Collinet-Adler S, Ward HD, 2010. Cryptosporidiosis: environmental, therapeutic, and preventive challenges. Eur J Clin Microbiol Infect Dis 29: 927–935.
Leav BA, Mackay M, Ward HD, 2003. Cryptosporidium species: new insights and old challenges. Clin Infect Dis 36: 903–908.
Dillingham RA, Lima AA, Guerrant RL, 2002. Cryptosporidiosis: epidemiology and impact. Microbes Infect 4: 1059–1066.
Huang DB, White AC, 2006. An updated review on Cryptosporidium and Giardia. Gastroenterol Clin North Am 35: 291–314.
Snelling WJ, Xiao L, Ortega-Pierres G, Lowery CJ, Moore JE, Rao JR, Smyth S, Millar BC, Rooney PJ, Matsuda M, Kenny F, Xu J, Dooley JS, 2007. Cryptosporidiosis in developing countries. J Infect Dev Ctries 1: 242–256.
Borad A, Ward H, 2010. Human immune responses in cryptosporidiosis. Future Microbiol 5: 507–519.
O'Connor RM, Shaffie R, Kang G, Ward HD, 2011. Cryptosporidiosis in patients with HIV/AIDS. AIDS 25: 549–560.
Cabada MM, White AC Jr, 2010. Treatment of cryptosporidiosis: do we know what we think we know? Curr Opin Infect Dis 23: 494–499.
Abubakar I, Aliyu SH, Arumugam C, Usman NK, Hunter PR, 2007. Treatment of cryptosporidiosis in immunocompromised individuals: systematic review and meta-analysis. Br J Clin Pharmacol 63: 387–393.
de Graaf DC, Spano F, Petry F, Sagodira S, Bonnin A, 1999. Speculation on whether a vaccine against cryptosporidiosis is a reality or fantasy. Int J Parasitol 29: 1289–1306.
Perryman LE, Jasmer DP, Riggs MW, Bohnet SG, McGuire TC, Arrowood MJ, 1996. A cloned gene of Cryptosporidium parvum encodes neutralization-sensitive epitopes. Mol Biochem Parasitol 80: 137–147.
Enriquez FJ, Riggs MW, 1998. Role of immunoglobulin A monoclonal antibodies against P23 in controlling murine Cryptosporidium parvum infection. Infect Immun 66: 4469–4473.
Arrowood MJ, Sterling CR, Healey MC, 1991. Immunofluorescent microscopical visualization of trails left by gliding Cryptosporidium parvum sporozoites. J Parasitol 77: 315–317.
Arrowood MJ, Mead JR, Mahrt JL, Sterling CR, 1989. Effects of immune colostrum and orally administered antisporozoite monoclonal antibodies on the outcome of Cryptosporidium parvum infections in neonatal mice. Infect Immun 57: 2283–2288.
Riggs MW, Schaefer DA, Kapil SJ, Barley-Maloney L, Perryman LE, 2002. Efficacy of monoclonal antibodies against defined antigens for passive immunotherapy of chronic gastrointestinal cryptosporidiosis. Antimicrob Agents Chemother 46: 275–282.
Perryman LE, Kapil SJ, Jones ML, Hunt EL, 1999. Protection of calves against cryptosporidiosis with immune bovine colostrum induced by a Cryptosporidium parvum recombinant protein. Vaccine 17: 2142–2149.
Sturbaum GD, Schaefer DA, Jost BH, Sterling CR, Riggs MW, 2008. Antigenic differences within the Cryptosporidium hominis and Cryptosporidium parvum surface proteins P23 and GP900 defined by monoclonal antibody reactivity. Mol Biochem Parasitol 159: 138–141.
Schaefer DA, Auerbach-Dixon BA, Riggs MW, 2000. Characterization and formulation of multiple epitope-specific neutralizing monoclonal antibodies for passive immunization against cryptosporidiosis. Infect Immun 68: 2608–2616.
Wyatt CR, Perryman LE, 2000. Detection of mucosally delivered antibody to Cryptosporidium parvum p23 in infected calves. Ann N Y Acad Sci 916: 378–387.
Wyatt CR, Brackett EJ, Savidge J, 2001. Evidence for the emergence of a type-1-like immune response in intestinal mucosa of calves recovering from cryptosporidiosis. J Parasitol 87: 90–95.
