Morphological effects and tegumental alterations induced by mefloquine on schistosomula and adult flukes ofSchistosoma mansoni

Parasitology - Tập 137 Số 1 - Trang 85-98 - 2010
Theresia Manneck1, Yolanda Haggenmüller1, Jennifer Keiser1
1Department of Medical Parasitology and Infection Biology, Swiss Tropical Institute, CH-4002 Basel, Switzerland

Tóm tắt

SUMMARYThere is a pressing need to develop novel anti-schistosomal drugs, as current treatment relies largely on praziquantel (PZQ). To further strengthen current evidence of the anti-schistosomal properties of mefloquine (MQ), we studied the temporal effect of this compoundin vitroandin vivo, and examined alterations on the tegumental surface of schistosomula and adults ofS. mansoniby means of scanning electron microscopy (SEM). Schistosomula and adults were each incubatedin vitrousing MQ over a wide concentration range (1–100 μg/ml). In addition, mice infected with adultS. mansoniwere treated with a single oral dose of 400 mg/kg MQ, and worms were recovered 24, 48, 72, 96 and 120 h following treatment. MQ showed a rapid onset of action on schistosomulain vitro; 100 and 75 μg/ml of MQ killed schistosomula immediately; the minimal lethal and effective concentrations of MQ on schistosomula after 1 h were 25 and 5 μg/ml, respectively. Adult worms incubated with 100 and 10 μg/ml of MQ were dead after 1 h and 24 h of incubation, respectively. A hepatic shift of adult schistosomes was observed in mice already 24 h after treatment, and 120 h following treatment >98% of all worms had translocated to the liver. SEM observations revealed extensive tegumental destruction, including blebbing, shrinking and sloughing, particularly followingin vitroincubation and on the tegument of female worms.

Từ khóa


Tài liệu tham khảo

10.1371/journal.pmed.0040014

10.1517/17460441.2.S1.S1

10.1590/S0074-02762001000700022

10.1007/BF00389899

10.1016/j.tmaid.2008.06.006

10.1016/0020-7519(88)90068-9

10.1371/journal.pntd.0000350

10.1017/S003118200006193X

10.1016/j.cbpa.2007.05.031

Wilson, 1974, The tegument of Schistosoma mansoni: observations on the formation, structure and composition of cytoplasmic inclusions in relation to tegument function, Parasitology, 68, 239, 10.1017/S0031182000045765

10.1017/S0031182000060121

10.2307/3278293

10.1016/0020-7519(73)90004-0

10.2307/3280632

Xiao, 1983, Observation on tegument damage of Schistosoma japonicum and penetration of host leucocytes into the worm body caused by pyquiton, Acta Pharmaceutica Sinica, 18, 241

2004, The Global Burden of Disease: 2004 Update

10.1016/S0065-308X(08)60188-8

2002, Prevention and control of schistosomiasis and soil-transmitted helminthiasis; report of a WHO expert committee, Geneva 2002, WHO Technical Report Series, 912, 1

10.1371/journal.pmed.0030102

Xiao, 2001, Artemether administered together with haemin damages schistosomes in vitro, Transactions of the Royal Society of Tropical Medicine and Hygiene, 95, 67, 10.1016/S0035-9203(01)90336-0

10.1517/17460441.2.S1.S9

10.1126/science.130.3373.432

10.1016/S0001-706X(03)00029-9

10.1074/jbc.271.42.26117

10.1016/j.ijpara.2003.12.003

10.1517/17460441.2.S1.S35

10.1016/S0006-2952(97)00510-8

10.1016/S0001-706X(00)00067-X

10.1002/med.2610010304

10.1016/0040-8166(92)90079-M

10.1016/S1473-3099(06)70521-7

10.1016/j.parint.2005.04.001

Xiao, 1981, Ultrastructural changes of the tegument, syncithium, vitelline cells and muscles of Schistosoma japonicum caused by pyquiton, Acta Zoologica Sinica, 27, 305

10.1017/S0031182000055311

Brindley, 1987, The chemotherapeutic effect of praziquantel against Schistosoma mansoni is dependent of host antibody response, The Journal of Immunology, 139, 215, 10.4049/jimmunol.139.1.215

Caffrey, 2009, Drug Discovery in Infectious Diseases: from Molecular Targets to Drug Candidates, 301

Cioli, 2003, Praziquantel, Parasitology Research, 90, 3, 10.1007/s00436-002-0751-z

10.1097/QCO.0b013e328318978f

10.1016/S0140-6736(06)69440-3

10.1177/1742395307084407

10.1038/269147a0

10.1016/0014-4894(74)90076-9

10.1517/17460441.2.S1.S53

Rogers, 1983, Schistosoma mansoni adults: Uptake and incorporation of epimeric monosaccharides by the tegument, Proceedings of the Oklahoma Academy of Science, 63, 12

10.1038/nm1737

10.1007/BF00934012

10.1017/S0031182000086248

10.1517/14656566.5.2.263

Utzinger, 2007, Artemisinins for schistosomiasis and beyond, Current Opinion in Investigational Drugs, 8, 105

10.2307/3281955

10.1128/AAC.01537-06

Xiao, 2000, Tegumental changes in adult Schistosoma mansoni harbored in mice treated with artemether, The Journal of Parasitology, 86, 1125, 10.1645/0022-3395(2000)086[1125:TCIASM]2.0.CO;2

10.2307/3273678

10.1007/s00436-009-1341-0