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Browsing by Subject "Onchocerca volvulus"

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  • Tuononen, Maija Liisa (2011)
    River blindness (onchocerciasis) is a human helminth disease that is caused by Onchocerca volvulus filaria. It is endemic in tropical areas in Africa and Latin America. About 37 million people are infected. River blindness manifests in cutaneous and eye symptoms that are caused by the youngest forms (microfilariae). Against river blindness there has been mass drug treatments with ivermectin which has an effect on microfilariae. There is a need for a drug that kills adults or sterilizes females. A vaccine would be even better. Antibiotics are a new treatment because O. volvulus has Wolbachia bacterium as an obligate symbiont. Doxycycline kills at least 60 per cent of adults and sterilizes females. But the course lasts many weeks. A promising compound is emodepside that has a new mechanism of action for an anthelmintic drug. Numerous compounds has been examined to get drugs for filarial diseases. Some of them inhibit enzymes with which filariae evade human immune defence. Others disturb moulting that takes place four times. A good target for a drug is essential for the parasite but absent from mammals. Betulin is a triterpene that is abundant in birch bark. Betulin and many of its derivatives are pharmacologically active compounds that are examined particularly as cancer and HIV drugs. The research group of medicinal chemistry in University of Helsinki has synthesized and examined many derivatives. Some of them are promising for example against Leishmania protozoans, Chlamydia pneumoniae bacterium and alphaviruses. That is why those compounds should be tested against other causes of diseases like filariae. Both Wolbachia and C. pneumoniae have the same lipid biosynthesis pathway that is essential for both. Heterocycloadducts between betulin and nitrogen heterocycle were synthesized whose alcohols were oxidized to carbonyls. In both Leishmania donovani and L. braziliensis examinations the most effective compound was heterocycloadduct of formylbetulin. Although the compounds have not been examined against filariae, in future it would be worth an effort to synthesize derivatives that has nitrogen instead of carbonyls because the compound effective on C. pneumoniae is dioxime.