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Better treatments for hookworm are on the horizon after the genome of Ancylostoma ceylanicum, the less common of the two hookworm species that affect humans, was sequenced in the United States.

The genome data offers more targets for drug and vaccine research. Hookworm infects around 440 million people in low- and middle-income countries. It is a leading cause of iron-deficiency, which can cause disability and even death, says Peter Hotez, a professor of tropical pediatrics at Baylor College of Medicine in the US.

The research, published in Nature Genetics this month (2 March), found an extensive set of genes that control the hookworm’s ability to survive by suppressing the host’s immune system.

The paper identifies some essential hookworm enzymes as likely vaccine targets. Without these enzymes, called proteases, hookworms cannot digest human proteins such as haemoglobin, the research found.

“An inexpensive, safe vaccine administered once to small children would abolish their risk of contracting this disease.”

Erich Schwarz, Cornell University

Because hookworm infection stunts physical and mental development, it can have a crippling cost on the economy and choke economic growth, says Erich Schwarz, a researcher at US-based Cornell University, who led the study.

More than three-quarters of hookworm infections in humans are caused by Necator americanus, the genome of which was sequenced last year.

Schwarz estimates that A. ceylanicum infects about 40 million people, largely in South-East Asia and particularly in Vietnam. Now that Schwarz and his colleagues have sequenced this hookworm’s genome, they plan to start testing vaccine candidates for A. ceylanicum in hamsters this year.

Even though N. americanus infects more people, A. ceylanicum is used more in laboratories, because it infects both humans and other mammals, meaning treatments can be tested more easily.

A. ceylanicum already has a treatment, a single-dose drug called albendazole. However, albendazole doesn’t protect people living in hookworm-endemic areas from becoming reinfected. “An inexpensive, safe vaccine administered once to small children would abolish their risk of contracting this disease,” says Schwarz.

Schwarz and his colleagues were able to compare the genes they found in the newly sequenced genome with those in N. americanus. They identified some gene families common to the two species, which suggests that they are conserved between all hookworms. Schwarz says that a vaccine for N. americanus, which was developed by Hotez and has passed clinical trials in Brazil, may also work on A. ceylanicum.

However, Schwarz underlines the importance of using the genome to identify other targets for vaccines. “Even if this vaccine works, until we devise more than one vaccine, it’s probably not going to be clear what the best and most effective vaccine can be,” he says.
>Link to full paper in Nature Genetics

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