Strongyloides

The Strongyloides genus of nematodes are common parasites of terrestrial vertebrates, and ones that have a fascinating biology. In humans, they are one of the soil-transmitted helminthiases (STH) a WHO-recognized neglected tropical disease (NTD). But, compared with the other STH parasites – Ascaris, hookworms and Trichuris – Strongyloides is the poor relative, arguably itself rather neglected. Strongyloides was discovered 140 years ago in French troops returning from modern-day Vietnam. After its discovery, and following some great taxonomic complexity, its name was settled, coming from the Greek words ‘strongylos’ meaning ‘round’, and ‘eidos’ meaning ‘similar’, together intending to show that Strongyloides was close to the genus Strongylus (Grove, 1989). With today’s perspective this is a sadly unimaginative name, but perhaps slightly better than Strongylus itself. Notwithstanding, the intervening century and a half has now given us an unprecedented understanding of Strongyloides biology, which is brought together in this volume. Parasitologists of all flavours are (rightly) fascinated with life cycles, but this is perhaps particularly appropriate with Strongyloides. Here this life cycle is described, to save it being repeated in everypaper contributing to this volume. The following description is largely based on the life cycle of Strongyloides ratti in rats, simply because this species has been most thoroughly studied, and because its life cycle is generally representative of different Strongyloides species. Compared with most other parasitic nematodes, the Strongyloides life cycle is unusual because it has two adult generations – one in the host and one outside (Fig. 1). The parasitic adult generation is female-only and these reproduce by parthenogenesis, which is genetically mitotic (Fig. 2). The parasitic females produce eggs that are, genetically, male and female. These eggs, or the L1s that hatch from the eggs, pass out of the host in its feces (which stage is passed being a species-specific character), where the larvae then grow, develop and moult. Males and females have different developmental fates. Male eggs (or larvae) moult through four larval stages (L1–L4) and then into free-living adult male worms (Fig. 3). The female eggs (or larvae) have a developmental choice. In one option, they can develop analogously to males (moulting through four larval stages) finally moulting into free-living adult female worms (Fig. 3). Alternatively the female larvae can moult through three larval stages into third-stage larvae (L3s), which are infectious to a new host. The free-living males and females sexually reproduce, and the female then lays eggs. These hatch and the resulting larvae moult via an L2 stage into thirdstage larvae (as above). Crucially, there is only a single free-living adult generation and all the freeliving females’ progeny develop into host infective L3s. [This contrasts with the close relative, Parastrongyloides, where there can be multiple free-living adult generations (Grant et al. 2006)]. Because the aim of this free-living life cycle is to produce infective third-stage larvae, the two developmental routes to producing these are known as direct (or homogonic) and indirect (or heterogonic) (Fig. 1). Infective larvae are developmentally arrested, and only reinitiate development when they successfully penetrate the skin of a suitable host. These larvae migrate through the host, moulting via an L4 stage before settling in the host gut where they moult into parasitic females, and the cycle is then complete. One notable species-specific difference in this life cycle is for the parasite of humans, Strongyloides stercoralis, where infective L3s can precociously develop within the host causing internal auto-infection, which makes human infections chronic. The two adult generations are quite distinct. Apart from one being parasitic and parthenogenetic and the other being free-living and sexual, they differ morphologically. This is most easily seen with the oesophageal morphology, where the parasitic females have a filariform-style oesophagus that occupies about a third of their body length, whereas the free-living adults’ is rhabditiform and about 10% of their body length. All of the freeliving larval stages also have a rhabditiform-style oesophagus, except for the infective L3s, which is filariform, as is the parasitic females’ into which * Corresponding author: School of Biological Sciences, University of Bristol, Bristol BS8 1TQ, UK. E-mail: [email protected] 259