Gereon Schares

Experimental chemotherapy of filariasis: comparative evaluation of the efficacy of filaricidal compounds in Mastomys coucha infected with Litomosoides carinii, Acanthocheilonema viteae, Brugia malayi and B. pahangi

Eleven types/classes of compound with antifilarial activity were comparatively evaluated in Mastomys coucha infected with Litomosoides carinii, Acanthocheilonema viteae, Brugia malayi or B. pahangi. The paper deals with the efficacy of (i) predominantly microfilaricidal compounds [diethylcarbamazine, levamisole, avermectins (ivermectin, milbemycin), nitrofurans (nitrofurantoin, hydroxymethylnitrofurantoin, nifurtimox, furazolidone, furapyrimidone), organophosphorals (metrifonate, haloxon), and aminophenyl-amidines], (ii) predominantly macrofilaricidal compounds [suramin, benzimidazoles (flubendazole, mebendazole, oxfendazole, ciclobendazole, albendazole, cambendazole, fenbendazole), and arsenicals (thiacetarsamide, Mel PH, R7/45)], and (iii) micro- and macrofilaricidal compounds [benzazole derivatives (CGP 20376 and other benzothiazoles) and nitrophenylamines (amoscanate, CGP 6140)]. Minimum effective doses against microfilariae and minimum curative doses against adult filariae as well as detailed data on dose-efficacy relationships are reported for the various drugs. The results obtained in M. coucha are compared with those published for other experimental in vivo filarial systems, thus attempting to describe a general status of in vivo antifilarial activity of the compounds.

The gene coding for the major sheath protein of Litomosoides carinii microfilariae, gp22, is transcribed in oocytes and embryonic cells

The transcription and translation of the gene encoding gp22, a major constituent of the microfilarial sheath of the filarial parasite Litomosoides carinii were studied by in situ hybridisation and immunohistology. Transcription of the gp22 gene is confined to oocytes and embryos in the reproductive organs of adult female worms. It starts in oocytes in the rhachis zone, is maximal in multicellular embryos and decreases slowly as the microfilariae develop. Blood microfilariae lack the gp22 transcript. The gp22 gene product is first detectable in parasites recovered on day 32 post infection. Expression of gp22 begins in multicellular embryos in the uteri of mature female worms and can be detected in all further developed intrauterine stages. The gp22 gene product appears to be exported by the embryonic cells and becomes integrated into the sheath where it may contribute to the flexibility of the latter structure.