Angiostrongyliasis is an infection by a nematode

Nematode

The nematodes or roundworms are the most diverse phylum of pseudocoelomates, and one of the most diverse of all animals. Nematode species are very difficult to distinguish; over 28,000 have been described, of which over 16,000 are parasitic. It has been estimated that the total number of nematode...

 from the Angiostrongylus

Angiostrongylus

Angiostrongylus is a genus of parasitic nematodes in the family Metastrongylidae.- Species :Species in the genus* Angiostrongylus cantonensis * Angiostrongylus costaricensis Morera & Cespedes, 1971...

 genus of kidney and alimentary tract roundworms. For example, infection with Angiostrongylus cantonensis can occur after consuming raw Giant African land snail

Giant African land snail

Giant African land snail may refer to two genera and three species within the family Achatinidae, a family of unusually large African terrestrial snails.* Achatina, an African snail genus in the family Achatinidae....

s, Great Grey Slug

Great Grey Slug

Limax maximus , also known by common names such as the great grey slug, or the leopard slug, is one of the largest kinds of keeled air-breathing land slug in the world, . It is in the family Limacidae, the keeled slugs.Limax maximus is the type species of the genus Limax...

s, or other molluscs.

In humans, Angiostrongylus is the most common cause of eosinophilic meningitis

Meningitis

Meningitis is inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges. The inflammation may be caused by infection with viruses, bacteria, or other microorganisms, and less commonly by certain drugs...

 or meningoencephalitis

Meningoencephalitis

Meningoencephalitis is a medical condition that simultaneously resembles both meningitis, which is an infection or inflammation of the meninges, and encephalitis, which is an infection or inflammation of the brain.-Causes:...

. Frequently the infection will resolve without treatment or serious consequences, but in cases with a heavy load of parasites the infection can be so severe it can cause permanent damage to the CNS or death.

Early symptoms

Infection first presents with severe abdominal pain, nausea, vomiting, and weakness, which gradually lessens and progresses to fever, and then to CNS symptoms and severe headache and stiffness of the neck.

Severe/CNS infection

CNS symptoms begin with mild cognitive impairment and slowed reactions, and in a very severe form often progress to unconsciousness. Patients may present with neuropathic pain early in the infection. Eventually severe infection will lead to ascending weakness, quadriparesis, areflexia, respiratory failure, and muscle atrophy, and will lead to death if not treated. Occasionally patients present with cranial nerve palsies, usually in nerves 7 and 8, and rarely larvae will enter ocular structures. Even with treatment, damage to the CNS may be permanent and result in a variety of negative outcomes depending on the location of the infection, and the patient may suffer chronic pain as a result of infection.

Eye invasion

Symptoms of eye invasion include visual impairment, pain, keratitis

Keratitis

Keratitis is a condition in which the eye's cornea, the front part of the eye, becomes inflamed. The condition is often marked by moderate to intense pain and usually involves impaired eyesight.-Types:...

, and retinal edema. Worms usually appear in the anterior chamber

Anterior chamber

The anterior chamber is the fluid-filled space inside the eye between the iris and the cornea's innermost surface, the endothelium. Aqueous humor is the fluid that fills the anterior chamber. Hyphema and glaucoma are two main pathologies in this area. In hyphema, blood fills the anterior chamber...

 and vitreous

Vitreous humour

The vitreous humour or vitreous humor is the clear gel that fills the space between the lens and the retina of the eyeball of humans and other vertebrates...

 and can sometimes be removed surgically.

The parasite is rarely seen outside of endemic areas, and in these cases patients generally have a history of travel to an endemic area.

Transmission

Transmission of the parasite is usually from eating raw or undercooked snails or other vectors. Infection is also frequent from ingestion of contaminated water or unwashed salad that may contain small snail and slugs, or have been contaminated by them. Therefore it is very important to avoid raw snails, wash and cook vegetables thoroughly, and avoid open water sources that may be contaminated.

Reservoirs

Rats are the definitive host and the main reservoir for A. cantonensis, though other small mammals may also become infected. While angiostrongylus can infect humans, humans do not act as reservoirs since the worm cannot reproduce in humans and therefore humans cannot contribute to their life cycle.

Vectors

A. cantonensis has many vectors, with the most common being several species of snails, including the giant African land snail (Achatina fulica) in the Pacific islands and snails of the genus Pila in Thailand and Malaysia. The golden apple snail, A. canaliculatus, is the most important vector in areas of China. Freshwater prawns, crabs, or other paratenic

Paratenic

In parasitology, the term paratenic describes a host which is not needed for the development of the parasite, but nonetheless serves to maintain the life cycle of the parasite. Alaria americana may serve as an example: the so-called mesocercarial stages of this parasite reside in tadpoles, which...

, or transport, hosts can also act as vectors.

Incubation period

The incubation period in humans is usually from 1 week to 1 month after infection, and can be as long as 47 days. This interval varies, since humans are intermediate hosts and, the life cycle does not continue predictably as it would in a rat.

Morphology

A. cantonensis is a nematode roundworm with 3 outer protective collagen layers, and a simple stomal opening or mouth with no lips or buccal cavity leading to a fully developed gastrointestinal tract. Males have a small copulatory bursa at the posterior. Females have a “barber pole” shape down the middle of the body, which is created by the twisting together of the intestine and uterine tubules. The worms are long and slender - males are 15.9-19 mm in length, and females are 21-25 mm in length.

