Rat Lungworm Frequently Asked Questions

Research shows that slug slime can contain infective rat lungworm larvae. One study showed infective larvae passed spontaneously from Microparmarion malayanus when it was feeding. The larvae were embedded in the mucus trail and remained viable for at least 72 hours. Another study showed that worms were recovered from washed lettuce leaves when infected slugs were placed on the leaves and later removed. These recovered larvae were fed to rats and adult worms were recovered from the lungs and hearts ~35 days later. There are no confirmed reports of human infection through skin contact, however, a mouse study showed infection was possible through non-oral routes. Mice were exposed to infective stage larvae via routes that included oral, intraperitoneal, sub-cutaneous, anal, vaginal and conjuctival mucosa, lacerated skin, unabraded skin, foot pad, and tail penetration. The study revealed that third stage larvae were able to infect the mouse host and mature to fifth stage larvae through all exposure methods with the exception of tail penetration. The highest worm recovery rates were from lacerated skin, and anal, vaginal, and conjuctival mucosa.  There have been victims of rat lungworm disease (RLWD) from Hawaiʻi Island who believe they were infected through skin contact or from the use of rainwater catchment water. Studies have shown that rainwater catchment has the potential for transmission of RLWD and filtration is important. Slugs have been shown to shed large numbers of rat lungworms (RLW) including infective stage larvae when drowned, and slugs and snails are often found in rainwater catchment tanks. Direct handling of slugs is not advised. The use of gloves, baggies or picking up slugs with disposable chopsticks or tongs is recommended. The use of gloves and shoes when working in gardens and outdoor settings when conditions are wet is advised as studies have shown that infective third stage larvae (L3) can survive as free living organisms in a wet environment. Slug and snail slime is very difficult to get off. Further studies would need to be done to determine the most effective and safe way of removing the slime, however, a strong bleach solution (10%) has been used as a method for removing slime from disection tools. It is is quite effective at cutting slime and is effective for killing larvae including the L3 stage. A mouse study showed that a 1.5% bleach solution had a 97% efficacy on killing infective stage Angiostrongylus costaricensis, a nematode closely related to A. cantonensis. The Jarvi Lab has observed bleach to be highly effective at immobilizing and even dissolving A. cantonensis L3 larvae.

References:

  • Cheng, TC, JE Alicata (1964). Possible role of water in the transmission of Angiostrongylus cantonensis (Nematoda: Metastrongylidae). Journal of Parasitology. 2: 39-40. 
  • Crook, JR, SE Fulton, K Supangwong. 1971. The infectivity of third stage Angiostrongylus cantonensis larvae shed from drowned Achatina fulica snails and the effect of chemical agents on infectivity. Transactions of The Royal Society of Tropical Medicing and Hygiene. 65: 602-605. 
  • Heyneman D, Lim BL. 1967. Angiostrongylus cantonensis: Proof of direct transmission with its epidemiological implications. Science. 158: 1057-1058. DOI: 10.1126/science.158.3804,1057
  • Howe, K., L. Kaluna, A. Lozano, B. Torres-Fischer, Y. Tagami, R. McHugh, S. Jarvi. 2019. Water transmission potential of Angiostrongylus cantonensis: Larval viability and effectiveness of rainwater catchment sediment filters. Plos One. https://doi.org/10.137/journal.pone. 0209813.
  • Qvarnstrom, Y., 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. Applied and Environmental Microbiology 73(5): 1415–1419.  
  • Jarvi SI, MEM 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). Molecular Biochemistry and Parasitology. 185(2): 174-176.  https://doi.org/10.1016/j.molbiopara.2012.08.002
  • Wang, L-C, D Chao, E-R Chen. 1991. Experimental infection routes of Angiostrongylus cantonensis in mice. Journal of Helminthology. 65: 296-300.
  • Zanini, G.M., C. Graeff-Teixeira. 1999. Inactivation of infective larvae of Angiostrongylus costaricensis with short time incubations in 1.5% bleach solution, vinegar or saturated cooking salt solution. Acta Tropica. 78:17-21. 

Early cases of rat lungworm disease (RLWD) contracted in Hawaiʻi have shown that conditions and symptoms may persist for an indefinite length of time. To date there have been no follow-up studies of long-term recovery rates. From meetings with RLWD victims we have observed that some recoveries have been more successful than others. 

Supplements and other treatments may be useful in gradually restoring health over the long term. Some victims have reported benefits from acupuncture and chinese herbal formulas along with therapies such as intravenous vitamin and glutathione administrations, however these treatments can be prohibitively expensive as they are not covered by most insurance companies. It is generally reported by those who have had serious cases of rat lungworm disease that recovery is slow and very often incomplete. Pain management therapy can be helpful. A support group to provide an avenue for victims to communicate with each other about recoveries and methods for relief from long-term symptoms is recommended. 

References:  

  • Reports from survivors and caregivers of rat lungworm disease survivors during Rat Lungworm Support Group meetings hosted by the Hilo Medical Center, and from personal communications with survivors and caregivers. 
  • Howe, K. 2013. A severe case of rat lungworm disease in Hawai‘i. Hawaii Journal of Medicine and Public Health. 72:(supp. 2): 46-48.

Nerve damage often occurs in more serious cases of rat lungworm disease (RLWD). It can persist for months or years, becoming chronic. One RLWD expert in the medical field reports the following:

 “…Tissue damage resulting from a combination of direct mechanical and chemical disruption increases with time. Many larvae do succumb to the host immuno-inflammatory response, stopping dead in their tracks, but this leads to the formation of dense, fixed inflammatory foci.  The more advanced the larva, the bigger the lesion, and the longer it will take to resolve; it’s very likely that the remains of an immature adult worm (L5) could persist in the CNS for months or possibly years, with surrounding chronic inflammation causing the deposition of permanent scar tissue. Many patients suffer prolonged, sometimes permanent, clinical sequelae.  While some become convinced the parasite has survived, even multiplied, in their brain, the simple explanation is that their CNS lesions have been too extensive for complete resolution.  They may be affected by irritating and debilitating symptoms indefinitely, with the only treatment available being non-specific, as offered by physiotherapy and pain clinics.”  

Parasthesia, or extreme skin sensitivity, has been frequently reported as pain, numbness, itching, or a sensation fo worms crawling under the skin. Skin sensitivity, particularly on extremities (arms, legs) and similar in sensation to a very bad sunburn, has been reported to persist for years by some who have had rat lungworm disease. 

References: 

  • Personal Communication: Hilo Medial Center, Rat Lungworm Support Group. 
  • Wang et al. 2008. Human angiostrongyliasis. Lancet Infectious Diseases 8: 621–630.  
  • Jarvi S., P. Prociv. 2020. Angiostrongylus cantonensis and neuroangiostrongyliasis (Rat lungworm disease). Parasitology (accepted for publication). 

A study would have to be done to absolutely confirm this, but it is not highly probable especially if the trail is old and well dried. The rat lungworm (RLW) could possibly survive in slime under very moist conditions as a study showed that RLW larvae which survived for more than 72 hours were able to infect rats. Other studies had RLW larvae held in water alive at 21 days, however it is not known if they were capable of infection. Dry conditions, however, have an adverse impact on the RLW. A recent study by the Jarvi Lab found that while only an average of 14.3% of infective L3 larvae were immobilized by one minute of drying, the greatest variability in immobility rates occurred at the two-minute mark, ranging from as little as 36% to as much as 100%. These results, which showed that the majority of L3 larvae die after 2 minutes of drying, agree with previous findings in the literature. Campbell and Little (1988) found that infective stage L3 larvae died within minutes outside their intermediate and paratenic hosts without sufficient moisture. Richards and Merritt (1967) tested the viability of L3 larvae 2 and 10 minutes after allowing their surrounding water to evaporate and found that while all larvae survived for 2 minutes, none survived for 10 minutes. Thus, it appears clear that A. cantonensis L3 larvae are unable to survive desiccation for more than a few minutes on hard, impermeable surfaces such as benchtops. On the other hand, larval survival might well be extended in moist environments such as sinks and food preparation areas, or possibly within moist snail or slug mucus.

References: 

  • Campbell, B. G. and M. D. Little. 1988. The finding of Angiostrongylus cantonensis in rats in New Orleans. The American Journal of Tropical Medicine and Hygiene 38: 568–573. doi:10.4269/ajtmh.1988.38.568.
  • Cheng, T.C. & J.E. Alicata. 1964. Possible role of water in the transmission of Angiostrongylus cantonensis (Nematoda: Metastrongylidae). Journal of Parasitology 50 Section 2: 39-40.
  • Howe, K., L. Kaluna, A. Lozano, B. Torres Fischer, Y. Tagami, R. McHugh, S. Jarvi. 2019. Water transmission potential of Angiostrongylus cantonensis: Larval viability and effectiveness of rainwater catchment sediment filters. PLoS ONE doi:10.1371/journal.pone.0209813.
  • Richards, C. S. and J. Merritt. 1967. Studies on Angiostrongylus cantonensis in molluscan intermediate hosts. Journal of Parasitology 53: 382–388.
  • Steel, A., J. Jacob, I .Klasner, K. Howe, S.H. Jacquier, W.C. Pitt, R. Hollinngsworth, S. Jarvi. 2020. In Vitro comparison of treatments and commercially available solutions on mortality of  Angiostrongylus cantonensis third-stage larvae. Parasitology 1-9. doi.org/10.1017/S0031182020001730. 

It is not known if near-shore saltwater mollusks, such as snails or opihi, can be infected with the rat lungworm (RLW). There was a case of rat lungworm disease (RLWD) once reported by the Hawaii  Department of Health that was thought to have come from opihi consumption but was not confirmed. It may be possible that fresh water opihi could carry the parasite however no studies have yet reported it. Fresh water snails, particularly the apple snail Pomacea canaliculata, has caused many cases of human infection particularly in S.E. Asia where this snail is consumed. There are organisms other than slugs/snails that can host the RLW and can carry the infective stage larvae (L3) and cause disease if eaten raw or undercooked. These organisms are referred to as paratenic hosts and include flatworms (Platydemus manokwari) prawns, shrimp, frogs, toads, centipedes, and lizards including monitor lizards. 

References: 

  • Niebuhr, C.N., S.I. Jarvi, L. Kaluna, B.L. Torres Fischer, A.R. Deane, I.L. Leinbach, S.R. Siers. 2020. Occurrence of rat lungworm (Angiostrongylus cantonensis) in invasive coqui frongs (Eleutherodactylus coqui) and other hosts in Hawaii. Journal of Wildlife diseases. 56(1). DOI: 10.75892018-12-294
  • Wang, H., L. Lu, D. She, Z .Wen, Z .Mo, J. Li, H. Li. 2018. Eating centipedes can result in Angiostrongylus cantonensis infection: Two case reports and pathogen investigation. American Journal of Tropical Medicine. 99:743-748. 
  • Wang, Q.P., D.H. Lai, X.Q. Zhu, X.G. Chen, Z.R. Lun. 2008. Human angiostrongliasis. Lancet Infectious Disease. 8:621-630.
  • Yang, T-B., Z-D. Wu, Z-R. Rong. 2013. The apple snail Pomacea canaliculata, a novel vector of the rat lungworm, Angiostrongylus cantonensis: its introduction, spread, and control in China. 72(6 Suppl 2): 23-25.  

There have been no confirmed cases of rat lungworm disease (RLWD) in humans or other animals that have been contracted in Oregon, however there may be cases that were diagnosed or treated in Oregon but the infection originated in Hawaiʻi; we know of one infection where this was the case (personal communication).

