Address for correspondence: Peter Hotez, MD, PhD, Ross Hall 736, 2300 I St., NW, Washington DC, 20037. Voice: 202-994-3532; fax: 202-994-2913. firstname.lastname@example.org, email@example.com Scientific Approaches to Understanding and Reducing Poverty Annals of the New York Academy of Sciences
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.
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 sub-Saharan 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
Table 1. Hookworm prevalence by region (adapted from Ref. 3)
No. of estimated hookworm cases (millions)
East Asia Pacific
India and South Asia
Latin America and Caribbean
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 are typically laden with hundreds of thousands of eggs. Under the right conditions, the eggs hatch and give rise to larvae that feed on organic debris and bacteria in the soil. Over several days, these larvae molt twice to the infective larval stages. Hookworm infective larvae are slightly longer than 0.5 mm, and to the naked eye they appear as small white dust specs.
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. In his classic monograph, Hookworm Disease, 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.7 Recently, through satellite mapping and remote sensing, Brooker and his colleagues have determined that the environmental stages of hookworm have higher thermal limits than those of other soil-transmitted helminths, such as Ascaris lumbricoides and Trichuris trichiura. This finding accounts for their observation that hookworm is endemic throughout most of Mali and southern Chad, in contrast to ascariasis and trichuriasis.6,8 On the other hand, hookworms exhibit a lower tolerance for cold temperatures than do either Ascaris or Trichuris, which explains why hookworms are seldom found at high altitudes.6 In Africa, 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. Thus, there is a high degree of geographic overlap and coendemicity between hookworm and malaria in sub-Saharan Africa.9
Soil conditions are equally important for ensuring hookworm larval transmission. Infective larvae directly penetrate human skin, 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. For infection to occur, the infective larvae must be able to reach the soil surface. However, the larvae are extremely vulnerable to desiccation and direct sunlight. During dry conditions, the larvae retreat deeper into the soil. Therefore, sufficient rainfall is necessary to support the hookworm life cycle. Soil type is also important. Sandy soils allow greater hookworm mobility than clay soils. Because coastal areas in the developing world have sandy soil, and they are at low altitudes (and therefore high temperatures), these regions can exhibit particularly high hookworm endemicity.10,11
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.6 For instance, a Chinese national parasite survey conducted between the late 1980s and early 1990s, in which fecal exams were conducted on 1,477,742 individuals in every province, found the highest hookworm prevalence among vegetable growers and farmers,12,13 whereas on the Indian subcontinent, high rates of infection are found in association with working in the tea gardens.14 Historically, hookworm has been a major occupational hazard for agricultural laborers throughout the developing world (reviewed in Ref. 15). In China and Southeast Asia, the relationship between hookworm and agriculture has been partly linked to the handling of human feces as nightsoil fertilizer12,13,16; however, usually the daily exposure of soil contaminated with hookworm infective larvae mostly accounts for the rural component of hookworm transmission.
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, at the turn of the 20th century, the coastal regions of East Texas, Louisiana, Mississippi, Florida, Georgia, and the Carolinas exhibited high prevalence rates of hookworm and other tropical diseases including malaria and typhoid fever, as well as epidemics of yellow fever. Today, 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. Figure 1 shows the relationship between human development index, a measure of poverty, and hookworm infection, as well as showing the tight link between hookworm and poverty.17 Indeed, several studies have confirmed a significant negative association between socioeconomic status and hookworm infection prevalence or intensity (number of hookworms per individual). For example, in rural Cote d'Ivoire, poor schoolchildren showed a significantly higher infection prevalence of hookworm than that of children of families of better means,18 whereas in Panama poorer children exhibited higher hookworm intensities.19
To understand the concept of hookworm intensity, understanding the rest of the parasite life cycle is important. After skin penetration, 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. From there, the larvae migrate up the respiratory tree and are coughed up and swallowed. In the gut, the larvae develop into sexually mature adult hookworms. The adult female hookworm produces thousands of larvae daily, and the eggs exit the body in the feces. Each adult hookworm causes blood loss ranging from 0.03 to 0.20 mL/day. Higher-intensity infections mean that there are more hookworms causing blood loss, eventually causing enough blood loss to produce hookworm disease, which is characterized by iron deficiency anemia and protein malnutrition.1 Typically, one assesses hookworm intensity by measuring the number of hookworm eggs in the feces, because higher hookworm burdens lead to higher fecal egg counts. In this way, intensity is better reflective of hookworm disease burden than is prevalence. In many hookworm-endemic communities, the intensity of hookworm increases with age.20 The relationship between poverty and parasite prevalence and intensity is true not only for hookworm but also for other soil-transmitted helminth infections in developing countries, especially ascariasis.19,21–23
The exact mechanisms by which poverty leads to higher hookworm prevalence and intensities are still not well established. To date, research has identified at least three major factors:
1Inadequate sanitation. Because the propagation of the hookworm life cycle depends on inadequate sanitation and the deposition of human feces on soil, hookworm is associated with the absence of a latrine.24,25 Therefore, people living in poverty who presumably do not have regular access to a latrine would be at higher risk of exposure to hookworm, as well as to other soil-transmitted helminths and schistosomes.
