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Biomedical subjects

M C Zambon

Publications and source records attributed to M C Zambon.

At least 19 recordsLinked to original sources
PubMed2003

Sialic acid receptor specificity on erythrocytes affects detection of antibody to avian influenza haemagglutinin.

Haemagglutination-inhibition tests (HI) are used to detect increases in influenza antibody in serum. However, they are relatively insensitive for the detection of human antibody responses to avian haemagglutinin, even in the presence of high titres of neutralising antibody after confirmed infection or vaccination. Human influenza viruses bind preferentially sialic acid containing N-acetylneuraminic acid alpha2,6-galactose (SAalpha2,6Gal) linkages while avian and equine viruses bind preferentially those containing N-acetylneuraminic acid alpha2,3-galactose (SAalpha2,3Gal) linkages. Increasing the proportion of SAalpha2,3Gal linkages on the erythrocytes used, by enzymatic modification or change of species, improves the ability of erythrocytes to bind to avian influenza strains and thereby improves the sensitivity of detection of antibody to avian and equine HA in a range of mammalian and human sera using HI tests.

Animals↗
PubMed2003

Three years of low influenza activity--no reason for complacency.

Influenza activity in England and Wales has been unusually low over the last three years. Despite this, substantial morbidity and mortality has occurred in subgroups of the population. Furthermore, the influenza season 2001/02 was characterised by the emergence of a new subtype of the influenza A virus (H1N2), a timely reminder that it is not possible to assess the impact of a change in the virus strains circulating without having a comprehensive surveillance infrastructure in place.

Adolescent↗
PubMed2002

Contribution of RSV to bronchiolitis and pneumonia-associated hospitalizations in English children, April 1995-March 1998.

Estimates of the number of hospitalizations attributable to specific pathogens are required to predict the potential impact of vaccination. All hospital admissions for lower respiratory tract infection (LRI) in children < 5 years in England in 1995-8 were reviewed. Most admissions (76.8%) were not associated with specific organisms. Seasonality in pathogens that cause bronchiolitis and pneumonia was used to predict the proportion of cases with unspecified aetiology attributable to different organisms using multiple linear regression. Of 12,298 admissions for LRI, 17.5% were due to RSV infection. An estimated 74.8% (95% CI, 72.0-77.7%) of 'unspecified bronchiolitis' admissions and 16.3% (95% CI, 13.7-18.8%) of unspecified pneumonia' admissions were RSV related. The total mean annual incidence of hospital admissions attributable to RSV is 28.3/1000 children < 1 year of age, and 1.3/1000 children 1-4 years old. The greater burden of RSV infection than indicated through discharge data is revealed through applying simple statistical methods.

Bronchiolitis↗
PubMed2001

Contribution of influenza and respiratory syncytial virus to community cases of influenza-like illness: an observational study.

BACKGROUND: Respiratory syncytial virus (RSV) is an important cause of lower-respiratory-tract infection in children and elderly people, but its effect in other age-groups is uncertain. We did a community-based observational study of RSV infection in community-dwelling individuals of all ages who presented to general practices in the UK with influenza-like illnesses during three successive winters (1995-96, 1996-97, and 1997-98). METHODS: Nasopharyngeal swabs routinely submitted for virological surveillance were examined by multiplex reverse transcription PCR for influenza A and B viruses and RSV A and B, and findings were related to the clinical incidence of influenza-like illness and acute bronchitis at that time. RSV strains identified were compared with those obtained from hospital admissions. FINDINGS: 480 RSV and 709 influenza viruses were identified from a total of 2226 swabs submitted. Both types of virus were found in all age-groups for between 12 and 20 weeks in each winter. RSV A accounted for 60% of RSV detections. Similar strains of RSV were present in hospital and community patients within the same year, but there were different lineages each year. INTERPRETATION: In individuals diagnosed with influenza-like illness, there is a substantial potential for confusion between illnesses caused by influenza and those caused by RSV. The burden of illness attributable to each needs to be clarified to define optimum management routines.

Adolescent↗
PubMed2001

Safety and antigenicity of non-adjuvanted and MF59-adjuvanted influenza A/Duck/Singapore/97 (H5N3) vaccine: a randomised trial of two potential vaccines against H5N1 influenza.

