Novel treatment strategies and drugs in development for cryptosporidiosis

References

• Checkley W, White AC J, Jaganath D, et al. A review of the global burden, novel diagnostics, therapeutics, and vaccine targets for cryptosporidium. Lancet Infect Dis. 2015;15(1):85–94.
   PubMed Web of Science ®Google Scholar
• Kotloff KL, Nataro JP, Blackwelder WC, et al. Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the global enteric multicenter study, GEMS): a prospective, case-control study. Lancet. 2013;382(9888):209–222.
   PubMed Web of Science ®Google Scholar
• Platts-Mills JA, Babji S, Bodhidatta L, et al. Pathogen-specific burdens of community diarrhoea in developing countries: a multisite birth cohort study (MAL-ED). Lancet Glob Health. 2015;3(9):e564–e575.
   PubMed Web of Science ®Google Scholar
• Checkley W, Gilman RH, Epstein LD, et al. Asymptomatic and symptomatic cryptosporidiosis: their acute effect on weight gain in Peruvian children. Am J Epidemiol. 1997;145(2):156–163.
   PubMed Web of Science ®Google Scholar
• Collaborators GDD. Estimates of global, regional, and national morbidity, mortality, and aetiologies of diarrhoeal diseases: a systematic analysis for the global burden of disease study 2015. Lancet Infect Dis. 2017;17(9):909–948.
   PubMed Web of Science ®Google Scholar
• 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(5):e0004729.
   PubMed Web of Science ®Google Scholar
• Hlavsa MC, Roberts VA, Kahler AM, et al. Outbreaks of illness associated with recreational water–United States, 2011–2012. MMWR Morb Mortal Wkly Rep. 2015;64(24):668–672.
   PubMed Web of Science ®Google Scholar
• Ehrenman K, Wanyiri JW, Bhat N, et al. Cryptosporidium parvum scavenges LDL-derived cholesterol and micellar cholesterol internalized into enterocytes. Cell Microbiol. 2013;15(7):1182–1197.
   PubMed Web of Science ®Google Scholar
• Amadi B, Mwiya M, Musuku J, et al. Effect of nitazoxanide on morbidity and mortality in Zambian children with cryptosporidiosis: a randomised controlled trial. Lancet. 2002;360(9343):1375–1380.
   PubMed Web of Science ®Google Scholar
• Rossignol JF, Kabil SM, el-Gohary Y, Younis AM. Effect of nitazoxanide in diarrhea and enteritis caused by Cryptosporidium species. Clin Gastroenterol Hepatol. 2006;4(3):320–324.
   PubMed Web of Science ®Google Scholar
• Rossignol JF, Ayoub A, Ayers MS. Treatment of diarrhea caused by Cryptosporidium parvum: a prospective randomized, double-blind, placebo-controlled study of Nitazoxanide. J Infect Dis. 2001;184(1):103–106.
   PubMed Web of Science ®Google Scholar
• Cabada MM, White AC Jr. Treatment of cryptosporidiosis: do we know what we think we know? Curr Opin Infect Dis. 2010;23(5):494–499.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Hashmey R, Smith NH, Cron S, et al. Cryptosporidiosis in Houston, Texas. A Report of 95 Cases Medicine (Baltimore). 1997;76(2):118–139.
   PubMed Web of Science ®Google Scholar
• White AC Jr., Chappell CL, Hayat CS, et al. Paromomycin for cryptosporidiosis in AIDS: a prospective, double-blind trial. J Infect Dis. 1994;170(2):419–424.
   PubMed Web of Science ®Google Scholar
• Hussien SM, Abdella OH, Abu-Hashim AH, et al. Comparative study between the effect of nitazoxanide and paromomycine in treatment of cryptosporidiosis in hospitalized children. J Egypt Soc Parasitol. 2013;43(2):463–470.
   PubMedGoogle Scholar
• Allam AF, Shehab AY. Efficacy of azithromycin, praziquantel and mirazid in treatment of cryptosporidiosis in school children. J Egypt Soc Parasitol. 2002;32(3):969–978.
   PubMedGoogle Scholar
• Bhadauria D, Goel A, Kaul A, et al. Cryptosporidium infection after renal transplantation in an endemic area. Transpl Infect Dis. 2015;17(1):48–55.
   PubMed Web of Science ®Google Scholar
• Lee S, Harwood M, Girouard D, et al. The therapeutic efficacy of azithromycin and nitazoxanide in the acute pig model of Cryptosporidium hominis. PLoS One. 2017;12(10):e0185906.
   PubMed Web of Science ®Google Scholar
• Smith NH, Cron S, Valdez LM, et al. Combination drug therapy for cryptosporidiosis in AIDS. J Infect Dis. 1998;178(3):900–903.
   PubMed Web of Science ®Google Scholar
• Lanternier F, Amazzough K, Favennec L, et al. Cryptosporidium spp. infection in solid organ transplantation: the nationwide “TRANSCRYPTO” Study. Transplantation. 2017;101(4):826–830.
