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Biomedical subjects

R B Couch

Publications and source records attributed to R B Couch.

At least 19 recordsLinked to original sources

Age distribution of patients with medically-attended illnesses caused by sequential variants of influenza A/H1N1: comparison to age-specific infection rates, 1978-1989.

Since influenza A/H1N1 viruses reappeared during the 1977-1978 season, this subtype has contributed 27% of 6,609 documented influenza infections of persons with acute respiratory disease presenting to clinics serving as surveillance sites of the Influenza Research Center in Houston for the 12-year period ending June 1989. Wide differences in the distribution of H1N1 viruses occurred by age group: more than 50% of H1N1 infections were detected among persons aged 10-34 years, compared with 28% for influenza A/H3N2 and 35% for influenza B. Over age 35 years, the contribution of H1N1 viruses dropped to only 4%, compared with 20% and 16% for influenza A/H3N2 and influenza B, respectively. When birth dates of persons with positive cultures were examined, it was found that most of the H1N1-positive persons were born after 1950. Concurrently, longitudinal studies of families and other adults under intensive surveillance for infection, including cultures of all respiratory illnesses and tests for serum antibody rise over the respiratory disease season, revealed appreciable infection rates for adults born before 1950. Furthermore, the annual peak of hospitalization of older persons with pneumonia and other acute respiratory illnesses was significantly correlated with the peak of H1N1 virus activity in 1978-1979, a year when H1N1 viruses were the only influenza viruses prevalent. These observations indicate that many persons infected with influenza A/H1N1 viruses that circulated from 1946 through 1953 have immunity which has persisted for more than 25 years but this immunity is not complete. Reinfection that may result in serious illness in older vulnerable adults does occur but with lower frequency than with influenza A/H3N2 infection. Currently prevalent H1N1 variants are antigenically different from those that circulated in the 1950s; however, older adults readily acquire immunity to these new variants--perhaps as a result of immunologic priming that occurred in childhood.

Acute Disease

Comparison of heterotypic protection against influenza A/Taiwan/86 (H1N1) by attenuated and inactivated vaccines to A/Chile/83-like viruses.

Children (n = 192) aged 3-19 years from 98 families completed this double-blind, placebo-controlled study comparing the efficacy of a bivalent attenuated (CR) vaccine with trivalent inactivated (TI) vaccine. Both vaccines contained A/Chile/83 (H1N1)-like antigens. After vaccination the geometric mean titer to A/Taiwan/86 (H1N1) was 1:36 in the CR group, 1:92 in the TI group, and 1:5 in the placebo group. During the influenza A/Taiwan/86 (H1N1) epidemic, 21.4% of CR recipients, 16.7% of TI recipients, and 43.9% of placebo recipients were infected with influenza A/Taiwan. TI vaccine provided better heterotypic protection than did CR vaccine for children aged 10-18 years (infection rate, 0 vs. 24%, respectively; P less than .025); in contrast, in the younger children (3-9 years), CR vaccine tended to be more protective (19% vs. 26% for TI).

Adolescent

Live attenuated and inactivated influenza vaccine in school-age children.

In 1985, we enrolled 189 school-age children by family in a double-blind study to determine protection against influenza by a single dose of cold-recombinant bivalent A vaccine or commercial trivalent inactivated vaccine compared with placebo. All children in school or day care, 3 to 18 years of age, in an enrolled family received the same preparation. Following vaccination, 60% and 21% of cold-recombinant bivalent A vaccine recipients and 73% and 83% of trivalent inactivated vaccine recipients demonstrated fourfold or greater response in hemagglutination-inhibition antibody titer to A/H1N1 and A/H3N2, respectively. Sixty-seven percent of all trivalent inactivated vaccine recipients demonstrated a fourfold or greater serologic response to H1N1, H3N2, and influenza B following a single dose of vaccine. During the 1985-1986 influenza B/Ann Arbor epidemic, heterotypic protection afforded by the influenza B/USSR component of trivalent inactivated vaccine was 62% compared with placebo. A single dose of trivalent inactivated vaccine protected school-age children, 6 to 19 years of age, from influenza B infection; the rate of protection was 64% against infection and 73% against febrile illness.

Adolescent

Effect of live attenuated, cold recombinant (CR) influenza virus vaccines on pulmonary function in healthy and asthmatic adults.

