Hostname: page-component-8448b6f56d-sxzjt Total loading time: 0 Render date: 2024-04-16T01:55:17.266Z Has data issue: false hasContentIssue false
  • English
  • Français

Predisposition to ascariasis: patterns, mechanisms and implications

Published online by Cambridge University Press:  19 May 2009

C. V. HOLLAND
C. V. HOLLAND*
Affiliation:
Department of Zoology, School of Natural Sciences, Trinity College Dublin, Dublin 2, Ireland
*
*Corresponding author. Tel: +353 1-8961096. E-mail: cholland@tcd.ie
Get access Rights & Permissions [Opens in a new window]

Summary

Ascaris lumbricoides, the human roundworm, is a remarkably infectious and persistent parasite. It is a member of the soil-transmitted helminths or geohelminths and infects in the order of 1472 million people worldwide. Despite, its high prevalence and wide distribution it remains along with its geohelminth counterparts, a neglected disease. Ascariasis is associated with both chronic and acute morbidity, particularly in growing children, and the level of morbidity assessed as disability-adjusted life years is about 10·5 million. Like other macroparasite infections, the frequency distribution of A. lumbricoides is aggregated or overdispersed with most hosts harbouring few or no worms and a small proportion harbouring very heavy infections. Furthermore, after chemotherapeutic treatment, individuals demonstrate consistency in the pattern of re-infection with ascariasis, described as predisposition. These epidemiological phenomena have been identified, in a consistent manner, from a range of geographical locations in both children and adults. However, what has proved to be much more refractory to investigation has been the mechanisms that contribute to the observed epidemiological patterns. Parallel observations utilizing human subjects and appropriate animal model systems are essential to our understanding of the mechanisms underlying susceptibility/resistance to ascariasis. Furthermore, these patterns of Ascaris intensity and re-infection have broader implications with respect to helminth control and interactions with other important bystander infections.

Keywords

Ascaris lumbricoidesepidemiologyaggregationpredispositionsusceptibilityresistancemechanismcontrol
Type
Research Article
Information
Parasitology , Volume 136 , Special Issue 12: Special Centenary Issue – Parasitology 1908–2008 , October 2009 , pp. 1537 - 1547
Copyright
Copyright © Cambridge University Press 2009

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Albonico, M., Allen, H., Chitsulo, L., Engels, D., Gabrielli, A.-F. and Savioli, L. (2008). Controlling soil-transmitted helminthiasis in pre-school age children through preventive chemotherapy. PLOS Neglected Tropical Diseases 2, e126.CrossRefGoogle ScholarPubMed
Albonico, M., Montresor, A., Crompton, D. W. T. and Savioli, L. (2006). Intervention for the control of soil-transmitted helminthiasis in the community. Advances in Parasitology 61, 311–348.CrossRefGoogle ScholarPubMed
Anderson, R. M. (1986). The population dynamics and epidemiology of intestinal nematode infections. Transactions of the Royal Socity of Tropical Medicine and Hygiene 80, 686–696.CrossRefGoogle ScholarPubMed
Anderson, R. M. and May, R. M. (1991). Infectious Diseases of Humans. Dynamics and Control. Oxford University Press, Oxford, UK.Google Scholar
Anderson, R. M. and Medley, G. (1985). Community control of helminth infections of man by mass and selective chemotherapy. Parasitology 90, 629–660.CrossRefGoogle Scholar
Anderson, T. J. C., Blouin, M. S. and Beech, R. N. (1998). Population biology of parasitic nematodes: applications of genetic markers. Advances in Parasitology 41, 219–283.CrossRefGoogle ScholarPubMed
