Citation: Adema CM, Bayne CJ, Bridger JM, Knight M, Loker ES, et al. (2012) Will All Scientists Working on Snails and the Diseases They Transmit Please Stand Up? PLoS Negl Trop Dis 6(12): e1835. doi:10.1371/journal.pntd.0001835
Published: December 27, 2012
Copyright: © 2012 Adema et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: The authors received no funding for this work.
Competing interests: The authors have declared that no competing interests exist.
Dr. Coen Adema, Associate Professor, studies snail immunity and genomics at the Center of Theoretical and Evolutionary Immunology, Biology, University of New Mexico. Dr. Christopher J. Bayne is a comparative immunologist with interests in the evolution of immunity. His research focuses on gaining a deeper understanding of innate immune systems and their modulation, and exploits two model organisms: the rainbow trout, in which he studies the inflammatory components of the acute phase response and effects of stress on innate immunity, and molluscan schistosomiasis, in which he investigates the mechanisms that determine susceptibility and resistance in this host–parasite system. Dr. Joanna Bridger is a Reader and a group leader at Brunel University in London, UK, has spent over 20 years studying the spatial relationship between the structures in cell nuclei and the regulation of genome behavior and gene expression in a variety of organisms, including the schistosome snail host. Dr. Matty Knight is a principal investigator at the Biomedical Research Institute. For over 20 years, her research has focused on elucidating the molecular and genetic mechanisms underlying snail–schistosome interactions. Dr. Eric Loker (Sam) has interests in the biological interplay between larval schistosomes and the snails that serve as their intermediate hosts, particularly as they influence the epidemiology of schistosomiasis in Africa. In addition, his research focuses on the use of the snail as a model system to provide new insights into the nature of invertebrate defense responses. Dr. Loker also investigates the diversity inherent among both mammalian and avian schistosomes using molecular phylogenetic and other methods. He is also involved in promoting and developing genomic resources for snails involved in the transmission of schistosomiasis. Dr. Timothy Yoshino currently is a Professor of Parasitology and Director of the NIH-supported Cellular and Molecular Parasitology Training Program in the Department of Pathobiological Sciences, School of Veterinary Medicine, at the University of Wisconsin-Madison. His research is focused on the molecular mechanisms regulating larval schistosome–snail interactions. Dr. Si-Ming Zhang, Research Associate Professor, is interested in immunological and genetic mechanisms of snail and parasite interactions, and works at Center for Evolutionary & Theoretical Immunology, University of New Mexico.
If this request had been made during the presidential address at the ASTMH meeting in Philadelphia in 2011, even though the room was filled beyond capacity, only a few people would have stood up. Yet, 300 million disadvantaged people suffer from snail-transmitted infections, with consequences ranging from life-threatening cholangiocarcinoma to subtle morbidity effects that stunt physical and mental development. The disability-adjusted life year (DALY) scores for these diseases have long been underestimated. The term “neglected tropical diseases” truly applies to all snail-borne infections, including schistosomiasis, fascioliasis, fasciolopsiasis, paragonimiasis, opisthorchiasis, clonorchiasis, and angiostrongyliasis –. The prevalence of most of the parasites involved has scarcely diminished in recent decades. The resilience of the snails that transmit them, such as Biomphalaria hosting Schistosoma mansoni in Africa, Yemen, or South America, or lymnaeid snails supporting Fasciola hepatica in Bolivia and elsewhere, provides a remarkable stability to the life cycles involved. Snail-borne infections provide a worthy challenge for any young parasitologist looking for an exciting career.
The recent World Health Organization (WHO) announcement of a global effort to eliminate human schistosomiasis by 2025  is an inspiring clarion call that underscores the need for more emphasis on snail-related research. Future control of snail-borne parasites needs to be considered outside of the box of current, almost exclusive, reliance on chemotherapy. Although it is essential and surely must continue, chemotherapy alone may never achieve transmission control or elimination , and resistance is an ever-present possibility –, especially when drug options are few, the extent of treatment is broadened, and the size of drug-sensitive parasite refugia diminishes .
So, how can study of relevant snails contribute to eliminating schistosomiasis and other snail-borne parasites? A detailed grasp of the role of snails in transmission is essential for developing integrated control strategies that also target the intramolluscan larval stages of parasites. For example, what determines the population structure and geographical distribution of snails that define endemic areas for parasite transmission, and how will global warming affect these ? To what extent is the number of infected snails dictated by immuno-compatibility between parasite and snail versus ecological factors that limit infections? Precise information from the field is lacking for how long infected snails continue to shed cercariae, and the number of cercariae produced per snail. Deciphering properties of immunity and virulence that have evolved to influence snail–parasite compatibility reveals determinants of host competence that will facilitate monitoring, predicting, and ultimately modifying transmission of schistosomiasis and other snail-borne parasites.
