Search PubMed⌕ Search

Biomedical subjects

D I Grove

Publications and source records attributed to D I Grove.

At least 73 records · Page 4Linked to original sources

The effects of 22, 23-dihydroavermectin B1 on Strongyloides ratti and S. stercoralis infections in mice.

The efficacy of the avermectin compound 22, 23-dihydroavermectin B1 against murine strongyloidiasis has been examined. A daily dose of 4 micrograms (200 micrograms kg-1) totally suppressed excretion of Strongyloides ratti larvae in the faeces. A similar marked suppression was seen when 10 micrograms (500 micrograms kg-1) of the drug was given on two days during the phase of larval migration or during the intestinal phase. Avermectin did not affect larval numbers in the skin but reduced larval numbers in the lungs by 91%. Administration of avermectin during the phase of larval migration completely prevented the subsequent appearance of adult worms in the gut. A single dose of 50 micrograms (2.5 mg kg-1) eradicated intestinal adult worms. Some variability was noted in dose-response studies, but the drug was very potent and a dose of 50 micrograms (2.5 mg kg-1) always eradicated the worms. Avermectin greatly reduced the numbers of S. stercoralis larvae in the muscles, whether it was given early or late in the infection. Eradication of S. stercoralis larvae from muscle followed a single dose of 100 micrograms (5 mg kg-1). It is concluded that this avermectin could be valuable in the treatment of human strongyloidiasis.

Animals↗

Immunisation of mice against Strongyloides ratti.

Experimental infections of C57Bl/6 mice with strongyloides ratti produced marked resistance to challenge. Resistance to reinfection was induced by as few as six filariform larvae. The degree of resistance produced by soluble somatic antigens prepared from filariform larvae of S. ratti was comparable to that seen after a primary infection. The addition of Freund's adjuvants to the antigen did not increase resistance significantly. Intraperitoneal implantation of micropore chambers containing filariform larvae failed to induce resistance to reinfection. Considerable resistance to a challenge infection with S. ratti was found after infection with S. stercoralis.

Animals↗

Treatment of strongyloidiasis with thiabendazole: an analysis of toxicity and effectiveness.

The effects of therapy with thiabendazole were investigated in 43 men who had been infected with Strongyloides stercoralis for 35 years. Side effects of drug treatment were frequent and sometimes severe; nausea was the most common symptom. Six months later, approximately one third of patients had persistent diarrhoea, recurrent urticaria or considered that their general health had not improved. Parasites were found in 7% of persons six months after treatment. Blood eosinophil counts fell dramatically but the falls in serum IgE levels and serum Strongyloides antibody titres were less marked. Assessment of response to treatment is difficult because of the insensitivity of parasitological techniques and the ability of this parasite to replicate. It is concluded that thiabendazole cannot always be relied upon to eradicate infection.

Aged↗

Infection and immunity in dogs infected with a human strain of Strongyloides stercoralis.

The course of infection and immunological responses in dogs infected with a strain of Strongyloides stercoralis of human origin were investigated. The first dog infected developed a chronic infection lasting at least 15 months. Larvae disappeared from the faeces by three months after infection in another four dogs; these animals were resistant to challenge infection. A further dog developed a chronic infection of low intensity which could not be boosted by repeated heavy infections. These differences may be genetically determined. Immune responses in primary infections were measured in four dogs. A blood eosinophilia occurred in infected animals. Anti-Strongyloides antibodies of the IgM class appeared one week after infection, peaked at three weeks then slowly declined in titre while IgG antibodies appeared slightly later and then persisted in high titre. When compared with uninfected control dogs, no significant differences were seen in PHA stimulation of peripheral blood lymphocytes, nor did significant lymphocyte proliferation occur in the presence of Strongyloides antigen. Infected dogs showed marked immediate hypersensitivity to antigen injected intradermally, but Arthus and delayed hypersensitivity reactions were not seen. This model of human strongyloidiasis merits further investigation.

Animals↗

Attempts to establish infections with Strongyloides stercoralis in mice and other laboratory animals.

Infection of a dog with Strongyloides stercoralis filariform larvae resulted in a persistent infection. Patent infections were not seen in rabbits, guinea-pigs, rats and 11 inbred strains and one outbred strain of mice. Manipulation of factors known to influence S. ratti infections in mice, such as age and sex of the host and the route of larval presentation, did not facilitate the appearance of rhabditiform larvae in the stools. Administration of immunosuppressive doses of corticosterioids to rabbits, guniea-pigs and C57Bl/6 mice did not permit complete development. Similarly, th course of infection was not altered in T cell-deficient hypothymic (nu/nu) mice. The fate of filariform larvae applied to the skin of mice was ascertained; filariform larvae were observed to migrate from the skin via the lungs to the muscles within several days of infection. Although S. Stercoralis does not develop to maturity in the small intestine of mice, this system does allow in vivo studies of the actions of anthelmintics against filariform larvae as well as a number of aspects of the immune response to this parasite.