Bonafonte MT, Smith LM, Mead JR, 2000. A 23-kDa recombinant antigen of Cryptosporidium parvum induces a cellular immune response on in vitro stimulated spleen and mesenteric lymph node cells from infected mice. Exp Parasitol 96: 32–41.
de Graaf DC, De Coninck H, De Clercq C, Peeters JE, 2002. Screening of the T- and B-cell antigenicity in neonatal calves of the His-tagged Cryptosporidium parvum antigens CP15, CP15/60, P23 and TRAP-C1. Folia Parasitol (Praha) 49: 319–322.
Ehigiator HN, Romagnoli P, Priest JW, Secor WE, Mead JR, 2007. Induction of murine immune responses by DNA encoding a 23-kDa antigen of Cryptosporidium parvum. Parasitol Res 101: 943–950.
Geriletu, Xu R, Jia H, Terkawi MA, Xuan X, Zhang H, 2011. Immunogenicity of orally administrated recombinant Lactobacillus casei Zhang expressing Cryptosporidium parvum surface adhesion protein P23 in mice. Curr Microbiol 62: 1573–1580.
Shirafuji H, Xuan X, Kimata I, Takashima Y, Fukumoto S, Otsuka H, Nagasawa H, Suzuki H, 2005. Expression of P23 of Cryptosporidium parvum in Toxoplasma gondii and evaluation of its protective effects. J Parasitol 91: 476–479.
Takashima Y, Xuan X, Kimata I, Iseki M, Kodama Y, Nagane N, Nagasawa H, Matsumoto Y, Mikami T, Otsuka H, 2003. Recombinant bovine herpes virus-1 expressing p23 protein of Cryptosporidium parvum induces neutralizing antibodies in rabbits. J Parasitol 89: 276–282.
Hong-Xuan H, Lei C, Cheng-Min W, Kai Z, Yi T, Xi-Ming Q, Ming-Xing D, 2005. Expression of the recombinant fusion protein CP15-23 of Cryptosporidium parvum and its protective test. J Nanosci Nanotechnol 5: 1292–1296.
Liu K, Zai D, Zhang D, Wei Q, Han G, Gao H, Huang B, 2010. Divalent Cp15-23 vaccine enhances immune responses and protection against Cryptosporidium parvum infection. Parasite Immunol 32: 335–344.
Wang C, Luo J, Amer S, Guo Y, Hu Y, Lu Y, Wang H, Duan M, He H, 2010. Multivalent DNA vaccine induces protective immune responses and enhanced resistance against Cryptosporidium parvum infection. Vaccine 29: 323–328.
Priest JW, Kwon JP, Moss DM, Roberts JM, Arrowood MJ, Dworkin MS, Juranek DD, Lammie PJ, 1999. Detection by enzyme immunoassay of serum immunoglobulin G antibodies that recognize specific Cryptosporidium parvum antigens. J Clin Microbiol 37: 1385–1392.
Priest JW, Bern C, Xiao L, Roberts JM, Kwon JP, Lescano AG, Checkley W, Cabrera L, Moss DM, Arrowood MJ, Sterling CR, Gilman RH, Lammie PJ, 2006. Longitudinal analysis of Cryptosporidium species-specific immunoglobulin G antibody responses in Peruvian children. Clin Vaccine Immunol 13: 123–131.
Moss DM, Bennett SN, Arrowood MJ, Wahlquist SP, Lammie PJ, 1998. Enzyme-linked immunoelectrotransfer blot analysis of a cryptosporidiosis outbreak on a United States Coast Guard cutter. Am J Trop Med Hyg 58: 110–118.
Frost FJ, Calderon RL, Muller TB, Curry M, Rodman JS, Moss DM, de la Cruz AA, 1998. A two-year follow-up survey of antibody to Cryptosporidium in Jackson County, Oregon following an outbreak of waterborne disease. Epidemiol Infect 121: 213–217.
Priest JW, Bern C, Roberts JM, Kwon JP, Lescano AG, Checkley W, Cabrera L, Moss DM, Arrowood MJ, Sterling CR, Gilman RH, Lammie PJ, 2005. Changes in serum immunoglobulin G levels as a marker for Cryptosporidium sp. infection in Peruvian children. J Clin Microbiol 43: 5298–5300.
