Biomedical subjects
Publications and source records attributed to D I Grove.
A case of corneal ulceration due to infection with Nocardia asteroides is described. Microbiological examination of corneal scrapings permitted accurate diagnosis and suggested appropriate therapy. Nineteen other cases that have been described in the world literature are reviewed.
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A survey was undertaken of all of the consultant staff members of Perth's major teaching hospitals together with all the fellows of The Royal Australian College of General Practitioners in Western Australia in order to define their views on the issues of informed consent, compulsion in relation to surgery, and confidentiality in a particular circumstance, when testing for infection with the human immunodeficiency virus (HIV). Of the 701 individuals surveyed, 548 (78.2%) responded. Of these, 74.3% considered that it was not always necessary to gain informed consent, 22.0% believed that it was always necessary to do so, while 2.3% were undecided. General practitioners (38.4%) were more likely to think it necessary to obtain consent than were hospital consultants (19.0%), but otherwise the field of specialty had little effect on opinion. Of the respondents, 39.0% believed that testing before elective surgery is mandatory for all patients, while 53.0% considered that it should be compulsory in high-risk groups. Similar views were held about compulsory HIV antibody testing after emergency surgery. Similar responses were obtained from all specialty groups. When asked about whether they would tell a sexual partner of a patient's HIV status when the patient refused, 10.5% of doctors stated they would never advise the partner, 24.7% of doctors would on some occasions, 41.0% of doctors would tell a partner, and 23.8% always were undecided. Many individuals commented that they failed to see why HIV infection was being treated differently from other serious diseases. We have found that the majority opinion of the most senior members of the medical profession is that specific, informed consent should not always be required, that there is great support for compulsory testing, and that confidentiality may be broken under certain circumstances. These views must be recognized by administrators and legislators when framing measures to control this infection.
The protein composition of Strongyloides stercoralis infective larvae and adult worms solubilized sequentially in water, sodium deoxycholate and sodium dodecyl sulphate (SDS) and their excretory/secretory products were analysed by one- and two-dimensional SDS-polyacrylamide electrophoresis. These extracts were demonstrated to be complex mixtures containing many proteins, some of which were common and others which were stage-specific. Western blot analysis of these antigens with infected human sera showed most sero-reactivity against larval antigens, whilst normal human sera were unreactive. These data identify immunogenic antigens which may be available for detection in an antigen assay.
The generation of protective immunity by various stages in the life-cycle of Strongyloides ratti and the phases against which resistance is directed has been examined in murine strongyloidiasis. Mice were exposed to natural, complete infections, were treated with thiabendazole (which largely resembles the natural infection), were treated with cambendazole (which restricts infection to the larval stage), or infected directly by oral transfer of adult worms. Mice that were infected with infective larvae alone did not become resistant to infective larvae or the complete infection but were resistant to adult worms implanted directly into the gut. Mice exposed to adult worms alone were resistant to natural infections and adults worms implanted directly but were not resistant to infective larvae. On the other hand, mice that had received prior natural infections showed evidence of resistance to infective larvae, adult worms, and natural, complete infections. It is concluded that there is immunological cross-reactivity between infective larvae and adult worms but that under certain circumstances the infective larvae are able to evade the host's protective immune response.
Various methods of radioiodination were compared for their efficacy in labelling the surface of Strongyloides ratti infective larvae and adult worms. The Iodogen method was chosen as the optimal technique for this parasite. The surface location of 125-iodine was confirmed with light microscope autoradiography of transverse sections of labelled worms. Stage-specific surface components were identified when the sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) profiles of infective larvae and adult worms were compared. Labelled surface molecules were solubilized with either the non-ionic detergent Triton-X-100, the anionic detergents sodium deoxycholate (DOC) or sodium dodecyl sulphate (SDS), or the cationic detergent cetyl trimethyl-ammonium bromide (CTAB). The CTAB extract yielded most labelled proteins that retained their antigenicity in an immunoprecipitation assay with hyperimmune mouse sera. Immunoprecipitation analysis with stage-specific mouse sera revealed that the surface of infective larvae is immunogenic and that there are no cross-reactions with adult worms. Adult worms resident in the intestine were not found to be immunogenic and showed a complete absence of reactivity. Antigenic determinants shared between S. ratti and S. stercoralis were identified. Patients infected with S. stercoralis precipitated bands with molecular weights 32 and 34 kD which were not reactive with normal sera. These reactions suggest the potential usefulness of the surface of S. ratti as a source of diagnostic antigens.
The effects of three benzimidazole anthelmintics in dogs infected with a human strain of Strongyloides stercoralis were investigated. Cambendazole, but not thiabendazole or mebendazole, abrogated the subsequent development of a patent infection when administered at the same time as infection to immunocompetent dogs. None of the drugs eradicated infection when given after the onset of patency in immunosuppressed animals, although worm burdens were greatly reduced in dogs treated with cambendazole. The implications of these findings for the treatment of patients with strongyloidiasis, particularly those with disseminated infections, are discussed.
In view of conflicting clinical reports, the effects of albendazole on Strongyloides were examined in vitro and in experimentally-infected animals. Albendazole inhibited the hatching and moulting of S. ratti eggs and larvae and prevented the development in vitro of S. stercoralis first-stage larvae. Pre-exposure to the drug did not impair the infectivity of either S. ratti or S. stercoralis third-stage larvae. Albendazole had a dose-dependent inhibitory effect on S. ratti migrating larvae in mice when measured in terms of the numbers of larvae recovered from the skin or lungs or the subsequent development of a patent infection. Likewise, killing of adult S. ratti in the gut and eradication of S. stercoralis third-stage larvae from the muscles of mice were dose-dependent. Albendazole in a dose of 100 mg twice daily for three days given at the time of infection with S. stercoralis of immunocompetent dogs prevented completely the subsequent development of patent infection. When the drug was given in the same dosage to immunosuppressed dogs with patent infections, the larvae disappeared from the stools transiently; when the animals were killed seven weeks after treatment, small numbers of adult worms and rhabditiform larvae were found in the gut. It is concluded that albendazole may be effective treatment for strongyloidiasis if it is given in sufficiently large doses.
