Chapter 329. Hookworm

Hookworm infection remains a major health burden in developing countries.1 As many as 740 million people in the world are infected with Ancylostoma duodenale, Necator americanus, or both.2 Infections with A duodenale occur in focal regions of Africa, Asia, and South America, whereas N americanus is the predominant hookworm worldwide, with the greatest number of infections in North and South America, equatorial Africa, much of Southeast Asia, and some Pacific islands. It is important to recognize that there is significant overlap in the geographic pattern of infection and that mixed infections occur frequently. Although common in southern states in the early part of the 20th century, today there is little evidence of hookworm transmission in the United States. Other species that occasionally cause intestinal disease in humans include Ancylostoma ceylanicum, found in India and Southeast Asia,3 and the dog hookworm Ancylostoma caninum, which has been associated with eosinophilic enteritis in Australia.4 Zoonotic infection with Ancylostoma braziliense causes cutaneous larva migrans.5

Populations at highest risk for significant disease sequelae include preschool and school-age children, adolescents, and women of childbearing age, although adults who work in agricultural occupations are also at risk for high-intensity infection. Vulnerable populations such as young children and pregnant or lactating women are at greater risk of anemia due to relatively high iron requirements.6 Unlike Ascaris lumbricoides and Trichuris trichiura, the intensity of hookworm infection appears to increase with age, defining the elderly as another high-risk group for severe disease.7

The hookworm life cycle begins with the excretion of fertilized eggs within the feces of an infected individual. The eggs hatch to release first-stage (L1) larvae, which undergo two subsequent molts to the infective third stage (L3). These L3 hookworm larvae migrate along moisture and temperature gradients within the soil until they encounter a permissive host. When larvae contact the skin, they quickly penetrate the epidermis and dermis, ultimately invading small blood vessels and entering the venous circulation. They are then carried passively to the heart and lungs, where they lodge in the pulmonary capillaries and break through to the alveolar space. Larvae then migrate up the respiratory tree, are swallowed, and undergo their final developmental molts to the adult stage when they reach the small intestine. Once in the proximal small bowel, the adult worms attach to the mucosal surface and begin to feed (Fig. 329-1 and eFig. 329.1). Adult hookworms secrete anticoagulants, platelet inhibitors, and hemoglobin-degrading proteases that facilitate blood feeding and digestion of red blood cells.8-10 When the plug of intestinal mucosa at the site of attachment has been digested, the worm releases and reattaches at a new site. Male and female worms mate, and the female releases 10,000 to 30,000 eggs per day into the intestinal lumen. It takes approximately 6 weeks for eggs to appear in the feces of an infected individual.

Two important features of the life cycle distinguish Ancylostoma hookworms from Necator. First, A duodenale can cause infection when ingested, whereas N americanus can only complete its life cycle in humans following skin penetration. Second, there is epidemiologic evidence to suggest that third-stage larvae of A duodenale may arrest within various tissues of their host, ultimately resuming development and completing their life cycle months to years later.11 Reports of severe disease manifestations in young infants raises the possibility that A duodenale may also be transmissible through breast milk.12

Clinical Manifestations

As third-stage larvae penetrate the skin, a local urticarial eruption, known as ground itch, may occur. Although hookworms frequently penetrate the soles of the feet, it is important to recognize that the parasite will invade any exposed skin surface. The pulmonary migration of hookworms is rarely associated with significant clinical symptoms, although cough and wheezing may develop following infection with a large inoculum. Of note, the pulmonary phase is associated with the development of peripheral eosinophilia and precedes the appearance of eggs in the feces.13

The clinically significant manifestations of hookworm infection are primarily attributable to loss of blood and serum proteins that are a consequence of feeding by the adult worm. In light infections, subclinical iron deficiency can also develop if daily iron intake cannot compensate for iron lost through intestinal bleeding. In chronic infections, significant iron deficiency leads to a microcytic, hypochromic anemia. Particularly heavy infections may also manifest as severe protein malnutrition, as the worm drains serum proteins in addition to red blood cells as it feeds.14 Rarely, high-output heart failure develops as a consequence of chronic, severe hookworm anemia. Importantly, even children with mild infections may suffer impairment of physical and intellectual development, particularly when they also harbor other intestinal nematodes.15

Intestinal infection with the dog hookworm A caninum is associated with eosinophilic enteritis, an unusual syndrome characterized by abdominal pain, tenderness, and gastrointestinal bleeding.4,16 Results of biopsies of the small bowel routinely show massive eosinophilic infiltrates, and occasionally a single adult canine hookworm has been identified attached to the mucosa. However, there is frequently no direct evidence of hookworm infection in patients with eosinophilic enteritis.

Diagnosis

The definitive diagnosis of hookworm infection is made by finding characteristic ova in the feces. These thin-shelled, ovoid eggs with granular-appearing contents measure 60 by 40 µm and are generally in the 2- to 4-cell stage when passed in feces. It is important to recognize that many children from the developing world who are infected with hookworm frequently harbor other intestinal nematodes as well, including Ascaris lumbricoides and Trichuris trichiura, which are also associated with anemia and malnutrition. Because hookworm egg excretion can be intermittent, multiple stool examinations may be required to confirm the diagnosis. Routine microscopy cannot differentiate between the eggs of A duodenale and N americanus, although polymerase chain reaction methods have been developed for research purposes. The differentiation between species is not necessary with regard to treatment options. In addition, there are no routinely used serum antibodies or fecal antigen tests for diagnosing hookworm infection. Evaluation for possible hookworm infection is warranted in any traveler, immigrant, or refugee from an endemic area who presents with iron-deficiency anemia or peripheral blood eosinophilia.17 It is important to note that the degree of eosinophilia may vary and in light infections is often mild.

Treatment and Prevention

The treatment of choice for the eradication of intestinal hookworms is a single oral dose of albendazole (400 mg) or mebendazole (500 mg). Pyrantel pamoate (11 mg/kg/day for 3 days) is an alternative.15 Nitazoxanide, which has activity against hookworm, is approved for use in children, but not specifically for this indication, and should not be considered a first-line treatment.18 Additionally, iron supplementation can be considered if anemia is present. Children treated for hookworm frequently experience significant short-term catch-up growth, and studies show short-term improvement in a number of developmental parameters following therapy. Unfortunately, in endemic areas reinfection with hookworms occurs rapidly, and the benefits of intermittent chemotherapy may be short-lived.19

Proper sanitation, health education, and proper footwear have helped prevent soil-transmitted helminth infections. However, the improvements in economic development and reduction of poverty have been the most substantial influences on the decreases in helminth infections. School-based deworming programs have offered many benefits to high-risk populations but neglect other vulnerable groups (eg, adults) and may not significantly reduce the transmission of hookworm.1 In 2001, a resolutionwas put forward by the World Health Assembly urging countriesto control schistosomiasis and the soil-transmitted helminthiases—ascariasis, trichuriasis, and hookworm infection.20 By 2010, the goal is to provide treatment for three quarters of young children at risk for infection.

Decreasing efficacy of benzimidazoles in some highly endemic areas has raised concerns about the emergence of hookworm resistance to benzimidazole anthelminthics.21 For this reason there has been renewed interest in the development of vaccines and novel chemotherapeutic agents to control hookworm worldwide. Including anthelminthics as part of integrated control programs targeting multiple tropical diseases may confer benefit at both the individual and population level, including those with coinfections such as HIV, malaria, and tuberculosis.22,23 Clinical trials of recombinant vaccines designed to prevent or ameliorate the clinical sequelae of hookworm infection are currently in progress.24