Priest JW, Li A, Khan M, Arrowood MJ, Lammie PJ, Ong CS, Roberts JM, Isaac-Renton J, 2001. Enzyme immunoassay detection of antigen-specific immunoglobulin g antibodies in longitudinal serum samples from patients with cryptosporidiosis. Clin Diagn Lab Immunol 8: 415–423.
Sandhu SK, Priest JW, Lammie PJ, Hubbard A, Colford JM Jr, Eisenberg JN, 2006. The natural history of antibody responses to Cryptosporidium parasites in men at high risk of HIV infection. J Infect Dis 194: 1428–1437.
Moss DM, Chappell CL, Okhuysen PC, DuPont HL, Arrowood MJ, Hightower AW, Lammie PJ, 1998. The antibody response to 27-, 17-, and 15-kDa Cryptosporidium antigens following experimental infection in humans. J Infect Dis 178: 827–833.
Frost FJ, Tollestrup K, Craun GF, Fairley CK, Sinclair MI, Kunde TR, 2005. Protective immunity associated with a strong serological response to a Cryptosporidium-specific antigen group, in HIV-infected individuals. J Infect Dis 192: 618–621.
Smith LM, Priest JW, Lammie PJ, Mead JR, 2001. Human T and B cell immunoreactivity to a recombinant 23-kDa Cryptosporidium parvum antigen. J Parasitol 87: 704–707.
Jenkins MC, 2004. Present and future control of cryptosporidiosis in humans and animals. Expert Rev Vaccines 3: 669–671.
Xiao L, 2010. Molecular epidemiology of cryptosporidiosis: an update. Exp Parasitol 124: 80–89.
Wanyiri J, Ward H, 2006. Molecular basis of Cryptosporidium-host cell interactions: recent advances and future prospects. Future Microbiol 1: 201–208.
Allison G, Rogers K, Borad A, Karim M, Ahmed S, Kane A, Hibberd P, Naumova E, Calderwood S, Ryan E, Khan W, Ward H, 2011. Antibody responses to the immunodominant Cryptosporidium gp15 antigen and gp15 polymorphisms in a case-control study of cryptosporidiosis in children in Bangladesh. Am J Trop Med Hyg 85: 97–104.
O'Connor RM, Burns PB, Ha-Ngoc T, Scarpato K, Khan W, Kang G, Ward H, 2009. Polymorphic mucin antigens CpMuc4 and CpMuc5 are integral to Cryptosporidium parvum infection in vitro. Eukaryot Cell 8: 461–469.
Sturbaum GD, Jost BH, Sterling CR, 2003. Nucleotide changes within three Cryptosporidium parvum surface protein encoding genes differentiate genotype I from genotype II isolates. Mol Biochem Parasitol 128: 87–90.
Khan WA, Rogers KA, Karim MM, Ahmed S, Hibberd PL, Calderwood SB, Ryan ET, Ward HD, 2004. Cryptosporidiosis among Bangladeshi children with diarrhea: a prospective, matched, case-control study of clinical features, epidemiology and systemic antibody responses. Am J Trop Med Hyg 71: 412–419.
Hira KG, Mackay MR, Hempstead AD, Ahmed S, Karim MM, O'Connor RM, Hibberd PL, Calderwood SB, Ryan ET, Khan WA, Ward HD, 2011. Genetic diversity of Cryptosporidium spp. from Bangladeshi children. J Clin Microbiol 49: 2307–2310.
Ajjampur SS, Gladstone BP, Selvapandian D, Muliyil JP, Ward H, Kang G, 2007. Molecular and spatial epidemiology of cryptosporidiosis in children in a semiurban community in South India. J Clin Microbiol 45: 915–920.
Ajjampur SS, Liakath FB, Kannan A, Rajendran P, Sarkar R, Moses PD, Simon A, Agarwal I, Mathew A, O'Connor R, Ward H, Kang G, 2010. Multisite study of cryptosporidiosis in children with diarrhea in India. J Clin Microbiol 48: 2075–2081.
Dereeper A, Guignon V, Blanc G, Audic S, Buffet S, Chevenet F, Dufayard JF, Guindon S, Lefort V, Lescot M, Claverie JM, Gascuel O, 2008. Phylogeny.fr: robust phylogenetic analysis for the non-specialist. Nucleic Acids Res 36: W465-9.
