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Biomedical subjects

R F Betts

Publications and source records attributed to R F Betts.

At least 55 records · Page 3Linked to original sources
PubMed1986

Resistance of adults to challenge with influenza A wild-type virus after receiving live or inactivated virus vaccine.

The efficacy of live attenuated cold-adapted (ca) reassortant influenza A H3N2 and H1N1 virus vaccines against experimental challenge with homologous wild-type virus 7 months after vaccination was compared with that of licensed inactivated virus vaccine in 106 seronegative (hemagglutination-inhibiting antibody titer less than or equal to 1:8) college students. The live attenuated virus vaccines induced as much resistance against illness as did the inactivated vaccine. Vaccine efficacy, measured by reduction in febrile or systemic illness in vaccines, compared with that in controls was 100% for ca H3N2 vaccine, 84% for inactivated H3N2 vaccine, 79% for ca H1N1 vaccine, and 67% for inactivated H1N1 vaccine. Less protection was conferred against upper respiratory tract illness; there was 50 and 77% protection in ca and inactivated H3N2 vaccines, respectively, but there was no protection in ca or inactivated H1N1 vaccinees. The duration, but not the magnitude, of H1N1 wild-type virus shedding in both ca and inactivated vaccinees was significantly reduced compared with controls. In contrast, a significant reduction in the duration and magnitude of H3N2 virus shedding was observed in ca vaccinees but not in inactivated vaccines. After wild-type virus challenge, live ca virus vaccinees demonstrated resistance at least as great 7 months postvaccination as did inactivated virus vaccinees. These observations indicate that live virus vaccines may be a satisfactory alternative to inactivated vaccines for healthy persons.

Adult↗
PubMed1986

Evaluation of live avian-human reassortant influenza A H3N2 and H1N1 virus vaccines in seronegative adult volunteers.

An avian-human reassortant influenza A virus deriving its genes coding for the hemagglutinin and neuraminidase from the human influenza A/Washington/897/80 (H3N2) virus and its six "internal" genes from the avian influenza A/Mallard/NY/6750/78 (H2N2) virus (i.e., a six-gene reassortant) was previously shown to be safe, infectious, nontransmissible, and immunogenic as a live virus vaccine in adult humans. Two additional six-gene avian-human reassortant influenza viruses derived from the mating of wild-type human influenza A/California/10/78 (H1N1) and A/Korea/1/82 (H3N2) viruses with the avian influenza A/Mallard/NY/78 virus were evaluated in seronegative (hemagglutination inhibition titer, less than or equal to 1:8) adult volunteers for safety, infectivity, and immunogenicity to determine whether human influenza A viruses can be reproducibly attenuated by the transfer of the six internal genes of the avian influenza A/Mallard/NY/78 virus. The 50% human infectious dose was 10(4.9) 50% tissue culture infectious doses for the H1N1 reassortant virus and 10(5.4) 50% tissue culture infectious doses for the H3N2 reassortant virus. Both reassortants were satisfactorily attenuated with only 5% (H1N1) and 2% (H3N2) of infected vaccines receiving less than 400 50% human infectious doses developing illness. Consistent with this level of attenuation, the magnitude of viral shedding after inoculation was reduced 100-fold (H1N1) to 10,000-fold (H3N2) compared with that produced by wild-type virus. The duration of virus shedding by vaccines was one-third that of controls receiving wild-type virus. At 40 to 100 50% human infectious doses, virus-specific immune responses were seen in 77 to 93% of volunteers. When vaccinees who has received 10(7.5) 50% tissue culture infectious doses of the H3N2 vaccine were experimentally challenged with a homologous wild-type human virus only 2 of 19 (11%) vaccinees became ill compared with 7 of 14 (50%) unvaccinated seronegative controls ( P < 0.025; protective efficacy, 79%). Thus, three different virulent human influenza A viruses have been satisfactorily attenuated by the acquisition of the six internal genes of the avian influenza A/Mallard/NY/78 virus. The observation that this donor virus can reproducibly attenuate human influenza A viruses indicates that avian-human influenza A reassortants should be further studied as potential live influenza A virus vaccines.

Adult↗
PubMed1986

Serum and nasal wash antibodies associated with resistance to experimental challenge with influenza A wild-type virus.

To identify immunological predictors of resistance to influenza A infection and illness, the immunological status of live and inactivated virus vaccines subsequently challenged with H1N1 or H3N2 wild-type virus was examined. We refer to prechallenge antibodies of vaccinees receiving live attenuated virus as infection induced and those receiving inactivated virus as inactivated vaccine induced. Inactivated vaccine-induced protection against wild-type virus infection or illness correlated with the level of neuraminidase-inhibiting antibody in serum, local hemagglutinin immunoglobulin G (IgG) (but not IgA) enzyme-linked immunosorbent assay antibody, and hemagglutination-inhibiting antibody in serum. In contrast, infection-induced resistance to wild-type virus infection correlated with local hemagglutinin IgA antibody and neuraminidase-inhibiting antibody in serum, but not with hemagglutination-inhibiting antibody in serum. These observations suggest that live vaccine virus infection-induced and inactivated vaccine-induced immunity may involve different compartments of the immune system; sufficient antibody in either serum or nasal secretions is capable of conferring resistance.

