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Biomedical subjects

F G Hayden

Publications and source records attributed to F G Hayden.

At least 55 records · Page 3Linked to original sources
PubMed1998

The efficacy of live attenuated, cold-adapted, trivalent, intranasal influenzavirus vaccine in children.

BACKGROUND: Influenzavirus vaccine is used infrequently in healthy children, even though the rates of influenza in this group are high. We conducted a multicenter, double-blind, placebo-controlled trial of a live attenuated, cold-adapted, trivalent influenzavirus vaccine in children 15 to 71 months old. METHODS: Two hundred eighty-eight children were assigned to receive one dose of vaccine or placebo given by intranasal spray, and 1314 were assigned to receive two doses approximately 60 days apart. The strains included in the vaccine were antigenically equivalent to those in the inactivated influenzavirus vaccine in use at the time. The subjects were monitored with viral cultures for influenza during the subsequent influenza season. A case of influenza was defined as an illness associated with the isolation of wild-type influenzavirus from respiratory secretions. RESULTS: The intranasal vaccine was accepted and well tolerated. Among children who were initially seronegative, antibody titers increased by a factor of four in 61 to 96 percent, depending on the influenza strain. Culture-positive influenza was significantly less common in the vaccine group (14 cases among 1070 subjects) than the placebo group (95 cases among 532 subjects). The vaccine efficacy was 93 percent (95 percent confidence interval, 88 to 96 percent) against culture-confirmed influenza. Both the one-dose regimen (89 percent efficacy) and the two-dose regimen (94 percent efficacy) were efficacious, and the vaccine was efficacious against both strains of influenza circulating in 1996-1997, A(H3N2) and B. The vaccinated children had significantly fewer febrile illnesses, including 30 percent fewer episodes of febrile otitis media (95 percent confidence interval, 18 to 45 percent; P<0.001). CONCLUSIONS: A live attenuated, cold-adapted influenzavirus vaccine was safe, immunogenic, and effective against influenza A(H3N2) and B in healthy children.

Administration, Intranasal↗
PubMed1998

Local and systemic cytokine responses during experimental human influenza A virus infection. Relation to symptom formation and host defense.

To further understand the role of cytokine responses in symptom formation and host defenses in influenza infection, we determined the levels of IL-1beta, IL-2, IL-6, IL-8, IFN-alpha, TGF-beta, and TNF-alpha in nasal lavage fluid, plasma, and serum obtained serially from 19 volunteers experimentally infected with influenza A/Texas/36/91 (H1N1) and correlated these levels with various measures of infection and illness severity. We found that IL-6 and IFN-alpha levels in nasal lavage fluids peaked early (day 2) and correlated directly with viral titers, temperature, mucus production, and symptom scores. IL-6 elevations were also found in the circulation at this time point. In contrast, TNF-alpha responses peaked later (day 3 in plasma, day 4 in nasal fluids), when viral shedding and symptoms were subsiding. Similarly, IL-8 peaked late in the illness course (days 4-6) and correlated only with lower respiratory symptoms, which also occurred late. None of IL-1beta, IL-2, or TGF-beta levels increased significantly. These data implicate IL-6 and IFN-alpha as key factors both in symptom formation and host defense in influenza.

Cytokines↗
PubMed1998

Polymerase chain reaction-based detection of rhinovirus, respiratory syncytial virus, and coronavirus in otitis media with effusion.

OBJECTIVES: To study the association of human rhinovirus (HRV), respiratory syncytial virus (RSV), and human coronavirus infections in children aged 6 months to 12 years with otitis media with effusion (OME). To determine how long HRV RNA can be detected after HRV infection. METHODS: Middle ear effusion (MEE) samples collected at the time of tympanostomy tube placement from 100 children with OME were examined. Viral RNA was detected by reverse-transcriptase polymerase chain reaction. For HRV the results were compared with virus isolation in cell culture. In vitro studies of the persistence of HRV infectivity and RNA were conducted by combining approximately 10(5) median cell culture infectious doses of HRV with pooled MEE at 37 degrees C and assaying serial samples for 12 weeks. RESULTS: Virus RNA was detected in 30 children. HRV was detected by reverse-transcriptase polymerase chain reaction in 19 children with OME and by virus isolation in 5 children. RSV RNA was found in 8 and HCV in 3 children with OME. No dual viral infection was found. Bacterial pathogens were isolated from 35 MEE samples and were associated with viral RNA in 11 cases, most often with HRV (9 cases). Under in vitro conditions, HRV culture positivity declined rapidly (<2 days), but RNA was detectable for up to 8 weeks. CONCLUSIONS: These results suggest that virus infection, particularly HRV infection, either alone or concurrent with bacteria, is present in a larger percentage of children with OME than previously suspected. It remains to be determined how often the presence of viral RNA in MEE represents persistent RNA, ongoing viral replication, or recurrent infection.

