In an earlier post, I outlined WHO’s goal to be free of elephantiasis by 2020. Global elimination efforts currently rely on multiple rounds of mass drug administration, where doses of medicine are given to entire populations on an annual basis. This is preventative treatment (controlling the spread of parasites), and has worked quite well, as we have seen. In the past, the recommended regimen involves a combination of two antibiotics that target the larval stage, diethylcarbamazine and albendazole.

They are capable of clearing almost all microfilariae from the blood, but come with some unfortunate side effects including fever, headache and dizziness. Making matters worse, the adult worms are long-lived. To break the transmission cycle by killing only larvae requires prolonged drug delivery with extensive coverage; hardly ideal in countries where resources are scarce. Instead, drugs that target the adult worms are desperately needed.

I’ve talked about how the worms rely on their bacterial symbionts for survival, making Wolbachia an obvious target in the elimination of elephantiasis: if you stop the bacteria, you also kill the worm. This has been demonstrated with doxycycline, an antibiotic which belongs to the tetracycline family of antibiotics. These work by binding ribosomes, an important cellular factory, thereby stopping the bacteria from making proteins and reproducing.

Crucially, doxycycline is more effective than the combined treatment, and has none of the problematic side effects as it eliminates the adult worms. Through this novel method of targeting the symbiont, treatment reduces the level of Wolbachia to a level where adult female worms became infertile: a safe, macrofilaricidal treatment.

Doxycycline is the best drug treatment we have, but it has two standout problems: it can be harmful to children and pregnant women, and it takes at least four weeks to work. But, since the drug concept has clinical evidence to support it, the idea has taken off. The initiative was granted funding from the Bill & Melinda Gates Foundation, giving rise to the Anti-Wolbachia Consortium, A·WOL. Their headquarters are at the Liverpool School of Tropical Medicine, and you can see the team in the video below, squashing mosquitos:

The real goal here is to find a treatment which clears infection in under a week. To this end, A·WOL has screened over 2 million compounds, an onerous task. They’ve since identified 20,000 candidates, all active against Wolbachia, and ready for further investigation. That’s pretty much where we are today, with people in lab coats wading through a pile of ‘drug-like compounds’ in search of something that meets the criteria.