Hookworms

Three species of hookworm infect humans, Ancylostoma duodenale, Ancylostoma ceylanicum, and Necator americanus. The most serious of the three is A. duodenale since each worm sucks about 5 times the amount of blood as N. americanus, 0.2 ml/worm per day versus 0.04 ml/worm per day (Crompton 2000). A. ceylanicum is found in Asia and Australia and appears to be able to infect humans, dogs and cats.

Hookworms live in the small intestine, attach to the mucosa using their large mouths and suck blood. They release many active compounds to stop blood coagulating (so they can drink it much easier) and to reduce the immune response of the host. By suppressing the inflammatory and allergic reactions at their attachment site hookworms can survive for many years (Croese et al 2006, Croese and Speare 2006). Some experimental infections with N. americanus have lasted for 15 years.

Hookworms are classified as Soil Transmitted Helminths (STH). This is because hookworm eggs hatch after being passed in faeces and the larvae develop in the soil-faeces mix, growing by feeding on faecal bacteria. Infective larvae develop usually within 7 days at 25C. Hookworm can not develop in toilets or water. STH fall into the category of Neglected Tropical Diseases (NTDs). STH are markers of poverty since a high prevalence indicates that faeces are being deposited on the soil, usually due to lack of safe sanitation.

In developing countries public health activities are focussed on reducing the impact of hookworms on the health of the most vulnerable members of the society, children and pregnant women (Crompton 2000). This is called morbidity control. There is an increasing call for STH control programs to change from morbidity control to transmission control, progressing to elimination.

STH may not be all bad! Allergic diseases and autoimmune diseases have a much lower incidence in populations with a high prevalence of STH. The evidence suggests that the allergic response may have evolved in humans to help them cope with STH and when this action is no longer needed (ie, no intestinal nematode parasites), the allergic response may be directed against other antigens. If this includes self-antigens, autoimmune disease can occur. If it includes external antigens on mucosal surfaces, allergic diseases (eg, asthma, eczema, hay fever) may result.

Hence, research has started to understand what role STH play in modifying allergic or autoimmune diseases. No clear answers have been found. However, there is some indication of an effect of whipworm on ulcerative colitis (Summers et al 2005) and of hookworm in Crohn's disease (Croese et al 2006), coeliac disease (Daveson et al 2009, 2011, McSorley et al 2011, Gaze et al 2012), and asthma (Feary et al 2010). The implications of the research is that N. americanus may dampen or down-regulate the Th1 response that is driving these diseases. No one has been cured, but results are interesting and there does seem to be a trend towards improved control.

Download the slideshow by Rick Speare "Insights from experimentally infecting humans with hookworms". This lecture was given to a weekly research meeting of the Medical Research Council (Gambia) in October 2012.

References:

Croese J, O’Neil J, Masson J, Cooke S, Melrose W, Pritchard D, Speare R. A proof of concept study establishing Necator americanus,/i> in Crohn’s patients and reservoir donors. Gut 2006;55:136-137.

Croese J, Speare R, Wood M, Melrose W. Allergy controls the population density of Necator americanus in the small intestine. Gastroenterology 2006;131(2):402-409.

Croese J, Speare R. Intestinal allergy expels hookworms: seeing is believing. Trends in Parasitology 2006;22(12):547-550.

Crompton DW. The public health importance of hookworm disease. Parasitology 2000;121 Suppl:S39-50.

Daveson AJ, Jones DM, Gaze S, McSorley H, Clouston A, Pascoe A, Cooke S, Speare R, Macdonald GA, Anderson R, McCarthy JS, Loukas A, Croese J. Effect of hookworm infection on wheat challenge in celiac disease--a randomised double-blinded placebo controlled trial. PLoS One 2011;6(3):e17366.

Daveson AJM, Jones D, Mcsorley H, Gaze S, Mccarthy J, Clouston A, Pascoe A, Macdonald G, Speare R, Anderson R, Loukas A, Croese J. A phase 2A randomized double blinded placebo controlled study evaluating immunity and gluten sensitivity by inoculating coeliac disease patients with the human hookworm Necator americanus. Journal of Gastroenterology and Hepatology 2009;24:A221-A222.

Feary JR, Venn AJ, Mortimer K, Brown AP, Hooi D, Falcone FH, Pritchard DI, Britton JR. Experimental hookworm infection: a randomized placebo-controlled trial in asthma. Clinical and Experimental Allergy 2010;40(2):299-306.

Gaze S, McSorley HJ, Daveson J, Jones D, Bethony JM, Oliviera LM, Speare R, Mccarthy JS, Engwerda CR, Croese J, Loukas A. Characterising the mucosal and systemic immune responses to experimental human hookworm infection. PLoS Pathogens 2012;8(2):e1002520.

McSorley HJ, Gaze S, Daveson J, Jones D, Anderson RP, Clouston A, Ruyssers NE, Speare R, McCarthy JS, Engwerda CR, Croese J, Loukas A. Suppression of inflammatory immune responses in celiac disease by experimental hookworm infection. PLoS One 2011;6(9):e24092.

Summers RW, Elliott DE, Urban JF Jr, Thompson RA, Weinstock JV. Trichuris suis therapy for active ulcerative colitis: a randomized controlled trial. Gastroenterology 2005;128(4):825-832.

Page by Rick Speare - updated 3 November 2012

A N. americanus attached to the small intestinal mucosa, captured by capsule endoscopy.

A N. americanus can be seen feeding in the small intestine in this video constructed from capsule endoscopy images. The hookworm appears as a white worm with a central red stripe. It's gut is red since it contains blood. Although this worm "waves" in the intestinal current and gives the impression of swimming freely, it is attached to the mucosa by a plug of tissues sucked into its mouth. For fabulous images of hookworm mouths see the Taxonomy of Hookworms page. This worm was from an experimental infection (Croese & Speare 2006).