martes, 27 de noviembre de 2012

Workshop on Research Priorities for Management and Treatment of Angiostrongyliasis1 - - Emerging Infectious Disease journal - CDC

Workshop on Research Priorities for Management and Treatment of Angiostrongyliasis1 - - Emerging Infectious Disease journal - CDC

Conference Summary

Workshop on Research Priorities for Management and Treatment of Angiostrongyliasis1

Robert H. CowieComments to Author , James R. Hollyer, Alexandre J. da Silva, Robert G. Hollingsworth, Marlena C. Dixon, Praphathip Eamsobhana, LeAnne M. Fox, William L. Gosnell, Kathleen Howe, Stuart Johnson, Jaynee R. Kim, Kenton J. Kramer, Phaik Eem Lim, John F. Lindo, Zhao-Rong Lun, Arnaldo Maldonado, Alessandra L. Morassutti, Gerald S. Murphy, Sarah Y. Park, Yvonne Qvarnstrom, Ralph D. Robinson, Kittisak Sawanyawisuth, John Teem, Silvana C. Thiengo, Cheridah D. Todd, Hung-Chin Tsai, Gordon D. Wallace, Cecelia A. Waugh, A. Christian Whelen, Patricia P. Wilkins, Ting-Bao Yang, and Hoi-Sen Yong
Author affiliations: University of Hawaii at Manoa, Honolulu, Hawaii, USA (R.H. Cowie, J.R. Hollyer, J.R. Kim); Centers for Disease Control and Prevention, Atlanta, Georgia, USA (A.J. da Silva, Y. Qvarnstrom, L.M. Fox., P.P. Wilkins),; Hawaii Department of Health, Honolulu (M.C. Dixon, S.Y. Park, A.C. Whelen); John A. Burns School of Medicine, Honolulu (W.L. Gosnell, K.J. Kramer, G.D. Wallace); Mahidol University, Bangkok, Thailand (P. Eamsobhana); US Department of Agriculture, Hilo, Hawaii, USA (R. G. Hollingsworth); Hilo, Hawaii, USA (K. Howe); Loyola University Medical Center and Hines VA Hospital, Hines, Illinois, USA (S. Johnson); University of Malaya, Kuala Lumpur, Malaysia (P.E. Lim, H.-S. Yong); Sun Yat-Sen University, Guangzhou, People’s Republic of China (Z.-R. Lun, T.-B. Yang); Instituto Oswaldo Cruz/Fiocruz, Rio de Janeiro, Brazil (A. Maldonado, Jr, S.C. Thiengo); Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil (A.L. Morassutti); Tripler Army Medical Center, Honolulu (G.S. Murphy); University of the West Indies, Mona, Kingston, Jamaica (J.F. Lindo, R.D. Robinson, C.D. Todd, C. A. Waugh); Khon Kaen University, Khon Kaen, Thailand (K. Sawanyawisuth); Florida Department of Agriculture and Consumer Services, Tallahassee, Florida, USA (J. Teem); and Kaohsiung Veterans General Hospital, Kaosiung City, and National Yang-Ming University, Taipei, Taiwan (H.-C. Tsai).
Suggested citation for this article
An international transdisciplinary workshop on angiostrongyliasis was held August 16–18, 2011, in Honolulu, Hawaii, USA, expanding on an inaugural workshop in Thailand in 2010 (1,2). The workshop convened scientists and clinicians from regions and countries as far apart as Brazil, China, Jamaica, Taiwan, Thailand, and the United States, with expertise in a range of fields including parasitology, ecology, food safety, epidemiology, diagnosis, and treatment. The workshop’s goal was to develop a rigorous research agenda to address the parasitic infection known as rat lungworm disease at a global scale through advancing an integrated understanding of the infection.
Angiostrongyliasis, which is caused by ingestion of uncooked/undercooked food containing third-stage larvae of Angiostrongylus cantonensis, the rat lungworm (Nematoda), is associated with eosinophilic meningitis (3). Common sources are infected snails and slugs as well as infected paratenic hosts (e.g., freshwater shrimp, certain fish). Snails and slugs (intermediate hosts) become infected by ingesting first-stage larvae from feces of rats (definitive hosts). These larvae then develop to third-stage larvae in the snails/slugs. The natural cycle continues when rats eat these hosts. The third-stage larvae migrate to the central nervous system, specifically the brain, where they mature to the fifth stage (young adults). They then return to the circulatory system where they reproduce in the pulmonary artery. Eggs are carried to the lungs, hatch, and move up the trachea and down the gut to be released in the feces.
In humans, after the larvae are ingested, the cycle breaks when the worms reach the fifth stage, typically in the brain, where they die (3). The physical damage caused by worms moving within the brain and the intense inflammatory immune reaction stimulated, especially by dead or dying worms, are thought to be responsible for the symptoms of angiostrongyliasis, which can lead to coma and, rarely, death.
Angiostrongyliasis is mainly a tropical disease, but with the increasing spread of invasive species, including rats and mollusks (4), and global warming, which may increase the hosts’ potential range, it has become an important emerging infectious disease. The link between human infection by this nematode and manifestation of eosinophilic meningitis was first recognized in Hawaii in 1961 (5); the stimulus for this workshop was an increase in recent cases (6). The keynote address, by a key researcher of that time (7,8), summarized the history of angiostrongyliasis in Hawaii. The workshop then continued with presentations that dealt with the biology, life cycle, and hosts of A. cantonensis lungworms. Key points made by the speakers were that many taxonomically unrelated snail/slug species, including temperate species introduced into tropical regions, can act as intermediate hosts and that a wide range of mammals, birds, fish, and invertebrates may be infected as accidental hosts or serve as paratenic hosts.
The second session summarized the global status of angiostrongyliasis, with presentations by participants from China, Taiwan, Thailand, Jamaica, Brazil, and the United States, including Hawaii. The disease is particularly widespread in China and Thailand, especially where raw snails, notably, introduced apple snails, are considered a delicacy (1,9,10). The potential role of slime-contaminated vegetables in transmission in Jamaica was also suggested.
The next sessions focused on diagnostic and clinical aspects. Presentations included clinical descriptions of the disease and clinical reports of cases of angiostrongyliasis acquired in Jamaica and Hawaii. Issues regarding the role of the immune response in the pathophysiology of infection were described. Reports on the current state of immunodiagnosis and future expectations for diagnostic methods noted the identification of the 31-kDa protein as a glycoprotein complex (the main antigen for angiostrongyliasis diagnosis). Presentations on detection of A. cantonensis lungworms in the environment described dramatically increased incidence in China and Thailand and increased cases in the Caribbean, Pacific Islands, Europe, and North America (9), methods for sample collection in hosts, and detection methods, including molecular (PCR) assays, which triggered discussion of the potential diagnostic use of PCR.
The next focus was on relative risks of infection and host control methods. The primary pathway of infection is the ingestion of raw snails or slugs, either deliberately or accidentally on contaminated food (10). Laboratory studies show that snail/slug slime may contain infective larvae, but no studies have confirmed this mode of infection, and the risk for infection is probably low because worm density is much lower than in the mollusks themselves. Infection by drinking contaminated water (caused by an infected snail or slug drowning in it) or through broken skin has not been documented. Presentations on disease control efforts in China and Hawaii emphasized control of snails and slugs rather than rats.
An acute need exists to raise awareness of angiostrongyliasis within the medical community and by the public. Opportunities for information dissemination include the Internet, press releases, and traditionally published review articles. Highly visible, large-scale clinical trials, perhaps in China or Pacific Islands, were suggested. Diagnostic considerations and options for clinicians include a preliminary standardized protocol, involving clinical signs, case inclusion criteria, and lumbar puncture findings. A reliable, rapid test is needed, possibly consisting of performing PCR on cerebrospinal fluid. In Hawaii, factsheets have been distributed (11), but outreach efforts have faced difficulties because farmers (and retailers) do not want their produce associated with a potentially serious illness. A series of community forums has been initiated to distil the information from the proceedings to inform the wider public.
In a concluding session of the workshop, the participants developed a list of 115 research and outreach needs, outlining the top 5–7 needs in each of 8 areas (Table). For complete information, including presenter details and abstracts, visit the workshop website at Web Site Icon.
Dr Cowie is a researcher in the Pacific Biosciences Research Center at the University of Hawaii. His interests focus on nonmarine mollusk biodiversity, especially the biology of invasive species, including those species that may act as hosts of A. cantonensis lungworms.


