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Biomedical subjects

A F Slater

Publications and source records attributed to A F Slater.

41 records · Page 3Linked to original sources

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↗

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↗

Chloroquine: mechanism of drug action and resistance in Plasmodium falciparum.

Quinoline-containing drugs such as chloroquine and quinine have had a long and successful history in antimalarial chemotherapy. Although these drugs are known to accumulate by a weak base mechanism in the acidic food vacuoles of intraerythrocytic trophozoites and thereby prevent hemoglobin degradation from occurring in that organelle, the mechanism by which their selective toxicity for lysosomes of malaria trophozoites is achieved has been subject to much discussion and argument. In this review the recent discovery that chloroquine and related quinolines inhibit the novel heme polymerase enzyme that is also present in the trophozoite food vacuole is introduced. The proposal that this inhibition of heme polymerase can explain the specific toxicity of these drugs for the intraerythrocytic malaria parasite is then developed by showing that it is consistent with much of the disparate information currently available. The clinical usefulness of chloroquine, and in some recent cases of quinine as well, has been much reduced by the evolution and spread of chloroquine resistant malaria parasites. The mechanism of resistance involves a reduced accumulation of the drug, although again the mechanism involved is controversial. Possible explanations include an energy-dependent efflux of preaccumulated drug via an unidentified transmembrane protein pump, or an increase in vacuolar pH such that the proton gradient responsible for drug concentration is reduced. New data are also presented which show that heme polymerase isolated from chloroquine resistant trophozoites retains full sensitivity to drug inhibition, consistent with the observation that resistance involves a reduced accumulation of the drug at the (still vulnerable) target site. The significance of this result is discussed in relation to developing new strategies to overcome the problem presented by chloroquine resistant malaria parasites.

Animals↗