CRYPTOSPORIDIA AND MACROORGANISM: FACTORS THAT INFLUENCE ON THE DEVELOPMENT OF CRYPTOSPORIDIOSIS

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Abstract


Cryptosporidiosis is a disease caused by unicellular parasites belonging to the Cryptosporidium genus. The small intestine is the primary site of localization of infection which predicts the main clinical symptom of the disease — diarrhea. The most important factors influencing Cryptosporidium infection and the course of disease are molecular genetic variability of the parasite, its virulence and infectivity, and viability of the mucosa of the digestive tract and local and systemic immunity of the macroorganism. The immune status of the host plays a key role in determining sensitivity to infection and the severity of the disease. Cryptosporidium infection differs in outcomes: asymptomatic in some patients, acute enteritis accompanied by profuse diarrhea, lesions of internal organs, and fatal outcome in others. Current therapeutic approaches to the treatment of cryptosporidiosis are ineffective. Despite the existence of a large number of drugs with antiparasitic effect, there are no medications with a specific effect on cryptosporidia. Understanding the factors that determine both the pathogenicity of Cryptosporidia and the protective properties of host defense systems will allow developing effective prevention measures and therapeutic interventions of this protozoosis.


E. G. Starikova

Siberian state medical university

Author for correspondence.
Email: elena.g.starikova@gmail.com
ORCID iD: 0000-0002-8899-0795

Russian Federation

Starikova Elena Grigorievna - PhD, MD.

Tomsk

O. V. Voronkova

Siberian state medical university

Email: voronkova-ov@yandex.ru

Russian Federation

Voronkova Olga Vladimirovna - PhD, Professor.

Tomsk

Yu. V. Kovshirina

Siberian state medical university

Email: yulia.v.kovshirina@gmail.com
ORCID iD: 0000-0001-6818-9792

Russian Federation

Kovshirina Yulia Vikotorovna - PhD, MD.

Tomsk

N. I. Shubina

Health care unit № 2

Email: natalya.i.shubina@gmail.com
ORCID iD: 0000-0003-4736-3370

Shubina Nataya Ivanovna - MD.