Antibodies, Viral↗
PubMed1985

Serological diagnosis of influenza A/USSR/77 H1N1 infection: value of ELISA compared to other antibody techniques.

Serologic diagnosis of influenza is an important but imperfect tool. During an outbreak of natural H1N1 A/USSR/77 infection, volunteers who received either amantadine, rimantadine, or placebo were tested to determine serologic response to infection by four different antibody techniques. Hemagglutination inhibition (HAI) and complement fixation (CF) were least sensitive, detecting only about half of the virus-positive subjects, whereas neutralization detected 81% and enzyme-linked immune peroxidase (ELISA) detected 95%. Failure to detect significant antibody response was associated with a higher titer of antibody in acute serum specimens and with a history of receipt of A/New Jersey/76 Hsw1N1 vaccine. Although antibody response measured by ELISA was of lower magnitude in vaccinees, it still was sufficient to be diagnostic. Thus, in situations where there is no access to viral isolation facilities, ELISA antibody techniques appear to be an excellent measure of assessing the rate of influenza infection.

Adolescent↗
PubMed1985

New observations regarding killing of fibroblasts infected with herpes simplex virus: cooperation between elutable factor and peripheral mononuclear cells.

With a standard chromium release assay, natural killing (NK) activity of peripheral mononuclear cells (PMCs) from 28 individuals was compared based on the ability of sera to support antibody-dependent cell-mediated cytotoxicity (ADCC) for cells infected with herpes simplex virus (HSV). PMCs from all 20 individuals whose sera produced ADCC were capable of killing HSV-infected cells compared with none of the PMCs from the eight individuals whose sera did not produce ADCC (mean specific release, 33.2% vs. 6.8%). Results could not be explained by contaminating serum in the assay or by ineffective NK by the PMCs from the eight negative subjects because many of them killed the k562 myeloid cell line as effectively as PMCs from other individuals. In addition, NK could be eliminated by preincubation of effector cells at 37 C, and the capacity to kill by PMCs could be reconstituted by incubation in serum. Killing was more a function of source of serum rather than source of cells.

Adult↗
PubMed1985

Multicenter seroepidemiologic study of the impact of cytomegalovirus infection on renal transplantation.

The effects of cytomegalovirus (CMV) infection on patient and allograft survival were determined in 1245 renal transplant recipients from 46 transplant centers. When an antilymphocyte preparation was administered to cadaveric allograft recipients, those at risk for primary CMV had a worse outcome than similar patients treated with prednisone and azathioprine (53.1% alive at 6 months with a functioning allograft vs. 70.8%, P = .05) or patients at risk for reactivation CMV (53.1% vs. 71.1%, P = .035). Patients at risk for reactivation CMV had a better outcome if they received an antilymphocyte preparation (71.1% vs. 60.8%, P less than .01). The type of immunosuppression had no effect on patients without CMV. Living-related donor transplantation was not significantly influenced by CMV or type of immunosuppression. We conclude that CMV infection is strongly influenced by the form of immunosuppression employed, and that both are important determinants of the outcome of cadaveric renal transplantation.

Age Factors↗
PubMed1984

Advantage of live attenuated cold-adapted influenza A virus over inactivated vaccine for A/Washington/80 (H3N2) wild-type virus infection.

The efficacy of live attenuated cold-adapted (ca) reassortant influenza virus vaccine against experimental challenge with homologous wild-type virus 5 to 8 weeks after vaccination was compared with that of licensed inactivated vaccine in 81 seronegative (haemagglutination-inhibition antibody titre less than or equal to 1:8) college students. At a dose of 10(7.5) 50% tissue culture infectious dose (TCID50) (70 HID50, human 50% infectious doses) the live virus vaccine, given intranasally, completely protected against illness caused by wild-type virus, whereas the inactivated vaccine, administered intramuscularly, provided 72% protection. Wild-type virus was recovered from only 13% of live virus vaccinees (10(7.5) TCID50 dose of ca virus) compared with 63% of inactivated virus vaccinees and the few infected live virus vaccinees shed 1000 times less wild-type virus than did infected inactivated virus vaccinees or unvaccinated controls. This striking reduction in virus shedding suggests that influenza transmission may be more efficiently interrupted with live than with inactivated virus vaccination.

Administration, Intranasal↗
PubMed1984

Etiological diagnosis of influenza A virus by enzymatic radioimmunoassay.

