Marguerite S. Pereira

Diagnostic assays with monoclonal antibodies for the human serum parvovirus-like virus (SPLV).

Monoclonal antibodies to the serum parvovirus-like virus (SPLV) were prepared by the hybridoma technique. They provided an antibody reagent which was used to develop solid phase antibody-capture assays for anti-SPLV IgM and IgG and for SPLV antigen. These assays were more sensitive than those based on human convalescent antibody as a reagent, and were more economical in the use of SPLV antigen. Their use enabled the serological responses to SPLV to be studied more fully and their sensitivity revealed the extent of SPLV infection. SPLV antigen was detected in four patients by both counter-immuno electrophoresis (CIE) and radioimmunoassay (RIA) and in two others by RIA alone. Parvovirus particles were seen in all six by electron microscopy. The anti-SPLV IgM response was measured in patients infected by SPLV. It was strong 5-18 days after the onset of illness, then declined and was only detectable in trace amounts after 6 months. Anti-SPLV IgG was also formed early, and persisted for at least 6 months. In a survey of 310 blood donors anti-SPLV was detected in 134 (43%) by CIE, but in 190 (61%) by IgG antibody capture RIA.

Prevalence of Antibody to Current Influenza Viruses and Effect of Vaccination on Antibody Response

The extent of antibody to the influenza virus A/Hong Kong/68 (H3N2) after four years of prevalence was investigated in Britain and in the U.S.A. The results indicated a high incidence in both populations. The prevalence of antibody to a variant A/England/42/72 (H3N2) which has been causing epidemics of influenza in the southern hemisphere during the middle months of 1972 was also investigated. The differences reflect the shift in antigenic content of this variant, and although the overall proportion of the sera with antibody at > 1/40 was 37%, some age groups had an incidence of only 20% or less with antibody at this level. A commercial inactivated A/Hong Kong/68 influenza vaccine was given to a group of volunteers in Britain to see how effective it might be in stimulating antibody to the variant A/England/42/72. The antibody responses were better than expected from earlier vaccine studies, and 63% of the vaccinees developed antibody to the A/England/42/72 to levels thought likely to be protective. This suggested that until a vaccine made with the variant A/England/42/72 becomes available the present A/Hong Kong/68 vaccine would be of use to protect those at special risk this winter.

Antigenic Variants of Influenza B Virus

From 1967 to 1971 little antigenic variation was detected in the prevalent influenza B viruses but in December 1972 a new antigenic variant of influenza B was isolated in Hong Kong from sporadic cases of influenza. The new variant, B/Hong Kong/5/72, possessed a haemagglutinin antigen which showed considerable antigenic differences from that of former influenza B strains while its neuraminidase antigen was closely related to that of the earlier, 1967-71, isolates. The B/Hong Kong/5/72 variant became the predominant influenza B strain in the United Kingdom by early summer 1973, and in both the United Kingdom and Japan this strain was associated with outbreaks of influenza. Strains antigenically intermediate between the 1967-71 isolates and B/Hong Kong/5/72 were isolated in a number of countries, often concurrently with B/Hong Kong/5/72-like strains. Serological studies indicated that antibody to B/Hong Kong/5/72 was infrequent in the populations in the United Kingdom and the U.S.A., suggesting the possibility of future epidemic activity associated with the new variant. In addition, conventional inactivated influenza vaccines containing the older influenza B isolates given to volunteers stimulated poor antibody responses to B/Hong Kong/5/72 virus. These studies indicate the desirability of immunizing high risk patients against B/Hong Kong/5/72-like viruses before the coming influenza season. Vaccine containing the new variant influenza B strain are currently available in the United Kingdom.

Influenza in the United Kingdom 1982-85.

Influenza surveillance in the UK between the years 1982 and 1985 has demonstrated the regular winter appearance of influenza A virus of both H1N1 and H3N2 subtypes and influenza B. Their antigenic diversity is described and correlated with the national statistics for morbidity and mortality for influenza. One unexpected finding has been that despite the wide circulation of influenza viruses there has been a continuation of winters without significant increases in influenza deaths or morbidity. A previous report of influenza surveillance (Pereira & Chakraverty, 1982) noted an already unusual series of three consecutive winters with this pattern. This report records a further 4 years bringing a total of seven successive winters without evidence of epidemics of severe disease associated with influenza viruses, as indicated by the national UK statistics.

Influenza in the United Kingdom 1977–1981

The laboratory surveillance of influenza in the UK has continued to demonstrate the regularity of influenza outbreaks each winter even in the absence of increase in the other indices which reflect the morbidity and mortality associated with influenza. The period of five years from 1976 to 1981 has seen the appearance of a second sub-type of influenza. A with the return of the historic H1N1 virus; and the continued circulation of H3N2 concurrently with H1N1 virus. Variants of both these influenza A viruses have been demonstrated as well as further changes in the strains of influenza B virus isolated during this time.

