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Biomedical subjects

R F Betts

Publications and source records attributed to R F Betts.

At least 19 recordsLinked to original sources
PubMed2005

A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults.

BACKGROUND: The incidence and severity of herpes zoster and postherpetic neuralgia increase with age in association with a progressive decline in cell-mediated immunity to varicella-zoster virus (VZV). We tested the hypothesis that vaccination against VZV would decrease the incidence, severity, or both of herpes zoster and postherpetic neuralgia among older adults. METHODS: We enrolled 38,546 adults 60 years of age or older in a randomized, double-blind, placebo-controlled trial of an investigational live attenuated Oka/Merck VZV vaccine ("zoster vaccine"). Herpes zoster was diagnosed according to clinical and laboratory criteria. The pain and discomfort associated with herpes zoster were measured repeatedly for six months. The primary end point was the burden of illness due to herpes zoster, a measure affected by the incidence, severity, and duration of the associated pain and discomfort. The secondary end point was the incidence of postherpetic neuralgia. RESULTS: More than 95 percent of the subjects continued in the study to its completion, with a median of 3.12 years of surveillance for herpes zoster. A total of 957 confirmed cases of herpes zoster (315 among vaccine recipients and 642 among placebo recipients) and 107 cases of postherpetic neuralgia (27 among vaccine recipients and 80 among placebo recipients) were included in the efficacy analysis. The use of the zoster vaccine reduced the burden of illness due to herpes zoster by 61.1 percent (P<0.001), reduced the incidence of postherpetic neuralgia by 66.5 percent (P<0.001), and reduced the incidence of herpes zoster by 51.3 percent (P<0.001). Reactions at the injection site were more frequent among vaccine recipients but were generally mild. CONCLUSIONS: The zoster vaccine markedly reduced morbidity from herpes zoster and postherpetic neuralgia among older adults.

Aged↗
PubMed2000

Approaches to improved influenza vaccination.

Inactivated influenza vaccine (Ivac) has had an important impact on reducing attack rates of influenza and reducing the severity of illness amongst the vaccinees who still acquire infection. Ivac is most efficacious amongst young, otherwise healthy subjects and least effective against elderly at high risk. This is in part because Ivac does not appear to significantly reduce infection rates and in part because response rate and final antibody titer are lower in the elderly. Therefore Ivac does not eliminate disease in the elderly who are prone to complications when any virus replication occurs. Simultaneous administration of intra-nasal live attenuated influenza vaccine (Livac) and Ivac reduces the infection rate and thus illness rate amongst high-risk elderly. Presumably this is because of the ability of Livac to stimulate secretory antibody which neutralizes virus at the mucosal surface. Other approaches are examining the benefit of baculovirus recombinant vaccine or adjuvanted Ivac to determine if the higher serum antibody these vaccines produce compared to Ivac, will diffuse onto the mucosal surfaces and in a similar fashion, neutralize virus at that site.

Adolescent↗
PubMed1999

Evaluation of trivalent, live, cold-adapted (CAIV-T) and inactivated (TIV) influenza vaccines in prevention of virus infection and illness following challenge of adults with wild-type influenza A (H1N1), A (H3N2), and B viruses.

Trivalent, live, cold-adapted influenza vaccine (CAIV-T) is highly effective in the prevention of influenza in children, and a variety of monovalent and bivalent cold-adapted influenza vaccines have been efficacious in adults. In order to determine the efficacy of CAIV-T in healthy adults, we administered CAIV-T, trivalent inactivated influenza vaccine (TIV) or placebo to 103 adults in randomized double-blind fashion, and then challenged those subjects who had pre-screening serum hemagglutination-inhibition antibody titers of 1:8 or less with wild-type influenza viruses corresponding to the strains contained in the vaccine. CAIV-T was well tolerated. Upon challenge with wild-type influenza virus, laboratory documented influenza illness (respiratory symptoms with either isolation of wild-type influenza virus from nasal secretions or 4-fold and/or greater HAI antibody response to challenge) occurred in 14/31 (45%) placebo recipients, 4/32 (13%) TIV recipients, and 2/29 (7%) CAIV-T recipients. The estimated protective efficacy of CAIV-T was therefore 85% and of TIV was 71%. These results are consistent with those of previous studies using monovalent preparations of cold-adapted influenza vaccine in this model, and indicate that CAIV-T will be an effective means to prevent influenza illness in adults.