Bacterial Infections↗
PubMed1998

Emergence of drug resistance during an influenza epidemic: insights from a mathematical model.

A model was developed for the emergence of drug-resistant influenza viruses during a closed population influenza epidemic that occurs in a single wave. The model was used to consider several treatment and chemoprophylaxis strategies and to determine their effects on the spread of the infection. The model predicts frequent emergence and transmission of drug-resistant viruses with certain treatment scenarios. According to the model, chemoprophylaxis of susceptible persons (without treatment of those who are symptomatic) may be the best way to reduce the force of an epidemic and to keep development of drug resistance low. The model predictions indicate that the relative transmissibility of resistant variants compared with wild type virus and the choice of the treatment or chemoprophylaxis strategy can be decisive for the spread of drug-resistant viruses, a feature that may be crucial in a pandemic.

Amantadine↗
PubMed1998

Effect of rimantadine treatment on clinical manifestations and otologic complications in adults experimentally infected with influenza A (H1N1) virus.

Susceptible adults (n = 105) were enrolled into a randomized double-blind study of rimantadine treatment of experimental influenza A infection. Subjects were cloistered for 8 days and challenged with a rimantadine-sensitive strain of influenza A H1N1 virus at the end of the first day. Forty-eight hours after challenge and for 8 days, 54 subjects received placebo and 51 received rimantadine (100 mg orally, twice a day). Symptoms, signs, and pathophysiologies were monitored. Nine subjects were not infected. Seventeen subjects (38%) in the rimantadine and 26 (53%) in the placebo group became ill. A beneficial effect of rimantadine was documented for virus shedding, symptom load, and sinus pain. Rimantadine had no effect on nasal patency, mucociliary clearance, nasal signs, or on symptoms and signs of otologic complications. These results do not support a preventive effect of rimantadine on the development of otologic manifestations of influenza A infection in adults.

Adolescent↗
PubMed1998

A dose response study of hepatitis A vaccine in healthy adults who are > or = 30 years old and weigh > or = 77 kg.

The dose response relationship of 25-, 50-, and 100-U doses of an inactivated hepatitis A vaccine was examined in 358-seronegative volunteers in a 2-dose schedule. The 50-U and 100-U groups had statistically significantly higher seroconversion rates than the 25-U group at weeks 2, 4, 8, and 24. Seroconversion was statistically significantly greater for the 100-U compared with the 25- and 50-U doses 2 weeks after the first injection but was not significantly different by 4 weeks after the first injection in the 50- and 100-U dose groups. After 2 injections, all subjects in all groups seroconverted. The vaccine was well tolerated at all dosage levels.

Adult↗
PubMed1998

Increased interleukin-6 levels in nasal lavage samples following experimental influenza A virus infection.

Interleukin-6 (IL-6) is a pleotropic cytokine implicated in the pathogenesis of local inflammation during viral upper respiratory infections. This study determined if experimental influenza A virus infection causes local IL-6 production. Seventeen healthy, adult subjects were intranasally inoculated, by course drops, with a safety-tested strain of influenza A/Kawasaki/86 (H1N1) virus. Nasal lavage samples were collected, symptoms were recorded, and expelled nasal secretions were weighed once before and then daily for 8 days after the virus inoculation. Lavage samples were submitted for virus culture and were examined for IL-6 and IL-4 by enzyme-linked immunosorbent assay. The IL-6, but not IL-4, levels were significantly increased in the nasal lavage samples of the 12 subjects who shed virus but not in those of the 5 subjects who did not shed virus. Moreover, the elevations in IL-6 levels were related temporally to the development of nasal symptoms and secretions but not to systemic symptoms. These results suggest a role for locally produced IL-6 in the pathogenesis and expressed symptomatology of influenza A virus infection.

Adult↗
PubMed1998

Detection of rhinovirus, respiratory syncytial virus, and coronavirus infections in acute otitis media by reverse transcriptase polymerase chain reaction.

