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Biomedical subjects

R B Couch

Publications and source records attributed to R B Couch.

At least 91 records · Page 5Linked to original sources

Epidemiologic observations of influenza B virus infections in Houston, Texas, 1976-1977.

Influenza B virus infections were documented in Houston, Texas, in 726 patients with febrile respiratory illnesses who presented to representative primary care facilities during the 1976-1977 respiratory disease season. This epidemic followed a "herald wave" of illness associated with influenza B during the preceding spring. Over one-half the virus isolates were from children aged 5-19 years, and school absenteeism rates indicated that about 40 per cent of the students in the Houston area were ill enough to miss school during the epidemic. The rapid rise in the number of cases among students after the school holiday recess demonstrated the importance of school attendance for the rapid dissemination of influenza viruses. During the later phase of the epidemic, most of the cases were preschool children and adults. In addition to disease of the respiratory tract, the epidemic was accompanied by cases of Reye's syndrome at a rate expected for an urban area.

Absenteeism↗

Amantadine and ribavirin aerosol treatment of influenza A and B infection in mice.

Ribavirin, amantadine, and the two drugs in combination given in small-particle aerosol were highly effective in the treatment of influenza A infection in mice. Treatment was started 72, 96, and 120 h after inoculation and was given continuously for 4 days. With increasing delay in start of treatment, there was a pronounced reduction in effectiveness of ribavirin but not in that of amantadine. The combination treatment reflected the loss of ribavirin activity. Leukocyte infiltration and virus titers in the lungs were inversely related to the effectiveness of treatment. Influenza B infection treated 72 h after inoculation responded only to ribavirin, as indicated by the criteria described for influenza A. Intraperitoneal administration of drug begun 72 h after inoculation in regimens equivalent to aerosol afforded less protection than aerosol treatment.

Aerosols↗

Evaluation of influenza A/Hong Kong/123/77 (H1N1) ts-1A2 and cold-adapted recombinant viruses in seronegative adult volunteers.

Two attenuated influenza A donor viruses, the A/Udorn/72 ts-1A2 and the A/Ann Arbor/6/60 cold-adapted (ca) viruses, are being evaluated for their ability to reproducibly attenuate each new variant of influenza A virus to a specific and desired level by the transfer of one or more attenuating genes. Each of these donor viruses has been able to attenuate influenza A viruses belonging to the H3N2 subtype by the transfer of one or more attenuating genes. To determine whether these two donor viruses could attenuate a wild-type virus that belonged to a different influenza A subtype, ts-1A2 and ca recombinants of a wild-type virus representative of the A/USSR/77 (H1N1) Russian influenza strain were prepared and evaluated in adult doubly seronegative volunteers at several doses. The recombinants derived from both donor viruses were attenuated for the doubly seronegative adults. Less than 5% of infected vaccinees developed a febrile or systemic reaction, whereas five of six recipients of wild-type virus developed such a response. The 50% human infectious dose (HID(50)) for each recombinant was approximately 10(5.0) 50% tissue culture infective doses. The virus shed by the ts-1A2 and ca vaccinees retained the ts or ca phenotype, or both. This occurred despite replication of the recombinant viruses for up to 9 days. No evidence for transmission of the ca or ts-1A2 recombinant virus to controls was observed. A serum hemagglutination inhibition response was detected in less than 50% of the infected vaccinees. However, with the more sensitive enzyme-linked immunosorbent assay, a serological response was detected in 100% of the ca vaccinees given 300 HID(50) and approximately 70% of ca or ts vaccinees who received 10 to 32 HID(50) of virus. These results indicate that the recombinants derived from both donor viruses were satisfactorily attenuated and were stable genetically after replication in doubly seronegative adults although they induced a lower serum hemagglutination inhibition response than that found previously for H3N2 ts and ca recombinants.

Adult↗

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↗

The lymphocyte response to influenza in humans.

Enumeration of total lymphocytes and T, B, and null lymphocyte subpopulations in peripheral blood of normal volunteers was performed before and at intervals after inoculation with type A influenza virus. Volunteers who subsequently developed infection and illness had larger T-cell counts before inoculation and exhibited an increased number of B lymphocytes during the incubation period and a decrease in all subpopulations during illness, although the greatest decrease occurred in T cells. A decrease in B-cell counts occurred on day 3 in volunteers who exhibited infection, but no illness and no changes occurred in uninfected, well volunteers. Values had returned to baseline by day 21 after inoculation. Thus, the lymphopenia that accompanies influenza involves all subpopulations, but is primarily a decrease in T cells; in addition, differences in T-cell and B-cell populations before and during the incubation period may identify persons who will subsequently develop febrile influenza.

