Hookworm vaccines: past, present, and future

George Washington University, Washington, Washington, D.C., United States
The Lancet Infectious Diseases (Impact Factor: 22.43). 12/2006; 6(11):733-41. DOI: 10.1016/S1473-3099(06)70630-2
Source: PubMed


Hookworms are gastrointestinal nematodes that infect almost 1 billion people in developing countries. The main clinical symptom of human hookworm infections is iron-deficiency anaemia, a direct consequence of the intestinal blood loss resulting from the parasite's feeding behaviour. Although treatment is available and currently used for the periodic removal of adult hookworms from patients, this approach has not effectively controlled hookworm in areas of rural poverty. Furthermore, treated individuals remain susceptible to reinfection following exposure to third-stage infective hookworm larvae in the soil as early as 4-12 months after drug treatment. Therefore, a prophylactic vaccine against hookworm infection would provide an attractive additional tool for the public-health control of this disease. The feasibility of developing a vaccine is based on the previous success of an attenuated larval vaccine against canine hookworm. Several laboratory and field studies have explored the development of a human anti-hookworm vaccine, describing potential protective mechanisms and identifying candidate antigens, one of which is now in clinical trials. The current roadmap that investigators have conceived has been influenced by vaccine development for blood-feeding nematodes of livestock and companion animals; however, recombinant vaccines have yet to be developed for nematodes that parasitise animals or human beings. The roadmap also addresses the obstacles facing development of a vaccine for developing countries, where there is no commercial market.

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    • "An ultimate human hookworm vaccine is likely to require at least two antigens, ideally from different developmental stages such as the infective third-stage larva (L3) and the adult worm, to achieve maximum efficacy [7]. Na-APR-1 is an ideal candidate antigen from the adult stage parasite, however it is not abundantly expressed in the L3. "
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    • "This level of protection would ensure that pasture was not contaminated with large numbers of worm eggs, but in the case of a more prolific egg producer, such as Haemonchus, a vaccine efficacy of 70% would be needed to ensure that pasture contamination was minimized. Successful protection against challenge infection requires to meet three parameters: first, a reduction in the infectivity of larvae, so that establishment of adult worms is compromised, and the worm burden is lower; second, a concomitant lowering of the pathogenicity; and third, an effect on female worm fecundity so that egg numbers are decreased (Loukas et al. 2006). Nematode parasites have been controlled for many years using anthelminthic drugs, but the progressive development of drug resistance can compromise their ability to control infection . "
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    • "The dioecious adults attach to the intestinal mucosa, rupture capillaries and feed on blood. Consequently, hookworm disease is characterized by anaemia, and often leads to physical and mental retardation and sometimes death in children and adverse maternal-fetal outcomes (Bethony et al., 2006; Loukas et al., 2006). Although anthelmintic drugs are used to reduce the burden of disease in a range of countries, mass treatment programs carry a significant risk of inducing drug resistance in hookworm populations (Cantacessi et al., 2010). "
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