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INTRODUCTION

Helminths are invertebrates featuring elongated, flat or round bodies. According to their morphology and the host organ they inhabit, they are classified as flatworms or platyhelminths, which include flukes (lung flukes [Paragonimus spp.], liver flukes [Fasciola spp., Clonorchis sinensis, Opisthorchis spp.], intestinal flukes, or blood flukes [Schistosoma spp.]), tapeworms (cestodes [including Taenia solium, T. saginata], Diphyllobothrium latum, Hymenolepis nana, and Echinococcus spp.), and roundworms (nematodes). The nematodes of major medical importance include the soil-transmitted helminths (STHs) (Ascaris lumbricoides, Trichuris trichiura, Necator americanus, Ancylostoma duodenale, Strongyloides stercoralis) and the filarial worms. Lymphatic filariasis is caused by Wuchereria bancrofti, Brugia malayi, and Brugia timori. Subcutaneous filariasis is caused by Loa loa, Mansonella streptocerca, and Onchocerca volvulus. Mansonella perstans and Mansonella ozzardi are the causative helminths for serous cavity filariasis.

The blood flukes and nematodes are bisexual, while all other flukes and tapeworm species infecting humans are hermaphroditic. The development of all helminths includes egg, larval (juvenile), and adult stages, but the life cycles greatly differ. The prevalence of helminth infection worldwide is quite extensive (Figure 68–1).

Figure 68–1

Relative incidence of helminth infections worldwide.

ABBREVIATIONS

Abbreviations

AUC: area under the curve

BZ: benzimidazole

CDC: U.S. Centers for Disease Control and Prevention

CYP: cytochrome P450

dADT: p-(1-dimethylamino ethylimino) aniline

DEC: diethylcarbamazine

GABA: γ-aminobutyric acid

GI: gastrointestinal

MDA: mass drug administration

STH: soil-transmitted helminth

TPAC: terephalic acid

TPAL: terephthalaldehyde

WHO: World Health Organization

ANTHELMINTIC DRUGS

Although a large number of anthelmintic drugs have been approved for human use, only a small number are widely used. These include two drugs in the benzimidazole (BZ) class, albendazole and mebendazole, which are widely used in intestinal nematode and cestode infections; the macrocyclic lactone ivermectin, used to treat a variety of nematode and ectoparasite infections; and praziquantel, which is used to treat trematode and some cestode parasites. Because of their role in programs of mass drug administration (MDA), these drugs are among the most commonly used agents worldwide. The World Health Organization (WHO) estimated that through MDA approximately 1.24 billion people received one or more anthelmintic drugs in 2019 (WHO, 2020). In many resource-poor developing countries, several different anthelmintic drugs can be provided together through integrated programs of MDA in order to simultaneously target intestinal and filarial nematodes and trematodes (Webster et al., 2014). A number of clinical trials have been undertaken to ensure that there are not unknown pharmacokinetic interactions or toxicologic consequences of coadministration of these drugs. This is especially the case for ivermectin, diethylcarbamazine, and albendazole, which have been shown to have synergistic activity as treatment for lymphatic filariasis (King et al., 2018...

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