thus the cycle is completed.
Humans become infected by
consuming raw or improperly cooked fish which contain the third stage larvae.
The larvae reach a length of
50mm with a diameter of 1-2 mm. (Diag.
2) Classification of the Anisakids is made by the structure of the
After ingestion of the raw
fish by humans, the larvae penetrate the intestinal wall resulting in
inhabitation of the stomach or duodenum but can be found in any part if the
alimentary canal or outside the gut in various viscera. The end result is
abdominal pain, nausea, and sometimes vomiting and diarrhoea, often occurring
within 6 hours of eating an infected meal.
Abdominal irritation may mimic gastric ulcer, carcinoma, appendicitis
or other conditions requiring surgery. Eosinophilic granulosus
Transient anisakiasis which
has been reported in North America, is characterised by some vomiting and
distress within a few hours of ingesting the fish and then quickly subsides.
The larvae can be coughed up a few days later.
Low grade eosinophilia and occult blood in the stool are common.
Diagram 2. Line
diagram respresenting the morphology of the third stage larvae of Anisakis
simplex (from fish), it is
the causative organism of anisakiasis in
man. (Smyth, J.D, 1994)
Diagnosis can only be confirmed by endoscopy and the removal of the worms by biopsy forceps and microscopical identification.
Epidemiology and prevention
Anisakis larvae are usually found in herring, mackerel and North American salmon. Pseudoterranova
are found in cod, halibut, rockfish, sardine and squid.
Human infections result from eating raw fish, insufficiently cooked or smoked fish, marinated or salted fish. Freezing fish at -20°C for a minimum of 5 days kills the larvae and thus the fish is suitable for consumption in dishes like sushi. Smoking the fish at temperatures >65°C renders it suitable for consumption. Marinating or salting the fish cannot be depended on to kill the larvae, however adequately cleaning the fish can render it safe for consumption. Human anisakiasis has been virtually eliminated from the Netherlands due to the mandatory freezing of herring.
species of the genus Gnathostoma are responsible for zoonotic infections in
man. Gnathostoma spinigerum is a nematode found in dogs, cats and several other
carnivores. Human infections of
the disease have been reported from Japan, China, Thailand, Far East and
Philippines, with man acquiring the infection from eating various freshwater
The life cycle of
this parasite involves 2 intermediate hosts, cyclops and birds, snakes, fish
and frogs where they mature before developing into adults in the definititve
hosts. (Diag. 3)
Diagram 3. Diagram
illustrating the life cycle of Gnathostoma
In the definitive hosts, which normally are carnivores, the adult nematodes live in nodules in the stomach wall. The larvae develop inside the eggs, which are passed in the faeces and then into water where they are ingested by species of Cyclops. They, in turn, are ingested by a number of fresh water fish, frogs, snakes and birds. The larvae pierce their gastric wall and develop into 3rd stage larvae and become encysted in the muscle. Cats and dogs ingest the raw flesh of these animals and the larvae excyst and mature into adults in the stomach of cats and dogs.
If the infected fish or frogs are eaten by other hosts, apart from the definitive hosts, (paratenic host), such as herons, pigs and man, they do not mature but migrate through the subcutaneous tissues causing visceral and cutaneous larva migrans.
The adult female
worms measure 25 - 54 mm whereas the male measures 11 - 25 mm. (Fig. 5) The anterior half of the worm is covered with leaf like
spines. The male worms have a red tail whilst the larger females have a more
curved tail. The larval worms are 4mm long.
Figure 5. Adult
worms of Gnathostoma spinigerum. The
males are smaller than the females and possess a red tail. The males measure
between 11- 25mm whilst the females are larger, measuring between 25 – 54mm
long. (x 1.3) (Peters & Gilles, 1995)
Humans are accidental hosts and after ingestion, the larvae do not mature but migrate throughout the body via the intestinal wall. Symptoms include epigastric pain, vomiting and anorexia. These symptoms subside as the larvae continue their migratory path through the cutaneous tissue. Evidence of migration appears as either lesions similar to cutaneous larvae migrans or migratory swellings accompanied by inflammation, redness or pain. The swelling is hard and non-pitted and lasts for several days. These migratory lesions may be accompanied by pruritis and pain. There is marked eosinophilia in patients with cutaneous involvement. Ocular involvement resulting in blindness may occur in serious disease. Eosinophillic myeloencephalitis may result from migration of the worms along the nerve tracks. Symptoms may include pain, paralyses, seizures, coma and death. The CSF may be xanthochromic or bloody.