Exciting science can be done! Snails (and trematodes parasites) are lophotrochozoan protostomes, an animal lineage to which little attention has yet been paid—fundamental discoveries consequently lie ahead in a field that is not cluttered by many competing research groups. Recent novel basic insights into host–parasite interactions include the discovery of somatic diversification of immune molecules in invertebrates (Biomphalaria); the involvement of antigenic variation by Schistosoma to survive in snails; and the epigenetic modification of snail host chromosomes during the course of infection –. Much work is needed to clarify the mechanisms involved, work that can in today's difficult funding climate be justified by its applicability to alleviating the largely undiminished burden of snail-borne diseases. An excellent modern research toolkit justifies optimism that novel insights into Biomphalaria's role in schistosomiasis transmission will be forthcoming. Microarray platforms , , next-generation sequencing , and RNA interference enable functional transcriptomic studies of Biomphalaria snails –. A draft assembly of the B. glabrata genome sequence is fully available , comprising the third component of the genome triad—human definitive host, parasite, and snail intermediate host—pertinent to schistosomiasis. The prospects for rapid development of similar tool kits for other important snail such as Bulinus, Lymnaea, and Oncomelania  are excellent.
Such new molecular capabilities have great potential for application to field investigations and disease control. These include identifying genetic markers for compatibility, developing sensitive means to detect transmission in areas subjected to control, and assessing receptors involved in chemoattraction of parasite to host. Next-generation sequencing can identify third party symbionts (bacteria or viruses) influencing snail-trematode interactions. The characterization of regulators of parasite transmission in natural snail population can contribute to the development of novel, ecologically friendly snail control methods (e.g., feeding or pheromone traps), and open up new lines of study such as introduction of snail transgenes capable of disrupting larval growth/differentiation. With so many snail-transmitted infections still at large, and so many obvious approaches awaiting investigation, we sincerely hope that the decline in snail-related funding, with a concomitant decline in the number of trained investigators, can be reversed. The availability of young workers even able to identify medically relevant snails has dropped to a shockingly low level.
To conclude, it is an unchanging reality that snails are essential for the continued flourishing of snail-borne parasites, including those that cause schistosomiasis. Given the recent call for global elimination of schistosomiasis, it is imperative we pursue a broader agenda that incorporates basic and applied snail research. From such efforts can emerge integrated and more sustainable control strategies. This will also help to arrest the alarming decline in young investigators, particularly in endemic countries. Given the considerable attention currently focused on other parasitic diseases such as malaria, could it be that the greatest opportunities to make significant new advances in parasitology now lie in other fields that have been truly neglected?
The constructive comments of three anonymous reviewers helped improve the manuscript.
- 1. Bruun B, Aagaard-Hansen J (2008) The social context of schistosomiasis and its control. An introduction and annotated bibliography. Geneva: World Health Organization, Special Programme for Research and Training in Tropical Disease.
- 2. McManus DP, Gray DJ, Li Y, Feng Z, Williams GM, et al. (2010) Schistosomiasis in the People's Republic of China: the era of the Three Gorges Dam. Clin Microbiol Rev 23: 442–466. doi: 10.1128/cmr.00044-09
- 3. Mas-Coma S, Valero MA, Bargues MD (2009) Fasciola, lymnaeids and human fascioliasis, with a global overview on disease transmission, epidemiology, evolutionary genetics, molecular epidemiology and control. Adv Parasitol 69: 41–146. doi: 10.1016/s0065-308x(09)69002-3
- 4. Keiser J, Utzinger J (2009) Food-borne trematodiases. Clin Microbiol Rev 22: 466–483. doi: 10.1128/cmr.00012-09
- 5. Aka NA, Adoubryn K, Rondelaud D, Dreyfuss G (2008) Human paragonimiasis in Africa. Ann Afr Med 7: 153–162. doi: 10.4103/1596-3519.55660
- 6. Attwood SW (2010) Studies on the parasitology, phylogeography and the evolution of host-parasite interactions for the snail intermediate hosts of medically important trematode genera in Southeast Asia. Adv Parasitol 73: 405–440. doi: 10.1016/s0065-308x(10)73013-x
- 7. Morley NJ (2010) Aquatic molluscs as auxiliary hosts for terrestrial nematode parasites: implications for pathogen transmission in a changing climate. Parasitology 137: 1041–1056. doi: 10.1017/s0031182010000016
- 8. World Health Organization (2012) Accelerating work to overcome the global impact of neglected tropical diseases - a roadmap for implementation. Geneva: Department of Control of Neglected Tropical Diseases. Available: http://www.who.int/entity/neglected_diseases/NTD_RoadMap_2012_Fullversion.pdf. Accessed November 2012.
