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Biomedical subjects

A E Keymer

Publications and source records attributed to A E Keymer.

30 records · Page 2Linked to original sources

Heligmosomoides polygyrus (Nematoda): the dynamics of primary and repeated infection in outbred mice.

The population dynamics of Heligmosomoides polygyrus were studied in outbred male MF1 mice subject either to primary or repeated experimental infection. Little variability in susceptibility was observed between mice, but heterogeneity increased with both duration and intensity of primary infection; this result indicates that there are differences in parasite survival between hosts. The rate of parasite-induced host mortality was 4 X 10(-4) per parasite per host per parasite lifespan. The mortality rates of male and female larvae during their development in the intestinal wall were estimated as 0.033 and 0.021 per parasite per day respectively, and estimates of the expected lifespans of the adult male and female parasites in primary infection of 11.22 and 9.92 weeks were obtained. Approximately 40% of female worms were observed in copula at any one time, although this proportion was significantly depressed in hosts harbouring fewer than 50 parasites and during the first four weeks of infection. Parasite fecundity was markedly age-dependent; each female worm produced approximately 31,000 eggs during its lifespan. No density dependence in either worm survival or fecundity in primary infection was apparent. The only detectable effect of worm density was in association with spatial distribution in the intestine; high levels of infection were associated with a posterior shift in the location of a proportion of the parasite population. Characterization of the dynamics of primary infection allowed predictions to be made about the expected dynamics of repeated infection. The comparison of predicted results and observed data revealed unequivocal epidemiological evidence for the density-dependent regulation of parasite population growth during repeated infection, affecting both parasite survival and parasite fecundity. The results also demonstrated the existence of two types of host individual in which the dynamics of repeated infection were markedly different. It is concluded that immunological differences between mice (possibly under genetic control) may be responsible for the observed effects; approximately 25% of MF1 mice seem unable to generate any protective immunity against H. polygyrus, whereas 75% become almost completely refractory to reinfection. This experimental system could be used for quantitative investigation of the impact of acquired immunity and genetic heterogeneity on helminth population dynamics. Both are of obvious relevance with respect to the control of infections of medical and veterinary significance.

Animals↗

Heligmosomoides polygyrus (Nematoda): the influence of dietary protein on the dynamics of repeated infection.

The influence of the protein component in the diet of the host on the population dynamics of gastrointestinal helminth infection was studied by using a mouse-H. polygyrus experimental model. Mice fed a 2% (by mass) protein diet ad libitum maintained body weight during the experiment, but gained weight steadily when fed a diet containing 8% (by mass) protein. When repeatedly infected with 5, 10, 20 or 40 larvae every 2 weeks, the mice fed the 2% (by mass) protein diet accumulated adult worms in direct proportion to exposure to the infective stages. Under similar infection régimes, mice fed an 8% (by mass) protein diet acquired a partly effective immunity to reinfection by the nematode. Acquired immunity was principally manifest as a reduction in the survival of adult worms, although a slight increase in the mortality rate and/or the development time of the tissue-dwelling larval phase was observed. Worm fecundity per head was significantly depressed in hosts fed the 8% protein diet. In conclusion, in these experiments it is demonstrated that the nutritional status of the host can influence the population dynamics of helminth infection.

Animal Nutritional Physiological Phenomena↗

The population dynamics of acquired immunity to helminth infection.

Based on experimental evidence we develop and exploit a mathematical model to describe the role of acquired immunity in host-helminth interactions. We show that the model gives a quantitative description of the population dynamics in a laboratory situation involving a host immunological response. We make practical predictions based on these results.

Animals↗

Epidemiology of Heligmosomoides polygyrus in mice: experiments on natural transmission.

An experimental system is described for the study of the community dynamics of helminth-host populations, using Heligmosomoides polygyrus in the laboratory mouse. The results of a preliminary experiment using closed populations of 50 mice revealed that coexistence of host and parasite occurs for at least 4 months in the absence of immigration, with the generation of epidemiological patterns similar to those observed in the real world. In well-nourished mice the prevalence and intensity of infection initially increased with time and then declined, probably as a result of acquired immunity. The prevalence and intensity of infection increased less rapidly among hosts fed on a low protein diet, but continued to rise over the entire duration of the experiment. This continued rise is interpreted as evidence of a negative effect of protein malnutrition on host immunocompetence. The frequency distributions of parasite numbers/host were over-dispersed in each mouse population. No density dependence in parasite fecundity was detected. Aspiculuris tetraptera was also found to be present in the mouse populations. This parasite was not transmitted between mice fed on a high protein diet, but rose to a prevalence of 80% in protein malnourished animals. No association between the intensity of A. tetraptera and H. polygyrus could be detected in individual hosts. The results are discussed in terms of the future potential of the system for the investigation of the role of acquired immunity (and its genetic control) in the generation of epidemiological patterns.

Animals↗

Faecal egg counts and nematode fecundity: Heligmosomoides polygyrus and laboratory mice.

