N. brasiliensis L3 fed with APC labelled RBC (anti-Ter119). Picture shows specific uptake of RBC into the larval intestine, and the accompanying dark pigment formation.

Asthma research accidentally helps treat hookworm infections

23 March 2018, Hookworm, Parasites, Professor Graham Le Gros

Asthma research has inadvertently led to a new treatment for hookworm infections, a huge issue in developing nations. Hookworms routinely infect humans through the skin (usually the foot), migrating to the lungs and eventually establishing themselves in the gut where they can persist for years, feeding off blood. Australasian researchers found that the worm starts feeding off blood as soon as it enters the body — in the first three days of infection. The researchers were able to stop them from feeding before they reached the gut by treating infected mice with a type of antimalarial drug, preventing the hookworms from taking root in the body.

Published in PLOS Pathogens, the asthma, allergy and parasitic disease programme at the Malaghan Institute of Medical Research, led by Professor Graham Le Gros, made the accidental study while researching cures for asthma.

Over one billion people worldwide are currently affected by parasitic worm infections, mostly in developing nations. Helminths, such as Necator americanus routinely infect humans through the skin (usually the foot), migrating to the lungs and eventually establishing themselves in the gut where they can persist for years, feeding off blood. This can lead to iron and blood deficiency in the human host, affecting growth and development.

While traditional thinking has been that helminth blood feeding only occurs once in the gut, postdoctoral researcher Tiffany Bouchery at the Malaghan Institute demonstrated using a preclinical model of human hookworm infection that blood feeding occurs as soon as the worm enters the host’s body.

“What we’ve found, quite unexpectedly, is that the worm starts blood feeding as soon as it enters the body, in the first three days of infection,” says Prof Le Gros. “This insight could lead to new ways of targeting the species of hookworm that commonly infect humans, because once it is in the gut it’s very hard to deal with.”

Using this insight Prof Le Gros’ team used quinolones – antimalarial drugs – to inhibit the parasites’ ability to blood feed even before it reaches the gut, preventing them from growing and persisting in the body. The drug inhibits the iron-detoxification pathway which allows the worm to safely process iron in the blood.

“While not what we set out to find, this piece of research is very exciting. In terms of its potential and where it could lead, improved therapies for the billion people suffering from hookworm will be a major milestone in the fight against tropical diseases.

“It also gives us a deeper mechanistic insight into how other worms may be similarly affected when they first start migrating into the body and how we might use this knowledge to work with worms to our advantage.”

The findings suggest that further investigation of the iron-detoxification pathway could one day lead to the development of other drugs or vaccine targets against hookworm.

The work was a strong collaborative effort involving researchers at the Malaghan Institute, James Cook University, Cairns and Baylor College, Houston. The work was funded by the Health Research Council of New Zealand.