These larvae migrate through the host body such that from 24 hours post infection (p.i.) they are found in the naso-frontal region of the host from where they are, presumably, swallowed to reach the small intestine (Tindall and Wilson, 1988).https://www.ncbi.nlm.nih.gov/books/NBK19795/
A prominent and intriguing subgroup of disseminated strongyloidiasis cases are of former far-east prisoners of war (World War II) who now reside in Europe, Australasia, or North America and present with the disease as much as 50 years after leaving the endemic area. Corticosteroid therapy and/or concurrent cancer treatment are common features of these cases (Gill and Bell, 1979; Gill et al., 2004).
The life-cycle of Strongyloides is both complicated and somewhat tricky to understand, but also one part of the fascination of the genus. This description is primarily based on the life-cycle of S. ratti (a parasite of the rat), which has been extensively studied; some of these details are likely to vary in other species.
Hosts become infected when free-living infective L3s penetrate the skin. Naturally this occurs by the chance coming together of host skin and larvae, though this is facilitated by dispersal and nictation behaviours of the larvae. In the laboratory this comes about by the deliberate application of infective L3s to host skin or by subcutaneous injection (Tindall and Wilson, 1988). These larvae migrate through the host body such that from 24 hours post infection (p.i.) they are found in the naso-frontal region of the host from where they are, presumably, swallowed to reach the small intestine (Tindall and Wilson, 1988). This naso-frontal route of migration has been most thoroughly determined in S. ratti; in other species of Strongyloides (and other genera of skin-penetrating nematodes) migration through the lungs is also thought to be important. During this migration they moult via an L4 stage so that there are adult parasitic female worms present in the gut from approximately 4 days p.i., with reproduction commencing shortly thereafter, detected by the presence of eggs and/or larvae in the faeces (Kimura et al., 1999).
In the host faeces the eggs hatch to release first-stage larvae (L1) (Figure 6). Larvae are either male or female. Male larvae develop via L2-L4 stages into rhabditiform males. Analogously, female larvae can develop into rhabditiform females. Together, this type of development is known as indirect, sexual, or heterogonic development. The free-living adults mate and the female lays eggs that hatch to release L1s that moult via an L2 into infective filariform L3 stages. All the progeny of the free-living adult generation are female. These infective L3 stages are long lived and can persist in the environment until they encounter a suitable host. Their behaviour is to move away from the host faeces in which they have developed, a behaviour likely to enhance their probability of finding a host. In addition, female L1s that hatch from eggs passed in faeces have an alternative fate, to moult via an L2 into infective L3s. This type of development is known as direct, asexual, or homogonic development. Infective L3s that have developed via the direct or indirect route are, apparently, the same.
For most Strongyloides species only one free-living adult generation occurs. However, up to nine (decreasingly fecund) free-living generations have been observed for S. planiceps, though in the same study S. stercoralis had only one free-living adult generation (Yamada et al., 1991). Strongyloides therefore differs from its relative Parastrongyloides which has apparently unlimited successive free-living generations (Grant et al., 2006a).
The free-living adult generation of Strongyloides (and Parastrongyloides) is therefore rather similar to the life-cycle of C. elegans, that is, L1-L4 stages that develop into free-living adults that mate to produce eggs and L1 progeny. However, the major difference is that the progeny of Strongyloides spp. free-living adults develop into infective L3s, the hypothesised analogue of dauer larvae (Hotez et al., 1993).
S. stercoralis can undergo autoinfection, that is, repeated generations of development in the same host individual. Autoinfection appears to be unique to S. stercoralis within the genus (and also essentially unique among other genera of gastrointestinal parasites of vertebrates; only Enterobius spp. and Capillaria spp. also have this phenomenon) and largely accounts for it being a serious pathogen of humans. Autoinfection involves accelerated development by larval progeny of parasitic females such that they develop into infective L3s within the gut, which then penetrate directly into the tissues of the primary host. Thus here, the entire life cycle is completed within a host and there are no stages external to the host. Autoinfection may result in dissemination of L3 through many organs and tissues of the host, as well as the establishment of new parasitic females in the gut. In the absence of treatment, subsequent rounds of autoinfection are possible, resulting in fulminant expansion of parasite populations and multi-organ involvement with potentially fatal consequences for the host (Igra-Siegman et al., 1981). Groups at risk of such so-called disseminated S. stercoralis infections include patients who are immunocompromised as a result of corticosteroid therapy, various neoplasms, or infection with the human T lymphotropic virus-1 (Carvalho and Da Fonseca Porta, 2004; Lim et al., 2004; Buofrate et al., 2013).
A prominent and intriguing subgroup of disseminated strongyloidiasis cases are of former far-east prisoners of war (World War II) who now reside in Europe, Australasia, or North America and present with the disease as much as 50 years after leaving the endemic area. Corticosteroid therapy and/or concurrent cancer treatment are common features of these cases (Gill and Bell, 1979; Gill et al., 2004). The onset of disseminated strongyloidiasis decades after the last possible exposure to the parasite is extremely serious for elderly patients. But, this also makes clear a salient feature of the infection biology of S. stercoralis, namely the capacity to maintain exceedingly chronic infections in hosts. Such hyperchronic infections usually go undiagnosed due to the paucity or absence of larvae in the faeces. Alternative hypotheses for the chronicity of these infections are that either there are dormant larvae in the tissues or senescent non-reproductive female worms in the intestine, with immunosuppression triggering either reactivation of dormant larvae or resumption of egg laying by barren parasitic females. Data from studies conducted over a relatively short time frame (77 days) in experimentally infected dogs favour the latter mechanism involving resumed oviposition by barren female worms (Mansfield et al., 1996). The importance of people with chronic asymptomatic strongyloidiasis as a group at risk of disseminated hyperinfection has recently been emphasised (Caumes and Keystone, 2011).
Hypobiosis or dormancy of Strongyloides L3s may or may not be central to the maintenance of chronic infections, but it is key to another mode of transmission: transmammary transmission. There is evidence of transmammary transmission in S. ratti and S. venezuelensis in rats (Nolan and Katz, 1981; Kawanabe et al., 1988), S. stercoralis in dogs (Shoop et al., 2002), S. fuelleborni kellyi in humans (Ashford et al., 1992), and several species affecting livestock including S. ransomi in swine (Stewart et al., 1976), S. westeri in horses (Lyons, 1994), and S. papillosus in ruminants (Moncol and Grice, 1974). Infective L3s transmitted by the transmammary route presumably arrest their development and migration in the mammary glands, and then re-activate at lactation. Transmammary transmission also occurs in other parasitic nematodes that have a phase of within-host tissue migration during their life cycles, including ascarid roundworms and hookworms (Stone and Smith, 1973; Shoop and Corkum, 1987).