Role of Gastropod Mucus in the Transmission of Angiostrongylus

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The Role Of Gastropod Mucus In The Transmission of Angiostrongylus cantonensis, A Potentially Serious Neurological Infection Kenton J. Kramer, Jourdan Posner, and William L. Gosnell ACS Chem. Neurosci., Just Accepted Manuscript • DOI: 10.1021/acschemneuro.7b00491 • Publication Date (Web): 21 Feb 2018 Downloaded from http://pubs.acs.org on March 3, 2018

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The Role Of Gastropod Mucus In The Transmission Of Angiostrongylus cantonensis, A Potentially Serious Neurological Infection Kenton J. Kramer*, Jourdan Posner and William L. Gosnell Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 96813 Abstract: Angiostrongylus cantonensis, the rat lungworm, is endemic to Hawaii. A recent increase in the number of cases has drawn intense local and national media attention. As a result there is an increased fear of acquiring the disease from local produce, which has the potential to adversely affect the income of local farmers. The most common means of transmission is by the ingestion of an infected intermediate host. Other modes of transmission have been suggested including infectious larvae being released into the mucus trail of gastropods. This literature review indicates that mucus trails from infected gastropods poses a minimal risk to humans. Keywords: Angiostrongylus cantonensis, rat lungworm, eosinophilic meningitis, nematode, parasite, mucus, gastropods. Angiostrongylus cantonensis, the rat lungworm, is a zoonotic nematode infection that is one cause of human eosinophilic meningitis. In nature the normal life-cycle involves rats as the definitive host and gastropods (snails and slugs) as the intermediate host. There is also an array of paratenic hosts such as fresh water prawns, land crabs, predacious planarians, frogs and monitor lizards that have been a source of human infection.1 Rats acquire the infection when they ingest third-stage larvae (L3) in infected gastropods or paratenic hosts. The larvae enter the blood stream and reach the rat’s central nervous system, where they molt twice before migrating to the pulmonary arteries, where the parasite develops into sexually mature adults. Female worms produce eggs that lodge in the capillaries of the lungs. When the eggs hatch the released first-stage larvae (L1) break out into the air spaces and migrate up the trachea before being swallowed and excreted with the rat’s feces. L1 larvae are ingested by gastropods feeding on rat feces and develop into L3 larvae in the tissues, thus completing the parasite’s life cycle. 1, 2, 3 Humans occasionally acquire A. cantonensis when they eat poorly cooked or uncooked gastropods or one of its paratenic hosts.4 Humans are an accidental dead-host in which the parasite is able to partially complete its life-cycle. The parasite dies in the subarachnoid

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space or in the parenchyma of the brain leading to inflammation.3 A recent cluster of angiostrongyliasis in Hawaii renewed the debate on how some patients become infected in the absence of knowingly ingesting a gastropod. This review examines the possible role of larval contaminated gastropod mucus as an alternate route of transmission to humans as suggested by other researchers. 5, 6 Gastropod Anatomy & Mucus Production Gastropod mucus is a multipurpose secretion. It is used for locomotion, adhesion, homing, reproduction, and lubrication and as a defense against predators.7 Mucus used for locomotion is made up of > 80% water combined with high molecular weight glycoproteins. Adhesive mucus, with higher amounts of glycoproteins, allows the gastropod to climb surfaces, form epiphragms and to avoid being dislodged by adverse environmental conditions.7 There will be differences in mucus glands and their products between slugs and snails and even between species within each group. The following is an example of mucus production by Helix pomatia.8 The epidermis of the foot lies over a thick layer of connective tissue and muscle. In the dorsal foot, three mucus glands can be identified by their morphology and contents. In the ventral foot, 2 mucus glands can be identified. All five glands are unicellular, teardropped shaped, embedded in the connective tissue and secrete mucus through a duct to the surface of the foot. The glands range in size from 70-200 by 35-50 microns. The mucus from the ventral glands of H. pomatia is involved in creating mucus for locomotion.8 It is translucent and non-adhesive; the type of mucus that is left behind as the gastropod moves (mucus trail). The mucus from the dorsal glands serves as a lubricant between the skin and shell and also acts as adhesive mucus.

