Therapeutika und (hypothetische) Impfungen gegen humane Kryptosporidien

Zusammenfassung

Kryptosporidien bzw. die von ihnen ausgelöste Kryptosporidiose gehört zu den relevantesten Infektionen des Darmtraktes. Die einzelligen Parasiten infizieren die Darmzellen und lösen Krämpfe, Gewichtsverlust und Durchfall aus. Eine besondere Rolle nehmen Kryptosporidien bei AIDS-Patienten ein. Hier werden sie zu jenen Krankheiten gezählt, die AIDS-definierend sind. Aufgrund dieser Relevanz ist die Suche nach Impfstoffen ein relevantes Ziel der gastroenterologischen Forschung. Doch wie realistisch sind solche Impfstoffe? Dieser Artikel beschreibt die Krankheit Kryptosporidiose und gibt einen Überblick über die aktuellen Therapeutika wie auch die möglichen Impfstoffkandidaten.

Abstract

Cryptosporidium (or cryptosporidiosis caused by them) is one of the most relevant infections of the intestinal tract. The unicellular parasites infect the intestinal cells and cause cramps, weight loss and diarrhea. Cryptosporidia play a special role in AIDS patients. Here they are counted among the diseases that define the acquired immunodeficiency syndrome. Because of this relevance, the search for vaccines is a relevant goal of gastroenterological research. But how realistic are such vaccines? This article describes the disease cryptosporidiosis and reviews current therapeutics and hypothetical vaccine candidates.

Schlüsselwörter

Apicomplexa - Durchfallerkrankungen - Impfungen - Kryptosporidien - Parasitologie

