Genetic Factors Involved in Human Susceptibility to Infection by Schistosomiasis


Three hundred million individuals are at risk of infection by schistosomes, which cause severe kidney and liver disease, and 280 000 deaths annually. Infection levels are mainly under the control of a major locus, SM1 (Schistosoma mansoni 1), mapped in 5q31q33 region. An association between the rs1800925 polymorphism in the IL13 promoter and infection levels was detected. Subjects bearing the rs1800925T/T genotype were much less infected than individuals with other genotypes. We went on to investigate whether other polymorphisms in genes involved in the TH2 cytokine immune response could affect susceptibility to schistosome infection. An association between STAT6 rs324013 polymorphism and infection levels was also found. These two polymorphisms which have an additive effect were not strongly correlated with any other tested markers surrounding the two genes. Moreover, these polymorphisms affect transcription factor binding to the promoter regions. These results are consistent with the TH2 cytokine pathway enhancing resistance to schistosome infection.

Key concepts:

  • IL13 gene is associated to the control of infection levels in schistosomiasis.

  • STAT6 gene is associated to the control of infection levels in schistosomiasis.

  • IL13 and STAT6 polymorphisms have synergic effect.

Keywords: schistosomiasis; infection; IL13; STAT6; gene; parasitic

Figure 1.

Parasitic cycle for S. haematobium. Infection occurs when cercariae penetrate the skin (1). It loses its tail becoming a schistosomulae (2) which moves to the veins. Adults mature in the veins surrounding the intestines or bladder, depending on the species. Schistosoma haematobium matures in veins around the bladder whereas S. mansoni and S. japonicum mature in veins around the intestines (3). Females release eggs which move from the veins to the lumen of the intestine (S. mansoni and S. japonicum) or the bladder (S. haematobium). The eggs are then passed from the body in the feces or urine (4). They hatch in fresh water and release motile larvae called miracidium (5). The miracidium infect the intermediate host (6) and multiplie asexually inside it. After 4–6 weeks, a cercariae emerge (7).

Figure 2.

Results of the linkage analysis that maps the SM1 locus into the 5q31–q33 region. In this figure are also indicated the main putative candidate genes that may be involved in the control of infection levels in schistosomiasis.

Figure 3.

Multiple roles of the IL‐13 in the protection against infection by Schistosoma. aaM, alternatively activated macrophage and caM, classically activated macrophage.

Figure 4.

Subjects carrying the genotypes rs1800925C/C and rs324013C/T have higher levels of infection than subjects carrying the other genotypes. This effect was visible on the whole population, on male and on Boul village (that included the most infected subjects).

Figure 5.

Different roles of STAT6 in the protection against infection by Schistosoma and in the regulation of the gene expression in the TH2 locus.



Abel L, Demenais F, Prata A, Souza AE and Dessein A (1991) Evidence for the segregation of a major gene in human susceptibility/resistance to infection by Schistosoma mansoni [see comments]. American Journal of Human Genetics 48: 959–970.

Boros DL (1989) Immunopathology of Schistosoma mansoni infection. Clinical Microbiological Review 2: 250–269.

Boros DL and Warren KS (1970) Delayed hypersensitivity‐type granuloma formation and dermal reaction induced and elicited by a soluble factor isolated from Schistosoma mansoni eggs. Journal of Experimental Medicine 132: 488–507.

Butterworth AE, Capron M, Cordingley JS et al. (1985) Immunity after treatment of human schistosomiasis mansoni. II. Identification of resistant individuals, and analysis of their immune responses. Transactions of the Royal Society of Tropical Medicine and Hygiene 79: 393–408.

Butterworth AE (1977) The eosinophil and its role in immunity to helminth infection. Current Topics in Microbiology and Immunology 77: 127–168.

Cameron L, Webster RB, Strempel JM et al. (2006) Th2 cell‐selective enhancement of human IL13 transcription by IL13‐1112C>T, a polymorphism associated with allergic inflammation. Journal of Immunology 177: 8633–8642.

Capron A, Dessaint JP, Capron M and Bazin H (1975) Specific IgE antibodies in immune adherence of normal macrophages to Schistosoma mansoni schistosomules. Nature 253: 474–475.

Capron A, Dessaint JP, Capron M, Joseph M and Pestel J (1980) Role of anaphylactic antibodies in immunity to schistosomes. American Journal of Tropical Medicine and Hygiene 29: 849–857.

Capron M, Bazin H, Joseph M and Capron A (1981a) Evidence for IgE‐dependent cytotoxicity by rat eosinophils. Journal Immunology 126: 1764–1768.

Capron M, Capron A, Dessaint JP et al. (1981b) Fc receptors for IgE on human and rat eosinophils. Journal Immunology 126: 2087–2092.

Capron M, Spiegelberg HL, Prin L et al. (1984) Role of IgE receptors in effector function of human eosinophils. Journal Immunology 132: 462–468.

