Antibody Responses to the Immunodominant Cryptosporidium gp15 Antigen and gp15 Polymorphisms in a Case–Control Study of Cryptosporidiosis in Children in Bangladesh

Genève M. Allison Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center and Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, Massachusetts; Clinical Sciences Division, Centre for Health and Population Research, International Center for Diarrheal Disease Research, Dhaka, Bangladesh; Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts

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Kathleen A. Rogers Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center and Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, Massachusetts; Clinical Sciences Division, Centre for Health and Population Research, International Center for Diarrheal Disease Research, Dhaka, Bangladesh; Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts

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Anoli Borad Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center and Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, Massachusetts; Clinical Sciences Division, Centre for Health and Population Research, International Center for Diarrheal Disease Research, Dhaka, Bangladesh; Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts

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Sabeena Ahmed Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center and Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, Massachusetts; Clinical Sciences Division, Centre for Health and Population Research, International Center for Diarrheal Disease Research, Dhaka, Bangladesh; Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts

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Mohammad Mahbubul Karim Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center and Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, Massachusetts; Clinical Sciences Division, Centre for Health and Population Research, International Center for Diarrheal Disease Research, Dhaka, Bangladesh; Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts

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Anne V. Kane Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center and Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, Massachusetts; Clinical Sciences Division, Centre for Health and Population Research, International Center for Diarrheal Disease Research, Dhaka, Bangladesh; Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts

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Patricia L. Hibberd Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center and Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, Massachusetts; Clinical Sciences Division, Centre for Health and Population Research, International Center for Diarrheal Disease Research, Dhaka, Bangladesh; Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts

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Elena N. Naumova Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center and Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, Massachusetts; Clinical Sciences Division, Centre for Health and Population Research, International Center for Diarrheal Disease Research, Dhaka, Bangladesh; Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts

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Stephen B. Calderwood Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center and Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, Massachusetts; Clinical Sciences Division, Centre for Health and Population Research, International Center for Diarrheal Disease Research, Dhaka, Bangladesh; Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts

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Edward T. Ryan Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center and Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, Massachusetts; Clinical Sciences Division, Centre for Health and Population Research, International Center for Diarrheal Disease Research, Dhaka, Bangladesh; Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts

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Wasif A. Khan Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center and Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, Massachusetts; Clinical Sciences Division, Centre for Health and Population Research, International Center for Diarrheal Disease Research, Dhaka, Bangladesh; Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts

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Honorine D. Ward Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center and Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, Massachusetts; Clinical Sciences Division, Centre for Health and Population Research, International Center for Diarrheal Disease Research, Dhaka, Bangladesh; Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts

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Although Cryptospridium hominis is the dominant Cryptosporidium species infecting humans, immune responses to cognate antigens in C. hominis-infected persons have not been reported. We investigated antibody responses to the immunodominant gp15 antigen from C. hominis and C. parvum, in C. hominis-infected Bangladeshi children less than five years of age with diarrhea (cases) and uninfected children with diarrhea (controls). We also investigated polymorphisms in the C. hominis gp15 sequence from cases. Serum IgG responses to gp15 from both species were significantly greater in cases than controls. In spite of polymorphisms in the gp15 sequence, there was a significant correlation between antibody levels to gp15 from both species, indicating cross-reactivity to conserved epitopes. Cases with acute diarrhea had a significantly greater serum IgA response to gp15 compared with those with persistent diarrhea, suggesting that this response may be associated with protection from prolonged disease. These findings support further investigation of gp15 as a vaccine candidate.

Author Notes

*Address correspondence to Honorine D. Ward, Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center, Box 041, 800 Washington Street, Boston, MA 02111. E-mail: hward@tuftsmedicalcenter.org
†These authors contributed equally to this article.

Financial support: This study was supported by an opportunity pool grant and in part by grants UO1 AI45508, U01 AI058935, and RO1 AI52786, all from the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH) and K24 AT003683 from the National Center for Complementary and Alternative Medicine, NIH. Genève M. Allison and Kathleen Rogers were supported by T32 AI07389, and Anoli Borad was supported by T32 AI007438 from the National Institute of Allergy and Infectious Diseases, NIH.

Authors' addresses: Genève M. Allison, Anne V. Kane, and Honorine D. Ward, Division of Geographic Medicine and Infectious Diseases, Department of Medicine, Tufts Medical Center, Boston, MA, E-mails: gallison@tuftsmedicalcenter.org, akane@tuftsmedicalcenter.org, and hward@tuftsmedicalcenter.org. Kathleen A. Rogers, University of North Carolina Center for AIDS Research, Chapel Hill, NC, E-mail: rogerska@med.unc.edu. Anoli Borad, Division of Infectious Diseases, Department of Medicine, Yale School of Medicine, New Haven, CT, E-mail: anoli.borad@yale.edu. Sabeena Ahmed, Mohammad Mahbubul Karim, and Wasif A. Khan, Clinical Sciences Division, Centre for Health and Population Research, International Center for Diarrheal Disease Research, Dhaka, Bangladesh, E-mails: mahbubul@icddrb.org, sabeena@hotmail.com, and wakhan@icddrb.org. Patricia L. Hibberd, Division of Global Health, Department of Pediatrics, Massachusetts General Hospital, Boston, MA, E-mail: phibberd@partners.org. Elena N. Naumova, Tufts Initiative for the Forecasting and Modeling of Infectious Diseases, Tufts University School of Engineering, Medford, MA, E-mail: elena.naumova@tufts.edu. Stephen B. Calderwood and Edward T. Ryan, Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, E-mails: scalderwood@partners.org and etryan@partners.org.

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