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Biomedical subjects

R B Couch

Publications and source records attributed to R B Couch.

At least 73 records · Page 4Linked to original sources

Immunity to influenza in man.

The observations summarized in this review indicate immunity to infection with type A influenza viruses is subtype specific since little or none is conveyed to subtypes possessing immunologically distinct HA and NA proteins. However, within a subtype, a prior antigenic experience with one variant may prevent or modify illness to another. The resulting degree of subtype immunity depends on the extent of relatedness between variants. Observations with H3N2 viruses indicate that homotypic resistance to subsequent infection and illness with the same virus is potent and of relatively long duration. The long lasting durability of such immunity was indicated by the epidemiologic pattern following the reappearance of H1N1 virus. Knowledge of the duration and specificity of immunity aids considerably in assessing mechanisms that account for host resistance to influenza. Recovery from influenza virus infection must involve a variety of humoral and cell-mediated immune mechanisms, and conclusions regarding the relative importance of each one are not possible at present. To prevent infection, involved immune mechanism(s) must account for: (a) subtype specificity, (b) reduced cross-reactivity of immunity for succeeding antigenic variants, (c) a long duration of immunity, and (d) immunity at the mucosal surface. Only antibody directed toward the HA molecule presently satisfies these properties and thus should be considered the major mediator of resistance to infection. Study of naturally occurring infection is needed for determining the duration and specificity of secretory IgA in nasal and lower respiratory secretions so as to establish its relative importance as a mediator of immunity. However, the described duration, specificity, and consistent relationship to immunity suggest that IgG antibody in respiratory secretions, derived entirely or partly from serum, is the most likely mediator of resistance to natural influenza.

Antibodies, Viral↗

Ribavirin aerosol treatment of influenza B virus infection.

In a randomized, controlled study, ribavirin small particle aerosol was found to be effective in the treatment of influenza B virus infection in a group of college students. Eleven treated patients experienced significantly more rapid defervescence, disappearance of systemic illness, and reduction of virus shedding in nasal secretions than 10 control patients treated with a saline aerosol. Antibody response to infection was similar in both groups. The treatment was well tolerated and hematologic and clinical chemical tests revealed no toxicity. The estimated dose of ribavirin aerosol retained was about 2 g in 35.5 hr of treatment during the first 60 hr in the hospital.

Adult↗

Surveillance of influenza in Houston, Texas, USA: gradual transition from A/Victoria/75 (H3N2) to A/Texas/77 (H3N2) predominance and antigenic characterization of "intermediate" strains.

Influenza epidemics in Houston, Texas, USA, during the winters of 1975-76, 1976-77, and 1977-78 were attributed to A/Victoria/3/75 (H3N2), B/Hong Kong/5/72, and A/Texas/1/77 (H3N2)-like viruses, respectively. Both A/Victoria and A/Texas viruses were detected towards the end of the 1976-77 epidemic and throughout the 1977-78 epidemic. To determine if there had been a gradual transition in the predominant strain, 267 viral isolates from the 1975-76 epidemic were tested for A/Texas virus. Eight specimens (3%) that appeared to contain A/Texas antigens were cloned and retested with specific antisera prepared in guinea-pigs and ferrets. One virus was identical to A/Texas/1/77 virus, two reacted like A/Victoria/3/75 and five reacted equally well with antisera prepared against A/Victoria/3/75 and A/Texas/1/77 viruses (bridging strains). The six viral isolates containing A/Texas antigens were obtained at different times during the epidemic, from all parts of the city, from males and females aged between 1 and 20 years.Characterization of type A influenza virus isolates obtained during the 1976-77 and 1977-78 epidemics revealed a progressive increase in the frequency of viruses containing A/Texas antigens, from 2.2% in 1975-76 to 32% in 1976-77 to 70% in 1977-78. Thus, both type A (H3N2) variants were present in the Houston community in 3 successive years.An antigenic analysis of the bridging viruses was performed by competition radio-immunoprecipitation assays and by reactivity with a set of monoclonal antibodies prepared against A/Texas/1/77 virus. These assays confirmed the identity of the A/Texas isolate with the prototype virus and indicated that the bridging strains shared antigenic determinants with both A/Vic/75 and A/Tex/77 viruses, but were more closely related to A/Victoria/3/75 virus.It seems clear that new variants of a subtype of type A influenza may not immediately displace the existing variant and that seeding in a community and transition from predominance of one variant to another may be a gradual process.

Adolescent↗

Herpes zoster-associated encephalitis: clinicopathologic report of 12 cases and review of the literature.