We know as well of cases of RLWD reported in the U.S. where the infection was contracted in Hawaiʻi or another location but were diagnosed, or were not diagnosed but had symptoms of RLWD, when the traveler(s) returned home. The parasite is endemic on the U.S. mainland in the Gulf States from Florida through and into Texas, and is beginning to move north with infection found in cotton rats in Oklahoma.

The first human case of RLWD on the U.S. mainland was reported in Louisiana in 1993. Twelve additional cases reported from the continental U.S. (excludes Hawaiʻi) were discussed in a study that examined confirmed cases of RLWD reported from 2011-2017. Of these 12 cases, six had no travel history outside of the continental U.S. and were deemed to have originated in the state of residence. Four were from Texas and one each from Tennessee and Alabama. And in 2019 the Alaska Division of Public Health reported a case of RLWD acquired by an Alaskan resident who had vacationed in Hawaii.

References below highlight the first report of the rat lungworm Angiostrongylus cantonensis in North America, it range expansion, and human cases of rat lungworm disease acquired on the U.S. mainland, in Hawaiʻi, and in Jamaica.   

References:

  • New, D., M.D. Little, J. Cross. 1995. Angiostrongylus cantonensis Infection from Eating Raw Snails. New England Journal of Medicine. 332:1105-1106.  
  • Campbell, B. G. and M.D. Little. 1988. The finding of Angiostrongylus cantonensis in rats in New Orleans. American Journal of Tropical Medicine and Hygiene 38::568–573.  
  • Flerlage, T., Y Qvarnstrom, J Noh, JP Devincenzo, A Madni, B Bagga, N Hysmith. 2017. Angiostrongylus cantonensis eosinophilic meningitis in an infant, Tennessee USA. Emerging Infectious Diseases. 23(10): 1756-1758. DOI: 3201/eid2310.170978. 
  • Hammoud, R.A., S.L. Nayes, J.R. Murphy, G.P. Heresi, I.J. Butler, N. Perez. 2017. Angiostrongylus cantonensis meningitis and myelitis, Texas, USA. Emerging Infectious Diseases. 23(6): 1037-1038. DOI:https:..dx.doi.org/10.3201/eid2306.161683.
  • Kim, D.Y., T.B. Stewart, R.W. Bauer, M. Mitchell. 2002. Parastrongylus (=Angiostrongylus) cantonensis now endemic in Louisiana wildlife. Journal of Parasitology. 88(5): 1024-1026. https://doi.org/10.1645/0022-3395(2002)088[1024:PACNEI]2.0.CO;2
  • Lindo, J.F., C.T. Escoffery, B. Reid, G. Codrington, C. Cunningham-Myrie, M.L. Eberhard. 2004. Fatal autochthonous eosinophilic meningitis in a Jamaican child caused by Angiostrongylus cantonensis. American Journal of Tropical Medicine and Hygiene. 70: 425-428. 

Black rats (Rattus rattus), and Polynesian rats (Rattus exulans) have been confirmed as carriers in Hawaii, and Norway rats (Rattus norvegicus) very likely are carriers. Mice (Mus musculus) have not been confirmed carriers in Hawaii or any other location and are not considered hosts but are used in research studies to model disease. Norway rats (Rattus norvegicus) are confirmed carriers of the rat lungworm in Louisiana, and cotton rats (Sigmodon hispidus) have been confirmed carriers in Oklahoma.

A wood rat (Neotoma floridanus) in Louisiana was also found infected with A. cantonensis although it has not been confirmed that they are an effective host carrier and was likely an accidental host. 

References: 

  • Jarvi, S.I., S. Quarta, S. Jacquier, K. Howe, D. Bicakci, C. Dasalla, N. Lovesy, K. Snook, R. McHugh, C.N. Niebuhr. 2017. High prevalence of Angiostrongylus cantonensis (rat lungworm) on eastern Hawaiʻi island: A closer look at life cycle traits and patterns of infection in wild rats (Rattus spp.) Plos One. DOI.org/10.1371/journal.pone.0189458
  • Kim, D.Y., T.B. Stewart, R.W. Bauer, M. Mitchell. 2002. Parastrongylus (=Angiostrongylus) cantonensis now endemic in Louisiana wildlife. Journal of Parasitology. 88(5): 1024-1026.
  • Simões, R.O., F.A. Monteiro, E .Sánchez, S.C. Thiengo, J.S. Garcia, S.F. Costa-Neto, J.L. Luque, A. Maldonado Jr. 2011. Endemic Angiostrongyliasis, Rio de Janeiro, Brazil. Emerging Infectious Disease. 17(7): 1331-1333. 
  • York, E.M., J.P. Creecy, W.D. Lord, W. Caire. 2015. Geographic range expansion for the rat lungworm in North America. Emerging Infectious Diseases. 21(7):1234-1236.

We know of no studies that demonstrate that Pepto Bismol is preventative against the rat lungworm (RLW) parasite. Steps to prevent infection include carefully washing produce with potable running water, cooking (3-5 or more minutes) and freezing (>48 hours) food, never handling slugs/snails with bare hands, covering beverages so slugs/snails cannot enter, and properly filtering water used for drinking.

In cases of known exposure, such as finding a slug in a salad or seeing a child put a slug into their mouth, preventative measures should be taken immediately. The Hilo Medical Center recommends taking pinworm medication (pyrantel pamoate), used to kill intestinal worms.

This medication, available over the counter in drug stores, has been shown in a laboratory study to immobilze the infectious stage rat lungworm which should then be expelled through stool without causing an infection. This must be done very quickly after known exposure as the medication only works in the gut and rat lungworm larvae can and will burrow and move throughout the body. Immediate notification of oneʻs doctor is essential and treatment with albendazol should begin to prevent development of the larvae. 

References

  • Cheng, T.C. & J.E. Alicata. 1964. Possible role of water in the transmission of Angiostrongylus cantonensis (Nematoda: Metastrongylidae). Journal of Parasitology 50 Section 2: 39-40.
  • Howe, K., L. Kaluna, A. Lozano, B .Torres Fischer, Y. Tagami, R. McHugh, S. Jarvi. 2019. Water transmission potential of Angiostrongylus cantonensis: Larval viability and effectiveness of rainwater catchment sediment filters. PLoS ONE 14. e0209813–20. 

   doi:10.1371/journal.pone.0209813.

  • Jacob, J. Tan, G., Lange, I., Saeed, H., Date, A., and S. Jarvi. 2020. In vitro efficacy of anthelmintics on Angiostrongylus cantonensis L3 larvae. Parasitology. DOI: 10.1017/S0031182020001146
  • Kramer, K., J .Yates, J.K. McMilan, W. Gosnell, G.S. Murphy, E. Blalock. L. Lteif, O .smith, M. Kahili-Heede, V. Ansdell. 2020. Diagnosis and treatment of neuroangiostrongyliasis in Hawaiʻi. Hawaiʻi Journal of Health and Social Welfare. 79(12): 353-357.
  • Steel, A., J .Jacob, I. Klasner, K. Howe, S.H. Jacquier, W.C .Pitt, R .Hollignsworth, S. Jarvi. 2020. In Vitro comparison of treatments and commercially available solutions on mortality of  Angiostrongylus cantonensis third-stage larvae. Parasitology 1-9. DOI.org/10.1017/S0031182020001730

The first step to be sure your produce is free of slugs and snails is through careful washing with potable water and careful observation, inspecting for slugs/snails, especially small ones, that may be hidden deeply within or on leafy greens (lettuces, kale, etc.) and clumped stalk vegetables (bok choy, celery, etc.).

A recent study was done by the Jarvi Lab using a death assay with propidium iodide followed by a rat study to confirm infective stage larvae mortality. Treatments tested included common household products, consumer vegetable washes and agriculture crop washes. Minimal larvicidal efficacy was found amount the consumer-grade fruit and vegetable washes or botanical extracts such as ginger, garlic, and oils from neem, lemongrass, and peppermint. Vinegar, a weak acid, was not effective and in fact could excite larvae.

Alkaline solutions, bleach and chlorine dioxide, did show larvicidal potential however bleach is not approved for use on food by the FDA and has carcinogenic byproducts. Larvae exposed to a 10-15% salt solution for 24-48 hours achieved 100% mortality. Drying is an effective safety method for rat lungworm prevention and drying (fruit, vegetables, surfaces) will cause death. In two out of four tests no rat lungworms survived longer than 3 mintues under dry conditions. 

References

  • Steel, A., J. Jacob, I .Klasner, K .Howe, S.H. Jacquier, W.C .Pitt, R.. Hollingsworth, S.I. Jarvi. 2020. In vitro comparison of treatments and commercially available solutions on mortality of Angiostrongylus cantonensis third-stage larvae. Parasitology. https://doi.org/10.1017/S0031182020001730 
  • Yeung, N.W., K.A. Hayes, R.H .Cowie. 2013. Effects of washing produce contaminated with the snail and slug hosts of Angiostrongylus cantonensis with three common household solutions. Hawaii Journal of Medicine and Public Health. 72(6 Suppl 2): 83-86. 

The rat lungworm (RLW) Angiostrongylus cantonensis is believed to have originated in Southeast Asia. This nematode was first discovered in China in 1935 but is now endemic in Asia, Australia, the Caribbean islands and the Pacific Islands and has spread to the Americas where it is reported in the southern United States, Brazil, Equador, and the Guiana Shield on the northern coast of South America.

A paper from China in 2008 states more than 2,800 cases of human infection have been reported in 30 countries and certainly that number has grown in the past twelve years.  A. cantonensis has been documented as a parasitic disease of humans in Hawaiʻi and other Pacific islands since the early 1960’s. Numerous studies were conducted in Hawaiʻi from 1960 to 1970 after which research dropped off, only to be resumed after the year 2000. It is certain there were cases of rat lungworm disease (RLWD) that occured in the interim but it was only in 2007 that the Hawaii Deptartment of Health made angiostrongyliasis (RLWD) a reportable disease. 

The flatworm Platydemus manokwari, a paratenic host for the parasite, and the semi-slug Parmarion martensi, immigrated to Japan and were thought to be the probable cause of an outbreak of angiostrongyliasis in the year 2000. The semi-slug, a relatively recent arrival to the Hawaiian Islands, is thought to be responsible for outbreaks of disease cases on the Island of Hawaiʻi that began around 2005 and continue to the present. In the Puna District, where outbreaks first occurred, P. martensi were numerous and some were heavily infected (>75% infected) with L3 A. cantonensis larvae.

The semi slug has since spread as have cases of rat lungworm disease in Hawaiʻi. In 2016 the Governor created a task force to assess the threat of the disease. Until 2017, P. martensi had only been reported on Hawaiʻi and Oahu, however, investigations following an outbreak of human cases on Maui confirmed its presence on that island.

In 2019 a case of RLWD was reported in the North Kohala District on Hawaiʻi Island and reports of the arrival of P. martensi were made and confirmed. The RLW parasite is known to be present on all of the Hawaiian Islands with the possible exception of Molokaʻi, however the lack of findings there may be due to the lack of thorough investigation. Human cases of RLWD have been reported from Kauai, Oahu, Maui, Lanai, and Hawaiʻi Island.

There are a number of studies that have been done on RLW in China, Thailand and Taiwan, where the majority of human cases have originated globally. Recently in Hawaiiʻi, the collaborative efforts of researchers and educators have made advancements in the prevention and treatment of RLWD.

References:

  • Asato, R., K. Taira, M. Nakaurma, J. Kudaka, K. Itokazu, M. Kawanaka. 2004. Changing epidemiology of Angiostrongylus cantonensis in Okinawa Prefecture, Japan. Japan Journal of Infectious Disease 57:184-186.
  • Chen H.T. 1935. A new pulmonary nematode of rats, Pulmonema cantonensis ng, nsp from Canton. Annals of Parasitology 13: 312–17.

