Genetic Consequences of Mass Human Chemotherapy for Schistosoma mansoni: Population Structure Pre- and Post-Praziquantel Treatment in Tanzania

Alice J. Norton Department of Infectious Disease Epidemiology, Imperial College, Faculty of Medicine, London, United Kingdom; Department of Zoology, The Natural History Museum, London, United Kingdom; Mwanza Research Centre, National Institute for Medical Research, Mwanza, Tanzania

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Charlotte M. Gower Department of Infectious Disease Epidemiology, Imperial College, Faculty of Medicine, London, United Kingdom; Department of Zoology, The Natural History Museum, London, United Kingdom; Mwanza Research Centre, National Institute for Medical Research, Mwanza, Tanzania

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Poppy H. L. Lamberton Department of Infectious Disease Epidemiology, Imperial College, Faculty of Medicine, London, United Kingdom; Department of Zoology, The Natural History Museum, London, United Kingdom; Mwanza Research Centre, National Institute for Medical Research, Mwanza, Tanzania

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Bonnie L. Webster Department of Infectious Disease Epidemiology, Imperial College, Faculty of Medicine, London, United Kingdom; Department of Zoology, The Natural History Museum, London, United Kingdom; Mwanza Research Centre, National Institute for Medical Research, Mwanza, Tanzania

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Nicholas J. S. Lwambo Department of Infectious Disease Epidemiology, Imperial College, Faculty of Medicine, London, United Kingdom; Department of Zoology, The Natural History Museum, London, United Kingdom; Mwanza Research Centre, National Institute for Medical Research, Mwanza, Tanzania

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Lynsey Blair Department of Infectious Disease Epidemiology, Imperial College, Faculty of Medicine, London, United Kingdom; Department of Zoology, The Natural History Museum, London, United Kingdom; Mwanza Research Centre, National Institute for Medical Research, Mwanza, Tanzania

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Alan Fenwick Department of Infectious Disease Epidemiology, Imperial College, Faculty of Medicine, London, United Kingdom; Department of Zoology, The Natural History Museum, London, United Kingdom; Mwanza Research Centre, National Institute for Medical Research, Mwanza, Tanzania

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Joanne P. Webster Department of Infectious Disease Epidemiology, Imperial College, Faculty of Medicine, London, United Kingdom; Department of Zoology, The Natural History Museum, London, United Kingdom; Mwanza Research Centre, National Institute for Medical Research, Mwanza, Tanzania

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Recent shifts in global health policy have led to the implementation of mass drug administration (MDA) for neglected tropical diseases. Here we show how population genetic analyses can provide vital insights into the impact of such MDA on endemic parasite populations. We show that even a single round of MDA produced a genetic bottleneck with reductions in a range of measures of genetic diversity of Schistosoma mansoni. Phylogenetic analyses and indices of population differentiation indicated that schistosomes collected in the same schools in different years were more dissimilar than those from different schools collected within either of the study's 2 years, in addition to distinguishing re-infection from non-clearance (that might indicate putatively resistant parasites) from within those children infected at both baseline and follow-up. Such unique results illustrate the importance of genetic monitoring and examination of long lived multi-cellular parasites such as these under novel or increased chemotherapeutic selective pressures.

Author Notes

*Address correspondence to Joanne P. Webster, Department of Infectious Disease Epidemiology, Imperial College, Faculty of Medicine, London, W2 1PG, United Kingdom. E-mail: joanne.webster@imperial.ac.uk

Financial support: Field work, analyses and/or authors were supported by grants from the Bill and Melinda Gates Foundation, the European Union (CONTRAST EU/INCO.Dev contract no.: 032203), the Wellcome Trust (grant number WT063774), and the Royal Society (JPW as a Royal Society University Research Fellow, Charlotte Gower as a Dorothy Hodgkin Fellow).

Authors' addresses: Alice J. Norton, Charlotte M. Gower, Poppy H. L. Lamberton, Lynsey Blair, Alan Fenwick, and Joanne P. Webster, Department of Infectious Disease Epidemiology, Imperial College, Faculty of Medicine, London, UK, E-mails: a.norton@wellcome.ac.uk, charlotte.gower@imperial.ac.uk, poppy.lamberton@imperial.ac.uk, lynsey.blair@imperial.ac.uk, alan.fenwick@imperial.ac.uk, and joanne.webster@imperial.ac.uk. Alice J. Norton current address: The Wellcome Trust, London, UK. Bonnie L. Webster, Department of Zoology, The Natural History Museum, London, UK, E-mail: b.webster@nhm.ac.uk. Nicholas J. S. Lwambo, Mwanza Research Centre, National Institute for Medical Research, Mwanza, Tanzania, E-mail: lwambon@live.co.uk.

  • 1.

    Hotez P, Raff S, Fenwick A, Richards F, Molyneux D, 2007. Recent progress in integrated neglected tropical disease control. Trends Parasitol 23: 511–514.

  • 2.

    Fenwick A, Webster JP, 2006. Schistosomiasis: challenges for control, treatment and drug resistance. Curr Opin Infect Dis 19: 577–582.

  • 3.

    Webster JP, Gower CM, Norton AJ, 2008. Application of evolutionary concepts to predicting and evaluating the impact of mass-chemotherapy schistosomiasis control programmes. Evolutionary Applications 1: 66–83.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    King CH, Dickman K, Tisch DJ, 2005. Reassessment of the cost of chronic helmintic infection: a meta-analysis of disability-related outcomes in endemic schistosomiasis. Lancet 365: 1561–1569.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Steinmann P, Keiser J, Bos R, Tanner M, Utzinger J, 2006. Schistosomiasis and water resources development: systematic review, meta-analysis and estimates of people at risk. Lancet Infect Dis 6: 411–425.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Rollinson D, Kaukas A, Johnston DA, Simpson AJ, Tanaka M, 1997. Some molecular insights into schistosome evolution. Int J Parasitol 27: 11–28.