Anderson, T. J. C., Romero-Abal, M. E. and Jaenike, J. (1995). Mitochondrial DNA and Ascaris microepidemiology: the composition of parasite populations from individual hosts, families and villages. Parasitology 110, 221–229.CrossRefGoogle ScholarPubMed
Asaolu, S. O., Holland, C. V. and Crompton, D. W. T. (1991). Community control of Ascaris lumbricoides in rural Oyo State, Nigeria: mass, targeted and selective treatment with levamisole. Parasitology 103, 291–298.CrossRefGoogle ScholarPubMed
Behnke, J. M., Iraq, F., Menge, D., Baker, R. L., Gibson, J. and Wakelin, D. (2003). Chasing the genes that control resistance to gastrointestinal nematodes. Journal of Helminthology 77, 99–109.CrossRefGoogle ScholarPubMed
Bellaby, T., Robinson, K. and Wakelin, D. (1995). Induction of differential T-helper-cell responses in mice infected with variants of the parasitic nematode Trichuris muris. Infection and Immunity 64, 791–795.CrossRefGoogle Scholar
Bliss, C. I. and Fisher, R. A. (1953). Fitting the negative binomial distribution to biological data. Biometrics 9, 176–199.CrossRefGoogle Scholar
Boes, J., Medley, G. F., Eriksen, L., Roepstorff, A. and Nansen, P. (1998). Distribution of Ascaris suum in experimentally and naturally infected pigs in comparison with Ascaris lumbricoides infections in humans. Parasitology 177, 589–596.CrossRefGoogle Scholar
Bundy, D. A. P., Cooper, E. S., Thompson, D. E., Didier, J. M., Anderson, R. M. and Simmons, L. (1987). Predisposition to Trichuris trichiura in humans. Epidemiology and Infection 98, 65–71.CrossRefGoogle ScholarPubMed
Bundy, D. A. P., Wong, M. S., Lewis, L. L. and Horton, J. (1990). Control of geohelminths by delivery of targeted chemotherapy through schools. Transactions of the Royal Society of Tropical and Medicine and Hygiene 84, 115–120.Google Scholar
Chan, L., Bundy, D. A. P. and Kan, S. P. (1994 a). Aggregation and predisposition at the familial level. Transactions of the Royal Society of Tropical and Medicine and Hygiene 88, 46–48.Google Scholar
Chan, L., Bundy, D. A. P. and Kan, S. P. (1994 b). Genetic relatedness as a determinant of predisposition to Ascaris lumbricoides and Trichuris trichiura infection. Parasitology 108, 77–80.CrossRefGoogle ScholarPubMed
Chan, L., Kan, S. P. and Bundy, D. A. P. (1992). The effect of repeated chemotherapy on age-related predisposition to Ascaris lumbricoides and Trichuris trichiura. Parasitology 104, 371–377.CrossRefGoogle ScholarPubMed
Cliffe, L. J. and Grencis, R. K. (2004). The Trichuris muris system: a paradigm of resistance and susceptibility to intestinal nematode infection. Advances in Parasitology 57, 255–307.Google Scholar
Coates, S. (2000). Modelling the population dynamics of Ascaris suum in pigs. Ph.D. thesis. University of Warwick, Coventry, UK.Google Scholar
Combes, C. (2001). Parasitism the Ecology and Evolution of Intimate Interactions. The University of Chicago Press, Chicago, IL, USA.Google Scholar
Cooper, P. J., Chico, M. E., Sandoval, C., Espinel, I., Guevara, A., Kennedy, M. W., Urban, J. F. Jr., Griffin, G. E. and Nutman, T. B. (2000). Human infection with Ascaris lumbricoides is associated with a polarized cytokine response. The Journal of Infectious Diseases 182, 1207–1213.CrossRefGoogle ScholarPubMed
Crofton, H. D. (1971). A quantitative approach to parasitism. Parasitology 63, 343–364.Google Scholar
Croll, N. A. and Ghadirian, F. (1981). Wormy persons: contributions to the nature and patterns of overdispersion with Ascaris lumbricoides, Ancylostoma duodenale, Necator americanus and Trichuris trichiura. Tropical Geographical Medicine 33, 241–248.Google Scholar
Crompton, D. W. T. (1994). Ascaris lumbricoides. In Parasitic and Infectious Diseases Epidemiology and Ecology (ed. Scott, M. E. and Smith, G.), pp. 175–196. Academic Press, San Diego, CA, USA.Google Scholar
Crompton, D. W. T. (2001). Ascaris and ascariasis. Advances in Parasitology 48, 285–375.CrossRefGoogle ScholarPubMed
