Onchocerciasis treatment

Turner, P.F., Rockett, K.A., Ottesen, E.A., Francis, H., Awadzi, K. and Clark, I.A. (1994) Interleukin-6 and tumor necrosis factor in the pathogenesis of adverse reactions after treatment of lymphatic filariasis and onchocerciasis. Journal of Infectious Diseases 169, 1071-1075. 

When used for the treatment of onchocerciasis a potentially fatal Mazotti reaction may occur, with severe skin reactions, tachycardia, hypotension and fever. 

For obvious reasons of structural analogy to heparinoids the focus of this review is on sulfated carbohydrate derivatives. While it is not in all cases clear that these compounds really mimic the physiological activity of heparinoids, it is even less so for non-carbohydrate sulfates or sulfonates. Examples of the latter class include suramin and the simple 1,3-propanediol disulfate. Suramin is a sulfonat-ed bis-naphthalene derivative used as a drug to treat African trypanosomiasis and onchocerciasis (a filarial infection) it was also tested in a number of other indications including adrenocortical carcinomas and AIDS. A wider use is, however, restricted by various toxic effects [66]. 1,3-Propanediol disulfate reduced inflammation-associated amyloid progression in vivo after oral administration which may be relevant to the treatment of Alzheimer s disease [67]. 

Diethylcarbamazine is a drug of choice in the treatment of filariasis, loiasis, and tropical eosinophilia. It has been replaced by ivermectin for the treatment of onchocerciasis. 

Ivermectin also now plays a key role in onchocerciasis control. Annual mass treatments have led to major reductions in disease transmission. However, evidence of diminished responsiveness after mass administration of ivermectin has raised concern regarding selection of drug-resistant parasites. 

Note Ivermectin is approved for use in the USA for the treatment of onchocerciasis and strongyloidiasis. See Chapter 65 for comment on the unlabeled use of drugs. 

Udall DN Recent updates on onchocerciasis Diagnosis and treatment. Clin Infect Dis 2007 44 53. 

Onchocerciasis -ivermectin treatment [ANTIPARASITIC AGENTS - AVERMECTINS] (Vol 3) -pesticide control of [PESTICIDES] (Vol 18)... 

Ivermectin (Mectizan, Stromectol) is the primary treatment for filarial nematode infections (onchocerciasis) that invade ocular tissues and cause loss of vision (river blindness). Ivermectin may also be used in filarial infections in other tissues (lymphatics, skin). This drug is a secondary agent for treating intestinal nematodes such as strongyloidosis. 

During the last four decades, microfilaricidal diethylcarbamazine [46] and macrofilaricidal suramin [47,48] have been used for the treatment of filariasis however, iboth of these drugs possess unwanted side-effects such as mazzotti reaction, toxicity, etc. Suramin is highly active against the adult worm of 0. volvulus [47] in humans, but it is very toxic to the kidney, liver and bone marrow and has other side-effects similar to DEC. DEC in the treatment of onchocerciasis produces severe mazzotti reaction (an allergic response due to rapid death of microfilariae) along with other side-effects such as pruritus and anaphylactic shock. However, the mass treatment of lymphatic filariasis with DEC was successful due to a lower and milder incidence of these adverse... 

A thiourea derivative CGP 6140 (32) [54], developed by Ciba-Geigy represents a new class of compound, which shows significant macrofilaricidal activity at 50-100 mg/kg in a variety of animal models. The further extension of this work generated two more new compounds, benzothiazole and benzoxazole derivatives (CGP 20376 and CGP 24914) which both possess potent micro- and macrofilaricidal activities [55], However, CGP 20376 has also been found orally effective against Brugia infections at a dose of 6.25 mg/kg [38]. Further studies with these compounds in the treatment of onchocerciasis and other filarial infections are currently under evaluation. 

Another important class of anti-infective natural products introduced in recent years is the avermectins, polyketide-derived macrolides that were originally isolated from several species of Streptomyces. The major drug in this class, ivermectin, was originally developed to treat and control nematodes and parasites in livestock. In recent years, however, the potential of ivermectin for the treatment of human disease has also been realized, and it is now used to treat onchocerciasis (river blindness), a disease that afflicts 40 million people worldwide (De Smet, 1997). 

Ivermectin also now plays a key role in onchocerciasis control. Annual mass treatments have led to major reductions in disease transmission. 

Onchocerciasis (river bNndnossJ ivermectin Cures with single dose. Suppressive treatment a I... 

Awadzi K, Opoku NO, Attah SK, Addy ET, Duke BO, Nyame PK, Kshirsagar NA. The safety and efficacy of amocarzine in African onchocerciasis and the influence of ivermectin on the clinical and parasitological response to treatment. Ann Trop Med Parasitol 1997 91(3) 281-96. 

Mass treatment with diethylcarbamazine is a key measure for control of the transmission of bancroftian filariasis. However, severe adverse reactions can occur in patients with onchocerciasis treated with high doses of diethylcarbamazine, which may hmit the prospects for the use of common salt medicated with diethylcarbamazine in many parts of Africa. However, the daily dose of diethylcarbamazine-medicated salt is considerably lower than that of conventional tablets (25-50 mg od for the first 1 or 2 days followed by 100 mg bd for 5-7 days). 

Adverse reactions to treatment with diethylcarbamazine vary with the infecting filarial species and are most severe in onchocerciasis. Minor reactions include malaise, nausea, and headache, but diethylcarbamazine also depresses the central nervous system in some individuals, resulting in dizziness and somnolence reversible coma has been reported in patients in poor physical condition. Nicotine-like properties can produce autonomic effects. A degree of eosinophilia during treatment is usual. 

---