Adult↗

Interpandemic influenza in the Houston area, 1974-76.

Prospective virologic surveillance has defined two influenza epidemics representing the fifth and sixth outbreaks attributed to H3N2 viruses since the prototype, A/Hong Kong/68 ((H3N2), emerged in 1968. The 1975 epidemic was caused by influenza A/Port Chalmers and yielded an estimated attack rate of 9 per cent; the second, attributed to influenza A/Victoria, produced an explosive outbreak, with an estimated attack rate of 18 per cent in 1976. The highest morbidity occurred in preschool children, with an estimated attack rate of over 30 per cent. During the early stages of both epidemics there was a predominance of cases among school-aged children, and school absenteeism peaked earlier than other nonvirologic indexes. These observations support the concept of rapid dissemination of influenza among schoolchildren and suggest that control of epidemic influenza might be facilitated by prophylaxis for that age group and other accessible, healthy populations.

Adolescent↗

Antiviral activity of intranasally applied human leukocyte interferon.

Previous studies in our laboratory have demonstrated that the development of antiviral activity of human leukocyte interferon (IF) in nasal epithelial cells is time and concentration dependent and that the loss of intranasally applied human leukocyte IF is rapid. The present studies compared the activity of IF applied intranasally either by nasal drops or by a saturated cotton pledget. Adult volunteers had IF applied to an area of nasal mucosa (2 by 2 cm(2)) either by repeated nose drops or by a saturated cotton pledget that was applied to the nasal mucosa and left in place for 1 h. Nasal epithelial cells scraped from the area of application, as well as the control, untreated side of the same volunteers, were challenged with vesicular stomatitis virus. No significant reduction in mean virus yield was found in volunteers who received 80,000 U by nose drops. Significant reduction (P < 0.025) in mean virus yield was found in cells obtained 4 h after 80,000, 50,000, or 20,000 U was applied by cotton pledget or in volunteers pretreated with oral antihistamines prior to receiving 80,000 U by nose drops. These experiments indicate that nasal epithelial cells can be made antiviral in vivo by application of human leukocyte IF. However, practical usefulness of human leukocyte IF for prophylaxis against respiratory viral infections may depend on the method of local application.

Adult↗

Lymphocyte cytotoxicity to influenza virus-infected cells: response to vaccination and virus infection.

Peripheral blood leukocytes obtained from volunteers at various times following influenza vaccine or live influenza virus infection were assayed for cytotoxicity against influenza virus-infected cells. Cytotoxicity was highest on days 3 and 7 following vaccination with commercial A/Port Chalmers/1/73 inactivated influenza virus vaccine. Maximal cytotoxicity was found 9 days after infection induced by intranasal inoculation of a strain of A/Scotland/840/74 influenza virus. Individuals naturally infected with A/Victoria/3/75 were also found to have elevated cytotoxicity approximately 1 week after onset of illness. Cytotoxicity levels decreased toward base line approximately 30 days after the virus exposure. The effector mechanism(s) responsible for the early, transient elevation in specific immune release to influenza virus-infected cells may be different from the antibody-dependent cell cytotoxicity demonstrated in the peripheral blood leukocytes from volunteers who had a remote experience with influenza virus.

Adolescent↗

Temperature-sensitive mutants of influenza A virus: evaluation of A/Victoria/3/75-ts-1[E] recombinant viruses in volunteers.