Encapsulation of A. cantonensis in gastropods


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Gastropods have an open circulatory system containing defensive cells called hemocytes. Hemocytes are involved in phagocytosis and the encapsulation process in response to foreign material.9, 10 The infection of Biomphalaria glabrata by A. cantonensis has been described.11 Briefly, the gastropod ingests the L1 larvae in rat feces. The larvae penetrate the gastrointestinal tract and migrate into the body cavity. Twelve hours post ingestion the majority of L1 larvae are found in the foot and mantle collar. Encapsulation of the larva occurs in two phases: 1) 24-48 hours after ingestion hemocytes surround the parasite and 2) over the next 6-12 days an aggregate of various cells surround the larvae and a compact fibrous nodule begins to form. The maximum size of the capsule is reach by day 20. The mature capsule is a mixture of fibrous cells and fiber-like elements interspersed with some larger less elongated cells11. On day 11 post ingestion and within a capsule, the L1 larva molts into a second-stage (L2) larva. By day 21, the L2 larva molts into the infectious L3 larva. L3 larvae are approximately 480 microns long by 25 microns wide.3 By the 8th week the L3 larvae are found encapsulated in a large fibrous nodule.11 The encapsulation process shows intra-species variation in Biomphalaria.10 Encapsulated L3 larvae are seen in land snails and slugs and fresh water snails.13 The encapsulated L3 larvae can survive up to 12 months in B. glabrata.14 Although Biomphalaria is an aquatic snail, the host parasite interaction is similar in terrestrial gastropods and the encapsulation process is dependent on the ambient temperature and species of gastropod.3 Cheng and Alicata noted that L1 larvae are also capable of penetrating the foot of the African snail, Achatina fulica, but are still encapuslated.13 Once fully encapsulated the L3 larva is believed to enter a dauer state and remain inactive until ingested by a rat or released in a dying gastropod.15 Experimentally the A. cantonensis Acan-daf-16 gene is capable of restoring dauer formation in Caenorhabditis elegans mutants.16 In the dauer state the



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larvae are quiescent but may periodically become active. Further research is needed to characterize the dauer state in A. cantonensis and to determine conditions that would stimulate activation of the encapsulated larvae within the living gastropod. Host-Parasite Relationship Parasites have evolved strategies to maximize their chances of coming in contact with essential host(s) needed to complete its life cycle. A. cantonensis has a limited number of definitive hosts but takes advantage of a wide range of gastropods and paratenic hosts to complete its life-cycle.1, 3 In Hawaii, three species of Rattus are the definitive hosts and at least 16 gastropod species serve as intermediate hosts.17, 18 For A. cantonensis the most efficient means of completing its life cycle is for the gastropod to feed on rat feces containing L1 larvae and for rats to ingest gastropods containing L3 larvae. The preference of gastropods to feed on rat feces is partially reflected in the variable larval burden seen between gastropod genera.18, 19 Although other routes of infection for rats have been proposed, ingestion of an infected gastropod maximizes the parasite’s chance of completing its life-cycle. 20, 21 Gastropod mucus contaminated with L3 larvae is often mentioned as a alternate source of infection for rats and humans.6, 22 If releasing larvae into gastropod mucus were a major transmission strategy used by A. cantonensis we would expect to see a large number of L3 larvae in mucus trails and for rats to prefer eating gastropod mucus. An example of a parasite that is dependent on gastropod mucus to complete it life cycle is Dicrocoelium dendriticum. 23 Epidemiological studies show that human angiostrongyliasis is commonly acquired by individual and cultural food practices.24-29 Recently, infected snails drowned in an aqueous kava1 preparation was a source of human infection in Hawaii.30 Circumstantial evidence suggests that handling infected gastropods or not washing your hands after outdoor activities can be a risk factor for

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Kava is prepared from Piper methysticum and consumed for social, cultural and medicinal reasons throughout the Pacific.