The association of viruses with clinical pertussis.

This study describes the results of attempts to grow viruses from per-nasal swabs taken from 136 children with clinical pertussis.Altogether 37 strains of a variety of different viruses were isolated. Adenovirus was the most frequent, making up 30% of the total. Besides these, herpes simplex, measles, influenza A2, influenza B, mumps, poliovirus and respiratory syncytial virus were detected.Bordetella pertussis was isolated from 22% of the cases.It appears that a pertussis-like syndrome can be caused by many agents besides Bord. pertussis and an accurate diagnosis requires laboratory confirmation.

The laboratory surveillance of influenza epidemics in the United Kingdom 1968-1976.

The extensive laboratory investigations of respiratory disease in the U.K. over many years have demonstrated the frequency with which influenza viruses, both A and B, are found each winter. Only rarely are none isolated. These findings correlate well with other indicators of influenza such as increases in sickness benefit claims and in deaths attributed to influenza and pneumonia. However, outside these demonstrable peaks of incidence influenza viruses have been found to circulate over considerably longer periods often first appearing as early as November and continuing through to April or even May. But there has been no regular or predictable pattern determined. The period of 1968-76 has seen a series of differently developing influenza winter epidemics caused by a series of the H3N2 virus. The contributions of virus isolation and serology to influenza surveillance is discussed.

Hong Kong influenza in the Royal Air Force 1968–70

A prospective serological and clinical study of the epidemics due to the A2/Hong Kong/68 influenza virus was made during the winters 1968-9 and 1969-70 in volunteer subjects in the Royal Air Force. In October 1968 nearly all subjects had haemagglutination inhibiting (HI) antibody to the A2/Singapore/57 virus and more than half had antibody to strains more recently prevalent in Britain. The proportion with HI antibody to A2/Hong Kong/68 increased from 31% in October 1968 (most at low titres) to 44% after the first epidemic and 72% after the second (most at high titres). Serological infection rates were much lower in those who had detectable antibody at the beginning of each winter than in those who did not. Respiratory illnesses coupled with serological evidence of influenza infection during the winter were rare in persons with an initial titre of HI antibody of 1/40 or more. Infection in the first winter conferred complete protection against infection, with or without illness, in the second. In both epidemics about half those with serological evidence of infection had no reported illness.

Live influenza B vaccine in volunteers. A report to the Medical Research Council by their Committee on Influenza and Other Respiratory Virus Vaccines.

In this paper we describe our experience with a. live vaccine made from an influenza type B virus. Type B was chosen for a number of reasorls. We had had no previous experience with it, an attenuated virus with an acceptable passage history was available, and the low incidence of haemagglutination-inhibiting (HI) antibodies in the population was likely to make it easier to find susceptible volunteers than when an A virus was used. In addition, because different antigenic subtypes of influenza B circulate at the saxnel time (Coinmunicable Disease Center Report, 1965) we wished to look at the evidence for cross-protection. We a]so wished to assess the importance of repeated vaccinatiorls, on which some Russian workers lay considerable stress (SmorodintseJv et al., 1965). Previous trials of live influerlza vaccines in Great Britain (in which repeated vaccinations had not been given) had used vaccines made from a 1957 Russian A 2 virus (McDonald et al. 1 962; Andrews et al. 1 966; Beare et al. 1 967). The results showed that attenuated live viruses infected fairly readily when serum antibody was low or absent, that infection was followed by resistance to challenge with the sarne virus, and that there was a significant rise of antibody in a proportion of people.

The influence of antigenic variation on influenza A2 epidemics

The pattern of epidemics due to influenza A 2 virus can be determined by several means: by following changes in sickness benefit claims, mortality rates and general practitioner consultation rates (Miller & Lee, 1969) and by accumulating laboratory evidence of the presence of influenza viruses in the population. Over the past decade information from these various sources has been found to correlate very closely and a clear picture can be drawn of the epidemics which have occurred every winter but three since 1957. The factors which allow such epidemics to develop are only partly understood but there are two which can be measured and which certainly play a part. One of these is the antigenic structure of the prevalent virus and the other is the antibody directed against it in the exposed population. Both these factors are unstable because of the antigenic variation which influenza A virus undergoes from time to time and because serum antibody is not necessarily maintained at high titre against the original infecting strain and, indeed, may become undetectable against a sufficiently changed new variant. Attempts have been made to assess the importance of these factors in explaining the repeated epidemics due to influenza A2 virus which have occurred in Britain since 1957.