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Diseases caused by protozoans and helminthes are some of the most common afflicting humans around the world, and yet they are some of the most scientifically neglected regarding their pathogenesis, diagnosis, and treatment. In this chapter, principles of molecular pathogenesis of the most common protozoan and helminth infections are discussed. Emphasis is placed on immunopathology (innate and adaptive immune responses), parasitic proteases, and immunomodulation by parasites. Selected protozoan and helminth infections are discussed in detail.

Microsporidia are a group of unusual intracellular parasites that infect a wide range of animal cells. They are important pathogens of humans, very commonly causing eye and intestinal infections in people in the late stages of AIDS. Microsporidia use a distinctive infection strategy, which involves the rapid expulsion of a polar tube from a spore to pierce a host cell, allowing the direct transfer of the spore contents into the host cell cytoplasm. Their extreme adaptation to the exploitative parasitic lifestyle has allowed their metabolism and molecular biology to become highly streamlined. They commonly have very small genomes encoding few proteins, with numerous typical eukaryotic processes in the cell being whittled down to what may be minimal functional pathways, making them a fascinating model system for understanding reductive evolution of eukaryotic cellular functions. Despite their unusual cellular features, it is now widely accepted that microsporidia are fungi or a closely related sister lineage to the fungi. Here we discuss the lines of evidence that link microsporidia to fungi, and the evolutionary processes which have driven the transformation of these highly specialized cells from a free-living eukaryotic lineage.

Microsporidia are a group of tiny obligate intracellular parasites with a unique mode of infecting cells via an eversible polar tube within a highly resistant spore. Infection within the animal kingdom is common, but pre-1985 human infection by microsporidia was considered to be rare, as only a handful of cases had been published in the scientific literature. In 1985 a new species of microsporidian, Enterocytozoon bieneusi, was described from a French AIDS patient with symptoms of chronic diarrhoea [1]. Following this publication, more microsporidial infections have been recognised in humans and electron microscopy of biopsy samples has proven to be an important diagnostic method in such investigations [2]. Microsporidia are emerging pathogens and at least sixteen species are now recognised from humans.

The idea that Fungi form a kingdom distinct from 5 plants and animals (Necker 1783) became widely accepted only recently (Whittaker 1969). Progress in defining a monophyletic kingdom Fungi has been even slower, because the two most obvious features of typical fungi, a trophic state consisting of walled hyphae and dispersion by aerial spores, have arisen polyphyletically and been lost or modified several times. Thus, the organisms traditionally studied by mycologists, and grouped in Whittaker’s kingdom, are polyphyletic. Some, notably Mycetozoa and Plasmodiophorida, are related to certain Protozoa more closely than to true fungi; others are evolutionarily closer to certain algae. Conversely, organisms often thought to be very distinct from fungi (notably lichens) or previously outside the domain of mycology and botany (namely Microsporidia, formerly regarded as Protozoa) turn out to be true fungi, whereas oomycete moulds and “white rusts” are not!