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infection.27, 31. Although these papers did not identify the source of infection it is presumed to be from released L3 larvae. In addition, if released larvae were a major transmission route we would expect to see L3 larvae adapted to survive for long-periods of time in the environment and exhibit host seeking behavior, as is seen with the L3 larvae of hookworm and Strongyloides stercoralis.23, 32 Without proper moisture, Angiostrongylus L3 larvae survive for a few minutes to a few hours outside of the intermediate host. 14, 29, 33 Host seeking behavior by Angiostrongylus L3 larvae has not been reported. In this article, we reviewed the literature for studies that demonstrated A. cantonensis larvae are being released into gastropod mucus and for evidence that such larvae were infectious to animals or humans. To find published articles we searched PubMed, Web of Science, CAB Direct and OneSearch/Primo using keywords Angiostrongylus cantonensis, angiostrongyliasis, mucus and gastropod. The search identified 490 papers. Six papers met our criteria and are summarized in this review. To our knowledge no publication was missed or overlooked that would be relevant to this review. Evidence that A. cantonensis L3 larvae are found in gastropod mucus It has been postulated that during locomotion, A. cantonensis L3 larvae are released into the mucus trail of slugs and snails, which would then serve as a source of infection for the definitive host.6, 22, 34 For this to occur larvae would have to become active and migrate from the tissues to the surface of the gastropod or break into a mucus gland, which is less likely due to the size difference between the mucus glands and the larvae. In either case, L3 larvae would be expected to be found in the gastropod’s secretions. Waugh, et al., reported preliminary observations on the release of A. cantonensis L3 larvae by two genera of snails. After feeding, two of 15 Thelidomus asper snails released three L3 larvae over a 10-15 minute. Zero of 11 Pleurodonte species released larvae under similar conditions. Challenge studies in rats were not done to determine the infectiousness of the released



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larvae. The authors’ concluded that the small number of released larvae in their study would not explain the cluster of cases documented in Jamaica in 2000, which was associated with the consumption a Caesar salad. 35 Jarvi, et al., used qPCR to detect A. cantonensis DNA in the tissues and secreted mucus of Parmarion martensi (semi-slugs) in Hawaii. Their results showed numerous larvae in the semi-slug’s tissues. The authors’ estimated that DNA from less than one larva per milligram of mucus was present. No challenge studies in rats were done to determine if the mucus contained infectious larvae. The authors’ concluded that such larvae, if found on lettuce, could be a source of angiostrongyliasis.36 Qvarnstrom et al., tested P. martensi from various locations on the Island of Hawaii.37 The semi-slugs were tested for the release of larvae by either microscopy or PCR amplification followed by DNA sequencing. Microscopy revealed mucus from two of 12 semi-slugs contained motile L3 A. cantonensis larvae; one larva was found in one sample and 4 larvae in the other mucus sample. Using PCR they found that 1 of 25 semi-slugs had A. cantonensis DNA in their mucus. No challenge studies were done to determine the infectiousness of the mucus. Campbell, B et al., could not demonstrate A. cantonensis L3 larvae being released from twenty infected Limacus flavus slugs during a 2 month observation period.33 Heyneman and Lim found small numbers of Angiostrongylus larvae in the mucus from Microparmarion malayanus.38 They estimated the slugs released 2-3 larvae per 50 grams of lettuce. The authors fed released larvae to rats and showed that the larvae were infectious. However, they did not consider the infectious dose from the released larvae to be a significant risk to humans. Ash reported that veronicellid slugs in New Caledonia rarely shed larvae in their mucus, although no data were given. Individuals eating raw vegetables were more likely to develop eosinophilic meningitis than those that did not eat


