Filarial infections

The timing of the collection of blood specimens depends on the parasite disease suspected. For example, for certain filarial infections, specimens are best obtained between 10 00 p.m. and midnight, whereas for other infections, specimens are best obtained during the day. In malaria, the numbers and stages of parasites in the peripheral blood vary with different parts of the cycle. 

A number of procedures have been described for the concentration of blood specimens. Most of these procedures have been developed to diagnose filarial infections. 

Steel C, Nutman TB CTLA-4 in filarial infections imphcations for a role in diminished T-cell reactivity. J Immunol 2003 170 1930-1938. 

Babu S. Blauvelt CP. Kumaraswami V. Nutman TB Diminished T cell TLR expression and function modulates the immune response in human filarial infection. J Immunol 2006 176 3885-3889. 

Diethylcarbamazine is the drug of choice for certain filarial infections, such as Wuchereria bancrofti, Brugia malayi and Loa loa. Since diethylcarbamazine is not universally active against hlarial infections, a specihc diagnosis based on blood smears, biopsy samples, and a geographic history is important. Dosage should be adjusted in patients with renal impairment. 

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]. 

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. 

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. 

Diethylcarbamazine is an antihelminthic drug used in the treatment of filarial infections. With some infecting species it is effective in both the adult and microfilarial stages, whilst with others it is active only against the microfilarial stages and does not eradicate the infection. 

There are several indications, mainly in the patent literature, of possible uses of tetrahydroquinoxalines. Derivatives related in structure to Hetrazan (l-diethylcarbamoyl-4-methylpiperazine) have been prepared as potential drugs for the treatment of filarial infections. Other tetrahydroquinoxalines of type 43 have been screened for antineoplastic activity and bisindolyl derivatives of type 44 have been claimed to have a wide spectrum of biological activity. Tetrahydroquinoxaline phosphates and thiophosphates have been patented as insecticides, and other tetrahydroquinoxalines have been patented for protecting rubber against... 

THERAPEUTIC USES Recommended regimens for filarial infections differ according to whether the drug is used for population-based chemotherapy, control of filarial disease, or prophylaxis against infection. 

Toxicity, Side Effects, and Precautions Ivermectin generally is well tolerated. In infected humans, ivermectin toxicity nearly always results from reactions to dying microfilariae the intensity and nature of these reactions relate to the microfilarial burden and the duration and type of filarial infection. 

Filarial infections. Both the adult and larval (microtiluriiie) forms of the tilariac occur in humans. Transmission is by the bite of bloodsucking insects. The adult worms arc very long-lived, and the shedding of microfi loriae la-sts for many years. The severil y of the disease depends on the adult worm burden of the host. 

Gusmao RD, Stanley AM, Ottesen EA. Brugia pahangi immunologic evaluation of the differential susceptibility of filarial infection in inbred Lewis rats. Exp Parasi-tol 1981 52 147-159. 

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