The effects of intranasal inoculation with live attenuated, CR influenza virus vaccines on pulmonary function in healthy and asthmatic adults were evaluated in placebo-controlled, double-blind studies. In 46 healthy adult volunteers, there were no statistically significant alterations in pulmonary function as measured by spirometry and histamine bronchoprovocation tests in the first week following monovalent CR influenza virus vaccine [type A (H3N2, H1N1) and type B]. Among healthy adults with pre-inoculation PC20s less than 10 mg ml-1, 8/12 were infected following vaccination but no significant alterations occurred in histamine bronchoprovocation. In 11 asthmatic adults, no statistically significant alterations in pulmonary function, as measured by spirometry, were noted during the first 7 days postinoculation with bivalent CR influenza virus vaccine type A (H3N2 and H1N1). Postinoculation respiratory illnesses were more common in CR influenza virus vaccine recipients than placebo recipients, but they were mild, consisting of afebrile pharyngitis and transient rhinorrhea. Attenuated CR influenza virus vaccines do not appear to impair pulmonary function during the first week following immunization of healthy and asthmatic adults.

Adolescent

Cold recombinant influenza B/Texas/1/84 vaccine virus (CRB 87): attenuation, immunogenicity, and efficacy against homotypic challenge.

Healthy susceptible young adults were inoculated intranasally with increasing doses of wild-type influenza B/Texas/1/84, or the cold-adapted vaccine possessing the genes specifying the hemagglutinin and neuraminidase of the wild-type parent and the six internal genes of cold adapted B/Ann Arbor/1/66 (CRB 87). Most volunteers inoculated with 10(6.6)-10(7.6) TCID50 of CRB 87 were infected, but a high frequency of serum antibody responses was seen only at the highest dose (17/29; 59%). The dose of CRB 87 necessary to infect 50% of all human volunteers (1 HID50) was approximately 10(5.4) TCID50. All volunteers given 10(3.9)-10(7.1) TCID50 of the wild-type virus were infected (i.e., 1 HID50 was less than 10(3.9) TCID50). The frequency of mild febrile reactions, mean peak titer of virus in respiratory secretions, and duration of virus shedding were significantly greater in volunteers given 10(7.1) TCID50 of wild-type virus than in those given 10(7.6) TCID50 of CRB 87. Thirteen volunteers were rechallenged with a second 10(7.6) TCID50 dose of CRB 87 3-4 months after vaccination. The frequencies of mild upper respiratory symptoms and signs, virus shedding, and infection were significantly reduced in prior vaccinees compared with volunteers inoculated with a similar dose for the first time. These data suggest that CRB 87 is attenuated, immunogenic, and can confer protection against homotypic virus challenge in this susceptible population.

Adaptation, Physiological

Safety and pharmacokinetics of rimantadine small-particle aerosol.

The safety and pharmacokinetics of rimantadine administered by small-particle aerosol were assessed in healthy adults and adults with acute influenza virus infection. Aerosolized rimantadine delivered at a concentration of 40 micrograms/liter of air was associated with nasal burning and irritation in normal volunteers. A concentration of 20 micrograms/liter of air was well tolerated for up to 12 h by normal volunteers and was not associated with any changes in pulmonary function, as measured by routine spirometry, plethysmography, or diffusion capacity of carbon monoxide. Mean peak levels of drug in serum were approximately 10-fold lower after 12 h of aerosol administration than they were after oral administration of 200 mg (29.7 versus 255 ng/ml, respectively), while mean nasal wash levels were approximately 100-fold higher (6,650 versus 66.6 ng/ml, respectively). Elimination half-lives were similar after both aerosol and oral administration (24.1 and 25.2 h, respectively), and rimantadine urinary excretion was less than 1% per 24 h in both groups. Twenty micrograms of aerosolized rimantadine per liter of air given 12 h daily for 3 days to nine adults with acute influenza virus infection was well tolerated. Levels in plasma after 12 h of aerosol inhalation were similar to those in normal volunteers, but were higher at the end of the third treatment than they were at the end of the first treatment (88.3 versus 47.9 ng/ml, respectively). Thus, rimantadine delivered via small-particle aerosol at a dose of 20 micrograms/liter of air was well tolerated in normal volunteers and in those with acute influenza and was associated with high local concentrations.