The results are presented of an experimental investigation of the relationship between faecal egg counts and worm burden in outbred MF1 mice infected with Heligmosomoides polygyrus (Nematoda). The sex-ratio of the adult parasites was found to be significantly female biased, but independent of parasite burden. Evidence was also found to suggest a significant association between parasite density and mating success. The linear logarithmic relationship (gradient of approximately 2) between the variance and mean of repeated egg counts from individual mice could not be disrupted by controlled experimental conditions, and is therefore concluded to be an inherent feature of the biology of helminth-host interactions. A significant positive association was detected between host faecal output and parasite fecundity; further investigation of the cause of this association is now required. Average faecal production was found to be inversely related to worm burden. In combination, the above two factors account partly, but not completely, for the observed density dependence in the absolute rate of parasite egg production. Two epidemiological consequences of the relationship between faecal production and parasite fecundity are discussed. First, absolute rates of egg production can only be estimated by temporal egg counts (epd). Secondly, measurements of egg production/g of faecal material (epg) are more reliable indicators of worm burden than measurements of epd. Both faecal output and worm fecundity respond as might be predicted to a period of host food deprivation; faecal egestion and measurements of epd are significantly depressed, and measurements of epg are significantly increased. The data are consistent with the hypothesis that egg production and faecal output are causally associated, but that other factors relating to parasite density also influence egg production. Of the possible causes for the high variability in parasite egg production between mice harbouring low number of worms, the most likely explanation seems to be host heterogeneity (possible genetic in origin). This is discussed in relation to similar patterns observed in data collected from human populations in areas of endemic helminth infection.

Analysis of Variance↗

Investigating over-dispersion; Moniliformis (Acanthocephala) and rats.

An analysis of the frequency distribution of numbers of Moniliformis dubius in rats of an outbred strain of Wistar origin (CFHB) and feeding ad libitum on Oxoid 41B diet, showed that over-dispersion occurred regardless of the age and sex of the rats and the infective dose given (12, 20 or 40 cystacanths/rat). Over-dispersion was also shown to be independent of variability in the age and sex of the cystacanths given. The analysis demonstrated that the over-dispersion declined as the course of the infection proceeded. As expected, parasite survival was found to be age-dependent with female worms living longer, on average, than males, and both male and female worms living longer in rats given 12 as opposed to 20 cystacanths. Possible mechanisms for generating the over-dispersion observed during this work are discussed and a tentative hypothesis, invoking host heterogeneity with regard to carbohydrate availability in the small intestine, is proposed for further experimental investigation.

Acanthocephala↗

The influence of Hymenolepis diminuta on the survival and fecundity of the intermediate host, Tribolium confusum.

An experimental study of the effects of parasitism by H. diminuta on the intermediate host, Tribolium confusum, is described. No density-dependent constraints on parasite establishment within individual hosts are evident, although a reduction in cysticercoid size at high parasite burdens is demonstrated. The relationship between parasite burden, host mortality and host fecundity is investigated. Host mortality is linearly related to parasite burden, whereas the relationship between parasite burden and host fecundity is non-linear. There is no difference in viability between eggs from infected and uninfected females. The generative causes of these effects are not investigated experimentally, although it is postulated that survival is related to the degree of damage to the midgut wall caused by parasite penetration, and fecundity to the biomass of parasites harboured by the host. The significance of these effects is discussed in relation to the overall dynamics of the host-parasite association.

Animals↗

The dynamics of infection of Tribolium confusum by Hymenolepis diminuta: the influence of infective-stage density and spatial distribution.

The mean parasite burden of a population of Tribolium confusum is shown to rise to a plateau as the exposure density of infective eggs of Hymenolepis diminuta increases. The level of this plateau is shown to be dependent on the nutritional status of the host population, being depressed from approximately 18 cysticeroids/beetle in hosts which have been starved prior to experimentation, to approximately 2 cysticercoids/beetle in satiated hosts. A simple model is used to describe the shape of this infection functional response in terms of the predator-prey interaction between hosts (T. confusum) and parasite infective stages (H. diminuta eggs). The distribution of successful infections/host is shown to be over-dispersed, even when hosts are exposed to infective stages arranged in a uniform spatial pattern. The over-dispersion of parasite numbers/host is shown to become more severe as the spatial pattern of infective stages changes from under-dispersed, through random, to over-dispersed. Experimental results are discussed in relation to the dynamics of parasite-host interactions, in which infection takes place by host ingestion of a free-living infective stage.

Feeding Behavior↗

Hookworm (Necator americanus) infection and storage iron depletion.

The relationship between iron status and the intensity of infection with hookworm was investigated in a rural population on Karkar Island, Mandang Province, Papua New Guinea. There was a significant negative correlation between plasma ferritin level and hookworm burden, which was strongest in males. In contrast, there was no correlation between plasma ferritin and hookworm egg count, and no consistent correlation between haemoglobin level or haematocrit and either measure of hookworm intensity. The results suggest that the role of hookworm in the aetiology of anaemia may be difficult to assess without the accurate measurement of hookworm burden.

Age Factors↗

Antigenic cross-reactivity between Necator americanus and Ascaris lumbricoides in a community in Papua New Guinea infected predominantly with hookworm.

Sero-epidemiological data are presented in which antigenic cross-reactivity between Necator americanus and Ascaris lumbricoides has been investigated in a community in Papua New Guinea infected predominantly with N. americanus. It is our contention that the antigenic cross-reactivity which undoubtedly exists between these species accounted for (i) a peak in antibody levels against N. americanus in 10-13 years old children (driven by infection with A. lumbricoides), and (ii) the maintenance of apparent antibody levels against A. lumbricoides in older age groups (driven by infection with N. americanus in the absence of overt infection with A. lumbricoides). Cross-reactivity was analysed further, and apparently N. americanus-specific epitopes identified, by immunoblotting. These observations could have considerable bearing on the interpretation of data from sero-epidemiological studies which failed to take account of concurrent infection with these parasites.

Adolescent↗