The east side of the Big Island (Hawaiʻi Island) has ideal conditions that support an environment favorable to slugs, snails and flatworms; it is wet, and there is a great deal of vegetation. The semi-slug Parmarion martensi, a primary carrier of the rat lungworm (RLW), made its arrival to the island in the area of Paradise Park in the Puna District on the east side of Hawaiʻi Island sometime around the year 2000.

Studies published in 2007 showed that this newly arrived invasive pest carried extremely high numbers of infective stage RLW larvae and the slug has unusual behavior; it is relatively fast, will climb easily, and seems to like to get into dwellings, food, and beverages. Juvenile slugs are small, can be infected, and can easily be missed when cleaning greens such as lettuces etc.

The Puna District stands out as one of the most impoverished districts in the state. The primary industry is agriculture and many people residing in this area grow their own food for household consumption, sometimes without adequately inspecting or washing it.

It is very easy for a small slug or snail to hide in leafy greens and headed vegetables that are eaten raw, and this is one source of disease transmission. Juvenile semi slugs and neonates, which are newly hatched slugs and about the size of a grain of rice, have been found to be infected with RLW larvae and this is why it is stressed that careful cleaning, drying, peeling, or cooking (3-5 minutes)/freezing (48 hours or more) produce, are the best methods of prevention of rat lungworm disease (RLWD).

Another possible reason for the majority of cases originating in that area is the large number of households using rainwater catchment systems for their primary water supply. In the 1950ʻs and 60ʻs very large subdivisions in the Puna District were approved by Hawaiʻi County and were constructed with no infrastructure for water.

As there is no state or federal oversight for individual rainwater catchment systems, residents are responsible for the design and maintenance of their own systems. Many people have reported finding slugs and snails in their catchment tanks, often drowned, and preliminary studies at the Jarvi Lab have shown the potential for infected, drowned slugs, especially the semi slug, to shed large numbers of infective RLW larvae. The larvae can survive for some time in water and have been observed passing through a range of filters, including  20, 10, and 1 micron filters.

More studies to determine the likelihood of catchment systems as a source of transmission need to be done. The Jarvi Lab has also been conducting research to determine infection rates for slugs/snails on Hawaiʻi Island and compares the information collected with data from other islands in the Hawaiian Island chain. The Jarvi Lab research also includes tracking the range and spread of various mollusk species, especially Parmarion martensi, on Hawaiʻi Island.

The compiled data is shown in a presentation given by L. Kaluna from the UHH Jarvi Lab at Hawaii Invasive Species Council, Brown Bag Lunch Presentation #30 and is available for viewing online.

Other studies have been done at UH Manoa to look at the distribution of the RLW, slug and snail hosts that have been found to be carriers, and the potential for expansion of the range of RLW in Hawaiʻi with expected climate change.

Reference: 

  • Hollingsworth et. al. 2007. Distribution of Parmarion cf. martensi (Pulmonata: Helicarionidae), a New Semi-Slug Pest on Hawaiʻi Island, and Its Potential as a Vector for Human Angiostrongyliasis. Pacific Science. 457-467.  
  •   Howe, K., L. Kaluna, A. Lozano, B .Torres Fischer, Y. Tagami, R. McHugh, S. Jarvi. 2019. Water transmission potential of Angiostrongylus cantonensis: Larval viability and effectiveness of rainwater catchment sediment filters. PLoS ONE 14. e0209813–20. 

doi:10.1371/journal.pone.0209813.

  • Kim, J.R., T.M. Wong, P.A. Curry, N.W. Yeung, K.A. Hayes, R.H. Cowie. 2108. Modelling the distribution in Hawaii of Angiostrongylus cantonensis (rat lungworm) in its gastropod hosts. Parasitology 1-8. DOI.org/10.1017/S0031182018001026
  • Hawaii Invasive Species Council. April 1, 2020. Brown Bag #30: Rat lungworm update (Lisa Kaluna, UH Hilo). http://dlnr.hawaii.gov/hisc/news/brown-bag-30-rat-lungworm-update-lisa-kaluna-uh-hilo/

There have been no confirmed cases of rat lungworm disease (RLWD) in cats from veterinarians in Hawaiʻi. Although cats are predators of rats, rats do not harbor the infective third stage (L3), which makes it  extremely unlikely that cats would be infected from rats.

If there were to be an infection in cats it would more likely be caused by infected slugs getting into cat food, drowning in water that is then consumed by a cat, or a cat/kitten playing with a slug or snail, as it is slugs and snails that harbor the infective, third stage (L3) RLW. Dogs have been infected, especially puppies as they are very curious. Dogs and puppies tend to eat their food faster that cats, making it more likely for them to consume a slug, especially if food is left outside.

This is why we recommend bringing pet food inside, especially at night when slugs and snails are active. There have been cases in Hawaiʻi and the mainland United States of dogs, horses, some birds, lemurs, monkeys, and apes that have been confirmed to have RLWD.

Wild horses in Waipio Valley on Hawaiʻi Island had symptoms that were indicative of RLWD and tissue samples taken from a horse that was put down were positive for RLW by laboratory anaylisis at the Jarvi Lab. 

References:

  • Personal communication with veterinarians and the Jarvi Lab.
  • Burns, R.E., E.J. Bicknese, Y. Qvarnstrom, M. DeLeon-Carnes, C.P. Drew, C.H. Gardiner, B.A. Rideout. 2014. Cerebral Angiostrongylus cantonensis infection in a captive African pygmy falcon (Polihierax semitorquatus) in southern California. Journal of Veterinary Diagnostic Investigation. 26(5): 695-698. 
  • Kim, D.Y., T.B. Stewart, R.W. Bauer, M. Mitchel. 2002. Parastrongylus (=Angiostrongylus) cantonensis now endemic in Louisiana Wildlife. Journal of Parasitology. 88(5): 1024-1026. https://doi.org/10.1645/0022-3395(2002)088[1024:PACNEI]2.0.CO;2
  • Stockdale-Walden, H.D., J. Slapcinsky, Y. Qvarnstrom, A. McIntosh, H.S. Bishop, B. Rosseland. 2015. Angiostrongylus cantonensis in introduced gastropods in southern Florida. Journal of Parasitology. 101(2): 156-159. 

While some bird species have been infected by the rat lungworm (RLW) and exhibited neurological symptoms of rat lungworm disease (RLWD), there have been no confirmed reports of chickens or ducks getting the disease from eating slugs or snails.

And while it cannot be totally ruled out, there are a few studies using chicks that provide some evidence as to their resistance to the RLW. A study conducted in 1963 failed to recover larvae 15 days post-infection from chicks given a dose of 1,000 infective stage RLW larvae.

Another study found no evidence of larvae in chicks 28 hours post-infection. However, a few poultry owners from areas on Hawaiʻi Island where infection rates in slugs and snails is high have mentioned having a chicken or duck exhibiting paralysis in the legs, symptoms common to RLWD (personal communication). 

Eventually the birds did recover, however it is unknown if the cause of the illness was RLWD. Generally speaking, chickens and ducks are excellent natural predators of slugs and snails. As to whether the RLW can be passed on via the meat or eggs, early studies showed that following infection of cows and pigs with large numbers of RLW larvae (50,000), live larvae were recovered in the spleen, liver, lungs, and stomach, and the larvae were infective to rats.

It is highly improbable that the rat lungworm (RLW) parasite is passed on to humans via chicken or duck eggs or meat especially if the meat or eggs are eaten cooked. Cooking can prevent infection from of a number of food-borne disease-causing organisms and adequately cooking, steaming, boiling foods, or boiling water for sterilization, is a proven method for the prevention of RLWD.

References: 

  • Alicata, J.E. 1967. Effect of freezing and boiling on the infectivity of third-stage larvae of Angiostrongylus cantonensis present in land snails and freshwater prawns. The Journal of Parasitology. 53(5): 1064-1066. 
  • Ash, L. R. 1968. The occurrence of Angiostrongylus cantonensis in frogs of New Caledonia with observations on paratenic hosts of Metastrongyles. The Journal of Parasitology. 54(3): 432-436.
  • Burns, R.E., E.J. Bicknese, Y. Qvarnstrom, M. DeLeon-Carnes, C.P. Drew, C.H. Gardiner, B.A. Rideout. 2014. Cerebral Angiostrongylus cantonensis infection in a captive African pygmy falcon (Polihierax semitorquatus) in southern California. Journal of Veterinary Diagnostic Investigation. 26(5): 695-698. 
  • Monks, D. J., M.S. Carlisle, M Carrigan, K. Rose, D. Spratt, A. Gallagher, P. Prociv. 2005. Angiostrongylus cantonensis as a couse of cerebrospinal disease in a yellow-tailed black cockatoo (Calyptorhynchus funereus) and two tawny frogmouths (Podargus strigoides). Journal of Avian Medicine and surgery. 19(4): 289-293. 

There is no reason that the fish, in sushi and poke, would have the rat lungworm (RLW) parasite, although fish and shellfish can contain other nematode parasites that, if eaten raw, can infect a person.

If poke or sushi were to be contaminated by the RLW nematode it would have to be from an outside source, such as a slug crawling onto the sushi/poke and a person accidentally ingesting said item.

Food items consumed that have been reported from individuals who were exposed to slugs/snails or actually infected from slugs/snails in Hawaii are salads, raw vegetables, spring rolls (personal communication), and kava. Kava is a traditional beverage of Pacific Islanders and in one case the kava was prepared, left uncovered, and consumed.

After finishing the beverage a slug was found in the bottom of the container and this resulted in six cases of rat lungworm disease. It is important to cover any beverages taken outside as others have reported finding slugs, especially the semi slug, in a beverage being consumed.

Infections on the US mainland or other countries have come from the consumption of raw or undercooked frog legs, prawns, shrimp, monitor lizards, centipedes, and snails. 

References: 

  • Wang, Q-P., et al. 2008. Human angiostrongyliasis. Lancet Infectious Diseases 8: 621–630. 
  • Wang, H. et al.  2018. Eating centipedes can result in Angiostrongylus cantonensis infection: two case reports and pathogen investigation. The American Society of Tropical Medicine and Hygiene. https://doi.org/10.4269/ajtmh.18-0151
  • Rat Lungworm Disease in Hawaii. Control and Prevention Legislative Report. Hawaii State Department of Health. March 2018.  
  • https://www.seafoodhealthfacts.org/seafood-safety/general-information-patients-and-consumers/seafood-safety-topics/parasites

It is known that frogs, prawns, and lizards can potentially become infected by eating infected slugs or snails. A recent study conducted on Hawaiʻi Island confirmed that coqui frogs, Cuban tree frogs, cane toads, and centipedes can act as reservoirs for the rat lungworm (RLW) and can be considered paratenic hosts capable of causing infection.

Tissue was collected from the stomach, intestine, muscle, liver, heart, and brain of the frogs and toads and analyzed using real time PCR. Of those organisms tested, 21/24 coqui frogs, 4/4 Cuban frogs, and  2/2 cane toads were infected.

Whole centipedes internal organs were scraped and analyzed using PCR and 3/3 were infected. Reports in China have confirmed human infection from consumption of raw centipedes, and a human case in Louisiana in 2006 was caused by consumption of raw, green tree frog legs.

It is not known at this time if coqui feces could contain the RLW nematode.