Life cycle

The adult form of A. cantonensis resides in the pulmonary arteries of rodents, where it reproduces. After the eggs hatch in the arteries, larvae migrate up the pharynx and are then swallowed again by the rodent and passed in the stool. These first stage larvae then penetrate or are swallowed by snail intermediate hosts, where they transform into second stage larvae and then into third stage infective larvae. Humans and rats acquire the infection when they ingest contaminated snails or paratenic (transport) hosts including prawns, crabs, and frogs, or raw vegetables containing material from these intermediate and paratenic hosts. After passing through the gastrointestinal tract, the worms enter circulation. In rats, the larvae then migrate to the meninges and develop for about a month before migrating to the pulmonary arteries, where they fully develop into adults.

Humans are incidental hosts; the larvae cannot reproduce in humans and therefore humans do not contribute to the A. cantonensis life cycle. In humans, the circulating larvae migrate to the meninges, but do not move on to the lungs. Sometimes the larvae will develop into the adult form in the brain and CSF, but they quickly die, inciting the inflammatory reaction that causes symptoms of infection.

Diagnostic tests

Diagnosis of Angiostrongyliasis is complicated due to the difficulty of presenting the angiostrongylus larvae themselves, and will usually be made based on the presence of eosiniphilic meningitis and history of exposure to snail hosts. Eosiniphilic meningitis is generally characterized as a meningitis with >10 eosiniphils/μL in the CSF or at least 10% eosiniphils in the total CSF leukocyte count. Occasionally worms found in the cerebrospinal fluid or surgically removed from the eye can be identified in order to diagnose Angiostrongyliasis.

Lumbar puncture

Lumbar puncture should always be done is cases of suspected meningitis. In cases of eosiniphilc meningitis it will rarely produce worms even when they are present in the CSF, because they tend to cling to the end of nerves. Larvae are present in the CSF in only 1.9-10% of cases. However, as a case of eosiniphilic meningitis progresses, intracranial pressure and eosiniphil counts should rise. Increased levels of eosinophils in the CSF is a trademark of the eosiniphilic meningitis.

Brain imaging

Brain lesions, with invasion of both gray and white matter, can be seen on a CT or MRI. However MRI findings tend to be inconclusive, and usually include nonspecific lesions and ventricular enlargement. Sometimes a hemorrhage, probably produced by migrating worms, is present and of diagnostic value.

Serology

In patients with elevated eosiniphils, serology can be used to confirm a diagnosis of Angiostrongylias rather than infection with another parasite. There are a number of immunoassays that can aid in diagnosis, however serologic testing is available in few labs in the endemic area, and is frequently too non-specific. Some cross reactivity has been reported between A. cantonensis and trichinosis, making diagnosis less specific.

The most definitive diagnosis always arises from the identification of larvae found in the CSF or eye, however due to this rarity a clinical diagnosis based on the above tests is most likely.

Management and therapy

Treatment of angiostrongyliasis is not well defined, but most strategies include a combination of anti - parasitics to kill the worms, steroids to limit inflammation as the worms die, and pain medication to manage the symptoms of meningitis.

Anti-helminthics

Anti-helminthics are often used to kill off the worms, however in some cases this may cause patients to worsen due to toxins released by the dying worms. Albendazole, ivermectin, mebendazol, and pyrantel are all commonly used, though albendazole is usually the drug of choice. Studies have shown that anti-helminthic drugs may shorten the course of the disease and relieve symptoms. Therefore anti-helminthics are generally recommended, but should be administered gradually so as to limit the inflammatory reaction.

Anti-inflammatories

Anti-helminthics should generally be paired with corticosteroids in severe infections to limit the inflammatory reaction to the dying parasites. Studies suggest that a two week regimen of a combination of mebedizole and prednisolone significantly shortened the course of the disease and length of associated headaches without observed harmful side effects. Other studies suggest that albendazole may be more favorable, because it may be less like to incite an inflammatory reaction. The Chinese herbal medicine long-dan-xie-gan-tan (LDGXT) has also been shown to have a similar anti inflammatory effect, and in mild cases may be used alone to relieve symptoms while infection resolves itself.

Symptomatic treatment

Symptomatic treatment is indicated for symptoms such as nausea, vomiting, headache, and in some cases, chronic pain due to nerve damage or muscle atrophy.

Epidemiology

A. cantonensis and its vectors are endemic to Southeast Asia and the Pacific Basin. The infection is becoming increasingly important as globalization allows it to spread to more and more locations, and as more travelers encounter the parasites. The parasites probably travel effectively through rats traveling as stowaways on ships, and through the introduction of snail vectors outside endemic areas.

Although mostly found in Asia and the Pacific where asymptomatic infection can be as high as 88%, human cases have been reported in the Caribbean, where as much as 25% of the population may be infected. In the US, cases have been reported Hawaii, which is in the endemic area [5]. The infection is now endemic in wildlife and a few human cases have also been reported in areas where the parasite was not originally endemic, such as New Orleans and Egypt.

Public health and prevention

There are many public health strategies that can drastically limit the transmission of A. cantonensis by limiting contact with infected vectors. Vector control may be possible, but has not been very successful in the past. Education to prevent the introduction of rats or snail vectors outside endemic areas is important to limit the spread of the disease. There are no vaccines in development for angiostrongyliasis.

Recommendations for individuals

To avoid infection when in endemic areas, travelers should:

• Avoid consumption of uncooked vectors, such as snails and freshwater prawns
• Avoid drinking water from open sources, which may have been contaminated by vectors
• Prevent young children from playing with or eating live snails