Skip to main content

Advertisement

SpringerLink
Log in

Evaluation of possible prophylactic and therapeutic effect of mefloquine on experimental cryptosporidiosis in immunocompromised mice

  • Original Article
  • Published:
Journal of Parasitic Diseases Aims and scope Submit manuscript

Abstract

Cryptosporidiosis is an imperative global health concern. Unfortunately, Nitazoxanide (NTZ) (the nowadays drug of choice) is not effective in treatment of immunocompromised patients. We aimed to assess the possible anti-cryptosporidial prophylactic and therapeutic effects of Mefloquine (MQ) on infected immunosuppressed murine models. Mice were divided into five groups; GI: received Mefloquine (400 mg/kg/day), GII: received NTZ (100 mg/kg/bid), GIII: received a combination, half dose regimen of both drugs, GIV: infected untreated and GV: non-infected untreated. Each treated group was divided into three subgroups; Ga prophylaxis (PX), thereafter infection, Gb first and Gc second treatment doses. Assessment was done by parasitological, histopathological and serological techniques. A significant oocyst clearance was detected in all prophylactically treated groups. GIa showed 77% reduction of the mean oocyst count in stool while GIb and GIIIc showed100% oocyst clearance. Histopathologically, the ileocecal sections from GIV showed loss of brush borders with marked villous atrophy. GIa induced a moderate improvement of those pathological changes. Moreover, the villi in GIb and GIIIc retained their normal appearance with minimal inflammatory cells. Serum interferon gamma levels showed highly significant increases in GI&GIII compared to GIV while a non-significant increase was observed in GIIa only. On the contrary, serum interleukin-17 levels showed a highly significant down-regulation in all treated groups in comparison to GIV. This study proved a marvelous effect of MQ-PX on cryptosporidiosis in immunosuppressed mice and thus it could be introduced as one of the most promising re-purposed prophylactic and therapeutic anti-cryptosporidial agents.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Abdou AG, Harba NM, Afifi AF, Elnaidany NF (2013) Assessment of Cryptosporidium parvum infection in immunocompetent and immunocompromised mice and its role in triggering intestinal dysplasia. Int J Infect Dis 17(8):e593–e600

    CAS  PubMed  Google Scholar 

  • Abou-Shady OM, Mohammed SS, Attia SS, Yusuf HA, Helmy DO (2016) Therapeutic effect of mefloquine on Schistosoma mansoni in experimental infection in mice. J Parasit Dis 40(2):259–267

    PubMed  Google Scholar 

  • AbuEl-Ezz NT, Khalil FA, Shaapan RM (2011) Therapeutic effect of onion (Allium cepa) and cinnamon (Cinnamomum zeylanicum) oils on cryptosporidiosis in experimentally infected mice. Glob Vet 7(2):179–183

    Google Scholar 

  • Ajjampur SSR, 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

    CAS  PubMed  PubMed Central  Google Scholar 

  • Al-Ghandour AMF, Yousef AM, Mohamed RMSM, Tealeb AM, Ahmed HK, And AHA, Farag TI (2020) Prophylactic anticryptosporidial activity of atorvastatin versus nitazoxanide on experimentally infected immunosuppressed murine models. J Egypt Soc Parasitol 50(3):535–546

    Google Scholar 

  • Aly NSM, Selem RF, Zalat RS, Khalil H, Hussien BEST (2017) An innovative repurposing of mefloquine; assessment of its therapeutic efficacy in treating cryptosporidium parvum infection of both immunocompetent and immunocompromized mice. J Egypt Soc Parasitol 47(2):253–262

    Google Scholar 

  • Amadi B, Mwiya M, Sianongo S, Payne L, Watuka A, Katubulushi M, Kelly P (2009) High dose prolonged treatment with nitazoxanide is not effective for cryptosporidiosis in HIV positive Zambian children: a randomised controlled trial. BMC Infect Dis 9(1):195

