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Abstract
The following account is based on a review lecture given recently at the British Society of Parasitology. We point out that nematode parasites cause very widespread infections of humans, particularly in economically underdeveloped areas where sanitation and hygiene are not adequate. In the absence of adequate clean water and effective vaccines, control and prophylaxis relies on anthelmintic drugs. Widespread use of anthelmintics to control nematode parasites of animals has given rise to the development of resistance and so there is a concern that similar problems will occur in humans if mass drug administration is continued. Recent research on the cholinergic anthelmintic drugs has renewed enthusiasm for the further development of cholinergic anthelmintics. Here we illustrate the use of three parasite nematode models, Ascaris suum, Oesophagostomum dentatum and Brugia malayi, microfluidic techniques and the Xenopus oocyte expression system for testing and examining the effects of cholinergic anthelmintics. We also show how the combination of derquantel, the selective nematode cholinergic antagonist and abamectin produce increased inhibition of the nicotinic acetylcholine receptors on the nematode body muscle. We are optimistic that new compounds and combinations of compounds can limit the effects of drug resistance, allowing anthelmintics to be continued to be used for effective treatment of human and animal helminth parasites.
Highlights
It writhes! – it writhes! – with mortal pangs The mimes become its food, And seraphs sob at vermin fangs In human gore imbued (The Conqueror Worm, Edgar Allan Poe, 1843)We start our account with a quote from a poem, The Conqueror Worm, which was first published in 1843 in Graham’s Magazine
Anthelmintic drugs are used for treatment and prophylaxis but there are concerns about the development of resistance in humans (Diawara et al, 2009, 2013) as in animals (Kaplan, 2004)
There is a need for effective drugs against soil-transmitted nematodes (Hu et al, 2013) and filaria (Prichard, 2005)
Summary
It writhes! – it writhes! – with mortal pangs The mimes become its food, And seraphs sob at vermin fangs In human gore imbued (The Conqueror Worm, Edgar Allan Poe, 1843). The NTDs are mostly caused by parasitic nematodes They may not kill, but they produce malnutrition that leads to debility, poor growth, reduced intellectual development, limb disfigurement and an increase in HIV/AIDS infection rates (Bentwich et al, 2008). STNs are the major cause of morbidity in schoolchildren aged 5 – 14 years (Hotez, 2007) Lymphatic filariasis is another important NTD, produced by filarial nematodes like B. malayi The increased albendazole/mebendazole use appears to be leading to development of resistance in STNs of humans (Albonico et al, 2005) as it did in animals (Jackson, 1993; Kaplan, 2004) To address this problem of benzimidazole resistance, additional drugs are required, with a different site of action and suitable for prophylactic mass treatment with easy administration. New microfluidic techniques (fig. 3) allow drug effects on the neuromuscular system to be dissected and quantitated through recording and analysing the sinusoidal movement of L3 larvae, using measurements of the amplitude (a), frequency (N), Drug port
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