Trickle or clumped infection process? An analysis of aggregation in the weights of the parasitic roundworm of humans, Ascaris lumbricoides
Graphical abstract
Introduction
The distribution of parasitic helminth body size within a population of definitive hosts offers a number of potential insights into the population biology of worms. Body size is almost universally related to egg production (fecundity) (Poulin, 1998), and size inequalities have been used frequently to approximate variability in reproduction success (VRS). VRS has important implications for the population genetics of the parasite as high levels can purge genetic diversity (Criscione and Blouin, 2005, Dobson, 1986). High VRS has been detected in a number of parasitic helminths such as species of pseudophyllidean, tetraphyllidean and cyclophyllid (Hymenolepis) cestodes (Dobson, 1986, Shostak and Dick, 1987), acanthocephalans (Dobson, 1986), and anisakid nematodes (Szalazi and Dick, 1989).
Body size may also be used to estimate the time individual parasites have been established within the host (parasite age). From this, inference on the mode of acquisition by the host could be gained: aggregates of parasites of similar ages presumably have been acquired at the same or a similar moment in time. For soil-transmitted helminths (STHs), the mode of acquisition of infective stages from the environment has long been a theoretical consideration in population dynamical models (initially considered by Tallis and Leyton (1969)). Such models have demonstrated that the mode of acquisition may have a considerable impact on STH population biology, not least because it could explain some of the over-dispersion (relative to the Poisson distribution) of the number of worms per host (Grenfell et al., 1995, Isham, 1995, Pugliese et al., 1998, Tallis and Leyton, 1969), a characteristic feature of STH populations (Anderson and May, 1992). Despite this, there have been very few attempts at analysing data with the purpose of discerning the predominant mode by which hosts acquire infective stages from the environment (Heinzmann et al., 2009).
The size of a worm within the human gut will depend on its size at establishment, the time since establishment (for Ascaris lumbricoides, we define the worm’s age to be this period plus an approximately 2 week migratory phase (Crompton, 1989)) and on the relationship between size and age (determined by the growth rate). A worm’s rate of growth will depend on both host-parasite (such as immune responses) and parasite-parasite (such as resource competition) interactions. Innate (genetically determined) factors will also affect growth. Variation in growth rates among worms can be roughly separated into two types: that which is driven by systematic differences between infrapopulations (the parasite population within a host (Esch et al., 1977)), and that resulting from differences between individual worms, independently of the infrapopulation.
Systematic variation in the body size of worms within different infrapopulations may arise from a number of well-characterised phenomena. For example, if body size is density dependent, the size of all worms within a host will be affected by the total number of worms present, although not necessarily uniformly or in a constant way through time. This results in variation in the average body size of worms among hosts harbouring different intensities of infection (worm burden). There are numerous published examples of density dependence in the body size of gastro-intestinal (GI) nematode infections of animals (Michael and Bundy, 1989, Tompkins and Hudson, 1999, Dezfuli et al., 2002), and in A. lumbricoides infections of humans (Monzon et al., 1990, Walker et al., 2009).
Host-parasite interactions may also induce variability in the size of worms among infrapopulations. The strength of these interactions may also be mediated by worm density (Paterson and Viney, 2002). In sheep, acquired antibody-based responses to the GI nematode Teladorsagia (=Ostertagia) circumcincta reduces the size of worms (Stear et al., 1997; Stear et al., 1999). Similar associations have been documented in human hookworm infections (Pritchard et al., 1995). Experimental infections of rats with Strongyloides ratti have shown that worms are larger in immunosuppressed hosts and smaller in immunized animals than worms in controls (Wilkes et al., 2004). Heterogeneity in immunocompetence will depend on the nature of the immune response: if it is predominantly acquired, it will depend on cumulative past exposure to parasite antigens and so, where worms are endemic, it is likely to be associated with the age of the host or, if principally innate, it will depend on host genetic factors. Most likely it will be a combination of both. Human immune responses to helminth infections remain only partially understood (reviewed by Anthony et al. (2007)).
Variation in the size of worms within an infrapopulation will crucially depend on the mode of parasite acquisition and establishment: whether immature stages are acquired singly and at random points in time in a “trickle” type manner (equivalent to a homogeneous Poisson process) or in clusters (termed a “clumped” infection process) (Tallis and Leyton, 1969, Grenfell et al., 1995, Isham, 1995). Assuming that the size of worms is related to their age (Seo and Chai, 1980) and that innate variability in growth rates is independent of the infrapopulation (which may be a less robust assumption in areas with highly focal transmission (Criscione et al., 2010)), under trickle infections, the size of worms within a host will be mutually independent. Conversely, clumped infections will result in aggregates of similarly-sized worms.
In this analysis we had two aims: first, to assess the extent of size inequality in A. lumbricoides in order to estimate VRS. To achieve this, we used Lorenz curves (Lorenz, 1905) and Gini coefficients (Gini, 1921) to evaluate levels of weight inequality in worms collected at endemic equilibrium and after two 6 month periods of re-infection following chemo-expulsion therapy. These are techniques of choice for this type of analysis in the parasitological literature (Dobson, 1986, Shostak and Dick, 1987, Szalazi and Dick, 1989, Hanelt, 2009, Poulin and Latham, 2002). Second, we aimed to contribute to the elucidation of the modality of the infection process in A. lumbricoides: is it a trickle or clumped?. To achieve this, we used statistical models to evaluate the evidence for worms of similar weights being aggregated within infrapopulations. We adjusted for the effects of variables known to affect the size of A. lumbricoides which, if ignored, would inflate the estimated degree of aggregation. Aggregation was measured by the intraclass correlation coefficient (ICC), which provides a quantitative measure of similarity between the weights of worms infecting the same host (Ridout et al., 1999).
Section snippets
Study area and data collection
Data were collected in a poor urban suburb of Dhaka, Bangladesh between 1988 and 1989 by Hall et al. (1992). Briefly, households were visited and all of their occupants invited to take part in the study with the aim of recruiting as many individuals as possible. All participants were asked to provide a faecal sample from which the number of A. lumbricoides eggs were counted using a quantitative ether sedimentation technique (Hall, 1981) and the concentration of eggs per gram of faeces (EPG)
Average weight, variability and inequality
The Lorenz curves constructed using the data from the three populations show a modest degree of concavity (Fig. 1). The estimated Gini coefficients indicate that the levels of weight inequality are fairly low compared with similar estimates in other parasitic helminths of vertebrates (Hanelt, 2009), suggesting that the female worms in this population have a low variability in reproductive success. Modest levels of inequality are also indicated by the relatively small skew of the three weight
Discussion
There are two main findings of this study. First, we showed that the degree of inequality in the weight of female A. lumbricoides is fairly low and is similar at endemic equilibrium and after two 6 month periods of re-infection. This suggests that levels of VRS are not particularly high in A. lumbricoides. Second, we demonstrated that female worms of similar weights are statistically significantly aggregated within hosts suggesting that larval worms establish in clumps rather than singly.
The
Acknowledgements
We are extremely grateful to Dr. Melissa Haswell-Elkins for sharing her data with us and providing an invaluable means of comparison between populations of Ascaris in India and Bangladesh. We thank the Medical Research Council (MRC, UK) for funding this work through a Doctoral Training Account (MW) and a Career Establishment Grant (M-GB).
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