Clinical effects

Iron deficiency anaemia
Hookworms suck blood from the site where they are attached in the small intestine. Hence, they cause loss of iron (as haemoglobin (Hb) in red blood cells (RBC)). This can result in iron deficiency, particularly in people whose diet does not contain enough iron to compensate for the iron lost in blood. The end result is iron deficiency anaemia with a microcytic (RBC with smaller volume), hypochromic (lower than normal concentration of Hb in each RBC) anaemia.
Of course whether a person gets anaemia depends on the amount of blood lost (number of worms and species of hookworm), their iron stores, and their dietary intake of iron (Crompton 2000). An individual hookworm of A. duodenale sucks more blood than an individual N. americanus; about five times as much. Choose your hookworms carefully!

Abdominal pain
When a hookworm infective larva penetrates the skin, the larva goes on a journey through the body which takes them through the lungs, up the trachea, down the oesophagus, through the stomach, arriving at their new home in the small intestine. This is called the blood-lung cycle. In the duodenum the juvenile worms attach, start sucking blood and grow into adults. Life is sweet for 3 weeks after skin penetration, but then the defences of the human host recognise a hookworm is present and start to attack it. The most effective response appears to be a local allergic reaction at the hookworm bite site. Eosinophils invade the area from the blood. However, the hookworm responds by pumping out compounds to suppress the host's response. A battle follows! If the allergic reaction at the bite site is too great, the hookworm lets go of the intestine and is swept away by the peristaltic current. It may attach lower down in the gut. Remember that the duodenum is prime real estate; jejunum and ileum are OK, but not quite Yarrawonga! If the allergic response is very effective, the hookworm can loose completely, and find itself in the toilet bowl. In this way, an infected host may reject many of the hookworms that arrived in the duodenum. See the two papers that describe this rejection process (Croese et al 2006, Croese & Speare 2006).

What is the clinical effect? Abdominal pain! In experimental infections "normal" subjects developed central abdominal pain about 3 weeks after infection. The pain was relatively constant (not colicky). Occasionally it reached a stage where the brave subjects had to resort to oral analgesia. It was accompanied by intermittent diarrhoea, but this was a minor sign. The pain lasted about a month (during the period of the battle royale) and then stopped (Fig. 1). At this stage a truce has been called between the surviving hookworms and the host.

Fig. 1: Abdominal pain after experimental infection with 101 infective larvae of Necator americanus. Scale: grade 1 = pain, but not requiring analgesia; grade 2 = severity of pain requires oral analgesia; grade 3 = severe pain, not adequately controlled by oral analgesia, prompting the thought "Why did I do this?".

Does this abdominal pain occur in natural infections? Probably, but it is poorly documented. In a community wide hookworm treatment program in Na'au village, Malaita, Solomon Islands, administration of albendazole cured the abdominal pain of two men who had hookworms.

Lesions at penetration sites of infective larvae
To penetrate the skin hookworm infective larvae first have to gain a mechanical purchase (ie, get their anterior end into the skin). They do this by wriggling into hair follicles or under skin scales. Once they have a physical beachhead, they then secrete compounds that digest host tissue; so they move through the epidermis, enter the dermis and burrow into a dermal capillary or lymphatic. The host reacts to the chemicals secreted.

The initial reaction is a pin-point itching sensation (like an annoying mosquito bite that persists). This appears as a small area of erythema (redness). Within 24 hours this area is more distinct and a papule (small raised lump on skin) starts to form. This is very useful for researchers as for each larvae that penetrated the host marks its entry with a papular lesion. We can count the number of hookworm larvae that were successful!

In most people that is it! The papules slowly fade and by 7 days the skin is back to normal. Very rarely the reaction is more severe; papules are larger and last longer. See the PPT presentation showing one of these responses. However, even in these severe reactions the skin does return to normal, but it may take 2 to 3 weeks. Reactions to penetration extend along a spectrum from mild to severe; the one shown in the presentation is at the severe end and is rare.

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.

Literature cited
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.

Page by Rick Speare 22 July 2012

An infective larvae of Necator americanus ready to go!

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