Adult

Vaccination with inactivated influenza A virus during pregnancy protects neonatal mice against lethal challenge by influenza A viruses representing three subtypes.

A single intraperitoneal injection of pregnant mice with a monovalent Formalin-inactivated influenza A virus vaccine protected their offspring against a lethal challenge dose of the same influenza A virus H3N2, H2N2, and H1N1 subtypes, as well as against challenge with the other two subtypes. Degree of protection was vaccine dose related. Cross-fostering of neonates indicated that protection was conferred by breast milk antibodies. Serum virus-specific neutralizing antibodies in the mothers and neonates correlated with resistance to vaccine virus, but were detected against other subtypes only in a complement enhancement test or when high doses of vaccine were given.

Animals

Efficacy of sequential annual vaccination with inactivated influenza virus vaccine.

Inactivated influenza virus vaccine efficacy after annual revaccination has been reported to be less than that after first vaccination in boarding school children. We prospectively examined the immunogenicity and efficacy of this vaccine in healthy 30- to 60-year-old volunteers in Houston, Texas, over two epidemic seasons (1983-1985) encompassing outbreaks due to influenza A (H3N2 and H1N1) and influenza B viruses. A placebo group that had never (or not in recent years) received inactivated influenza virus vaccine, a group that received the vaccine for the first time (first vac), and a group given two or more recent vaccinations (multivac) were evaluated in a double-blind fashion each year. Vaccination induced higher frequencies of rise in serum antibody titer to vaccine components in first vac than in multivac volunteers, but mean postvaccination titers were similar. Clinical and virologic evaluations of illnesses during both epidemics and of influenza infections diagnosed serologically over the epidemic seasons revealed no overall reduction in illness from that in the placebo group for either vaccine group; modest reductions in influenza infection-related illness that were significant only for the multivac group against A/H3N2-related illness (55%; p less than 0.04); reduction in moderate-to-severe lower respiratory and/or systemic illness due to influenza for multivac (73%, p less than 0.025) but not first vac (15%, p greater than 0.10) volunteers during the A/H3N2 epidemic; reduction in influenza virus shedding in the multivac (54%, p less than 0.05) but not the first vac (16%, p greater than 0.10) group when compared with the placebo group for both years; and overall 63-81% reductions in documented infections with each influenza virus for both vaccine groups with the exception of A/H1N1 for the first vac group (24%, p greater than 0.10) and type B for the multivac group (58%, p = 0.067). Vaccine efficacy was only modest in these studies, but in contrast to the earlier report in boarding school children, efficacy appeared to be somewhat greater after repeated annual vaccination than after first administration.

Adult

Rimantadine prophylaxis in children: a follow-up study.

In a randomized, double-blind placebo-controlled clinical trial, we evaluated the prophylactic effectiveness of rimantadine in children (ages 1 to 18 years) against infection with influenza A (H3N2) and associated illness and the prevention of transmission of infection to adult members of the child's family. One hundred ten volunteers from 29 families completed this study during a naturally occurring outbreak of influenza A (H3N2). Influenza infections, defined as a positive viral throat culture or a 4-fold increase in antibody titer, occurred in 31.0% of children in the placebo group and 7.4% in the rimantadine group (P = 0.026). Clinical illness with laboratory evidence of influenza infection occurred in 24.1% of children in the placebo group and none in the rimantadine group (P = 0.007). Rimantadine was well-tolerated by the children, with no significant difference in reported adverse effects between the placebo and rimantadine groups. A combined analysis by families of these data and those of our similarly designed 1984 study, revealed that families in whom the children were given rimantadine had a significantly lower rate of influenza A infection and influenza-like illness compared with the families in whom the children were given placebo (68.8% vs. 18.8%, P less than 0.001) and (56.3% vs. 12.5%, P less than 0.001), respectively. We conclude that rimantadine prophylaxis of children appears to be an effective method to prevent influenza A (either H1N1 or H3N2) infection and illness in children.

Adamantane

Safety and immunogenicity of a purified hepatitis B virus vaccine prepared by using recombinant DNA technology.