Herpes-zoster associated encephalitis (HZAE) is an uncommon complication of herpes zoster. Over 8 years, we evaluated 12 patients with this clinical diagnosis. The majority of our patients were elderly, immunosuppressed, and found to have disseminated skin lesions prior to the onset of CNS symptoms. All patients had abnormal EEGs, and CSF pleocytosis was found in most. In the seven patients who were tested, specific antibody to the varicella-zoster membrane antigen (FAMA) was detected in spinal fluid during the course of the illness. Although three patients died during the period of active infection, the virus could not be definitively implicated as the cause of death. These HZAE patients could not be distinguished from our other herpes zoster patients on the basis of age, initially involved dermatome, or mortality rate. However, among herpes zoster patients who survived, duration of hospitalization was significantly longer in those with a diagnosis of HZAE. All surviving HZAE patients had a slow but eventual return to their prior cognitive status.

Adult↗

Prophylactic effect of low doses of human leukocyte interferon against infection with rhinovirus.

The prophylactic effect of low doses of human leukocyte interferon (HuIFN-alpha) against infection with rhinovirus was measured in double-blind, placebo-controlled studies with volunteer subjects. An antihistamine (chlorpheniramine) was given before administration of single or multiple doses of HuIFN-alpha but saturated cotton pledget or by aerosol; volunteers were then challenged with rhinovirus. When the results for all groups were combined, a lower frequency of respiratory illness was demonstrated in the HuIFN-alpha-treated volunteers (20 of 39 vs. 11 of 38, P less than 0.05). A significant improvement in mean symptom scores was found only in the volunteers who received HuIFN-alpha by cotton pledget. The total numbers of isolates of rhinovirus and seroconversions were similar for HuIFN-alpha-treated and control volunteers. No significant side effects were noted in the HuIFN-alpha-treated volunteers. Higher concentrations or improved methods of delivery of HuIFN-alpha will be necessary for improving the clinical efficacy of HuIFN-alpha against viral infections in the respiratory system.

Adolescent↗

The influenza herald wave.

For three successive years (1976-1979), the community surveillance system of the Influenza Research Center identified a wave of influenza virus infections which occurred during the latter half of one epidemic period and which heralded the epidemic virus for the following year. Recognition of the herald waves required consistent and continuous sampling of respiratory illnesses occurring among persons who constituted a substantial proportion of the population of over two million people in Harris County, TX. The herald wave infections consisted of only 0.4-2.0% of the 2500 to 3000 respiratory illnesses examined for virus. During the first two epidemic periods, the herald wave was easily detected as a wave of influenza B virus infections occurring during an influenza A virus epidemic and then a wave of influenza A virus infections during an influenza B virus epidemic. The third herald wave was obscured because it consisted of a small number of infections caused by viruses antigenically like A/Brazil/11/78(H1N1) which occurred at the end of the outbreak caused by influenza A/USSR/90/77 (H1N1). The herald wave infections were detected among persons who lived in widely scattered areas of the county and who were representative of all age and socioeconomic groups. the herald wave phenomenon has the obvious benefit of providing information about the virus most likely to produce an epidemic during the next respiratory disease season. Under optimal conditions, this could allow six to nine months to prepare and administer control measures.

Humans↗

Live influenza A/Victoria/75 (H3N2) virus vaccines: reactogenicity, immunogenicity, and protection against wild-type virus challenge.

Four live influenza A/Victoria/75 (H3N2) recombinant virus vaccines were administered intranasally to a total of 50 volunteers who had little or no detectable serum neutralizing antibody. A recombinant with ts-1[E] having a 38 degrees C shut-off temperature caused febrile reactions or systemic reactions or both in 21% of the volunteers, but one with ts-1A2 having a 37 degrees C shut-off temperature caused no illness. Two recombinants prepared with cold-adapted A/Ann Arbor/6/60 caused 9% febrile reactions or systemic reactions or both. Virus shedding occurred in a minority of the 50 volunteers, but 90% developed a serum neutralizing antibody response. Wild-type A/Victoria/75 virus challenge of 34 of the vaccinated volunteers and 12 others who had had prior natural A/Victoria/75 virus infection revealed similar and significant protection when compared with the 96% infection and 68% febrile illness or systemic illness or both observed in 25 unvaccinated volunteers with little or no serum antibody. These results encourage continued efforts toward development of live influenza virus vaccines.

Adult↗

Ribavirin small-particle aerosol treatment of influenza.

In an outbreak of influenza virus A/England/333/80(H1N1) infections in college students, 14 randomly selected patients were treated by inhalation of ribavirin small-particle aerosol through a face mask. They retained an average estimated 1.15 g of drug in 23 h of treatment given over 3 days. 17 patients served as controls. Ribavirin aerosol treatment had a therapeutic effect judged by the highly significant reduction in height and duration of fever, reduction in systemic illness, and disappearance of influenza virus from respiratory secretions. 1 additional patient with influenzal pneumonia caused by a strain of influenza virus A/Bangkok/79(H3N2) recovered promptly with ribavirin aerosol treatment.