Dold, C., Cassidy, J. P., Behnke, J. M. and Holland, C. V. (2008). Exploiting the Ascaris suum mouse model to identify the mechanistic basis of resistance/susceptibility. Abstracts of the Proceedings of the Xth European Multicolloquim of Parasitology, Paris August 24–28, p. 50.Google Scholar
Elkins, D., Haswell-Elkins, M. R. and Anderson, R. M. (1986). The epidemiology and control of intestinal helminths in the Pulicat region of Southern India. I Study design and pre- and post-treatment observations on Ascaris lumbricoides infection. Transactions of the Royal Society of Tropical Medicine and Hygiene 80, 774–792.Google Scholar
Fraser, E. M. and Kennedy, M. W. (1991). Heterogeneity in the expression of surface-exposed epitopes among larvae of Ascaris lumbricoides. Parasite Immunology 13, 219–225.CrossRefGoogle ScholarPubMed
Forrester, J. E., Scott, M. E., Bundy, D. A. P. and Golden, M. H. N. (1990). Predisposition of individuals and families in Mexico to heavy infection with Ascaris lumbricoides and Trichuris trichiura. Transactions of the Royal Society of Tropical Medicine and Hygiene 84, 272–276.Google Scholar
Frontera, E., Roepstorff, A., Gazquez, A., Reina, D., Serrano, F. J. and Navarrete, I. (2003). Immunohistochemical distribution of antigens in liver of infected and immunized pigs with Ascaris suum. Veterinary Parasitology 111, 9–18.CrossRefGoogle ScholarPubMed
Hagel, I., Lynch, N. R., Di Prisco, M. C., Rojas, E., Perez, M. and Alvarez, N. (1993). Ascaris reinfection of slum children: relation with the IgE response. Clinical and Experimental Immunology 94, 80–83.Google Scholar
Hall, A., Anwar, K. S. and Tomkins, A. (1992). Intensity of reinfection with Ascaris lumbricoides and its implications for parasite control. Lancet 339, 1253–1257.CrossRefGoogle ScholarPubMed
Hall, A. and Holland, C. V. (2000). Geographical variation in Ascaris lumbricoides fecundity and its implications for helminth control. Parasitology Today 61, 540–544.CrossRefGoogle Scholar
Haswell-Elkins, M. R., Elkins, D. B. and Anderson, R. M. (1987). Evidence for predisposition in humans to infection with Ascaris, hookworm, Enterobius and Trichuris in a South Indian fishing village. Parasitology 95, 323–337.CrossRefGoogle Scholar
Henry, F. J. (1988). Reinfection with Ascaris lumbricoides after chemotherapy: a comparative study in three villages with varying sanitation. Transactions of the Royal Society of Tropical Medicine and Hygiene 82, 460–464.CrossRefGoogle ScholarPubMed
Holland, C. V. (2005). Ascaris, Trichuris, hookworm and Enterobius. In Topley and Wilson's Parasitology, 10th edn, pp. 712–736. Hodder Arnold, UK.Google Scholar
Holland, C. V., Asaolu, S. O., Crompton, D. W. T., Crichton, W. B., Torimiro, S. E. A. and Walters, D. E. (1992). A possible genetic factor influencing protection from infection with Ascaris lumbricoides. Journal of Parasitology 78, 915–916.CrossRefGoogle ScholarPubMed
Holland, C. V., Asaolu, S. O., Crompton, D. W. T., Stoddart, R. C., MacDonald, R. and Torimiro, S. E. A. (1989). The epidemiology of Ascaris lumbricoides and other soil-transmitted helminths in primary school children from Ile-Ife, Nigeria. Parasitology 99, 275–285.Google Scholar
Holland, C. V. and Boes, J. (2002). Distributions and predisposition: people and pigs. In The Geohelminths: Ascaris, Trichuris and Hookworm (ed. Holland, C. V. and Kennedy, M. W.),pp. 1–24. Kluwer Academic Publishers, The Netherlands.CrossRefGoogle Scholar
Holland, C., O'Shea, E., Asaolu, S. O., Turley, O. and Crompton, D. W. T. (1996). A cost-effective analysis of anthelmintic intervention for community control of soil-transmitted helminth infection: Levamisole and Ascaris lumbricoides. Journal of Parasitology 82, 527–530.CrossRefGoogle ScholarPubMed