Molloy SF, Smith HV, Kirwan P, Nichols RA, Asaolu SO, Connelly L, Holland CV, 2010. Identification of a high diversity of Cryptosporidium species genotypes and subtypes in a pediatric population in Nigeria. Am J Trop Med Hyg 82: 608–613.
Abrahamsen MS, Templeton TJ, Enomoto S, Abrahante JE, Zhu G, Lancto CA, Deng M, Liu C, Widmer G, Tzipori S, Buck GA, Xu P, Bankier AT, Dear PH, Konfortov BA, Spriggs HF, Iyer L, Anantharaman V, Aravind L, Kapur V, 2004. Complete genome sequence of the apicomplexan, Cryptosporidium parvum. Science 304: 441–445.
Xu P, Widmer G, Wang Y, Ozaki LS, Alves JM, Serrano MG, Puiu D, Manque P, Akiyoshi D, Mackey AJ, Pearson WR, Dear PH, Bankier AT, Peterson DL, Abrahamsen MS, Kapur V, Tzipori S, Buck GA, 2004. The genome of Cryptosporidium hominis. Nature 431: 1107–1112.
Wong PH, Ong CS, 2006. Molecular characterization of the Cryptosporidium cervine genotype. Parasitology 133: 693–700.
Hu Y, Mi R, Chen Z, Yu H, Yue C, 2010. Cloning and sequence comparison of P23 gene of different Cryptosporidium genotypes. Dongwu Yixue Jinzhan (Chinese) 31: 14–18.
Frost FJ, Muller TB, Calderon RL, Craun GF, 2004. Analysis of serological responses to Cryptosporidium antigen among NHANES III participants. Ann Epidemiol 14: 473–478.
Egorov A, Frost F, Muller T, Naumova E, Tereschenko A, Ford T, 2004. Serological evidence of Cryptosporidium infections in a Russian city and evaluation of risk factors for infections. Ann Epidemiol 14: 129–136.
Guk SM, Chai JY, Shin YO, Seo M, 2008. Antibody responses to Cryptosporidium antigen in HIV-positive patients in the Republic of Korea. Korean J Parasitol 46: 71–75.
Kozisek F, Craun GF, Cerovska L, Pumann P, Frost F, Muller T, 2008. Serological responses to Cryptosporidium-specific antigens in Czech populations with different water sources. Epidemiol Infect 136: 279–286.
Frost F, Craun G, Mihaly K, Gyorgy B, Calderon R, Muller T, 2005. Serological responses to Cryptosporidium antigens among women using riverbank-filtered water, conventionally filtered surface water and groundwater in Hungary. J Water Health 3: 77–82.
Frost FJ, Roberts M, Kunde TR, Craun G, Tollestrup K, Harter L, Muller T, 2005. How clean must our drinking water be: the importance of protective immunity. J Infect Dis 191: 809–814.
Riggs MW, 2002. Recent advances in cryptosporidiosis: the immune response. Microbes Infect 4: 1067–1080.
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Cryptosporidium is a major cause of diarrhea in children in developing countries. However, there is no vaccine available and little is known about immune responses to protective antigens. We investigated antibody responses to p23, a putative vaccine candidate, in children in Bangladesh with cryptosporidiosis and diarrhea (cases) and uninfected children with diarrhea (controls), and p23 gene polymorphisms in infecting species. Serum IgM, IgG, and IgA responses to p23 were significantly greater in cases than controls after three weeks of follow-up. Cases with acute diarrhea had significantly greater serum IgA and IgM responses than those with persistent diarrhea, which suggested an association with protection from prolonged disease. The p23 sequences were relatively conserved among infecting species and subtype families. Although most children were infected with Cryptosporidium hominis, there was a cross-reactive antibody response to C. parvum antigen. These results support further development of p23 as a vaccine candidate.
Financial support: This study was supported by an opportunity pool grant and in part by grants UO1 AI45508, U01 AI058935, and RO1 AI52786 from the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) and K24 AT003683 from the National Center for Complementary and Alternative Medicine, NIH. Anoli J. Borad was supported by T32 AI007438, and Geneve M. Allison was supported by T32 AI07389 from NIAID, NIH.
