Filariasis treatment

Diethylcarbama2iae (9) (orally administered) has been successful for decades in the treatment of filariasis, eg, elephantiasis (32). It kills microfilariae in the blood of the filarial worms Wuchereria bancrofti Brugia malaji and lj)a loa. 

Two forms of lymphatic filariasis are found in India. The Bancroftian form is the most common and accounts for more than 90% of the disease whereas Bmgian filariasis accounts for the rest. In a study carried out in India (6) in 40 patients with Wuchereria Bancwfti filariasis treated with single oral doses, all of the dose levels chosen (25, 50, 100, and 200 mg/kg) were efficacious in clearing microfilariae from the blood of all patients treated. However, after three months some microfilaria recurred in the blood of most patients (Table 5). Further studies are planned and some are underway using different doses and regimens. Ivermectin still appears to hold promise as a new treatment for lymphatic filariasis. 

Table 5. Efficacy of Ivermectin in the Treatment of Wuchereria Filariasis...

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. 

Arsenic effectively controls filariasis in cattle new protective uses are under investigation. The control of parasitic nematodes (Parafllaria bovicola) in cattle was successful after 30 weekly treatments in plungement dips containing 1600 mg As203/L. However, the muscle of treated cattle... 

Our perspective is thus one of general significance to chronic infection, as well as one that will provide specific pathways to novel treatments of human schistosomiasis, and lymphatic filariasis. These two diseases represent a massive public health problem with 300 million people infected in the world today. Intervention by ablating parasite-specific Tregs in these patients will solve the specific problems of schistosomiasis and filarial diseases, while at the same time proving a principle which will be applicable to chronic infections in general. 

Diethylcarbamazine citrate (9.118), a synthetic piperazine derivative, is used for the treatment of filariasis and loiasis. Although its mechanism of action is basically unknown, it appears to somehow alter the surface structure of the helminth, rendering it more susceptible to destruction by the host defenses. 

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. 

Bockarie MJ et al Mass treatment to eliminate filariasis in Papua New Guinea. N Engl J Med 2002 347 1841. [PMID 12466508]... 

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... 

The present review demonstrates the extensive applicability of benzimidazole-2-carbamates in the treatment of filariasis. The generation of a new class of... 

Shenoy RK, Dalia S, John A et al. (1999) Treatment of the mi-crofilaraemia of asymptomatic brugian filariasis with single doses of ivermectin, diethylcarbamazine or albendazole, in various combinations. Ann Trop Med Parasitol 93 643-651... 

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). 

Brugia malayi is more susceptible to diethylcarbamazine than W. bancrofti. A study of the former, undertaken to explain the very severe effects often associated with diethylcarbamazine treatment of Ijmiphatic filariasis, provided evidence of the involvement of the cytokine mterleukin-6 (IL-6), concentrations of which were raised during treatment (12). 

Ivermectin, a dihydroavermectin Bl, is an effective microfilaricide used in the treatment of strongyloides, scabies, and aU types of filariasis except Dipalonema (Mansonelta) perstans infections. 

Early-stage elephantiasis caused by bancroftian filariasis in a 27-year-old traveller was treated with a single-dose oral combination of ivermectin 24 mg plus albendazole 400 mg, followed by albendazole 800 mg for 21 days (14). To avoid a severe Mazzotti-like reaction, he was given oral glucocorticoids and antihistamines for 3 days. He had a transient rash, pruritus, and mild hypotension on the days after the initial treatment, but otherwise remained well and the swelling subsided. Within 1 month he was free of symptoms. At the last follow-up examination, 3 years after treatment, there was no clinical or laboratory evidence of relapse. The authors thought that this type of treatment should be evaluated on a wider scale, given the minimal adverse events and apparent therapeutic efficacy. 

In the treatment of Wuchereria bancrofti filariasis in 23 patients with single doses up to 200 micrograms/kg respiratory capacity was evaluated there was a transient but significant fall in vital capacity some 24—30 hours after administration, apparently due to bronchodilatation (30). Frank dyspnea occurred in 2% of cases in the study cited... 

Moulia-Pelat JP, Nguyen LN, Glaziou P, Chanteau S, Gay VM, Martin PM, Cartel JL. Safety trial of single-dose treatments with a combination of ivermectin and diethylcarbamazine in bancroftian filariasis. Trop Med Parasitol 1993 44(2) 79-82. 

Shenoy RK, George LM, John A, Suma TK, Kumaraswami V. Treatment of microfilaraemia in asymptomatic brugian filariasis the efficacy and safety of the combination of single doses of ivermectin and diethylcarbamazine. Ann Trop Med Parasitol 1998 92(5) 579-85. 

Dunyo SK, Nkrumah FK, Simonsen PE. A randomized double-blind placebo-controlled field trial of ivermectin and albendazole alone and in combination for the treatment of lymphatic filariasis in Ghana. Trans R Soc Trop Med Hyg 2000 94(2) 205-ll. 

Kumaraswami V, Ottesen EA, Vijayasekaran V, Devi U, Swaminathan M, Aziz MA, Sarma GR, Prabhakar R, Tripathy SP. Ivermectin for the treatment of Wuchereria bancrofti filariasis. Efficacy and adverse reactions. JAMA 1988 259(21) 3150-3. 

Although a number of natural products have enjoyed wide usage in the treatment of various helminth diseases of man and domestic animals prior to 1960, with the advent of more effective and safer synthetic anthelmintics most of them were eventually abandoned and are now of historical value only [52]. For example, santonin was included in 25th edition of the United States Dispensary (1955), but was removed from the U.S. Medical Compendium of National Formulary (1960). Similarly, aspidium oleoresin was included in the U.S. Pharmacopeia of 1960 and the full clinical usage of this drug was available in the U.S. Dispensary only until 1973 [1]. This makes the description of SAR and synthesis of most of the anthelmintic natural products less meaningful and is, therefore, not discussed in the present text. However, the SAR profile of avermectins and milbemycins is discussed, of which the former have in recent years been used extensively in the treatment of onchocerciasis and lymphatic filariasis in humans [20]. 

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