Angiostrongylus cantonensis central nervous system infection in captive callitrichids in Texas

Journal Pre-proof Angiostrongylus cantonensis central nervous system infection in captive callitrichids in Texas

Erin E. Edwards, Mindy M. Borst, Barbara C. Lewis, Gabriel Gomez, Joseph P. Flanagan PII:

S2405-9390(19)30263-1

DOI:

https://doi.org/10.1016/j.vprsr.2019.100363

Reference:

VPRSR 100363

To appear in:

Veterinary Parasitology: Regional Studies and Reports

Received date:

24 September 2019

Revised date:

4 December 2019

Accepted date:

6 December 2019

Please cite this article as: E.E. Edwards, M.M. Borst, B.C. Lewis, et al., Angiostrongylus cantonensis central nervous system infection in captive callitrichids in Texas, Veterinary Parasitology: Regional Studies and Reports(2019), https://doi.org/10.1016/ j.vprsr.2019.100363

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© 2019 Published by Elsevier.

Journal Pre-proof Title Angiostrongylus cantonensis central nervous system infection in captive callitrichids in Texas

Authors

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Erin E. Edwardsa, Mindy M. Borsta, Barbara C. Lewisa, Gabriel Gomeza, Joseph P. Flanaganb

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Author Affiliations:

Texas A&M Veterinary Medical Diagnostic Laboratory, College Station, Texas, USA

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Houston Zoo, Houston, Texas, USA

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Corresponding Author

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Erin Edwards, Texas A&M Veterinary Medical Diagnostic Laboratory, PO Drawer 3040, College Station, TX 77841-3040; phone: 979-845-3414; e-mail: [email protected]

Present Address Author Barbara C. Lewis has retired since the start of this study.

Journal Pre-proof Abstract Angiostrongylus cantonensis is a tropical lungworm of rats known for central nervous system migration in aberrant primate hosts. Here, we describe A. cantonensis infection in three captive callitrichids from a Texas zoo. The affected animals included a Goeldi’s monkey (Callimico goeldii), a cotton-top tamarin (Saguinus oedipus), and a pied tamarin (Saguinus

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bicolor) that ranged from 8 to 18 years old. Clinical signs included lethargy, ataxia, and seizures. Histologically, these animals had an eosinophilic meningoencephalitis to myelitis and some areas

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had abundant macrophages and parasite migration tracts. All cases had intralesional

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metastrongyle parasites, and nematodes were extracted from the formalin-fixed brain specimen

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in one case. This extracted parasite was identified as Angiostrongylus cantonensis based on

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morphologic features and diagnosis was confirmed with PCR. These cases represent the first report of this parasite in non-human primates in Texas, highlighting the western spread of A.

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cantonensis in the continental United States.

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Keywords: Angiostrongylus; encephalitis; parasite; primate

1. Introduction Angiostrongylus cantonensis is a metastrongylid parasite that is endemic to Southeast Asia and the Pacific Basin. This parasite can cause neurologic abnormalities in aberrant hosts, including humans and other animals. As such, this parasite represents an important public health threat. The geographic range of this parasite is expanding and cases have been documented in the southeastern United States for the past few decades.

Journal Pre-proof Rats are the definitive host for A. cantonensis. In rats, larvae travel to the central nervous system before migrating to the pulmonary arteries, the final site of maturation and reproduction. Humans and other mammals can serve as aberrant hosts (Wang et al., 2008; Cowie, 2013; Spratt, 2015). These species are infected following ingestion of gastropods, the intermediate host. Ingestion of vegetation contaminated with gastropod slime trails is another postulated route of exposure. Paratenic hosts, such as crustaceans, frogs, and lizards, can also play important roles in

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parasite transmission (Wang et al., 2008; Cowie, 2013; Spratt, 2015). In accidental hosts, the

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parasite is neurotropic and neural larval migrans can cause eosinophilic meningitis with

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associated clinical neurological signs.

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Among aberrant hosts, humans and non-human primates appear to be most susceptible to

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clinical disease. There have been multiple reports of aberrant infection in non-human primates in zoological settings along the Gulf Coast (Gardiner et al., 1990; Kim et al., 2002; Duffy et al.,

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2004; Emerson et al., 2013; Kottwitz et al., 2014). However, no non-human primate cases have

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been reported farther west than Louisiana. In this report we describe A. cantonensis infection in three callitrichids species from the same zoo in Houston, Texas, representing the most western

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documented cases of this parasite in non-human primates in the continental United States.

1.2 Case Presentation 1.2.1 Clinical Histories

The first case in this series was a 13-year-old, male, Goeldi’s monkey (Callimico goeldii) that presented with acute onset of lethargy with weakness, diarrhea, ataxia, and seizures. Supportive treatment was initiated, but the patient died two days later following a seizure.

Journal Pre-proof Two months following the death of case one, an 18-year-old, male, cotton-top tamarin (Saguinus oedipus) developed neurological signs manifested primarily as ataxia. The animal was also in poor body condition with gradual weight loss over the past several months and rapid weight loss noted over the preceding week. Euthanasia was elected following continued ataxia and unresponsive anorexia.