    PubMed  PubMed Central  Google Scholar 

  • Arrowood MJ, Donaldson KIMBERLEY (1996) Improved purification methods for calf-derived Cryptosporidium parvum oocysts using discontinuous sucrose and cesium chloride gradients. J Eukaryot Microbiol 43(5):89S-89S

    CAS  PubMed  Google Scholar 

  • Atia MM, Abdul Fattah MM, Abdel Rahman HA, Mohammed FA, Al-Ghandour AMF (2016) Assessing the efficacy of nitazoxanide in treatment of Cryptosporidiosis using PCR examination. J Egypt Soc Parasitol 46(3):683–692

    Google Scholar 

  • Bayoumy AS, Helmy Y, Zaalouk T, Agamawy A (2020) In vitro Model for Cryptosporidium parvum infection. Al-Azhar Int Med J Artic 1(1):12–15

    Google Scholar 

  • Benamrouz S, Guyot K, Gazzola S, Mouray A, Chassat T, Delaire B, Chabe´M, Gosset P, Viscogliosi E, Dei-Cas E, Creusy C, Conseil V, Certad G, (2012) Cryptosporidium parvum infection in SCID Mice Infected with only one oocyst: qPCR assessment of parasite replication in tissues and development of digestive cancer. PLoS ONE 7(12):e51232

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bermudez LE, Inderlied B, Kolonoski P, Chee CB, Aralar P, Petrofsky M, Parman T, Green CE, Lewin AH, Ellis WY, Young S (2012) Identification of (+)-erythro-mefloquine as an active enantiomer with greater efficacy than mefloquine a gainst Mycobacterium avium infection in mice. Antimicrob Agents Chemother 56(8):4202–4206

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bermudez LE, Kolonoski P, Wu M, Aralar PA, Inderlied CB, Young LS (1999) Mefloquine is active in vitro and in vivo againstmycobacterium avium complex. Antimicrob Agents Chemother 43(8):1870–1874

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bermudez LE, Meek L (2014) Mefloquine and its enantiomers are active against Mycobacterium tuberculosis in vitro and in macrophages. Tuberc Res Treat. https://doi.org/10.1155/2014/530815

    Article  PubMed  PubMed Central  Google Scholar 

  • Borad A, Ward H (2010) Human immune responses in cryptosporidiosis. Future Microbiol 5:507–519

    CAS  PubMed  Google Scholar 

  • Cavicchi M, Whittle BJR (1999) Potentiation of cytokine induced iNOS expression in the human intestinal epithelial cell line, DLD-1, by cyclic AMP. Gut 45:367–374

    CAS  PubMed  PubMed Central  Google Scholar 

  • Checkley W, White AC Jr, Jaganath D, Arrowood MJ, Chalmers RM, Chen XM, Fayer R, Griffiths JK, Guerrant RL, Hedstrom L, Huston CD, Kotloff KL, Kang G, Mead JR, Miller M, Petri WA, Priest JW, Roos DS, Striepen B, Thompson RCA, Ward HD, Van Voorhis WA, Xiao L, Zhu G, Houpt ER (2015) A review of the global burden, novel diagnostics, therapeutics, and vaccine targets for cryptosporidium. Lancet Infect Dis 15(1):85–94

    PubMed  Google Scholar 

  • Chen W, Harp J, Harmsen AG (1993) Requirements for CD41 cells and gamma interferon in resolution of established Cryptosporidium parvum infection in mice. Infect Immun 61:3928–3932

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chen W, Harp JA, Harmsen AG, Havell EA (1993) Gamma interferon functions in resistance to Cryptosporidium parvum infection in severe combined immunodeficient mice. Infect Immun 61:3548–3551

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chen XM, Keithly JS, Paya CV, LaRusso NF (2002) Cryptosporidiosis. N Engl J Med 346:1723–1731

    PubMed  Google Scholar 

  • Choudhry N, Korbel DS, Edwards LA, Bajaj-Elliott M, McDonald V (2009) Dysregulation of interferon-γ-mediated signalling pathway in intestinal epithelial cells by Cryptosporidium parvum infection. Cell Microbiol 11(9):1354–1364

