Hook in the gut
A HAU-INCH long parasite that thrives on blood extracted ftom the gut of the host, the hookworm is playing havoc with the health of about 900 million people worldwide, predominantly in the Third World. According to the World Health Organization, the parasite affects 132 million people in Africa, 104 million in Central and South America and about 685 million people in Asia. Now, some recent discoveries have suggested excellent possibilities of developing a vaccine to conquer the worm (Scientific American, Vol 272, No 6).
The life cycle of a hookworm begins with the initial development of larvae in the ground. Infective larvae generally sneak into the body through the skin, enter the blood circulatory system and then break out of it and attach themselves to the small intestine. Tliere they mature into adults and mate to produce fertilised eggs that are transported back to the ground through excrement. The larvae can also be ingested along with contaminated food.
In the intestines, the parasite extracts a fraction of a teaspoon of blood from the circulatory system everyday with its sharp teeth. The infection causes anaernia and protein malnutrition in the host. The worst hit are children, in which the parasite can cause irreversible retardation of physical and intellectual growth. Among infants, the worm can even prove fatal.
The hookworm menace has been aggravated by the unavailability of medicines in places where the disease is common. Also, there is a tendency of the dormant larvae of the parasite to cause reinfection after the treatment is complete. Moreover, the larvae can also enter the mammary gland of pregnant women, and get passed on to newborns through breast milk. Scientists at the Institute of Parasitic Diseases in Shanghai recently identified many infants with severe hookworm infection.
For this reason, researchers at the Yale University School of, Medicine have started investigations on the molecular aspects of hookworm infections. Two genera of hookworms, Ancylostoma and Necator, are being explored to identify hookworm proteins that can serve as preventive vaccines. Unexpectedly, many of these proteins also seem to have therapeutic value for cardiovascular and immunological disorders.
Researchers have set out to identify molecules that enable hookworms to burrow through the skin, mature and survive in the human body. As part of the efforts to identify and isolate molecules that could be enlisted as vaccines, biochemical events that occur after a hookworm fastens to the intestinal wall are being examined. Some enzymes secreted by the hookworm that cause tissue breakdown and vascular rupture have been identified. These include proteases which degrade host proteins, as well as hyaluronidase that breaks down other structural components of the intestine.
The human host's defence to the hookworm invasion involves coagulating blood at the site of vascular damage. An immunologic defence is also launched by activating leukocytes and despatching antibody molecules especially Immunoglobin E, which act in concert with leukocytes.
Investigators have established that hookworms secrete a protein that inhibits blood clotting, thus thwarting the host's vascular defence. This small, highly potent protein has now been isolated from A caninum, the hookworm infecting dogs. The molecule is called ACAP (A caninum anticoagulant peptide). Larvap of hookworm are also shown to produce interesting chemicals. For instanc@, A caninum larvae secrete a proteas@ that helps the organism to bore through, the skin. Another protein - Asp (An 4Mostoma secreted polypeptide) - is shown to help in its maturation.
The discovery that hookworms act as chemical factories suggests exciting ideas lor, vaccine development. Taking assistance of genetic engineering techniques, researchers are all set to test hookworm products like ASP, AcAP and other anticlotting factors, as potential vaccines.
Though the best approach to control the infection is to improve sanitation conditions in vulnerable places, and also to popularise protective clothing to reduce exposure, these measures are unlikely to be successful in developing countries at present. So the most logical alternative is the admin 'istration of vaccines to boost host defences. But funding for fighting hookworm infection, which mainly afflicts the Third World, is scarce and this factor could slow down development of a hookworm vaccine.
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