Rat lungworm disease
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Angiostrongyliasis is an infection by a
roundworm The nematodes ( or grc-gre, Νηματώδη; la, Nematoda) or roundworms constitute the phylum Nematoda (also called Nemathelminthes), with plant-parasitic nematodes also known as eelworms. They are a diverse animal phylum inhabiting a bro ...
of the '' Angiostrongylus'' type. Symptoms may vary from none, to mild, to meningitis. Infection with ''
Angiostrongylus cantonensis ''Angiostrongylus cantonensis'' is a parasitic nematode (roundworm) that causes angiostrongyliasis, the most common cause of eosinophilic meningitis in Southeast Asia and the Pacific Basin. The nematode commonly resides in the pulmonary arteries ...
'' (rat lungworm) can occur after ingestion of raw or undercooked snails or slugs, and less likely unwashed fruits and vegetables. In humans, ''A. cantonensis'' is the most common cause of eosinophilic meningitis or
meningoencephalitis Meningoencephalitis (; from ; ; and the medical suffix ''-itis'', "inflammation"), also known as herpes meningoencephalitis, is a medical condition that simultaneously resembles both meningitis, which is an infection or inflammation of the menin ...
. 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
central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...
or death.David, John T. and Petri, William A Jr. Markell and Voge's Medical Parasitology. St. Louis, MO: El Sevier, 2006.


Symptoms

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


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 experience chronic pain as a result of infection.


Eye invasion

Symptoms of eye invasion include visual impairment, pain,
keratitis Keratitis is a condition in which the eye's cornea, the clear dome on the front surface of the eye, becomes inflamed. The condition is often marked by moderate to intense pain and usually involves any of the following symptoms: pain, impaired e ...
, and retinal edema. Worms usually appear in the
anterior chamber The anterior chamber ( AC) is the aqueous humor-filled space inside the eye between the iris and the cornea's innermost surface, the endothelium. Hyphema, anterior uveitis and glaucoma are three main pathologies in this area. In hyphema, blood f ...
and vitreous and can sometimes be removed surgically.


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 accidental hosts and the life cycle does not continue predictably as it would in a rat.


Cause


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 snails and slugs, or have been contaminated by them.


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

''Angiostrongylus cantonensis'' has many vectors among
invertebrate Invertebrates are a paraphyletic group of animals that neither possess nor develop a vertebral column (commonly known as a ''backbone'' or ''spine''), derived from the notochord. This is a grouping including all animals apart from the chordate ...
s, with the most common being several species of snails, including the
giant African land snail Giant African land snail is the common name of several species within the family Achatinidae, a family of unusually large African terrestrial snails: * ''Achatina achatina'', also known as the agate snail or Ghana tiger snail * ''Lissachatina fulic ...
(''
Achatina ''Achatina'' is a genus of medium-sized to very large, air-breathing, tropical land snails, terrestrial pulmonate gastropod mollusks in the family Achatinidae.Bouchet, P. (2014). Achatina Lamarck, 1799. Accessed through: World Register of Marine ...
'') in the Pacific islands and
apple snail Ampullariidae, commonly known as the apple snails, is a family of large freshwater snails, aquatic gastropod mollusks with a gill and an operculum. These snails simultaneously have a gill and a lung as functional respiratory structures, wh ...
s of the genus ''Pila'' in Thailand and Malaysia. The golden apple snail, ''
Pomacea canaliculata ''Pomacea canaliculata'', commonly known as the golden apple snail or the channeled apple snail, is a species of large freshwater snail with gills and an operculum, an aquatic gastropod mollusc in the family Ampullariidae, the apple snails ...
'', is the most important vector in areas of China. Freshwater prawns, crabs, or other
paratenic In biology and medicine, a host is a larger organism that harbours a smaller organism; whether a parasitic, a mutualistic, or a commensalist ''guest'' ( symbiont). The guest is typically provided with nourishment and shelter. Examples include ...
, or transport, hosts can also act as vectors.


Organism


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.


Diagnosis

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 eosinophilic meningitis and history of exposure to snail hosts. Eosinophilic meningitis is generally characterized as a meningitis with >10
eosinophil Eosinophils, sometimes called eosinophiles or, less commonly, acidophils, are a variety of white blood cells (WBCs) and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. A ...
s/μL in the CSF or at least 10% eosinophils 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 in cases of suspected meningitis. In cases of eosinophilc 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 eosinophilic meningitis progresses, intracranial pressure and eosinophil counts should rise. Increased levels of eosinophils in the CSF is a hallmark of the eosinophilic 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 eosinophils, serology can be used to confirm a diagnosis of angiostrongyliasis 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.


Prevention

There are public health strategies that can 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


Treatment

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.


Anthelmintics

Anthelmintics Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. They may ...
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, mebendazole, and pyrantel are all commonly used, though albendazole is usually the drug of choice. Studies have shown that anthelmintic drugs may shorten the course of the disease and relieve symptoms. Therefore, anthelmintics are generally recommended, but should be administered gradually so as to limit the inflammatory reaction.


Anti-inflammatories

Anthelmintics 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 mebendazole 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.


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 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
United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territori ...
, cases have been reported in
Hawaii Hawaii ( ; haw, Hawaii or ) is a state in the Western United States, located in the Pacific Ocean about from the U.S. mainland. It is the only U.S. state outside North America, the only state that is an archipelago, and the only state ...
, which is in the endemic area. 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 New Orleans ( , ,New Orleans
and
Egypt Egypt ( ar, مصر , ), officially the Arab Republic of Egypt, is a transcontinental country spanning the northeast corner of Africa and southwest corner of Asia via a land bridge formed by the Sinai Peninsula. It is bordered by the Medit ...
. The disease has also arrived in
Brazil Brazil ( pt, Brasil; ), officially the Federative Republic of Brazil (Portuguese: ), is the largest country in both South America and Latin America. At and with over 217 million people, Brazil is the world's fifth-largest country by area ...
, where there were 34 confirmed cases from 2006 to 2014, including one death. The
giant African land snail Giant African land snail is the common name of several species within the family Achatinidae, a family of unusually large African terrestrial snails: * ''Achatina achatina'', also known as the agate snail or Ghana tiger snail * ''Lissachatina fulic ...
, which can be a vector of the parasite, has been introduced to Brazil as an invasive species and is spreading the disease. There may be more undiagnosed cases, as Brazilian physicians are not familiar with the eosinophilic meningitis associated to angiostrongyliasis and misdiagnose it as bacterial or viral. The parasite is rarely seen outside of endemic areas, and in these cases patients generally have a history of travel to an endemic area.


See also

* Schistosomiasis, a parasitic disease also spread by snails *
List of unusual deaths This list of unusual deaths includes unique or extremely rare circumstances of death recorded throughout history, noted as being unusual by multiple sources. Antiquity Middle Ages Renaissance Early modern period 19th centur ...
lists Australian man Sam Ballard as dying from Angiostrongyliasis in 2018, as a result of eating a garden slug eight years earlier on a dare


References


Further reading

* * Tabs for Parasite Biology, Image Gallery, Laboratory Diagnosis, and Treatment Information.


External links

{{Helminthiases Helminthiases Rodent-carried diseases Zoonoses