    CAS  PubMed  Google Scholar 

  • Current WL, Garcia LS (1991) Cryptosporidiosis. Clin Microbiol Rev 4:325–358

    CAS  PubMed  PubMed Central  Google Scholar 

  • Da Matta Guedes PM, Gutierrez FR, Maia FL, Milanezi CM, Silva GK, Pavanelli WR, Silva JS (2010) IL-17 produced during Trypanosoma cruzi infection plays a central role in regulating parasite-induced myocarditis. PLoS Negl Trop Dis 4:e604

    PubMed  Google Scholar 

  • Davami MH, Bancroft GJ, McDonald V (1997) Cryptosporidial infection in MHC congenic strains of mice: variation in susceptibility and the role of T-cell cytokine responses. Parasitol Res 83:257–263

    CAS  PubMed  Google Scholar 

  • Davis MA, Flaws JA, Young M, Collins K, Colburn NH (2000) Effect of ceramide on intracellular glutathione determines apoptotic or necrotic cell death of JB6 tumor cells. Toxicol Sci 53:8–55

    Google Scholar 

  • Drinkalla E, Wassa MJ, Coffeya TJ, Flynn RJ (2017) A rapid IL-17 response to Cryptosporidium parvum in the bovine intestine. Vet Immunol Immunopathol 191:1–4

    Google Scholar 

  • Drury RAB, Wallington EA (1980) Carleton’s Histological Technique. 5th ed. Oxford, New York, Toronto: Oxford University Press (5): 41–54

  • Duncan MJ, Shin J-S, Abraham SN (2002) Microbial entry through caveolae: variations on a theme. Cell Microbiol 4:783–791

    CAS  PubMed  Google Scholar 

  • Dutra MS, Béla SR, Peixoto-Rangel AL, Fakiola M, Cruz AG, Gazzinelli A, Quites HF, Bahia-Oliveira LM, Peixe RG, Campos WR, HiginoRocha AC, Miller NE, Blackwell JM, Antonelli LR, Gazzinelli RT (2013) Association of a NOD2 gene polymorphism and T-helper 17 cells with presumed ocular toxoplasmosis. J Infect Dis 207:152–163

    CAS  PubMed  Google Scholar 

  • El-Bahnasawy MM, Khalil HHM, Morsy TA (2011) Babesiosis in an Egyptian boy acquired from pet dog and a general review. J Egypt Soc Parasitol 41(1):99–108

    PubMed  Google Scholar 

  • El-Lakkany NM (2011) Seif el-Din SH. Sabra AA, Hammam OA

    Google Scholar 

  • El-Sayed NM, Fathy GM (2019) Prophylactic and therapeutic treatments’ effect of moringa oleifera methanol extract on cryptosporidium infection in immunosuppressed mice. Anti-Infect Agents 17(2):130–137

    CAS  Google Scholar 

  • Fichtenbaum CJ, Zackin R, Feinberg J, Benson C, Griffiths, JK, AIDS Clinical Trials Group New Works Concept Sheet Team 064 (2000) Rifabutin but not clarithromycin prevents cryptosporidiosis in persons with advanced HIV infection. Aids 14(18): 2889-2893

  • Franchimont D (2004) Overview of the actions of glucocorticoids on the immune response: a good model to characterize new pathways of immunosuppression for new treatment strategies. Ann N Y Acad Sci 1024:124–137

    CAS  PubMed  Google Scholar 

  • Gaafar MR (2012) Efficacy of Allium sativum (garlic) against experimental cryptosporidiosis. AJM 48:59–66

    Google Scholar 

  • Gaffen SL (2009) Structure and signalling in the IL-17 receptor family. Nat Rev Immunol 9:556–567

    CAS  PubMed  PubMed Central  Google Scholar 

  • Garcia LS (2007) Clinically important human parasites: Intestinal protozoa: Cryptosporidium spp. In: Diagnostic Medical Parasitology. Garcia LS 5th ed ASM press Washington DC (2): 771–812

  • Gargala G (2008) Drug treatment and novel drug target against Cryptosporidium. Parasite 15:275–281