Reference:  

  • Wang, H., L. Lu, D. She, Z. Wen, Z. Mo, J. Li, H. Li. 2018. Eating centipedes can result in Angiostrongyluls cantonensis infection: two case reports and pathogen investigation. The American Journal of Tropical Medicine and Hygiene. https://doi.org/10.4269/ajtmh.1800151
  • Niebuhr, C. N., S.I. Jarvi, L. Kaluna, B.L.Torres Fischer, A.R. Deane, I.L. Leinbach, S.Rs Siers. 2020. Occurrence of rat lungworm (Angiostrongylus cantonensis) in invasive coqui frogs (Eleutherodactylus coqui) and other hosts in Hawaii. Journal of Wildlife Disease. 56(1): 000-000. DOI: 10.7589/2018-12-294. 
  • Angiostrongylus cantonensis. Lousiana Office of Public Health-Infectious Disease Epidemiology Section_Annual Report. 

It is up to the consumer where they buy their kale. It is the responsibility of the consumer to wash and inspect  any fruit or vegetable thoroughly before using or eating for the prevention of rat lungworm (RLW) and other food-borne diseases.

There have been cases of rat lungworm disease (RLWD) reported from the Hamakua Coast as well as the Puna District and other districts on Hawaiʻi Island, and on the other islands as well. Some lettuce growers are using hydroponic or aquaponic systems to grow these crops as the systems present more of a barrier that might deter slugs or snails. Other deterents have been trialed including electric snail fences. While a grower might be doing all they can to keep slug and snail populations down, it is still important for the consumer to be responsible for the careful and thorough cleaning of all produce, especially any leafy greens that are to be eaten raw.

Studies have shown there are no wash or rinse solutions that will remove slugs/snails from deep inside headed vegetables. This is why it is recommended that any headed or clumped produce be taken completely apart and to carefully examine and wash each leaf (rubbing to dislodge any unwanted objects) under running, potable water.

A 2020 rinse study from the Jarvi Lab tested a number of commercial-grade fruit and vegetable washes, botanical extracts, and acidic solutions such as vinegar, and found they were all largely ineffective. Alkaline solutions and oxidizers (bleach, chlorine dioxide) showed potential, and dodecylbenzene sulfonic acid was effective in the time and thoroughness in which it killed infective stage RLW.

While results are promising for future studies, none of these are approved for use on food by the FDA. To be absolutely safe, if residing in or visiting an area where the rat lungworm is known to be present, it is best to eat cooked vegetables. Cooking or steaming for 3-5 minutes has been shown to kill the infective stage RLW. 

References:

  • Alicata, J.E. 1967. Effect of freezing and boiling on the infectivity of third-stage larvae of Angiostrongylus cantonensis present in land snails and freshwater prawns. Journal of Parasitology. 53: 1064-1066. 
  • Steel, A., J. Jacob, I. Klasner, K. Howe, S.H. Jacquier, W.C. Pitt, R. Hollingsworth, S.I. Jarvi. 2020. In vitro comparison of treatments and commercially available solutions on mortality of Angiostrongylus cantonensis third-stage larvae. Parasitology 109. https://doi.org/10.1017/S0031182020001730
  • Yeung, N.W., K.A. Hayes, R.H. Cowie. 2013. Effects of washing produce contaminated with the snail and slug hosts of Angiostrongylus cantonensis with three common household solutions. Hawaiʻi Journal of Midicine and Public Health. 72(6 Suppl 2): 83-86. 

A study published in 1967 by an early researcher from Hawaii examined the effects of boiling and freezing on the rat lungworm (RLW) larvae. The study analyzed the effects of heat on infective RLW larvae in prawns and giant African snails (Lissachatina fulica) and determined that boiling for 1 minuted resulted in larval mortality in prawns but required 2 minutes for snails (being larger bodied).

The thermal point reached is crucial; rats became infected with larvae exposed to temperatures of 45 and 50º C (113 -122º F) but not those exposed to 55ºC (131º F). The difficulty in answering this question is whether the individual parasite might be on the greens or is encased inside a slug or snail. Because of this uncertainty it is important to clean greens well to remove any slug or snail, and then boil, steam, or sautee leafy greens for 3-5 minutes to ensure any possible RLW larvae are killed.

In addition to cooking, dry conditions have been found to cause larval mortality, and washing and drying vegetables and fruits is recommended to help prevent infection. Also, freezing at -15°C  or 5º F can help prevent infection (a standard freezer temperature is 0º F). A large bodied snail, such as the giant African snail, takes about 48 to 72 hours before the animal freezes completely solid and reaches temperatures that will kill the RLW.

If kale is to be used raw, such as in a green drink or smoothie, careful washing, drying, and freezing leaves for 48 hours is an excellent practice for preventing RLW infection. Or kale can be frozen and then cooked, again an excellent method to destroy any possible parasites. Freezing is not very practical for more delicate greens, such as lettuce. Refrigeration is not sufficient to destroy the RLW. 

References: 

  • Alicata, J. E. (1967). Effect of freezing and boiling on the infectivity of third-stage larvae of Angiostrongylus cantonensis present in land snails and freshwater prawns. Journal of Parasitology. 53(5): 1064-1066.
  • Steel, A., J. Jacob, I .Klasner, K. Howe, S.H. Jacquier, W.C. Pitt, R. Hollingsworth, S. Jarvi. 2020. In Vitro comparison of treatments and commercially available solutions on mortality of  Angiostrongylus cantonensis third-stage larvae. Parasitology 1-9. doi.org/10.1017/S0031182020001730. 

During the 2005 survey the dangers of rat lungworm (RLW) were explained to survey participants at the time the property was visited and searched for invasive slugs, particularly the semi slug.

It was already known in 2004 that the Asian semi-slug Parmarion martensi was potentially an important carrier of RLW based on information from the Center for Disease Control (CDC), and from Japan where the semi slug was thought to be responsible for an outbreak of human cases of rat lungworm disease (RLWD). There may have been some knowledge of the RLW parasite and RLWD by some Hawaiʻi residents as the first two cases of RLWD in Hawaiʻi occurred in 1959 and 1960. The Hawaii Dept. of Health made RLWD a reportable disease in 2007 and began providing some educational materials for the general public on Hawaiʻi Island where cluster cases continued to occur.

The Jarvi Lab began to provide information and educational materials on Hawaii Island in 2012 (see educational resources section of this website). A concerted, statewide education effort by the Hawaii Department of Health began in 2018.  

References:

  • Asato, R., K. Taira, M. Nakaurma, J. Kudaka, K. Itokazu, M. Kawanaka. 2004. Changing epidemiology of Angiostrongylus cantonensis in Okinawa Prefecture, Japan. Japan Journal of Infectious Disease 57:184-186.
  • Hollingsworth, R.G., R. Kaneta, J.J. Sullivan, H.S. Bishop, Y. Qvarnstrom, A.J.da Silva, D.G.Robinson. 2007. Distribution of Parmarion  cf. martensi  (Pulmonata: Helicarionidae), a new semi-slug pest on Hawaii Island, and it’s potential as a vector for human angiostrongyliasis. Pacific Science 61: 457-467.
  • Rosen, L., R. Chappell, G.L. Laqueur, G.D. Wallace, P.P. Weinstein, 1962. Eosinophilic Meningoencephalitis caused by a Metastrongylid lung-worm of rats. Journal of the American Medical Association. 179(8): 620-624. 
  • Rat Lungworm Disease in Hawaii. Control and Prevention Legislative Report. Hawaii State Department of Health, March 2018. https://health.hawaii.gov/docd/files/2018/05/RLWD_2018_Leg_Report_032218.pdf
  • Robert Hollingsworth (personal communication)

The first two cases of rat lungworm disease (RLWD) were reported in Hawaii on the island of Oahu in 1959 and 1960. Both victims perished, demonstrating how serious this disease can be. Seventeen additional cases were reported in Hawaii between the 1959-1965 time period, and one case was reported in 1979.

There is no data from 1966-1978 and from 1980-2000. Cases of RLWD that occured between 2001- 2004 were identified in a study conducted in 2005 by the Center for Disease Control (CDC) and the Hawaii Department of Health (HDOH). At that time, cluster cases of RLWD were being reported on Hawaii Island in an area where a new semi slug species Parmarion martensi was introduced.

This particular species is capable of carrying very high parasite loads. Before the introduction of the semi slug doctors stated severe cases were rare, but after the slug became established there was a significant change in the nature of the disease with serious cases becoming much more common. In 2007 RWLD was made a reportable disease by the HDOH. Reports from survivors of these more recent cases of RLWD describe recovery taking many months or even years for symptoms to resolve, and some report symptoms never resolving or having permanent disability. Sadly, there have been deaths from complications caused by RLWD. The 2019 report to the Hawaii State Legislature from the HDOH shows a total of 151 confirmed cases of RLWD from 1959 to 2019.

As confirmation of the disease requires a spinal tap and finding DNA evidence of the parasite in cerebral spinal fluid, it is widely accepted that these numbers are low and only reflect the more serious cases of RLWD. A more accurate figure for disease incidence will not be known until the development of a less invasive test is approved.  Additionally, the medical differences and recovery time between serious versus mild cases of RLWD cannot be known without conducting a long-term study of survivors.

Reference: 

  • Howe, K., S. I. Jarvi. 2017. Angiostrongyliasis (rat lungworm disease): Viewpoints from Hawaiʻi Island. ACS Chemical, Neuroscience. DOI: 10.1021/acschemneuro.7b00299
  • Jarvi, S. I., P. Eamsobhana, S. Quarta, K. Howe, S. Jacquier, A. Hanlon, K. Snook, R. McHugh, Z. Tman, J. Miyamura, K. Kramer, M. Meyers. 2020. Estimating human exposure to rat lungworm (Angiostrongylus cantonensis) on Hawaiʻi Island: A pilot study. American Journal of Tropical Medicine and Hygiene. 00(0): 1 – 9. Doi:10.4269/ajtmh.18-0242
  • Rosen, L., R. Chappell, G.L. Laqueur, G.D. Wallace, P.P. Weinstein, 1962. Eosinophilic Meningoencephalitis caused by a Metastrongylid lung-worm of rats. Journal of the American Medical Association. 179(8): 620-624. 
  • Jon Martel, MD. University of Hawaiʻi, John A. Burns School of Medicine (personal communication).
  • Hawaii State Department of Health. March 2018. Rat lungworm disease in Hawaii. Control and Prevention Legislative Report. 
  • Hawaii State Department of Health. October 2019. Rat Lungworm Disease in Hawaii. Supplemental Legislative Report on FY 2019 Prevention and Collaboration Efforts.

https://health.hawaii.gov/docd/files/2019/10/DOH-2019_RLWD-Supplemental-Leg-Report-FINAL-101519.pdf

  • Reports from survivors and caregivers of rat lungworm disease survivors during Rat Lungworm Support Group meetings hosted by the Hilo Medical Center, and from personal communications with survivors and caregivers. 

Ralph Robinson, a researcher from Jamaica, tested approximately 150 mongooses (same mongoose species as in Hawaiʻi) and found no evidence that mongoose are hosts of Angiostrongylus cantonensis the rat lungworm (RLW) (personal communication).

A recent study on Hawaiʻi Island looked for evidence of infection in wild mongooses (n=15) and found no adult RLW in the lungs of mongoose (personal communication). This makes it highly unlikely that mongoose are definitive hosts and therefore cannot infect slugs and snails with their feces and are not contributing to the RLW life cycle. People cannot get infected with RLW from mongooses or from rats.

Reference: 

  • Robert Cowie, Ph.D. K. Howe, S.I. Jarvi. Personal Communication at 2011 International Rat Lungworm Workshop in Honolulu Hawaii.
  • Chris Niebuhr, PhD. Vertebrate Ecologist, Mannaaki Whenua – Landcare research. New Zealand

We know of no studies at this time that have been done that has determined if fermentation will kill the rat lungworm (RLW) parasite or prevent disease. Any raw juice could potentially transmit rat lungworm disease (RLWD) if an infected slug or snail were to crawl, be blended, or chopped into the juice.