An enzymatic radioimmunoassay for influenza A virus was developed by using polystyrene beads coated with rabbit immunoglobulin G to capture viral hemagglutinins (H1 and H3). Captured hemagglutinin was detected with goat immunoglobulin G followed by affinity-purified rabbit anti-goat immunoglobulin G labeled with alkaline phosphatase. [3H]AMP was added to quantify alkaline phosphatase activity, and free [3H]adenosine was measured with a scintillation counter. The assay detected as little as 0.1 ng of purified hemagglutinin. It was specific for hemagglutinin subtype and, depending on the source of the goat immunoglobulin G used, detected either H1 or H3. There was no reaction with neuraminidase or core antigens of influenza strain WSN-33. The clinical efficacy of the assay was evaluated with sequential nasal washes from 33 patients with naturally acquired H1N1 influenza. In the first 3 days of infection, the assay was consistently less sensitive than the viral culture, although detectable antigen persisted in secretions longer than did the infectious virus. Testing of multiple samples greatly increased the number of individuals in whom an etiological diagnosis could be made by immunoassay (81% of patients were positive for viral antigens at some point in their illness), and such testing was necessary to achieve the sensitivity of a single culture. Mean antigen levels were highest in nasal washes with the highest titers of infectious virus.

Animals↗
PubMed1984

Five-year surveillance of aminoglycoside usage in a university hospital.

Because an increased incidence of nosocomial bacteremia due to gentamicin-resistant organisms occurred in our hospital, amikacin was substituted for gentamicin as the primary empiric aminoglycoside. Prospective surveillance of aminoglycoside use and of bacterial resistance to aminoglycosides was done before and after the substitution. We compared the baseline period when gentamicin was the primary aminoglycoside with the subsequent period when amikacin accounted for 81% of aminoglycoside used. During the two periods the patient population did not differ with regard to indications for aminoglycoside therapy. Among the gram-negative organisms isolated, rates of amikacin resistance during the baseline (1.1%) and usage (1.05%) periods were not significantly different (p greater than 0.6). Resistance to gentamicin and tobramycin during the period of amikacin use showed a statistically significant decrease (p greater than 0.001) due to decreased resistance to gentamicin of Providencia, Serratia, indole-positive Proteus, and decreased resistance to tobramycin of Pseudomonas aeruginosa. Unrestricted use of amikacin does not necessarily lead to increase in amikacin resistance but may lead to a decrease in resistance to gentamicin and tobramycin among gram-negative organisms.

Amikacin↗
PubMed1983

Ribavirin treatment of experimental respiratory syncytial viral infection. A controlled double-blind study in young adults.

The effect of ribavirin aerosol on experimental respiratory syncytial virus (RSV) infection was evaluated in a double-blind controlled study of 16 young adult volunteers. Two days after intranasal inoculation with RSV, half of the subjects were treated with a small-particle aerosol of ribavirin and half with placebo for a total of 12 hours each day for three days. Seven of eight placebo-treated and six of eight ribavirin-treated subjects became infected. Viral shedding was diminished in the ribavirin-treated group. The proportion of infected volunteers still shedding virus on days 6 through 9 was significantly less than in the placebo-treated group. Ribavirin appeared to have no effect on minor upper respiratory tract signs, but systemic complaints and fever occurred significantly less often in the ribavirin-treated group. Ribavirin aerosol therapy was well tolerated and produced no significant changes in pulmonary function test results or signs of toxicity. This suggests that such therapy might be further evaluated in infants with RSV lower respiratory tract disease.

Adult↗
PubMed1983

Reduction in fever and symptoms in young adults with influenza A/Brazil/78 H1N1 infection after treatment with aspirin or amantadine.

During an outbreak of influenza A/Brazil/78 H1N1 infection, 47 volunteers with clinical and virological influenza of less than 2 days duration were treated in a randomized double-blind fashion for 5 days with 100 or 200 mg of amantadine daily or with 3.25 g of aspirin daily. The aspirin treatment group defervesced more rapidly (10.3 h versus 21.5 h and 23.6 h; P less than 0.01), but by the second daily follow-up visit, both groups of amantadine recipients exhibited greater symptomatic improvement. Bothersome side effects resulted in discontinuation of therapy by 35% of the aspirin treatment group but only 3% of the amantadine treatment group (P less than 0.05). Individuals who present to a physician during an influenza A epidemic with characteristic symptoms will experience symptomatic benefit from amantadine treatment, with negligible toxicity.

Adolescent↗
PubMed1982

Neutralization and sensitization of cytomegalovirus by IgG antibody, anti-IgG antibody, and complement.

Human cytomegalovirus (CMV) strain Ad 169 was reacted with IgG antibody obtained from infected renal transplant patients, and the degree of neutralization was determined. The mixture of antibody and virus was then incubated with anti-human IgG (A-IgG) or complement (C) to measure additional neutralization by these agents and thus to estimate the concentration of infectious virus-antibody complexes which had been formed. Neutralization and formation of infectious complexes susceptible to neutralization by A-IgG or C decreased with lower concentrations of antibody. The rate of neutralization of preformed complexes by A-IgG or C was more rapid than the formation of complexes or the neutralization of native virus. If equally infectious suspensions of native virus and virus plus antibody were challenged with additional CMV antibody both solutions were neutralized to the same degree. The data are most compatible with the suggestion that the formation of infectious virus-antibody complexes is the initial step in the neutralization process. These complexes do not appear to be protected from further neutralization.

Antibodies, Anti-Idiotypic↗