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The third case, an eight-year-old, male, pied tamarin (Saguinus bicolor), presented with clinical signs 33 months later. This patient had a sudden onset of seizures and also had a recent

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history of weight loss. During a three-day period of hospitalization, the animal developed rear

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limb paresis and paralysis and was reported to move with an army crawl locomotion. The

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progression of clinical signs with no improvement prompted euthanasia.

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1.2.2 Gross Examination

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A necropsy was promptly performed on all animals by the housing zoological institution. All animals were described to be in a poor body condition and the tamarins had a mildly

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thickened and dilated intestinal tract. No macroscopic lesions were noted in the central nervous

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system. Tissue samples were collected in 10% neutral buffered formalin and submitted to the Texas A&M Veterinary Medical Diagnostic Laboratory for histologic processing and examination. 1.2.3 Histopathology In all cases, there was a meningitis that ranged from mild to severe and affected the cerebrum, cerebellum, and brainstem. The spinal cord was only examined in case three and in this animal the meningitis extended multifocally along the entire length of the cord. Eosinophils predominated in two cases and in one other case the infiltrate was primarily composed of

Journal Pre-proof macrophages. Metastrongyle larval parasites were identified in all three cases and were found in the meninges and/or neural parenchyma in the cerebrum, cerebellum, and/or pons (Fig. 1A). These nematodes measured ~200 μm wide and identifiable features included an eosinophilic cuticle, polymyarian coelomyarian musculature, lateral chords, accessory hypodermal cords, and a large intestine (Fig. 1B). In case one, the parasites were more immature and slightly smaller than in the other cases. Meningeal nematodes in case two were occasionally degenerate and

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surrounded and partially engulfed by multinucleated giant cells. In cases one and two there was

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evidence of associated parasite migration throughout the cerebral and cerebellar parenchyma,

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and in case three there were similar lesions in the thoracic spinal cord. These areas were

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characterized by cavitation, hemorrhage, histiocytic inflammation, edema, axon degeneration, and gliosis. In case three, a cross section of a metastrongyle parasite was found within a large

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pulmonary artery. This nematode had identical features to those found in the meninges.

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Histologic lesions in other tissues included chronic pancreatitis in case one and colonic

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adenocarcinoma, glomerulonephritis, and mild myocardial fibrosis in case two.

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1.2.4 Parasitology and Molecular Diagnostics Following histologic identification of the parasites in case three, sections of the formalinfixed brain were examined under a dissecting microscope and parasites were manually extracted from the subarachnoid space. One complete, male nematode measuring ~12 mm long and two partial nematodes were recovered. Specific morphologic features identified in the complete specimen included a copulatory bursa with rays and two spicules that measured ~1230 um long (Fig. 2). Based on these anatomical features, the spicule length, and considering the host species and affected anatomical location, this parasite was identified as A. cantonensis (Duffy et al.,

Journal Pre-proof 2004). Angiostrongylus cantonensis PCR was performed at the Centers for Disease Control and Prevention on one of the extracted nematode fragments and was positive (Qvarnstrom et al., 2016).

1.3 Discussion

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Angiostrongylus cantonensis is most prevalent in Southeast Asia and in the Pacific Basin.

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In recent decades, cases have been documented worldwide in tropical and subtropical regions,

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with the first described reports in the continental United States occurring in the 1980s in New

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Orleans, Louisiana, presumably introduced through a shipping port (Campbell and Little, 1988). Since then, A. cantonensis has been described in many species in the southeastern United States

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along the Gulf Coast, including rats, snails, humans, non-human primates, a miniature horse,

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opossums, and nine-banded armadillos (Gardiner et al., 1990; Costa et al., 2000; Kim et al., 2002; Duffy et al., 2004; Emerson et al., 2013; Kottwitz et al., 2014; Foster et al., 2016; Dalton

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et al., 2017; Flerlage et al., 2017; Stockdale et al., 2017). Infection has also been reported in a

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captive pygmy falcon in southern California, though ingestion of imported geckos from southeast Asia, an endemic region for angiostrongylosis, was speculated to be the source of infection (Burns et al., 2014). Human cases have been reported in young children as far west as Houston and as far north as Tennessee (Foster et al., 2016; Flerlage et al., 2017). Until this point, cases in non-human primates have been limited to Louisiana, Alabama, and Florida and have been described in a howler monkey (Abouatta caraya), Geoffroy’s tamarins (Saguinus geoffroyi), a white-handed Gibbon (Hylobates lar), a red-ruffed lemur (Varecia rubra), and an orangutan (Pongo pygmaeus) (Gardiner et al., 1990; Kim et al., 2002; Duffy et al., 2004;

Journal Pre-proof Emerson et al., 2013; Kottwitz et al., 2014). The cases described in this report are the most western documented cases in captive non-human primates in the mainland United States. A potential limitation in this study is that definitive parasite identification was only pursued in one of the three animals (case three), as samples were no longer available from the other two animals. Based on the identical histologic parasite features and lesions, shared

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zoological environment, and similarly affected host species, a confident presumptive diagnosis

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was made for the other two primates.

