Biomedical subjects
K G Nicholson
Publications and source records attributed to K G Nicholson.
Antiviral therapy. Herpes simplex encephalitis, neonatal herpes infections, chronic hepatitis B.
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Antiviral therapy. Varicella-zoster virus infections, herpes labialis and mucocutaneous herpes, and cytomegalovirus infections.
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Antiviral therapy. Respiratory infections, genital herpes, and herpetic keratitis.
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Properties of antiviral agents. 2.
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Properties of antiviral agents. 1.
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Multi-site intradermal and multi-site subcutaneous rabies vaccination: improved economical regimens.
Neutralising antibody responses to six post-exposure regimens of human diploid cell strain rabies vaccine with or without human rabies immune globulin (HRIG) were studied in 98 patients. The total amount of vaccine used was 22-34% of that required by conventional regimens. Vaccine was given at multiple sites intradermally or subcutaneously with or without adjuvant. Antibody was detectable within 7 days of the first dose in all subjects only in the groups given 0.1 ml intradermally at 8 sites. From day 14 onwards all groups showed an excellent antibody response; there was little difference between the various regimens. Suppression of the response to 8-site intradermal vaccination by a large dose of HRIG could be prevented by giving the second dose of vaccine on day 7 rather than day 14.
Lack of effect of influenza and pneumococcal vaccines on anticoagulation by warfarin.
The effects on anticoagulation of a purified trivalent sub-unit influenza vaccine and a 14-valent pneumococcal vaccine were investigated in a single-blind controlled study involving 69 well-stabilised warfarin recipients. There were no clinically or statistically significant alterations of anticoagulant control in vaccine recipients as compared with controls at 2, 7 and 21 days after vaccination. On the basis of these data, concern about warfarin-vaccine interaction should not deter practitioners from immunising warfarin recipients against influenza or infection with Streptococcus pneumoniae.
Human rabies in the United States, 1960 to 1979: epidemiology, diagnosis, and prevention.
Thirty-eight cases of human rabies occurred in the United States and its territories from 1960 to 1979. The major source of exposure to rabies has changed from indigenous dogs and cats in the 1940s and 1950s to wild carnivores and bats (11 of the 27 cases with known exposures); unusual exposures (3 cases) and exposures in a foreign country (7 cases) have also become more important. No exposure could be identified for 6 of the 38 cases. Two patients received optimal prophylaxis, 14 suboptimal, and 22 no prophylaxis after exposure. Some cases might have been prevented by an increased awareness of the risks and treatment for exposure to rabies, and use of the new rabies vaccines. The diagnosis was often made late in the clinical course including after death in 8 cases. This delay, in part, resulted from the diversity in the clinical presentation. Rabies should be considered in any case of encephalitis or myelitis. Laboratory confirmation of the diagnosis was often delayed. Testing for serum antibodies was the most reliable test in unvaccinated patients, and isolation of virus was the test most likely to be positive early in the illness.
Live influenza vaccines.
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An economical regimen of human diploid cell strain anti-rabies vaccine for post-exposure prophylaxis.
Vaccine regimens using 0.1 ml human diploid cell strain vaccine (HDCSV) given intradermally (id) in single and multiple sites, or with aluminum hydroxide adjuvant given subcutaneously (sc), were compared with the regimens of HDCSV and Semple vaccine currently suggested by WHO. Some groups were also given human rabies-immune globulin (HRIG). Neutralising antibody titres were monitored for 3 months. Antibody was detected earliest in subjects given 0.1 ml HDCSV id at each of eight sites. The highest antibody titres from day 14 onwards were found after intramuscular (im) administration of HDCSV, but the multiple-site id regimen, which requires only one quarter of the volume of vaccine required for the im regimen, gave similar results, provided that a booster was given on day 91. This finding suggests that a treatment schedule based on this regimen would be suitable for post-exposure prophylaxis. Adjuvanted vaccine gave similar results to the same amount of antigen given id. Semple vaccine produced the lowest titres. HRIG, given at the high dose of 40 IU per kg, suppressed the antibody response to some of the regimens.
Stability of human diploid-cell-strain rabies vaccine at high ambient temperatures.
A batch of lyophilised human diploid-cell-strain rabies vaccine was divided into three batches, which were exposed to different temperatures during their distribution to and storage at three centres in Pakistan. Vaccine potency after exposure to these temperatures was tested by measuring antibody response in those given the vaccine, and by three different laboratory tests. The results indicate that the vaccine retains its antigenicity for man and for laboratory tests despite continuous exposure to high ambient temperatures for up to 11 weeks. These findings, together with current developments in vaccine manufacture and treatment schedules, offer considerable hope to many countries with low budgets for health care and where rabies is poorly controlled.