  • 7.

    Agola LE, Mburu DN, DeJong RJ, Mungai BN, Muluvi GM, Njagi EN, Loker ES, Mkoji GM, 2006. Microsatellite typing reveals strong genetic structure of Schistosoma mansoni from localities in Kenya. Infect Genet Evol 6: 484–490.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Barral V, Morand S, Pointier JP, Theron A, 1996. Distribution of schistosome genetic diversity within naturally infected Rattus rattus detected by RAPD markers. Parasitology 113: 511–517.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Curtis J, Minchella D, 2000. Schistosome population genetic structure: when clumping worms is not just splitting hairs. Parasitol Today 16: 68–71.

  • 10.

    Rollinson D, Webster JP, Nyakanna S, Stothard AJ Jr, 2009. Genetic diversity of schistosomes and snails: implications for control. Parasitology 136: 1801–1811.

  • 11.

    Stothard JR, Webster BL, Weber T, Nyakaana S, Webster JP, Kazibwe F, Kabatereine NB, Rollinson D, 2009. Molecular epidemiology of Schistosoma mansoni in Uganda: DNA barcoding reveals substantive genetic diversity within Lake Albert and Lake Victoria populations. Parasitology 136: 1813–1824.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Colley DG, LoVerde PT, Savioli L, 2001. Infectious disease. Medical helminthology in the 21st century. Science 293: 1437–1438.

  • 13.

    Fenwick A, Webster JP, Bosque-Oliva E, Blair L, Fleming FM, Zhang Y, Garba A, Stothard JR, Gabrielli AF, Clements AC, Kabatereine NB, Toure S, Dembele R, Nyandindi U, Mwansa J, Koukounari A, 2009. The Schistosomiasis Control Initiative (SCI): rational, development and implementation from 2002–2008. Parasitology 136: 1719–1730.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    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.

  • 15.

    Doenhoff MJ, Pica-Mattoccia L, 2006. Praziquantel for the treatment of schistosomiasis: its use for control in areas with endemic disease and prospects for drug resistance. Expert Rev Anti Infect Ther 4: 199–210.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Danso-Appiah A, De Vlas SJ, 2002. Interpreting low praziquantel cure rates of Schistosoma mansoni infections in Senegal. Trends Parasitol 18: 125–129.

  • 17.

    Alonso D, Munoz J, Gascon J, Valls ME, Corachan M, 2006. Failure of standard treatment with praziquantel in two returned travelers with Schistosoma haematobium infection. Am J Trop Med Hyg 74: 342–344.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18.

    Gower CM, Shrivastava J, Lamberton PH, Rollinson D, Emory A, Webster BL, Kabatereine NB, Webster JP, 2007. Development and application of an ethical and epidemiologically appropriate assay for the multi-locus microsatellite analysis of Schistosoma mansoni. Parasitology 134: 523–536.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Shrivastava J, Gower CM, Balolong E Jr, Wang TP, Qian BZ, Webster JP, 2005. Population genetics of multi-host parasites—the case for molecular epidemiological studies of Schistosoma japonicum using naturally sampled larval stages. Parasitology 131: 617–626.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    Wang T-P, Shrivastava J, Johansen MV, Zhang ZK, Webster JP, 2006. Does multiple hosts mean multiple parasites? Population genetic structure of Schistosoma japonicum between definitive host species. Int J Parasitol 36: 1317–1325.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    Curtis J, Sorensen RE, Minchella DJ, 2002. Schistosome genetic diversity: the implications of population structure as detected with microsatellite markers. Parasitology 125: S51–S59.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22.

    Durand P, Sire C, Theron A, 2000. Isolation of microsatellite markers in the digenetic trematode Schistosoma mansoni from Guadeloupe Island. Mol Ecol 9: 997–998.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23.

    Blair L, Webster JP, Barker GC, 2001. Isolation and characterization of polymorphic microsatellite markers in Schistosoma mansoni from Africa. Mol Ecol Notes 1: 93–95.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24.

    Lui K, Muse S, 2005. PowerMarker: integrated analysis environment for genetic marker data. Bioinformatics 21: 2128–2129.

  • 25.

    Goudet J, 1995. Fstat version 1.2: a computer program to calculate F-statistics. J Hered 86: 485–486.

  • 26.

    Cavalli-Sforza LL, Edwards AW, 1967. Phylogenetic analysis. Models and estimation procedures. Am J Hum Genet 19: 233–257.

  • 27.

    Langella O, 1999. Populations 1.2.28 genetic software. CNRS CNRS UPR9034. Available at: www.cnrs-gif.fr/pge.

  • 28.

    Lewis PO, Zaykin D, 2001. Genetic data analysis: computer program for the analysis of allelic data, version 1.1.

  • 29.

    Ardelli BF, Guerriero SB, Pritchard RK, 2006. Ivermectin imposes selection pressure on P-glycoprotein from Onchocerca volvulus: linkage disequilibrium and genotype diversity. Parasitology 132: 370–386.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30.

    Correa-Oliveira R, Caldas IR, Martins-Filho OA, Queiroz CC, Lambertucci JR, Cunha-Melo JR, Silveira AS, Prata A, Wilson A, Gazzinelli G, 2000. Analysis of the effects of treatment of human Schistosoma mansoni infection on the immune response of patients in endemic areas. Acta Trop 77: 141–146.

    • PubMed
    • Search Google Scholar
    • Export Citation
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