• 1

    Haynes RK, 2001. Artemisinin and derivatives: the future for malaria treatment? Curr Opin Infect Dis 14 :719–726.

  • 2

    Li Y, Wu YL, 2003. An over four millennium story behind qing-haosu (artemisinin) - a fantastic antimalarial drug from a traditional Chinese herb. Curr Med Chem 10 :2197–2230.

    • Search Google Scholar
    • Export Citation
  • 3

    Chen DJ, Fu LF, Shao PP, Wu FZ, Fan CZ, Shu H, Ren CX, Sheng XL, 1980. Studies on the efficacy of artemether in experimental schistosomiasis. Zhong Hui Yi Xue Zha Zhi 60 :422–425.

    • Search Google Scholar
    • Export Citation
  • 4

    Le W, You J, Yang Y, Mei J, Guo H, Yang H, Zang C, 1982. Studies on the efficacy of artemether in experimental schistosomiasis. Acta Pharm Sin 17 :187–193.

    • Search Google Scholar
    • Export Citation
  • 5

    Le WJ, You JQ, Mei JY, 1983. Chemotherapeutic effect of artesunate in experimental schistosomiasis. Acta Pharm Sin 18 :619–621.

  • 6

    Utzinger J, Keiser J, Xiao SH, Tanner M, Singer BH, 2003. Combination chemotherapy of schistosomiasis in laboratory studies and clinical trials. Antimicrob Agents Chemother 47 :1487–1495.

    • Search Google Scholar
    • Export Citation
  • 7

    Utzinger J, Keiser J, 2004. Schistosomiasis and soil-transmitted helminthiasis: common drugs for treatment and control. Expert Opin Pharmacother 5 :263–285.

    • Search Google Scholar
    • Export Citation
  • 8

    Xiao SH, Yang YQ, You QQ, Utzinger J, Guo HF, Jiao PY, Mei JY, Guo J, Bergquist R, Tanner M, 2002. Potential long-term toxicity of repeated orally administered doses of artemether in rats. Am J Trop Med Hyg 66 :30–34.

    • Search Google Scholar
    • Export Citation
  • 9

    Xiao SH, Wu YL, Tanner M, Wu WM, Utzinger J, Mei JY, Scorneaux B, Chollet J, Zhai Z, 2003. Schistosoma japonicum: in vitro effects of artemether combined with haemin depend on cultivation media and appraisal of artemether products appearing in the media. Parasitol Res 89 :459–466.

    • Search Google Scholar
    • Export Citation
  • 10

    Bergquist R, Al-Sherbiny M, Barakat R, Olds R, 2002. Blueprint for schistosomiasis vaccine development. Acta Trop 82 :183–192.

  • 11

    Hagan P, Sharaf O, 2003. Schistosomiasis vaccines. Expert Opin Biol Ther 3 :1271–1278.

  • 12

    Dean DA, 1983. Schistosoma and related genera: acquired resistance in mice. Exp Parasitol 55 :1–104.

  • 13

    Campbell WC, 1963. Attempts to demonstrate immunity to Schistosoma mansoni in mice previously subjected to chemically abbreviated infections. J Parasitol 49 :824–829.

    • Search Google Scholar
    • Export Citation
  • 14

    Colley DG, Secor WE, 2004. Immunoregulation and World Health Assembly resolution 54.19: why does treatment control morbidity? Parasitol Int 53 :143–150.

    • Search Google Scholar
    • Export Citation
  • 15

    Armitage P, Berry G, 1987. Statistical Methods in Medical Research. Oxford: Blackwell.

  • 16

    Smythies LE, Betts C, Coulson PS, Dowling MA, Wilson RA, 1996. Kinetics and mechanism of effector focus formation in the lungs of mice vaccinated with irradiated cercariae of Schistosoma mansoni. Parasite Immunol 18 :359–369.

    • Search Google Scholar
    • Export Citation
  • 17

    Harrop R, Jennings N, Mountford AP, Coulson PS, Wilson RA, 2000. Characterization, cloning and immunogenicity of antigens released by transforming cercariae of Schistosoma mansoni. Parasitology 121 :385–394.

    • Search Google Scholar
    • Export Citation
  • 18

    Dean DA, Cioli D, Bukowski MA, 1981. Resistance induced by normal and irradiated Schistosoma mansoni: ability of various worm stages to serve as inducers and targets in mice. Am J Trop Med Hyg 30 :1026–1032.

    • Search Google Scholar
    • Export Citation
  • 19

    Xiao SH, Catto BA, 1989. In vitro and in vivo studies of the effect of artemether on Schistosoma mansoni. Antimicrob Agents Chemother 33 :1557–1562.

    • Search Google Scholar
    • Export Citation
  • 20

    Utzinger J, Xiao SH, N’Goran EK, Bergquist R, Tanner M, 2001. The potential of artemether for the control of schistosomiasis. Int J Parasitol 31 :1549–1562.

