World Health Organization. 2010. Working to Overcome the Global Impact of Neglected Tropical Disease: First WHO Report on Neglected Tropical Diseases. World Health Organization, Geneva, Switzerland. http://whqlibdoc.who.int/publications/2010/9789241564090_eng.pdf.
chapter 2
“The Unholy Trinity”: the Soil-Transmitted
Helminth Infections Ascariasis,
Trichuriasis, and Hookworm Infection
As it was when I first saw it, so it is now, one of the most evil of infections. Not with dramatic pathology as are filariasis, or schistosomiasis, but with damage silent and insidious. Now that malaria is being pushed back, hookworm remains the great infection of mankind. In my view it outranks all other worm infections of man combined . . . in its production, frequently unrealized, of human misery, debility, and inefficiency in the tropics.
The neglected tropical diseases (NTDs) are the most common infections of the world’s poorest people, and the soil-transmitted helminth (STH) infections are the most common NTDs. The word helminth comes from the Greek έλμίνς, meaning “worm,”1 and the phrase soil-transmitted refers to the human acquisition of these worms through contact with soil contaminated with either parasite eggs or immature larval stages. STHs are also sometimes called intestinal helminths or intestinal worms because the adult stages of the parasite live in the human gastrointestinal tract. The STHs are also nematodes, a type of parasitic worm distinguished by their elongate and cylindroidal shape.
The three most important STH infections of humans, based on their prevalence and global disease burden, are:
Ascaris infection (also known as roundworm infection or ascariasis)
Hookworm infection (hookworm)
Trichuris infection (whipworm infection or trichuriasis)
Together, these helminth infections afflict more than 1 billion people in developing countries.
Humans have been infected with STHs since ancient times. We know this from accurate descriptions found in Egyptian medical papyri and the writings of Hippocrates in the 5th century BCE, including reports of large Ascaris roundworms being expelled from infected people and of the characteristic pallor and sallow complexion of people with hookworm.1 In addition, STH eggs have been recovered from coprolites, mummified feces thousands of years old, found in both the Old World and New World.1 Today, an estimated 800 to 900 million, 600 to 700 million, and 500 to 600 million people are infected with ascariasis, hookworm, and trichuriasis, respectively (Table 2.1).2 More often than not, a single individual living in a developing country, especially a school-age child, is infected with two and sometimes all three types of STH parasites simultaneously. Practically speaking, this observation means that the intestines of hundreds of millions of children living in Africa, Asia, and the Americas harbor a menagerie of worms. Harold Brown, the late former parasitology professor at Columbia University College of Physicians and Surgeons, frequently referred to Ascaris, Trichuris, and hookworms as “the unholy trinity” to indicate that it was extremely common for a child to be infected with all three parasites simultaneously. Typically, Ascaris roundworms and hookworms inhabit the small intestine, while Trichuris whipworms inhabit the large intestine.
How can we fathom the notion of approximately 1 billion people infected with STHs? To understand this concept better, we need to travel to a developing country where STH infections are endemic, meaning that the infections are constantly present in a particular region. Figure 2.1 shows children living in a rural village in Minas Gerais State, Brazil. The families of these children are mostly subsistence farmers involved with cultivation of manioc and beans. Looking at these children, one might not think that they appear terribly ill, unless one examines them more closely. The STH-infected children living in this Brazilian village are stunted in both weight and height because they are not growing normally. Moreover, they also do poorly on tests of cognition, memory, and intelligence. There is now strong evidence that such physical and mental disabilities result from the presence of intestinal worms.3
Table 2.1 The “unholy trinity”
Figure 2.1 Children (left) living outside the Brazilian village of Americaninhas, Minas Gerais State (right). About 75% of people living in the area are infected with hookworm. The effects of the disease—malnutrition and anemia—are worse in children. (Photos of the children courtesy of Brigid McCarthy of National Public Radio [© 2005 NPR].)
The reason we know that most of the children of Americaninhas, Minas Gerais State, Brazil, harbor intestinal worms is that we can diagnose their STH infections by examining their feces under a microscope. The adult male and female roundworms, whipworms, and hookworms mate in the intestines and produce eggs that exit the body in feces. Each type of STH produces characteristically shaped eggs that are easy to identify through microscopy. If we now do this test for all children in this particular rural Brazilian village, we get a result that is shown in Fig. 2.2, in which more than 70% of the children between the ages of 5 and 11 are infected with Ascaris worms and hookworms. It turns out that we can repeat this study in almost any rural Brazilian village or indeed almost any rural village in the tropical regions of the Americas, including Central America, and probably obtain a similar result or find that just as many children are also infected with Trichuris whipworms. Indeed, if we were to conduct fecal examinations on most of the rural villages in sub-Saharan Africa, on the Indian subcontinent, or in Southeast Asia, really wherever people live in poverty and depend on subsistence agriculture and where the soil and climate are suitable for survival of the parasite eggs and immature larval stages (typically the warm and moist soil of the tropics), we would find a similar paradigm of extraordinarily high rates of STH infections. Such observations suggest how it can be that hundreds of millions of people harbor the unholy trinity in their bellies.
Figure 2.2 Prevalence of STH infections among school-age children in Americaninhas, Brazil. (Data courtesy of Jeff Bethony and David Diemert, Human Hookworm Vaccine Initiative; modified from graph prepared by Sophia Raff.)
Beginning in the late 1980s, parasitologists of the Chinese Academy of Preventive Medicine, now known as the Chinese Center for Disease Control and Prevention, conducted a 4-year study of intestinal parasites on an almost unimaginable scale by performing fecal examinations on 1,477,742 individuals in every province of China. The results were impressive and demonstrated that approximately 531 million cases of ascariasis, 212 million cases of trichuriasis, and 194 million cases of hookworm infection had occurred in that country.4 In collaboration with the Institute of Parasitic Diseases in Shanghai, I began working in China shortly after the completion of this nationwide survey of parasites. What particularly impressed me was the very tight link between high endemicity of STH infections in rural China and the level of economic underdevelopment.5 Wherever rural poverty was extreme and the villagers were engaged in subsistence agriculture, and provided there were suitable moisture and warmth, it was almost guaranteed that high levels of hookworm and other STH infections were present. Conversely, in areas of