OBJECTIVE: To determine the frequencies of human rhinovirus (HRV), respiratory syncytial virus (RSV), and coronavirus (HCV) infection in children with acute otitis media (AOM). METHODS: Middle ear fluids (MEF) collected by tympanocentesis and nasopharyngeal aspirates (NPA) at the time of the AOM diagnosis were examined by reverse transcriptase polymerase chain reaction for HRV, RSV, and HCV RNA. PATIENTS: Ninety-two children aged 3 months to 7 years during a 1-year period. RESULTS: Virus RNA was detected in a total of 69 children (75%) and in 44 MEF samples (48%) and 57 NPA samples (62%) at the time of AOM diagnosis. HRV RNA was detected in both MEF and NPA in 18 (20%), in MEF alone in 4 (4%), and in NPA alone in 10 (11%). RSV was detected in both MEF and NPA in 12 (13%), in MEF alone in 5 (5%), and in NPA alone in 9 (10%). HCV RNA was detected in both MEF and NPA in 5 (5%), in MEF alone in 2 (2%), and in NPA alone in 9 (10%). Dual viral infections were detected in 5% of children. HRV and RSV were detected simultaneously in 2 MEF samples and in 2 NPA samples; RSV and HCV were detected in 1 NPA sample. Bacterial pathogens were detected in 56 (62%) MEF from 91 children. Viral RNA was detected in 20 (57%) MEF of 35 bacteria-negative and in 25 (45%) of 56 bacteria-positive MEF samples. No important differences in the risk of treatment failure, relapse, or occurrence of late secretory otitis media were noted between children with virus-positive and virus-negative MEF aspirates. CONCLUSION: These findings highlight the importance of common respiratory viruses, particularly HRV and RSV, in predisposing to and causing AOM in young children.

Acute Disease↗
PubMed1998

New approaches to influenza chemotherapy. Neuraminidase inhibitors.

Epidemic influenza continues to be associated with significant morbidity in the general population, and mortality in the elderly and other high risk patients. Although the case fatality rate averages less than 0.01%, tens of thousands of deaths occur each year. Control through immunisation programmes has not been possible due to incomplete protective efficacy and antigenic variations that occur frequently. Currently available anti-influenza medications (amantadine and rimantadine) have had limited success due to underutilisation, lack of activity against influenza B, the rapid development of viral resistance to the drugs, and adverse effects. A new class of antiviral agents designed to inhibit influenza neuraminidase, an important surface glycoprotein, is currently under active development for use in the prophylaxis and treatment of influenza A and B infections. Two of these compounds, zanamivir (GG167) and GS4104 (the ethyl ester prodrug of GS4071) have reached clinical trials. Most studies of zanamivir have involved topical administration by inhalation of dry powder aerosols and/or intranasal doses of aqueous solutions. These routes rapidly provide high local concentrations at the sites of delivery. GS4104 is administered orally, which allows for greater ease of administration, and probably more uniform distribution of the parent compound GS4071 in the respiratory tract. Both have shown potent inhibitory activity against influenza in animal models and experimental human influenza with excellent tolerability profiles. Zanamivir treatment has been shown to reduce the severity and duration of naturally occurring, uncomplicated influenza illness in adults. Clinical resistance to these drugs has not been recognised as a significant problem to date, although strains resistant to each agent have been produced in the laboratory. This class of agents shows considerable promise as a novel approach to prophylaxis and treatment of influenza infections. Ongoing studies should provide the data needed to allow the addition of 1 or more of the neuraminidase inhibitors to the clinician's anti-influenza armamentarium.

Acetamides↗
PubMed1998

Rhinoviruses: important respiratory pathogens.

The most frequent viruses associated with respiratory infections are human rhinoviruses (HRVs). Although the majority of HRV infections are mild and self-limited, HRV is an important cause of respiratory disease across all age groups. Recent studies using reverse transcriptase polymerase chain reaction to detect HRV genomes have established the importance of HRVs in predisposing to or causing otitis media, sinusitis and exacerbations of asthma, as well as other lower respiratory tract disorders. Among elderly people, infants and immunocompromised hosts HRV infections are often associated with lower respiratory tract morbidity and rarely mortality. How often active viral replication occurs in the middle ear, sinuses or the lower respiratory tract remains to be determined. However, the high incidence of HRV infections and their frequent association with upper and lower respiratory tract complications highlight the need for more effective means of prevention and treatment.