   PubMed Web of Science ®Google Scholar
• Huston CD, Spangenberg T, Burrows J, et al. Product profile and developmental cascade for new cryptosporidiosis treatments. PLoS Negl Trop Dis. 2015;9(10):e0003987.
   PubMed Web of Science ®Google Scholar
• Stancu C, Sima A. Statins: mechanism of action and effects. J Cell Mol Med. 2001;5(4):378–387.
   PubMed Web of Science ®Google Scholar
• Imlay L, Odom AR. Isoprenoid metabolism in apicomplexan parasites. Curr Clin Microbiol Rep. 2014;1(3–4):37–50.
   PubMedGoogle Scholar
• Bessoff K, Sateriale A, Lee KK, et al. Drug repurposing screen reveals FDA-approved inhibitors of human HMG-CoA reductase and isoprenoid synthesis that block Cryptosporidium parvum growth. Antimicrob Agents Chemother. 2013;57(4):1804–1814.
   PubMed Web of Science ®Google Scholar
• Madbouly Taha N, Salah AYHA, El-Sayed SH, et al. Atorvastatin repurposing for the treatment of cryptosporidiosis in experimentally immunosuppressed mice. Exp Parasitol. 2017;181:57–69.
   PubMed Web of Science ®Google Scholar
• Love MS, Beasley FC, Jumani RS, et al. A high-throughput phenotypic screen identifies clofazimine as a potential treatment for cryptosporidiosis. PLoS Negl Trop Dis. 2017;11(2):e0005373.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Feng J, McManus SA, et al. Design and solidification of fast-releasing clofazimine nanoparticles for treatment of cryptosporidiosis. Mol Pharm. 2017;14(10):3480–3488.
   PubMedGoogle Scholar
• Bondioli L, Ludovisi A, Tosi G, et al. The loading of labelled antibody-engineered nanoparticles with Indinavir increases its in vitro efficacy against Cryptosporidium parvum. Parasitology. 2011;138(11):1384–1391.
   PubMed Web of Science ®Google Scholar
• Huang MZ, Li J, Guan L, et al. Therapeutic effects of acetylspiramycin and garlicin on cryptosporidiosis among drug users. Int J Parasitol Drugs Drug Resist. 2015;5(3):185–190.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Castellanos-Gonzalez A, White AC Jr., 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.
   PubMed Web of Science ®Google Scholar
• Castellanos-Gonzalez A, Sparks H, Nava S, et al. A novel calcium-dependent kinase inhibitor, bumped kinase inhibitor 1517, cures cryptosporidiosis in immunosuppressed mice. J Infect Dis. 2016;214(12):1850–1855.
   PubMed Web of Science ®Google Scholar
• Schaefer DA, Betzer DP, Smith KD, et al. Novel bumped kinase inhibitors are safe and effective therapeutics in the calf clinical model for cryptosporidiosis. J Infect Dis. 2016;214(12):1856–1864.
   PubMed Web of Science ®Google Scholar
• Hulverson MA, Vinayak S, Choi R, et al. Bumped-kinase inhibitors for cryptosporidiosis therapy. J Infect Dis. 2017;215(8):1275–1284.
   PubMed Web of Science ®Google Scholar
• Lendner M, Bottcher D, Delling C, et al. A novel CDPK1 inhibitor–a potential treatment for cryptosporidiosis in calves? Parasitol Res. 2015;114(1):335–336.
   PubMed Web of Science ®Google Scholar
• Arnold SLM, Choi R, Hulverson MA, et al. Necessity of bumped kinase inhibitor gastrointestinal exposure in treating cryptosporidium infection. J Infect Dis. 2017;216(1):55–63.
   PubMed Web of Science ®Google Scholar
• Huang W, Choi R, Hulverson MA, et al. 5-Aminopyrazole-4-Carboxamide-based compounds prevent the growth of cryptosporidium parvum. Antimicrob Agents Chemother. 2017;61:8.
   Web of Science ®Google Scholar
• Kuhlenschmidt TB, Rutaganira FU, Long S, et al. Inhibition of Calcium-Dependent Protein Kinase 1 (CDPK1) in vitro by pyrazolopyrimidine derivatives does not correlate with sensitivity of cryptosporidium parvum growth in cell culture. Antimicrob Agents Chemother. 2015;60(1):570–579.
   PubMed Web of Science ®Google Scholar
• Osman KT, Ye J, Shi Z, et al. Discovery and structure activity relationship of the first potent cryptosporidium FIKK kinase inhibitor. Bioorg Med Chem. 2017;25(5):1672–1680.
   PubMed Web of Science ®Google Scholar
• Jefferies R, Yang R, Woh CK, et al. Target validation of the inosine monophosphate dehydrogenase (IMPDH) gene in Cryptosporidium using Phylomer((R)) peptides. Exp Parasitol. 2015;148:40–48.
   PubMed Web of Science ®Google Scholar
• Gorla SK, McNair NN, Yang G, et al. Validation of IMP dehydrogenase inhibitors in a mouse model of cryptosporidiosis. Antimicrob Agents Chemother. 2014;58(3):1603–1614.