Forty healthy adult males were given a 20-micrograms intramuscular dose of either a new recombinant hepatitis B virus (HBV) vaccine produced in mammalian cells (rHBsAg) or the currently licensed HBV vaccine derived from human plasma (HEPTAVAX-B), and booster doses were administered one month and six months later. The percentage of vaccinees who seroconverted on the 10th and 30th days after the first vaccination was higher for the rHBsAg vaccinees than for the recipients of plasma-derived vaccine (rHBsAg: 10% on day 10 and 70% on day 30; HEPTAVAX-B: 0% and 25%, respectively). The only statistically significant difference in titers of antibody to HBV surface antigen was noted 30 days after the first vaccination. Both vaccines induced a shift in antibody from the 19S to the 7S fraction and a specific antibody response to the a determinant. The rHBsAg vaccine was not associated with significant reactogenicity or toxicity and was somewhat more immunogenic than the currently licensed product.

Adult

Effectiveness of rimantadine prophylaxis of children within families.

With recent studies suggesting that children are the main introducers of influenza infections into families, we conducted a placebo-controlled, double-blind, randomized trial to study the prophylactic effectiveness of rimantadine hydrochloride in children on the transmission of influenza A infections within families. One hundred forty-five volunteers from 35 families completed this study during a naturally occurring outbreak of influenza A (H1N1) infection. Influenza infections, defined as a positive viral throat culture or a fourfold increase in antibody titer, occurred in 31.7% of children in the placebo group and 2.9% of children in the rimantadine group. Clinical illness with laboratory evidence of influenza infection occurred in 17.0% of children in the placebo group and 0% of children in the rimantadine group. Rimantadine was well tolerated by the children, with no significant difference in reported side effects between the placebo and rimantadine groups. Influenza A infection occurred in 19.0% of adults whose children were receiving a placebo and 8.8% of adults whose children were receiving rimantadine. On the basis of our study, rimantadine prophylaxis of children appears to be an effective method to prevent influenza A infection in children. Additional studies are needed to demonstrate the effects of rimantadine prophylaxis of children on the incidence of influenza A infection in their parents.

Adamantane

Ribavirin small-particle aerosol treatment of infections caused by influenza virus strains A/Victoria/7/83 (H1N1) and B/Texas/1/84.

In a double-blind study of influenza in a population of college students in 1984, ribavirin small-particle aerosol treatment of 38 patients (18 treated, 20 control) infected with a new antigenic variant, influenza virus strain A/Victoria/7/83 (H1N1), was associated with statistically significant reductions in the height and duration of fever, systemic symptoms, and virus shedding. Patients received a total of 2.4 g of ribavirin over 42 h during 68 h of hospitalization without any side effects. In addition, in a study of patients infected with influenza virus strain B/Texas/1/84 (seven treated, eight control) treated with ribavirin aerosol showed a trend of more rapid recovery than control patients.

Aerosols

Cell cytotoxicity due to specific influenza antibody production in vitro after recent influenza antigen stimulation.

Peripheral blood leukocytes, obtained from volunteers after vaccination or natural illness with influenza, were assayed for cytotoxicity against influenza virus-infected cells. Approximately 7 days after vaccination or the onset of respiratory illness, peak cytotoxicity was demonstrated in a chromium-release assay. Secretion of specific antibody against hemagglutinin from the leukocytes during in vitro incubation was demonstrated in quantities that would mediate the cell cytotoxicity observed. Antibody secretion was inhibited by exposure to cycloheximide but not by exposure to trypsin. The secretion of antibody against hemagglutinin from peripheral blood leukocytes occurred only at the time of maximal cytotoxicity. We thus demonstrate secretion of specific antibody in vitro after recent viral antigen stimulation. Moreover, this antibody is capable of conveying cytotoxic capacity to peripheral blood leukocytes that may be important in the recovery process from acute viral infection.

Antibodies, Viral

Efficacy of purified influenza subunit vaccines and relation to the major antigenic determinants on the hemagglutinin molecule.