We thank all other participants at the workshop and Carlos Graeff-Teixeira for their contributions; Vanessa Troegner, Janice Tamanaha, Stacy Yamasaki-Ige, and Dave Au for administrative assistance; and Jeanette Thurston for support.
The workshop was funded by National Institute of Food and Agriculture, US Department of Agriculture grant 2011-65213-20054.


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  8. Wallace GD, Rosen L. Studies of eosinophilic meningitis V. Molluscan hosts of Angiostrongylus cantonensis on Pacific islands. Am J Trop Med Hyg. 1969;18:20616.PubMedExternal Web Site Icon
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  10. Hollingsworth RG, Cowie RH. Apple snails as disease vectors. In: Joshi RC, Sebastian LC, editors. Global advances in ecology and management of golden apple snails. Muñoz, Nueva Ecija (Philippines): Philippine Rice Research Institute; 2006. p. 121–32.
  11. Hollyer JR, Troegner VA, Cowie RH, Hollingsworth RG, Nakamura-Tengan L, Castro LF, Best on-farm food safety practices: reducing risks associated with rat lungworm infection and human eosinophilic meningitis. Food Safety and Technology, College of Agriculture and Human Resources. University of Hawaii at Manoa. 2010;39:18.


Suggested citation for this article: Cowie RH, Hollyer JR, da Silva AJ, Hollingsworth RG, Dixon MD, Eamsobhana P, et al. Workshop on research priorities for management and treatment of angiostrongyliasis. Emerg Infect Dis [Internet]. 2012 Dec [date cited]. Web Site Icon
DOI: 10.3201/eid1812.120499
1This workshop was organized and conducted under a grant to the University of Hawaii, where the work was done.

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