Administration, Intranasal↗
PubMed1999

Use of the oral neuraminidase inhibitor oseltamivir in experimental human influenza: randomized controlled trials for prevention and treatment.

CONTEXT: Influenza virus neuraminidase is thought to be essential for virus replication in humans; however, to date, available neuraminidase inhibitors are limited to zanamivir, which is topically administered. OBJECTIVE: To determine the safety, tolerability, and antiviral activity of oral neuraminidase inhibitor oseltamivir (GS4104/Ro64-0796) for prevention and the early treatment of influenza in experimentally infected humans. DESIGN: Two randomized, double-blind, placebo-controlled trials conducted between June and July 1997. SETTING: Individual hotel rooms; 2 large US university medical schools. PARTICIPANTS: A total of 117 healthy adult volunteers (aged 18-40 years; median age, 21 years) who were susceptible (hemagglutination-inhibition antibody titer < or =1:8). INTERVENTIONS: All subjects were inoculated intranasally with influenza A/Texas/36/91 (H1N1) virus. For the prophylaxis study, oral oseltamivir (100 mg once daily [n = 12], 100 mg twice daily [n = 12], or matching placebo [n = 13], starting 26 hours before virus inoculation) was administered. For the treatment study, the same drug was given (20 mg, 100 mg, or 200 mg twice daily, 200 mg once daily, or matching placebo [n = 16], in each group starting 28 hours after inoculation). All regimens were continued for 5 days. MAIN OUTCOME MEASURES: Comparing placebo groups with pooled treatment groups, for prophylaxis, outcomes included frequency of infection and viral shedding; for treatment, viral shedding in titers. RESULTS: In the prophylaxis study, 8 (67%) of 12 placebo and 8 (38%) of 21 oseltamivir recipients became infected (P = .16; efficacy, 61%); 6 (50%) placebo compared with 0 oseltamivir recipients shed virus (P<.001; efficacy, 100%), and 33% of placebo but no oseltamivir recipient had infection-related respiratory illness (P<.01). Among infected subjects in the treatment study (n = 69), the viral titer area under the curve of the combined oseltamivir groups (n = 56) was lower (median [interquartile range [IQR]], 80 [23-151] vs 273 [79-306] log10 tissue culture-infective doses50 per milliliter x hour; P = .02) than the placebo group (n = 13), and the median (IQR) duration of viral shedding with therapy was reduced from 107 (83-131) to 58 (35-59) hours (P = .003). Oseltamivir treatment also reduced symptom scores (median [IQR] score-hours, 225 [97-349] vs 400 [189-645]; P = .05), and nasal proinflammatory cytokine levels. Transient mild to moderate nausea after dosing was observed in 15 (17%) of 88 oseltamivir and 2 (7%) of 29 placebo recipients (95% confidence interval for difference, -11% to 68%), which was largely prevented by ingestion with food. CONCLUSIONS: In these trials, prophylaxis and early treatment with oral oseltamivir were both associated with significant antiviral and clinical effects in experimental human influenza.

Administration, Oral↗
PubMed1998

Ciprofloxacin plus piperacillin is an equally effective regimen for empiric therapy in febrile neutropenic patients compared with standard therapy.

The purpose of this study was to test the comparative efficacy and toxicity of empiric gentamicin and ciprofloxacin, in combination with piperacillin, in febrile patients with treatment-induced neutropenia. Fifty patients were prospectively randomized to receive piperacillin plus gentamicin (PG), and 46 were randomized to receive piperacillin plus ciprofloxacin (PC). The groups were similar in age, sex, diagnosis, duration of neutropenia, and incidence of positive cultures. The two antibiotic regimens were associated with comparable rates of defervescence in the patients with gram-positive bacteremia. In the patients with gram-negative bacteremia and those with negative cultures, however, defervescence was more prompt in the PC group. In particular, 27% of the culture-negative patients on PC, compared to only 5% of those on PG, defervesced within 72 hr (P = 0.015). Because of the more prompt defervescence in the PC group, amphotericin B was used less frequently; 78% of the patients on PG compared with only 56% of those on PC were started on amphotericin B (P = 0.025). PC is an effective alternative to the more traditional PG for treatment of febrile neutropenic hosts who have not been given prophylactic quinolones. More important, PC appears to hasten defervescence compared with PG, especially in culture-negative patients and those with gram-negative bacteremia, and may decrease the necessity of additional antimicrobial agents such as amphotericin B.

