A HAU-INCH long parasite that thrives onblood extracted ftom the gut of the host,the hookworm is playing havoc with thehealth of about 900 million peopleworldwide, predominantly in the ThirdWorld. According to the World HealthOrganization, the parasite affects 132million people in Africa, 104 million inCentral and South America and about685 million people in Asia. Now, somerecent discoveries have suggested excellent possibilities of developing a vaccine to conquer the worm (ScientificAmerican, Vol 272, No 6).
The life cycle of a hookworm beginswith the initial development of larvae inthe ground. Infective larvae generallysneak into the body through the skin,enter the blood circulatory system andthen break out of it and attach themselves to the small intestine. Tliere theymature into adults and mate to producefertilised eggs that are transported backto the ground through excrement. Thelarvae can also be ingested along with contaminated food.
In the intestines, the parasiteextracts a fraction of a teaspoon ofblood from the circulatory systemeveryday with its sharp teeth.The infection causes anaerniaand protein malnutrition in thehost. The worst hit are children,in which the parasite can causeirreversible retardation of physical and intellectual growth.Among infants, the worm can even prove fatal.
The hookworm menace hasbeen aggravated by the unavailability of medicines in placeswhere the disease is common.Also, there is a tendency of thedormant larvae of the parasite tocause reinfection after the treatment is complete. Moreover, thelarvae can also enter the mammary gland of pregnant women,and get passed on to newbornsthrough breast milk. Scientists atthe Institute of Parasitic Diseases in Shanghai recently identified many infants with severe hookworm infection.
For this reason, researchers at theYale University School of, Medicinehave started investigations on the molecular aspects of hookworm infections.Two genera of hookworms, Ancylostoma and Necator, are being exploredto identify hookworm proteins thatcan serve as preventive vaccines.Unexpectedly, many of these proteinsalso seem to have therapeutic valuefor cardiovascular and immunological disorders.
Researchers have set out to identifymolecules that enable hookworms toburrow through the skin, mature andsurvive in the human body. As part ofthe efforts to identify and isolatemolecules that could be enlisted as vaccines, biochemical events that occurafter a hookworm fastens to the intestinal wall are being examined. Someenzymes secreted by the hookwormthat cause tissue breakdown andvascular rupture have been identified.These include proteases which degradehost proteins, as well as hyaluronidasethat breaks down other structural components of the intestine.
The human host's defence to thehookworm invasion involves coagulating blood at the site of vascular damage.An immunologic defence is alsolaunched by activating leukocytes anddespatching antibody molecules especially Immunoglobin E, which act inconcert with leukocytes.
Investigators have established thathookworms secrete a protein thatinhibits blood clotting, thus thwartingthe host's vascular defence. This small,highly potent protein has now been isolated from A caninum, the hookworminfecting dogs. The molecule is calledACAP (A caninum anticoagulant peptide).Larvap of hookworm are also shownto produce interesting chemicals. Forinstanc@, A caninum larvae secrete aproteas@ that helps the organism to borethrough, the skin. Another protein -Asp (An 4Mostoma secreted polypeptide)- is shown to help in its maturation.
The discovery that hookworms actas chemical factories suggests excitingideas lor, vaccine development. Takingassistance of genetic engineeringtechniques, researchers are all setto test hookworm products likeASP, AcAP and other anticlottingfactors, as potential vaccines.
Though the best approach tocontrol the infection is toimprove sanitation conditions invulnerable places, and also topopularise protective clothing toreduce exposure, these measuresare unlikely to be successful indeveloping countries at present.So the most logical alternative isthe admin 'istration of vaccines toboost host defences. But fundingfor fighting hookworm infection, which mainly afflicts theThird World, is scarce and thisfactor could slow down development of a hookworm vaccine.