One billion affected by ‘neglected’ diseases

Researchers have made a significant advance in the development of a vaccine for hookworm, a so-called “neglected tropical disease” (NTD) that affects up to three quarters of a billion people and is a leading global cause of anaemia.

A team, led by Jill Brelsford at George Washington University, developed a technique to monitor the potency of the vaccine during refrigerated storage – critical information for vaccines that need a prolonged shelf-life in developing countries.

The research, published in PLOS Neglected Tropical Diseases, had two parts.

First, the researchers showed that, over a five year period the vaccine maintained its ability to elicit an antibody response in both mice and human volunteers. But the team went further, developing an assay to measure how well the antibody neutralises an enzyme the hookworm uses to, essentially, go on a blood-sucking frenzy in the intestine of its human host.

In order to thrive in the bowel, the hookworm (Necator americanus, literally “American killer”, from the Latin) launches a cascade of enzymes that digest human blood. One of the end products is haem, the iron-containing bit of haemoglobin that carts oxygen around the body in red blood cells.

Haem would be toxic to N. americanus if it didn’t gobble it up with an enzyme called glutathione-S-transferase-1 (Na-GST-1). Enter the vaccine, which works by mounting antibodies against the enzyme and causing a haem build-up that gets ugly for the worm, crippling or killing it.

So how effective were the antibodies? In the mouse model the answer was “pretty good”,  inhibiting 90% of the enzyme’s action. The results in humans were less promising, with only 20% inhibition achieved in a small number of samples.

But the outcome didn’t undermine the research’s primary aim of refining a measure of vaccine potency.

“The results … provide, for the first time in an open access format, critical tools for the development of future NTD vaccines,” the authors write.

And that’s good news, a rare thing in the horror-filled world of neglected diseases.

The World Health Organisation groups 17 communicable diseases under the NTD rubric. Together they afflict a billion of the planet’s poorest citizens, but lack the funding of higher profile diseases such as HIV/AIDS and malaria.

It’s worth noting the term “neglected” shifts the nomenclature of these diseases beyond a mere description of pathology to what is, arguably, a politically loaded prescription for global action.

But when one steps into this nightmarish world it’s not hard to set aside quibbles about the politicisation of disease.

Consider the life cycle of the hookworm, whose larva dwells happily in soil for up to four weeks before being trodden on by an unfortunate passer-by.

The larva penetrates the skin, then hitches via the bloodstream to the lungs where it treks from the small airways up to the windpipe before exiting into the back of the throat. From there it descends into the gut, latches onto the intestinal wall, and tucks into its free banquet of blood.

The result is rarely death but, rather, anaemia and malnutrition, which induce lethargy, stunted growth and cognitive development and, on a 2016 estimate, a crippling $139 billion economic burden for affected countries.

Indeed, worms figure inordinately in the NTD catalogue of horrors. Take dracunculiasis, for example. It is caused by the guinea worm, which has a lifecycle best not studied while eating.

Endemic to sub-Saharan Africa, the larva enters the intestine from contaminated drinking water, and heads for the skin where it heralds its presence with a blister.

You can encourage the blister to pop by immersing the part, usually the leg, in water, whereupon the filament-like worm, now up to a metre long, is removed by rolling it painstakingly around a match stick. The task can take weeks and suffers a serious setback if you break the worm.

In January it was announced that guinea worm disease is, thankfully, approaching eradication, in no small part due to the efforts of a centre set up by former US President Jimmy Carter.

But another worm-based NTD, onchocerciasis, or “river blindness”, still affects 25 million people, leaving 300,000 blind and a further 800,000 visually impaired. Again, the venue for 99% of the misery is Africa.

Onchocerciasis is caused by the bite of the river-breeding black-fly, which deposits a roundworm larva under the skin.

The mature worm sets up camp in a hived-off nodule, impervious to the body’s immune defences, where it can remain for up to 15 years and grow to the unholy length of half a metre.

Breakaway parties of larvae migrate to the eye, where they set about destroying the cornea and optic nerve. In a cruel irony, when the worm does finally die it leaves sufferers with intolerable itching.

But the ravages of NTD are not limited to worms.

Yaws is caused by Treponema pertenue, a bacterium closely related to the one that causes syphilis, and begins as an area of swollen skin that eventually ulcerates – the so-called “mother yaw”.

Secondary yaws ensue some months later as the bacteria wend their way through the skin, causing unsightly nodules and sometimes entering bone to produce appalling disfigurement.

Perhaps its most horrific incarnation was goundou, a variation that produced gruesome bony facial disfigurement. Now eradicated thanks to surgery and antibiotics, it led nineteenth century visitors to Africa to describe sufferers as “horned men”.

In July 2016 India was declared yaws-free, thanks to antibiotics, but the disease still affects an estimated 46,000 people, mainly children, across Africa, Asia, Latin America and the Pacific.

Of course, no discussion of the NTDs would be complete without mentioning lymphatic filariasis, the common name of which – clearly not designed with stigma reduction in mind – is elephantiasis.

Mosquitoes transmit the culprit larvae, again a roundworm, which migrates to the lymphatic ducts, tube-like structures that drain lymph, a fluid filtered from body tissues.

These ducts get blocked by worm damage and the resulting back pressure causes lymph to bloat into the tissues, leaving the host with grotesquely swollen limbs and skin like the coarse grey hide of an elephant.

Filariasis affects around 125 million people and, although the parasite can be killed with the drug diethylcarbamazine, once lymphoedema sets in the deformity but can never be fully reversed.

All in all, given the litany of misery caused by the NTDs, one can only hope the moniker “neglected” will be exchanged for “eradicated” sooner rather than later.