Adult↗
PubMed1998

Evaluation of live, cold-adapted influenza A and B virus vaccines in elderly and high-risk subjects.

We have evaluated the use of live cold-adapted influenza A and B virus vaccines in the elderly. Cold-adapted influenza A and B virus vaccines are safe and modestly immunogenic in individuals over 65 years of age. However, our studies and those of other groups have shown that immune response to cold-adapted vaccines in this age group are modest. Administration of combined cold-adapted influenza A and inactivated influenza vaccine has resulted in slightly higher frequencies of local and systemic humoral immune responses than inactivated vaccine alone in some, but not all, studies. In a double-blind field trial conducted in nursing homes over a 3 year period, combined cold-adapted influenza A (H3N2) and trivalent inactivated influenza vaccine resulted in a 60% decrease (95% CI, 18-82%) in the rate of laboratory documented influenza A compared with inactivated vaccine alone. Further studies of multivalent cold-adapted influenza vaccines used in combination with inactivated vaccine should be performed.

Aged↗
PubMed1998

Mycobacterium bovis osteomyelitis involving a hip arthroplasty after intravesicular bacille Calmette-Guérin for bladder cancer.

Bacille Calmette-Guérin (BCG), an attenuated strain of Mycobacterium bovis, is one of the most effective agents in the treatment of superficial bladder cancer. BCG osteomyelitis is an infrequent complication of intravesicular BCG therapy; only five cases of BCG vertebral osteomyelitis have been reported in the literature. Similarly, the infection of an indwelling extravascular device by BCG is rare; there is only one previous report documenting infection associated with an automated implantable cardiac defibrillator. We report a case of BCG osteomyelitis involving a hip arthroplasty that occurred after intravesicular administration of BCG for bladder cancer, and we review the risk factors predisposing to such infections and their treatment.

Administration, Intravesical↗
PubMed1996

Evaluation of a recombinant hemagglutinin expressed in insect cells as an influenza vaccine in young and elderly adults.

Healthy subjects <45 years old (young adults) or >65 (elderly adults) were randomized in double-blind fashion to receive intramuscularly subvirion trivalent influenza vaccine, placebo, or 15, 45, or 135 microgram of the hemagglutinin (HA) of the influenza A/Beijing/32/92 (H3N2) virus expressed in insect cells by a recombinant baculovirus (rHA0). All vaccines were well tolerated. Both young and elderly adults manifested serum hemagglutination-inhibition, virus neutralizing, and HA-specific IgG ELISA antibody responses to rHA0 vaccine. In young adults given 135 microgram of rHA0, the vaccine was significantly more immunogenic than subvirion influenza vaccine. Elderly adults also had increased antibody responses to 135 microgram of rHA0 compared with subvirion vaccine, but the difference was not statistically significant. These results demonstrate that high-dose rHA0 vaccines are well tolerated and effectively induce both functional and binding serum HA-specific antibody in young and elderly adults.

Adolescent↗
PubMed1996

Recombinant baculovirus influenza A hemagglutinin vaccines are well tolerated and immunogenic in healthy adults.

In a prospective double-blind trial, the reactogenicity and immunogenicity of recombinant baculovirus influenza A vaccines containing purified full-length hemagglutinin (HA) were compared with standard trivalent inactivated vaccine (TIV). The recombinant baculovirus influenza A vaccines (rHA0) were monovalent (containing 45 micrograms of A/Beijing/92[H3] and 15, 45, and 135 micrograms of A/Texas/91[H1]) and bivalent (containing 45 micrograms of both A/Beijing/92 and A/Texas/91). The bivalent rHA0 vaccine produced fewer local side effects than the TIV (50% vs. 88%, P = .003). The hemagglutinin inhibition (HAI) responses (defined as a > or = 4 increase in HAI) to A/Beijing rHA0 in the monovalent A/Beijing/92, the bivalent vaccine, and the TIV were 68%, 76%, and 46%, respectively (P = .086). Increasing doses of A/Texas rHA0 (15 micrograms [60%], 45 micrograms [69%], and 135 micrograms [76%]) and bivalent HA (76%) gave better immunologic responses to H1 than did TIV (31%; P = .003).