Fruits and any medicinals, such as noni, that are going to be consumed raw should be well washed and dried. Neonate and young slugs are generally very small and difficult to see. Rinse well under running, potable (drinkable) water and then dry. The rat lungworm parasite will die within three minutes in dry conditions.

References:

Steel, A., J. Jacob, I. Klasner, K. Howe, S. H. Jacquier, W. C. Pitt, R. Hollingsworth, S. I. Jarvi. 2020. In vitro comparison of treatments and commercially available solutions on mortality of Angiostrongylus cantonensis third-stage larvae. Parasitology. https://doi.org/10.1017/S0031182020001730

There are individuals who think they have contracted rat lungworm disease (RLWD) more than once (personal communication), however at this time we do not have supportive evidence that prior infection with the rat lungworm (RLW) can create immunity in humans. As a human study to test the potential for resistance after an initial exposure is not feasible, there are a few studies that have investigated and discussed this possibility of immunity. It was shown in rats that exposure to low levels of infectious third stage RLW larvae (L3) did provide immunological protection from challenges of lethal doses of larvae.

Rats infected with a single dose of ten L3 larvae before being given a lethal challenge dose of 1000 L3 larvae survived significantly longer than unexposed control rats. If two or three exposures of smaller doses of five larvae were given, then even better rates of rat survival resulted. A human exposure paper published by the Jarvi Lab in the Puna District on Hawaiʻi Island, where a number of cases of RLWD have originated, provided questionnaires to volunteer participants who then provided blood for a serology test to detect antibodies for RLW. Some participants who self-reported never having had RLWD had antibody levels similar to some of those who reported having had RLWD. It may be that low level exposure from some source over time, such as contaminated catchment water, caused the production of these antibodies.

No human study has shown that immunity is produced from prior infection nor is there any evidence of a vaccine that can produce immunity. The Jarvi Lab conducted a study using a vaccine shown to have success against another closely related nematode, Angiostrongylus costaricensis, the causative agent of abdominal angiostrongyliasis. In our hands, the vaccine was ineffective and did not prevent the RLW Angiostrongylus cantonensis from maturing into adult worms in rats. Therefore it is best to always take precautions to prevent RLWD even if one has had it before, as the potential severity of the disease is too great and infection from RLWD can result in permanent disability, coma, and death.

References:

Heyneman, D., L.. B Liat.1965. Prolonged survival in rats immunied by a small number of low-level doses of Angiostrongylus cantonensis and challenged with a lethal level of infective larvae. University of California International Center for Medical Research and Training and Division of Medical Zoology, Institute for Medical Research, Kuala Lumpur. Laboratory Meeting. pp 162-163.
Jarvi, S. I., P. Eamsobhana, S. Quarta, K. Howe, S.. Jacquier, A. Hanlon, K. Snook, R. McHugh, Z. Tman, J. Miyamura, K. Kramer, M. Meyers. 2019. Estimating human exposure to rat lungworm (Angiostrongylus cantonensis) on Hawaiʻi Island: A pilot study. American Journal of Tropical Medicine and Hygiene. 00(0): 1-9. doi.10.4269/ajtmh.18-0242.
Rodriguez, R., R.M. Dequi, L. Peruzzo, P.M. Mesquita, E. Garcia, F. Fornari. 2008. Case report. Abdominal angiostrongylisasis: report of two cases with different clinical presentation. Revista do Instituto de Medicina Tropical de São Paulo. 50(6): 339-341. doi: 10.1590/S0036-46652008000600005
Solono-Parada, et al. 2010. Effectiveness of intranasal vaccination against Angiostrongylus costaricensis using a serine/threonine phosphatase 2 A synthetic peptide and recombinant antigens. Vaccine (28) 5185-5196.

At this time in the United States there is no antigen-based diagnostic test available for neuroangiostrongyliasis, commonly referred to as rat lungworm disease (RLWD). Currently, real-time polymerase chain reaction (qPCR) of cerebral spinal fluid obtained by lumbar puncture is used to diagnose RLWD. At one time Clinical Laboratories of Hawaiʻi worked with Parasitic Disease Consultants in Georgia and offered an enzyme-linked immunosorbent assay (ELISA), to detect antibodies in blood against Angiostrongylus cantonensis the rat lungworm (RLW). The test is not 100% specific; cross-reactions can affect its accuracy as a diagnostic tool and so the test is no longer offered.

Research has been underway in other countries to develop a better test; one that is less invasive, less expensive, can diagnose infection more rapidly, and is more accurate (producing less false-negative results). Researchers in Thailand isolated the 31-kD glycoprotein as a diagnostic antigen of A. cantonensis and then developed a rapid dot immunogold filtration assay (DIGFA) test followed by a more rapid lateral flow immunochromatographic assay (LFIA) (AcQuickDx) to detect A. cantonensis antibodies in human serum (blood). The antibody test is easy to perform, rapid, and highly specific and sensitive.

Antibodies take some time for the immune system to produce and as time is an essential factor in the successful treatment of this disease, an antigen test is preferable for early detection of infection. The most recent Thai development is the sandwich dot-immunogold filtration assay (AcDIGFAAg), which detects circulating antigens of A. cantonensis and can distinguish an active infection from a past infection. China has developed a lateral flow immunoassay (LFIA) based on 2 monoclonal antibodies against antigens of A. cantonensis adults. The test is said to be rapid, simple, and highly sensitive and specific.

The Jarvi lab has collaborated with Thai researchers to develop a similar antibody -based blood test for Hawaiʻi. Additionally, the Jarvi lab is working with veterinarians treating dogs with symptoms of RLWD and is using qPCR to detect A. cantonensis DNA in blood. A more sensitive qPCR developed at the National Institute of Allergies and (NIAID) Infectious Disease at the National Institute of Health (NIH) is now being trialed by RLW researchers and may prove useful in the efforts to develop a better diagnostic tool for detection of RLWD.

References:

Chen, M-X, J-X Chen, S-H Chen, D-N Huang, L. Ai, R-L, Zhang. 2016. Development of Lateral Flow Immunoassay for antigen detection in human Angiostrongylus cantonensis infection. Korean Journal of Parasitology. 54(3): 375-380. doi: 10.3347/kjp.2016.54.3.375
Eamsobhana P, A. Yoolek, N. Kreethapon, 2003. Blinded multilaboratory
evaluation of an in-house dot-blot ELISA kit for diagnosing
human parastrongyliasis. Southeast Asian Journal of Tropical
Medicing and Public Health 34: 1–6.
Eamsobhana P, A.Yoole, P. Punthuprapasa, 2003. Dot-blot
ELISA for the immunological detection of specific antibody to
Parastrongylus cantonensis. Tropical Biomedicing 20: 1–6.
Eamsobhana P, A. Tungtrongchitr, D. Wanachiwanawin, H. S. Yong.
2018. Immunochromatographic test for rapid serological diagnosis
of human angiostrongyliasis. International Journal of Infectious Disease 73: 69– 71.
Eamsobahna, P., A Tungtrongchitr, H-S Yong, A Prasartvit, D Wanachiwanawin, X-X Gan. 2020. Sandwich dot-immunogold filtration assay (DIGFA) for specific immunodiagnosis of active neuroangiostrongyliasis. Parasitology. Doi: 10.1017/S0031182020001894
Jarvi, S.I., W.C. Pitt, M.E. Farias, L. Shiels, M.G. Severino, K.M. Howe, S.H. Jacquier, A.B. Shiels, K.K Amano, B.C. Luiz, D.E. Maher, M.L. Allison, Z.C. Holtquist, N.T. Scheibelhut. 2015. Detection of Angiostrongylus cantonensis in the blood and peripheral tissues of wild Hawaiian rats (Rattus rattus) by a quantitative PCR (qPCR) assay. Plos One. https://doi.org/10.1371/journal.pone.0123064.
Jarvi, S.I. et al. 2019. Estimating human exposure to rat lungworm (Angiostrongylus cantonensis) on Hawaiʻi Island: A pilot study. American Journal of Tropical Medicing and Hygiene. doi:10.4269/ajtmh.18-0242
Lee, R. et al. 2020. Further studies of neuroangiostrongyliasis (rat lungworm disease) in Australian dogs: 92 new cases (210-2020) and results for a novel, highly sensitive PCR assay. Parasitology 1-9. https://doi.org/10.1017/S0031182020001572

Definitely not a life-style choice disease, rat lungworm disease (RLWD) is a serious and widespread problem for Hawaiʻi. Agencies, including the Hawaii Department of Health (HDOH), do have a responsibility to reduce the danger of RLWD and inform the public of actions necessary for disease prevention. The complexity of the problem, however, indicates a need for a shared responsibility to address it.

Agencies responsible for public health include the Center for Disease Control (CDC), a federal agency working in public health, infectious disease, and epidemiology, and the HDOH, which is responsible for protecting and improving the health and environment of all people in Hawaiʻi. In 2005 the CDC and the HDOH did collaborate on a study when a cluster of RLWD cases appeared in a localized area of the lower Puna District on Hawaiʻi Island. Laboratory analysis of host animals (rats, slugs and snails) collected in the area of the disease outbreak confirmed approximately 78% of a newly arrived semi slug species Parmarion martensi were infected with exceptionally high loads of Angiostrongylus cantonensis the rat lungworm (RLW), and 100% of rats were infected with the parasite. Additionally, the semi slug had unusual behavior which increased the potential for contact with humans. The CDC and HDOH also observed that individuals diagnosed with RLWD in the area where the outbreak occured tended to grow and eat raw greens grown in backyard vegetable gardens, often without washing or not sufficiently washing produce. The HDOH concluded disease transmission was a result of these actions, which led to statements that a number of people heard from the agency, that RLWD was a lifestyle choice disease.

This effectively passed the responsibility for disease prevention on to the individual in spite of the evidence of high infection rates in host organisms. Initially confined to a small locality on Hawaiʻi Island, the threat of RLWD was considered to be a relatively small risk in the local food supply. Agencies feared that a large-scale media and education campaign could have an adverse economic impact on Hawaiʻiʻs agriculture. However, the high infection levels detected in host animals, especially slugs and snails that harbor the infective stage RLW larvae and are agricultural pests, warranted the need for the agencies responsible for food production, food safety, and pest control, to get involved.

Federal agencies responsible for agriculture and food-related issues are the Food and Drug Administration (FDA) and the United States Department of Agriculture (USDA). The FDAʻs Food Safety Modernization Act (FSMA) aims to prevent foodborne illness, and the USDAʻs National Institute of Food and Agriculture (NIFA) agency funds programs and projects that support research, education, and extension activities that promote pest management in general and reduced risk pest managment in particular. The Pacific Basin Agriculture Resource Center (PBARC) located in Hilo, Hawaiʻi is a USDA agriculture research center often focusing on agricultural pest issues in Hawaiʻi. It was a researcher from PBARC who collaborated with the CDC and HDOH in 2005, playing a key role in identifying the semi slug as an important vector of the RLW. The Hawaii State Department of Agriculture (HDOA) and the University of Hawaiʻi Manoa’s College of Tropical Agriculture and Human Resources (CTHAR) are involved with Hawaiʻiʻs food production, supply, and safety. In 2010, five years after the CDC/HDOH study, CTHAR released a publication for on-farm practices to reduce risks of RLWD.

