Forgotten People, Forgotten Diseases. Peter J. Hotez
More than 300 million children in 77 countries received low-cost deworming in 2010.27 While this number is impressive, it is still far short of the almost 900 million children who would need to be treated annually in order to meet the targets specified by World Health Assembly Resolution 54.1927 (Fig. 2.11). Because many school-age children do not attend school in developing countries, as an alternative or complementary approach to school-based interventions, many children are being targeted worldwide through community-based interventions, such as child health days. In such programs, deworming is linked to vitamin A distribution as well as to some immunizations, such as measles vaccinations.24 Child health days and other community-based interventions are particularly suitable in regions of STH infection endemicity where preschool children, i.e., children under the age of five, also suffer from moderate and heavy infections. By some estimates, almost 200 million children have received vitamin A in more than 50 countries,24 so that this mechanism provides an added opportunity to scale up deworming. Also, as pointed out earlier, in some developing countries pregnant women are at high risk for hookworm infection, and the WHO and other international agencies have therefore expanded their recommended targets to include this group in areas of high transmission.
Although for most school-based and community-based interventions a single dose of either mebendazole or albendazole is provided on an annual basis, in areas of intense transmission deworming may need to be conducted more frequently. STH reinfection can occur over a period of just a few months, so that sometimes two or three dewormings must take place in a single year. Currently, the WHO recommends two or three deworming treatments annually in areas of high prevalence (typically greater than 70% prevalence) or high intensity (where more than 10% of the population have moderate or heavy infections).
Figure 2.11 Proportion of children (1 to 14 years of age) by country requiring preventive chemotherapy for soil-transmitted helminthiases, worldwide, 2010. (See http://gamapserver.who.int/mapLibrary/Files/Maps/Global_STH_2010.PNG [© 2011 WHO].)
When frequent and periodic dewormings are required in order to control STH infections for large populations, there are concerns that STH parasites, like any other infectious agent, could over time become resistant to either mebendazole or albendazole. Indeed, BZA resistance is now widespread among intestinal helminth parasites of sheep and cattle in Australia, New Zealand, South America, South Africa, and elsewhere in the Southern Hemisphere.28 The mechanisms by which BZA resistance occurs will be discussed later (in chapter 11). To date, there is no convincing evidence of the emergence of drug resistance to the BZAs used for human STH infections. However, a systematic review conducted by Jennifer Keiser and Juerg Utzinger from the Swiss Tropical and Public Health Institute revealed that single-dose mebendazole currently exhibits a cure rate for human hookworm infection of only 15%, with egg count reductions for N. americanus hookworm infections ranging from 0 to 68%.28 Thus, while albendazole is still generally effective for N. americanus hookworm infection, single-dose mebendazole can no longer be considered a standard treatment for hookworm infection. Today, the high rate of drug failures for single-dose mebendazole and high rates of STH infection in areas of high transmission, coupled with emerging evidence of BZA resistance in animal nematodes, have led to international calls for increased monitoring of the effectiveness of the BZAs and for the development of new-generation STH drugs.
Given the enormous health and educational benefits of deworming, I believe that we should try to do everything possible to scale up the use of BZAs in developing countries. We now have in hand some very promising geostatistical tools for increasing the efficiencies of deworming in resource-poor settings.29 At the same time, however, we must try to develop backup control tools. Unfortunately, the absence of a commercial market for such drugs has hampered a substantive research and development effort on this front. As an alternative or complementary approach to STH control, there has been a concerted effort to develop a recombinant anthelmintic vaccine, which would prevent reinfection following deworming.30 In chapter 11, I will discuss the efforts of our nonprofit product development partnership, known as the Human Hookworm Vaccine Initiative, to develop a new hookworm vaccine as an important antipoverty measure.
Summary Points: “The Unholy Trinity”
STH infections are caused by intestinal worms, with Ascaris roundworms, Trichuris whipworms, and hookworms being the most common.
Ascariasis, hookworm infection, and trichuriasis are the world’s most common NTDs.
STH infections are highly prevalent in sub-Saharan Africa, Asia, and the Americas, especially in areas where rural poverty overlaps with tropical environments and adequate rainfall.
Children typically exhibit heavier STH infections with higher worm burdens than do adults.
The STHs live for years in the gastrointestinal tract.
In children, chronic STH infections impair physical growth and development as well as cognition, memory, and school performance. Therefore, STHs produce educational deficits as well as ill health. These poverty-promoting features probably result from parasite-induced malnutrition.
Hookworms cause malnutrition by producing intestinal blood loss, which leads to iron deficiency anemia, especially in children and pregnant women with low underlying iron reserves. The DALYs lost to hookworm infection rank the highest for any worm infection.
Global control of STH infections currently focuses on morbidity reductions through frequent and periodic deworming with BZAs. School-based deworming is being frequently emphasized in order to target at-risk children.
There are both theoretical and actual concerns about BZA drug resistance; a human hookworm vaccine is under development.
Notes
1. The Greek derivation of “helminth” is from Faust et al., 1970, p. 251. References to the historical documentation of human ascariasis and hookworm infection are found in Cox, 2002; Grove, 1990; and Sherman, 2006, p. 349–352.
2. Prevalence numbers are modified from Bethony et al., 2006.
3. The impact of STHs on child growth and development and cognition is summarized (with references) in Bethony et al., 2006; and Crompton and Nesheim, 2002. The Crompton and Nesheim reference also describes the nutritional basis of these deficits.
4. The results of the nationwide parasite survey are summarized in Hotez et al., 1997. The survey was later repeated (but on a smaller scale) between 2002 and 2004 and demonstrated that the incidence had since decreased dramatically in areas of economic development.