Infection with influenza A H1N1. 2. The effect of past experience on natural challenge.

Following its reintroduction in 1978 influenza A H1N1 spread widely in the child population. By the autumn of 1979, 75% of 11-year olds entering a boys' boarding school had detectable antibody. The protective effect of previous experience could be assessed during two outbreaks in the school. In the first outbreak in 1979, 90% of those known to have been infected in the previous year were protected against reinfection. In 1983 after strains of the H1N1 subtype had undergone antigenic drift a large outbreak occurred. It was estimated that past infection conferred protection against clinical influenza in 55%. Where past infection resulted in the presence of antibody which reacted with the outbreak strain the attack rate was further reduced. A large number of sub-clinical infections was detected in all groups.

Reinfection with influenza A (H2N2, H3N2, and H1N1) viruses in soldiers and students in Japan.

Reinfection with influenza A virus was studied by measuring hemagglutination-inhibiting antibody responses to infection in paired sera taken from groups of soldiers and students. Among 62 soldiers severely infected during the first wave of the A/Asian/57 (H2N2) pandemic in 1957, 17 were asymptomatically reinfected with the same virus within six months. In the 1962 epidemic the rate increased to 41%. Among reinfected soldiers studied, 68% had an asymptomatic infection; only 10% were severely symptomatic, and they were found to be infected with a virus closely related to A/Asian/57. For H3N2 epidemics, the rate of reinfection was 17% among students studied in 1970 who were reinfected with a virus closely related to the prototype A/Hong Kong/68 (H3N2). Reinfection with an extremely drifted variant of H3N2 was found to be 32% and 69% in two groups of students studied in 1972. Reinfection with a related virus was 32% in another group studied in 1983. Among the students studied who were reinfected with H3N2 viruses, the rates of asymptomatic infection were similar to those of symptomatic infection. The reinfection rates with a virus related to A/USSR/77 (H1N1) were 9.3% and 20% in two groups studied in 1980.

Analysis of antigenic determinants on internal and external proteins of influenza virus and identification of antigenic subpopulations of virions in recent field isolates using monoclonal antibodies and immunogold labelling.

An electron microscopic immunogold labelling technique employing monoclonal antibodies has been applied to the antigenic analysis of influenza A and B viruses. Reassortant influenza A H3N2 viruses containing haemagglutinin molecules from viruses isolated between 1968 and 1982 were analysed with a panel of monoclonal antibodies raised against viruses which appeared over the same period. The immunogold labelling technique clearly demonstrated the antigenic drift in the haemagglutinin molecule that occurred between 1968 and 1982. When the technique was applied to the examination of viruses from a more geographically restricted influenza epidemic in a semi-closed community, antigenic variants were found. Furthermore the technique enabled the identification of distinct antigenic variant subpopulations within a single clinical isolate. Analysis of the HA of MDCK cell or egg grown virus by this procedure provided data to support the hypothesis that the host cell exerts selective pressure on subpopulations of virus resulting in the emergence of antigenic variants.

Antibody status to influenza A/Singapore/1/57(H2N2) in Finland during a period of outbreaks caused by H3N2 and H1N1 subtype viruses.

The incidence of haemagglutination inhibition (HI) antibody (titre greater than or equal to 12) to influenza A/Singapore/1/57(H2N2) in sera collected from a Finnish population in the summer of 1981 was 58%. Subjects born after 1968 were essentially seronegative, and a comparable low HI antibody status was also recorded among the elderly, the lowest being in people born during the period 1901-10. A small increase in antibody titre to the H2N2 virus was observed in the different age groups after infections with the H3N2, but not the H1N1, subtype influenza A viruses. The heterotypic response, which could be due to HI or NA antibodies, was restricted almost exclusively to subjects already exhibiting this antibody in acute phase sera. Moreover, the anamnestic boosting was not as strong as that described in earlier studies from samples collected at the beginning of the present era of H3N2 viruses. At population level, the HI antibody status to H2N2 was about the same at the beginning and end of the follow-up period which covered eight epidemic seasons. The results are discussed with respect to the doctrine of 'original antigenic sin' and to the threat of re-emergence of the H2N2 viruses.

Subclinical rubella in pregnancy--occurrence and outcome.

Between the years 1972 and 1979, 40,589 pregnant women were tested for rubella antibodies following suspected illness or exposure, using hemagglutination-inhibition (HI), complement fixation and staphylococcal absorption for determination of specific immunoglobulin M (IgM). Recent primary infection was confirmed by antibody rise in paired sera and/or the presence of specific IgM. Reinfection was differentiated from primary asymptomatic rubella by absence of specific IgM. Determination of neutralizing antibodies was also useful in confirming reinfections. Clinical rubella was confirmed in 1,448 patients (3.6%). In 154 cases asymptomatic rubella infection was detected; 98 had primary infection and 56 experienced reinfection. In a selected group of 2,200 women exposed to confirmed rubella, 6.8% had clinical rubella, 3.8% asymptomatic infection, and in 7.1% the results were doubtful. Reinfection was detected in 12.4% of 265 women with initially low HI titers. The prospective follow-up on pregnancy outcome was available in 87 women with asymptomatic infection. Seven cases of congenital rubella were detected in the group of primary infections, while all 25 children born following reinfection were healthy.