    • Search Google Scholar
    • Export Citation
  • 21

    Bout D, Deslèe D, Capron A, 1986. Antischistosomal effect of cyclosporin A: cure and prevention of mouse and rat schistosomiasis mansoni. Infect Immun 52 :823–827.

    • Search Google Scholar
    • Export Citation
  • 22

    Smith SR, Pennline K, Terminelli C, DaFonseca M, Pellerito F, Umland S, 1988. Inhibition of graft-vs-host induced immuno-deficiency with immunosuppressive therapy. Immunopharmacol Immunotoxicol 10 :545–578.

    • Search Google Scholar
    • Export Citation
  • 23

    Price R, van Vugt M, Phaipun L, Luxemburger C, Simpson J, McGready R, ter Kuile F, Kham A, Chongsuphajaisiddhi T, White NJ, Nosten F, 1999. Adverse effects in patients with acute falciparum malaria treated with artemisinin derivatives. Am J Trop Med Hyg 60 :547–555.

    • Search Google Scholar
    • Export Citation
  • 24

    van Agtmael MA, Shan CQ, Jiao XQ, Mull R, van Boxtel CJ, 1999. Multiple dose pharmacokinetics of artemether in Chinese patients with uncomplicated falciparum malaria. Int J Antimicrob Agents 12 :151–158.

    • Search Google Scholar
    • Export Citation
  • 25

    Woolhouse MEJ, 1995. Human schistosomiasis: potential consequences of vaccination. Vaccine 13 :1045–1050.

  • 26

    Woolhouse MEJ, Hagan P, 1999. Seeking the ghost of worms past. Nat Med 5 :1225–1227.

  • 27

    Mutapi F, Ndhlovu PD, Hagan P, Spicer JT, Mduluza T, Turner CMR, Chandiwana SK, Woolhouse MEJ, 1998. Chemotherapy accelerates the development of acquired immune responses to Schistosoma haematobium infection. J Infect Dis 178 :289–293.

    • Search Google Scholar
    • Export Citation
  • 28

    Grzych JM, Grezel D, Xu CB, Neyrinck JL, Capron M, Ouma JH, Butterworth AE, Capron A, 1993. IgA antibodies to a protective antigen in human schistosomiasis mansoni. J Immunol 150 :527–535.

    • Search Google Scholar
    • Export Citation
  • 29

    Karanja DM, Hightower AW, Colley DG, Mwinzi PN, Galil K, Andove J, Secor WE, 2002. Resistance to reinfection with Schistosoma mansoni in occupationally exposed adults and effect of HIV-1 co-infection on susceptibility to schistosomiasis: a longitudinal study. Lancet 360 :592–596.

    • Search Google Scholar
    • Export Citation
  • 30

    de Clercq D, Vercruysse J, Verlé P, Niasse F, Kongs A, Diop M, 2000. Efficacy of artesunate against Schistosoma mansoni infections in Richard Toll, Senegal. Trans R Soc Trop Med Hyg 94 :90–91.

    • Search Google Scholar
    • Export Citation
 
 
 

 

 
 
 

 

 

 

 

 

 

TRIGGERING OF HIGH-LEVEL RESISTANCE AGAINST SCHISTOSOMA MANSONI REINFECTION BY ARTEMETHER IN THE MOUSE MODEL

View More View Less
  • 1 Ingerod 407, Brastad, Sweden; Swiss Tropical Institute, Basel, Switzerland; National Institute of Parasitic Diseases, Chinese Centre for Disease Control and Prevention, Shanghai, People’s Republic of China

Artemether, a methyl ether derivative of dihydroartemisinin, not only exhibits antimalarial properties, but also possesses strong activity against schistosomula, the immature stages of a parasitic worm that can cause schistosomiasis. To test if the effect would be similar to that of irradiation with respect to the induction of immunologic protective responses, groups of mice were infected with Schistosoma mansoni cercariae and treated with artemether at 1–3 weeks post-infection. Control mice were either infected with normal cercariae or with cercariae exposed to radiation that permitted early development but not maturation of the parasites. The mice were challenged six weeks after the initial infection, and the mean numbers of schistosomes recovered in the various groups were calculated upon dissection eight weeks post-challenge. The administration of artemether two weeks after the initial infection resulted in 58% protection, while giving the drug three weeks post-infection increased the level of protection to 81%. This level of protection is as high as that normally obtained by immunization with irradiated cercariae (84% in the present study) and is superior to the level of resistance obtained with any individual schistosome vaccine candidate antigen thus far reported.

Author Notes

Reprint requests: Marcel Tanner, Swiss Tropical Institute, PO Box, CH-4002 Basel, Switzerland, Telephone: 41-61-284-8283, Fax: 41-61-271-5179, E-mail: marcel.tanner@unibas.ch.
Save