    CAS  PubMed  Google Scholar 

  • Gonzalez-Lombana C, Gimblet C, Bacellar O, Oliveira WW, Passos S, Carvalho LP, Goldschmidt M, Carvalho EM, Scott P (2013) IL-17 mediates immunopathology in the absence of IL-10 following Leishmania major infection. PLoS Pathog 9:e100324

    Google Scholar 

  • Griffiths JK, Balakrishnan R, Widmer G, Tzipori S (1998) Paromomycin and geneticin inhibit intracellular Cryptosporidium parvum without trafficking through the host cell cytoplasm: implications for drug delivery. Infect Immun 66:3874–3883

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hannun YA (1996) Functions of ceramide in coordinating cellular responses to stress. Science 274:1855–1859

    CAS  PubMed  Google Scholar 

  • Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, Weaver CT (2005) Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 6:1123–1132

    CAS  PubMed  Google Scholar 

  • Holmberg SD, Moorman AC, Von Bargen JC, Palella FJ, Loveless MO, Ward DJ (1998) HIV outpatient study (hops) investigators possible effectiveness of clarithromycin and rifabutin for cryptosporidiosis chemoprophylaxis in HIV disease. JAMA 279(5):384–386

    CAS  PubMed  Google Scholar 

  • Hosking BC, Watson TG, Leathwick DM (1996) Multigeneric resistance to oxfendazole by nematodes in cattle. Vet Rec 138:67–68

    CAS  PubMed  Google Scholar 

  • Ingram K, Ellis W, Keiser J (2012) Antischistosomal activities of mefloquine-related arylmethanols. Antimicrob Agents Chemother 56(6):3207–3215

    CAS  PubMed  PubMed Central  Google Scholar 

  • Keiser J, Chollet J, Xiao SH, Mei JY, Jiao PY, Utzinger J, Tanner M (2009) Mefloquine an aminoalcohol with promising antischistosomal properties in mice. PLoS Negl Trop Dis 3(1):e350–e358

    PubMed  PubMed Central  Google Scholar 

  • Keiser J, Duthaler U, Utzinger J (2010) Update on the diagnosis and treatment of foodborne trematode infections. Curr Opin Infect Dis 23:513–520

    PubMed  Google Scholar 

  • Keiser J, N’Guessan NA, Adoubryn KD, Silué KD, Vounatsou P, Hatz C, …N’Goran EK, (2010) Efficacy and safety of mefloquine, artesunate, mefloquine-artesunate, and praziquantel against Schistosoma haematobium: randomized, exploratory open-label trial. Clin Infect Dis 50(9):1205–1213

    CAS  PubMed  Google Scholar 

  • Keiser J, Odermatt P, Tesana S (2009) b) Dose response relationships and tegumental surface alterations in opisthorchis viverrini following treatment with mefloquine in vivo and in vitro. Parasitol Res 105:261–266

    PubMed  Google Scholar 

  • Kelly MN, Kolls JK, Happel K, Schwartzman JD, Schwarzenberger P, Combe C, Moretto M, Khan IA (2005) Interleukin-17/interleukin-17 receptor-mediated signaling is important for generation of an optimal polymorphonuclear response against Toxoplasma gondii infection. Infect Immun 73(1):617–621

    CAS  PubMed  PubMed Central  Google Scholar 

  • Keusch GT, Rosenberg IH, Denno DM, Duggan C, Guerrant RL, Lavery JV, Tarr PI, Ward HD, Black RE, Nataro JP, Ryan ET, Bhutta ZA, Coovadia H, Lima A, Ramakrishna B, Anita KMZ, Burgess DCH, Brewer T (2013) Implications of acquired environmental enteric dysfunction for growth and stunting in infants and children living in low- and middle-income countries. Food Nutr Bull 34(3):357–364

    PubMed  PubMed Central  Google Scholar 

  • Korn T, Bettelli E, Oukka M, Kuchroo VK (2009) IL-17 and Th17 Cells. Annu Rev Immunol 27:485–551

