Abstract

Six cases of angiostrongylosis were seen in nonhuman primates at the Audubon Zoo over a 6-yr period. Affected animals included two howler monkeys (Alouatta caraya), three black and white ruffed lemurs (Lemur variegatus), and a talapoin monkey (Cercopithecus talapoin). All manifested with varying degrees of neurologic signs. In general, antihelmintic treatment was contraindicated, as clinical signs were attributed to host inflammatory responses, which increase with the death of the migrating nematode larvae. Two of the lemurs were euthanatized and one howler monkey died as a result of the infection. Angiostrongylus cantonensis was confirmed on histopathologic sections of the brains and spinal cords. The absence of cases since 1992 is attributed to the physical removal of the intermediate hosts, slugs and snails, from exhibit areas. The life cycle, clinical signs, diagnosis, treatment, and prevention of A. cantonensis in humans, nonhuman primates, and other species are reviewed.

Introduction

The nematode Angiostrongylus cantonensis is the lungworm of rats. Humans and other mammals can be aberrant hosts of the parasite. In humans, Angiostrongylus cantonensis infection is most often characterized by eosinophilic meningoencephalitis, although an ocular form and pulmonary involvement have been described.⁵ Naturally occurring neural infections have been described in a variety of nonhuman primates (tamarin, cynomolgus monkey, howler monkey, white-handed gibbon), wallaby, bettong, horse, and dog.^{3,6,7,10-12,15} The pathogenesis of the disease process is produced by motile larvae and young adults migrating through the CNS, and by the host’s granulomatous reaction. Eosinophilic meningoencephalitis occurs widely in the tropics and has recently been reported in North America. Causes for the spread of this host parasite system are many and include cultural and economic factors. Infection occurs via the ingestion of the intermediate host (snails or slugs) or paratenic host (freshwater prawns, land crabs, frogs, or lizards) in an uncooked or undercooked state. In humans, antemortem diagnosis is dependent on serologic testing, although peripheral absolute eosinophilia is highly suggestive. Radiographs, computerized tomography or magnetic resonance imaging may also provide results consistent with Angiostrongylus infection; however, a negative result cannot rule out presence of the organism. Treatment is palliative and should be aimed at preventing damage caused by inflammation associated with parasite migration and secondary infection. Use of anthelmintics is not recommended. Prevention is paramount and should involve preventing ingestion of the intermediate or paratenic hosts. Although prognosis is generally considered good in humans, prognosis in nonhuman primates and other mammalian hosts, especially those exhibiting signs of lower motor neuron dysfunction, is guarded.

Life Cycle

The definitive host of A. cantonensis is a variety of rodents of the genus Rattus and Bandicota. In one study, 21.4% of 94 rats caught in New Orleans, Louisiana were found to be infected.² Adults of A. cantonensis inhabit the pulmonary arteries, where eggs are laid and hatch. The first stage larvae enter the alveolar space, migrate up the trachea and then down the alimentary tract, and are excreted in the feces. Terrestrial snails, slugs, and aquatic snails serve as intermediate hosts, with infection occurring by percutaneous or oral (ingestion) routes. Larvae develop to third stage within the mollusk. Third stage larvae were recovered from slugs but not snails found at the Audubon Zoo. Rats then become infected by ingestion of infected snails or slugs. The larvae migrate from the intestine to the central nervous system where development through two more stages occurs in 2–3 wk. Larvae then migrate to the subarachnoid space, enter the venous system, and make their way to the pulmonary arteries for maturation and reproduction.⁵

In human and other aberrant hosts, infection occurs secondary to ingestion of raw or undercooked snails or slugs (intermediate hosts), contaminated vegetables, or paratenic hosts (freshwater prawns, land crabs, frogs, lizards)¹⁴ which feed on the intermediate host. In humans, larvae migrate to the CNS, where development stops. Humans and nonhuman primates are considered dead end hosts. Pulmonary involvement has been reported but is considered rare. The incubation period ranges from 1–5 wk with an average of 2 wk.⁵