Chitsulo L, Engels D, Montresor A and Savioli L (2000) The global status of schistosomiasis and its control. Acta Tropica 77: 41–51.

Chitsulo L, Loverde P and Engels D (2004) Schistosomiasis. Nature Review of Microbiology 2: 12–13.

Clarke Vde V, Warburton B and Blair DM (1970) The Katayama syndrome: report on an outbreak in Rhodesia. Central African Journal of Medicine 16: 123–126.

Couissinier P and Dessein AJ (1995) Schistosoma‐specific helper T cell from subjects resistant to infection by Schistosoma mansoni are ThO/2. European Journal of Immunology 25: 2295–2302.

Demeure CE, Rihet P, Abel L et al. (1993) Resistance to Schistosoma mansoni in humans: influence of the IgE/IgG4 balance and IgG2 in immunity to reinfection after chemotherapy. Journal of Infectious Disease 168: 1000–1008.

Dessein A, Chevillard C, Arnaud V et al. (2009) Variants of CTGF are associated with hepatic fibrosis in Chinese, Sudanese, and Brazilians infected with schistosomes. Journal of Experimental Medicine 206(11): 2321–2328.

Dessein AJ, Couissinier P, Demeure C et al. (1992) Environmental, genetic and immunological factors in human resistance to Schistosoma mansoni. Immunological Investigation 21: 423–453.

Dessein AJ, Hillaire D, Elwali NE et al. (1999a) Severe hepatic fibrosis in Schistosoma mansoni infection is controlled by a major locus that is closely linked to the interferon‐gamma receptor gene. American Journal of Human Genetics 65: 709–721.

Dessein AJ, Marquet S, Henri S et al. (1999b) Infection and disease in human schistosomiasis mansoni are under distinct major gene control. Microbes Infection 1: 561–567.

Dunne DW, Butterworth AE, Fulford AJ et al. (1992a) Immunity after treatment of human schistosomiasis: association between IgE antibodies to adult worm antigens and resistance to reinfection. European Journal of Immunology 22: 1483–1494.

Dunne DW, Butterworth AE, Fulford AJ, Ouma JH and Sturrock RF (1992b) Human IgE responses to Schistosoma mansoni and resistance to reinfection. Memórias do Instituto Oswaldo Cruz 87: 99–103.

Graves PE, Kabesch M, Halonen M et al. (2000) A cluster of seven tightly linked polymorphisms in the IL‐13 gene is associated with total serum IgE levels in three populations of white children. Journal of Allergy and Clinical Immunology 105: 506–513.

Hagan P, Blumenthal UJ, Dunn D, Simpson AJ and Wilkins HA (1991) Human IgE, IgG4 and resistance to reinfection with Schistosoma haematobium. Nature 349: 243–245.

He H, Isnard A, Kouriba B et al. (2008) A STAT6 gene polymorphism is associated with high infection levels in urinary schistosomiasis. Genes and Immunity 9: 195–206.

de Jesus AR, Silva A, Santana LB et al. (2002) Clinical and immunologic evaluation of 31 patients with acute schistosomiasis mansoni. Journal of Infectious Disease 185: 98–105.

Joseph M, Auriault C, Capron A, Vorng H and Viens P (1983) A new function for platelets: IgE‐dependent killing of schistosomes. Nature 303: 810–812.

Kimani G, Chunge CN, Butterworth AE et al. (1991) Eosinophilia and eosinophil helminthotoxicity in patients treated for Schistosoma mansoni infections. Transactions of the Royal Society of Tropical Medicine and Hygiene 85: 489–492.

Kouriba B, Chevillard C, Bream JH et al. (2005) Analysis of the 5q31‐q33 locus shows an association between IL13‐1055C/T IL‐13‐591A/G polymorphisms and Schistosoma haematobium infections. Journal of Immunology 174: 6274–6281.

Marquet S, Abel L, Hillaire D and Dessein A (1998) Full results of the genome‐wide scan which localises a locus controlling the intensity of infection by Schistosoma mansoni on chromosome 5q31‐q33. European Journal of Human Genetics.

Marquet S, Abel L, Hillaire D et al. (1996) Genetic localization of a locus controlling the intensity of infection by Schistosoma mansoni on chromosome 5q31‐q33. Nature Genetics 14: 181–184.

Mohamed‐Ali Q, Elwali NE, Abdelhameed AA et al. (1999) Susceptibility to periportal (Symmers) fibrosis in human Schistosoma mansoni infections: evidence that intensity and duration of infection, gender, and inherited factors are critical in disease progression. Journal of Infectious Disease 180: 1298–1306.

Muller‐Myhsok B, Stelma FF, Guisse‐Sow F et al. (1997) Further evidence suggesting the presence of a locus, on human chromosome 5q31‐q33, influencing the intensity of infection with Schistosoma mansoni. American Journal of Human Genetics 61: 452–454.

