An explosive outbreak of Mycoplasma pneumoniae infection in a summer camp.

An outbreak of Mycoplasma pneumoniae infection occurred in the summer of 1978 in a boys' camp in northern Wisconsin and affected 139 of 196 persons (71%); 115 (59%) had laboratory evidence of infection. In 77% of the cases, onset of disease occurred within three weeks after arrival at camp, in contrast to the usually indolent spread of the disease. Attack rates decreased with increasing age. The sensitivity of serology for detecting M pneumoniae disease may have been as low as 79%. There was shorter duration of cough in those treated with erythromycin within four days after onset of symptoms.

Epizootic of parainfluenza-3 virus infection in gibbons.

A laboratory-housed breeding colony of white-handed gibbons (Hylobates lar) experienced an epizootic of upper respiratory tract disease characterized by lethargy, anorexia, coughing, and serous rhinorrhea. Signs were more severe in adults than in offspring, and all animals recovered without complications. Base-line, acute, and convalescent sera from the most severely affected gibbons were tested for antibodies against a wide spectrum of infectious agents. For personnel known to have had contact with the gibbons, testing for the same agents was done on base-line sera and sera obtained at the same time as the acute and convalescent sera were obtained from the gibbons. Rising titers against parainfluenza-3 virus were detected in 6 of 7 gibbons tested. An increase in titer was not seen in the sera of personnel.

Seroepidemiologic survey of coronavirus (strain 229E) infections in a population of children.

The indirect hemagglutination (IHA) test for coronavirus 229E antibodies was used for serodiagnostic and seroepidemiologic studies in a population of children. Subjects ranged in age from 5 to 19 years and lived in a home which participated in a longitudinal surveilance of respiratory illness (1960-1968). During this period 1477 respiratory illnesses were observed; 63 (4%) were associated with sero-response (fourfold or greater antibody rises) to 229E. An additional 105 sero-responses were associated with unreported or subclinical illness. The frequency of these infections was cyclical, and 229E and coronavirus OC 43 infections peaked in different years among the same population. Sero-responses occurred mainly in the fall, winter and spring quarters. Preexisting antibody was demonstrated in one-third of the children with 229E sero-responses. Clinical studies indicated that the most frequent complaints with 229E infections were sore throat, coryza and cough, and the most frequent findings were pharyngeal injection, coryza and fever.

Detection of coronavirus 229E antibody by indirect hemagglutination.

Tannic-acid treated sheep erythrocytes (fresh or glutaraldehyde preserved) were sensitized with 229E antigens from human embryonic lung (RU-1) cell cultures. Indirect hemagglutination (IHA) antigen titers in 229E-infected cell cultures paralleled virus infectivity and complement fixation (CF) antigen titers. The identity of the IHA antigen was confirmed by testing extracts from inoculated and control cell cultures for ability to inhibit IHA. Also, significant increases in IHA antibody were demonstrated with acute and convalescent serum pairs from patients with proven 229E infections. A comparison of IHA, neutralization and CF titers for 229E antibodies was made on human sera drawn from different populations. The IHA and neutralization results were in agreement on 93% of the 129 sera found to be positive by at least one of three tests. The number of antibody titers detected by the CF test was insufficient to permit comparison. Hyperimmune sera from animals immunized with OC 43 did not react with 229E by IHA. Also no increase in IHA antibody was demonstrated with acute and convalescent serum pairs from patients with seroconversions to OC 43. These findings suggest that the IHA test provides (i) a rapid and sensitive method for serodiagnosis of 229E infections and (ii) a simple and inexpensive method for seroepidemiological studies.

Antigenic relationship between human coronavirus strain OC 43 and hemagglutinating encephalomyelitis virus strain 67N of swine: antibody responses in human and animal sera.

Hemagglutinating encephalomyelitis virus of swine (HEV) was adapted to growth in suckling mouse brain. Electron micrographs of HEV-infected suckling mouse brain, prepared by negative staining and thin-section techniques, exhibited typical morphological characteristics shared with other members of the Coronaviridae. The adaptation of HEV to suckling mouse brain facilitated serologic testing by the use of common host reagents and compatible animal systems. With hemagglutination inhibition, complement-fixation, and neutralization tests, an antigenic relationship was demonstrated between human coronavirus OC 43 and HEV in specific immune and hyperimmune animal sera. Children and adults with seroconversion to OC 43 antigen had diagnostic rises in titer of antibody to HEV antigens. Individuals with seroconversion to human coronaviruse 229E and B814 demonstrated antibody to HEV but not diagnostic rises in titer. Swine with titers of antibody to HEV had lower or no detectable titers of antibody to coronavirus OC 43. Although the prevalence and geometric mean titer of antibody to OC 43 were higher than the titer of antibody to HEV in every group of normal humans tested, significant differences in antibody response to coronavirus OC 43 and HEV were seen between populations that did or did not have possible contact with swine. The evidence suggested that antibody to HEV in humans probably represented a heterologous response to infection with coronavirus OC 43. However, a heterotypic response to unknown or uncharacterized strains of coronavirus cannot be excluded.

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.

Evaluation of the single radial hemolysis test for measuring hemagglutinin- and neuraminidase-specific antibodies to H3N2 influenza strains and antibodies to influenza B.