Pathogenesis/Clinical Signs

In humans, headache, stiffness, vomiting and myalgia in the arms and shoulders are complaints in mild cases. Paresthesias involving the trunk, lower extremities, bowel and bladder dysfunction, weakness and hyporeflexia of the legs have been reported with involvement of the brain, spinal cord and nerve roots.⁹ Pathogenesis depends on the damage caused by the larvae and young adults, as well as the host’s inflammatory response. Cranial nerve palsies (III, IV, VI, VII) are also common clinical signs.⁵ In a study of Taiwanese children, common additional initial signs were fever, cough, rhinorrhea, marked abdominal distension, and hepatomegaly.⁸

At the Audubon Zoo, clinical signs in nonhuman primates have invariably been restricted to the nervous system and have included posterior paresis progressing to paralysis, loss of balance, nystagmus, facial hemiparalysis, head tremors, ataxia, abnormal forelimb extension, and progressive hemi- or tetraparesis. Based on clinical experience, animals showing upper motor neuron signs tend to recover with supportive care, while animals showing progressive lower motor neuron signs evolve into deeper states of paresis until they become unsalvageable. Similar patterns have been noted in affected dogs.¹¹

Primates surviving initial onset are occasionally left with permanent sequelae, such as hypermetria and head tilt.

Previous cases of Angiostrongylus infections in nonhuman primates manifested constitutional signs such as weakness, lethargy, anorexia, loss of body condition and vomiting.^3,6,7,10 Neurologic signs have included progressive tetraparesis, incoordination, an inability to walk, sit, stand, climb, or eat, and paralysis of extremities. In addition, diarrhea, urinary incontinence, tail chewing, ptyalism, tremors, and disorientation were seen in tamarins.³ In dogs, clinical signs were primarily limited to tail and ascending paresis, bladder paresis, lumbar hyperalgesia, and muscle wasting.¹² In the horse, tetraparesis, hyporeflexia of all limbs, urinary incontinence, and an inability to rise were common presenting signs in two foals.¹⁵ In three bettongs (Aepyprymnus rufescens), progressive hindlimb dysfunction from paresis to paralysis, deterioration of proprioception and superficial sensation, along with bladder dysfunction and flank lesions caused by excessive grooming were noted.⁷ In a single Bennett’s wallaby (Macropus rufogriseus), poor body condition and incoordination progressed to posterior paresis, followed by recumbency, bilateral mydriasis, nystagmus, and opisthotonic spasms.¹²

Diagnostics

In humans, laboratory diagnosis is based on the findings of eosinophilic CSF pleocytosis (500–5,000 cell/mm³ with 20–90% eosinophils), elevated CSF proteins, and normal to slightly decreased CSF glucose. Charcot-Leyden crystals may be observed in the CSF.⁵ Blood leukocytosis (>10,000) with eosinophilia (>10%) is uncommon in adults; however, in children this appears to be a frequent finding, accounting for 80% of the cases documented in Thailand.^5,8 In humans, diagnosis may be confirmed by serologic testing by means of IF or EIA.⁵

Signs of peripheral eosinophilia and leukocytosis are noticeable in most affected mammals that become aberrant hosts. In bettongs, consistent elevations were noted in cerebrospinal leukocytes and eosinophils.⁷ In all nonhuman primate cases seen at Audubon Zoo, peripheral eosinophilia and leukocytosis were observed consistently. However, eosinophilia did not always correlate with onset of clinical disease and was seen as late as 2 mo after clinical signs ceased.

Serology was used successfully in nonhuman primates in the initial cases diagnosed at the Audubon Zoo (J. Cross, personal communication). A reagent was changed in 1991, and cross-reactivity with nonhuman primate serum ceased. The samples taken from a male black and white lemur euthanatized in 1992 were sent to Taiwan, where cross-reaction was not observed, in spite of known infection. Magnetic resonance imaging was attempted in a suspected positive female howler monkey, but the size of the animal produced artifactual images that were not diagnostic. At present, there is no effective serologic means for diagnostic confirmation in nonhuman primates.