In 2016 the severity and increasing numbers of cases of RLWD was finally recognized. The Governor of Hawaiʻi established a joint task force to combat rat lungworm disease. In 2017, twelve years after the CDC/HDOH study, the state provided the HDOH with funds to develop a RLWD public education campaign. However, the delay in interventions and actions led to the spread of the semi-slug. In 2017 a cluster of RLWD cases occured on Maui, some involving tourists which drew national attention and led to a loss of contracts and support for Hawaiʻi farmers. The semi slug, which had only been reported on Oahu and Hawaiʻi Island, was found to have arrived on Maui. In 2019 the semi slug was detected in North Kohala on Hawaiʻi Island, prior to which it had not been reported. Shortly afterwards, a human case of RLWD that originated in North Kohala was reported. In 2018 the Hawaii RLWD Task Force published the Preliminary Guidelines for the Diagnosis and Treatment of Human Neuroangiostrongyliasis (Rat Lungworm Disease) in Hawaii, and in 2020 the Diagnosis and Treatment of Neuroangiostrongyliasis in Hawaiʻi was published. In the same year the Hilo Medical Center, where most cases of RLWD on Hawaiʻi Island have been treated, circulated a treatment protocol for RLWD.

While considerable progress has been made there is more work to be done. The continued spread of highly infected host organisms, annual cases of RLWD some of which are severe and disabling, that the RLW is also on the U.S. mainland and its range is expanding, indicates the need for attention and intervention by federal agencies, better coordination between state agencies, and more funding to address the problem. Vigilance in areas where the semi slug had not arrived is crucial. Research and education efforts, in which the Jarvi lab has been active, must be continued. Farmers, school gardens and agriculture projects must have control programs for slugs and snails in place. Grocers and farmers’ markets must provide information informing customers of RLWD and best practices for disease prevention Food establishments must train personnel how to clean produce and make educated choices as to what produce to serve raw, if at all. Consumers, both residents and tourists, must be informed and know how to prevent infection. Medical personnel must have a thorough understanding of RLWD in Hawaiʻi and be provided with up-to-date information regarding diagnosis and treatment of RLWD. A well-organized, properly funded, and collaborative effort is the best route to reduce RLWD.

References:

Cowie, R.H., K.A. Hayes, J.R. Kim, K.M. Bustamente, N.W. Yeung. 2018. Parmarion martensi Simroth, 1893 (Gastropoda: Ariophantidae), and intermediate host of Angiostrongylus cantonensis (rat lungworm), on Maui. Records of the Hawaii Biological Survey for 2017. Bishop Museum Occasional Papers. 123: 7-10. ISSN (online) 2376-3191
Hochberg, N.S., B.G. Blackburn, S.Y. Park, P.V. Effler, B.L. Herwaldt, 2011. Eosinophilic meningitis attributable to Angiostrongylus cantonensis infection in Hawaii: Clinical characteristics and potential exposures. American Journal of Tropical Medicine and Hygiene. 85(4): 685-690.
Hollingsworth, R.G., R. Kaneta, J.J. Sullivan, H.S. bishop, Y. Qvarnstrom, A.J. daSilva, D.G. Robinson. 2007. Distribution of Parmarion cf. martensi (Pulmonata: Helicarionidae), a new semi-slug pest on Hawaiʻi Island, and itʻs potential as a vector for human angiostrongyliasis. Pacific Science. 61(4): 457-467. http://dx.doi.org/10.2984/1534-6188(2007)61[457:DOPCMP]2.0.CO;2
Hollingsworth, R.G., K. Howe, S.I. Jarvi. 2013. Control measures for slug and snail hosts of Angiostrongylus cantonensis, with special reference to the semi-slug Parmarion martensi. Hawaiʻi Journal of Medicine and Public Health. 72(6)(Supp 2). 75-80.
Hollyer, J.R., V.Z. Troegner, R.H. Cowie, R.G. Hollingsworth, L.C. Nakamura-Tengan, L.F. Castro, A.E. Buchholz. Best on-farm food safety practices: Reducing risks associated with rat lungworm infection and human eosinophilic meningitis. College of Tropical Agricluture and Humand Resources. Food Safety and Technology. Jan. 2010. FST-39.
Kramer, K., J. Yates, J.K. McMillan, W. Gosnell, G.S. Murphy, E. Blalock, L. Lteif, O. Smith. 2020. Diagnosis and treatment of neuroangiostrongyliasis in Hawaiʻi. Hawaiʻi Journal of Health and Social Welfare. 79(12): 353-357.
https://governor.hawaii.gov/newsroom/latest-news/doh-news-release-joint-task-force-established-to-combat-rat-lungworm-disease-in-hawaii/
https://www.mauinews.com/news/local-news/2017/04/stores-make-changes-in-response-to-rat-lungworm-concerns/
https://www.biisc.org/semi-slug-found-in-kohala/
https://www.westhawaiitoday.com/2019/04/22/north-hawaii-news/get-in-the-know-rat-lungworm-disease-meeting-tonight-in-north-kohala/
https://health.hawaii.gov/docd/files/2018/08/RLWD_Preliminary_Clinical_Guidelines_FINAL_082918.pdf#:~:text=Preliminary%20Guidelines%20for%20the%20Diagnosis%20and%20Treatment%20of,the%20end%20of%20the%20document.%20August%2029%2C%202018
https://www.hilomedicalcenter.org/wp-content/uploads/2020/02/Rat-Lungworm-for-ED-Doctors-2020.pdf

The use of anthelmintics (anti-parasitic medicines) such as albendazole, for the treatment of neuroangiostrongyliasis (NAS) or rat lungworm disease (RLWD) has been controversial. The combination of corticosteroid and anthelmintic drugs are commonly used for treatment of RLWD cases in Asia, however, as no randomized, double-blind, placebo-controlled human trials have been performed, the benefits of anthelmintic drugs are still suspect within the medical community in the U.S. However, there are cases in Hawaiʻi where these drugs have been used and when administered, especially after known exposure or in the early stages of rat lungworm (RLW) infection, anthelmintics, such as albendazole, can lessen symptoms and hopefully prevent onset of the disease.

The administration of corticosteroids (dexamethasone or prednisone) is essential in treatment of more severe cases of RLWD. Corticosteroids reduce the immune system response to the larval invasion, lessening inflammation in the brain and the severity and duration of headaches, and possibly reducing or preventing long-term neurological damage. Albendazole is the preferred anthelmintic drug for treatment of RLWD for its efficacy in the treatment of helminths (parasitic worms) and its ability to cross the blood brain barrier. Albendazole has been shown to be a safe and effective treatment for helminths, having been prescribed to several hundred millions of individuals, including children, with very few adverse events. The timing of the administration of anthelmintics (albendazole) is crucial when treating RLWD. Lakwo et al. (1998) conducted a rat study to examine the effectiveness of albendazole in eliminating or reducing the numbers of RLW larvae that grow to adult worms. Rats were infected with Angiostrongylus cantonensis (rat lungworm) third-stage larvae and albendazole was given to the rats at 7 and 14 days post infection (PI). The rats were euthanized 11 weeks PI and the number of adult worms recovered, heart and lung weight, and visual damage to lung tissue was recorded. The administration of albendazole to rats 7 days PI greatly reduced or killed all worms, significantly lowered the heart and lung weight, and lessened damage to lung tissue, while albendazole administration 14 days PI was less effective, with little reduction in the number of adult worms recovered, and little or no significant difference between heart weights and lungs damage between treated and untreated rats. The most marked effect of treatment 14 days PI was a suppressive effect on female worm reproductive capabilities.

Much of the controversy regarding albendazole for treatment of RLWD stems from the potentially adverse response of the immune system to dead worms leading to increased inflamation and greater brain injury. Within 7 days of infection, worms that have made it to the brain begin to grow from 3rd stage larvae to 4th and then 5th stage (young adult) larvae. While killing these worms can cause more inflammation, live worms burrowing in the brain and shedding as they molt can cause significant damage as well. By the time the worms become young adults, a parasitologist familiar with autopsies of victims of RLWD suggests the young adult worms do leave the brain, entering the heart, pulmonary artery, and lungs, and therefore does not recommend the use of albendazole beyond 21 days PI. It is better to let the worms exit the brain rather than die in the brain, contradicting the most commonly accepted belief that the worms will die in the brain at the end of their life cycle.

While the discussion regarding albendazole for treatment of RLWD continues, one thing is certain; in areas where the RLW is endemic, especially Hawaiʻi, physicians should consider RLWD if a patient displays disease symptoms or has been exposed to a slug/snail (or paratenic host) and immediately begin treatment with anthelmintics and corticosteroids. If a slug or snail is found in food, a beverage, or accidentially or intentionally is eaten, whether it is known if the slug/snail is infected or not, it is essential that a physician initiates treatment with albendazole. Once ingested the microscopic RLW larvae grow rapidly, increasing in bulk up to three orders of magnitude (1000 times) in size by the time they are adults. Diagnosis for RLWD in the United States requires a spinal tap with DNA evidence of the RLW. Elevated eosinophil levels in the cerebral spinal fluid (CSF) or blood are indicators of RLWD, as are antibodies, but these along with DNA evidence may take weeks to appear. By the time the disease is confirmed the administration of albendazole will be less effective and considerably more damage will have occured. With the knowledge that albendazole is quite safe, it should be prescribed when a physican first suspects the disease, the larvae are small, and the drug has a better potential for killing the RLW larvae.

In a case of known exposure, finding a slug/snail in food or a beverage or seeing a child put a slug in their mouth, an over-the-counter pin worm medication (pyrantel palmoate) has been shown through trials at the Jarvi lab to be effective in paralyzing the infective L3 larvae. The immediate administration of this medication may buy time in preventing the larvae from moving beyond the gut until a physician can prescribe albendazole https://www.hilomedicalcenter.org/hilo-medical-center-updates-early-treatment-protocol-for-rat-lungworm/. If a slug/snail is found in food, a beverage, or a child is observed to put a slug in his/her mouth, the slug/snail can be saved and sent to the Jarvi lab at the University of Hawaiʻi, Hilo (UHH), Daniel K. Inouye College of Pharmacy for testing to determine if it is infected with RLW. The slug/snail should be put into a plastic bag (using gloves/tongs/chopsticks). If the slug/snail is alive, arrangements can be made to deliver a slug alive if cleared with the Jarvi lab and hand-delivered expeditiously. If the slug/snail is dead or needs to be shipped, or if it cannot be delivered promptly, it is best to freeze for 24 hours before shipping and then transporting it on ice. Follow instructions on the on the UHH Jarvi website (http://devpharm.uhh.hawaii.edu/rat-lungworm/biological-tissues-sample-submission-form/). The organism, along with a filled out form (http://devpharm.uhh.hawaii.edu/wp-content/uploads/2020/11/Jarvi-Lab_BiologicalTissues_SampleSubmission_Form.pdf) can then be submitted to the Jarvi lab for testing for RLW infection for a small fee.