Keywords

Apicomplexa - Diarrhea - Vaccination - Cryptosporidia - Parasitology

Publication History

Received: 11 May 2024

Accepted after revision: 20 February 2025

Article published online:
29 April 2025

• Literatur

• 1 Gerace E, Di Marco Lo Presti V, Biondo C. Cryptosporidium Infection: Epidemiology, Pathogenesis, and Differential Diagnosis. Eur J Microbiol Immunol 2019; 9 (04) 119-123
• 2 Widmer G, Carmena D, Kváč M. et al. Update on Cryptosporidium spp.: highlights from the Seventh International Giardia and Cryptosporidium Conference. Parasite 2020; 27: 14
• 3 Shrivastava AK, Kumar S, Smith WA. et al. Revisiting the global problem of cryptosporidiosis and recommendations. Trop Parasitol 2017; 7 (01) 8-17
• 4 Mavridou A, Pappa O, Papatzitze O. et al. Exotic Tourist Destinations and Transmission of Infections by Swimming Pools and Hot Springs–A Literature Review. Int J Environ Res Public Health 2018; 15 (12) 2730
• 5 Rengifo-Herrera C, Ortega-Mora LM, Gómez-Bautista M. et al. Detection and characterization of a Cryptosporidium isolate from a southern elephant seal (Microunga leonina) from the Antarctic peninsula. Appl Environ Microbiol 2011; 77 (04) 1524-1527
• 6 Lim PKC, Lee XC, Mohd Nazmi NMA. et al. Parasites in soil samples from Signy Island, Antarctica. Trop Biomed 2018; 35 (04) 1007-1016
• 7 Power ML. Biology of cryptosporidium from marsupial hosts. Exp Parasitol 2010; 124 (01) 40-44
• 8 Global Health, Division of Parasitic Diseases and Malaria (2019) DPDx – Laboratory Identification of Parasites of Public Health Concern. Cryptosporidiosis. Centers for Disease Control and Prevention. Accessed August 07, 2023 at: https://www.cdc.gov/dpdx/cryptosporidiosis/index.html
• 9 Tandel J, English ED, Sateriale A. et al. Life cycle progression and sexual development of the apicomplexan parasite cryptosporidium parvum. Nat Microbiol 2019; 4 (12) 2226-2236
• 10 Chen XM, Keithly JS, Paya CV. et al. Cryptosporidiosis. N Engl J Med 2002; 346 (22) 1723-1731
• 11 Chalmers RM, Davis AP. Minireview: clinical cryptosporidiosis. Exp Parasitol 2010; 124 (01) 138-146
• 12 Desai AN. Cryptosporidiosis. JAMA 2020; 323 (03) 288
• 13 Dumaine JE, Tandel J, Striepen B. Cryptosporidium parvum. Trends Parasitol 2020; 36 (05) 485-486
• 14 Kosek M, Alcantara C, Lima AA. et al. Cryptosporidiosis: an update. Lancet Infect Dis 2001; 1 (04) 262-269
• 15 Boehmer TK, Alden NB, Ghosh TS. et al. Cryptosporidiosis from a community swimming pool: outbreak investigation and follow-up study. Epidemiol Infect 2009; 137 (11) 1651-1654
• 16 van der Laan K, Schriemer PJ, de Vries TW. Cryptosporidiose bij een dreumes. Ned Tijdschr Geneeskd 2023; 167: D6901
• 17 Turrientes MC, López-Vélez R. Criptosporidiosis respiratoria. Entferm Infecc Microbiol Clin 1996; 14 (10) 627
• 18 Sponseller JK, Griffiths JK, Tzipori S. The evolution of respiratory Cryptosporidiosis: evidence for transmission by inhalation. Clin Microbiol Rev 2014; 27 (03) 575-586
• 19 Travis WD, Schmidt K, MacLowry JD. et al. Respiratory cryptosporidiosis in a patient with malignant lymphoma. Report of a case and review of the literature. Arch Pathol Lab Med 1990; 114 (05) 519-522
• 20 Meynard JL, Meyohas MC, Binet D. et al. Pulmonary cryptosporidiosis in the acquired immunodeficiency syndrome. Infection 1996; 24 (04) 328-331
• 21 Arora DR, Arora B. AIDS-associated parasitic diarrhoea. Indian J Med Microbiol 2009; 27 (03) 185-190
• 22 Maĭstrenko NA, Chumasov EI, Petrova ES. et al. Криптоспоридиоз поджелудочной железы. Vestn Khir Im I I Grek 2014; 173 (04) 92-94
• 23 Wang RJ, Li JQ, Chen YC. et al. Widespread occurrence of Cryptosporidium infections in patients with HIV/AIDS: Epidemiology, clinical feature, diagnosis, and therapy. Acta Trop 2018; 187: 257-263
• 24 Pantke A, Kollan C, Gunsenheimer-Bartmeyer B. et al. AIDS-defining events among people living with HIV who have been under continuous antiretroviral therapy for more than one year, a German cohort study 1999–2018. Infection 2024; 52 (02) 637-648