Mice were infected once, twice or many times with Strongyloides ratti infective larvae, and the parasite was allowed to complete its development. Other mice were infected many times with either infective larvae only, by aborting the infection with cambendazole, or with adult worms transferred by intra-oesophageal intubation. Sera from these animals were analysed by immunoblotting against SDS-PAGE separations of larval and adult worm water-soluble, deoxycholate-soluble, sodium dodecyl sulphate-soluble and excretory/secretory antigens. Minimal antibody responses were observed after primary and secondary infections. Mice exposed to multiple complete infections reacted strongly to both larval and adult antigens but greater responses were observed against the larval preparations. Stage-specific effects were noted in mice infected with larvae only or adult worms only. Mice exposed only to larvae reacted with larval antigens and to a minor degree to somatic adult worm antigens while those mice which were exposed only to adult worms failed to react with any of the antigen preparations. Some cross-reactions were found, however, as mice infected only with larvae displayed strong reactions against both larval and adult excretory/secretory products. These data demonstrate differences in sero-reactivity to infective larvae and adult worms and suggest that humoral immunity is induced by larvae migrating through the tissues and not by adult worms in the gut.
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The prevalence of antibodies against Strongyloides in the serum of newly-arrived Indochinese immigrants was determined. Sera that had been stored in the State Health Laboratories, Perth, were stratified according to age and sex, then samples were selected at random. Two hundred and ninety sera that had been obtained from persons between the ages of one and 69 years were examined by an indirect fluorescent antibody test. Five per cent of children who were aged between one and two years gave positive reactions. The positive reaction rate in this population increased by approximately 7% per year until the age of seven to eight years at which point it levelled off. Approximately half of all older children, teenagers and adults had positive antibody responses, indicating past or present infection with Strongyloides stercoralis. This parasite is an extremely unusual worm in that it is able to replicate within the human host. Consequently, infection may persist for years. Furthermore, immunosuppression may result in fatal, disseminated infection. Strongyloidiasis is now recognized in three major Australian population groups: Aborigines who are living in the north of the country; World War II veterans who were prisoners in southeast Asia; and Indochinese immigrants. The salient features of the clinical manifestations, diagnosis and treatment of strongyloidiasis are reviewed.
We report observations on infestations with the tick, Amblyomma triguttatum, in soldiers who were bivouacked in two areas near Perth; 34% of 175 persons were infested with varying stages of the ectoparasite. Most persons were infested with only one tick but some troops had multiple infestations. Local skin reactions to tick-bites were frequent; they usually developed 24-48 h after removal of the tick and may indicate delayed hypersensitivity reactions. A small number of persons developed secondary bacterial infections. Management and prevention of these infestations is reviewed briefly.
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The protein composition of Strongyloides ratti infective larvae and adult worms extracted sequentially in water, sodium deoxycholate and sodium dodecyl sulphate (SDS) and their excretory/secretory products were analysed by both one- and two-dimensional SDS-polyacrylamide gel electrophoresis. While many bands common to all preparations and both stages of the worm were seen, a number of bands unique to each stage and preparation were identified. Western blot analysis of these larval and adult preparations for reaction with IgG and IgM antibodies in hyperimmune mouse sera revealed a large number of antigens. These data provide a framework for analysis of protective and diagnostically useful antigens.
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Previous indications using radiolabelled larvae that Strongyloides ratti free-living infective larvae lose a surface coat during penetration of the skin were further investigated by transmission electron microscopy of the cuticle of S. ratti infective larvae in the free-living stage, after penetration of mouse skin, and after migration to the lungs. These studies demonstrated the presence of a faint electron-dense surface coat external to the epicuticle on free-living worms which was absent from larvae recovered from the skin and lungs. When free-living infective larvae were incubated in 10% CO2 at 37 C and then examined with phase-contrast microscopy, worms were observed in the process of losing this coat. These observations confirm the hypothesis that S. ratti infective larvae lose a surface coat during penetration of the skin.
A model of human hookworm infection has been developed which shows that dogs currently infected with small numbers of hookworms are considerably resistant to a challenge infection with a large inoculum of infective larvae. Two groups of dogs were infected with 500 larvae and four weeks after infection one group together with a previously uninfected control group were infected with 5,000 larvae and followed for six weeks. When compared with the secondary infection control dogs, faecal egg excretion and adult worm burdens were reduced by an average of 83 and 78% respectively. Infections had no significant effect on total white cell counts, platelet levels or spontaneous, phytohaemagglutinin- and antigen-induced lymphocyte transformation among the three groups of dogs. Dogs previously uninfected with hookworm developed a marked anaemia when infected with 5,000 larvae but this was not observed in the superinfected group. An eosinophilia developed in all groups and there were no significant differences among the three groups of animals. Specific IgM antibodies developed transiently in all groups of dogs two weeks after infection. IgG antibody levels were significantly greater in the superinfected animals one, two and three weeks after challenge infection compared with the secondary infection control animals; by four weeks there was no significant difference between the two groups of animals. Both groups given the large inoculum of larvae developed specific IgA antibodies one week after the challenge infection and these continued to rise in the superinfected group until termination of the experiment. It is concluded that dogs currently infected with the hookworm, Ancylostoma ceylanicum, demonstrate the development of functional protective immunity.