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raw produce. He reported the most likely source of infection was the paratenic carnivorous planarian.29 Our literature review demonstrates that small numbers of A. cantonensis L3 larvae are released into the mucus trail of some gastropod species. If the mucus is kept moist, the released L3 larvae may survive for a short time.3 29 We postulate that dried mucus would trap the larvae in the glycoprotein matrix and lead to the desiccation and death of the infectious larvae. L3 Angiostrongylus larvae released from drowned gastropods have been shown to survive and be infectious after a few days in fresh water.15 Xie, et al., showed that under ideal conditions A. cantonensis L3 larvae can survive for 30 days in Weymouth media, but these larvae were not infectious after 8 days.39 Further studies are needed to identify environmental factors that are important for the survival and infectiousness of released L3 A. cantonensis larvae. The infectious dose of L3 Angiostrongylus larvae needed to produce clinical disease in humans is unknown. In 1967, Rosen, et al. stated that the infectious dose might be small. They proposed that it might be possible for individuals to transfer a small number of L3 larvae from their hands, contaminated with smashed gastropods, to their mouths.27 However, infected slugs and snails contain 100’s to 100,000’s of larvae per organism, which would suggest that the oral infectious dose is probably high.18, 36, 37 If a consumer is concerned about contracting angiostrongyliasis from produce contaminated with mucus trail(s), they have a few options on what to do with the product. The product could be returned to the vendor, thrown out, washed thoroughly, although the gastropod mucus is difficult to remove, or cook or freeze the product. Alicata found that cooking was more efficient at killing A. cantonensis L3 larvae than freezing.40 Alicata also reported that freezing infected snails or freshwater prawns for 24 hours at -15C was effective in killing the infectious larvae.41 In conclusion, it appears from the published evidence that mucus from slugs and snails has a negligible potential to contain sufficient numbers of



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Angiostrongylus L3 larvae to cause disease in humans. In fact, no epidemiological study was found implicating gastropod mucus as a source of infection in humans. As suggested by others, small gastropods or planarians hiding within green leafy vegetables or ripe fruit are a more likely source of human infection.27, 29, 33, 41-43 This seems especially plausible in Hawaii where juvenile semi-slugs, easily overlooked in green leafy vegetables, have been found to be infected with A. cantonensis.44 Washing produce under running water should minimize the risk of infection.45 Acknowledgements: We thank the Health Sciences Library at the John A Burns School of Medicine for their help in database searching and retrieving relevant articles.


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References 1.

Wang, Q. P., Lai, D. H., Zhu, X. Q., Chen, X. G., and Lun, Z. R. (2008) Human angiostrongyliasis. Lancet Infect Dis 8, 621-630.

2.

Jindrak, K. (1968) Early migration and pathogenicity of Angiostrongylus cantonensis in laboratory rats. Ann Trop Med Parasitol 62, 506-517.

3.

Alicata, J. and Jindrak, K. (1970) Angiostrongylosis in the Pacific and Southeast Asia. Charles C. Thomas, Springfield, Illinois.

4.

Wang, Q.P., Wu, Z. D., Wei, J., Owen, R. L., and Lun, R. Z. (2012) Human Angiostrongylus cantonensis: an update. Eur J Clin Microbiol Infect Dis 31, 389-395.

5.

Waugh, C. A., Shafir, S., Wise, M., Robinson, R. D. Eberhard, M. L. and Lindo, J. F. (2005) Human Angiostrongylus cantonensis in Jamaica, Emerg Infect Dis 11, 1977-1978.

6.

Giannelli, A., Colella, V., Abramo, F., do Nascimento Ramos, R.A., Falsone, L., Brianti, E., Varcasia, A., Dantas-Torres, F., Knaus, M., Fox, M. T. and Otranto, D. (2015) Release of lungworm larvae from snails in the environment: potential for alternative transmission pathways, PLoS Negl Trop Dis 9, e0003722. https://doi.org/10.1371/journal.pntd.0003722

7.

Ng, T. P., Saltin, S. H., Davies, M. S., Johannesson, K., Stafford R., and Williams, G. A. (2013) Snails and their trails: the multiple functions of trailfollowing in gastropods, Biological reviews of the Cambridge Philosophical Society 88, 683-700.

8.

Greistorfer, S., Klepal, W., Cyran, N., Gugumuck, A., Rudoll, L., Suppan, J., and von Byern, J. (2017) Snail mucus - glandular origin and composition in Helix pomatia, Zoology (Jena, Germany) 122, 126-138.

9.

Loker, E. (2010) Gastropod Immunobiology, In Invertebrate Immunity (Soderhall, K., Ed.), Landes Bioscience and Springer Science+Business Media.