Authors' addresses: Anoli J. Borad, Division of Infectious Diseases, Department of Medicine, Yale School of Medicine, New Haven, CT, E-mail: anoli.borad@yale.edu. Geneve M. Allison, Anne V. Kane, Joy Moy, 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, joy.moy@gmail.com, and hward@tuftsmedicalcenter.org. David Wang, Department of Biomedical Engineering, Tufts University School of Engineering, Medford, MA, E-mail: david.e.wang@gmail.com. Sabeena Ahmed, Mohammad M. Karim, and Wasif A. Khan, Clinical Sciences Division, Centre for Health and Population Research, International Center for Diarrheal Disease Research, Bangladesh, 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. Sitara Swarna Rao Ajjampur and Gagandeep Kang, Department of Gastrointestinal Sciences, Christian Medical College, Vellore, India, E-mails: sitararao@cmcvellore.ac.in and gkang@cmcvellore.ac.in. 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. Elena Naumova, Tufts Initiative for the Forecasting and Modeling of Infectious Diseases, Tufts University School of Engineering, Medford, MA, E-mail: elena.naumova@tufts.edu.
Collinet-Adler S, Ward HD, 2010. Cryptosporidiosis: environmental, therapeutic, and preventive challenges. Eur J Clin Microbiol Infect Dis 29: 927–935.
Leav BA, Mackay M, Ward HD, 2003. Cryptosporidium species: new insights and old challenges. Clin Infect Dis 36: 903–908.
Dillingham RA, Lima AA, Guerrant RL, 2002. Cryptosporidiosis: epidemiology and impact. Microbes Infect 4: 1059–1066.
Huang DB, White AC, 2006. An updated review on Cryptosporidium and Giardia. Gastroenterol Clin North Am 35: 291–314.
Snelling WJ, Xiao L, Ortega-Pierres G, Lowery CJ, Moore JE, Rao JR, Smyth S, Millar BC, Rooney PJ, Matsuda M, Kenny F, Xu J, Dooley JS, 2007. Cryptosporidiosis in developing countries. J Infect Dev Ctries 1: 242–256.
Borad A, Ward H, 2010. Human immune responses in cryptosporidiosis. Future Microbiol 5: 507–519.
O'Connor RM, Shaffie R, Kang G, Ward HD, 2011. Cryptosporidiosis in patients with HIV/AIDS. AIDS 25: 549–560.
Cabada MM, White AC Jr, 2010. Treatment of cryptosporidiosis: do we know what we think we know? Curr Opin Infect Dis 23: 494–499.
Abubakar I, Aliyu SH, Arumugam C, Usman NK, Hunter PR, 2007. Treatment of cryptosporidiosis in immunocompromised individuals: systematic review and meta-analysis. Br J Clin Pharmacol 63: 387–393.
de Graaf DC, Spano F, Petry F, Sagodira S, Bonnin A, 1999. Speculation on whether a vaccine against cryptosporidiosis is a reality or fantasy. Int J Parasitol 29: 1289–1306.
Perryman LE, Jasmer DP, Riggs MW, Bohnet SG, McGuire TC, Arrowood MJ, 1996. A cloned gene of Cryptosporidium parvum encodes neutralization-sensitive epitopes. Mol Biochem Parasitol 80: 137–147.
Enriquez FJ, Riggs MW, 1998. Role of immunoglobulin A monoclonal antibodies against P23 in controlling murine Cryptosporidium parvum infection. Infect Immun 66: 4469–4473.
Arrowood MJ, Sterling CR, Healey MC, 1991. Immunofluorescent microscopical visualization of trails left by gliding Cryptosporidium parvum sporozoites. J Parasitol 77: 315–317.
Arrowood MJ, Mead JR, Mahrt JL, Sterling CR, 1989. Effects of immune colostrum and orally administered antisporozoite monoclonal antibodies on the outcome of Cryptosporidium parvum infections in neonatal mice. Infect Immun 57: 2283–2288.
Riggs MW, Schaefer DA, Kapil SJ, Barley-Maloney L, Perryman LE, 2002. Efficacy of monoclonal antibodies against defined antigens for passive immunotherapy of chronic gastrointestinal cryptosporidiosis. Antimicrob Agents Chemother 46: 275–282.