Hotez, P. J., Molyneux, D. H., Fenwick, A., Kumaresan, J., Ehrlich Sachs, S., Sachs, J. and Savioli, L. (2007). Control of neglected tropical diseases. New England Journal of Medicine 357, 1018–1027.Google Scholar
Jackson, J. A., Turner, J. D., Rentoul, L., Faulkner, H., Behnke, J. M., Hoyle, M., Grencis, R. K., Else, K. J., Kamgno, J., Boussinesq, M. and Bradley, J. E. (2004). T helper cell type 2 responsiveness predicts future susceptibility to gastrointestinal nematodes in humans. The Journal of Infectious Diseases 190, 1804–1811.CrossRefGoogle ScholarPubMed
Javid, G., Wani, N. A., Gulzar, G. M., Khan, B. A., Shah, A. H., Shah, O. J. and Khan, M. (1999). Ascaris-induced liver abscess. World Journal of Surgery 23, 1191–1194.CrossRefGoogle ScholarPubMed
Keymer, A. E. and Pagal, M. (1990). Predisposition to helminth infection. In Hookworm Disease: Current Status and New Directions (ed. Schad, G. A. and Warren, K. S.), pp. 177–209. Taylor and Francis, London, UK.Google Scholar
Kirwan, P., Asaolu, S. O., Molloy, S. F., Abiona, T. C., Jackson, A. and Holland, C. V. (2009). Patterns of soil-transmitted helminth infection and impact of four-monthly albendazole treatments in preschool children from semi-urban communities in Nigeria: a double blind placebo-controlled randomised trial. BMC Infectious Diseases 9, 20.CrossRefGoogle ScholarPubMed
Kuris, A. M., Goddard, J. H. R., Torchin, M. E., Murphy, N., Gurney, R. and Lafferty, K. D. (2007). An experimental evaluation of host specificity: the role of encounter and compatability filters for a rhizocephalan parasite of crabs. International Journal for Parasitology 37, 539–545.CrossRefGoogle ScholarPubMed
Lewis, R., Behnke, J. M., Cassidy, J., Stafford, P., Murray, N. and Holland, C. V. (2007). The migration of Ascaris suum larvae, and the associated pulmonary inflammatory response in susceptible C57BL/6j and resistant CBA/Ca mice. Parasitology 134, 1301–1314.Google Scholar
Lewis, R., Stafford, P., Behnke, J. M. and Holland, C. V. (2006). The development of a mouse model to explore resistance and susceptibility to early Ascaris suum infection. Parasitology 132, 289–300.CrossRefGoogle ScholarPubMed
Loeffler, W. (1932). Zur Differentialdiagnose der Lungen-infiltrierungen. II Ueber fluchtige Succedanininfiltrate (mit Eosinophilie). Beiträge zur Klinik der Tuberkulose 79, 368–382.Google Scholar
Loeffler, W. (1956). Transient lung infiltrations with blood eosinophilia. International Archives of Allergy and Applied Immunity 8, 54–59.Google Scholar
Maizels, R. M. and Kurniawan-Atmadja, A. (2002). Variation and polymorphism in helminth parasites. Parasitology 125, S25–S37.CrossRefGoogle ScholarPubMed
Maizels, R. M. and Yazdanbakhsh, M. (2003). Immune regulation by helminth parasites: cellular and molecular mechanisms. Nature Reviews Immunology 3, 733–744.CrossRefGoogle ScholarPubMed
McCallum, H. I. (1990). Covariance of parasite burdens: the effect of predisposition to infection. Parasitology 100, 153–159.CrossRefGoogle ScholarPubMed
McSharry, C., Xia, Y., Holland, C. V. and Kennedy, M. W. (1999). Natural immunity to Ascaris lumbricoides associated with immunoglobulin E antibody to ABA-1 allergen and inflammation indicators in children. Infection and Immunity 67, 484–489.Google Scholar
Mitchell, G. E., Hogarth-Scott, R. S., Edwards, R. D., Lewers, H. M., Cousins, G. and Moore, T. (1976). Studies on the immune response to parasite antigens mice. 1 Ascaris suum larvae numbers and antiphorylcholine responses in infected mice of various strains and in hypothymic nu/nu mice. International Archives of Allergy and Applied Immunity 52, 64–78.Google Scholar
Montresor, A., Crompton, D. W. T., Gyorkos, T. W. and Savioli, L. (2002). Helminth control in school age children. World Health Organization, Geneva, Switzerland.Google Scholar
