Infections with helminths, or parasitic worms, affect more than two billion people worldwide. In regions of rural poverty in the tropics, where prevalence is greatest, simultaneous infection with more than one type of helminth is common. The relative incidence of common helminthic infections in humans worldwide is illustrated in Figure 51–1.
Relative incidence of helminth infections worldwide.
Worms pathogenic for humans are Metazoa and can be classified into roundworms (nematodes) and two types of flatworms, flukes (trematodes) and tapeworms (cestodes). These biologically diverse eukaryotes vary with respect to life cycle, bodily structure, development, physiology, localization within the host, and susceptibility to chemotherapy. Immature forms invade humans via the skin or GI tract and evolve into well-differentiated adult worms with characteristic tissue distributions. With few exceptions, such as Strongyloides and Echinococcus, these organisms cannot complete their life cycle and replicate within the human host to produce mature offspring. Therefore, the extent of exposure to these parasites dictates the number of parasites infecting the host, a characteristic recognized as infection intensity, which itself determines the morbidity caused by infection. Secondly, any reduction in the number of adult organisms by chemotherapy is sustained unless reinfection occurs. The burden of parasitic helminths within an infected population is not uniformly distributed, and it typically displays a negative binomial distribution whereby relatively few persons carry the heaviest parasite burden, resulting in increased morbidity in these individuals who also contribute disproportionately to transmission.
Anthelmintics are drugs that act either locally within the gut lumen to cause expulsion of worms from the GI tract, or systemically against helminths residing outside the GI tract. Safe and effective broad-spectrum anthelmintics, initially developed for veterinary use, are currently available for use in humans. However, therapy for many tissue-dwelling helminths, such as filarial parasites, is not fully effective. For many reasons, including their long-lived and relatively complex life cycles, acquired resistance to anthelmintics in humans has yet to become a major clinical problem. However, with the increasing deployment of mass drug therapy, and considering the veterinary experience with resistance, the potential for drug resistance among helminths in humans requires monitoring.
Primarily as a result of stepped-up advocacy by the World Health Organization (WHO), the World Bank, the Global Network for Neglected Tropical Diseases, and smaller nongovernmental organizations such as the London-based Partnership for Child Development (PCD), there is increasing appreciation for the impact of helminth infections on the health and education of school-aged children. These organizations have promoted the periodic and frequent use of anthelmintic drugs in schools as a means to control morbidity caused by soil-transmitted helminths and schistosomes in developing countries. In addition, interest has grown in eliminating arthropod-borne helminth infections by interrupting their transmission through the widespread use of anthelmintics. Today, control programs employing anthelmintics rank among the world's largest health efforts, and hundreds of millions of people receive treatment annually (Hotez et al., 2009).
This chapter is divided into two main parts:
- clinical presentation and recommended chemotherapy for common helminth infections in humans
- pharmacological properties of specific anthelmintics
The major nematode parasites of humans include the soil-transmitted helminths (STHs; sometimes referred to as "geohelminths") and the filarial nematodes.
The major STH infections (ascariasis [roundworm], trichuriasis [whipworm], and hookworm infection) are among the most prevalent infections in developing countries. Because STH worm burdens are higher in school-aged children than in any other single group, the WHO and the PCD advocate school-based administration of broad-spectrum anthelmintics on a periodic and frequent basis. The agents most widely employed for reducing morbidity are the benzimidazole anthelmintics (BZ), either albendazole (ALBENZA and ZENTEL) or mebendazole (vermox, others) (Table 51–1).
Table 51–1 Structure of the Benzimidazoles
Single dose therapy with a BZ reduces worm burden to a varying degree, with greatest efficacy for ascariasis, followed by whipworm and hookworm (Keiser and Utzinger, 2008) and subsequently reduces morbidity attributable to the parasite. Treatment improves host iron stores and hemoglobin levels, physical growth, cognition, educational achievement, and school absenteeism, as well as having a positive influence on the entire community by reducing transmission (Bethony et al., 2006). In 2001, the World Health Assembly adopted a resolution urging that by 2010 member states should regularly administer anthelmintics to at least 75% of all school-age children at risk for morbidity (WHO, 2002). Concerns with this recommendation have included:
- The scope of the undertaking
- The high rate of post-treatment reinfection that occur in areas of high transmission
- Documented drug failures against hookworm with mebendazole
- The possibility that widespread treatment will lead to the emergence of BZ drug resistance
- The possibility that by focusing exclusively on school-aged children, other groups and vulnerable populations, such as preschool children and women of reproductive age, will be omitted
In addition to targeting STH infections among school-aged children, there are ongoing programs to eliminate lymphatic filariasis (LF) and onchocerciasis (river blindness) over the next 10-20 years (Molyneux and Zagaria, 2002; Molyneux et al., 2003). The term elimination, as opposed to eradication, refers to the reduction of disease incidence to zero or close to zero, with a requirement for ongoing control efforts (Hotez et al., 2004). The major goals for the LF elimination program (and to some extent, the onchocerciasis elimination programs) are to interrupt arthropod-borne transmission by administering combination therapy with either diethylcarbamazine (DEC; HETRAZAN; available from CDC in the U.S.) and albendazole...