Age Factors↗

The occurrence of Strongyloides ratti in the tissues of mice after percutaneous infection.

The migration of infective larvae of Strongyloides ratti has been examined in C57Bl/6 mice after percutaneous infection of the anterior abdominal wall. Lateral migration of larvae through the skin and subcutaneous tissues was not seen. Large numbers of larvae were recovered from the muscles between 2 and 24 hours after infection and larvae were seen in the cerebrospinal fluid 24 and 48 hours after infection. Insignificant numbers of larvae were seen in the blood, serosal cavities, liver, spleen, kidneys, brain or nasopharynx. Larvae arrived in the lungs between 24 and 72 hours after infection and worms were first noted in the small intestines at 48 hours. It is concluded that larvae migrate preferentially to the muscles and CSF before passing to the lungs, but the exact mode of travel is uncertain.

Abdominal Muscles↗

Strongyloides ratti infections in congenitally hypothymic (nude) mice.

The course of infection with Strongyloides ratti was examined in congenitally hypothymic CBA/H, C57Bl/6 and BALB/c nude mice. The intensity of infection and the duration of faecal larval excretion were both increased in nude mice when compared with intact mice. Adult worms persisted in the small intestine of nude mice for at least 6 weeks. Greater worm burdens were found in such mice after subcutaneous injection as compared with percutaneous infection. Hypothymic mice did not acquire resistance to re-infection. It is concluded that both the spontaneous expulsion of worms in primary infection and resistance to challenge infection are T cell-dependent events. Autoinfection was not seen.

Animals↗

Humoral and cell-mediated immune responses in murine strongyloidiasis.

The immunological changes occurring after primary and challenge infections with Strongyloides ratti in C57B1/6 mice are described. Serum IgM and IgG antibodies against Strongyloides antigen appeared one week after primary infection. The levels of antibody in both immunoglobulin classes increased markedly after secondary infection and persisted for at least 6 weeks. Immediate hypersensitivity (15 min footpad) reactions were transient after a primary infection, but were marked and persistent after a secondary infection. Arthus (5 h footpad) reactions were mild and very transient after a primary infection, but a persistent anamnestic response was seen after challenge infection. Cell-mediated immune (24 h footpad) reactions were marked 1 week after both primary and secondary infections but were not sustained in either case. Antigen-reactive cells were present in the mesenteric lymph nodes 1 week after primary infection and 1-4 weeks after challenge infection. No antigen-reactive cells were noted in the spleen. Mesenteric lymph node (MLN) cells and spleen cells from infected or uninfected animals were stimulated with phytohaemagglutinin (PHA) or lipopolysaccharide (LPS) but did not differ significantly in their 3H thymidine incorporation. A transient eosinophilia was observed after primary infection and an anamnestic response was noted after challenge infection. The possible roles of these immunological responses to worm rejection and immunopathology are considered.

Animals↗

Description of an examination for the objective assessment of history-taking ability.

A novel examination of the ability of final-year medical students to take a targeted history is described. One hundred and nine students were examined in 1 day. Each student interviewed three patients, each with a different problem. One of these persons was a real patient, while the other two were simulated patients. Patients were able to give consistent histories and the use of simulated patients enabled a high degree of standardization to be achieved. The examination provided a useful degree of discrimination among students; the marks scored followed a normal distribution with a mean value of 22.2 and a range from 16 to 29 out of a maximum of 30 marks. We believe that this examination is valid, reliable and practical.

Australia↗

Strongyloidiasis: is it transmitted from husband to wife?

The possible transmission of Strongyloides stercoralis from men who had been infected for many years to their wives was investigated. None of the 24 wives was infected, as indicated by the absence of anti-Strongyloides antibodies in their serum. Thus, the risk of transmission from husband to wife seems small, although the likelihood among homosexuals is greater.

Female↗

Strongyloides ratti and S. stercoralis: the effects of thiabendazole, mebendazole, and cambendazole in infected mice.