    CAS  PubMed  Google Scholar 

  • Kumar N, Singh R, Rawat DS (2011) Retracted: tetraoxanes: synthetic and medicinal chemistry perspective. Med Res Rev 31(3):482–482

    Google Scholar 

  • Küster T, Stadelmann B, Rufener R, Risch C, Müller J, Hemphill A et al (2015) Oral treatments of Echinococcus multilocularis-infected mice with the antimalarial drug mefloquine that potentially interacts with parasite ferritin and cystatin. Int J Antimicrob Agents 46:546–551

    PubMed  Google Scholar 

  • Lean IS, McDonald V, Pollok RC (2002) The role of cytokines in the pathogenesis of cryptosporidium infection. Curr Opin Infect Dis 15:229–234

    CAS  PubMed  Google Scholar 

  • Lemieux MW, Sonzogni-Desautels K, Ndao M (2018) Lessons learned from protective immune responses to optimize vaccines against cryptosporidiosis. Pathogens 7(1):2

    Google Scholar 

  • Li X, Brasseur P, Agnamey P, Leméteil D, Favennec L, Ballet JJ, Rossignol JF, al, (2003) Long-lasting anticryptosporidial activity of nitazoxanide in an immun- osuppressed rat model. Folia Parasitol 50(1):19–22

    CAS  Google Scholar 

  • Manes S, del Real G, Martinez AC (2003) Pathogens: raft hijackers. Nat Rev Immunol 3:557–568

    CAS  PubMed  Google Scholar 

  • McDonald V, Bancroft GJ (1994) Mechanisms of innate and acquired resistance to Cryptosporidium parvum infection in SCID mice. Parasite Immunol 16:315–320

    CAS  PubMed  Google Scholar 

  • Miyazaki Y, Hamano S, Wang S, Shimanoe Y, Iwakura Y, Yoshida H (2010) IL-17 is necessary for host protection against acute-phase Trypanosoma cruzi infection. J Immunol 185:1150–1157

    CAS  PubMed  Google Scholar 

  • Munkhjargal T, AbouLaila M, Terkawi MA, Sivakumar T, Ichikawa M, Davaasuren B, Igarashi I et al (2012) Inhibitory effects of pepstatin a and mefloquine on the growth of babesia parasites. Am J Trop Med Hyg 87(4):681–688

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nelson JB, O’Hara SP, Small AJ, Tietz PS, Choudhury AK, Pagano RE, Chen XM, LaRusso NF (2006) Cryptosporidium parvum infects human cholangiocytes via sphingolipid-enriched membrane microdomains. Cell Microbiol 8(12):1932–1945

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ng JS, Pingault N, Gibbs R, Koehler A, Ryan U (2010) Molecular characterization of Cryptosporidium outbreaks in Western and South Australia. Exp Parasitol 125(4):325–328

    PubMed  Google Scholar 

  • Oppmann B, Lesley R, Blom B, Timans JC, Xu Y, Hunte B, Vega F, Yu N, Wang J, Singh K, Zonin F, Vaisberg E, Churakova T, Liu M, Gorman D, Wagner J, Zurawski S, Liu Y, Abrams JS, Moore KW, Rennick D, de Waal-Malefyt R, Hannum C, Bazan JF, Kastelein RA (2000) Novel p19 protein engages IL-12p40 to form a cytokine, IL23, with biological activities similar as well as distinct from IL-12. Immunity 13:715–725

    CAS  PubMed  Google Scholar 

  • Oyibo W, Okangba C, Obi R et al (2011) Diagnosis of intestinal cryptosporidiosis in Africa: prospects and challenges. J Appl Biosci 40:2659–2667

    Google Scholar 

  • Paget GE, Barnes JM (1964) Evaluation of drug activities. In: Laurence DR Backarach AL (eds.) Pharmacometrics London and New York: AcademicPress

  • Pankova-Kholmyansky I, Dagan A, Gold D, Zaslavsky Z, Skutelsky E, Gatt S, Flescher E (2003) Ceramide mediates growth inhibition of the Plasmodium falciparum parasites. Cell Mol Life Sci 60:577–587

