Forgotten People, Forgotten Diseases. Peter J. Hotez
(the basis for the high rates of hookworm in coastal areas will become clearer when we discuss the hookworm life cycle). In some regions where more than 50% of the children were infected, it was shown that hookworm was a major reason why children were malnourished, why their growth was stunted, and why they did poorly in school and were prevented from reaching their full economic potential.12,15
After Charles Wardell Stiles and Bailey K. Ashford identified Necator americanus as the predominant hookworm in the United States, it became known as the “germ of laziness” or the “vampire of the South.”1,15 It is believed that hookworm was introduced into the United States when N. americanus was imported by infected slaves from sub-Saharan Africa during the 17th, 18th, and 19th centuries.1,15 Up until the 1950s, hookworm was also common in Japan and South Korea. In each of these now developed countries, reductions in the prevalence of tropical infections occurred primarily because of overall reductions in poverty and a shift to a more urbanized economy. In her book Malaria, Poverty, Race, and Public Health in the United States, the medical historian Margaret Humphreys argues that the Agricultural Adjustment Act and other New Deal legislation, which Congress passed in 1933, promoted rural depopulation by providing investment capital for the purchase of machinery, which took agricultural workers out of cotton and tobacco production.16 Such legislation caused landlords to tear down rural shacks and forced former dwellers to move either north or into southern cities.16 There is a common misconception that during the first 2 decades of the 20th century, the Rockefeller Foundation and its forerunner, the Rockefeller Sanitary Commission, eradicated hookworm in the American South and later in parts of Asia and South America through a combination of aggressive sanitation and the widespread distribution of shoes. For reasons that we will see below, it turns out that shoes are not an effective hookworm prevention measure, while sanitation in the absence of parallel economic development frequently has little impact on the transmission of STH infections.17 Instead, rural depopulation, urbanization, and economic development in the United States during the 1930s and in Japan and Korea in the years following World War II were probably the major elements leading to control of STH infections. In Asia, control was further hastened through widespread deworming by using first-generation anthelmintic drugs. Similar changes in human ecology probably account for the reductions observed in eastern China over the last 2 decades. Therefore, urbanization and economic development represent two of the most powerful forces responsible for the control of hookworm infection and other NTDs. Far more than the Sanitary Commission, the major health legacy of John Rockefeller was his foresight in establishing The Rockefeller University as a biomedical research powerhouse and in endowing the first generation of public health schools in the United States, beginning with the flagship school at Johns Hopkins University.
Figure 2.6 Distribution of human hookworm infection in the American South at the turn of the 20th century. The map displays the rates of hookworm infection among children by county groups. Red areas indicate the highest infection rates, followed by orange, yellow, and green. (Data from Bleakley, 2006.)
Humans become infected with hookworm through contact with infective larvae that live in the soil.18 The major cause of human hookworm infection is the nematode parasite N. americanus, although a second but less common species, Ancylostoma duodenale, also causes hookworm infection. The life cycle of N. americanus is shown in Fig. 2.7. Soil-dwelling infective hookworm larvae exhibit the ability to directly penetrate human skin. The larvae are less than 1 mm long (Fig. 2.8) and are therefore largely invisible to people working in the fields or children playing on the ground. Larvae enter through any exposed skin, including the hands, the arms, the buttocks, the legs, and yes, sometimes even the feet. The ability of N. americanus larvae to penetrate all aspects of the skin explains why shoes have minimal if any impact on reducing the hookworm prevalence in affected communities. The higher rates of hookworm infection in coastal areas reflect the sandy soils present in these regions. Hookworm larvae can migrate through sandy soils better than through soils with a high clay content.19
Figure 2.7 Life cycle of the hookworm N. americanus. (From Hotez et al., 2005.)
Figure 2.8 An adult hookworm. (Photo courtesy of David Sharf [http://www.electronmicro.com].)
It is common for people exposed repeatedly to hookworm larvae in the soil to acquire a pruritic (itchy) inflammatory condition of the skin known as ground itch or dew itch. The larvae then follow a 5- to 8-week migratory path through the body tissues, which includes an obligatory migration through the lungs that results in a cough (in contrast, when Ascaris larvae migrate through the lungs, they cause wheezing and other allergic symptoms that resemble asthma). Eventually, the infective hookworm larvae pass up the respiratory tree, crawl over the epiglottis, and are swallowed, before they enter the intestine and develop into adult hookworms. As the larvae develop into adult worms, they initially cause a painful eosinophilic enteritis syndrome. Subsequently, the pain subsides and mature parasites proceed to feed on blood. Each adult hookworm has the ability to fasten deeply to the inner lining of the intestine and extract blood. The parasite lyses red blood cells and digests the hemoglobin component.20 While feeding, the adult male and female hookworms mate and the female hookworm sheds thousands of eggs daily, which exit the body via the feces. In poor rural environments lacking adequate sanitation, either promiscuous defecation occurs or, in some societies, human feces are applied as fertilizer for crops (sometimes referred to as night soil). When feces are deposited on soil with adequate warmth and moisture, the eggs hatch and give rise to immature larvae that molt to become infective larvae.
People infected with hookworms become sick because of intestinal blood loss. The presence of as few as 25 N. americanus hookworms in the intestine is sufficient to cause about 1 ml of blood loss per day.21 This amount of blood contains approximately 0.5 mg of iron, representing roughly a typical child’s daily iron requirement. Therefore, hookworms essentially rob growing children of their daily iron and, as a result, cause iron deficiency anemia.21 Higher hookworm loads cause even more blood loss and more-profound anemia. Therefore, the disease resulting from chronic hookworm infection (sometimes referred to as hookworm disease) is long-standing iron deficiency anemia, which in children is responsible for growth retardation and intellectual and cognitive impairments. Because children tend to have low iron reserves from the outset, they are particularly vulnerable to hookworm-associated blood loss. Blood is also rich in protein, so that chronic blood loss can result in profound protein malnutrition, which is associated with edema of the face and limbs (Fig. 2.9). Many such children acquire a yellowish or sallow complexion; in several cultures, hookworm is known as the “yellow disease” or the “yellow puffy disease” (in Chinese, huang zhong bing, and in Brazilian Portuguese, amarelao). In antiquity, there are numerous references to the yellow disease, and there is an older term in the English medical literature, chlorosis, that refers to this condition.18