Description, mechanisms and control of reactions to treatment in the human filariases.
Since diethylcarbamazine at the dosages used to treat filarial infections has little direct toxicity, most of the post-treatment reactions (termed Mazzotti reactions in onchocerciasis) result from the immunological inflammatory mechanisms activated in the process of clearing and killing the skin-swelling or blood-borne microfilariae. These reactions may be either localized to the skin, eyes or lymphatics or generalized systemically (e.g. headache, fever, adenopathy, arthralgia, tachypnoea, tachycardia, hypotension and even death). The occurrence and intensity of such reactions can be shown to be related to the intensity of infection. It had previously been speculated that the best candidates for triggering these post-treatment reactions were activation of complement, immediate hypersensitivity responses mediated by immunoglobulin E, and degranulation of eosinophils with resultant inflammatory reactivity. Recent detailed studies have given little support to the primacy of either complement or immediate hypersensitivity responses in triggering such reactions, but eosinophil degranulation with the release of inflammatory mediators into the tissues and peripheral blood is extremely prominent in all patients undergoing post-treatment reactions and develops with a time course generally consistent with what would be required of an initiator of such reactions. Other inflammatory mediators and pathways may be involved (e.g. kinins, prostaglandins, immune complexes, leukotrienes, platelets and parasite-derived inflammatory molecules), but there is currently no evidence to implicate any of these mechanisms as initiators of the response. Symptomatic treatment of these post-treatment reactions with analgesics, antipyretics, antihypotensive agents etc. has been successful, but their prevention has been achieved only with the broadly anti-inflammatory corticosteroids.
Ottesen
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D000818:Animals; D000871:Anthelmintics / Q000009:adverse effects*; D004049:Diethylcarbamazine / Q000009:adverse effects* / Q000627:therapeutic use; D004605:Elephantiasis, Filarial / Q000188:drug therapy* / Q000276:immunology; D005368:Filariasis / Q000188:drug therapy* / Q000276:immunology; D005369:Filaricides / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D008209:Lymphedema / Q000188:drug therapy*; D008842:Microfilariae / Q000276:immunology; D009855:Onchocerciasis / Q000188:drug therapy* / Q000276:immunology
D000871:Anthelmintics; D005369:Filaricides; D004049:Diethylcarbamazine