2Poor housing construction. Cement floors and slabs in homes are a protective factor for transmission.18 Because cement houses indicate wealth in developing countries,18 poverty probably operates as a risk factor for hookworm infection partly through the poor housing construction. Poor housing construction with dirt floors, thatch roofs, and walls with cracks and crevices is also responsible for the transmission of Chagas' disease in impoverished regions of Central and South America.
3Access to essential medicines. 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.18
One of the factors not listed is wearing shoes or other footwear. Shoes are not significantly protective20 because N. americanus penetrates all aspects of the skin surface, including the hands, although A. duodenale is also orally infective.1
Poverty Reduction and Urbanization
Rural environmental factors and poverty are the two most potent forces in promoting hookworm transmission in developing countries. Conversely, poverty reduction and urbanization are the most important elements for reducing hookworm transmission. Today, the effect of poverty reduction and urbanization is being played out throughout Eastern China where, because of intense economic growth, the prevalence and intensity of hookworm infection have reduced dramatically compared with 20 years earlier.13,26 In contrast, the poor and largely rural southern and southwest provinces of China, such as Hainan, Sichuan, Yunnan, and Guangxi, remain highly endemic for hookworm and other soil-transmitted helminth infections.13
There is a common misconception that wearing shoes was responsible for eradicating hookworm in the American South during the early 20th century. Instead, however, the elimination was most likely due to the same forces that are at work in China today, namely, a reduction in poverty together with a shift to a more urbanized economy, which led to a decrease in hookworm, as well as malaria and typhoid fever. 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.27 Over just two decades, rural shacks were demolished and the population of the rural American South began moving into small and large southern cities.27 These forces, more than any other, dramatically reduced the prevalence of hookworm and the other major tropical diseases in the United States.
Hookworm Promotes Poverty
Hookworm infection, like other neglected tropical diseases, not only occurs in the setting of poverty but also promotes poverty. Endemic hookworm infection keeps affected populations mired in a cycle of destitution and despair by affecting (1) child growth and development, (2) pregnancy outcome, and (3) worker productivity (reviewed in Ref. 15). These factors also account for the many disability-adjusted life years lost because of hookworm.1,2
1Child growth and development. Chronic infection with moderate-intensity and heavy-intensity hookworm burdens in childhood produces longstanding blood loss leading to iron deficiency and protein malnutrition.1 Chronic anemia from hookworm causes deficits in physical growth and fitness28 but also produces cognitive deficits and memory loss.29 The older literature even points to reduction in intelligence resulting from heavy infections (reviewed in Ref. 30). As a result, hookworm-infected children attend school less often and exhibit diminished school performance.31,32 The economist Hoyt Bleakley estimates that chronic hookworm infection in childhood, presumably through the mechanisms outlined above, reduces future wage earning capacity by 43%.33 There is also a high degree of coendemicity between hookworm and malaria,9 resulting in more severe anemia, and possible synergistic effects, including more clinical episodes of malaria as well as increased severity,4 which also fuel poverty.
