O'Connor RM, Shaffie R, Kang G, Ward HD, 2011. Cryptosporidiosis in patients with HIV/AIDS. AIDS 25: 549–560.
Abubakar I, Aliyu SH, Arumugam C, Hunter PR, Usman NK, 2007. Prevention and treatment of cryptosporidiosis in immunocompromised patients. Cochrane Database Syst Rev CD004932.
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.
UNAIDS, 2012. The Kenya AIDS Epidemic, Update 2011. Geneva Joint Nations Programme on HIV/AIDS. Available at: http://www.unaids.org/en/dataanalysis/knowyourresponse/countryprogressreports/2012countries/ce_KE_Narrative_Report.pdf. Accessed October 24, 2013.
NACC, 2009. Kenya Aids Indicator Survey 2007 (KAIS 2007) Final Report.
Mwachari C, Batchelor BI, Paul J, Waiyaki PG, Gilks CF, 1998. Chronic diarrhea among HIV-infected adult patients in Nairobi, Kenya. J Infect 37: 48–53.
Mwachari CW, Meier AS, Muyodi J, Gatei W, Waiyaki P, Cohen CR, 2003. Chronic diarrhea in HIV-1-infected adults in Nairobi, Kenya: evaluation of risk factors and the WHO treatment algorithm. AIDS 17: 2124–2126.
Batchelor BI, Kimari JN, Brindle RJ, 1996. Microbiology of HIV associated bacteremia and diarrhea in adults from Nairobi, Kenya. Epidemiol Infect 117: 139–144.
Estambale BB, Bwibo CR, Kang'ethe S, Chitayi PM, 1989. The occurrence of Cryptosporidium oocysts in fecal samples submitted for routine examination at Kenyatta National Hospital. East Afr Med J 66: 792–795.
Gatei W, Wamae CN, Mbae C, Waruru A, Mulinge E, Waithera T, Gatika SM, Kamwati SK, Revathi G, Hart CA, 2006. Cryptosporidiosis: prevalence, genotype analysis, and symptoms associated with infections in children in Kenya. Am J Trop Med Hyg 75: 78–82.
Mirza NB, Bhatt KM, Bhatt SM, Kanja C, 1994. Cryptosporidiosis in HIV positive patients at Kenyatta National Hospital, Nairobi, Kenya. East Afr Med J 71: 334–335.
Borad A, Ward H, 2010. Human immune responses in cryptosporidiosis. Future Microbiol 5: 507–519.
Pozio E, Rezza G, Boschini A, Pezzotti P, Tamburrini A, Rossi P, Di Fine M, Smacchia C, Schiesari A, Gattei E, Zucconi R, Ballarini P, 1997. Clinical cryptosporidiosis and human immunodeficiency virus (HIV)-induced immunosuppression: findings from a longitudinal study of HIV-positive and HIV-negative former injection drug users. J Infect Dis 176: 969–975.
Schmidt W, Wahnschaffe U, Schafer M, Zippel T, Arvand M, Meyerhans A, Riecken EO, Ullrich R, 2001. Rapid increase of mucosal CD4 T cells followed by clearance of intestinal cryptosporidiosis in an AIDS patient receiving highly active antiretroviral therapy. Gastroenterology 120: 984–987.
Leitch GJ, He Q, 2012. Cryptosporidiosis-an overview. J Biomed Res 25: 1–16.
Riggs MW, 2002. Recent advances in cryptosporidiosis: the immune response. Microbes Infect 4: 1067–1080.
Chappell CL, Okhuysen PC, Sterling CR, Wang C, Jakubowski W, Dupont HL, 1999. Infectivity of Cryptosporidium parvum in healthy adults with pre-existing anti-C. parvum serum immunoglobulin G. Am J Trop Med Hyg 60: 157–164.
Frost FJ, Muller T, Craun GF, Lockwood WB, Calderon RL, 2002. Serological evidence of endemic waterborne Cryptosporidium infections. Ann Epidemiol 12: 222–227.
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.
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.