References:

Horton, J. 2000. Albendazole: a review of anthelmintic efficacy and safety in humans. Parasitology. 121. S113- S1322. https://doi.org/10.1017/S0031182000007290
Howe, K. 2013. A severe case of rat lungworm disease in Hawaiʻi. Hawaiʻi Journal of Medicine and Public Health, 72(6)(Supp 2). 41-45.
Hwang, K-P., E-R. Chen. 1988. Larvicidal effect of albendazole against Angiostrongylus cantonensis in mice. The American Journal of Tropical Medicine and Hygiene. 39(2): 191-195. https://doi.org/10.4269/ajtmh.1988.39.191
Jacob, J., G. Tan, I. Lange, H. Saeed, A. Date, S.I. Jarvi. 2020. In vitro efficacy of anthelmintics on Angiostrongylus cantonensis L3 larvae. Parasitology. 1-11. https://doi.org/10.1017/S0031182020001146
Kwon, E., T.M. Ferguson, S.Y. Park, A. Manuzak, Y. Qvarnstrom, S. Morgan, P. Ciminera, G.S. Murphy. 2013. A severe case of angiostrongylus eosinophilic meningitis with enchephalitis and neurologic sequelae in Hawaiʻi. Hawaiʻi Journal of Medicine and Public Health, 72(6)(Supp 2). 41-45.
Lakwo, T.T., A. Ishih, M. Terada, M. Sano. 1998. Effects of albendazole agains larval and adult Angiostrongylus cantonensis in rats. Parasitology international. 47(1998): 281-288.
Prociv, P., M. Turner. 2017. Neuroangiostrongyliasis: The “subarachnoid phase” and its implications for anthelmintic therapy. The American Journal of Tropical Medicine and Hygiene. 98(2): 353-359. https://doi.org/10.4269/ajtmh.17-0206.
Prociv, P. 2019. Need for critical rethinking in clinical approaches to neuroangiostrongyliasis. The American Journal of Tropical Medicine and Hygiene. 101(4): 951. https://doi.org/10.4269/ajtmh.19-0546a
Takayanagui, O.M., P.S. Bonato, S.A.C. Dreossi, V.L. Lanchote. 2002. Enantioselective distribution of albendazole metabolites in cerebrospinal fluid of patients with neurocycticercosis. British Journal of Clinical Pharmacology. 54: 125-130. https://doi.org/10.1046/j.1365-2125.2002.01634.x
Wang, Q.-P., Z.-D. Wu, J. Wei, R.L. Owen, Z.-R. Lun. 2011. Human Angiostrongylus cantonensis: an update. European Journal of Clinical Microbiology and Infectious Diseases. 31:389-395.
Personal communication Dr. Jon Martel; Hilo Medical Center, Hilo, Hawaiʻi

The data for documented cases of rat lungworm disease (RLWD) is collected by the Hawaiʻi State Department of Health (HDOH) and is displayed on their website under the Summary of Reported Cases of Notifiable Disease and the heading Angiostrongylus cantonensis. Information on case numbers per island for 2010 can also be found in the HDOH, Rat Lungworm Disease in Hawaii – Control and Prevention Legislative Report, which states that of the nine documented cases from 2010 one was from Kauai, one from Maui, and seven were from Hawaiʻi Island. However, at the HDOH Summary of Reported Cases of Notifiable Disease there is a discrepancy. There are no cases reported from Kauai in 2010, reported instead are one case from Maui, one from Oahu, and seven from Hawaiʻi Island.

A 20-micron filter alone is really just a sediment filter, and while it may reduce the numbers of 3rd stage (L3 infective stage) rat lungworm (RLW) larvae passing through the filter it will not completely block them. The Jarvi lab conducted a pilot study to determine the efficacy of commercially available sediment filters, commonly used in rainwater catchment systems to prevent passage of the L3 larvae. Filters tested were the 20 and 10 micron wound polypropylene filter, the 5 and 1 micron spun polypropylene filter, and the 5 micron carbon-block filter. While all filters reduced numbers of larave, only the 5 micron-carbon block filter completely stopped passage of all larvae. The carbon-block filter tested is made of inflexible material with rubber seals on both ends. The L3 larvae were neither able to go around the seals nor burrow through the 100% coconut shell carbon material. More studies on catchment filtration and sterilization systems need to be conducted.

Reference:

Howe. K., L. Kaluna, A. Lozano, B. Torres-Fischer, Y. Tagami, R. McHugh, S. Jarvi. 2019. Water transmission potential of Angiostrongylus cantonensis: Larval viability and effectiveness of rainwater catchment sediment filters. Plos One. https://doi.org/10.1371/journal.pone.0209813
Rat Lungworm Disease in Hawaii, Control and Prevention Legislative Report. Hawaii State Department of Health, March 2018.
https://health.hawaii.gov/docd/files/2019/08/Disease-Summary-Table-2009_2018_State.pdf
https://health.hawaii.gov/docd/files/2019/11/Disease-Summary-Table-2009_2018_Hawaii.pdf
https://health.hawaii.gov/docd/files/2019/11/Disease-Summary-Table-2009_2018_Honolulu.pdf
https://health.hawaii.gov/docd/files/2019/11/Disease-Summary-Table-2009_2018_Maui.pdf

There are no waterproof posters to inform people about rat lungworm disease (RLWD) that we know of that are available for posting in the community. The Jarvi lab has developed informational brochures that have been given to grocery stores and rainwater catchment supply businesses. While at some point in time there may have been a laminated, educational poster from the Hawaii State Department of Health, we are unaware of such a poster at this point in time.

Copper barrier products do repel some slugs and snails but copper is not 100% effective. One study showed Veronicella cubensis (the Cuban slug) and Deroceras laeve (the marsh slug) breached a copper barrier within an hour. The study concluded copper based barriers were effective in barring some but not all species of snails. Wider bands (6 inch) of copper seem to be more effective, but copper is expensive and using wide bands of copper around garden beds to deter slugs may be cost prohibitive. The University of Californiaʻs Integrated Pest Management Program suggest using a Bordeaux mixture of copper sulfate and hydrated lime. Less expensive than copper bands, flashing, or screen, the mixture can be brushed or sprayed on trunks, bench legs, etc., and a treatment lasts for about one year. Foliar applications of copper hydroxide were shown to reduce but not entirely prevent feeding by slugs and snails. A 1-2% caffine solution as a soil drench was shown to rout slugs and snails from soil and was effective at killing slugs and snails. A 2% solutions of caffeine was more effecting in reducing snail presence that a 0.195% solution of metaldehyde, the active ingredient in slug baits such as Deadline, and was at least as effective as copper hydroxide in preventing foliar feeding by slugs and snails.

References: 

Robert Hollingsworth, Ph.D., USDA (personal communication).
Hollingsworth, R.G., J. W. Armstrong, E. Campbell. 2002. Caffeine as a repellent for slugs and snails. USDA National Wildlife Research Cener-Staff Publications. 470. https://digitalcommons.unl.edu/icwdm_usdawrc/470
Thompson, J. M., J. L. Sibley,, W. G., Foshee III, G. J. Keever, A.G Appel. 2005. Effect of copper hydroxide on slug feeding. Journal of Environmental Horticulture. 23(4): 167-170.
Yeung, N.W., R.H. Cowie. Alien snail control in nurseries. Report to the Oahu Army Natural Resources Program (OANRP). 30 November 2012.
http://ipm.ucanr.edu/PMG/r280500111.html

Ultraviolet (UV) light is made up of 3 types of UV rays: UVA, UVB, and UVC. The most common and abundant form of UV radiation is sunlight, which contains all 3 types of UV rays, however only UVA and UVB penetrate earth’s atmosphere. UVC rays are absorbed by the earth’s ozone layer, but UVC radiation from artificial sources is regularly used for germicidal uses. Genetic material, like RNA and DNA, absorbs all UV rays but most easily absorbs the energy from UVC rays, which creates lesions in the genetic material [1]. DNA and RNA are used to make proteins that are crucial for the growth, repair, and reproduction of an organism. Simple organisms like bacteria, viruses, and protozoans lack the ability to repair DNA lesions, and without the ability to repair, grow, or reproduce they die after available resources are used following UVC exposure [2].

Multicellular organisms, like nematodes, have a limited ability to repair some DNA or RNA damage caused by UV radiation [1,3]. Many organisms have other mechanisms to prevent UV light from reaching the genetic material within the cell, such as hair and pigmentation of the skin. Slugs and snails have many pigmented tissue layers, which should protect the genetic material of the slug or snail as well as any parasites within, by blocking the UV radiation from reaching the cell’s nucleus. The third-larval (L3) stage of the nematode Angiostrongylus cantonensis causes rat lungworm disease and develops inside slugs and snails. The L3 stage is translucent [4], so UV radiation should be able to penetrate the larvae and reach the genetic material within the cells, but only if the larvae is ‘free’ from a host and surrounded by clear or translucent material, like water. Other species of parasitic nematodes with free-living L3 larval stages found in pastures do generally show increased mortality with increasing solar radiation (UVA and UVB rays), and this might explain changes in population abundance of these species [5]. Generally, the rat lungworm parasite, A. cantonensis, persists because it is protected from environmental threats by residing within a host (rat or snail/slug) or host feces throughout its life cycle. There is currently no research on the prevalence of naturally occurring free-living A. cantonensis L3 larvae, nor on the effects of solar radiation on such populations.

In Hawaiʻi, the domestic water supply for many residents is from rainwater catchment systems. Slugs and snails can enter the water reservoir of catchment tanks, drown, and release live, infective A. cantonensis larvae into the water [6]. Water reservoirs are typically covered to prevent the growth of algae or other photosynthetic organisms; this plus other organic debris in the water would prevent solar radiation exposure to A. cantonensis larvae in the water reservoir. There are no local, state, or federal regulations regarding the treatment of rainwater for use in a residential home. The most widely used water treatment method on island includes a series of sediment filters and a UVC disinfection system [7]. The sediment filters are critical to ensure the water column is clear so UVC rays can penetrate water column and enter translucent organisms like bacteria, viruses, protozoan cysts. In a laboratory setting, a few sediment filters were found to trap some A. cantonensis larvae, potentially reducing the number of infectious larvae that enter a home [6]. However, there are other variables and factors that are different in a home system and these may affect the filtration effectiveness of the filters. A disinfection system, like UVC, is important to protect residents from bacterial infections and possibly rat lungworm disease.

A UVC dose is measured in milliJoules per squared centimeter (mJ/cm2). The Jarvi Lab has run some in vitro tests, exposing A. cantonensis L3 larvae in a petri dish of water to UVC doses ranging from 25- 5,000 mJ/cm2 (unpublished data). The results from these tests show a strong dose response of increased mortality with increased UVC dose. Larvae exposed to low dose UVC (<100 mJ/cm2) died very slowly with only 70-80% mortality at 30 days post exposure. Nematodes may be able to repair some damage to nuclear DNA and they have limited ability to remove (not repair) damaged DNA in the mitochondria [3]. Nematode mortality rates may be faster after exposure to high dose UVC because damage to both the nuclear and mitochondrial DNA is beyond the repair or removal capabilities of its cells.

Nematode mortality rates may be slower after exposure to low dose UVC because its cells are able to repair some of the damage, but not all. The National Sanitation Foundation certifies UVC disinfection systems used for residential water treatment at a dose of 40 mJ/cm2, which is effective for most pathogenic bacteria. Our in vitro tests show no immediate mortality of larvae following UVC dose in this range. We don’t know, however, if the UVC exposure weakened the larvae or caused damage that might restrict its ability to grow inside a host.
Studies on x-ray irradiation, another form of electromagnetic radiation, show A. cantonensis larvae exposed to x-ray irradiation are unable to grow into adults within its definitive host, a rat [8]. In the near future, we hope to be able to run a rat trial to see if larvae exposed to UVC irradiation, at doses similar to household UVC systems, are able to cause infection and complete their life cycle. Our hope is that the results of a rat trial might suggest that UVC exposure (~ 40 mJ/cm2) will weaken larvae enough to prevent human infection or restrict the larvae’s ability to grow from L3 to L4 to L5 inside a human brain, which may prevent the most serious effects of rat lungworm disease.

