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Biomedical subjects

W R Dowdle

Publications and source records attributed to W R Dowdle.

At least 37 records · Page 2Linked to original sources

Legionnaires' disease: isolation of a bacterium and demonstration of its role in other respiratory disease.

To identify the etiologic agent of Legionnaire's disease, we examined patients' serum and tissue specimens in a search for toxins, bacteria, fungi, chlamydiae, rickettsiae and viruses. From the lungs of four of six patients we isolated a gram-negative, non-acid-fast bacillus in guinea pigs. The bacillus could be transferred to yolk sacs of embryonated eggs. Classification of this organism is incomplete. We used yolk-sac cultures of the bacillus as antigen to survey suspected serum specimens, employing antihuman-globulin fluorescent antibody. When compared to controls, specimens from 101 to 111 patients meeting clinical criteria of Legionnaires' disease showed diagnostic increases in antibody titers. Diagnostic increases were also found in 54 recent sporadic cases of severe pneumonia and, retrospectively, in stored serum from most patients in two other previously unsolved outbreaks of respiratory disease. We conclude that Legionnaires' disease is caused by a gram-negative bacterium that may be responsible for widespread infection.

Adult↗

Identification and preliminary antigenic analysis of swine influenza-like viruses isolated during an influenza outbreak at Fort Dix, New Jersey.

The sequence of events and the laboratory procedures that resulted in the identification of swine influenza-like viruses isolated during an influenza outbreak at Fort Dix, New Jersey in January and February of 1976 are described. Preliminary antigenic analysis suggested that the isolates from Fort Dix are closely related to a 1975 isolate of swine influenza virus and distinguishable from earlier swine influenza strains.

Antigens, Viral↗

Swine influenza virus infections in humans.

Influenza in swine was first recognized as an epizootic disease in 1918. During that same year influenza virus in humans caused the worst pandemic on record. The virus of swine influenza was isolated in 1930. Swine influenza virus was first isolated from humans in 1974. Since then, including the cases at Fort Dix, there have been a total of nine viral isolations from humans in the United States. Serologic evidence of infections with swine influenza virus in humans has also been obtained. Evidence for transmission of swine influenza virus to humans before 1974 is minimal and circumstantial. Recent recognition of infections with swine influenza virus may be the result of better surveillance, increased numbers of susceptible humans, or increased viral infectivity for humans. Nevertheless, the apparent frequency of human infections and the declining levels of antibodies to swine influenza virus in the human population suggest that influenza viruses of swine may be a potential sources of epidemic disease for humans.

Adolescent↗

Neuraminidase content of influenza vaccines and neuraminidase antibody responses after vaccination of immunologically primed and unprimed populations.

Vaccines prepared with influenza A/swine/1976/37-like virus contained neuraminidase activity comparable to that of H3N2 vaccines, whereas little neuraminidase activity could be detected in influenza A/New Jersey/76 vaccines. In single-dose vaccine studies, A/swine/1976/37-like split-virus vaccine induced antibody to neuraminidase (NAAb) in about 20% of children younger than 18 years and this NAAb response was better than or equal to the antibody response to the vaccine's hemagglutinin (HAAb). In immunologically primed adults, the NAAb response to a single dose of Hsw1N1 or H3N2 vaccine was 38%-54%, but this value was about 1.7-fold lower than that for HAAb response. Children six to 17 years old given two doses of A/swine/1976/37-like vaccine had an overall 70% NAAb response, whereas children of similar age had an overall 30%-48% NAAb response to two doses of A/Victoria/3/75 (H3N2) virus. The findings support a hypothesis that the NAAb response to influenza vaccines can be suppressed if subjects receiving the vaccine are immunologically primed to its hemagglutinin component. NAAb responses in the absence of HAAb responses occur in only about 5% of vaccinated persons who are immunologically primed to both the hemagllutinin and neuraminidase of the vaccine.

Adolescent↗

Measurement of hemagglutination-inhibiting antibody to influenza virus in the 1976 influenza vaccine program: methods and test reproducibility.

Titers of hemagglutination-inhibiting (HAI) antibody were determined for all sera obtained from participants in the 1976 Influenza Vaccine Test Program. At least eight control sera were included in each test during the vaccine trial period for the purpose of monitoring HAI test reproducibility. Estimates of day-to-day reproducibility were defined as the percentages of duplicate aliquots of the same sera, tested on two separate days, having HAI antibody titers that did not differ by more than one twofold dilution. These reproducibility estimates ranged from 89% to 97% with influenza A/New Jersey/76 and A/Mayo Clinic/74 antigens. In contrast, within-day reproducibility estimates obtained from all sets of control sera ranged from 96% to 98%. Estimates of day-to-day test reproducibility obtained with selected sera taken after vaccination that were titrated on two differen days ranged from 90% to 98%. Geometric mean titers of these sera tested weeks or months apart differed on some occasions during the test period.

Antibodies, Viral↗

Age-related heterologous antibody responses to influenza virus vaccination.