diagnosis may be made on the basis of clinical symptoms. Definitive diagnosis
is the recovery and identification of the worm since the symptoms may be
suggestive of sparganosis, paragonimiasis and cutaneous larvae migrans and
myiasis. A bloody spinal fluid or
xanthochromia may resemble infection with Angiostrongylius
Trichinella spiralis was first seen by James Paget
but was named and described by his Pofessor, Richard Owen. The family
Trichinellidae contains only one single genus Trichinella
and was originally thought only to contain the one species, Trichinella
spiralis, which causes the serious and often fatal disease in man known as
It is a parasite of carnivorous animals and is especially common in rats and
in swine fed on uncooked garbage and slaughter house scraps, humans become
infected by eating raw pork, with sausages being the most common cause of
infection. It is a cosmopolitan parasite and prevalent in many European
countries with the highest interest being in China.
is now thought that there are four varieties of this species that exists
Trichinella spiralis spiralis
- temperate zone – high
infectivity for pigs, rats and man.
Trichinella spiralis nelsoni - Tropics - low infectivity
for pigs and rats and high infectivity for lions, hyenas.
Trichinella spiralis nativa - Arctic - low infectivity
for pigs, found in polar bears, resistant to freezing.
pseudospiralis- New Zealand – low
infectivity for pigs, rats and mice.
Trichinella spiralis is a ‘domestic’
parasitic nematode long recognised to cause a zoonosis transmitted to man by
the ingestion of infected pork.
in the definitive hosts is acquired by the hosts eating raw or undercooked
flesh e.g. pork, containing encapsulated larvae. (Diag.
4 & 6 & Fig. 7) Rats are probably the most highly infected
‘natural’ hosts and pigs become infected by eating infected pork scraps or
occasionally rats which inhabit their stalls. For man sausages are a dangerous
source of the parasite as a small fragment of infected pork, (after mincing),
may become widely distributed among a number of sausages.
Humans become infected by eating raw meat containing
encysted larvae. The cyst becomes
digested and releases the larvae which invade the intestinal mucosa. They
develop and mate in the second day. By
the 6th day of infection, the female adults deposit motile larvae which are
carried by the intestinal lymphatics or mesenteric venules to other tissues in
the body. The very active
muscles, such as the diaphragm, jaws, tongue, larynx and eyes, are invaded and
the larvae become encapsulated by the 21st day following infection.
Calcification of the cysts occurring as early as five months, but usually
begins after 6 –18 months. The cyst wall is derived from the host's muscle
fibre and the larvae remain viable for many years with no further development
occurring. When muscles are eaten by the definitive host, sexual maturation in
the intestinal phase, as explained earlier, rapidly occurs.
Diagram 4. Diagram
illustrating the life cycle of Trichinella
spiralis which is the causative agent of the disease trichinosis which is often terminally fatal in man.
The adult female worm
is about 2-3mm long and 90mm
in diameter. The male is smaller measuring 1.2mm long by 60mm
in diameter. (Diag. 5 & Fig. 6)
female adult worms are ovoviparous and up to 1500 larvae may be released by a
Diagram 5. Diagram illustrating the
morphology of the adult male and female nematodes, Trichinella spiralis. The adult female measures between 2 – 3cm
long whilst the male worms are smaller in size measuring approximately 1.2mm
Symptoms during the
intestinal phase may go unnoticed or may be severe.
Epidemics can result in outbreaks of gastro-enteritis, 2 to 7 days
after the ingestion of raw pork. Diarrhoea
with or without abdominal pain may last for several weeks. Eosinophilia and fever occur in most cases. Leucocytosis is
common and hyperglobulinaemia is characteristic. Myocytosis and circum orbital oedema are classic signs.
There can also be central nervous system involvement
primary pathogenic effect of Trichinella
comes from the destruction of the striated muscle fibres in which it
encysts. (Diag. 6 & Fig. 7)
There can be neurological manifestations of trichinosis and death may be
ascribed to myocarditis, encephalitis or pneumonitis.
of trichinosis depends on the clinical signs, such as myalgia, periorbital
oedema, fever and eosinophilia in a patient with a history of eating pork or
tests are available but may be negative if carried out within 3 - 4 weeks post
infection. Circulating antibodies to T. spiralis
appear from 2 – 4
weeks after infection. Redefined diagnostic antigens for their detection are
currently being developed. A simple IFAT employing fragments of larvae as
antigen is a useful diagnostic tool. Latex
tests with extracted larval antigens have also proved valuable in the acute
stage, during which high antibody titres develop.
Figure 6. Diagrammatic representation of the larvae encapsulated in striated muscle. (Smyth, J.D, 1994)
biopsy is available with the muscle being digested in pepsin, which frees the
encapsulated larvae or by a simple device whereby the muscle sample is
compressed between 2 glass plates to make it
semi-transparent, allowing you to see any encapsulated larvae using a
‘trichinoscope’ (a simple magnifying system). (Fig. 7)
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