Wanyiri J, Ward H, 2006. Molecular basis of Cryptosporidium-host cell interactions: recent advances and future prospects. Future Microbiol 1: 201–208.
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.
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.
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, 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.
Wanyiri JW, Kanyi H, Maina S, Wang DE, Ngugi P, O'Connor R, Kamau T, Waithera T, Kimani G, Wamae CN, Mwamburi M, Ward HD, 2013. Infectious diarrhea in antiretroviral therapy-naive HIV/AIDS patients in Kenya. Trans R Soc Trop Med Hyg 107: 631–638.
Xiao L, Escalante L, Yang C, Sulaiman I, Escalante AA, Montali RJ, Fayer R, Lal AA, 1999. Phylogenetic analysis of Cryptosporidium parasites based on the small-subunit rRNA gene locus. Appl Environ Microbiol 65: 1578–1583.
Vidal M, Kruger E, Duran C, Lagos R, Levine M, Prado V, Toro C, Vidal R, 2005. Single multiplex PCR assay to identify simultaneously the six categories of diarrheagenic Escherichia coli associated with enteric infections. J Clin Microbiol 43: 5362–5365.
Xiao L, 2010. Molecular epidemiology of cryptosporidiosis: an update. Exp Parasitol 124: 80–89.
Cohen S, Dalle F, Gallay A, Di Palma M, Bonnin A, Ward HD, 2006. Identification of Cpgp40/15 Type Ib as the predominant allele in isolates of Cryptosporidium spp. from a waterborne outbreak of gastroenteritis in South Burgundy, France. J Clin Microbiol 44: 589–591.
Cevallos AM, Zhang X, Waldor MK, Jaison S, Zhou X, Tzipori S, Neutra MR, Ward HD, 2000. Molecular cloning and expression of a gene encoding Cryptosporidium parvum glycoproteins gp40 and gp15. Infect Immun 68: 4108–4116.
Preidis GA, Wang HC, Lewis DE, Castellanos-Gonzalez A, Rogers KA, Graviss EA, Ward HD, White AC Jr, 2007. Seropositive human subjects produce interferon gamma after stimulation with recombinant Cryptosporidium hominis gp15. Am J Trop Med Hyg 77: 583–585.
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.
Ajjampur SS, Sarkar R, Allison G, Banda K, Kane A, Muliyil J, Naumova E, Ward H, Kang G, 2011. Serum IgG response to Cryptosporidium immunodominant antigen gp15 and polymorphic antigen gp40 in children with cryptosporidiosis in South India. Clin Vaccine Immunol 18: 633–639.
Allison GM, Rogers KA, Borad A, Ahmed S, Karim MM, Kane AV, Hibberd PL, Naumova EN, Calderwood SB, Ryan ET, Khan WA, Ward HD, 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.
Borad AJ, Allison GM, Wang D, Ahmed S, Karim MM, Kane AV, Moy J, Hibberd PL, Ajjampur SS, Kang G, Calderwood SB, Ryan ET, Naumova E, Khan WA, Ward HD, 2012. Systemic antibody responses to the immunodominant p23 antigen and p23 polymorphisms in children with cryptosporidiosis in Bangladesh. Am J Trop Med Hyg 86: 214–222.
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We investigated the epidemiological and clinical features of cryptosporidiosis, the molecular characteristics of infecting species and serum antibody responses to three Cryptosporidium-specific antigens in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients in Kenya. Cryptosporidium was the most prevalent enteric pathogen and was identified in 56 of 164 (34%) of HIV/AIDS patients, including 25 of 70 (36%) with diarrhea and 31 of 94 (33%) without diarrhea. Diarrhea in patients exclusively infected with Cryptosporidium was significantly associated with the number of children per household, contact with animals, and water treatment. Cryptosporidium hominis was the most prevalent species and the most prevalent subtype family was Ib. Patients without diarrhea had significantly higher serum IgG levels to Chgp15, Chgp40 and Cp23, and higher fecal IgA levels to Chgp15 and Chgp40 than those with diarrhea suggesting that antibody responses to these antigens may be associated with protection from diarrhea and supporting further investigation of these antigens as vaccine candidates.