Heterologous hemagglutination-inhibiting (HAI) antibody responses to influenza A/New Jersey/76 (Hsw1N1) virus vaccine were examined in individuals receiving doses of 200, 400, or 800 chick cell-agglutinating units of whole-virus or split-virus products during the 1976 National Influenza Vaccine Test Program. Vaccination with influenza A/New Jersey/76 virus produced a high rate of heterologous antibody response to influenza A/PR/8/34 (H0N1) and A/FM/1/47 (H1N1) viruses in persons whose original antigenic experience according to their age was with H0N1 or H1N1 strains, respectively. Vaccination with A/New Jersey/76 virus produced only low levels of HAI antibody to influenza A/Japan/305/57 (H2N2) and A/Victoria/3/75 (H3N2) viruses, and these responses were less clearly related to primary infections. Thus the greatest heterologous HAI antibody responses occurred when there were shared antigenic determinants between the hemagglutinins of the vaccine virus and the viruses that had caused the initial priming infection. However, when vaccinations or infections with H3N2 and Hsw1N1 strains may both be occurring in the population, even infrequent formation of heterologous antibody may make it difficult to interpret serologic data precisely.

Adolescent↗

Live, attenuated influenza A/England/42/72 (H3N2) virus vaccine: a field trial.

Two doses of a live, attentuated influenza A/England/42/72 (H3N2) vaccine virus (inhibitor-insensitive Alice strain) were administered intranasally to 130 university students, and placebo was given to 134 students. Fourfold or greater rises in titer of hemagglutination-inhibiting antibody occurred in 68% of all vaccine recipients and in 88% of those with initial titers of less than 1:8; the geometric mean titer of hemagglutination-inhibiting antibody increased from 1:15 to 1:77. A 3.2-fold rise in titer of neuraminidase-inhibiting antibody occurred in 24% of the students. Side effects produced by administration of the vaccine include mild rhinitis and sore throat, which were found only during the first four days after administration of the first dose. Inhibitor-insensitive virus was shed only by three of 31 intensively studied vaccine recipients; these three subjects all had initial serum titers of hemagglutination-inhibiting antibody of less than 1:8. No transmission of vaccine virus to spouses was detected. During a 12-month interval after vaccination, the geometric mean titer of hemagglutination-inhibiting antibody in serum and the prevalence of antibody decreased minimally among the 47 vaccine recipients still available for study.

Administration, Intranasal↗

Epidemiology of influenza in the elderly: evidence of virus recycling.

During the Hong Kong influenza epidemic of 1968-1969 the attack rate among persons born prior to 1890 was about one-third the rate among persons born after 1899. During an Asian influenza epidemic in the same community two years earlier there was no apparent age effect. Most persons born before 1890 had detectable pre-epidemic antibody against A/Hong Kong/68 whereas most persons born after 1899 had no detectable pre-epidemic antibody. The lower attack rate in the older age group is consistent with the hypothesis that influenza A viruses with similar or identical hemagglutinins can reemerge over time and that remote previous experience with the same or a similar strain can be protective. Also, no age group born after 1890 was found to have a high prevalence of antibody against A/England/72 or A/Dunedin/73, the successors to A/Hong Kong/68, indicating that recycling of hemagglutinin antigens is not strictly ordered.

Age Factors↗

Antigenic relationships among influenza virua A neuraminidase (N2) antigens by immunodiffusion and postinfection neutralization tests.

The antigenic relationships among the neuraminidases of influenza A strains from 1957 to 1973 were examined by postinfection application of neuraminidase antisera. This procedure causes inhibition of virus spread and apparent neutralization. Neuraminidase (apparent) neutralization and neuraminidase inhibition tests with chicken antisera gave similar results. Neuraminidase inhibition tests were more discriminating than neuraminidase neutralization tests when rabbit and goat antisera were used. Antibody absorption studies revealed that the neuraminidase, like the hemagglutinin, may possess two kinds of antigenic determinants, which can give rise to "common," or "cross-reacting," and "specific" antibodies. "Specific" antibody appears to be more effective in the inhibition of enzyme activity than in the inhibition of virus spread.

Animals↗

Influenza: its antigenic variation and ecology.

Influenza viruses have two surface antigens, the glycoprotein structures hemagglutinin (HA) and neuraminidase (NA). Antibodies to each of these are associated with immunity, but the structures themselves are antigenically variable. When an antigenic change is gradual over time it is referred to as a drift, while a sudden complete or major change in either or both antigens is termed a shift. The mechanism of antigenic drift is usually attributed to selection of preexisting mutants by pressure from increasing immunity in the human population. The mechanism of antigenic shift is less clear, but one tentative hypothesis is that shifts arise from mammalian or avian reservoirs, or through genetic recombination of human and animal influenza strains.

Animals↗

Marburg virus.

Marburg virus disease, which produced 20 per cent mortality when it first occured during 1967 in Germany and Yugoslavia, recently appeared again in South Africa. The source of the first outbreak was monkeys shipped from Africa; the origin of the second episode is unclear. Because distribution of the virus in nature is unknown, its threat to man cannot be readily determined. Differential laboratory diagnoses of hemorrhagic fevers should be encouraged in order to learn more about the epidemiology of these diseases and to better assess the risks which their etiologic agents may pose for attending medical personnel.

Animals↗