Murrell, K. D., Eriksen, L., Nansen, P., Slotved, H.-C. and Rasmussen, T. (1997). Ascaris suum: a revision of its early migratory path and implications for human ascariasis. Journal of Parasitology 83, 255–260.CrossRefGoogle ScholarPubMed
Mwangi, T. W., Bethony, J. and Brooker, S. (2007). Malaria and helminth interactions in humans: an epidemiological viewpoint. Annals of Tropical Medicine and Hygiene 100, 551–570.Google Scholar
Nejsum, P., Roepstorff, A., Anderson, T. J. C., Jorgensen, C. B., Fredholm, M. and Thamsborg, S. M. (2009 a). The dynamics of genetically marked Ascaris suum infections in pigs. Parasitology 136, 193–201.CrossRefGoogle ScholarPubMed
Nejsum, P., Roepstorff, A., Jorgensen, C. B., Fredholm, M., Goring, H. H. H., Anderson, T. J. C. & Thamsborg, S. M. (2009 b). High heritability for Ascaris and Trichuris infection levels in pigs. Heredity 102, 357–364.CrossRefGoogle ScholarPubMed
O'Lorcain, P. and Holland, C. V. (2000). The public health significance of Ascaris lumbricoides. Parasitology 121, S51–S71.CrossRefGoogle Scholar
Palmer, D. R., Hall, A., Haque, R. and Anwar, K. S. (1995). Antibody isotype responses to antigens of Ascaris lumbricoides in a case-control study of persistently heavily infected Bangladeshi children. Parasitology 111, 385–393.Google Scholar
Peng, W., Zhou, X., Cui, X., Crompton, D. W. T., Whitehead, R. R., Xiong, J., Wu, H., Yang, Y., Wu, W., Xu, K. and Yan, Y. (1998). Transmission and natural regulation of infection with Ascaris lumbricoides in a rural community in China. Journal of Parasitology 84, 252–258.Google Scholar
Perez, J., Garcia, P. M., Mozos, E., Bautista, M. J. and Carrasco, L. (2001). Immunohistochemical characterization of hepatic lesions associated with migrating larvae of Ascaris suum in pigs. Journal of Comparative Pathology 124, 200–206.Google Scholar
Petri, W. A., Kirkpatrick, B. D., Haque, R. and Duggal, P. (2008). Genes influencing susceptibility to infection. Journal of Infectious Diseases 197, 4–6.Google ScholarPubMed
Quinnell, R. J. (2003). Genetics of susceptibility to human helminth infection. International Journal for Parasitology 33, 1219–1231.CrossRefGoogle ScholarPubMed
Quinnell, R. J., Griffin, J., Nowell, M. A., Raiko, A. and Pritchard, D. I. (2001). Predisposition to hookworm infection in Papua New Guinea. Transactions of the Royal Society of Tropical Medicine and Hygiene 95, 139–142.Google Scholar
Read, A. F. and Viney, M. E. (1996). Helminth immunogenetics: why bother? Parasitology Today 12, 337–343.Google Scholar
Richard, M., Grencis, R. K., Humphreys, N. E., Renauld, J. C. and Van Snick, J. (2000). Anti-IL-9 vaccination prevents worm expulsion and blood eosinophilia in Trichuris muris-infected mice. Proceedings of the National Academy of Sciences, USA 97, 767–772.CrossRefGoogle ScholarPubMed
Roepstorff, A., Eriksen, L., Slotved, H. C. and Nansen, P. (1997). Experimental Ascaris suum infection in the pig: worm population dynamics following single inoculations with three doses of infective eggs. Parasitology 115, 443–452.CrossRefGoogle ScholarPubMed
Schad, G. A. and Anderson, R. M. (1985). Predisposition to hookworm infection in humans. Science 228, 1537–1540.Google Scholar
Schopf, L. R., Hoffman, K. F., Cheever, A. W., Urban, J. F. Jr. and Wynn, T. A. (2002). IL-10 is critical for host resistance and survival during gastrointestinal helminth infection. Journal of Immunology 168, 2383–2392.CrossRefGoogle ScholarPubMed
Shaw, D. J. and Dobson, A. P. (1995). Patterns of macroparasite abundance and aggregation in wildlife populations: a quantitative review. Parasitology 111, S111–S133.CrossRefGoogle ScholarPubMed
Slotved, H.-C., Eriksen, L., Murrell, K. D. and Nansen, P. (1998). Early Ascaris suum migration in mice as a model for pigs. Journal of Parasitology 84, 16–18.CrossRefGoogle Scholar
