Enhanced Larval Cyst Growth of Echinococcus multilocularis in Praziquantel-Treated Jirds (Meriones unguiculatus)

Alan A. MarchiondoFermenta Animal Health Company, Department of Zoology, Brigham Young University, Electron Microscopy Facility, Eastern Virginia Medical School of the Medical College of Hampton Roads, Upjohn Laboratories, Kansas City, Missouri

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Rujing MingFermenta Animal Health Company, Department of Zoology, Brigham Young University, Electron Microscopy Facility, Eastern Virginia Medical School of the Medical College of Hampton Roads, Upjohn Laboratories, Kansas City, Missouri

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Ferron L. AndersenFermenta Animal Health Company, Department of Zoology, Brigham Young University, Electron Microscopy Facility, Eastern Virginia Medical School of the Medical College of Hampton Roads, Upjohn Laboratories, Kansas City, Missouri

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James H. SlusserFermenta Animal Health Company, Department of Zoology, Brigham Young University, Electron Microscopy Facility, Eastern Virginia Medical School of the Medical College of Hampton Roads, Upjohn Laboratories, Kansas City, Missouri

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George A. ConderFermenta Animal Health Company, Department of Zoology, Brigham Young University, Electron Microscopy Facility, Eastern Virginia Medical School of the Medical College of Hampton Roads, Upjohn Laboratories, Kansas City, Missouri

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Jirds (Meriones unguiculatus) inoculated intraperitoneally with cystic material of Echinococcus multilocularis were given daily oral treatments of praziquantel at 300 mg/kg of body weight (bw) or dimethyl sulfoxide vehicle for five-day treatment regimens starting at 29 days postinoculation (PI) up to 69 days PI. At 39 or 49 days PI, the growth of the larval cystic mass (LCM) in jirds following a single or two five-day treatment regimens was significantly enhanced (P < 0.05) by 129.0% (2.3-fold) or 102.9% (2.0-fold), respectively. At 59 or 69 days PI following three or four five-day treatments with praziquantel, LCM growth was enhanced by 47.8% (1.5-fold) and 44.1% (1.4-fold), respectively, but was no longer significantly different than that in control jirds. A single five-day treatment on 29–33 days PI (with necropsy at 69 days PI) significantly enhanced the growth of the LCM by 87.6% (1.9-fold). Parasites from praziquantel treatment regimens examined ultrastructurally showed consistent damage to the germinal membrane evidenced by vacuolization and rupture of syncytial cytoplasm, rupture and coalescence of the electron-lucent vesicles just below the microvilli of the tegumental surface, and swelling and rounding of mitochondria. At 39 days PI, increased blebbing of the germinal membrane into the lumen of the LCM in praziquantel-treated animals was observed by scanning electron microscopy. The treatment-induced blebs were identified as nucleated germinal cells by transmission electron microscopy and appeared to be responsible for metastasis and enhanced growth of the LCM. Although praziquantel damaged the ultrastructural integrity of the LCM, treatment failed to inhibit larval cyst growth or protoscolex development. In conclusion, oral praziquantel treatment (300 mg/kg bw/day for single or multiple five-day treatment regimens from 29–69 days PI) of jirds infected with E. multilocularis enhanced the growth of the LCM (1.4–2.3-fold) apparently by inducing germinal cell release and metastasis.

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