Antibodies to the H3 hemagglutinin of influenza A virus could be specifically measured by single radial hemolysis (SRH) when test antigens were recombinant viruses containing the relevant H3 hemagglutinin antigen and irrelevant Neq1 neuraminidase of A/equine/Prague/1/56 virus. Antibodies to influenza B virus could also be measured by the SRH technique. Antibody rises to influenza A or B virus measured by SRH agreed with results of hemagglutination inhibition (HI) tests for about 80% of the sera tested, including sera from volunteers receiving killed influenza vaccine and sera from patients naturally infected with influenza. Correlation between antibody titers measured by SRH and HI was also good. Antibodies to the N2 neuraminidase of influenza A virus could be specifically measured by SRH when test antigens were recombinant viruses containing the relevant N2 neuraminidase antigen and irrelevant Heq1 hemagglutinin of A/equine/Prague/1/56 virus. The SRH test for neuraminidase antibodies was more strain specific than was the SRH test for hemagglutinin antibodies. Probably for this reason, agreement between neuraminidase antibody determinations in human sera by the SRH test and by the neuraminidase inhibition test was poorer than agreement between the SRH test for hemagglutinin antibodies and the HI test.

Studies with inactivated influenza vaccines purified by zonal centrifugation. 1. Adverse reactions and serological responses.

High (3000 CCA units) and standard low (300 CCA units) doses of formalin-inactivated influenza vaccines purified by zonal ultracentrifugation were evaluated in a double-blind manner for adverse reactions and antibody responses in a high school population and in 2 adult populations.The fewest local and systemic reactions were produced by subcutaneous administration of the low doses of purified monovalent A2/Aichi/2/68, A2/Japan/170/62, and B/Massachusetts/3/66 vaccines. The high doses of A2/Japan and A2/Aichi vaccines produced 2-3-fold greater incidence of adverse reactions but did not exceed that observed with the commercial vaccines. The 3000 CCA units of B/Mass. vaccine produced more frequent and more severe systemic reactions than the polyvalent vaccine.Neither the A2/Japan vaccine nor the commercial vaccines stimulated a significant serum antibody response to A2/Aichi.The homologous serum antibody response to an Aichi vaccine was excellent in all 3 populations. A2/Aichi vaccines produced higher heterologous A2/Japan titres than did the A2/Japan vaccines. It was demonstrated that high doses of purified influenza vaccine can be given safely, and that 10-fold increases in vaccine concentration produce 2-3-fold increases in antibody titre.

Studies with inactivated influenza vaccines purified by zonal centrifugation. 2. Efficacy.

High (3000 CCA units) and standard low (300 CCA units) doses of the monovalent purified vaccines described in an earlier paper were evaluated in a double-blind manner in 2 adult populations for protective effectiveness against illness caused by the Hong Kong influenza virus. Epidemics in both populations occurred 4-6 weeks after single injections of vaccine were given.The attack rates among recipients of low or high doses of A2/Japan vaccines in a prison were virtually identical to those among the control groups receiving B/Massachusetts vaccines. The attack rate among those receiving 3000 CCA units of Aichi vaccine was nearly 70% less than the rate among recipients of A2/Japan or B/Mass. vaccines. Similarly, in a retirement community the attack rate among the recipients of 3000 CCA units of Aichi vaccine was 50%-70% lower than the attack rate among the recipients of the A2/Japan vaccine. In both populations, recipients of high doses of Aichi vaccine who later became ill tended to have less morbidity, fewer and lower fevers, and shorter stays in bed. Attack rates among the groups receiving low doses of Aichi vaccine were somewhat lower than rates among those receiving A2/Japan or B/Mass. vaccines, but the effect was not statistically significant. Divalent and polyvalent commercial vaccines were also without protective effect.The results indicate that optimally constituted influenza vaccines at standard dosage levels have little, if any, effectiveness and that even very large doses of vaccine do not approach the high degrees of effectiveness that have been achieved with other virus vaccines.

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.

Persistence of influenza A/New Jersey/76 (Hsw1N1) antibody one year after vaccination.

Serum HI and neuraminidase-inhibiting (NI) antibody measurements were made at 3, 32 and 50 weeks after inactivated influenza Hsw1N1 vaccination of 438 adults in 1976. Although the highest postvaccination geometric mean HI titers were observed in persons greater than or equal to 52 years of age, the rate of antibody decline was similar in adults of all ages. In 14 children who had a seroconversion following two doses of whole virus or split virus vaccine, the geometric mean HI antibody titer was lower after the second vaccine dose than the peak titer observed in adults, and the decrease in titer was also more rapid by 4 to 7 months. One year after influenza Hsw1N1 vaccination of adults, the prevalence of homologous HI antibody greater than or equal to 40 was 71% to 97%, whereas only two of the 14 children maintained similar titers at 5 to 7 months. Neuraminidase-inhibiting antibody titer formation occurred more frequently in those without prevaccination NI antibody, but the rate of decline was also greatest in this initially seronegative group. The rate of antibody decline at one year in the population with preexisting antibody was similar to that observed for HI antibody decline in a primed population. Heterologous influenza A/Victoria/3/75 (H3N2) HI antibody formation occurred in 22% of adults aged 25 to 51 after Hsw1N1 vaccination and in 12% of those over the age of 51, but the rate of heterologous antibody decline was more rapid than that observed for homologous antibody.

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.