Stephenson, L. S. (1987). Ascariasis. In The Impact of Helminth Infections on Human Nutrition (ed. Stephenson, L. S.), pp. 89–127. Taylor and Francis, London and New York.Google Scholar
Tanguay, G. V. and Scott, M. E. (1992). Factors generating aggregation of Heligimosomoides polygyrus (Nematoda) in laboratory mice. Parasitology 104, 519–529.CrossRefGoogle Scholar
Tchuente, L. A., Behnke, J. M., Gilbert, F. S., Southgate, V. R. and Vercruysse, J. (2003). Polyparasitism with Schistosoma haematobium and soil-transmitted helminth infections among school children in Loum, Cameroon. Tropical Medicine and International Health 8, 975–986.CrossRefGoogle Scholar
Thein-Hlaing, , Than-Saw, and Myint-Lwin, (1987). Reinfection of people with Ascaris lumbricoides following single 6-month and 12-month interval mass chemotherapy in Opko village, rural Burma. Transactions of the Royal Society of Tropical Medicine and Hygiene 81, 140–146.CrossRefGoogle Scholar
Thein-Hlaing, , Than Saw, and Myat Lay Kyin, (1991). The impact of three-monthly age-targeted chemotherapy on Ascaris lumbricoides. Transactions of the Royal Society of Tropical Medicine and Hygiene 81, 519–522.CrossRefGoogle Scholar
Turner, J. D., Faulkner, H., Kamgno, J., Cormont, F., Van Snick, J., Else, K. J., Grencis, R. K., Behnke, J. M., Boussinesq, M. and Bradley, J. E. (2003). Th2 cytokines are associated with reduced worm burdens in a human intestinal helminth infection. The Journal of Infectious Diseases 188, 1768–1775.CrossRefGoogle Scholar
Urban, J. F. Jr., Katona, I. M., Paul, W. E. and Finkelman, F. D. (1991). Interleukin 4 is important in protective immunity to a gastrointestinal nematode infection in mice. Proceedings of the National Academy of Sciences, USA 88, 5513–5517.CrossRefGoogle ScholarPubMed
Wakelin, D. and Bradley, J. (2002). Parasite strain diversity and host immune responses. In The Geohelminths: Ascaris, Trichuris and Hookworm (ed. Holland, C. V. and Kennedy, M. W.), pp. 199–218. Kluwer Academic Publishers, The Netherlands.CrossRefGoogle Scholar
Wong, M. S., Bundy, D. A. P. and Golden, M. H. N. (1988). Quantitative assessment of geophageous behaviour as a potential source of exposure to geohelminth infection. Transactions of the Royal Society of Tropical Medicine and Hygiene 82, 621–625.CrossRefGoogle Scholar
World Health Organization (2002). Report of the WHO informal consultation on the use of Praziquantel during pregnancy and lactation and Albendazole/Medendazole in children under 24 months. WHO, WHO/CPE/PVC 2002.4, Geneva, Switzerland.Google Scholar
Williams-Blangero, S., Subedi, J., Upadhayay, R. P., Manral, D. B., Rai, D. R., Jha, B., Robinson, E. S. and Blangero, J. (1999). Genetic analysis of susceptibility to infection with Ascaris lumbricoides. American Journal of Tropical Medicine and Hygiene 60, 921–926.CrossRefGoogle ScholarPubMed
Williams-Blangero, S., VandeBerg, J. L., Subedi, J., Aivaliotis, M. J., Rai, D. R., Upadhayay, R. P., Jha, B. and Blangero, J. (2002). Genes on chromosomes 1 and 13 have significant effects on Ascaris infection. Proceedings of the National Academy of Sciences, USA 99, 5533–5538.Google Scholar
Williams-Blangero, S., VandeBerg, J. L., Subedi, J., Jha, B., Correa-Oiveira, R. and Blangero, J. (2008). Localization of multiple quantitative trait loci influencing susceptibility to infection with Ascaris lumbricoides. The Journal of Infectious Diseases 197, 66–71.CrossRefGoogle ScholarPubMed
Yan, M., Marsters, S. A., Grewal, I. S., Wang, H., Ashkenazi, A. and Dixit, V. M. (2000). Identification of a receptor for BlyS demonstrates a crucial role in humoral immunity. Nature Immunology 1, 37–41.Google Scholar
Yazdanbakhsh, M., Kremsner, P. G. and van Ree, R. (2002). Allergy, parasites and the Hygiene Hypothesis. Science 296, 490–494.CrossRefGoogle ScholarPubMed