Hookworm and Poverty

PETER HOTEZ
Sabin Vaccine Institute, Washington, DC, USA Department of Microbiology, Immunology, and Tropical Medicine, The George Washington University, Washington, DC, USA

Human hookworm infection is the leading cause of anemia and undernutrition and the second most important parasitic infection of humans. Hookworm occurs almost exclusively in the setting of rural poverty in the developing countries of the tropics. The rural dependency reflects the precise soil and temperature requirements of the environmental life history stages of the parasite, whereas the relationship between hookworm and poverty is based on multiple factors, including inadequate sanitation, the absence of concrete floors in home dwellings, and lack of access to essential medicines. Also, hookworm not only occurs in the setting of poverty but also promotes poverty because of its health and educational effects in children, its adverse effect on pregnancy outcome, and its effect on worker productivity. Since the middle of the 20th century, poverty reduction and urbanization have successfully reduced the prevalence of hookworm in the world’s industrialized nations and some middle-income countries. However, the control of hookworm in low-income countries still relies heavily on the frequent and periodic use of anthelminthic drugs either through deworming programs targeting school-aged children or through integrated control programs that simultaneously target the seven neglected tropical diseases, including hookworm. However, the high rates of hookworm reinfection and the possible emergence of drug resistance will ultimately require the development of new control tools—including the Human Hookworm Vaccine, one of several so-called antipoverty vaccines that could undergo development and testing over the next decade. Key words: hookworm; poverty; vaccine

Human hookworm infection is one of the most common diseases of poor people and a leading cause of anemia and undernutrition in developing countries.1,2 An estimated 576 million people are infected worldwide,3 with the most infections occurring in subSaharan Africa followed by Southeast Asia, India, and the Americas (TABLE 1). For disability, and using the disability-adjusted life year as a metric, hookworm infection is the second most important parasitic infection of humans, behind malaria.2,4 Hookworm is one of several so-called neglected tropical diseases, a group of 13 major poverty-promoting chronic and disabling tropical infections.5 There are multiple species of hookworm, but almost all cases of human hookworm infection are caused by the nematode parasites Necator americanus and Ancylostoma duodenale, with the former predominating in

most of the world.1 In the developing regions of the tropics, almost all hookworm cases occur in areas of extreme rural poverty. The roughly 600 million cases of hookworm are distributed predominantly in agricultural areas and among the estimated 2.7 billion people who live on less than $2 per day.5 Therefore, environment and socioeconomic status represent the two most important determinants for acquiring hookworm.

Effect of the Rural Environment on Hookworm
The key environmental components for ensuring hookworm transmission and endemicity are temperature, and soil moisture, and soil type.6 Such conditions are met predominantly in rural areas of the tropics and in coastal areas in particular. To appreciate the basis for this intimate link between hookworm and rural soil conditions, first understanding the environmental component of the hookworm life cycle is helpful. Because each female adult N. americanus hookworm living in the human gastrointestinal tract produces approximately 10,000 eggs per day, the feces of infected people

Address for correspondence: Peter Hotez, MD, PhD, Ross Hall 736, 2300 I St., NW, Washington DC, 20037. Voice: 202-994-3532; fax: 202994-2913. photez@gwu.edu, peter.hotez@sabin.org Scientific Approaches to Understanding and Reducing Poverty Annals of the New York Academy of Sciences

Ann. N.Y. Acad. Sci. 1136: 38–44 (2008). doi: 10.1196/annals.1425.000

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2008 New York Academy of Sciences. 38