References:

Schuch, A.P., Moreno, N.C., Schuch, N.J., Menck, C.F.M., and Garcia, C.C.M. (2017). Sunlight damage to cellular DNA: Focus on oxidatively generated lesions. Free Radical Biology and Medicine, 107, 110-124.
Hijnen, W.A.M., Beerendonk, E.F., and Medema, G.J. (2006) Inactivation credit of UV radiation for viruses, bacteria and protozoan (oo) cysts in water: a review. Water research 40.1 (2006): 3-22.
Leung, M.C.K., Rooney, J.P., Ryde I.T., Bernal, A.J., Bess, A.S., Crocker, T.I., Ji, A.Q., and Meyer, J.N. (2013) Effects of early life exposure to ultraviolet C radiation on mitochondrial DNA content, transcription, ATP production, and oxygen consumption in developing Caenorhabditis elegans. BMC Pharmacology and toxicology 14(9): 1-14.
Lv, S., Zhang, Y., Liu, H.X., Zhang, C.W., Steinmann, P., Zhou, X.N., and Utzinger, J. (2009) Angiostrongylus cantonensis: morphological and behavioral investigation within the freshwater snail Pomacea canaliculata. Parasitology research 104(6): 1351-1359.
van Dijk, J., de Louw, M.D.E., Kalis, L.P.A., and Morgan, E.R. (2009) Ultraviolet light increases mortality of nematode larvae and can explain patterns of larval availability at pasture. International Journal for Parasitology 39: 1151-1156.
Howe, K., Kaluna, L., Lozano, A., Torres Fisher, B., Tagami, Y., McHugh, R., and Jarvi, S. (2019) Water transmission potential of Angiostrongylus cantonensis: Larval viability and effectiveness of rainwater catchment sediment filters. PLoS ONE 14 (4): e0209813.
Donohue, M.J., Macomber, P.S.H., Okimoto, D., and Lerner, D.T. (2017) Survey of rainwater catchment use and practices on Hawaii Island. Journal of Contemporary Water Research & Education 161, 33-47.
Pai, H, Ko, Y., and Chen, E. (1993) Killing effects of gamma irradiation on Angiostrongylus cantonensis in snails. American Journal of Tropical Medicine and Hygiene 48(6): 827-830.

There is treatment for neuroangiostrongyliasis (NAS) commonly referred to as rat lungworm disease (RLWD). The Hilo Medical Center, which has treated many cases, has published guidelines for treatment of RLWD and the prophylactic treatment in cases of known exposure to a slug or snail.

The guidelines are summarized here:

DISEASE STRATIFICATION/TREATMENT
Mild Disease: Symptoms, able to function, but no paralysis
Treatment: Dexamethasone 4mg twice each day x 2 weeks (or pediatric appropriate
dose). Wean off over 2 weeks.

Moderate Disease: Symptoms, severe enough to interfere with normal activity/cannot
work, but no paralysis
Treatment: Dexamethasone 6mg twice each day x 2 weeks (or pediatric appropriate
dose). Wean off over 2 weeks. Albendazole 15mg/kg day divided bid to tid max
1200mg/day.

Severe Disease: Symptoms, plus paralysis or bladder and bowel dysfunction or CSF
glucose <60 or Protein >80
Treatment: Hospitalization for high dose steroids and anthelminthic.

  • POST–EXPOSURE PROPHYLAXIS
    Post-exposure prophylaxis may be given to any child or adult who has a verified ingestion of a snail or slug on the Big Island. Advice that can be given by telephone if a call is received:
    Induce vomiting, if it is possible and safe.
  • Go to nearest pharmacy and buy Pyrantel pamoate* over the counter. Read the
    instructions and warnings and administer per instructions if they choose. Time is important and the quicker the dose is administered, the better.
  • Freeze the fragment of snail or slug and take to Dr. Sue Jarvi’s lab at University of Hawaii at Hilo College of Pharmacy.**
  • Seek care from their primary care provider within 3 days.
  • Patients should, if possible, take a copy of the guidelines from Children’s Health
    Queensland Hospital and Health Services Paediatric guideline: Snail and slug
    ingestion (Prophylaxis against Angiostrongylus cantonensis infection), September 2019.

If a child has been observed or is strongly suspected to have ingested part or all of a snail or slug, early treatment (ideally within 7 days of exposure, but not beyond 14 days of exposure) with:

  • Oral Albendazole 20 mg/kg (maximum 400 mg/dose) once daily for 7 days. Infants and children older than 6 months of age only.
  • For ease of administration, round calculated dose to the nearest multiple of 100 mg.
  • Tablets can be taken whole, chewed or crushed.
    Doses can/should be taken with food (increases systemic absorption).
  • If the patient presents to the ED for post-exposure prophylaxis, treatment with albendazole*** per the protocol above should be offered.

* Pyrantel pamoate, according to a published study by John Jacob, Ingo Lange, Ghee Tan and Susan Jarvi, “In vitro efficacy of anthelmintic drugs on Angiostrongylus cantonensis L3 larvae,” has been shown to have excellent activity against ingested angiostrongylus larvae.

** Jarvi Lab: call 808. 932.7148. First time submitters of any sample should call first. An
initial phone call also allows us to schedule workflow around incoming samples. Tracking numbers are appreciated.

*** To be effective it must be taken while the larvae are still in the intestinal tract. Ideal within 4 hours, but no later

In addition to the guidelines published by the Hilo Medical Center, the following is the recommended NAS/RLWD treatment taken from the Kramer et al. (2020) publication from John Burns School of Medicine at the University of Hawaii, Manoa.

TREATMENT

  1. Start corticosteroids as soon as a presumptive diagnosis of NAS is made and assuming there are no contraindications. High-dose corticosteroids for 14 days have been shown to improve clincal outcomes.
  2. For ocular angiostrongyliasis, several treatment aptions are available to remove the parasite from the eye. Anthelmintic drugs are contraindicated for ocular angiostrongyliasis.
  3. The addition of albendazole…may provide additional benefits…
    a.  Dosage (adults): 15 mg/kg/day twice daily for 14 days with meals.
    b.  If albendazole is used, combine with corticosteroids to blunt any possible increase in the inflammatory response to dying larvae.
  4. Careful clinical monitoring is recommended in all patients and specialist constulation (eg. Infectious disease, neurology, pain management, etc) may be advisable.
    a.  Patients should be monitored until all symptoms have resolved, which may range from weeks to months.
    b.  Psychosocial issues may arise and should be indentified and addressed.

Regarding the use of albendazole, this drug is most effective at killing the L3 rat lungworm if taken within 7 days of infection. However, in most cases of RLWD, the time of exposure is not known. If living in an area where the rat lungworm is known to be endemic and symptoms presented are those known to be common to RLWD it is advisable to begin treatment with anthelmintics even if a diagnosis has not been made. Time is of the essence for the administration of albendazole as the drug becomes less effective in the later stages (L4, L5, adult) of growth.

While treatment has been established for the acute stages of RLWD, the chronic symptoms have been difficult to treat. Serious cases of RLWD often result in neurological injury and severe pain that can be difficult to control and very long-lasting. A number of rat lungworm disease survivors have reported using acupuncture, supplements, and other non-traditional therapies to attempt to resolve long-term symptoms. There are two published cases that report the successful treatment of severe pain, one with the use of ketamine and the other with lidocane. More research for the treatment of long-term symptoms of RLWD must be conducted.

References:

Busse, J., D. Gottlieb, K. Ferreras, J. Bain, W. Schechter. 2018. Pharmacological managmenent of severe neuropathic pain in a case of eosinophilic meningitis related to Angiostrongylus cantonensis. Case Reports in Anesthesiology. https://doi.org/10.1155/2018/5038272
Cucueco, K., K. Bathen, D. Fischberg. 2020. Lidocaine infusion for refractory pain from rat lungworm disease-Honolulu, Hawaiʻi. Hawaii Journal of Health and Social Welfare. 79(8): 246-248. PMC7417640
Hilo Medical Center. Treatment Protocol for Rat Lungworm, Angiostrongyliasis. January 10, 2020. https://www.hilomedicalcenter.org/wp-content/uploads/2020/02/Rat-Lungworm-for-ED-Doctors-2020.pdf
Howe, K. 2013. A severe case of rat lungworm disease in Hawaiʻi. Hawaiʻi Journal of Medicine and Public Health. 72(6)(Supp 2): 46-48.
Jacob, J., G. Tan, I. Lange, H. Saeed, A. Date, S. Jarvi.2020. In vitro efficacy of anthelmintics on Angiostrongylus cantonensis L3 larvae. Parasitology. https://doi.org/10.1017/S0031182020001146
Kramer, K., J. Yates, J.K. McMillan, W. Gosnell, G.S. Murphy, E. Blalock, L. Lteif, O. Smith, M. Kahili-Heede, V. Ansdell. 2020. Diagnosis and treatement of neuroangiostrongyliasis in Hawaiʻi. Hawaiʻi Journal of Health & Social Welfare. 79(12): 353-356.
Hilo Medical Center Rat Lungworm Survivor Group, personal communications.

No, rat lungworm disease (RLWD) cannot be contracted directly from rat droppings or rat urine. The infective, third stage larva (L3) are only harbored in intermediate hosts, (slugs and snails), or paratenic hosts (crabs, frogs, toads, centipedes, water monitor lizards). While first stage larvae (L1) can be found in rat droppings they cannot infect a person, and no larvae would be found in urine. However, there are other serious diseases that can be contracted from rat excreta (droppings, urine, saliva), such as the hantavirus and leptospirosis.

References:

Bi, Z., P.B.H. Formenty, C.E. Roth. 2008. Hantavirus infection: a review and global update. Journal of Infection Developing Countries. 2(1): 3-13.
Picardeau, M. 2013. Diagnosis and epidemiology of leptospirosis. Médecine et Maladies Infectiuses. Elsevier Masson France. (43)1-9. https://reader.elsevier.com/reader/sd/pii/S0399077X12003198?token=D528646FBAAB08DE42655CA6D9235415CDBBD2A4DC0F39322CADBADF80A55840C18D228EDEE24C43C3561F307EDD99E9
Wang, Q-P., D-H. Lai, X-Q. Zhu, X-G. Chen, Z-R Lun. 2008. Human angiostrongyliasis. Lancet Infectious Disease. 8: 621-30.

The Center for Disease Control (CDC) and the Hawaii Department of Health (HDOH) maintain that most cases resolve themselves in 2-8 weeks. This may be true for less severe cases of RLWD, however mild cases are rarely reported as diagnosis requires a spinal tap (lumbar puncture) and this procedure would only be prescribed by a doctor in the event a person presents with severe symptoms. There have been a few instances of interviews and follow-up surveys for survivors of rat lungworm disease (RLWD) but at this time no research paper has been written on the long-term treatment and recovery of those who have gotten the disease. In 2019 the Jarvi lab published a paper estimating human exposure to RLWD on Hawaiʻi Island. A questionaire provided to those in the study sought to identify long-term symptoms and these are reported.

From what we know from survivor reports, symptoms can persist for months, years, or may never resolve completely. It is finally now accepted that RLWD in Hawaii can often present in a much more serious illness than seen in other parts of the world where the disease is found. Following the recovery of severe cases of RLWD could provide insights into possible treatments. That many of those who have contracted RLWD have to live with unresolved pain and have their lives permanently changed, often being unable to work again or to have permanent disability, speaks to the need for the CDC and the HDOH to take this disease much more seriously and provide more funding for research into treatment of rat lungworm disease ʻlong-haulersʻ.

References:

Jarvi, S.I., P. Eamsobhana, S. Quarta, K. Howe, S. Jacquier, A. Hanion, K. Snook, R. McHugh, Z. Tman, J. Miyamura, K. Kramer, M. Meyers. 2019. Estimating human exposure to rat lungworm (Angiostrongylus cantonensis) on Hawaiʻi Island: A pilot study. American Journal of Tropical Medicine and Hygiene. 00(0):1-9. doi:10.4269/ajtmh.18-0242
https://www.westhawaiitoday.com/2018/01/11/hawaii-news/hawaii-rat-lungworm-cases-differ-from-others-around-globe/

Rat Lungworm