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Surrogate hosts: protozoa and invertebrates as models for studying pathogen-host interactions.

Animal models, primary cell culture systems and permanent cell lines have provided important information on virulence properties of pathogenic microorganisms. Recently, it has been shown that some inherent limitations of such models can be circumvented by using non-vertebrate hosts such as Caenorhabditis elegans, Drosophila melanogaster and Dictyostelium discoideum. These new models are helpful to follow infection processes at the molecular level. Persuasive support comes from the fact that processes such as phagocytosis, cell signaling or innate immunity can be studied in these surrogate hosts. This review describes the establishment and application of each of the three aforementioned and genetically tractable hosts. In addition, we will report on a number of approaches that led to the identification of host cell factors which influence the susceptibility of the hosts to infection.

Animals↗

The contribution of protozoa to the protein entering the duodenum of sheep.

1. Four sheep, each fitted with a rumen fistula and a re-entrant cannula at the proximal duodenum were fed a semi-purified diet containing urea as the only nitrogen source. The quantities of total protozoal amino acid-N (TPAN) present in the rumen and entering the duodenum were determined when the mean rumen dilution rate (D) was low (0.034/h) and when D was increased to 0.078/h by the intraruminal infusion of artificial saliva. 2. Increasing the dilution rate had no significant effect upon the proportions of TPAN present in the total microbial amino-acid-N (TMAN) of the rumen fluid and duodenal digesta. With both dilution rates the mean proportion of TPAN in the duodenal TMAN (0.24) was markedly less than the equivalent proportion (0.45) found in the rumen fluid. 3. The daily flow of TPAN, as measured at the duodenal cannula at both dilution rates were equivalent to only 41% of the flow of TPAN as predicted from measurements of rumen outflow, indicating that a substantial proportion of rumen protozoal protein was retained within the rumen.

Amino Acids↗

Evaluation of a range of antimicrobial agents against the parasitic protozoa, Plasmodium falciparum, Babesia rodhaini and Theileria parva in vitro.

Eighteen antimicrobials commonly used in tissue culture were screened in three different protozoan test systems in order to establish their suitability for routine inclusion in protozoal cultivation systems. The human malaria parasite, Plasmodium falciparum, was inhibited by more than half the antibiotics tested at concentrations recommended for normal tissue culture use. Eight compounds were well tolerated and thus could be used prophylactically to prevent microbial contamination. These antimicrobials were the bactericidal aminoglycoside antibiotics, streptomycin, gentamicin and kanamycin, the bacteriostatic protein synthesis inhibitors, chloramphenicol and chlortetracycline and the antifungals, 5-fluorocytosine, nystatin and amphotericin B. Babesia rodhaini and Theileria parva were less sensitive than P. falciparum and tolerated all 18 compounds at concentrations well above 100 micrograms ml-1. Extension of the study to examine direct antiprotozoal action of these and other antimicrobials not normally used in culture confirmed that P. falciparum was significantly more sensitive than the other parasites. Tylosin, rifamycin, gramicidin D and valinomycin were all strongly antimalarial with IC50 values of 0.245, 1.20, 1.3 X 10(-3) and 1.9 X 10(-3) micrograms ml-1 respectively. This compares with a value of 1.35 X 10(-2) micrograms ml-1 for the standard antimalarial, chloroquine. Only valinomycin and, more particularly, gramicidin D were significantly active against B. rodhaini and T. parva. Gramicidin D was more effective, but more toxic, than the standard antiprotozoal agents tested at curing in vivo malarial and babesial infections in mice.

Animals↗

Entamoeba polecki and other intestinal protozoa in Papua New Guinea Highland children.

Relatively few cases of humans infected with Entamoeba polecki have been reported world-wide. Where man and pig live in close association and where sanitation is poor, pig to man transmission is considered to be the most likely source of human infection. In our survey of 184 children only fresh faeces were used, thus allowing the identification of trophozoites as well as cysts. Thirty-five children (19%) were found positive for E. polecki, although in one community ten of 23 (43.4%) over five-year olds were infected. Sera from 20 positive children were tested against E. histolytica antigen, but no positive reactions were observed. We propose the possibility of man to man transmission of E. polecki where the prevalence rate and intensity of infection are high.

Antibodies↗