high rates of infection are found in association with working in the tea gardens. these regions can exhibit particularly high hookworm endemicity.6 In Africa. Chandler found that ambient temperatures between 20 ◦ C and 30 ◦ C are optimal for larval development in the soil but that larval viability still continues even when temperatures rise into the low 40s. Under the right conditions. sufficient rainfall is necessary to support the hookworm life cycle. Thus. Effect of Poverty on Hookworm The climate and the sandy soils of the Gulf Coast and the Atlantic Coast of the American South are ideal for propagating the hookworm life cycle. Indeed.477. found the highest hookworm prevalence among vegetable growers and farmers.5 mm. Florida. as well as epidemics of yellow fever.17 Indeed.10. and hookworm infection. 3) Region Sub-Saharan Africa East Asia Pacific India and South Asia Latin America and Caribbean China Middle East Total prevalence by region 39 No. at the turn of the 20th century. the relationship between hookworm and agriculture has been partly linked to the handling of human feces as nightsoil fertilizer12. hookworms exhibit a lower tolerance for cold temperatures than do either Ascaris or Trichuris. of estimated hookworm cases (millions) 198 149 130 50 39 10 576 are typically laden with hundreds of thousands of eggs. This finding accounts for their observation that hookworm is endemic throughout most of Mali and southern Chad. the larvae are extremely vulnerable to desiccation and direct sunlight.14 Historically.6 For instance.16 . In China and Southeast Asia. Hookworm (adapted from Ref. Because coastal areas in the developing world have sandy soil. a Chinese national parasite survey conducted between the late 1980s and early 1990s. and to the naked eye they appear as small white dust specs. For in- fection to occur. the infective larvae must be able to reach the soil surface. Therefore.7 Recently. the coastal regions of East Texas. the geographic range of temperatures and rainfall that make conditions suitable for hookworm larvae in the soil are similar to those conditions required for the Anopheles mosquito vector that transmits malaria.9 Soil conditions are equally important for ensuring hookworm larval transmission.6. Infective larvae directly penetrate human skin. in contrast to ascariasis and trichuriasis. hookworm has been a major occupational hazard for agricultural laborers throughout the developing world (reviewed in Ref. especially the hands and feet. making hookworm endemic in agricultural regions where people expose their skin to the damp and moist earth where hookworm larvae are abundant. as well as showing the tight link between hookworm and poverty. Hookworm infective larvae are slightly longer than 0. these larvae molt twice to the infective larval stages. 15). During dry conditions. such as Ascaris lumbricoides and Trichuris trichiura. Georgia. usually the daily exposure of soil contaminated with hookworm infective larvae mostly accounts for the rural component of hookworm transmission. the eggs hatch and give rise to larvae that feed on organic debris and bacteria in the soil. and they are at low altitudes (and therefore high temperatures). Mississippi. the larvae retreat deeper into the soil. through satellite mapping and remote sensing.11 Consistent with the factors that ensure hookworm endemicity in rural areas and the requirement for soil contact to acquire hookworm are the high rates of infection among agricultural laborers and their families. Over several days.12.Hotez: Hookworm and Poverty TABLE 1. Today. Hookworm Disease. Brooker and his colleagues have determined that the environmental stages of hookworm have higher thermal limits than those of other soiltransmitted helminths.8 On the other hand. in which fecal exams were conducted on 1. Louisiana. several studies have confirmed a significant negative association between socioeconomic status and hookworm infection prevalence or . and the Carolinas exhibited high prevalence rates of hookworm and other tropical diseases including malaria and typhoid fever.13 whereas on the Indian subcontinent. Sandy soils allow greater hookworm mobility than clay soils. Soil type is also important. a measure of poverty. there is a high degree of geographic overlap and coendemicity between hookworm and malaria in sub-Saharan Africa. which explains why hookworms are seldom found at high altitudes. however. In his classic monograph.742 individuals in every province.13. hookworm and other tropical diseases no longer occur in the United States because the extreme poverty also needed to sustain the endemicity of these diseases no longer exists. However. FIGURE 1 shows the relationship between human development index. The viability of hookworm eggs and larvae depends on whether egg-containing human feces are deposited in an environment where the ambient temperatures are high enough and the soil conditions appropriate for larval development.