   PubMed Web of Science ®Google Scholar
• Kumar VP, Cisneros JA, Frey KM, et al. Structural studies provide clues for analog design of specific inhibitors of Cryptosporidium hominis thymidylate synthase-dihydrofolate reductase. Bioorg Med Chem Lett. 2014;24(17):4158–4161.
   PubMed Web of Science ®Google Scholar
• Mukerjee A, Iyidogan P, Castellanos-Gonzalez A, et al. A nanotherapy strategy significantly enhances anticryptosporidial activity of an inhibitor of bifunctional thymidylate synthase-dihydrofolate reductase from Cryptosporidium. Bioorg Med Chem Lett. 2015;25(10):2065–2067.
   PubMed Web of Science ®Google Scholar
• Abdulla MH, Lim KC, Sajid M, et al. Schistosomiasis mansoni: novel chemotherapy using a cysteine protease inhibitor. PLoS Med. 2007;4(1):e14.
   PubMed Web of Science ®Google Scholar
• Ndao M, Nath-Chowdhury M, Sajid M, et al. A cysteine protease inhibitor rescues mice from a lethal Cryptosporidium parvum infection. Antimicrob Agents Chemother. 2013;57(12):6063–6073.
   PubMed Web of Science ®Google Scholar
• Dorlo TP, Balasegaram M, Beijnen JH, et al. Miltefosine: a review of its pharmacology and therapeutic efficacy in the treatment of leishmaniasis. J Antimicrob Chemother. 2012;67(11):2576–2597.
   PubMed Web of Science ®Google Scholar
• Sinkala E, Katubulushi M, Sianongo S, et al. A trial of the use of miltefosine to treat HIV-related cryptosporidiosis in Zambian adults, extreme metabolic disturbances contribute to high mortality. Ann Trop Med Parasitol. 2011;105(2):129–134.
   PubMed Web of Science ®Google Scholar
• Fortin A, Caridha DP, Leed S, et al. Direct comparison of the efficacy and safety of oral treatments with oleylphosphocholine (OlPC) and miltefosine in a mouse model of L. major cutaneous leishmaniasis. PLoS Negl Trop Dis. 2014;8(9):e3144.
   PubMed Web of Science ®Google Scholar
• Sonzogni-Desautels K, Renteria AE, Camargo FV, et al. Oleylphosphocholine (OlPC) arrests Cryptosporidium parvum growth in vitro and prevents lethal infection in interferon gamma receptor knock-out mice. Front Microbiol. 2015;6:973.
   PubMed Web of Science ®Google Scholar
• Manjunatha UH, Vinayak S, Zambriski JA, et al. A Cryptosporidium PI(4)K inhibitor is a drug candidate for cryptosporidiosis. Nature. 2017;546(7658):376–380.
   PubMed Web of Science ®Google Scholar
• Palencia A, Liu RJ, Lukarska M, et al. Cryptosporidium and toxoplasma parasites are inhibited by a benzoxaborole targeting leucyl-trna synthetase. Antimicrob Agents Chemother. 2016;60(10):5817–5827.
   PubMed Web of Science ®Google Scholar
• Jain V, Yogavel M, Kikuchi H, et al. Targeting prolyl-trna synthetase to accelerate drug discovery against malaria, leishmaniasis, toxoplasmosis, cryptosporidiosis, and coccidiosis. Structure. 2017;25(10):1495–1505.e1496.
   PubMed Web of Science ®Google Scholar
• Guo F, Zhang H, Fritzler JM, et al. Amelioration of Cryptosporidium parvum infection in vitro and in vivo by targeting parasite fatty acyl-coenzyme A synthetases. J Infect Dis. 2014;209(8):1279–1287.
   PubMed Web of Science ®Google Scholar
• Eltahan R, Guo F, Zhang H, et al. Discovery of ebselen as an inhibitor of Cryptosporidium parvum glucose-6-phosphate isomerase (CpGPI) by high-throughput screening of existing drugs. Int J Parasitol Drugs Drug Resist. 2018;8(1):43–49.
   PubMed Web of Science ®Google Scholar
• Jumani RS, Bessoff K, Love MS, et al. A novel piperazine-based drug lead for cryptosporidiosis from the medicines for malaria venture open access malaria box. Antimicrob Agents Chemother. 2018.
   PubMed Web of Science ®Google Scholar
• White AC Jr. Cryptosporidiosis and the ears of the hippopotamus. Clin Infect Dis. 2010;50(10):1373–1374.
   PubMed Web of Science ®Google Scholar
• Mor SM, Tumwine JK, Ndeezi G, et al. Respiratory cryptosporidiosis in HIV-seronegative children in Uganda: potential for respiratory transmission. Clin Infect Dis. 2010;50(10):1366–1372.
   PubMed Web of Science ®Google Scholar
• Castellanos-Gonzalez A, Perry N, Nava S, et al. Preassembled single-stranded rna-argonaute complexes: a novel method to silence genes in cryptosporidium. J Infect Dis. 2016;213(8):1307–1314.
   PubMed Web of Science ®Google Scholar