2Pregnancy outcome. Hookworm is also a major global public health problem in pregnancy. An estimated 44 million pregnant women are infected with hookworm,34 including 7.5 million women in sub-Saharan Africa.35 Particularly among multigravidae, hookworm anemia results in low birth weight and increased perinatal morbidity and mortality.36,37 Significant comorbidity between hookworm and malaria anemia is also likely.4
3Worker productivity. 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.5 However, 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. Hookworm is an important component of the sixth Millennium Development Goal, “to combat HIV/AIDS, malaria, and other diseases.”
Hookworm Control as a Means to Economic Growth
As urbanization and poverty reduction expand in the largest middle-income countries, especially Brazil, China, and India, we can expect significant global reductions in the prevalence of hookworm infection in the next few decades. However, the lowest-income countries are unlikely to benefit from these economic gains, so hookworm reduction will require more specific interventions. Without economic development, sanitation, and provision of drainage, factors such as sewerage, clean water, and other environmental measures often only minimally affect the prevalence and intensity of hookworm infection. For instance, in Iran, a program of sanitation as a solitary measure reduced the prevalence of hookworm only 4%, from 71% to 68% prevalence,38,39 whereas drainage and sewerage in a poor urban area of Salvador, Brazil, did not affect hookworm intensity.40
The possibility that environmental control alone has minimal effect on hookworm transmission urgently requires additional and larger studies. Currently, the major and most cost-effective approach to hookworm control worldwide is the regular and periodic use of anthelminthic drugs (typically albendazole or mebendazole), particularly to deworm school children. There are multiple benefits to periodic deworming, including catch-up growth, as well as improvements in physical fitness, cognition, memory, school performance, and school attendance.1,29,31,32 These findings provided a basis for World Health Assembly adoption of a resolution in 2001 that advocates for periodic deworming of all school children at risk for soil-transmitted helminths, including hookworm (http://www.who.int/wormcontrol). The World Health Organization currently recommends annual treatments of at-risk children with single-dose mebendazole or albendazole, or twice-yearly or thrice-yearly treatments in areas of high intensity infection and transmission. Widespread implementation of deworming should significantly affect economic development.15,41 To enhance the poverty-reducing effect of deworming, albendazole (or mebendazole, depending on availability) is also being packaged with other drugs, including ivermectin, praziquantel, and azithromycin, to simultaneously target the seven most prevalent neglected tropical diseases—ascariasis, trichuriasis, hookworm, schistosomiasis, lymphatic filariasis, trachoma, and onchocerciasis.4,42 The package is extremely low-cost, estimated at approximately just $0.50 per patient per year, because the drugs are either being donated by pharmaceutical companies or they are available as low-cost generics. Integrated control of neglected tropical diseases represents one of the most efficient and cost-effective means to improve child health and education, pregnancy outcome, and worker productivity, as well as to reduce anemia and prevent blindness and skin disease.4,42 Integrated control of the neglected tropical diseases could reduce the burden of disease caused by malaria and HIV/AIDS.4 To coordinate integration, the major partnerships dedicated to neglected tropical disease control have joined in an alliance known as the Global Network for Neglected Tropical Disease 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.5 However, for regions of high-intensity hookworm, relying solely on albendazole or mebendazole may not be adequate for control. 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. Also, frequent use of anthelminthics reduces efficacy over time and may lead to drug resistance (reviewed in Refs. 5 and 43). Through the Human Hookworm Vaccine Initiative, a product development partnership based at the Sabin Vaccine Institute and funded by the Bill and Melinda Gates Foundation, development and testing of recombinant hookworm vaccines are under way.2,15,43,44 The goal of the Human Hookworm Vaccine Initiative is to create a vaccine to prevent hookworm reinfection and disease. The Human Hookworm Vaccine represents one of several possible antipoverty vaccines, that is, vaccines for poverty-promoting neglected tropical diseases, that could be developed in the coming decade. There is an urgent need for financial innovation to support the development of vaccines intended exclusively for the world's poorest people.
Peter Hotez is partially supported by the Bill and Melinda Gates Foundation through the Human Hookworm Vaccine Initiative.