The End of the Line for Hookworm? An Update on Vaccine Development

H uman hookworms are parasitic nematodes infecting about 700 million individuals, largely in tropical regions of the world [1]. In endemic areas, most infected people carry a mixed worm burden, including Ascaris lumbricoides (roundworms), Trichuris trichuria (whipworms), and Ancylostoma duodenale and/or Necator americanus (both hookworms). Of these soil-transmitted helminths, hookworms are the most pathogenic because of their propensity to feed on blood, resulting in anaemia, particularly in those with low iron reserves such as children and women of reproductive age. Hookworms' blood-feeding (hematophagous) habits cause pathology in humans and animals. The worms attach to the wall of the small intestine using their mouthparts and feed on blood from ruptured capillaries. Each female worm is estimated to ingest a minimal 0.1 ml of blood per day. However, actual blood loss can be signifi cantly greater; the worms change their feeding sites several times a day, and the secretion of anti-coagulants means that the vacated sites continue to bleed, contributing greatly to blood loss. Hookworms do not kill, but they can cause subclinical disease, most notably anaemia and impaired physical and cognitive development in children. As hookworm infection is associated with low socioeconomic status, it adds signifi cantly to the burden of disease in such areas [1]. Hookworms have a simple life cycle in which the third-stage larvae (L3) infect humans, generally by skin penetration, although some species are also infective via oral ingestion. The parasites enter the bloodstream and migrate to the lungs; from there, they are coughed and swallowed to the small intestine (Figure 1). The adult parasites mature in the intestine, and following mating, the female worm produces many thousands of eggs that pass out in the faeces and develop on the ground to infective L3. Hookworms can be treated using anthelmintic drugs such as albendazole, but treated people soon become reinfected. Additionally, recent epidemiological studies from China and Brazil show the highest worm burden and the highest prevalence of infection in the elderly [2], contrasting with the intensity/prevalence curves for other soil-transmitted helminths, which typically peak in mid-to-late childhood. These data suggest that under natural conditions of exposure, little immunity is evoked. Given this immuno-epidemiological picture, developing a vaccine is a signifi cant challenge. Recent studies suggest that the hematophagous lifestyle of hookworms may prove their downfall. Hookworms are armed with an array of molecules that are essential for blood feeding and digestion; these include anticoagulants and a …