Hookworms 

Hookworms represent a widespread and clinically important human nematode infection. Prevalence figures indicate that the roundworms Ancylostoma duodenale and Necator americanus infect 576-740 million people and that they cause anemia in approximately 10% of those infected. Hookworms may persist for many years in the host and impair the physical and intellectual development of children and the economic development of communities.

Hookworm infection is acquired through skin exposure to larvae in soil contaminated by human feces. Adults, especially agricultural workers, are at equal or higher risk of exposure than children. Soil becomes infectious about 9 days after contamination and remains so for about 2 weeks. Individual hookworm treatment consists of iron replacement and anthelmintic therapy. Community eradication has proven difficult, even with intensive, yearly, school-based programs. Despite this, successful control and eradication of hookworms is a worthy goal for new methods that would offer huge economic and social benefits to much of Africa and Asia.

Necator and Ancylostoma adults are roundworms that range in length from 5-13 mm. Females release thousands of eggs into stool daily. In sandy moist soil, eggs hatch and must molt twice before developing into third-stage larvae.

Third-stage larvae are 500-700 µm long and are capable of rapid penetration into normal skin, most commonly of the feet. Transmission occurs after 5 or more minutes of skin contact with soil that contains viable larvae. They puncture and feed on mucosal capillaries in the jejunum. Ground itch at the site of penetration is more common with Ancylostoma species than with Necator.

The larvae burrow into venules and embolize the lungs, where they break into alveoli. A mild and usually asymptomatic alveolitis with eosinophilia ensues. (Hookworm is one of the causes of the pulmonary infiltrates and eosinophilia [PIE] syndrome, along with Ascaris and Strongyloides species.) Coughing brings the larvae to the mouth, where swallowing transports them to the intestine. Approximately 5 weeks after skin penetration, adult females begin to produce eggs. See the images below.

Ancylostoma larvae may also infect via ingestion, but they do not migrate into the body in this instance. This worm may lie dormant in tissues and later be transmitted through breast milk. Neither worm multiplies within the host. If the host is not reexposed, the infection disappears after the worm dies. Necator has a 5-year lifespan; Ancylostoma has a 1-year lifespan.

Each Necator worm ingests 0.03 mL of blood per day; each Ancylostoma worm ingests 0.2 mL of blood per day. Subsequent host anemia is proportional to diet, iron reserves, and worm burden. Threshold worm loads for anemia differ nationally, with as few as 40 worms producing anemia in countries with low iron consumption. Severe anemia affects intellectual and physical development in children and the cardiovascular performance in adults.

In the 19th century, an autopsy of an Italian tunnel worker who died of anemia revealed 1500 worms. Before worker sanitation was enforced, epidemic hookworm infection was common in mines and tunnels in Europe.

Recent work has suggested that malnutrition and immunocompromise, independent of anemia, can occur in children and adults with significant infection. This is the result of a protein-losing enteropathy, with immunoglobulins among the proteins lost, as a result of worm digestion. This results in stunted growth, as well as an increased susceptibility to infections such as malaria and gastrointestinal disease. This protein-losing enteropathy can also contribute to a more rapid progression of an HIV infection.

Apparently, the risk of atopy and dust-mite sensitization is inversely related to the burden of hookworm infestation in endemic areas. Whether this relationship is causative in either direction remains undetermined. The production of interleukin (IL)–5 during primary hookworm infection appears to enhance eosinophil function in limiting second-episode infection by invading larvae. Worms, however, also seem to provoke IL-10, IL-4, IL-5, and IL-13, which shift the cytokine response toward T helper 2 cells rather than toward T helper 1 cells. Hookworms also appear to secrete an inhibitor or natural killer cells, thereby suppressing production of gamma-interferon and the T helper 2 response that would be expected to clear the parasite. The increased prevalence of atopy, asthma, and food allergy in areas free of worm infestation has been cited as supportive of the hygiene hypothesis and even prompted investigation of worms astherapyforsuchdiseases.

In the search for possible vaccine targets, investigators have ascertained the existence of hookworm molecular inhibitors of coagulation factors Xa and VIIa-tissue factor and metalloproteases that degrade hemoglobin and intestinal mucosal cells. ASP-2, a protein isolated from larval N americanus, appears necessary for chemokine receptor binding and invasion and has shown some promise in animal vaccine trials.

Frequency

United States

Although hookworm infection is now thought to be rare in the United States, hookworm played an important role in the impoverishment of the South until the 1930s. Studies performed in the early 1970s indicated prevalence as high as 14.8% among schoolchildren from rural Kentucky and as high as 12% among schoolchildren from rural coastal Georgia. Infection and disease are now most likely to be found in immigrants and refugees from tropical countries. Occasionally, persons returning from travel abroad present with acute watery diarrhea with eosinophilia upon return to the United States.

International

Infection is widely distributed throughout tropical and subtropical areas, with prevalence in some communities as high as 90%. The disease flourishes in rural communities with moist shaded soil and inadequate latrines. Agricultural laborers have traditionally been at high risk of hookworm infection. Improper disposal of human feces and the common habit of walking barefoot are important epidemiologic features. However, the use of footwear has not been shown to affect hookworm prevalence, as the larvae can invade through any skin surface.

In 2005, The World Health Organization (WHO) estimated that 198 million individuals in sub-Saharan Africa were infected with hookworms, 149 million in East Asia/Pacific, 71 million in India, 59 million in other parts of South Asia, 50 million in Latin America and the Caribbean, 39 million in China, and 10 million in the Middle East and North Africa. Both Necator and Ancylostoma species have worldwide distribution, but Necator is more prevalent in Africa. Co-infection with Ascaris and Trichuris species is common in many parts of the world.

Infection is closely associated with poverty; inadequate sanitation, poor housing construction, and lack of access to essential medications are major factors in this relationship. As countries develop, these factors improve, and hookworm infestation decreases.^[1]

Mortality/Morbidity

• Adults carry larger worm burdens than children and are generally more subject to disease. However, the relationship is nonlinear and depends on diet and activity thresholds. The increasing prevalence of hookworm disease and higher worm burden among adults in many infected communities, especially China, suggests that hookworm is immunosuppressive.
• Young women, especially those who are pregnant, and laborers are most susceptible to symptomatic anemia. Adolescent girls and women of child-bearing age are particularly at risk for poor outcomes such as increased maternal mortality, prematurity, low birth weight, and impaired lactation. Up to 30-54% of moderate to severe anemia among Africa and Asian women is attributed to hookworm.
• Severe anemia retards childhood development and intellectual performance. Vigorous labor is possible only with hemoglobin levels of more than 7 g/dL.

Age

• Because infection is usually acquired by walking, handling, or lying in contaminated soil, hookworm infection is uncommon in young children. Studies performed in Brazil indicate that the prevalence and intensity of infection is higher among poorer households. Similar studies in Uganda indicate that, compared with the spotty geographic prevalence of ascariasis and trichuriasis, hookworm is more homogeneously distributed.^[2]
• Recent studies from China and Brazil indicate consistently increasing prevalence of disease, from 15% at age 10 years to 60% at age 70 years and older. Egg counts in stool also increase in a similar pattern. These data suggest the need for a larger control target than infected schoolchildren and the need to overcome what appears to be an immunocompromised state with respect to the parasite.