Perryman LE, Kapil SJ, Jones ML, Hunt EL, 1999. Protection of calves against cryptosporidiosis with immune bovine colostrum induced by a Cryptosporidium parvum recombinant protein. Vaccine 17: 2142–2149.
Sturbaum GD, Schaefer DA, Jost BH, Sterling CR, Riggs MW, 2008. Antigenic differences within the Cryptosporidium hominis and Cryptosporidium parvum surface proteins P23 and GP900 defined by monoclonal antibody reactivity. Mol Biochem Parasitol 159: 138–141.
Schaefer DA, Auerbach-Dixon BA, Riggs MW, 2000. Characterization and formulation of multiple epitope-specific neutralizing monoclonal antibodies for passive immunization against cryptosporidiosis. Infect Immun 68: 2608–2616.
Wyatt CR, Perryman LE, 2000. Detection of mucosally delivered antibody to Cryptosporidium parvum p23 in infected calves. Ann N Y Acad Sci 916: 378–387.
Wyatt CR, Brackett EJ, Savidge J, 2001. Evidence for the emergence of a type-1-like immune response in intestinal mucosa of calves recovering from cryptosporidiosis. J Parasitol 87: 90–95.
Bonafonte MT, Smith LM, Mead JR, 2000. A 23-kDa recombinant antigen of Cryptosporidium parvum induces a cellular immune response on in vitro stimulated spleen and mesenteric lymph node cells from infected mice. Exp Parasitol 96: 32–41.
de Graaf DC, De Coninck H, De Clercq C, Peeters JE, 2002. Screening of the T- and B-cell antigenicity in neonatal calves of the His-tagged Cryptosporidium parvum antigens CP15, CP15/60, P23 and TRAP-C1. Folia Parasitol (Praha) 49: 319–322.
Ehigiator HN, Romagnoli P, Priest JW, Secor WE, Mead JR, 2007. Induction of murine immune responses by DNA encoding a 23-kDa antigen of Cryptosporidium parvum. Parasitol Res 101: 943–950.
Geriletu, Xu R, Jia H, Terkawi MA, Xuan X, Zhang H, 2011. Immunogenicity of orally administrated recombinant Lactobacillus casei Zhang expressing Cryptosporidium parvum surface adhesion protein P23 in mice. Curr Microbiol 62: 1573–1580.
Shirafuji H, Xuan X, Kimata I, Takashima Y, Fukumoto S, Otsuka H, Nagasawa H, Suzuki H, 2005. Expression of P23 of Cryptosporidium parvum in Toxoplasma gondii and evaluation of its protective effects. J Parasitol 91: 476–479.
Takashima Y, Xuan X, Kimata I, Iseki M, Kodama Y, Nagane N, Nagasawa H, Matsumoto Y, Mikami T, Otsuka H, 2003. Recombinant bovine herpes virus-1 expressing p23 protein of Cryptosporidium parvum induces neutralizing antibodies in rabbits. J Parasitol 89: 276–282.
Hong-Xuan H, Lei C, Cheng-Min W, Kai Z, Yi T, Xi-Ming Q, Ming-Xing D, 2005. Expression of the recombinant fusion protein CP15-23 of Cryptosporidium parvum and its protective test. J Nanosci Nanotechnol 5: 1292–1296.
Liu K, Zai D, Zhang D, Wei Q, Han G, Gao H, Huang B, 2010. Divalent Cp15-23 vaccine enhances immune responses and protection against Cryptosporidium parvum infection. Parasite Immunol 32: 335–344.
Wang C, Luo J, Amer S, Guo Y, Hu Y, Lu Y, Wang H, Duan M, He H, 2010. Multivalent DNA vaccine induces protective immune responses and enhanced resistance against Cryptosporidium parvum infection. Vaccine 29: 323–328.
Priest JW, Kwon JP, Moss DM, Roberts JM, Arrowood MJ, Dworkin MS, Juranek DD, Lammie PJ, 1999. Detection by enzyme immunoassay of serum immunoglobulin G antibodies that recognize specific Cryptosporidium parvum antigens. J Clin Microbiol 37: 1385–1392.