Conversely.1 FIGURE 1. eventually causing enough blood loss to produce hookworm disease. the effect of poverty reduction and urbanization is being played out throughout Eastern China where.13. poverty reduction and urbanization are the most important elements for reducing hookworm transmission.18 whereas in Panama poorer children exhibited higher hookworm intensities. After skin penetration.19. Poor housing construction.18 poverty probably operates as a risk factor for hookworm infection partly through the poor housing construction. the poor and largely rural southern and southwest . Better-off families can afford anthelminthic drugs to treat hookworm on a frequent and periodic basis and therefore do not have to depend on government-sponsored deworming programs in schools or those conducted as part of child health days. because higher hookworm burdens lead to higher fecal egg counts. poor (3rd quartile).25 Therefore. and walls with cracks and crevices is also responsible for the transmission of Chagas’ disease in impoverished regions of Central and South America. Higher-intensity infections mean that there are more hookworms causing blood loss.24. The socioeconomic status of 94 countries was assessed according to several commonly used indicators. 3. intensity is better reflective of hookworm disease burden than is prevalence. 2.18 One of the factors not listed is wearing shoes or other footwear. very poor (2nd quartile)..19 To understand the concept of hookworm intensity. one assesses hookworm intensity by measuring the number of hookworm eggs in the feces. and the eggs exit the body in the feces.20 mL/day.2 with permission. Relationship between prevalence of hookworm and poverty. hookworm is associated with the absence of a latrine.21–23 The exact mechanisms by which poverty leads to higher hookworm prevalence and intensities are still not well established. The adult female hookworm produces thousands of larvae daily. Each adult hookworm causes blood loss ranging from 0. duodenale is also orally infective. although A. Error bars represent 95% confidence intervals. Shoes are not significantly protective20 because N. thatch roofs. to the least poor (4th quartile).20 The relationship between poverty and parasite prevalence and intensity is true not only for hookworm but also for other soil- Poverty Reduction and Urbanization Rural environmental factors and poverty are the two most potent forces in promoting hookworm transmission in developing countries. with poverty measures divided into quartiles ranging from the most poor (1st quartile). In many hookworm-endemic communities.03 to 0. poor schoolchildren showed a significantly higher infection prevalence of hookworm than that of children of families of better means.1 Typically. intensity (number of hookworms per individual). In this way. For example. the larvae enter small blood and lymph vessels and are swept passively via the circulation to the right side of the heart and then to the lungs.17 modified in Hotez et al.26 In contrast. the larvae migrate up the respiratory tree and are coughed up and swallowed. americanus penetrates all aspects of the skin surface. because of intense economic growth. the intensity of hookworm increases with age.40 Annals of the New York Academy of Sciences transmitted helminth infections in developing countries.. From there. In the gut. including the hands. the prevalence and intensity of hookworm infection have reduced dramatically compared with 20 years earlier. Because the propagation of the hookworm life cycle depends on inadequate sanitation and the deposition of human feces on soil. Cement floors and slabs in homes are a protective factor for transmission. To date.18 Because cement houses indicate wealth in developing countries. Poor housing construction with dirt floors. as well as to other soil-transmitted helminths and schistosomes. the larvae develop into sexually mature adult hookworms. understanding the rest of the parasite life cycle is important. research has identified at least three major factors: 1. which is characterized by iron deficiency anemia and protein malnutrition. Inadequate sanitation. in rural Cote d’Ivoire. Today. Access to essential medicines. From DeSilva et al. especially ascariasis. people living in poverty who presumably do not have regular access to a latrine would be at higher risk of exposure to hookworm.