Financial support: This study was supported by the NIH Fogarty International Clinical Research Fellows Program (R24 TW007988) to JWW and in part by NIH R01 AI072222 and R01 AI52786 to HDW and the Tufts-Brown Center for AIDS Research 5P30AI042853.
Authors' addresses: Jane W. Wanyiri, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, E-mail: jwanyir1@jhmi.edu. Henry Kanyi, Eastern and Southern Africa Centre of International Parasite Control (ESACIPAC), Kenya Medical Research Institute, Nairobi, Kenya, E-mail: hkanyi@kemri.org. Samuel Maina, International Emerging Infections Program, KEMRI/CDC Research and Public Health Collaboration, Kisumu, Kenya, E-mail: Smaina@ke.cdc.gov. David E. Wang, Roberta O'Connor, and Honorine D. Ward, Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center, Boston, MA, E-mails: d.wang@alumni.tufts.edu, Roconnor@tuftsmedicalcenter.org, and hward@tuftsmedicalcenter.org. Aaron Steen, Geisel School of Medicine at Dartmouth, White River Junction, VT, E-mail: Aaron.j.steen.dm@dartmouth.edu. Paul Ngugi, Comprehensive Care Center, Kenyatta National Hospital, Nairobi, Kenya, E-mail: ngugi.paul7@gmail.com. Timothy Kamau and Kimani Gachuhi, Center for Biotechnology, Research and Development, Kenya Medical Research Institute, Nairobi, Kenya, E-mails: Tkamau@kemri.org and Kgachuhi@kemri.org. Tabitha Waithera and Claire N. Wamae, Centre for Microbiology Research, Kenya Medical Research Institute, Nairobi, Kenya, E-mails: tiringu@kemri.org and nwamae@kemri.org. Mkaya Mwamburi, Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA, E-mail: Mkaya.Mwamburi@tufts.edu.
O'Connor RM, Shaffie R, Kang G, Ward HD, 2011. Cryptosporidiosis in patients with HIV/AIDS. AIDS 25: 549–560.
Abubakar I, Aliyu SH, Arumugam C, Hunter PR, Usman NK, 2007. Prevention and treatment of cryptosporidiosis in immunocompromised patients. Cochrane Database Syst Rev CD004932.
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.
UNAIDS, 2012. The Kenya AIDS Epidemic, Update 2011. Geneva Joint Nations Programme on HIV/AIDS. Available at: http://www.unaids.org/en/dataanalysis/knowyourresponse/countryprogressreports/2012countries/ce_KE_Narrative_Report.pdf. Accessed October 24, 2013.
NACC, 2009. Kenya Aids Indicator Survey 2007 (KAIS 2007) Final Report.
Mwachari C, Batchelor BI, Paul J, Waiyaki PG, Gilks CF, 1998. Chronic diarrhea among HIV-infected adult patients in Nairobi, Kenya. J Infect 37: 48–53.
Mwachari CW, Meier AS, Muyodi J, Gatei W, Waiyaki P, Cohen CR, 2003. Chronic diarrhea in HIV-1-infected adults in Nairobi, Kenya: evaluation of risk factors and the WHO treatment algorithm. AIDS 17: 2124–2126.
Batchelor BI, Kimari JN, Brindle RJ, 1996. Microbiology of HIV associated bacteremia and diarrhea in adults from Nairobi, Kenya. Epidemiol Infect 117: 139–144.
Estambale BB, Bwibo CR, Kang'ethe S, Chitayi PM, 1989. The occurrence of Cryptosporidium oocysts in fecal samples submitted for routine examination at Kenyatta National Hospital. East Afr Med J 66: 792–795.
Gatei W, Wamae CN, Mbae C, Waruru A, Mulinge E, Waithera T, Gatika SM, Kamwati SK, Revathi G, Hart CA, 2006. Cryptosporidiosis: prevalence, genotype analysis, and symptoms associated with infections in children in Kenya. Am J Trop Med Hyg 75: 78–82.