• 25 Rossi P, Rivasi F, Codeluppi M. et al. Gastric involvement in AIDS associated cryptosporidiosis. Gut 1998; 43: 476-477
• 26 Khurana S, Chaudhary P. Laboratory diagnosis of cryptosporidiosis. Trop Parasitol 2018; 8 (01) 2-7
• 27 Abreu BS, Pires LC, dos Santos KR. et al. Occurrence of Cryptosporidium spp. and its association with ponderal development and diarrhea episodes in nellore mixed breed cattle. Acta Vet Bras 2019; 13 (01) 24-29
• 28 Jelinek T, Lotze M, Eichenlaub S. et al. Prevalence of infection with Cryptosporidium parvum and Cyclospora cayetanensis among international travellers. Gut 1997; 41 (06) 801-804
• 29 Painter JE, Gargano JW, Yoder JS. et al. Evolving epidemiology of reported cryptosporidiosis cases in the United States, 1995 – 2012. Epidemiol Infect 2016; 144 (08) 1792-1802
• 30 RKI. Infektionsepidemiologisches Jahrbuch meldepflichtiger Krankheiten für 2020. Robert Koch-Institut. 2021 Accessed July 29, 2023 at: https://www.rki.de/DE/Content/Infekt/Jahrbuch/Jahrbuch_2020.pdf?__blob=publicationFile
• 31 Sharma S, Sachdeva P, Virdi JS. Emerging water-borne pathogens. Appl Microbiol Biotechnol 2003; 61: 424-428
• 32 Sow SO, Muhsen K, Nasrin D. et al. The burden of Cryptosporidium diarrheal disease among children < 24 months of age in moderate/high mortality regions of Sub-Saharan Africa and South Asia, utilizing data from the Global Enteric Multicenter Study (GEMS). PLoS Negl Trop Dis 2016; 10 (05) e0004729
• 33 Vermeulen LC, van Hengel M, Kroeze C. et al. Cryptosporidium concentrations in rivers worldwide. Water Res 2019; 149: 202-214
• 34 Chyzheuskaya A, Cormican M, Srivinas R. et al. Economic Assessment of Waterborne Outbreak of Cryptosporidiosis. Emerg Infect Dis 2017; 23 (10) 1650-1656
• 35 Hoffmann S, Batz MB, Morris Jr JG. Annual cost of illness and quality-adjusted life year losses in the United States due to 14 foodborne pathogens. J Food Prot 2012; 75 (07) 1292-1302
• 36 Batz M, Hoffmann S, Morris Jr JG. Disease-outcome trees, EQ-5D scores, and estimated annual losses of quality-adjusted life years (QALYs) for 14 foodborne pathogens in the United States. Foodborne Pathog Dis 2014; 11 (05) 395-402
• 37 ERS, USDA. Cost of foodborne illness estimates for Cryptosporidium parvum. Economic Research Service, U.S. Department of Agriculture. Accessed October 19, 2024 at: https://view.officeapps.live.com/op/view.aspx?src=https%3A%2F%2Fwww.ers.usda.gov%2Fwebdocs%2FDataFiles%2F48464%2FCryptosporidium_2013.xlsx%3Fv%3D343.9&wdOrigin=BROWSELINK
• 38 Rafferty ER, Schurer JM, Arndt MB. et al. Pediatric cryptosporidiosis: An evaluation of health care and societal costs in Peru, Bangladesh and Kenya. PLoS One 2017; 12 (08) e0182820
• 39 Wilcox BA, Aguirre AA, Daszak P. et al. Introduction. EcoHealth 2004; 1 (01) 1-2
• 40 von Hirschhausen E. World Health Summit High Level Event: Developing Strategies for Fighting COVID-19 around the World, October 27th 2020, 09:00 am – 12:30 pm. World Health Summit. Accessed September 14, 2023 at: https://www.bmz.de/resource/blob/75180/88359a742d1b40d1f6a13a4598f9a40b/Beitrag_Hirschhausen.pdf
• 41 White Jr AC, Cron SG, Chappell CL. Paromomycin in cryptosporidiosis. Clin Infect Dis 2001; 31 (10) 1516-1517
• 42 Parashar A, Arya R. Nitazoxanide. Indian Pediatr 2005; 42 (11) 1161-1165
• 43 Cabada MM, Clinton White Jr A. Treatment of cryptosporidiosis: do we know what we think we know?. Curr Opin Infect Dis 2010; 23 (05) 494-499
• 44 Squire SA, Ryan U. Cryptosporidium and Giardia in Africa: current and future challenges. Parasit Vectors 2017; 10 (01) 195
• 45 Ashigbie PG, Shepherd S, Steiner KL. et al. Use-case scenarios for an anti-Cryptosporidium therapeutic. PLoS Negl Trop Dis 2021; 15 (03) e0009057
• 46 Nguyen-Ho-Bao T, Ambe LA, Berberich M. et al. Octaarginine improves the efficacy of Nitazoxanide against Cryptosporidium parvum. Pathogens 2022; 11 (06) 653