Tomsk

  1. Rossle NF, Latif B. Cryptosporidiosis as threatening health problem: a review. Asian Pac J Trop Biomed. 2013;3(11):916−924. doi: 10.1016/S2221-1691(13)60179-3.
  2. Petry F, Jakobi V, Tessema TS. Host immune response to Cryptosporidium parvum infection. Exp Parasitol. 2010;126(3):304–309. doi: 10.1016/j.exppara.2010.05.022.
  3. McDonald V, Korbel DS, Barakat FM, et al. Innate immune responses against Cryptosporidium parvum infection. Parasite Immunol. 2013;35(2):55–64. doi: 10.1111/pim.12020.
  4. Caccio SM, Sannella AR, Mariano V, et al. A rare Cryptosporidium parvum genotype associated with infection of lambs and zoonotic transmission in Italy. Vet Parasitol. 2013;191(1–2):128–131. doi: 10.1016/j.vetpar.2012.08.010.
  5. Robertson LJ, Chalmers RM. Foodborne cryptosporidiosis: is there really more in Nordic countries? Trends Parasitol. 2013;29(1):3–9. doi: 10.1016/j.pt.2012.10.003.
  6. Egorov A, Frost F, Muller T, et al. Serological evidence of Cryptosporidium infections in a Russian city and evaluation of risk factors for infections. Ann Epidemiol. 2004;14(2):129–136. doi: 10.1016/S1047-2797(03)00122-4.
  7. Kucerova Z, Sokolova OI, Demyanov AV, et al. Microsporidiosis and Cryptosporidiosis in HIV/AIDS patients in St. Petersburg, Russia: serological identification of microsporidia and Cryptosporidium parvum in sera samples from HIV/AIDS patients. AIDS Res Hum Retroviruses. 2011;27(1):13–15. doi: 10.1089/aid.2010.0132.
  8. Osman M, El Safadi D, Benamrouz S, et al. Initial data on the molecular epidemiology of cryptosporidiosis in Lebanon. PLoS One. 2015;10(5):e0125129. doi: 10.1371/journal.pone.0125129.
  9. Puleston RL, Mallaghan CM, Modha DE, et al. The first recorded outbreak of cryptosporidiosis due to Cryptosporidium cuniculus (formerly rabbit genotype), following a water quality incident. J Water Health. 2014;12(1):41–50. doi: 10.2166/wh.2013.097.
  10. Levine ND. Taxonomy and review of coccidia genus Cryptosporidium (Protozoa, Apicomplexa). J Prozool. 1984;31(1):94−98. doi: 10.1111/j.1550-7408.1984.tb04296.x.
  11. Clode PL, Koh WH, Thompson RC. Life without a host cell: what is Cryptosporidium? Trends Parasitol. 2015;31(12):614–624. doi: 10.1016/j.pt.2015.08.005.
  12. Ryan U. Cryptosporidium in birds, fish and amphibians. Exp Parasitol. 2010;124(1):113-120. doi: 10.1016/j.exppara.2009.02.002.
  13. Isaza JP, Galván AL, Polanco V, et al. Revisiting the reference genomes of human pathogenic Cryptosporidium species: reannotation of C. parvum Iowa and a new C. hominis reference. Sci Rep. 2015;5:16324. doi: 10.1038/srep16324.
  14. Nichols GL, Chalmers RM. Molecular epidemiology of human cryptosporidiosis. In: Cacciò SM, Widmer G, editors. Cryptosporidium: parasite and disease. Vienna: Springer; 2014. pp. 81−147.
  15. Cama VA, Bern C, Roberts J, et al. Cryptosporidium species and subtypes and clinical manifestations in children, Peru. Emerg Infect Dis. 2008;14(10):1567–1574. doi: 10.3201/eid1410.071273.
  16. Cama VA, Ross JM, Crawford S, et al. Differences in clinical manifestations among Cryptosporidium species and subtypes in HIV-infected persons. J Infect Dis. 2007;196(5):684–691. doi: 10.1086/519842.
  17. Johansen OH, Hanevik K, Thrana F, et al. Symptomatic and asymptomatic secondary transmission of Cryptosporidium parvum following two related outbreaks in schoolchildren. Epidemiol Infect. 2015;143(8):1702–1709. doi: 10.1017/S095026881400243X.
  18. Hunter PR, Hadfield SJ, Wilkinson D, et al. Subtypes of Cryptosporidium parvum in humans and disease risk. Emerg Infect Dis. 2007;13(1):82–88. doi: 10.3201/eid1301.060481.
  19. Asma I, Sim BL, Brent RD, et al. Molecular epidemiology of Cryptosporidium in HIV/AIDS patients in Malaysia. Trop Biomed. 2015;32(2):310–322.
  20. Berahmat R, Spotin A, Ahmadpour E, et al. Human cryptosporidiosis in Iran: a systematic review and meta-analysis. Parasitol Res. 2017;116(4):1111–1128. doi: 10.1007/s00436-017-5376-3.
  21. Xiao L. Molecular epidemiology of cryptosporidiosis: an update. Exp Parasitol. 2010;124(1):80–89. doi: 10.1016/j.exppara.2009.03.018.