    CAS  PubMed  Google Scholar 

  • Pappu R, Ramirez-Carrozzi V, Sambandam A (2011) The interleukin-17 cytokine family: critical players in host defence and inflammatory diseases. Immunology 134:8–16

    CAS  PubMed  PubMed Central  Google Scholar 

  • Peat J, Barton B (2005) Medical statistics. A guide to data analysis and critical appraisal. First edition. Wiley-Blackwell 113–119

  • Peckham RK, Brill R, Foster DS, Bowen AL, Leigh JA, Coffey TJ, Flynn RJ (2014) Two distinct populations of bovine IL-17(+) T-cells can be induced and WC1(+)IL-17(+)gammadelta T-cells are effective killers of protozoan parasites. Sci Rep 4:5431

    CAS  PubMed  PubMed Central  Google Scholar 

  • Peters A, Yosef N (2014) Understanding Th17 cells through systematic genomic analyses. Curr Opin Immunol 28:42–48

    CAS  PubMed  Google Scholar 

  • Petry F, Jakobi V, Tessema TS (2010) Host immune response to Cryptosporidium parvum infection. Exp Parasitol 126:304–309

    CAS  PubMed  Google Scholar 

  • Pollok RC, Farthing MJ, Bajaj-Elliott M, Sanderson IR, Mcdonald V (2001) Interferon gamma induces enterocyte resistance against infection by the intracellular pathogen Cryptosporidium parvum. Gastroenterology 120(1):99–107

    CAS  PubMed  Google Scholar 

  • Raqib R, Lindberg AA, Bjork L, Bardham PK, Wretlind B, Andersson U, Andersson J (1995) Down-regulation of gamma interferon, tumor necrosis factor type I, interleukin 1 (IL-1) type I, IL-3, IL-4, and transforming growth factor beta type I receptors at the local site during the acute phase of Shigella infection. Infect Immun 63(8):3079–3087

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rasmussen KR, Healey MC (1992) Experimental Cryptosporidium parvum infections in immunesuppressed adult mice. J Inefct Immun 4:1648–1652

    Google Scholar 

  • Reese NC, Current WL, Ernst JV, Bailey WS (1982) Cryptosporidiosis of man and calf: a case report and results of experimental infections in mice and rats. Am J Trop Med Hyg 31(2):226–229

    CAS  PubMed  Google Scholar 

  • Reinecker HC, MacDermott RP, Mirau S, Dignass A, Podolsky DK (1996) Intestinal epithelial cells both express and respond to interleukin15. Gastroenterology 111(6):1706–1713

    CAS  PubMed  Google Scholar 

  • Reinecker HC, Podolsky DK (1995) Human intestinal epithelial cells express functional cytokine receptors sharing the common gamma chain of the interleukin 2 receptor. Proc Nat Acad Sci USA 92(18):8353–8357

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ruvolo PP (2001) Ceramide regulates cellular homeostasis via diverse stress signaling pathways. Leukemia 15(8):1153–1160

    CAS  PubMed  Google Scholar 

  • Ryan U, Zahedi A, Paparini A (2016) Cryptosporidium in humans and animals—a one health approach to prophylaxis. Parasite Immunol 38:535–547

    CAS  PubMed  Google Scholar 

  • Sanjabi S, Zenewicz LA, Kamanaka M, Flavell RA (2009) Antiinflammatory and pro- inflammatory roles of TGF-beta, IL-10, and IL-22 in immunity and autoimmunity. Curr Opin Pharmacol 9(4):447–453

    CAS  PubMed  PubMed Central  Google Scholar 

  • Schlagenhauf P (1999) Mefloquine for malaria chemoprophylaxis 1992–1998: a review. J Travel Med 6:122–133

    CAS  PubMed  Google Scholar 

  • Schlagenhauf P, Adamcova M, Regep L, Schaerer MT, Rhein HG (2010) The position of mefloquine as a 21st century malaria chemoprophylaxis. Malar J 9(1):357