Adult↗
PubMed1998

Safety of influenza vaccine in heart transplant recipients.

BACKGROUND: Influenza vaccine is recommended for heart transplant recipients, but its administration is often deferred because of anecdotal reports of rejection associated with the vaccine. We evaluated the safety of influenza vaccine in a group of stable heart transplant recipients over a 2-year period. METHODS: During the 1993 to 1994 influenza season, stable heart transplant recipients who had undergone transplantation a minimum of 1 year before study entry were randomized to vaccination with a single dose of influenza vaccine versus no vaccination. Routine endomyocardial biopsies and postvaccination influenza serologic studies were performed between 2 and 6 weeks after enrollment/immunization. During the 1994 to 1995 season, patients were given 2 doses of influenza vaccine, separated by 3 weeks; endomyocardial biopsies and serologic studies were performed between 2 and 6 weeks after the second immunization or enrollment (if control subject). Biopsy results were evaluated with respect to vaccine response, immunosuppressive regimens, and patient demographics. RESULTS: Eighteen patients were enrolled in the single vaccine trial and 10 in the booster vaccine trial. Four of 14 vaccine recipients had biopsy specimens consistent with International Society for Heart and Lung Transplantation grades 2 to 3A as compared with 1 of 14 control subjects (grade 2) (p = .326). All episodes of rejection in the vaccine recipients were asymptomatic and responded to a single course of treatment. Rejection was unrelated to the time from transplantation, doses of immunosuppression, age, or number of doses of or response to vaccine. CONCLUSIONS: Influenza vaccine can be safely administered to most heart transplant recipients but may be associated with low-level histologic rejection.

Adult↗
PubMed1997

Efficacy and safety of the neuraminidase inhibitor zanamivir in the treatment of influenzavirus infections. GG167 Influenza Study Group.

BACKGROUND: The sialic acid analogue zanamivir (GG167) is a selective inhibitor of influenza A and B virus neuraminidases. These viral enzymes are essential for the release of virus from infected cells, and they may also reduce the inactivation of virus by respiratory secretions. When administered experimentally directly to the respiratory tract, zanamivir has potent antiviral effects. We assessed the therapeutic activity of zanamivir in adults with acute influenza. METHODS: We conducted separate randomized, double-blind studies in 38 centers in North America and 32 centers in Europe during the influenza season of 1994-1995. A total of 417 adults with influenza-like illness of < or =48 hours' duration were randomly assigned to one of three treatments: 6.4 mg of zanamivir by intranasal spray plus 10 mg by inhalation, 10 mg of zanamivir by inhalation plus placebo spray, or placebo by both routes. Treatments were self-administered twice daily for five days. RESULTS: Of 262 patients with confirmed influenza-virus infection (63 percent of all patients), the median length of time to the alleviation of all major symptoms was one day shorter (four days vs. five days) in the 88 patients given inhaled and intranasal zanamivir (P=0.02) and the 85 patients given inhaled zanamivir alone (P=0.05) than in the 89 patients given placebo. Among the infected patients who were febrile at enrollment and among those who began treatment within 30 hours after the onset of symptoms, the median time to the alleviation of major symptoms was four days in both zanamivir groups and seven days in the placebo group (P< or =0.01). Viral titers of nasal washings in the group given inhaled and intranasal zanamivir were significantly lower than those in the placebo group. The topically administered zanamivir was well tolerated. CONCLUSIONS: In adults with influenza A or B virus infections, direct administration of a selective neuraminidase inhibitor, zanamivir, to the respiratory tract is safe and reduces symptoms if begun early.

Administration, Inhalation↗
PubMed1997

Prevention and treatment of influenza in immunocompromised patients.

Influenza A and B viruses cause serious, sometimes fatal, disease in immunocompromised patients, particularly bone marrow and solid organ transplant recipients. Protracted disease has also been recognized in certain oncology and HIV-infected patients. Currently available inactivated vaccines are variably immunogenic in such groups. Poor humoral immune responses are seen within 2 years of bone marrow transplantation, often following solid organ transplantation, and commonly in patients with advanced HIV infection. Oral amantadine and rimantadine are useful for prophylaxis and treatment of influenza A virus infections, but their efficacy, particularly in treatment of severe disease, has not been rigorously established in immunocompromised hosts. Case reports document the emergence of drug-resistant variants and prolonged viral shedding in some patients. Aerosol and intravenous ribavirin has been used to treat severe influenza in small numbers of immunosuppressed patients, but the efficacy of ribavirin by either route has not been established in such patients. The neuraminidase inhibitor GG167 is active in experimental influenza but requires topical application to the respiratory tract and has had limited clinical study in natural influenza. More effective interventions for serious influenza infections will likely require combinations of antiviral drugs.