  22. Bushkin GG, Motari E, Carpentieri A, et al. Evidence for a structural role for acid-fast lipids in oocyst walls of Cryptosporidium, Toxoplasma, and Eimeria. MBio. 2013;4(5):e00387–00313. doi: 10.1128/mBio.00387-13.
  23. Karanis P, Kimura A, Nagasawa H, et al. Observations on Cryptosporidium life cycle stages during excystation. J Parasitol. 2008;94(1):298–300. doi: 10.1645/GE-1185.1.
  24. Singh P, Mirdha BR, Srinivasan A, et al. Identification of invasion proteins of Cryptosporidium parvum. World J Microbiol Biotechnol. 2015;31(12):1923–1934. doi: 10.1007/s11274-015-1936-9.
  25. Swapna LS, Parkinson J. Genomics of apicomplexan parasites. Crit Rev Biochem Mol Biol. 2017;52(3):254–273. doi: 10.1080/10409238.2017.1290043.
  26. Perez-Cordon G, Yang G, Zhou B, et al. Interaction of Cryptosporidium parvum with mouse dendritic cells leads to their activation and parasite transportation to mesenteric lymph nodes. Pathog Dis. 2014;70(1):17–27. doi: 10.1111/2049-632X.12078.
  27. Lean IS, Lacroix-Lamande S, Laurent F, McDonald V. Role of tumor necrosis factor alpha in development of immunity against Cryptosporidium parvum infection. Infect Immun. 2006;74(7):4379–4382. doi: 10.1128/IAI.00195-06.
  28. Zhou R, Hu G, Liu J, et al. NF-kappaB p65-dependent transactivation of miRNA genes following Cryptosporidium parvum infection stimulates epithelial cell immune responses. PLoS Pathog. 2009;5(12):e1000681. doi: 10.1371/journal.ppat.1000681.
  29. Nordone SK, Gookin JL. Lymphocytes and not IFN-gamma mediate expression of iNOS by intestinal epithelium in murine cryptosporidiosis. Parasitol Res. 2010;106(6):1507−1511. doi: 10.1007/s00436-010-1837-7.
  30. Starikova EG, Tashireva LA, Novitsky VV, Ryazantseva NV. Nitric oxide donor NOC-5 increases XIAP and Aven level in Jurkat cells. Cell Biol Int. 2014;38(7):799–802. doi: 10.1002/cbin.10262.
  31. Ehigiator HN, McNair N, Mead JR. Cryptosporidium parvum: the contribution of Th1-inducing pathways to the resolution of infection in mice. Exp Parasitol. 2007;115(2):107–113. doi: 10.1016/j.exppara.2006.07.001.
  32. Якушенко Е.В., Лопатникова Ю.А., Сенников С.В. Интерлейкин 18 и его роль в иммунном ответе // Медицинская иммунология. ― 2005. ― Т.7. ― №4 ― С. 355−364. [Yakushenko EV, Lopatnikova JA, Sennikov SV. IL-18 and immunity. Meditsinskaya Immunologiya. 2005;7(4):355−364. (In Russ).]
  33. Чурина Е.Г., Уразова О.И., Новицкий В.В., и др. Роль γδТ- и NK-клеток в иммунном ответе // Бюллетень сибирской медицины. ― 2010. ― Т.9. ― №5 ― С. 138–142. [Churina YeG, Urazova OI, Novitskiy VV, et al. The role of γδТ- and NK-сells in immune response. Bulletin of Siberian medicine. 2010;9(5):138−142. (In Russ).]
  34. Bedi B, Mead JR. Cryptosporidium parvum antigens induce mouse and human dendritic cells to generate Th1-enhancing cytokines. Parasite Immunol. 2012;34(10):473–485. doi: 10.1111/j.1365-3024.2012.01382.x.
  35. DeLeo FR. Modulation of phagocyte apoptosis by bacterial pathogens. Apoptosis. 2004;9(4):399–413. doi: 10.1023/B:APPT.0000031448.64969.fa.
  36. Lendner M, Daugschies A. Cryptosporidium infections: molecular advances. Parasitology. 2014;141(11):1511–1532. doi: 10.1017/S0031182014000237.
  37. McCole DF, Eckmann L, Laurent F, Kagnoff MF. Intestinal epithelial cell apoptosis following Cryptosporidium parvum infection. Infect Immun. 2000;68(3):1710–1713. doi: 10.1128/Iai.68.3.1710-1713.2000.
  38. Gong AY, Zhou R, Hu GK, et al. Cryptosporidium parvum induces B7-H1 expression in cholangiocytes by down-regulating microRNA-513. J Infect Dis. 2010;201(1):160–169. doi: 10.1086/648589.
  39. Roche JK, Rojo AL, Costa LB, et al. Intranasal vaccination in mice with an attenuated Salmonella enterica Serovar 908htr A expressing Cp15 of Cryptosporidium: impact of malnutrition with preservation of cytokine secretion. Vaccine. 2013;31(6):912–918. doi: 10.1016/j.vaccine.2012.12.007.
  40. Козлов С.Н., Козлов Р.С. Современная антимикробная терапия. Руководство для врачей. ― М.: МИА; 2017. ― 400 с. [Kozlov SN, Kozlov RS. Sovremennaya antimicrobnaya terapiya. Rukovodstvo dlya vrachei. Moscow: MIA; 2017. 400 p. (In Russ).]