The use of IgM tests for analysis of the causes of measles vaccine failures: experience gained in an epidemic in Hungary in 1980 and 1981.

Following a period of 6 years of low measles incidence, an epidemic occurred in Hungary with more than 11,000 reported cases between September 1980 and August 1981. About 60% of the cases had a documented history of previous measles vaccination. Serum samples obtained from 7815 patients were examined for measles antibody by haemagglutination inhibition (HI). In addition to conventional antibody titration, most of the sera or their IgM fraction obtained by a simple ion exchange chromatography were tested for the presence of measles-specific IgM antibodies by 2-mercaptoethanol (2-ME) treatment, and in 300 patients also by the fluorescent antibody (FA) technique. Laboratory results confirmed the diagnosis of measles in 5356 patients and supported it in 685 cases. Primary antibody response was found in 96.1% of unvaccinated and in 77.4% of previously vaccinated patients. The percentage of secondary antibody responses increased with increasing time from vaccination only in patients vaccinated before their first birthday, whereas in those who were immunized when over 12 months old, the distribution of primary and secondary antibody responses was independent from the time that had elapsed since vaccination. Therefore, secondary vaccine failure due to waning immunity account for only 6.2% of previously vaccinated patients, whereas in 93.8% of patients, including the majority of those with secondary antibody response, a primary failure of vaccination due to unsuccessful immunization was incriminated.

Antigenic and biochemical analysis of field isolates of influenza B virus: evidence for intra- and inter-epidemic variation.

Detailed antigenic analysis using a panel of monoclonal antibodies was carried out on the haemagglutinin antigen of 53 influenza B viruses isolated from an epidemic in a single school. Thirteen distinguishable antigenic groupings of influenza B viruses could be detected but 26 of the viruses were in two groups (III and IV) which co-existed during the entire epidemic. Antigenically distinguishable influenza B viruses were isolated from an epidemic in a second nearby school. Influenza B viruses isolated from the two schools could be further distinguished by different electrophoretic mobilities of NS1 polypeptides and of genes 1, 2, 3 and 6, whereas viruses from a single school epidemic were very closely related as regards these biochemical characteristics. The findings are consistent with the hypothesis that the outbreak was initiated by a single individual who excreted antigenic mutants of which predominantly two spread and co-existed during the epidemic, although the additional occurrence of random mutations during the evolution of the epidemic cannot be excluded.

Liver function abnormalities in the course of a type A (H1N1) influenza outbreak: relation to Reye's syndrome.

In the course of the A/Brazil (H1N1) outbreak of 1978-1979, two cases of Reye's syndrome occurred in Grayling, Michigan, an area with a county-wide population of 2056 school age children. School absenteeism peaked at levels between 16-28 per cent. Clinical histories and paired blood specimens were collected from 860 school children; the initial blood was obtained shortly after the peak of the outbreak. Serologic results confirmed that type A H1N1 virus was the cause of the outbreak. Serum alanine aminotransferase (SGPT) and creatine phosphokinase (CPK) values were determined on all initial blood specimens and a sample of the second specimens. CPK results did not correlate with infection, illness or SGPT values. SGPT values of 60 IU/l or greater were found in 1.5 per cent of those tested. The elevated values were not associated with illness but were associated with influenza infection. Based on the excess number with elevated results in those with recent infection, it is estimated that at least 2.7 per cent of individuals infected by type A (H1N1) influenza had associated elevated SGPT.

[Comparative indices of the formation and protective activity of antibodies during Honk Kong influenza A epidemics]. / Sravnitel'nye pokazateli formirovaniia i zashchitnoi aktivnosti antitel v period épidemii grippa A/Gonkong.

In the period of circulation of influenza A/Hong Kong (H3N2) virus and its antigenic varieties in 1969-1976, more than 45,000 serum specimens from patients, donors, and subjects of various ages from permanently observed contingents were examined serologically by HI and CFT. The long persistence in the human population of heterologous immunity to viruses of new or old subtypes was shown to be due to its constant stimulation in the period of any subsequent influenza A epidemic. Under conditions of a natural epidemic process as well as in the studies of the epidemiological effectiveness of live influenza vaccines the protective role of not only homologous but also heterologous (although to a lower extent) antibody was confirmed. The protective role of heterologous antibody decreased gradually with progressive variability of influenza A virus.

Serum antibodies reactant with Korean haemorrhagic fever agent in Scandinavian epidemic (endemic) nephropathy (nephropathia epidemica) demonstrated by immunofluorescence utilizing an in vitro antigen source.