The Hong Kong/68-ts-1[E] virus and its Udorn/72 and Georgia/74 recombinants, which have a 38 degrees C shutoff temperature and a ts lesion(s) on the genes coding for the P3 and NP proteins, were adequately attenuated and immunogenic in adult volunteers who lacked serum hemagglutination-inhibiting antibody (titer, </=1:8), but who possessed serum neuraminidase-inhibiting antibody. Two Victoria/75-ts-1[E] clones that also had a 38 degrees C shutoff temperature and a ts lesion(s) on the same two genes were administered to adult volunteers who lacked both serum hemagglutination-inhibiting antibody (titer, </=1:8) and neuraminidase-inhibiting antibody (titer, </=1:4). In contrast to the behavior of the earlier ts-1[E] recombinants, the Vic/75-ts-1[E] recombinants retained the capacity to cause febrile, systemic illness. However, the recombinants were attenuated compared with wild-type virus. The Vic/75-ts-1[E] virus vaccinees shed a larger amount of virus for a longer time than the previous ts-1[E] vaccinees, but they shed less virus than volunteers infected with wild-type virus. The ts-1[E] virus shed retained its ts phenotype in most instances and failed to spread to susceptible contacts. Vaccinees were partially protected against homologous wild-type virus challenge. The failure of HK/68, Udorn/72, and Georgia/74 ts-1[E] vaccinees to develop systemic reactions may reflect the presence of neuraminidase immunity before infection. In this situation, attenuation probably resulted from the degree of defectiveness of the ts-1[E] recombinant virus and the existence of neuraminidase immunity in the recipients. The 50% human infectious dose of the Vic/75 ts-1[E] virus was less than 10(5.2) 50% tissue culture infective doses. This suggests that at the time of a pandemic shift involving both the hemagglutinin and neuraminidase glycoproteins, a small amount of live virus vaccine might be effective in initiating infection.

Antibodies, Viral↗

Herpes simplex encephalitis treated with vidarabine (adenine arabinoside).

Vidarabine, an antiviral chemotherapeutic agent shown to have in vitro activity against the herpes group of viruses, was administered to five patients with brain biopsy-proved herpes simplex virus encephalitis. The mortality in this small number of patients (one of five or 20%) was less than that in most published reports of patients receiving other treatment modalities or no treatment other than supportive measures. No apparent toxicity was found that was attributable to vidarabine. Neuropsychological impairment of varying degree was noted in four surviving patients tested at two months after treatment and again 12 to 21 months later. Progressive improvement had occurred in three.

Adolescent↗

Clinical trials of monovalent influenza A/New Jersey/76 virus vaccines in adults: reactogenicity, antibody response, and antibody persistence.

Responses to monovalent influenza A/New Jersey/76 virus vaccines were evaluated in 22-43-year-old, antibody-negative males. Three doses of vaccine (200, 400, and 800 chick cell-agglutinating [CCA] units) from each of four manufacturers and a placebo were given intramuscularly. Mild systemic complaints occurred in 12% of vaccines and moderate reactions in 5%, mostly in recipients of 800 CCA units of the vaccines. Reactogenicities of subvirion vaccines were intermediate, while different preparations of whole-virus vaccine were the most and the least reactogenic. Local reactions to 200-CCA unit doses of vaccines resembled reactions to placebo. Serum antibody responses against influenza A/swine/37 virus and current swine-like strains were similar for recipients of vaccines from three manufacturers. Among recipients of 200 CCA units of the vaccines, 79% developed antibody titers of greater than or equal to 1:20. Increasing antibody response was not uniformly associated with increasing vaccine dose but did correlate with increasing reactogenicity. Antibody titers fell about twofold over six months, and they fell slightly more for recipients of subvirion than for recipients of whole-virus vaccines.

Adult↗

The immunizing effect of influenza A/New Jersey/76 (Hsw1N1) virus vaccine administered intradermally and intramuscularly to adults.

2The immunogenicity and reactogenicity of inactivated influenza A/New Jersey/76 (Hsw1N1) whole-virus vaccine administered intradermally (40 chick cell-agglutinating units/0.1-ml dose) and intramuscularly (im; 200 chick cell-agglutinating units/0.5-ml dose) to human adults were evaluated. Among 18-24-year-old persons initially free of detectable antibody, intradermal vaccination induced lower titers of hemagglutination-inhibiting antibodies than did im vaccination, and a sequence of intradermal and im vaccinations did not offer any serologic advantage over one im dose. In contrast, persons over the age of 24 who initially lacked detectable antibody had as good a serologic response to intradermal vaccination as to im vaccination. Among individuals who had antibody before vaccination, immunization by either route induced greater increases in titers of hemagglutination-inhibiting antibody than occurred in initially antibody-negative persons, even when the latter were given two doses of vaccine. Somewhat fewer systemic reactions occurred after intradermal than after im vaccination, but the intradermal route was associated with local reactions in almost all vaccinees and with some residual pigmentary changes. These results suggest that intradermal vaccination should be used only in very selected circumstances.

Adolescent↗