AIDS-Related Opportunistic Infections↗
PubMed1997

Effects of the neuraminidase inhibitor zanamavir on otologic manifestations of experimental human influenza.

Middle ear pressure (MEP) abnormalities are frequently observed during influenza virus infection and may serve as surrogate markers for the risk of otitis media. MEP abnormalities were evaluated in adult volunteers who were inoculated with influenza A/Texas/36/91(H1N1) or B/Yamagata/88 virus and given the antiviral zanamivir (GG167) intranasally as prophylaxis or early treatment in randomized, double-blind, placebo-controlled trials. In the influenza A prophylaxis studies, 15% of 61 zanamivir recipients versus 61% of 33 placebo recipients showed significant MEP abnormalities (P < .01). In the influenza A early treatment trial, 32% of 31 infected zanamivir recipients versus 73% of 26 infected placebo recipients developed MEP abnormalities (P < .01). In the influenza B prophylaxis trial, 16% of 25 zanamivir versus 44% of 9 placebo recipients showed abnormalities (P = .09). These findings indicate that the neuraminidase inhibitor zanamivir, which is effective in reducing experimental influenza illness, provides protection against the development of MEP abnormalities.

Administration, Intranasal↗
PubMed1997

Antivirals for pandemic influenza.

Amantadine and rimantadine share features that would make them useful agents in responding to pandemic influenza. These include an antiviral spectrum encompassing influenza A viruses, favorable pharmacokinetics, a potential for stockpiling supplies, and documented prophylactic and therapeutic effectiveness in pandemic influenza. However, current production capability is insufficient to provide adequate drug for mass chemoprophylaxis in the event of vaccine unavailability. The risk of adverse drug effects, particularly central nervous system side effects, which occur more often with amantadine than rimantadine, and potential drug interactions are additional concerns. Short-course treatment of ill persons would provide symptom benefit, but convincing evidence that early antiviral treatment reduces bacterial and other influenza complications is currently lacking. Drug-resistant viruses emerge during therapy, appear to be fully pathogenic, and are transmissible to close contacts. Influenza neuraminidase inhibitors are promising investigational agents, but remaining issues include prophylactic efficacy, cost, efficient administration, and resistance emergence.

Amantadine↗
PubMed1997

Epidemiologic evidence for Lancefield group C beta-hemolytic streptococci as a cause of exudative pharyngitis in college students.

The isolation rates of strains of group C beta-hemolytic streptococci from throat swab cultures of patients with exudative pharyngitis, the common cold, and healthy controls were compared. By using a cohort study design in a college health service, patients with exudative pharyngitis were retrospectively identified by description of tonsillar exudate on chart review. Patients with rhinoviral infection were prospectively identified during a common cold study. Healthy controls were prospectively recruited from patients presenting with noninfectious conditions. Isolation of Lancefield group A and C beta-hemolytic streptococci from throat cultures was used as an outcome measurement. A total of 265 students (62% female; average age 20.2 years) with exudative pharyngitis were identified. A total of 75 students (60% female; average age, 21.7 years) from a common cold study with rhinoviral infection were identified. A total of 162 students (53% female; average age, 22.6 years) were recruited as healthy controls. Group A beta-hemolytic streptococci were isolated from 5% of patients with pharyngitis but none of those with rhinovirus (P = 0.045) and none of the controls (P = 0.007). Group C Streptococcus dysglactiae subsp. equisimilis was isolated from 11% of patients with pharyngitis but none of those with rhinovirus (P = 0.006) and 2% of controls (P = 0.001). Lancefield group C Streptococcus anginosus was isolated from 8% of patients with pharyngitis but 3% of those with rhinovirus (P = 0.18) and 1% of controls (P = 0.006). Heavier growth of colonies on the primary culture plate was observed for patients from whom S. equisimilis and group A beta-hemolytic streptococci were isolated. Lancefield group C beta-hemolytic streptococci appear to be associated with exudative pharyngitis in college students.

Adult↗