Biochemical and pathological evaluation of albendazole/thalidomide co-therapy against eosinophilic meningitis or meningoencephalitis induced by Angiostrongylus cantonensis

J Antimicrob Chemother. 2007 Feb;59(2):264-76. doi: 10.1093/jac/dkl492.

Abstract

Objectives: To evaluate the curative effect of albendazole/thalidomide co-therapy on eosinophilic meningitis in BALB/c mice caused by Angiostrongylus cantonensis.

Methods: Male mice were infected with 50 A. cantonensis larvae and treated with albendazole (5, 10 or 20 mg/kg per day) alone, thalidomide (25, 50 or 100 mg/kg per day) alone, or a combination of albendazole (10 mg/kg per day) and thalidomide (50 mg/kg per day) for 7 consecutive days on days 5, 10 and 15 post-inoculation (PI), respectively.

Results: Indicators used to measure this effect included: (i) worm recovery; (ii) histopathological score of meningitis; (iii) eosinophil counts; (iv) level of pro-inflammatory cytokines, such as tumour necrosis factor-alpha, interleukin-1beta and interleukin-5; (v) activity of enzymes, such as tissue-type plasminogen activator, urokinase-type plasminogen activator and matrix metalloproteinase-9; and (vi) CSF/serum albumin ratio. The results showed that albendazole/thalidomide co-therapy significantly decreased (P < 0.05) these factors when treatment was initiated on days 5 or 10 PI compared with treatment initiated on day 15 PI.

Conclusions: The timing of medication use is important and is closely related to the anthelmintic efficacy of a drug. For a given dosage, earlier medication use is more effective. This novel approach to treating parasitic meningitis may suggest other new methods of treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albendazole / administration & dosage
  • Albendazole / therapeutic use*
  • Angiostrongylus cantonensis / growth & development*
  • Animals
  • Antinematodal Agents / administration & dosage
  • Antinematodal Agents / therapeutic use*
  • Brain / parasitology
  • Brain / pathology
  • Disease Models, Animal
  • Drug Therapy, Combination
  • Eosinophilia* / blood
  • Eosinophilia* / cerebrospinal fluid
  • Leukocyte Count
  • Male
  • Meningitis* / blood
  • Meningitis* / enzymology
  • Meningitis* / parasitology
  • Meningitis* / pathology
  • Meningoencephalitis / blood
  • Meningoencephalitis / enzymology
  • Meningoencephalitis / parasitology
  • Meningoencephalitis / pathology
  • Mice
  • Mice, Inbred BALB C
  • Serum Albumin / analysis
  • Strongylida Infections* / blood
  • Strongylida Infections* / enzymology
  • Strongylida Infections* / parasitology
  • Strongylida Infections* / pathology
  • Thalidomide / administration & dosage
  • Thalidomide / therapeutic use*

Substances

  • Antinematodal Agents
  • Serum Albumin
  • Thalidomide
  • Albendazole