10. Lima, M. G., Tunholi-Alves, V. M., Gaudencio, F. N., Martins, F. G., Castro, R. N., Thiengo, S. C., Garcia, J. S., Maldonado, Jr, A., and Pinheiro, J. (2016) The influence of Angiostrongylus cantonensis (Nematoda, Metastrongylidae) infection on the aerobic metabolism of Biomphalaria straminea and Biomphalaria tenagophila (Mollusca, Gastropoda), Exp Parasitol 171, 1-9. 11. Harris, K. R. and Cheng, T. C. (1975) The encapsulation process in Biomphalaria glabrata experimentally infected with the metastrongylid Angiostrongylus cantonensis: light microscopy, Int J Parasitol 5, 521-528. 12. K. R. Harris, and T. C. Cheng. (1975) The encapsulation process in Biomphalaria glabrata experimentally infected with the metastrongylid



Kramer, K., et al

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Angiostrongylus cantonensis: enzyme histochemistry, J Invertebr Pathol 26, 367-374. 13. T. Cheng, and J. Alicata. (1965) On the modes of infection of Achatina fulica by the larvae of Angiostrongylus cantonensis, Malacologia 2, 267-274. 14. C. Richards, and J. Merritt. (1967) Studies on Angiostrongylus cantonensis in Molluscan Intermediate Hosts, J Parasitol 53, 382-388. 15. T. Cheng, and J. Alicata. (1964) Possible role of water in the transmission of Angiostrongylus cantonensis (Nematoda: Metastrongylidae), J Parasitol 50, 39-40. 16. B. Yan, W. Sun, L. Yan, L. Zhang, Y. Zheng, Y. Zeng, H. Huang and S. Liang. (2016) Structural and functional characterisation of FOXO/AcanDAF-16 from the parasitic nematode Angiostrongylus cantonensis, Acta Trop 164, 125-136. 17. L. R. Ash. (1962) The helminth parasites of rats in Hawaii and the description of Capillaria traverae sp.n, J Parasitol 48, 66-68. 18. J. R. Kim, K. A. Hayes, N. W. Yeung and R. H. Cowie. (2014) Diverse gastropod hosts of Angiostrongylus cantonensis, the rat lungworm, globally and with a focus on the Hawaiian Islands, PLoS One 9, e94969. 19. J. Barratt, D. Chan, I. Sandaradura, R. Malik, D. Spielman, R. Lee, D. Marriott, J. Harkness, J. Ellis and D. Stark. (2016) Angiostrongylus cantonensis: a review of its distribution, molecular biology and clinical significance as a human pathogen, Parasitology 143, 1087-1118. 20. H. Liu, and e. al. (2009) Establishment and observation of the life cycle of Angiostrongylus cantonensis in a laboratory setting, J Pathog Biol, 836-839. 21. R. H. Cowie. (2013) Pathways for transmission of angiostrongyliasis and the risk of disease associated with them, Hawaii J Med Public Health 72, 70-74. 22. T. W. Simpson, T. Yonamine, E. Henzan, T. Nishihira and S. S. Chinen. (1970) Eosinophilic meningitis in Okinawa. Three suspected cases of angiostrongyliasis in man, Am J Trop Med Hyg 19, 770-774. 23. L. Roberts, and J. Janony (2005) Gerald D. Schimdt & Larry S. Roberts’ Foundations of Parasitology, 7th edition ed., McGraw Hill, New York, NY. 24. S. R. Horio, and J. E. Alicata. (1961) Parasitic meningo-encephalitis in Hawaii. A new parasitic disease of man, Hawaii Med J 21, 139-140. 25. L. Rosen, J. Laigret and S. Bories. (1961) Observations on an outbreak of eosinophilic meningitis on Tahiti, French Polynesia, Am J Hyg 74, 26-42. 26. J. Alicata. (1965) Notes and observations on murine angiostrongylosis and eosinophilic meningoencephalitis in Micronesia, Canad J Zool 43, 667-672. 27. L. Rosen, G. Loison, J. Laigret and G. D. Wallace. (1967) Studies on eosinophilic meningitis. 3. Epidemiologic and clinical observations on Pacific