  41. Abubakar II, Aliyu SH, Arumugam C, et al. Prevention and treatment of cryptosporidiosis in immunocompromised patients. Cochrane Database Syst Rev. 2007;(1):CD004932. doi: 10.1002/14651858.CD004932.pub2.
  42. Amadi B, Mwiya M, Sianongo S, et al. High dose prolonged treatment with nitazoxanide is not effective for cryptosporidiosis in HIV positive Zambian children: a randomised controlled trial. BMC Infect Dis. 2009;9:195. doi: 10.1186/1471-2334-9-195.
  43. Cabada MM, White AC. Treatment of cryptosporidiosis: do we know what we think we know? Curr Opin Infect Dis. 2010;23(5):494–499. doi: 10.1097/QCO.0b013e32833de052.
  44. Hewitt RG, Yiannoutsos CT, Higgs ES, et al. Paromomycin: no more effective than placebo for treatment of cryptosporidiosis in patients with advanced human immunodeficiency virus infection. Clin Infect Dis. 2000;31(4):1084–1092. doi: 10.1086/318155.
  45. Giacometti A, Cirioni O, Barchiesi F, et al. Activity of nitazoxanide alone and in combination with azithromycin and rifabutin against Cryptosporidium parvum in cell culture. J Antimicrob Chemother. 2000;45(4):453–456. doi: 10.1093/jac/45.4.453.
  46. Abrahamsen MS, Templeton TJ, Enomoto S, et al. Complete genome sequence of the apicomplexan, Cryptosporidium parvum. Science. 2004;304(5669):441–445. doi: 10.1126/science.1094786.
  47. Xu P, Widmer G, Wang YP, et al. The genome of Cryptosporidium hominis. Nature. 2004;431(7012):1107–1112. doi: 10.1038/nature02977.
  48. Aurrecoechea C, Barreto A, Brestelli J, et al. EuPathDB: the eukaryotic pathogen database. Nucleic Acids Res. 2013;41(D1):D684–D691. doi: 10.1093/nar/gks1113.
  49. Larson ET, Ojo KK, Murphy RC, et al. Multiple determinants for selective inhibition of apicomplexan calcium-dependent protein kinase CDPK1. J Med Chem. 2012;55(6):2803–2810. doi: 10.1021/jm201725v.
  50. Murphy RC, Ojo KK, Larson ET, et al. Discovery of potent and selective inhibitors of calcium-dependent protein kinase 1 (CDPK1) from C. parvum and T. gondii. ACS Med Chem Lett. 2010;1(7):331–335. doi: 10.1021/ml100096t.
  51. Castellanos-Gonzalez A, White AC, Ojo KK, et al. A novel calcium-dependent protein kinase inhibitor as a lead compound for treating Cryptosporidiosis. J Infect Dis. 2013;208(8):1342–1348. doi: 10.1093/infdis/jit327.
  52. Arrowood MJ, Mead JR, Xie LT, You XD. In vitro anticryptosporidial activity of dinitroaniline herbicides. FEMS Microbiol Lett. 1996;136(3):245–249. doi: 10.1111/j.1574-6968.1996.tb08056.x.
  53. Madern D, Cai XM, Abrahamsen MS, Zhu G. Evolution of Cryptosporidium parvum lactate dehydrogenase from malate dehydrogenase by a very recent event of gene duplication. Mol Biol Evol. 2004;21(3):489–497. doi: 10.1093/molbev/msh042.
  54. Fritzler JM, Zhu G. Novel anti-Cryptosporidium activity of known drugs identified by high-throughput screening against parasite fatty acyl-CoA binding protein (ACBP). J Antimicrob Chemother. 2012;67(3):609–617. doi: 10.1093/jac/dkr516.
  55. Mead JR. Prospects for immunotherapy and vaccines against Cryptosporidium. Hum Vaccin Immunother. 2014;10(6):1505–1513. doi: 10.4161/hv.28485.
  56. Allison GM, Rogers KA, Borad A, et al. 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. 2011;85(1):97–104. doi: 10.4269/ajtmh.2011.11-0043.
  57. Ehigiator HN, Romagnoli P, Priest JW, et al. Induction of murine immune responses by DNA encoding a 23-kDa antigen of Cryptosporidium parvum. Parasitol Res. 2007;101(4):943–950. doi: 10.1007/s00436-007-0565-0.
  58. Benitez AJ, McNair N, Mead JR. Oral Oral immunization with attenuated Salmonella enterica serovar Typhimurium encoding Cryptosporidium parvum Cp23 and Cp40 antigens induces a specific immune response in mice. Clin Vaccine Immunol. 2009;16(9):1272–1278. doi: 10.1128/Cvi.00089-09.
  59. Okhuysen PC, Chappell CL, Sterling CR, et al. Susceptibility and serologic response of healthy adults to reinfection with Cryptosporidium parvum. Infect Immun. 1998;66(2):441–443.
  60. Chappell CL, Okhuysen PC, Sterling CR, et al. Infectivity of Cryptosporidium parvum in healthy adults with pre-existing anti-C. Parvum serum immunoglobulin G. Am J Trop Med Hyg. 1999;60(1):157–164. doi: 10.4269/ajtmh.1999.60.157.

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