Adolescent↗
PubMed1995

Respiratory syncytial virus and influenza A infections in the hospitalized elderly.

Respiratory syncytial virus (RSV) infections in the institutionalized elderly have been described; however, there is little information on the impact of RSV infection on community-dwelling elderly. The purpose of this study was to determine the relative numbers of hospitalizations associated with RSV infection and compare the clinical manifestations with influenza A infection. Between November and April during 1989-1992, persons > or = 65 years old hospitalized with acute cardiopulmonary conditions or influenza-like illnesses were evaluated. Evaluation included viral culture, RSV antigen detection, and serologic analysis; 159 (10%) of 1580 had RSV infection and 221 (11%) of 2091 had influenza A. RSV and influenza A cases occurred simultaneously throughout the 3 years. Clinical manifestations were similar; however, patients with RSV infection were more likely to receive therapy for bronchospasm. Death rates were 10% and 6% for RSV infection and influenza A, respectively. RSV infection is the cause of serious disease in community-dwelling older persons.

Aged↗
PubMed1995

Vaccines in the prevention of viral pneumonia.

Vaccines to control respiratory virus infections have been limited to inactivated whole virus or split virus product of influenza. Over the last few years, advances in the understanding of immunity to and importance of these infections has led to the development of newer, more immunogenic inactivated influenza vaccines and to the exploration of live attenuated influenza vaccines. In parallel, both inactivated and live attenuated vaccines against respiratory syncytial virus and parainfluenza virus have been undergoing evaluation. More effective or new vaccines could reduce morbidity, reduce the frequency of hospitalization, and decrease the death rate. Since viral respiratory disease would be decreased in frequency, vaccines could reduce the use of antibiotics, and by so doing, preserve the usefulness of our currently available antibiotics.

Adolescent↗
PubMed1994

Oral LY217896 for prevention of experimental influenza A virus infection and illness in humans.

The efficacy and safety of oral LY217896 for prevention of experimental influenza A/Kawasaki/86 (H1N1) virus infection were assessed in susceptible males randomly assigned to receive LY217896 (75 mg) or placebo once daily for 7 days beginning 24 h prior to viral challenge. The rates of virus shedding (100% in both groups), days of viral shedding (3.1 +/- 1.3 for the LY217896 group; 2.8 +/- 1.3 for the placebo group), and titers of virus in nasal washings did not differ between the groups. Mild upper respiratory tract illness (72% in the LY217896 group; 69% in the placebo group) developed in similar proportions of each group. LY217896 was associated with asymptomatic rises in serum uric acid levels and was ineffective in modifying the virologic or clinical course of experimental influenza A (H1N1) virus infection.

Adolescent↗
PubMed1994

Effect of simultaneous administration of cold-adapted and wild-type influenza A viruses on experimental wild-type influenza infection in humans.

On the basis of the ability of the attenuated cold-adapted strain of influenza A virus to suppress disease production in ferrets simultaneously infected with epidemic influenza virus (P. Whitaker-Dowling, H.F. Maassab, and J.S. Youngner, J. Infect. Dis. 164:1200-1202, 1991), an evaluation of the ability of the cold-adapted virus to modify clinical disease in humans was made. Adult volunteers with prechallenge serum hemagglutination-inhibition titers to the influenza A/Kawasaki/86 (H1N1) virus of < or = 1:8 received either 10(7) 50% tissue culture infective doses of the wild-type A/Kawasaki virus or a mixture of 10(7) 50% tissue culture infective doses of each of the wild-type virus and a cold-adapted A/Kawasaki reassortant virus by intranasal drops in a randomized, double-blind fashion. Symptoms and wild-type virus shedding were assessed daily for 6 days following challenge. Results were compared with those derived from another group of volunteers who received only cold-adapted virus. Volunteers who received the mixed inoculum of cold-adapted and wild-type viruses had lower symptom scores than those who received wild-type virus alone, suggesting that coinfection with the cold-adapted virus may modify wild-type virus infection, but the differences were not statistically significant in this small study. The data demonstrate that administration of cold-adapted influenza A virus to humans at the time of wild-type virus infection is a safe procedure.