- 9. Gray DJ, Mcanus DP, Li Y, Williams GM, Bergquist R, et al. (2010) Schistosomiasis elimination: lessons from the past guide the future. Lancet Infect Dis 10: 733–736. doi: 10.1016/s1473-3099(10)70099-2
- 10. Doenhoff MJ, Kusel JR, Coles GC, Cioli D (2002) Resistance of Schistosoma mansoni to praziquantel: is there a problem? Trans R Soc Trop Med Hyg 96: 465–469. doi: 10.1016/s0035-9203(02)90405-0
- 11. Seto EY, Wong BK, Lu D, Zhong B (2011) Human schistosomiasis resistance to praziquantel in China: should we be worried? Am J Trop Med Hyg 85: 74–82. doi: 10.4269/ajtmh.2011.10-0542
- 12. Melman SD, Steinauer ML, Cunningham C, Kubatko LS, Mwangi IN, et al. (2009) Reduced susceptibility to praziquantel among naturally occurring Kenyan isolates of Schistosoma mansoni. PLoS Negl Trop Dis 3: e504 doi:10.1371/journal.pntd.0000504.
- 13. Knox MR, Besier RB, Le Jambre LF, Kaplan RM, Torres-Acosta JF, et al. (2012) Novel approaches for the control of helminth parasites of livestock VI: Summary of discussions and conclusions. Vet Parasitol 186: 143–149. doi: 10.1016/j.vetpar.2011.11.054
- 14. Stensgaard A-S, Utzinger J, Vounatsou P, Hürlimann E, Schur N, et al. (2011) Large-scale determinants of intestinal schistosomiasis and intermediate host snail distribution across Africa: does climate matter? Acta Trop. E-pub ahead of print 28 November 2011 doi:10.1016/j.actatropica.2011.11.010.
- 15. Zhang S-M, Adema CM, Kepler TB, Loker ES (2004) Diversification of Ig superfamily genes in an invertebrate. Science 305: 251–254. doi: 10.1126/science.1088069
- 16. Mitta G, Adema CM, Gourbal B, Loker ES, Theron A (2012) Compatibility polymorphism in snail/schistosome interactions: from field to theory to molecular mechanisms. Dev Comp Immunol 37: 1–8. doi: 10.1016/j.dci.2011.09.002
- 17. Knight M, Ittiprasert W, Odoemelam EC, Adema CM, Miller A, et al. (2011) Non-random organization of the Biomphalaria glabrata genome in interphase Bge cells and the spatial repositioning of activated genes in cells co-cultured with Schistosoma mansoni. Int J Parasitol 41: 61–70. doi: 10.1016/j.ijpara.2010.07.015
- 18. Adema CM, Hanington PC, Lun CM, Rosenberg GH, Aragon AD, et al. (2010) Differential transcriptomic responses of Biomphalaria glabrata (Gastropoda, Mollusca) to bacteria and metazoan parasites, Schistosoma mansoni and Echinostoma paraensei (Digenea, Platyhelminthes). Mol Immunol 47: 849–860. doi: 10.1016/j.molimm.2009.10.019
- 19. Lockyer AE, Spinks J, Kane RA, Hoffmann KF, Fitzpatrick JM, et al. (2008) Biomphalaria glabrata transcriptome: cDNA microarray profiling identifies resistant- and susceptible-specific gene expression in haemocytes from snail strains exposed to Schistosoma mansoni. BMC Genomics 9: 634. doi: 10.1186/1471-2164-9-634
- 20. Deleury E, Dubreuil G, Elangovan N, Wajnberg E, Reichhart JM, et al. (2012) Specific versus non-specific immune responses in an invertebrate species evidenced by a comparative de novo sequencing study. PLoS ONE 7: e32512 doi:10.1371/journal.pone.0032512.
- 21. Baeza Garcia A, Pierce RJ, Gourbal B, Werkmeister E, Colinet D, et al. (2010) Involvement of the cytokine MIF in the snail host immune response to the parasite Schistosoma mansoni. PLoS Pathog 6: e1001115 doi:10.1371/journal.ppat.1001115.
- 22. Hanington PC, Forys MA, Dragoo JW, Zhang S-M, Adema CM, et al. (2010) A role for a somatically diversified lectin in resistance of an invertebrate to parasite infection. Proc Natl Acad Sci U S A 107: 21087–21092. doi: 10.1073/pnas.1011242107
- 23. Hanington PC, Forys MA, Loker ES (2012) A somatically diversified defense factor, FREP3, is a determinant of snail resistance to schistosome infection. PLoS Negl Trop Dis 6: e1591 doi:10.1371/journal.pntd.0001591.
- 24. Biomphalaria glabrata Genome Initiative. The draft assembly of Biomphalaria glabrata is available through combined efforts of the Biomphalaria Genome Initiative, WUGI and NHGRI. Available: http://biology.unm.edu/biomphalaria-genome/index.html. Accessed 26 November 2012.
- 25. Wang H, Zhao QP, Nie P, Jiang MS, Song J (2012) Identification of differentially expressed genes in Oncomelania hupensis chronically infected with Schistosoma japonicum. Exp Parasitol 130: 374–83. doi: 10.1016/j.exppara.2012.02.004