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The presence of A. cantonensis within the lung of the pied tamarin (case three) is interesting. Pulmonary infection has been described in one other non-human primate in the

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United States (Kottwitz et al., 2014). Although these parasites naturally migrate to the lung in

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rodent hosts, migration typically ceases in the nervous system of other hosts. Pulmonary migration has rarely been described in human cases of angiostrongyliasis (Cowie et al., 2013;

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Reece et al., 2013). In a group Australian gang-gang cockatoos with neuroangiostrongyliasis, the

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lungs contained verminous granulomas that were attributed to A. cantonensis (Reece et al.,

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2013). The presence of A. cantonensis in a pulmonary artery of the pied tamarin in this case indicates successful larval migration to the lungs. This finding suggests that parasite maturation and potentially reproduction may be possible in non-human primates and carries important transmission implications. Only one pulmonary nematode was found both in this case and in the previous reported case, and no eggs were found which would indicate active reproduction. Disease prevention in zoological settings is challenging, particularly in those with naturalistic enclosures. Preventative methods should include pest control targeting rodent primary hosts and gastropod intermediate hosts and frequent debris clean-up. Since snails and

Journal Pre-proof slugs prefer moist habitats, removal of dead leaves, branches, and other moisture-trapping materials from enclosures is pivotal for reduction of gastropod populations. Since it is impossible and undesirable to remove all trees, branches, and leaves from enclosures, primate habitats will face a continual risk of infection in endemic areas. Furthermore, primates are inquisitive animals with foraging behaviors that increase their risk of exposure. These animals should be closely monitored for any subtle or obvious neurological signs so supportive treatment can be initiated

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promptly.

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1.4 Conclusion

In conclusion, this report demonstrates the western spread of A. cantonensis in the

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continental United States, emphasizes that this disease should be considered a differential

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diagnosis for captive non-human primates and other animals with neurologic disease along the

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to prevent exposure.

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Gulf Coast, and highlights the importance of rodent and gastropod control in zoological settings

Acknowledgments

We would like to thank the TVMDL histopathology lab staff for their help trimming tissues and processing slides. We would also like to thank Dr. Thomas Craig and Dr. Yvonne Qvarnstrom for their confirmation of parasite identification.

Declarations of Interest

Journal Pre-proof The authors declare no conflicts of interest.

Funding This research did not receive any specific grant from funding agencies in the public,

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commercial, or not-for-profit sectors.

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cantonensis Infection: A Cause of Fever of Unknown Origin in Pediatric Patients. Clin. Infect. Dis. 63, 1475–1478. Gardiner, C.H., Wells, S., Gutter, A.E., Fitzgerald, L., Anderson, D.C., Harris, R.K., Nichols, D.K., 1990. Eosinophilic Meningoencephalitis Due to Angiostrongylus cantonensis as the Cause of Death in Captive Non-Human Primates. Am. J. Trop. Med. Hyg. 42(1), 70–74. Kim, D.Y., Stewart, T.B., Bauer, R.W., Mitchell, M., 2002. Parastrongylus (=Angiostrongylus) cantonensis Now Endemic In Louisiana Wildlife. J. Parasitol. 88(5), 1024–1026.

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Figure Captions

Journal Pre-proof Fig. 1. Histopathology of cerebral parasites in a pied tamarin (Saguinus bicolor) A) Photomicrograph of metastrongyle parasites in the cerebral meninges of a pied tamarin (case three) surrounded by inflammation. Hematoxylin and eosin (H&E); 40X magnification; scale bar = 200 μm. B) Higher magnification of the parasite (from another area), showing the following morphologic features: eosinophilic cuticle, coelomyarian musculature, lateral chords (LC), accessory hypodermal cords (AC), a uterus, and a large intestine (LI). H&E; 200X

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magnification; scale bar = 50 μm.

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Fig. 2.

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Wet mount of a male Angiostrongylus cantonensis nematode extracted from the cerebellar meninges of a pied tamarin (Saguinus bicolor, case three), showing spicules (S) and a copulatory

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bursa (B). 10X magnification; scale bar = 100 μm.

Journal Pre-proof Angiostrongylus cantonensis central nervous system infection in captive callitrichids in Texas Highlights

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Documentation of Angiostrongylus cantonensis infection in three captive primates from a Texas zoo Histologic infection of the brain, spinal cord, and lung Highlights the western spread of this parasite in the continental United States

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Journal Pre-proof Conflict of Interest

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The authors declare no conflicts of interest.

Journal Pre-proof Ethical statement

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This paper is a descriptive paper of postmortem parasitologic lesions. No live animals were used for experimentation. Proper welfare and ethical behaviors were ensured during handling and management of the sick patients.

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