    PubMed  PubMed Central  Google Scholar 

  • Schuetz A, Deleage C, Sereti I, Rerknimitr R, Phanuphak N, PhuangNgern Y, Estes JD, Sandler NG, Sukhumvittaya S, Marovich M, Jongrakthaitae S, Akapirat S, Fletscher JL, Kroon E, Dewar R, Trichavaroj R, Chomchey N, Douek DC, O Connell RJ, Ngauy V, Robb ML, Phanuphak P, Michael NL, Excler JL, Kim JH, de Souza MS, Ananworanich J, RV254/SEARCH 010 and RV304/SEARCH 013 Study Groups (2014) Initiation of ART during early acute HIV infection preserves mucosal Th17 function and reverses HIV-related immune activation. PLoS Pathog 10: e1004543

  • Shalaby HA, El Namaky AH, Kamel RO (2016) In vitro tegumental alterations on adult Fasciola gigantica caused by mefloquine. J Parasit Dis 40(1):145–151

    PubMed  Google Scholar 

  • Shirley D-AT, Moonah SN, Kotloff KL (2012) Burden of disease from cryptosporidiosis. Curr Opin Infect Dis 25:555–563

    PubMed  PubMed Central  Google Scholar 

  • Smith NH, Cron S, Valdez LM, Chappell CL, White AC Jr (1998) Combination drug therapy for cryptosporidiosis in AIDS. J Infect Dis 178(3):900–903

    CAS  PubMed  Google Scholar 

  • Sparks H, Nair G, Castellanos-Gonzalez A, White AC (2015) Treatment of Cryptosporidium: what we know, gaps, and the way forward. Curr Trop Med Rep 2(3):181–187

    PubMed  PubMed Central  Google Scholar 

  • Striepen B (2013) Parasitic infections: Time to tackle cryptosporidiosis. Nature 503:189–191

    PubMed  Google Scholar 

  • Tarazona R, David A, Belwett N, Manuel S, Carmona MD (1998) C. parvum infection in experimentally infected mice: infection dynamics and effect of immunosuppression. Folia Parasitol 45(2):101–107

    CAS  Google Scholar 

  • Tilley M, McDonald V, Bancroft GJ (1995) Resolution of cryptosporidial infection in mice correlates with parasite-specific lymphocyte proliferation associated with both Th1 and Th2 cytokine secretion. Parasite Immunol 17(9):459–464

    CAS  PubMed  Google Scholar 

  • Van Wyk BE, Wink M (2004) Medicinal plants of the world an illustrated scientific guide to important. Medicinal plants and their uses Timber press Portland OR USA

  • Wanyiri JW, Kanyi H, Maina S, Wang DE, Steen A, Ngugi P, Wamae CN (2014) Cryptosporidiosis in HIV/AIDS patients in Kenya: clinical features, epidemiology, molecular characterization and antibody responses. Am J Trop Med Hyg 91:319–328

    PubMed  PubMed Central  Google Scholar 

  • Waters WR, Harp JA (1996) Cryptosporidium parvum infection in T-cell receptor (TCR)-alpha- and TCR-delta-deficient mice. Infect Immun 64:1854–1857

    CAS  PubMed  PubMed Central  Google Scholar 

  • Weaver CT, Hatton RD, Mangan PR, Harrington LE (2007) IL-17 family cytokines and the expanding diversity of effector T cell lineages. Annu Rev Immunol 25:821–852

    CAS  PubMed  Google Scholar 

  • Xiao SH, Utzinger J, Tanner M, Keiser J, Xue J (2013) Advances with the Chinese anthelminthic drug tribendimidine in clinical trials and laboratory investigations. Acta Trop 126:115–126

    CAS  PubMed  Google Scholar 

  • Xiao SH, Xue J, Li-li X, Zhang YN, Qiang HQ (2010) Effectiveness of mefloquine against Clonorchis sinensis in rats and Paragonimus westermani in dogs. Parasitol Res 107:1391–1397

