David I. Grove

Suppression of cell-mediated immunity by metronidazole.

Metronidazole administered orally in doses of 20 and 200 mg/kg daily suppressed granuloma formation around Schistosoma mansoni eggs which were injected intravenously and lodged in the pulmonary microvasculature of mice. The same doses did not suppress granuloma formation in animals which had previously been sensitized to the eggs. Nonspecific granulomatous inflammation around divinyl benzene copolymer beads was unaffected by the drug. In a daily dose of 20 mg/kg, metronidazole inhibited delayed footpad reactions to soluble schistosome egg antigen, but 200 mg/kg on alternate days failed to suppress skin allograft rejection. The drug appears to suppress selectively some aspects of cell-mediated immunity.

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.

Humoral and cellular immunity in asthma

Parameters of humoral and cellular immunity have been measured in 91 asthmatic patients. Mean serum levels of IgG and IgE were raised. IgG levels were higher in those with a family history of asthma. IgE levels were higher in those with a past history of atopic eczema, but intrinsic and extrinsic asthma could not be differentiated on the basis of IgE levels. Thirteen of 74 patients failed to respond to tetanus immunization, while only 1 failed to respond to Salmonella typhi H antigen. Tetanus nonresponders had a raised mean serum IgA level, reduced spontaneous lymphocyte tritiated thymidine uptake, and reduced thymidine uptake in fetal calf serum. Eight of 87 patients failed to mount delayed hypersensitivity reactions to a battery of five intradermal antigens. The tritiated thymidine uptake of lymphocytes stimulated with phytohemagglutinin was normal in autologous serum, but reduced in fetal calf serum. The data support the hypothesis that asthma may be associated with immunodeficiency states.

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.

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.

Strongyloides ratti: Susceptibility to infection and resistance to reinfection in inbred strains of mice as assessed by excretion of larvae

Abstract Eleven inbred strains of mice, and one outbred strain, were infected with Strongyloides ratti and larvae in the faeces were quantitated. Three strains, C57B1/6, CBA and BALB/c mice were susceptible to infection while other strains demonstrated negligible infections as assessed by this method. Larvae were first seen in the faeces on day 5, peak levels were reached on days 6 and 7, and excretion ceased 10 days after infection. Factors influencing intensity of larval excretion were examined in C57B1/6 mice. Young mice (1 month of age) were found to be more susceptible to infection than 2 and 6 month old animals. Male mice were much more susceptible to infection than female animals. There was a direct relationship between the number of S. ratti injected and the number of larvae excreted over the range 200–1600 larvae; subsequent increments in dose of injected larvae failed to increase the larval output. Infection by the percutaneous route resulted in a heavier infection than did subcutaneous injection. Previous exposure to S. ratti induced a profound resistance to reinfection. It is suggested that S. ratti infections of C57B1/6 and CBA mice provide a useful model for the investigation of factors influencing the host-parasite relationship in strongyloidiasis.

Suppression of giardiasis during the intestinal phase of trichinosis in the mouse.

The interaction of the intestinal phases of Giardia muris and Trichinella spiralis was investigated in Swiss albino mice. Intraoesophageal inoculation of G. muris cysts seven days before, or seven days after, similar inoculation of T. spiralis larvae resulted in significant reduction in the numbers of Giardia trophozoites in small bowel and Giardia cysts in stools. This effect was not observed when G. muris cysts were administered after resolution of the intestinal phase of trichinosis. Giardiasis had no effect on trichinosis as assessed by numbers of adult worms in small bowel and larvae in skeletal muscles. Studies of small bowel morphology showed that the intestinal phase of trichinosis was associated with increased numbers of inflammatory cells in the lamina propria, a significant increase in Paneth cells in crypts, and a marked reduction in the villus:crypt ratio of jejunum. These observations suggest that the intestinal phase of trichinosis induced environmental changes in small bowel, perhaps related to inflammation, which resulted in suppression of proliferation of Giardia trophozoites.

