Strongyloides biology
Strongyloides spp. are a genus of parasitic nematode. It has been estimated that over 50 million people are infected with S. stercoralis (one of the two species of Strongyloides able to infect humans) although this is probably an underestimate.
Strongyloides infections of humans can be fatal in two situations. Firstly, individuals who are immunosuppressed (artificially or by other disease) are susceptible to a disseminated, and usually fatal, Strongyloides infection. In addition in areas of New Guinea Strongyloides is the causative agent of 'Swollen Baby (or Belly) Syndrome' in which young infants develop massive Strongyloides infections which are fatal unless rapid treatment is given. S. ratti is an endemic parasite of rats, which is amenable to laboratory study and manipulation.
The life-cycle of Strongyloides ratti
The life-cycle of S. ratti has both parasitic and free-living generations (Figure).
A parasitic female in rat gut
Infective L3s
A free-living female
A free-living male
Life-cycle of S. ratti with two discrete developmental switches: 1. a sex determination event; 2. a female-only developmental switch. Click on the names of the stages to see an image.
The parasitic generation consists solely of adult parasitic females which lie embedded in the mucosa of the small intestine of rats. The parasitic females reproduce by mitotic parthenogenesis. Male and female eggs produced by these females are passed with the faeces into the external environment.
In the environment male eggs hatch and larvae moult through four larval stages (not shown above) to finally develop into free-living adult males.
Female eggs similarly hatch in the environment, however, these larvae have a developmental choice. In female indirect (heterogonic) development, female larvae develop into free-living adult females. Free-living adult male and females mate and reproduce sexually and the female lays eggs. These eggs hatch, and larvae moult through larval stages (not shown above) into infective third stage larvae (iL3s), which infect new hosts by skin penetration. The iL3 stage is developmentally arrested and will not develop further until it encounters a host. In female direct (homogonic) development female develop via two larval stages into iL3s, which can similarly infect hosts.
Despite being an obligate parasite a significant part of the Strongyloides life-cycle occurs outside of the host. This has the practical advantage that the free-living stages can be readily grown and manipulated in faeces from infected animals.
The control of the developmental choice
The developmental choice in the life-cycle is affected by a number of factors. Different isofemale lines vary in the proportion of larvae which develop by each route. Isofemale lines can also be artificially selected for different developmental routes.
Analysis of the effect of environmental conditions on the development of the life-cycle of S. ratti has shown that the host immune response affects both the sex ratio of the eggs passed by an infected host (Box 1, above) and the female only developmental choice (Box 2, above), with a more male biased sex ratio and development of free-living adult females favoured by larvae passed from an immune host. The environmental temperature affects the female only developmental choice (Box 2, above) with development into free-living adult females favoured at higher environmental temperatures.
Together, these observations show that S. ratti integrates a number of different factors when making a developmental decision. This is presumably an indication of the importance of reaching the right developmental decision for the prevailing environmental conditions. It also means that the developmental route of young larvae can be readily manipulated in the laboratory.