• 47 Cotton M. The Mosquirix (RTS.S) malaria vaccine. Trop Doct 2020; 50 (02) 107
• 48 Borkens Y. Toxoplasma gondii – gegenwärtige Arzneimittel und zukünftige Impfstoffe gegen eine unterschätzte Protozoonose. Internist 2021; 62 (10) 1123-1132
• 49 Stanisic DI, Good MF. Malaria vaccines: progress to date. BioDrugs 2023; 37 (06) 737-756
• 50 Boulter-Bitzer JI, Lee H, Trevors JT. Molecular targets for detection and immunotherapy in Cryptosporidium parvum. Biotechnol Adv 2007; 25: 13-44
• 51 Wanyiri JW, O’Connor R, Allison G. et al. Proteolytic processing of the Cryptosporidium glycoprotein gp40/15 by human furin and by a parasite-derived furin-like protease activity. Infect Immun 2007; 75: 184-192
• 52 Mead JR. Prospects for immunotherapy and vaccines against Cryptosporidium. Hum Vaccin Immunther 2014; 10 (06) 1505-1513
• 53 da Silva DRR, de Oliveira TCB, Marta BBF. et al. Vaccine development for cryptosporidiosis: systematic review. Res Soc Dev 2021; 10 (06) e18910615540
• 54 Ehigiator NH, McNair N, Mead JR. IL-12 knockout C57BL/6 mice are protected from re-infection with Cryptosporidium parvum after challenge. J Eukaryot Microbiol 2003; (Suppl. 50) 539-541
• 55 Yu JR, Park WY. The effect of gamma-irradiation on the viability of Cryptosporidium parvum. J Parasitol 2003; 89: 639-642
• 56 Jenkins M, Higgins J, Kniel K. et al. Protection of calves against cryptosporidiosis by oral inoculation with gamma-irradiated Cryptosporidium parvum oocysts. J Parasitol 2004; 90: 1178-1180
• 57 McCann N, O’Connor D, Lambe T. et al. Viral vector vaccines. Curr Opin Immunol 2022; 77: 102210
• 58 Benitez AJ, McNair N, Mead JR. 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: 1272-1278
• 59 Bayart C, Mularoni A, Hemmani N. et al. Tetanus Toxin Fragment C: Structure, Drug Discovery Research and Production. Pharmaceuticals (Basel) 2022; 15 (06) 756
• 60 Manque PA, Tenjo F, Woehlbier U. et al. Identification and immunological characterization of three potential vaccinogens against Cryptosporidium species. Clin Vaccin Immunol 2011; 18: 1796-1802
• 61 Reh F, Antwerpes F, Dr. No, Wodarz G. Apyrase. DocCheck Flexikon. 2023 Accessed October 29, 2023 at: https://flexikon.doccheck.com/de/Apyrase
• 62 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: 912-918
• 63 Geriletu XR, Xu R, Jia H. et al. Immunogenicity of orally administrated recombinant Lactobacillus casei Zhang expressing Cryptosporidium parvum surface adhesion protein P23 in mice. Curr Microbiol 2011; 62: 1573-1580
• 64 Douradinha B, Reis V, Rogers M. et al. Novel insights in genetic transformation of the probiotic yeast Saccharomyces boulardii. Bioengineered 2013; 5 (01) 21-29
• 65 Di Cristina M, Ghouze F, Kocken CH. et al. Transformed Toxoplasma gondii tachyzoites expressing the circumsporozoite protein of Plasmodium knowlesi elicit a specific immune response in rhesus monkeys. Infect Immun 1999; 67: 1677-1682
• 66 O’Connor RM, Kim K, Khan F. et al. Expression of Cpgp40/15 in Toxoplasma gondii: a surrogate system for the study of Cryptosporidium glycoprotein antigens. Infect Immun 2003; 71: 6027-6034
• 67 Shirafuji H, Xuan X, Kimata I. et al. Expression of P23 of Cryptosporidium parvum in Toxoplasma gondii and evaluation of its protective effects. J Parasitol 2005; 91: 476-479
• 68 Jongert E, Roberts CW, Gargano N. et al. Vaccines against Toxoplasma gondii: challenges and opportunities. Mem Inst Oswaldo Cruz 2009; 104: 252-266
• 69 Barrier M, Lacroix-Lamandé S, Mancassola R. et al. Oral and intraperitoneal administration of phosphorothioate oligodeoxynucleotides leads to control of Cryptosporidium parvum infection in neonatal mice. J Infect Dis 2006; 193: 1400-1407
• 70 Wang C, Luo J, Amer S. et al. Multivalent DNA vaccine induces protective immune responses and enhanced resistance against Cryptosporidium parvum infection. Vaccine 2010; 29: 323-328
• 71 Loukas A. Frontiers in Parasitology Grand Challenge. Front Parasitol 2022; 1: 902098