Mirza NB, Bhatt KM, Bhatt SM, Kanja C, 1994. Cryptosporidiosis in HIV positive patients at Kenyatta National Hospital, Nairobi, Kenya. East Afr Med J 71: 334–335.
Borad A, Ward H, 2010. Human immune responses in cryptosporidiosis. Future Microbiol 5: 507–519.
Pozio E, Rezza G, Boschini A, Pezzotti P, Tamburrini A, Rossi P, Di Fine M, Smacchia C, Schiesari A, Gattei E, Zucconi R, Ballarini P, 1997. Clinical cryptosporidiosis and human immunodeficiency virus (HIV)-induced immunosuppression: findings from a longitudinal study of HIV-positive and HIV-negative former injection drug users. J Infect Dis 176: 969–975.
Schmidt W, Wahnschaffe U, Schafer M, Zippel T, Arvand M, Meyerhans A, Riecken EO, Ullrich R, 2001. Rapid increase of mucosal CD4 T cells followed by clearance of intestinal cryptosporidiosis in an AIDS patient receiving highly active antiretroviral therapy. Gastroenterology 120: 984–987.
Leitch GJ, He Q, 2012. Cryptosporidiosis-an overview. J Biomed Res 25: 1–16.
Riggs MW, 2002. Recent advances in cryptosporidiosis: the immune response. Microbes Infect 4: 1067–1080.
Chappell CL, Okhuysen PC, Sterling CR, Wang C, Jakubowski W, Dupont HL, 1999. Infectivity of Cryptosporidium parvum in healthy adults with pre-existing anti-C. parvum serum immunoglobulin G. Am J Trop Med Hyg 60: 157–164.
Frost FJ, Muller T, Craun GF, Lockwood WB, Calderon RL, 2002. Serological evidence of endemic waterborne Cryptosporidium infections. Ann Epidemiol 12: 222–227.
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.
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.
Wanyiri J, Ward H, 2006. Molecular basis of Cryptosporidium-host cell interactions: recent advances and future prospects. Future Microbiol 1: 201–208.
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.
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.
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, 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.
Wanyiri JW, Kanyi H, Maina S, Wang DE, Ngugi P, O'Connor R, Kamau T, Waithera T, Kimani G, Wamae CN, Mwamburi M, Ward HD, 2013. Infectious diarrhea in antiretroviral therapy-naive HIV/AIDS patients in Kenya. Trans R Soc Trop Med Hyg 107: 631–638.
Xiao L, Escalante L, Yang C, Sulaiman I, Escalante AA, Montali RJ, Fayer R, Lal AA, 1999. Phylogenetic analysis of Cryptosporidium parasites based on the small-subunit rRNA gene locus. Appl Environ Microbiol 65: 1578–1583.
Vidal M, Kruger E, Duran C, Lagos R, Levine M, Prado V, Toro C, Vidal R, 2005. Single multiplex PCR assay to identify simultaneously the six categories of diarrheagenic Escherichia coli associated with enteric infections. J Clin Microbiol 43: 5362–5365.
Xiao L, 2010. Molecular epidemiology of cryptosporidiosis: an update. Exp Parasitol 124: 80–89.
Cohen S, Dalle F, Gallay A, Di Palma M, Bonnin A, Ward HD, 2006. Identification of Cpgp40/15 Type Ib as the predominant allele in isolates of Cryptosporidium spp. from a waterborne outbreak of gastroenteritis in South Burgundy, France. J Clin Microbiol 44: 589–591.
Cevallos AM, Zhang X, Waldor MK, Jaison S, Zhou X, Tzipori S, Neutra MR, Ward HD, 2000. Molecular cloning and expression of a gene encoding Cryptosporidium parvum glycoproteins gp40 and gp15. Infect Immun 68: 4108–4116.
Preidis GA, Wang HC, Lewis DE, Castellanos-Gonzalez A, Rogers KA, Graviss EA, Ward HD, White AC Jr, 2007. Seropositive human subjects produce interferon gamma after stimulation with recombinant Cryptosporidium hominis gp15. Am J Trop Med Hyg 77: 583–585.
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.
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