Priest JW, Bern C, Xiao L, Roberts JM, Kwon JP, Lescano AG, Checkley W, Cabrera L, Moss DM, Arrowood MJ, Sterling CR, Gilman RH, Lammie PJ, 2006. Longitudinal analysis of Cryptosporidium species-specific immunoglobulin G antibody responses in Peruvian children. Clin Vaccine Immunol 13: 123–131.
Moss DM, Bennett SN, Arrowood MJ, Wahlquist SP, Lammie PJ, 1998. Enzyme-linked immunoelectrotransfer blot analysis of a cryptosporidiosis outbreak on a United States Coast Guard cutter. Am J Trop Med Hyg 58: 110–118.
Frost FJ, Calderon RL, Muller TB, Curry M, Rodman JS, Moss DM, de la Cruz AA, 1998. A two-year follow-up survey of antibody to Cryptosporidium in Jackson County, Oregon following an outbreak of waterborne disease. Epidemiol Infect 121: 213–217.
Priest JW, Bern C, Roberts JM, Kwon JP, Lescano AG, Checkley W, Cabrera L, Moss DM, Arrowood MJ, Sterling CR, Gilman RH, Lammie PJ, 2005. Changes in serum immunoglobulin G levels as a marker for Cryptosporidium sp. infection in Peruvian children. J Clin Microbiol 43: 5298–5300.
Priest JW, Li A, Khan M, Arrowood MJ, Lammie PJ, Ong CS, Roberts JM, Isaac-Renton J, 2001. Enzyme immunoassay detection of antigen-specific immunoglobulin g antibodies in longitudinal serum samples from patients with cryptosporidiosis. Clin Diagn Lab Immunol 8: 415–423.
Sandhu SK, Priest JW, Lammie PJ, Hubbard A, Colford JM Jr, Eisenberg JN, 2006. The natural history of antibody responses to Cryptosporidium parasites in men at high risk of HIV infection. J Infect Dis 194: 1428–1437.
Moss DM, Chappell CL, Okhuysen PC, DuPont HL, Arrowood MJ, Hightower AW, Lammie PJ, 1998. The antibody response to 27-, 17-, and 15-kDa Cryptosporidium antigens following experimental infection in humans. J Infect Dis 178: 827–833.
Frost FJ, Tollestrup K, Craun GF, Fairley CK, Sinclair MI, Kunde TR, 2005. Protective immunity associated with a strong serological response to a Cryptosporidium-specific antigen group, in HIV-infected individuals. J Infect Dis 192: 618–621.
Smith LM, Priest JW, Lammie PJ, Mead JR, 2001. Human T and B cell immunoreactivity to a recombinant 23-kDa Cryptosporidium parvum antigen. J Parasitol 87: 704–707.
Jenkins MC, 2004. Present and future control of cryptosporidiosis in humans and animals. Expert Rev Vaccines 3: 669–671.
Xiao L, 2010. Molecular epidemiology of cryptosporidiosis: an update. Exp Parasitol 124: 80–89.
Wanyiri J, Ward H, 2006. Molecular basis of Cryptosporidium-host cell interactions: recent advances and future prospects. Future Microbiol 1: 201–208.
Allison G, Rogers K, Borad A, Karim M, Ahmed S, Kane A, Hibberd P, Naumova E, Calderwood S, Ryan E, Khan W, Ward H, 2011. Antibody responses to the immunodominant Cryptosporidium gp15 antigen and gp15 polymorphisms in a case-control study of cryptosporidiosis in children in Bangladesh. Am J Trop Med Hyg 85: 97–104.
O'Connor RM, Burns PB, Ha-Ngoc T, Scarpato K, Khan W, Kang G, Ward H, 2009. Polymorphic mucin antigens CpMuc4 and CpMuc5 are integral to Cryptosporidium parvum infection in vitro. Eukaryot Cell 8: 461–469.
Sturbaum GD, Jost BH, Sterling CR, 2003. Nucleotide changes within three Cryptosporidium parvum surface protein encoding genes differentiate genotype I from genotype II isolates. Mol Biochem Parasitol 128: 87–90.
Khan WA, Rogers KA, Karim MM, Ahmed S, Hibberd PL, Calderwood SB, Ryan ET, Ward HD, 2004. Cryptosporidiosis among Bangladeshi children with diarrhea: a prospective, matched, case-control study of clinical features, epidemiology and systemic antibody responses. Am J Trop Med Hyg 71: 412–419.