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islands and the possible etiologic role of Angiostrongylus cantonensis, Am J Epidemiol 85, 17-44. 28. S. Punyagupta, T. Bunnag, P. Juttijudata and L. Rosen. (1970) Eosinophilic meningitis in Thailand. Epidemiologic studies of 484 typical cases and the etiologic role of Angiostrongylus cantonensis, Am J Trop Med Hyg 19, 950958. 29. L. R. Ash. (1976) Observations on the role of mollusks and planarians in the transmission of Angiostrongylus cantonensis infection to man in New Caledonia, Rev Biol Trop 24, 163-174. 30. Hawaii Department of Health. (2017) DOH News Release: Hawaii Department Of Health Confirms Two Cases Of Rat Lungworm On Hawaii Island With Four Probable Cases, In Residents accidentally consumed garden slugs in homemade drink. 31. K. Wan, and W. Weng. (2004) Eosinophilic meningitis in a child raising snails as pets, Acta Tropica 90, 51-53. 32. J. K. Udonsi, and G. Atata. (1987) Necator americanus: Temperature, pH, light, and larval development, longevity, and desiccation tolerance, Exptl Parasitol 63, 136-142. 33. B. G. Campbell, and M. D. Little. (1988) The finding of Angiostrongylus cantonensis in rats in New Orleans, Am J Trop Med Hyg 38, 568-573. 34. D. Chan, J. Barratt, T. Roberts, R. Lee, M. Shea, D. Marriott, J. Harkness, R. Malik, M. Jones, M. Aghazadeh, J. Ellis and D. Stark. (2015) The Prevalence of Angiostrongylus cantonensis/mackerrasae Complex in Molluscs from the Sydney Region, PLoS One 10, e0128128. 35. C. A. Waugh, J. F. Lindo, J. Lorenzo-Morales and R. D. Robinson. (2016) An epidemiological study of A. cantonensis in Jamaica subsequent to an outbreak of human cases of eosinophilic meningitis in 2000, Parasitology 143, 1211-1217. 36. S. I. Jarvi, M. E. Farias, K. Howe, S. Jacquier, R. Hollingsworth and W. Pitt. (2012) Quantitative PCR estimates Angiostrongylus cantonensis (rat lungworm) infection levels in semi-slugs (Parmarion martensi), Mol Biochem Parasitol 185, 174-176. 37. Y. Qvarnstrom, J. J. Sullivan, H. S. Bishop, R. Hollingsworth and A. J. da Silva. (2007) PCR-based detection of Angiostrongylus cantonensis in tissue and mucus secretions from molluscan hosts, Appl Environ Microbiol 73, 1415-1419. 38. D. Heyneman, and B. L. Lim. (1967) Angiostrongylus cantonensis: proof of direct transmission with its epidemiological implications, Science 158, 10571058.



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39. H. Xie, D. Yuan, S. Luo, X. Zeng, X. Zeng, P. He, Z. Lv and Z. Wu. (2017) Angiostrongylus cantonensis: An optimized cultivation of this parasitic nematode under laboratory conditions, Parasitol Res 116, 2231-2237. 40. J. E. Alicata. (1967) Effect of freezing and boiling on the infectivity of thirdstage larvae of Angiostrongylus cantonensis present in land snails and freshwater prawns, J Parasitol 53, 1064-1066. 41. J. E. Alicata (1970) Sources of infection and prevention of eosinophilic meningitis (cerebral angiostrongylosis). In H.D. Srivastava Commen. pp 545-554, Indian Veterinary Research Institute, India. 42. J. E. Alicata (1963) Experimental work on eosinophilic meningitis, Vol. 28, Plantation Health. 43. B. Gutteridge, and e. al. (1972) Human larval meningitis possibly following lettuce ingestion in Brisbane, Pathology 4, 63-64. 44. R. Hollingsworth, and e. al. (2007) Survey and life history observations for Parmarion cf. martensi Simroth (1893), a new slug pest in Hawaii Island, with notes on its potential as a vector for human angiostrongyliasis, Pac Sci 61, 457-467. 45. N. W. Yeung, K. A. Hayes and R. H. Cowie. (2013) Effects of washing produce contaminated with the snail and slug hosts of Angiostrongylus cantonensis with three common household solutions, Hawaii J Med Public Health 72, 83-86.


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Role of Gastropod Mucus in the Transmission of Angiostrongylus

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