    PubMed  Google Scholar 

  • Yang XO, Panopoulos AD, Nurieva R, Chang SH, Wang D, Watowich SS, Dong C (2007) STAT3 regulates cytokine-mediated generation of inflammatory helper T cells. J Biol Chem 282:9358–9363

    CAS  PubMed  Google Scholar 

  • Yang XO, Pappu BP, Nurieva R, Akimzhanov A, Kang HS, Chung Y, Ma L, Shah B, Panopoulos AD, Schluns KS, Watowich SS, Tian Q, Jetten AM, Dong C (2008) T helper 17 lineage differentiation is programmed by orphan nuclear receptors ROR alpha and ROR gamma. Immunity 28:29–39

    CAS  PubMed  Google Scholar 

  • Zhang H, Hu X, Liu X, Zhang R, Fu Q, Xu X (2012) The Treg/Th17 imbalance in Toxoplasma gondii-infected pregnant mice. Am J Reprod Immunol 67:112–121

    CAS  PubMed  Google Scholar 

  • Zhang K, Bangs JD, Beverley SM (2010) Sphingolipids in parasitic protozoa. Adv Exp Med Biol 688(238):248

    Google Scholar 

  • Zhang L, Liu R, Song M, Hu Y, Pan B, Cai J, Wang M (2013) Eimeria tenella: interleukin 17 contributes to host immunopathology in the gut during experimental infection. Exp Parasitol 133:121–130

    CAS  PubMed  Google Scholar 

  • Zhang Y, Chen L, Gao W, Hou X, Gu Y, Gui L, Huang D, Liu M, Ren C, Wang S, Shen J (2012) IL-17 neutralization significantly ameliorates hepatic granulomatous inflammation and liver damage in Schistosoma japonicum infected mice. Eur J Immunol 42(6):1523–1535

    CAS  PubMed  Google Scholar 

  • Zhao GH, Cheng WY, Wang W, Jia YQ, Fang YQ, Du SZ, Yu SK (2014) The expression dynamics of IL-17 and Th17 response relative cytokines in the trachea and spleen of chickens after infection with Cryptosporidium baileyi. Parasit Vectors 7:212

    PubMed  PubMed Central  Google Scholar 

  • Zhao GH, Fang YQ, Ryan U, Guo YX, Wu F, Du SZ, Chen DK, Lin Q (2016) Dynamics of Th17 associating cytokines in Cryptosporidium parvum-infected mice. Parasitol Res 115(2):879–887

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to acknowledge Dr. Samah M. Ahmed; Assistant Prof. of Histology Dept. Zagazig University, Egypt; and Dr. Hanaa A. Atwa; Assistant Prof. of Pathology Dept. Zagazig University, Egypt for their help in imaging, preparation and histopathological examination of mice tissue sections.

Funding

None.

Author information

Authors and Affiliations

  1. Department of Parasitology, Theodor Bilharz Research Institute, Giza, Egypt

    Eman S. El-Wakil

  2. Department of Clinical Pharmacology, Faculty of Medicine, Zagazig University, Zagazig, Egypt

    Amal E. Salem

  3. Department of Medical Parasitology, Faculty of Medicine, Zagazig University, Zagazig, Egypt

    Asmaa M. F. Al-Ghandour

Authors
  1. Eman S. El-Wakil
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Amal E. Salem
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Asmaa M. F. Al-Ghandour
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eman S. El-Wakil.

Ethics declarations

Conflicts of interest

None.

Ethical consideration

This study was approved by the Research Ethics Committee of TBRI (PT: 515). All applied experiments on animals were conducted according to the guidelines of the National Institutes of Health (NIH, 1996) and its amendments for the care and use of laboratory animals.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

El-Wakil, E.S., Salem, A.E. & Al-Ghandour, A.M.F. Evaluation of possible prophylactic and therapeutic effect of mefloquine on experimental cryptosporidiosis in immunocompromised mice. J Parasit Dis 45, 380–393 (2021). https://doi.org/10.1007/s12639-020-01315-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12639-020-01315-4

Keywords

Search

Navigation