A newly developed spot slide immunofluorescence method utilizing an in vitro antigen source was used for the first time for the assay of antibodies reactant with the Korean haemorrhagic fever (KHF) agent in sera from patients diagnosed with Scandinavian epidemic (endemic) nephropathy (nephropathia epidemica, NE) and from age-matched control patients living in the same area as the NE patients but suffering from other diseases. KHF antibodies were demonstrated in all of 14 NE patients who were followed prospectively, 7 of whom exhibited seroconversion and in 6 of 8 NE patients studied retrospectively, but in only one of 42 controls. Antibodies in NE appeared within the first week of onset of symptoms and persisted for long periods of time as seen in KHF. The time from the onset of the illness until maximum antibody titre was recorded varied from 9 days to 1 month. On an average, the level of the antibody titres measured in NE was lower than that usually encountered in the Korean disease. The results indicate a close antigenic relationship between the KHF and NE agents and demonstrate that the reliability of our new spot slide method is similar to that of another previously reported and more laborious immunofluorescence method using lung from infected rodents as antigen source.

Evaluation of amantadine in the prophylaxis of influenza A (H1N1) virus infection: a controlled field trial among young adults and high-risk patients.

The usefulness of amantadine in the protection of humans against influenza A (H1N1) virus was evaluated in a double-blind field trial with 555 volunteers in Finland in the winter of 1978. Three populations--patients in a general hospital, adults in a home for the aged, and two groups of military conscripts--were chosen. Epidemic influenza occurred only in the two groups of conscripts: the incidence of serologically verified influenza was 66% and 83% in the groups that received placebo and 43% and 51% in the groups that received amantadine, giving protection rates of 36% (P = 0.05) and 39% (P = 0.001). The evaluation of the effect of amantadine on the occurrence of illness was obscured by concomitant adenoviral infections that caused influenza-like symptoms. No clear difference in the occurrences of side effects was observed between the placebo and amantadine-treated groups; however, a significantly greater number of participants who took 200 mg of amantadine/day (16.9%) stopped medication during the trial as compared with the placebo groups (7.6%) (P < 0.02).

Antibody response to influenza A/New Jersey and A/Victoria virus vaccines in 1976 and subsequent antibody levels after influenza A epidemics, 1977-1979.

Antibody levels before and after vaccination were studied among schoolchildren and young adults given commercial A/New Jersey/76 (HswN1), A/Victoria/75 (H3N2), and B/Hong Kong/72 vaccines in the fall of 1976. Children responded better to a single dose of the A/New Jersey subvirion vaccine than had previously been observed, particularly to a new subvirion vaccine. Hemagglutination-inhibiting antibody titers decreased during the first six months after vaccination but appeared stable thereafter. Persistence seemed to depend on the antigenic mass in the first dose, since persons given one or two doses of the most potent whole-virus vaccine had by far the highest levels of antibody to A/New Jersey virus after 2 1/2 years, higher than for those given two doses of any of the other vaccines. Natural infection with A/USSR (H1N1) influenza virus boostered the titers of antibody to A/New Jersey virus, particularly in children. Persons given a bivalent subvirion vaccine had the best response to A/Victoria antigen. Subvirion vaccines induced complement-fixing antibodies in half of the children.

Antibody studies in natural bovine cowpox.

Serological studies on cows recovered from natural cowpox indicated that Haemagglutinin-Inhibiting (HAI) antibody persisted for at least 27 weeks, and Virus Neutralizing (VN) antibody persisted for at least 98 weeks.

[Immunologic memory in influenza patients according to the blast transformation reaction to specific antigen]. / Immunologicheskaia pamiat' u bol'nykh grippom po dannym reaktsii blasttransformatsii na spetsificheskii antigen.

One hundred-sixty patients with the laboratorily confirmed diagnosis of influenza were examined in the study on the capacity of T-and B-lymphocytes to retain immunological memory for influenza infection by the method of lymphocyte blast-cell transformation (LBT). The studies were carried out in the epidemic periods of influenza A2, A1, and B at various stages of the disease and convalescence. The LBT test was positive in 21--70% of tests depending on the time after the onset. Memory cells were detectable as early as by the end of the 1st week of the disease. The optimal results were found within 2--4 months after the disease. Early in the disease LBT was detected mostly in influenza A2, less frequently in influenza A1 and was practically absent in influenza B. The specificity of reaction in response to the stimulation with influenza A2 and B viruses was demonstrated. The accompanying bacterial pneumonia, a severe course of the disease, concurrent other viral infections did not prevent immunological memory formation.

Role of the natural immunity to diphtheria in preventing an outbreak of the disease in the community.

PIP: The presence of immunity to diphtheria in children with no history of diphtheria vaccination from Tambon Chiang Rak Noi, Bang-Pa-In District, central Thailand was determined by Schick tests and throat and skin cultures. 69 or 36.3% of 190 children aged 1-9 had negative, or immune, Schick tests. 39 children showed Corynebacterium organisms, 6 of which were positive for C. diphtheriae. 37 of the positive isolates were from throat swabs, 3 of them were from skin lesions, and 1 child had positive cultures of both throat and skin. Diphtheria organisms are known to persist in the mucous membrane of the nose and throat for years in about 1% of convalescents of the disease.^ieng