Enzyme-linked immunosorbent assay: a rapid reproducible test for the measurement of rabies antibody.
An enzyme-linked immunosorbent assay (ELISA) was developed for detecting IgG antibodies to the Pitman Moore strain of rabies virus in sera from subjects immunised wih HDCS vaccine. End-point titres of antibody were determined using a pocket calculator preprogrammed to analyse absorbence values of test sera and negative controls. The assay was highly reproducible, and very close agreement was achieved when the results were compared with those of the mouse neutralization test. Rabies enzyme-linked immunosorbent assay is easy to perform, the results are obtained within 48 hours, and because it employs inactivated virus, the test can be used safely without special containment facilities.
Neonatal rotavirus infection: role of lacteal neutralising alpha1-anti-trypsin and nonimmunoglobulin antiviral activity in protection.
Expressed breast milks (EBMs) were collected from mothers of rotavirus (RV)-excreting babies and from mothers whose babies were RV free during an outbreak of asymptomatic RV infection in a newborn nursery to determine the role of lacteal anti-RV neutralising activity, alpha1-anti-trypsin activity, and nonimmunoglobulin antiviral factor in protection of neonates from RV infection, and although all of the above factors were present in the majority of the EBMs, no correlation could be found between their presence in EBM and protection from RV infection. A significant rise in both neutralising activity and subgroup 2 antibodies, was demonstrated in the EBM of one mother who experienced a subgroup 2 RV-associated diarrhoea during lactation. However, the alpha1-anti-trypsin activity and the nonimmunoglobulin antiviral levels remained the same. The importance of these factors in passive immunity with reference to virus dose is discussed.
Evaluation of a human diploid cell strain rabies vaccine: final report of a three year study of pre-exposure immunization.
The antibody responses of 194 volunteers were studied for up to 3 years after primary immunization with one, two or three doses of human diploid cell rabies vaccine, administered either in 0.1 ml volumes intradermally (i.d.) or as 1.0 ml intramuscularly (i.m.). Sero-conversion occurred in 95% of subjects after the first injection and in 100% after the second. The highest titres and most durable antibody responses were induced by three injections of vaccine. Booster doses were administered either by the subcutaneous (s.c.) or i.d. route, after 6, 12 or 24 months to randomly grouped volunteers; these induced responses greater than or equal to 5.0 i.u. per ml in 95% of subjects. The responses were rapid and were neither influenced by the primary regimen nor by the timing and route of the booster dose. Antibody titres after i.d. immunization were only two-fold lower than those induced by the larger volume of vaccine. The findings suggest that the i.d. route is both effective and economic.
Multisite intradermal antirabies vaccination. Immune responses in man and protection of rabbits against death from street virus by postexposure administration of human diploid-cell-strain rabies vaccine.
Lymphocyte transformation, production of neutralising antibody, and the development of antirabies IgG antibody were studied in ten healthy volunteers in response to 0.8 ml of human diploid-cell strain (HDCS) rabies vaccine administered on one occasion in divided doses in 8 intradermal (i.d.) sites. All ten volunteers rapidly developed substantial titres of rabies antibody, and eight of the ten had T lymphocytes that were immunologically stimulated by HDCS rabies-virus antigen. Postexposure treatment with 0.8 ml of HDCS vaccine given at 4 i.d. sites completely protected fourteen rabbits from death by street virus. The results suggest that in developing countries patients could be protected with small volumes of potent tissue-culture vaccine administered intradermally shortly after exposure.
Coincident cytomegalovirus infection and toxoplasmosis in an uncompromised host.
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Enteric inoculation with ERA rabies virus: evaluation of a candidate wildlife vaccine in laboratory rodents.
A series of experiments on the safety and efficacy of enteric vaccination was carried out in laboratory rodents using the ERA strain of rabies virus both live and inactivated. In the first and second experiments in white Norway rats, several methods of inoculation were compared for the development of rabies neutralizing antibody. In later experiments, the potential for disease transmission through salivary excretion of ERA strain, or through scavenging, or cannibalism were evaluated. Enteric inoculation of rats with high doses of live ERA virus often failed to give an antibody response yet would occasionally kill adult animals. Rabies antigen was demonstrable in the trigeminal ganglion and tongue of one of these rats, and 14 of 65 (21.5 percent) adult mice died from rabies after eating infants infected with the ERA strain.