Treatment and Prognosis

In humans, the disease is usually benign and self-limiting, with symptoms persisting for only 2–4 wk. Death is rare. Treatment is aimed at control of pain and inflammation with analgesics and sedatives, while corticosteroids are reserved for cases with neurologic deficit or severe inflammation. No treatment has been recognized as effective. Anthelmintics are generally not recommended as the death of the parasites is associated with a worsening of clinical signs or death due to an increased reaction to the dead or dying worms.⁵ Nevertheless, in a study in affected Taiwanese children, albendazole and levamisole were used with good results.⁸

In the nonhuman primate cases at Audubon Zoo, 4/6 were treated with anthelmintics, 6/6 were placed on at least one form of antibiotic, 5/6 were placed on steroids, and 1/6 was placed on nonsteroidal anti-inflammatories. A female howler (age 6 yr) and a female talapoin monkey (age 3 yr) experienced complete resolution of clinical signs. Two male black and white ruffed lemurs (ages 4 and 5 yr) had to be euthanatized due to irreversible neurologic damage, while a female black and white ruffed lemur (age 4 yr) recovered with a permanent head tilt. A male howler monkey (age 9 yr) was found dead, while a talapoin monkey recovered without visible sequelae.

Other affected mammals reported to be infected showed similar patterns. Two foals reported with angiostrongylosis were euthanatized.¹⁵ In macropods reported to have suffered visceral larva migrans secondary to Angiostrongylus cantonensis, a wallaby died and bettongs were euthanatized.^7,12 All five of the tamarins (Saguinus sp.) reported to be infected died.³ In a study of 55 cases of canine neurostrongylosis, only puppies with the most severe neurologic signs consisting of complete hind limb paralysis, urinary overflow incontinence, flaccid tail paresis, and hind limb paralysis were euthanatized. This followed 2 wk of supportive care and corticosteroids with no clinical improvement noted. Most other puppies in the study recovered uneventfully.¹¹ There is a single report of infection in a reptile, a yellow tree monitor (Varanus bengalensis).¹⁴

The poor prognosis in mammals other than humans remains unexplained, but may be due in part to the large dose of parasites received relative to body size, or an inability to treat as early due to common clinical signs such as headache and myalgia, which are difficult to evaluate in animals.

Prevention in Zoos

Successful resolution of angiostrongylosis in the primate collection at the Audubon Zoo depended on repeated physical removal of slugs and snails from animal and public contact areas. Attempts at organic and safe baiting were unsuccessful. Treatment of the area with copper-based compounds was deemed to be too risky due to the possibility of secondary toxicity to collection mammals. Beer traps, citrus rind and other low toxicity natural methods had no appreciable results. Initial removals were bi-annual, until low total slug and snail counts were achieved in exhibits considered to be high risk. The now annual Slugathon has between 30–60 volunteer participants, with first prize and recognition going to the Slugmaster, the person who collects the most slugs and snails from a single enclosure. Slugs and snails collected were initially submitted to the Tulane School of Tropical Medicine for analysis. A total infection rate of 1–2% was estimated from 200 animals dissected and examined in 1994 (Little, personal communication). Instituting an aggressive and effective pest control program has reduced the total population of rodents on zoo grounds, so the cycle has fewer possibilities of perpetuating itself. Snail and slug removal has been subjectively deemed to be effective. The first Slugmaster collected over 400 slugs and snails (over 500 g in weight) from a single outdoor howler exhibit, while the runner up had over 200 gastropods from the same enclosure. The last contest, only 40 gastropods could be removed from the entire area around the exhibit. There has not been a suspected case of angiostrongylosis since the inception of the removal program.

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