Successful control of Scedosporium prolificans septic arthritis and probable osteomyelitis without radical surgery in a long-term renal transplant recipient

Abstract: Scedosporium species are increasingly isolated from immunocompromised and immunocompetent patients. Scedosporium infections are generally resistant to multiple antifungals, and Scedosporium prolificans is particularly resistant to all single antifungal agents currently in use with in vitro testing. We report here a long‐term renal transplant recipient who developed isolated S. prolificans septic monoarthritis and probable osteomyelitis. The infection was successfully treated with a combination of voriconazole and terbinafine in addition to joint washout but did not require radical surgery. This combination has been shown to have synergistic in vitro effect, and anecdotal in vivo success has also been reported recently. We also review the clinical presentation, treatment, and outcome of S. prolificans infection in patients with solid organ transplantation.

Kinetics of primary and secondary infections with Strongyloides ratti in mice.

Abstract Dawkins H. J. S. and Grove D. I. 1981 Kinetics of primary and secondary infections with Strongyloides ratti in mice. International journal for Parasitology 11 : 89–96. The kinetics of infection with S. ratti were quantitated in normal and previously exposed C57B1 /6 mice. In primary infections, larvae penetrated the skin rapidly and were seen in peak numbers 12 h after infection. By 24 h after infection, larval numbers had declined appreciably and there was a slow decrease in numbers thereafter. Larvae were first observed in the lungs at 24 h and maximal recovery occurred at 48 h. It is thought that larval migration through the lungs is rapid. Worms were first seen in the intestines two days after infection. Maximum numbers were seen on the fifth day and worm expulsion was complete by day 10. Two moults took place in the small intestine during days 3 and 4 after infection. Rhabditiform larvae were first noted on the fourth day after infection. Mice exposed to S. ratti four weeks previously had significantly less larvae in the skin 4 and 12 h after infection but by 24 h there was no difference when compared with mice with primary infections. Peak recovery of larvae from the lungs occurred 24 h after infection; significantly less larvae were recovered on days 2 and 3 when compared with normal mice. There was a marked reduction in the adult worm burden in the gut; the number of worms recovered was less than one fifth of that seen in primary infections. Those worms which did mature were less fecund and were expelled from the intestines within 7 days of infection. It is suggested that in previously exposed animals, the migration of larvae from the skin is hastened, many of these larvae are destroyed in the lungs and that expulsion of worms which do mature in the intestines is accelerated.

Histopathological appearances in primary and secondary infections with Strongyloides ratti in mice

Abstract Dawkins H. J. S. , Muir G. M. & Grove D. I. 1981. Histopathological appearances in primary and secondary infections with Strongyloides ratti in mice. International Journal for Parasitology 11 : 97–103. The histological appearances of the skin, lungs and small intestines of mice with primary and secondary infections with S. ratti are described. When the skins of mice with a primary infection were examined, larvae were seen scattered throughout the dermis. An inflammatory reaction of neutrophils and eosinophils was first noted around larvae 12 h after infection. By 48 h, mononuclear cells were prominent. The intensity of the inflammatory reaction gradually increased to a maximum on the fifth day and the larvae were destroyed. Very few larvae were seen in the lungs; those observed were located in the alveolar spaces and were not surrounded by an inflammatory infiltrate. Worms in the small intestines were found mostly in the crypts of Leiberkuhn, and were probably located within the epithelial layer; there was no significant villous atrophy or cellular infiltration. Marked differences were found in the tissues of mice with secondary infections. In the skin, oedema and neutrophils and eosinophils were seen around worms as early as 2 h after infection. By 24 h after infection, there was a mixed inflammatory infiltrate and worms were undergoing disintegration. Larvae in the lungs were surrounded by polymorphonuclear and mononuclear cells 48 h and 72 h after infection and the engulfed larvae were undergoing lysis. Only a few worms were seen in the intestines of mice with a secondary infection; the histological appearances were similar to that found in animals with primary infections. It is suggested that the rapid development of an oedematous reaction in the skins of immune mice may facilitate the entry of larvae into the bloodstream and that inflammatory cells destroy many larvae in the lungs of immune mice.