Inactivated whole-virus vaccine of influenza A/Scotland/74 (H3N2) virus containing 700 or 1,400 chick cell-agglutinating (CCA) units, a purified subunit vaccine of equivalent dosage, or placebo were studied in 186 adult volunteers. Placebo was least reactogenic, 1,400-CCA unit whole-virus vaccine was most reactogenic, and others were intermediate. Vaccines were equally antigenic, and delineation of antibody specificities revealed antibody cross-reacting with A/Hong Kong/68 (H3N2) virus in all sera. Antibody specific for A/Hong Kong/68 virus was found in 82% of sera and for A/Scotland/74 virus in 46%. When compared with volunteers given placebo, volunteers given 700 CCA units of subunit or whole-virus vaccine exhibited significant protection against infection with live A/Scotland/74 virus. Infections in vaccinees occurred only in those with low titers of antibody to A/Scotland/74 virus, and this antibody was of the cross-reacting type. Persons with moderate and high levels of antibody resisted infection regardless of the absence or presence of antibody specific for A/Scotland/74 virus. Purified subunit vaccines provide an alternative to whole-virus preparations in primed individuals. Efficacy of vaccines may be dependent on the nature of the antibody response.

Adolescent

Reinfection with influenza A (H3N2) virus in young children and their families.

The frequency and consequences of reinfection with influenza A virus were studied by longitudinal observation of families for a three-year period in which two epidemics of influenza A (H3N2) occurred. Seven children followed from birth were reinfected 10-25 months after their first infection. Two children were reinfected by the same H3N2 virus while the others were reinfected with a closely related variant. At least five of these reinfections were accompanied by respiratory illness. Reinfection illness was similar to that accompanying primary infection. For children in the second and third year of life during the 1978 epidemic, the rate of infection was the same for those who had been previously infected (seven of 12) as for those who had not been previously infected (22 of 40). Reinfection was detected in 26% of older siblings and 6% of parents. The occurrence of reinfection may have important implications for elucidation of the protective immune response and for development of prophylaxis for influenzal infections.

Antibodies, Viral

Temperature-sensitive mutants of influenza A virus: evaluation of the A/Victoria/75-ts-1A2 temperature-sensitive recombinant virus in seronegative adult volunteers.

An influenza A virus recombinant bearing the surface antigens of the A/Victoria/3/75 (H3N2) strain and the two ts genes of the A/Udorn/72-ts-1A2 virus was evaluated for attenuation, antigenicity, and protective effect in 42 doubly seronegative adult volunteers (i.e., individuals who lacked detectable serum antibodies for the hemagglutinin and neuraminidase antigens). This recombinant, which had a 37 degrees C shutoff temperature for plaque formation and ts mutations on the genes thought to code for the P1 and P3 polymerase proteins, infected 90% of the volunteers. Of the volunteers, 5% developed mild coryza or rhinitis but other signs or symptoms were not observed, indicating that the A/Victoria/75-ts-1A2 recombinant was more attenuated than the A/Victoria/75-ts-1[E] recombinant. Vaccinees shed virus for a shorter interval and at a lower titer than did the A/Victoria/75-ts-1[E] vaccinees. Each ts-1A2 isolate retained the ts phenotype indicating that the recombinant was stable genetically in doubly seronegative adults. Finally, the ts-1A2 recombinant induced significant resistance to subsequent challenge with A/Victoria/75 wild-type virus.

Adult

Comparison of different tissue cultures for isolation and quantitation of influenza and parainfluenza viruses.

Rhesus and cynomolgus monkey kidney tissue cultures and two continuous lines, Madin-Darby canine kidney (MDCK) and LLC-MK2, were compared in titrations and isolations of influenza and parainfluenza viruses. Tube cultures were inoculated with laboratory virus strains or stored patient specimens and observed for hemadsorption. Trypsin was added to the medium of the continuous lines to increase sensitivity. All four tissue cultures gave similar titers of influenza A/USSR (H1N1), A/Texas (H3N2), and B/HK, but lower titers of parainfluenza 1, 2, and 3 were observed with MDCK. Cynomolgus kidney was the best single tissue culture for reisolation of the six viruses, but foamy-virus contamination of many lots was a serious problem. Reisolation of influenza viruses was as successful with MDCK as with primary monkey kidney. LLC-MK2 was similar to rhesus kidney but less successful than cynomolgus kidney. For reisolation of parainfluenza viruses, LLC-MK2 was superior to rhesus monkey kidney and similar to cynomolgus kidney. MDCK was less useful for parainfluenza viruses. Thus, LLC-MK2 would be an acceptable single tissue alternative to primary monkey kidney. The combination of MDCK and LLC-MK2 would provide optimal sensitivity for isolation of all six viruses.

Animals