The effects of benzimidazole anthelmintics in murine strongyloidiasis were examined. Thiabendazole 50 mg/kg daily produced a 91% reduction in the numbers of Strongyloides ratti larvae in the feces. A similar suppression was seen when thiabendazole was given during the intestinal phase, but no effect was noted when the drug was administered during the phase of larval migration. Thiabendazole had no effect on larvae in the skin or lungs, did not inhibit maturation of worms, and did not expel adult worms from the gut, but did reduce fecundity of adult worms in the intestines by 84%. Mebendazole and cambendazole 50 mg/kg daily totally suppressed excretion of S. ratti in the feces. A similar suppression was seen when the two drugs were given during the phase of larval migration or during the intestinal phase. They had no effect on larvae in the skin, and the reduction in larval numbers in the lungs was not statistically significant. When given during the migratory phase and early intestinal phase, they reduced the numbers of fourth stage larvae recovered from the gut by 95%. Mebendazole and cambendazole totally eliminated intestinal adult worms. Dose response studies indicated that in terms of orally administered dose, cambendazole was 100-1,000 times more active than mebendazole. Thiabendazole and mebendazole had no significant effect on S. stercoralis larvae in the muscles. In contrast, cambendazole 50 mg/kg daily for 4 days eradicated S. stercoralis larvae from the muscles. It is concluded that cambendazole may have significant advantages over both thiabendazole and mebendazole in the treatment of strongyloidiasis.

Animals↗

Inhibition of human blood clotting by extracts of Ascaris suum.

The effects of soluble extracts of Ascaris suum on human blood coagulation were investigated. Whole worm supernatant solution prolonged the whole blood clotting time and the kaolin-activated, partial thromboplastin time but it did not alter the prothrombin time. These data indicate impairment of the intrinsic pathway of blood coagulation. Whole worm supernate inhibited platelet aggregation induced by ADP and ristocetin. This supernate did not affect fibrinolysis. The maximal concentration of anticoagulant activity was found in the pseudocoelomic fluid of the worm. Activity was also noted in the cuticle and secretory/excretory products. Perhaps inhibition of blood clotting by helminths may facilitate their passage through the blood stream.

Adenosine Diphosphate↗

Serodiagnosis of human strongyloidiasis by an enzyme-linked immunosorbent assay.

The sensitivity specificity of an enzyme-linked immunosorbent assay (ELISA) for the serodiagnosis of strongyloidiasis has been investigated. 45 men with long-standing strongyloidiasis were compared with the same number of age- and sex-matched control subjects. The ELISA detected antibody in 84% of patients with parasitologically proven strongyloidiasis. When the technique was compared with an indirect immunofluorescent assay (IFA), a high correlation coefficient was obtained. Specificity was demonstrated by observing a marked fall in optical density of pooled positive serum after prior incubation with Strongyloides ratti soluble antigen but not after incubation with antigens derived from Ascaris suum or Dirofilaria immitis. The test is simple and offers a useful method for the diagnosis of strongyloidiasis. In these patients it was more reliable than a single parasitological examination of faeces or duodenal contents.

Antibody Specificity↗

Effects of prednisolone on murine strongyloidiasis.

The effects of prednisolone were investigated in C57Bl/6 mice infected with Strongyloides ratti. In primary infections, the numbers of adult worms in the small intestine and larvae in the stools were increased and there was a slight delay in the spontaneous expulsion of worms. In secondary infections, there was an initial suppression of acquired resistance, with larvae appearing normally in the stools on the 5th day after infection. This was followed, however, by a rapid development of resistance and expulsion of worms over the next few days. Prednisolone treatment did not alter fecundity in primary or secondary infections. There was no evidence of autoinfection in control or corticosteroid-treated animals. Prednisolone abrogated innate resistance to infection in C3H mice. It is concluded that prednisolone probably facilitated infection by non-specific mechanisms as well as by suppressing specific acquired immunity.

Animals↗

Diagnosis of human strongyloidiasis by immunofluorescence, using Strongyloides ratti and S. stercoralis larvae.

The sensitivity and specificity of an indirect immunofluorescent antibody assay for the diagnosis of human strongyloidiasis has been investigated. Sera were obtained from 160 Australian ex-servicemen who had been prisoners-of-war in Southeast Asia during World War II, 44 of whom proven parasitologically to have strongyloidiasis; these men did not have concurrent infections with other helminths. In addition, sera were collected from 44 age- and sex-matched Australians who were not thought to have been exposed to S. stercoralis, and from 44 Filipino subjects. Antibodies were measured by using living filariform S. ratti larvae as the source of antigen. The assay was highly sensitive; antibodies were found at a titer of 1:4 or greater in 98% of men with strongyloidiasis and in 2% of Australian control subjects. Fifteen percent of exposed ex-servicemen in whom parasites had not been found had antibody titers of 1:4 or more, and it is thought that they had cryptic infections. Incubation of pooled positive sera with soluble S. ratti antigen produced a marked fall in antibody titer, but no changes were seen after incubation with soluble Ascaris suum or Dirofilaria immitis antigens. It is thought that this indicates that the test is specific and that the 84% of Filipinos with antibody titers of 1:4 or greater had unsuspected strongyloidiasis. When antibody titers against S. ratti were compared with those obtained using living filariform S. stercoralis larvae, a high correlation was found (r = 0.89, P less than 0.001). It is concluded that this assay provides a simple, safe, and specific method for the diagnosis of strongyloidiasis.

Adult↗