Adaptation, Physiological↗
PubMed1993

Evaluation of live attenuated cold-adapted influenza B/Yamagata/16/88 reassortant virus vaccine in healthy adults.

The safety and immunogenicity of a new cold-adapted reassortant influenza B/Yamagata/10/88 virus vaccine was evaluated in healthy young adults with low levels of preinoculation serum antibody to the vaccine virus, and symptoms and viral shedding after vaccination were compared with those following administration of the homologous B/Yamagata/88 wild-type virus. Administration of the cold-adapted virus was well tolerated and resulted in a significantly lower frequency of respiratory symptoms and viral shedding than did the wild-type virus. Twelve of 14 subjects who received the cold-adapted virus had an antibody response to the vaccine virus following vaccination. These data suggest that the B/Yamagata/88 virus is safe and immunogenic in seronegative adults and support the concept that the attenuation phenotype can be transferred reliably and reproducibly to successive new influenza B wild-type viruses along with the six internal gene segments of the cold-adapted influenza B/Ann Arbor/1/66 master vaccine virus.

Adaptation, Physiological↗
PubMed1993

Acquired immunodeficiency syndrome-related visceral leishmaniasis presenting in a pleural effusion.

Visceral leishmaniasis is increasingly reported in immunocompromised patients, including patients with AIDS. We report a case of visceral leishmaniasis in an AIDS patient who presented with pulmonary symptoms and bilateral pleural effusions. Histologic evaluation of pleural fluid and bone marrow revealed histiocytes with intracellular Leishmania amastigotes. Visceral leishmaniasis should be considered in AIDS patients with a significant travel history who present with unexplained pulmonary symptoms.

AIDS-Related Opportunistic Infections↗
PubMed1992

Protective efficacy of combined live intranasal and inactivated influenza A virus vaccines in the elderly.

OBJECTIVE: To evaluate the efficacy of adding intranasal live attenuated cold-adapted influenza A vaccine to inactivated influenza vaccine to prevent influenza A in elderly residents of long-term-care institutions. DESIGN: Randomized, double-blind, placebo-controlled study conducted over 3 years. SETTING: Three large nursing homes. PARTICIPANTS: A total of 523 residents of nursing homes (mean age, 84.2 years). INTERVENTIONS: All participants received trivalent inactivated influenza vaccine parenterally and were randomly assigned to receive either live attenuated influenza A (H3N2) virus vaccine or placebo intranasally. MEASUREMENTS: Laboratory-documented influenza A was defined as a respiratory illness plus isolation of influenza A virus from nasal secretions, significant serologic response, or both. Participants were considered to have been exposed to influenza A if they resided in an institution in which cases of influenza A were documented. Outbreak-associated illnesses were defined as those occurring between the first and last isolation of influenza virus from within the institution, +/- 3 days. RESULTS: Participants who received intranasal vaccine and were subsequently exposed to influenza A had significantly lower rates of laboratory-documented influenza A (9 of 162 vaccine recipients compared with 24 of 169 placebo recipients; vaccine protective efficacy, 60.6%; 95% CI, 18% to 82%), outbreak-associated respiratory illnesses (13 of 162 vaccine recipients compared with 34 of 169 placebo recipients; vaccine protective efficacy, 56.8%; CI 23% to 76%), and outbreak-associated influenza-like illnesses (6 of 162 vaccine recipients compared with 18 of 169 placebo recipients; vaccine protective efficacy, 65.0%; CI 17% to 86%). CONCLUSIONS: Intranasal immunization with live attenuated influenza A virus vaccine provided additional protection against influenza A when added to parenteral trivalent inactivated influenza vaccine among elderly nursing home residents.

Administration, Intranasal↗