Endemic hookworm infection keeps affected populations mired in a cycle of destitution and despair by affecting (1) child growth and development. a program of sanitation as a solitary measure reduced the prevalence of hookworm only 4%. including more clinical episodes of malaria as well as increased severity. more than any other. Yunnan. and provision of drainage. like other neglected tropical diseases.5 However. and Guangxi. as well as malaria and typhoid fever. in Iran. not only occurs in the setting of poverty but also promotes poverty. such as Hainan. clean water. and (3) worker productivity (reviewed in Ref. such assessments are a high priority given the emerging evidence that hookworm and other neglected tropical diseases are not only significant global health problems but also important impediments to economic development. and Hookworm Control as a Means to Economic Growth As urbanization and poverty reduction expand in the largest middle-income countries.9 resulting in more severe anemia. and other diseases. “to combat HIV/AIDS. which led to a decrease in hookworm.Hotez: Hookworm and Poverty 41 provinces of China. factors such as sewerage. 15). the lowest-income countries are unlikely to benefit from these economic gains. China.4 which also fuel poverty.2 1. did not affect hookworm intensity. reduces future wage earning capacity by 43%. namely. rural shacks were demolished and the population of the rural American South began moving into small and large southern cities. Sichuan. hookworm anemia results in low birth weight and increased perinatal morbidity and mortality. These factors also account for the many disability-adjusted life years lost because of hookworm.1.40 The possibility that environmental control alone has minimal effect on hookworm transmission urgently .27 These forces. sanitation. hookworm-infected children attend school less often and exhibit diminished school performance. Hookworm is an important component of the sixth Millennium Development Goal.36.32 The economist Hoyt Bleakley estimates that chronic hookworm infection in childhood. Chronic infection with moderate-intensity and heavy-intensity hookworm burdens in childhood produces longstanding blood loss leading to iron deficiency and protein malnutrition.37 Significant comorbidity between hookworm and malaria anemia is also likely. a reduction in poverty together with a shift to a more urbanized economy.4 3. 30).13 There is a common misconception that wearing shoes was responsible for eradicating hookworm in the American South during the early 20th century. especially Brazil. so hookworm reduction will require more specific interventions. Instead. presumably through the mechanisms outlined above. Hookworm is also a major global public health problem in pregnancy.34 including 7. and India. The effect of hookworm anemia on agricultural worker productivity was a topic widely written about during the early 20th century7 and has been reviewed.15 We are still in the early stages of fully assessing the economic and poverty-promoting effect of hookworm infection and other neglected tropical diseases. dramatically reduced the prevalence of hookworm and the other major tropical diseases in the United States. Brazil. Child growth and development. however.31. (2) pregnancy outcome. Without economic development. the elimination was most likely due to the same forces that are at work in China today. For instance. remain highly endemic for hookworm and other soil-transmitted helminth infections. Pregnancy outcome. 2.33 There is also a high degree of coendemicity between hookworm and malaria.” Hookworm Promotes Poverty Hookworm infection. As a result. we can expect significant global reductions in the prevalence of hookworm infection in the next few decades. possible synergistic effects. and other environmental measures often only minimally affect the prevalence and intensity of hookworm infection. from 71% to 68% prevalence.5 million women in sub-Saharan Africa. Worker productivity.39 whereas drainage and sewerage in a poor urban area of Salvador. An estimated 44 million pregnant women are infected with hookworm.27 Over just two decades. malaria.1 Chronic anemia from hookworm causes deficits in physical growth and fitness28 but also produces cognitive deficits and memory loss.38.35 Particularly among multigravidae.29 The older literature even points to reduction in intelligence resulting from heavy infections (reviewed in Ref. However. Humphreys argues that New Deal legislation passed during the 1930s helped to transform the agrarian landscape of the American South to a more modern and urbanized economy.

or twice-yearly or thriceyearly treatments in areas of high intensity infection and transmission. estimated at approximately just $0. New York. et al. P. 8.42 Integrated control of the neglected tropical diseases could reduce the burden of disease caused by malaria and HIV/AIDS.C. relying solely on albendazole or mebendazole may not be adequate for control.5 Integrated control through a package of low-cost drugs is currently the means being widely advocated for controlling the most common neglected tropical diseases in developing countries and as a means for sustainable poverty reduction. New England Journal of Medicine 351: 799–807. that is.4 To coordinate integration.. PLoS Medicine 2: e67. M. J. Treatment. 6. BROOKER. Integrated control of neglected tropical diseases represents one of the most efficient and costeffective means to improve child health and education. because the drugs are either being donated by pharmaceutical companies or they are available as lowcost generics. Macmillan. J. Incorporating a rapid-impact package for neglected tropical diseases with programs for HIV/AIDS. MOLYNEUX. et al. Studies conducted over the last decade have revealed that single-dose mebendazole often achieves a lower than expected cure rate for hookworm or results in rapid posttreatment reinfection... P. particularly to deworm school children. 2006. 2002. A. HOTEZ. albendazole (or mebendazole.2. Through the Human Hookworm Vaccine Initiative. P. memory. BROOKER. A. Its Distribution.. Acknowledgments Peter Hotez is partially supported by the Bill and Melinda Gates Foundation through the Human Hookworm Vaccine Initiative. and Control. The Human Hookworm Vaccine represents one of several possible antipoverty vaccines. 4. depending on availability) is also being packaged with other drugs. CLEMENTS. school performance. 7. D. trichuriasis. J. 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FENWICK. pregnancy outcome. a product development partnership based at the Sabin Vaccine Institute and funded by the Bill and Melinda Gates Foundation. NDINAROMTAN. BEASLEY. MOLYNEUX. including ivermectin.41 To enhance the poverty-reducing effect of deworming. 1929. that could be developed in the coming decade. the major partnerships dedicated to neglected tropical disease control have joined in an alliance known as the Global Network for Neglected Tropical Disease Control. the major and most cost-effective approach to hookworm control worldwide is the regular and periodic use of anthelminthic drugs (typically albendazole or mebendazole). S.

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