Angiostrongylus cantonensis (ie, rat lungworm [RLW]) is a metastrongyloid nematode that uses various rat species as definitive hosts and snails and slugs as intermediate hosts.1,2
Life Cycle
Adult A cantonensis (average length, 25-35 mm) are found in the right ventricle and pulmonary artery of rats.2 First-stage larvae (L1) hatch from eggs in the lung parenchyma, migrate up the trachea, are coughed up and swallowed by the patient, and enter the intestine (Figure 1).2 L1s are passed in the feces and ingested by snail or slug intermediate hosts, in which the larvae develop into infective third-stage larvae (L3; Figures 2 and 3). Following ingestion of an infected snail or slug, L3s penetrate the intestine, enter the circulation, and subsequently enter the CNS. The larvae continue to develop in the brain before re-entering the circulation and passing to the heart, where they mature into adult males and females (Figure 4).2 Paratenic hosts include various species of crustaceans, flatworms, fish, centipedes, lizards, frogs, and toads and are an important part of this life cycle, acquiring and harboring infective L3s until being ingested by a definitive host.3
FIGURE 1 A cantonensis larvae cluster near a rat’s trachea. 200× magnification
Global Distribution
A cantonensis likely originated in Southeast Asia or East Africa and has spread to Australasia, North America, South America, Europe, and islands in the Pacific Ocean and Caribbean Sea.4 In the United States, A cantonensis is considered endemic in Hawaii and has been reported in several southeastern states in humans, rats, snails, slugs, and other paratenic and incidental hosts.3-5
Neuroangiostrongyliasis in Humans
Humans are considered incidental or accidental hosts of A cantonensis and can become infected through ingestion of L3s via snail or slug intermediate hosts—either directly (purposeful or accidental ingestion) or indirectly (water or food contamination)—or via paratenic hosts.2,6 When a snail intermediate host dies, particularly from drowning, larvae leave the host and can contaminate water intended for drinking or washing produce, thus allowing direct ingestion of infective L3s.6 Once ingested, L3s penetrate the intestine and enter the circulation and later the CNS, where they mature to subadults. Presence or movement of worms, growth of worms from L3 to subadult, and subsequent inflammation are thought to cause neurologic disease.2 Neuroangiostrongyliasis can result in a variety of symptoms, ranging from headache to coma, and may lead to death. Disease severity is often a result of the quantity of L3s ingested and the host’s reaction.7 As the parasite enters the GI tract, nausea and vomiting may occur. Once the parasite leaves the intestine and enters the CNS, neurologic signs (eg, paresthesia, hyperesthesia, limb weakness, photophobia, fever, severe headache with limited relief) may develop. Infection can also lead to meningitis and encephalitis.7
Neuroangiostrongyliasis in Dogs
Like humans, dogs are considered incidental or accidental hosts of RLW and become infected through ingestion of L3s via intermediate or paratenic hosts.
Distribution
Known A cantonensis infections in dogs have occurred in Hawaii for several years. Many published case reports are of natural RLW infections in dogs in Australia and Hawaii (Table),4,8-11 and multiyear studies of naturally infected dogs have been performed in Australia.12-16 The majority of dogs included in these reports and studies were <1 year of age. One study of 26 dogs found neuroangiostrongyliasis was most often diagnosed in younger animals, which was attributed to a propensity to play with or ingest intermediate snail hosts and minimal immune system exposure to nematode infections.14 Intact dogs also had a significantly increased risk for RLW infection.14
Clinical Presentation
Presentation of neuroangiostrongyliasis in dogs is typically consistent and similar to other accidental hosts. In a laboratory study of experimentally infected dogs, neurologic signs occurred 11 days after infection.17 Pelvic-end weakness, whining when the skin was grasped, listlessness, and uncertain gait were initially demonstrated. Larvae were found throughout the CNS but were heavily distributed in the medulla and spinal cord, with some larvae in the sciatic nerve and diaphragm. Histology revealed a heavy infiltrate of eosinophils in associated nervous tissue.
Lumbar and tail hyperesthesia and pelvic limb paresis have been described in many cases.11 Ascending paralysis, urinary incontinence, vomiting, and diarrhea have also been noted as larvae leave the intestinal tract and are transported via circulation to the CNS, eliciting an inflammatory response.2,18 Eosinophilic pleocytosis in CSF is commonly reported.13,18 Both upper and lower neuron disease are typically present and thought to be due to larval migration.11 As with human infections, movement and growth of worms and associated inflammation are the likely cause of neurologic disease in dogs.2,11
Diagnosis
RLW infection cannot be diagnosed based on eosinophilic pleocytosis in CSF alone; however, eosinophilic pleocytosis in conjunction with negative test results for other differentials (eg, Neospora caninum, Toxoplasma gondii, canine distemper virus, fungal infections), additional clinical signs, history of association with intermediate or paratenic hosts, or travel to/residence in RLW-endemic areas indicate A cantonensis is a likely diagnosis.10,14,18 Because dogs are not definitive hosts, larvae are not present in feces. Definitive diagnosis in dogs and other accidental hosts can be difficult. PCR or ELISA of CSF is typically the optimal diagnostic test for confirmation of A cantonensis infection, although no commercial tests were available at the time this article was written.10,11,14,16,18 Real-time PCR using peripheral blood has yielded promising results, but the level of parasite DNA is lower in blood compared with CSF because A cantonensis spends more time in the CNS than circulating blood.19 MRI in addition to patient history, clinical signs, and molecular and serologic assays may help with diagnosis.15
Despite available diagnostics, A cantonensis infection may be cryptic, and treatment based on presumptive diagnosis may be necessary.
Treatment
Treatment involves supportive care with or without anthelmintics (eg, fenbendazole, moxidectin, milbemycin). Pain management is essential; gabapentin and tramadol are often used.11 Additional supportive care should also be considered and may include padded bedding, administration of fluids, physiotherapy, and massage (if tolerated by the patient).13 Use of antibiotics has also been reported.11,13,14,18 Antibiotics (eg, doxycycline, sulfa-/trimethoprim, clindamycin) have been used to treat progressive encephalomyelitis, which may occur due to bacteria transferred from migrating larvae after leaving the intestine of the host, as well as other potential causes of encephalomyelitis (ie, Neospora spp, Toxoplasma spp) until RLW is definitively diagnosed.11,13
Inflammation is typically treated with glucocorticoids, which may result in rapid improvement in cases of infection with low or moderate numbers of worms.13 Anthelmintic use is controversial due to the concern for additional damage caused by inflammation from worm die-off.18 Patients given anthelmintics should be monitored closely. Administration of glucocorticoids in combination with gradually increased doses of anthelmintics can be helpful, as glucocorticoids can minimize some of the inflammatory response as anthelmintics target the worms.13,18 Dogs with severe neurologic signs may have difficulty recovering; early treatment typically results in the best prognosis.11
Transmission
Awareness and prevention are key to minimizing transmission of RLW. Prevention involves avoiding ingestion of raw or undercooked intermediate or paratenic hosts that may harbor infective L3s and removing small snails or slugs from produce by washing thoroughly with clean water. Global movement of humans and animals allows for introduction of invasive parasites (eg, RLW) to new geographic areas, facilitating interaction with new hosts. Dogs may be sentinels for potential human RLW infections because of the close association between humans and companion animals. Understanding the dynamics of RLW transmission can help minimize spread and accidental infection.