Administration, Oral↗

Comparison of amantadine and rimantadine for prevention of type A (Russian) influenza.

The efficacies of 200 mg of daily doses of amantadine and of rimantadine for prevention of infection and illness due to influenza A/USSR/77 (H1N1) virus were compared in a double-blind, placebo-controlled study on a college campus. Frequencies of symptoms that might have been side effects of the drugs were not significantly different from those in placebo recipients. Analyses indicated that the trial was initiated late in the epidemic and that an age-related protective effect against A/USSR virus existed; seroconversion frequencies were 52/139 (37%) among 18-19-year-olds, 33/130 (25%) among 20-21-year-olds, and 5/39 (12.8%) among 22-24-year-olds. Among initially antibody-negative (less than 1 : 4 in complement fixing and neutralizing tests and less than 1 : 8 in hemagglutination inhibition tests) 18-19-year-old students, amantadine was associated with significantly fewer seroconversions (P = 0.01) and both less infection and milder illness than occurred in placebo recipients (P less than 0.05). Although rimantadine was not accompanied by reduction in frequency of seroconversions in the same age group, illness frequency and severity among seroconverters were significantly reduced when compared to placebo recipients (P less than 0.01). Amantadine and rimantadine appear suitable for use in young adults. Although other studies have suggested greater effectiveness of rimantadine than of amantadine against influenza, no evidence for this was seen in the present study which used both drugs at the same dose.

Adamantane↗

Infection with influenza A/Victoria virus in Houston families, 1976.

In 1976, an epidemic caused by infections with an influenza virus antigenically similar to A/Victoria/75 (H3N2) occurred in Houston, Texas. During this outbreak, 37 families (155 members) enrolled in the Houston Family Study were under observation. The families lived throughout the metropolitan area (Houston, Texas), and were representative of low income groups. The overall frequency of infection in family members was 27.7%. The frequency of infection was the highest for infants under one year of age and for their older siblings, 14 (37.8%) of 37 and 17 (33.3%) of 51, respectively. Eighteen (48.6%) of the 37 families had at least one infected member. Twelve of the 18 'infected' families had school aged children, whereas only three of the 19 'non-infected' families had school aged children (P less than 0.01). These infected families were also larger and had increased household density (persons/rooms). The levels of pre-existing HI antibodies to A/Victoria/75 and A/Port Chalmers/73 were inversely related to frequencies of infection and illness associated with A/Victoria/75 virus. Three children required hospitalization as direct consequence of their infection with this H3N2 influenza virus. Antibody response to infection was related to previous experience with antigenically-related influenza A (H3N2) viruses according to Francis', 'doctrine of original antigenic sin.'

Antibodies, Viral↗

A polysaccharide-protein complex from Haemophilus influenzae type b. III. Vaccine trial in human adults.

Polysaccharide-protein complex prepared from Haemophilus influenzae type b strain Eagan was evaluated for toxicity and immunogenicity in adult volunteers given intramuscular injection. Most subjects had moderate local inflammation that was maximal the day after vaccination. No lot of vaccine significantly exceeded a saline placebo in production of systemic symptoms. Neither the local nor the systemic reactions of individual subjects appeared to be related to prevaccination serum antibody titers. Serum antibody responses to the capsular polysaccharide (polyribosylribitolphosphate [PRP]) component were detected in approximately 80% of the subjects. The PRP content of the vaccine antigens varied, and the rate and extent of responses were as expected for an equivalent dose of purified PRP vaccine. Antibody responses were not enhanced by aluminum phosphate. There was no booster response to a second injection given after six months. Responses to the residual lipopolysaccharide component occurred in 80% of the subjects, primarily in the IgG class. Responses to the nonlipopolysaccharide somatic components were detected less frequently.

Adult↗

Genetic approaches to attenuation of influenza A viruses for man.

The explosion of new information concerning the influenza A viral genome provides a basis for deliberate manipulation of its genes with the intent of introducing specific mutations that render influenza virus attenuated and useful for prevention of disease. Currently there is considerable effort to develop a defined set of mutant genes that confer a specific and desired level of attenuation upon any viral recombinant into which they are transferred. In this manner new antigenic variants of influenza A virus may be satisfactorily attenuated after transfer of the mutant genes. The mutant genes must be readily identifiable by simple in-vitro techniques, thus enabling the genetic basis of attenuation to be monitored directly during all phases of vaccine development, manufacture and utilization in man. We describe our experience with two sets of ts mutant genes which affect viral RNA transcription or synthesis and which effect a reproducible level of attenuation in wild-type influenza A virus.

Animals↗