Around the world, even in 2016, about 450 million people are infected with hookworms. Before 1980, up to 15 percent of the population of the southeastern United States was also infected with the worm. Hookworms are common wherever sanitary conditions are suboptimal and people often go barefoot.
The Creepy Life Cycle of One of the World's Most Common Bloodsucking Parasites
Female hookworms release their eggs inside the human small intestine. These eggs are swept away in feces, and if the fecal material lands on open ground, they hatch into infectious larvae, feeding on the feces in which they were laid. They rapidly from blob-like hatchling to something that looks like a tiny string of vermicelli capable of infecting any human with which it comes in contact for five minutes or more.
Hookworm larvae burrow into the skin, sometimes causing a local skin inflammation known as ground itch. Ground itch can be intensely itchy, but many people feel nothing at all. The larvae enter the bloodstream and after about 10 days find their way into the lungs, where they burst through the linings of the alveoli. At this stage there can be cough and fever, a severe complication known as rLöffler syndrome with shortness of breath and pneumonia-like symptoms, or, again, no symptoms at all.
From the lungs hookworms climb into the throat, waiting to be swallowed, so they can swim down to the small intestine. Once in the gut, they molt again and develop teeth (or, in the case of North American hookworms, cutting plates) that allow them to cling to the sides of the intestine. They release an enzyme called hyalouronidase, which eats through the lining of the gut so the worms can feed on human blood. This can result in obvious symptoms such as diarrhea, vague abdominal pain, colic, flatulence, nausea, or loss of appetite, or it might just result in poor absorption so that the infected person (especially if a child) is malnourished despite being provided a good diet. The hookworm then usually dies of "old age." Most of the world's varieties of hookworms live about a year, although North American hookworms live 5 years.
A mature female hookworm living in the human intestine releases from 5,000 to 30,000 eggs every day. When infected people relieve themselves outdoors, hookworm eggs lie in wait for their next human host. Hookworms in dogs and cats can also infect people through the skin, but they do not usually mature from larvae into reproducing adults. Hookworm symptoms in dogs and cats are analogous to those in people, but most people who catch hookworm from their pets will only develop a rash, not the lung or intestinal symptoms.
Defeating Hookworm Symptoms Seems to Result in Autoimmune Symptoms
Getting rid of hookworms with simple sanitary measures and anthelminthic drugs such as albendazole and mebendazole would seem to be an unquestionably good thing, but for many years scientists have observed that when hookworms are wiped out, immune system conditions like asthma and celiac disease become more common. Scientists have even develop a "hygiene hypothesis" that explains the growing frequency of these diseases with "too much" sanitation. But why should getting hookworms make some people sicker and other people healthier?
Why Hookworm Infections May Result in More Good Than Harm
Science writer Sarah Kaplan likens an infectious hookworm to a good cat burglar. Like a cat burglar, a hookworm breaks in and steals, but it knows better than to make a mess. It releases chemicals that eat through the lining of the intestine, but it also secretes chemicals that repair the damage once the parasite has a connection to the blood system. It only takes a few drops of blood a day for its own needs. It thoughtfully releases its offspring in dumps of poop rather than scattering them all over the host body. It secretes other chemicals that turn off alarm bells to alert the immune system.
A hookworm is almost like a symbiote, not a parasite, because it needs its human host to be happy and healthy. And with that in mind, Dr. Severine Navarro and colleagues at James Cook University in Australia tried a bold experiment.
Hookworms Help People with Celiac Disease Tolerate Gluten
Navarro's team recruited 12 sufferers of celiac disease (the condition of extreme insensitivity to gluten protein in wheat and other grains) to be intentionally infected with hookworms. Dr. Navarro counsels that this is something no one should try at home. Parasites can cause serious health problems in children, in pregnant women, and in anyone who is taking an immunosuppressant medication.
However, in the 12 people with celiac disease who were given a hookworm infection, celiac symptoms improved. In fact, they improved enough that most of them were able to tolerate the equivalent of a medium-sized bowl of spaghetti.
Getting the Benefits of Hookworms without the Actual Parasite
The problem for future research was that there aren't a lot of people who are willing to be infected with hookworms. To get around this problem, Severine Navarro and colleagues isolated a protein in hookworm saliva called AIP-2 that the parasites release to hide themselves from the immune system of their human hosts. She then gave injections of this protein, rather than the actual hookworms, to asthmatic mice daily for five days. The mice improved, and their symptoms continued to be improved for 10 weeks (which probably corresponds to several years in humans). The protein had a calming effect on the immune system's dendritic cells, which patrol the body looking for signs of invading microorganisms.
Navarro said that the protein rewired T-cells to make them super-efficient. In autoimmune conditions like asthma and celiac disease, overactive T-cells attack a variety of proteins, some of which are actually parts of healthy, functioning human cells. AIP-2 helps T-cells focus their reactions on actual foreign organisms rather than on proteins that are just similar to those on the surface of infectious agents that might in fact be part of healthy cells.
An AIP-2 pill is under development. Navarro speculates that it might be useful for as many as 230 million people in the world who have asthma. It may also help people who have inflammatory bowel disease or multiple sclerosis.
Getting infected with a parasite isn't really a good thing. Sometimes parasites make people very sick. However, harnessing the power of mild parasitic infection to modify the immune system may become an important part of curing autoimmune diseases.