Peisong G, Yamasaki A, Mao XQ et al. (2004) An asthma‐associated genetic variant of STAT6 predicts low burden of ascaris worm infestation. Genes and Immunity 5: 58–62.

van der Pouw Kraan TC, van Veen A, Boeije LC et al. (1999) An IL‐13 promoter polymorphism associated with increased risk of allergic asthma. Genes and Immunity 1: 61–65.

Rihet P, Demeure CE, Bourgois A, Prata A and Dessein AJ (1991) Evidence for an association between human resistance to Schistosoma mansoni and high anti‐larval IgE levels. European Journal of Immunology 21: 2679–2686.

Rihet P, Demeure CE, Dessein AJ and Bourgois A (1992) Strong serum inhibition of specific IgE correlated to competing IgG4, revealed by a new methodology in subjects from a S. mansoni endemic area. European Journal of Immunology 22: 2063–2070.

Rodriguez V, Piper K, Couissinier‐Paris P et al. (1999) Genetic control of Schistosome infections by SM1 locus of the 5q31‐q33 region is linked to differentition of type 2 helper T lymphocytes. Infection and Immunity 67.

Von Lichtenberg F (1962) Host response to eggs of S. mansoni I. Granuloma formation in the unsensitized laboratory mouse. American Journal of Pathology 41: 711–731.

Warren KS, Cook JA, Littell AS, Kagan IG and Jordan P (1973a) Immunologic diagnosis of schistosomiasis. II. Further studies on the sensitivity and specificity of delayed intradermal reactions. American Journal of Tropical Medicine and Hygiene 22: 199–204.

Warren KS, Kellermeyer RW, Jordan P et al. (1973b) Immunologic diagnosis of schistosomiasis. I. A controlled study of intradermal (immediate and delayed) and serologic tests in St. Lucians infected with Schistosoma mansoni and in uninfected St. Vincentians. American Journal of Tropical Medicine and Hygiene 22: 189–198.

Warren KS (1973) Regulation of the prevalence and intensity of schistosomiasis in man: immunology or ecology? Journal of Infectious Disease 127: 595–609.

Warren KS (1977) Modulation of immunopathology and disease in schistosomiasis. American Journal of Tropical Medicine and Hygiene 26: 113–119.

van der Werf MJ, de Vlas SJ, Brooker S et al. (2003) Quantification of clinical morbidity associated with schistosome infection in sub‐Saharan Africa. Acta Tropica 86: 125–139.

Zinn‐Justin A, Marquet S, Hillaire D, Dessein A and Abel L (2001) Genome search for additional human loci controlling infection levels by Schistosoma mansoni. American Journal of Tropical Medicine and Hygiene 65: 754–758.

Further Reading

Abel L and Dessein AJ (1997) The impact of host genetics on susceptibility to human infectious diseases. Current Opinion in Immunology 9: 509–516.

Arnaud V, Li J, Wang Y et al. (2008) Regulatory role of interleukin‐10 and interferon‐gamma in severe hepatic central and peripheral fibrosis in humans infected with Schistosoma japonicum. Journal of Infectious Disease 198: 418–426.

Bucheton B, Abel L, Kheir MM et al. (2003) Genetic control of visceral leishmaniasis in a Sudanese population: candidate gene testing indicates a linkage to the NRAMP1 region. Genes and Immunity 4: 104–109.

Campino S, Kwiatkowski D and Dessein A (2006) Mendelian and complex genetics of susceptibility and resistance to parasitic infections. Seminar in Immunology 18: 411–422.

Dessein AJ, Chevillard C, Marquet S et al. (2001) Genetics of parasitic infections. Drug Metabolism and Disposition 29: 484–488.

Dessein AJ, Parker WL, James SL and David JR (1981) IgE antibody and resistance to infection. I. Selective suppression of the IgE antibody response in rats diminishes the resistance and the eosinophil response to Trichinella spiralis infection. Journal of Experimental Medicine 153: 423–436.

Marquet S, Doumbo O, Cabantous S et al. (2008) A functional promoter variant in IL12B predisposes to cerebral malaria. Human Molecular Genetics 17: 2190–2195.

Ranque S, Safeukui I, Poudiougou B et al. (2005) Familial aggregation of cerebral malaria and severe malarial anemia. Journal of Infectious Disease 191: 799–804.

Rodrigues V Jr, Piper K, Couissinier‐Paris P et al. (1999) Genetic control of schistosome infections by the SM1 locus of the 5q31‐q33 region is linked to differentiation of type 2 helper T lymphocytes. Infection and Immunity 67: 4689–4692.

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Isnard, Amandine, He, Hongbin, Kouriba, Bourema, and Chevillard, Christophe(Mar 2010) Genetic Factors Involved in Human Susceptibility to Infection by Schistosomiasis. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0022394]