Etiology

Two major genera of hookworms, which are nematodes or roundworms, infect humans. Necator americanus, the only representative of its genus, is a major anthropophilic hookworm and is the most common cause of human hookworm infection. Hookworms of the genus Ancylostoma includes the major anthropophilic hookworm Ancylostoma duodenale that also causes classic hookworm infection and the less common zoonotic species A. ceylanicum, A. caninum, and A. braziliense. Human zoonotic infection with the dog hookworm A. caninum is associated with an eosinophilic enteritis syndrome. The larval stage of A. braziliense, whose definitive hosts include dogs and cats, is the principal cause of cutaneous larva migrans.

The infective larval stages of the anthropophilic hookworms live in a developmentally arrested state in warm, moist soil. Larvae infect humans either by penetrating through the skin (N. americanus and A. duodenale) or when they are ingested (A. duodenale). Larvae entering the human host by skin penetration undergo extraintestinal migration through the venous circulation and lungs before they are swallowed, whereas orally ingested larvae may undergo extraintestinal migration or remain in the gastrointestinal tract. Larvae returning to the small intestine undergo 2 molts to become adult sexually mature male and female worms ranging in length from 5 to 13 mm. The buccal capsule of the adult hookworm is armed with cutting plates (N. americanus) or teeth (A. duodenale) to facilitate attachment to the mucosa and submucosa of the small intestine. Hookworms can remain in the intestine for 1-5 yr, where they mate and produce eggs. Although approximately 2 mo is required for the larval stages of hookworms to undergo extraintestinal migration and develop into mature adults, A. duodenale larvae may remain developmentally arrested for many months before resuming development in the intestine. Mature A. duodenale female worms produce about 30,000 eggs/day; daily egg production by N. americanus is <10,000/day (Fig. 284-1). The eggs are thin shelled and ovoid, measuring approximately 40-60 µm. Eggs that are deposited on soil with adequate moisture and shade develop into 1st stage larvae and hatch. Over the ensuing several days and under appropriate conditions, the larvae molt twice to the infective stage. Infective larvae are developmentally arrested and nonfeeding. They migrate vertically in the soil until they either infect a new host or exhaust their lipid metabolic reserves and die.

Figure 284-1 Adult male and female soil-transmitted helminths.

(From Bethony J, Brooker S, Albonico M, et al: Soil-transmitted helminth infections: ascariasis, trichuriasis, and hookworm, Lancet 367:1521–1532, 2006.)

Epidemiology

Hookworm infection is one of the most prevalent infectious diseases of humans, affecting an estimated 576 million individuals worldwide. Because of the requirement for adequate soil moisture, shade, and warmth, hookworm infection is usually confined to rural areas, especially where human feces are used for fertilizer or where sanitation is inadequate. Hookworm is an infection associated with economic underdevelopment and poverty throughout the tropics and subtropics. Sub-Saharan Africa, East Asia, and tropical regions of the Americas have the highest prevalence of hookworm infection. High rates of infection are often associated with cultivation of certain agricultural products such as tea in India; sweet potato, corn, cotton, and mulberry trees in China; coffee in Central and South America; and rubber in Africa. It is not uncommon to find dual N. americanus and A. duodenale infections. N. americanus predominates in Central and South America as well as in Southern China and southeast Asia, whereas A. duodenale predominates in North Africa, in northern India, in China north of the Yangtze River, and among aboriginal people in western Australia. The ability of A. duodenale to withstand somewhat harsher environmental and climatic conditions may reflect its ability to undergo arrested development in human tissues. A. ceylanicum infection occurs in India and southeast Asia.

Eosinophilic enteritis caused by A. caninum was 1st described in Queensland, Australia, with 2 reported cases in the USA. Because of its global distribution in dogs, it was initially anticipated that human A. caninum infections would be identified in many locales, but this has not been found.

Pathogenesis

The major morbidity of human hookworm infection is a direct result of intestinal blood loss. Adult hookworms adhere tenaciously to the mucosa and submucosa of the proximal small intestine by using their cutting plates or teeth and a muscular esophagus that creates negative pressure in their buccal capsules. At the attachment site, host inflammation is downregulated by the release of antiinflammatory polypeptides by the hookworm. Rupture of capillaries in the lamina propria is followed by blood extravasation, with some of the blood ingested directly by the hookworm. After ingestion, the blood is anticoagulated, the red blood cells are lysed, and the hemoglobin released and digested. Each adult A. duodenale hookworm causes loss of an estimated 0.2 mL of blood/day; blood loss is less for N. americanus.