Nematode infections, drugs used

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. 

Piperazine and DEC are the two important drugs of this class, which have been used to treat various nematode infections in humans and animals [52-57]. 

The salicylanilide drugs have been widely used to treat intestinal tapeworm and liver fluke infections in humans and animals. Their use in the treatment of hydatid diseases, schistosomiasis and nematode infections is limited [11]. 

Worms are known as helminths and the majority is not parasitic. Classes of worms that parasitize man are round worms (nematodes) and flat worms (platyhelminths). The flat worms are divided into tapeworms (cestodes) and flukes (trematodes). Only a few human parasitic worms are common in the United Kingdom, for example threadworms and round worms. In tropical and subtropical parts of the world, where abundant water and high temperatures provide an optimal environment for the larvae and intermediate hosts, parasitic worms are common and widespread. Table 9.8 lists some parasitic worms that can infect man, their effect and drugs used to treat them. 

The nervous system in helminths has important differences from that of humans and these differences form the basis of the selective toxicity of most drugs used to treat such infections. For example, nematode muscles have both excitatory and inhibitory neuromuscular junctions. The neurotransmitters are acetylcholine and gamma-aminobutyric acid (GABA), respectively. 

Pyrantel pamoate is a broad-spectrum antihelmintic. It is useful in the eradication of a wide variety of nematodes. Due to its broad-spectrum action, it is considered a drug of second choice in nematode infections. 

Mepacrine (Fig. 25.14) can be used in resistant giardiasis. This drug was developed during the Second World War to treat malaria but has been re-introduced to treat giardiasis and is also the subject of research into the treatment of Alzheimer s disease. Albendazole may also be used as an alternative and is described below under the treatment of nematode infections. 

Several benzimidazoles are in use for the treatment of helminthic infections. Three of these, mebendazole, thiabendazole and albendazole, are described in this section. They have a broad range of activity against many nematode and cestode parasites, including cutaneous larva migrans, trichinosis, disseminated strongyloidiasis, and visceral larva migrans. A fourth, triclabendazole, is considered as the drug of choice for Easciola hepatica therapy. 

Metrifonate (9.121), an organophosphate compound, is a low-cost antihelminthic used to treat Schistosoma hematobium infections. The drug appears to alter cholinesterase activity in the nematode, temporarily paralysing the adult worm and causing the worm to die. Because of its activity against the cholinesterase enzyme, this drug has also been evaluated as a treatment for Alzheimer s disease. 

Another group of drugs that bind to microtubules are benzimidazole and related compounds. These have been used widely to treat infection by parasitic nematodes in both humans and animals. Unfortunately resistance has developed rapidly. 

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). 

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