Hira KG, Mackay MR, Hempstead AD, Ahmed S, Karim MM, O'Connor RM, Hibberd PL, Calderwood SB, Ryan ET, Khan WA, Ward HD, 2011. Genetic diversity of Cryptosporidium spp. from Bangladeshi children. J Clin Microbiol 49: 2307–2310.
Ajjampur SS, Gladstone BP, Selvapandian D, Muliyil JP, Ward H, Kang G, 2007. Molecular and spatial epidemiology of cryptosporidiosis in children in a semiurban community in South India. J Clin Microbiol 45: 915–920.
Ajjampur SS, Liakath FB, Kannan A, Rajendran P, Sarkar R, Moses PD, Simon A, Agarwal I, Mathew A, O'Connor R, Ward H, Kang G, 2010. Multisite study of cryptosporidiosis in children with diarrhea in India. J Clin Microbiol 48: 2075–2081.
Dereeper A, Guignon V, Blanc G, Audic S, Buffet S, Chevenet F, Dufayard JF, Guindon S, Lefort V, Lescot M, Claverie JM, Gascuel O, 2008. Phylogeny.fr: robust phylogenetic analysis for the non-specialist. Nucleic Acids Res 36: W465-9.
Molloy SF, Smith HV, Kirwan P, Nichols RA, Asaolu SO, Connelly L, Holland CV, 2010. Identification of a high diversity of Cryptosporidium species genotypes and subtypes in a pediatric population in Nigeria. Am J Trop Med Hyg 82: 608–613.
Abrahamsen MS, Templeton TJ, Enomoto S, Abrahante JE, Zhu G, Lancto CA, Deng M, Liu C, Widmer G, Tzipori S, Buck GA, Xu P, Bankier AT, Dear PH, Konfortov BA, Spriggs HF, Iyer L, Anantharaman V, Aravind L, Kapur V, 2004. Complete genome sequence of the apicomplexan, Cryptosporidium parvum. Science 304: 441–445.
Xu P, Widmer G, Wang Y, Ozaki LS, Alves JM, Serrano MG, Puiu D, Manque P, Akiyoshi D, Mackey AJ, Pearson WR, Dear PH, Bankier AT, Peterson DL, Abrahamsen MS, Kapur V, Tzipori S, Buck GA, 2004. The genome of Cryptosporidium hominis. Nature 431: 1107–1112.
Wong PH, Ong CS, 2006. Molecular characterization of the Cryptosporidium cervine genotype. Parasitology 133: 693–700.
Hu Y, Mi R, Chen Z, Yu H, Yue C, 2010. Cloning and sequence comparison of P23 gene of different Cryptosporidium genotypes. Dongwu Yixue Jinzhan (Chinese) 31: 14–18.
Frost FJ, Muller TB, Calderon RL, Craun GF, 2004. Analysis of serological responses to Cryptosporidium antigen among NHANES III participants. Ann Epidemiol 14: 473–478.
Egorov A, Frost F, Muller T, Naumova E, Tereschenko A, Ford T, 2004. Serological evidence of Cryptosporidium infections in a Russian city and evaluation of risk factors for infections. Ann Epidemiol 14: 129–136.
Guk SM, Chai JY, Shin YO, Seo M, 2008. Antibody responses to Cryptosporidium antigen in HIV-positive patients in the Republic of Korea. Korean J Parasitol 46: 71–75.
Kozisek F, Craun GF, Cerovska L, Pumann P, Frost F, Muller T, 2008. Serological responses to Cryptosporidium-specific antigens in Czech populations with different water sources. Epidemiol Infect 136: 279–286.
Frost F, Craun G, Mihaly K, Gyorgy B, Calderon R, Muller T, 2005. Serological responses to Cryptosporidium antigens among women using riverbank-filtered water, conventionally filtered surface water and groundwater in Hungary. J Water Health 3: 77–82.
Frost FJ, Roberts M, Kunde TR, Craun G, Tollestrup K, Harter L, Muller T, 2005. How clean must our drinking water be: the importance of protective immunity. J Infect Dis 191: 809–814.
Riggs MW, 2002. Recent advances in cryptosporidiosis: the immune response. Microbes Infect 4: 1067–1080.
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