BACKGROUND: In 1997, pathogenic avian influenza A/Hong Kong/97 (H5N1) viruses emerged as a pandemic threat to human beings. A non-pathogenic variant, influenza A/Duck/Singapore/97 (H5N3), was identified as a leading vaccine candidate. We did an observer-blind, phase I, randomised trial in healthy volunteers to assess safety, tolerability, and antigenicity of MF59-adjuvanted and non-adjuvanted vaccines. METHODS: 32 participants were randomly assigned MF59, and 33 non-adjuvanted vaccine. Two doses were given 3 weeks apart, of 7.5, 15, or 30 microg haemagglutinin surface-antigen influenza A H5N3 vaccine. Antibody responses were measured by haemagglutination inhibition, microneutralisation, and single radial haemolysis (SRH). The primary outcome was geometric mean antibody titre 21 days after vaccination. FINDINGS: The A/Duck/SIngapore vaccines were safe and well tolerated. Antibody response to non-adjuvanted vaccine was poor, the best response occurring after two 30 microgram doses: one, four, four, and one person of eleven seroconverted by haemagglutination inhibition, microneutralisation, H5N3 SRH, and H5N1 SRH, respectively. The geometric mean titres of antibody, and seroconversion rates, were significantly higher after MF59 adjuvanted vaccine. Two 7.5 microg doses of MF59 adjuvanted vaccine gave the highest seroconversion rates: haemagglutination inhibition, six of ten; microneutralisation, eight of ten; H5N3 SRH, ten of ten; H5N1 SRH, nine of ten. Geometric mean titre of antibody to the pathogenic virus, A/Hong Kong/489/97 (H5N1), was about half that to A/Duck/Singapore virus. INTERPRETATION: Non-adjuvanted A/Duck/Singapore/97 (H5N3) vaccines are poorly immunogenic and doses of 7.5-30 microg haemagglutinin alone are unlikely to give protection from A/Hong Kong/97 (H5N1) virus. Addition of MF59 to A/Duck/Singapore/97 vaccines boost the antibody response to protection levels. Our findings have implications for development and assessment of vaccines for future pandemics.

Adult↗
PubMed2001

Combined PCR-heteroduplex mobility assay for detection and differentiation of influenza A viruses from different animal species.

Transfer of influenza A viruses from animal hosts to man may lead to the emergence of new human pandemic strains. The early detection and identification of such events are therefore paramount in the surveillance of influenza viruses. To detect and partially characterize influenza A viruses from different animal species, a combined reverse transcription (RT)-PCR heteroduplex mobility assay (HMA) was designed. This M gene RT-PCR was shown to be sensitive and specific for the detection of human, avian, and swine influenza A viruses. PCR amplicons from human, avian, and swine viruses of 15 different subtypes, with between 1.9 and 21.4% nucleotide divergence, were differentiated by HMA. Sequencing of the amplicons showed that the heteroduplex mobility patterns correlated with the sequence divergence between test and reference DNA. The application of the RT-PCR HMA method for rapid screening of samples was assessed with a reference panel of viruses of human, avian, and swine origin. The avian H9N2 virus A/HongKong/1073/99, which crossed the species barrier to humans, was screened against the reference panel. It was found to be most closely related to the avian A/Quail/HongKong/G1/97 H9N2 reference PCR product. Sequence analysis showed a nucleotide divergence of 1.1% between the A/Quail/HongKong/G1/97 and A/HongKong/1073/99 amplicons. From the results of our work, we consider the RT-PCR HMA method described to offer a rapid and sensitive means for screening for novel or unusual influenza viruses.

Animals↗
PubMed2001

Detection of influenza a subtypes in community-based surveillance.

A rapid microtitre cell enzyme immuno assay (cell-EIA) was developed for the detection of influenza A subtypes in nasopharyngeal(NPS) swabs taken for surveillance. During the 1997/1998 influenza season in the United Kingdom, cell-EIA was compared to cell culture for the detection and typing of influenza A viruses in NPS obtained by sentinel general practitioners in community surveillance. The cell EIA can also be used to detect different influenza A subtypes (H3N2, H1N1, H5N3, H5N1, H7N7, and H9N2) and was used as a rapid detection assay for the screening of individuals returning from Hong Kong with influenza-like illness suspected to be due to H5N1 in 1997/98, providing a rapid, efficient, inexpensive method for the screening of influenza A cases during an outbreak or pandemic situation. The cell-EIA results reflected the results obtained by traditional virus culture within the age distribution of samples, clinical symptoms, and time between date of illness onset and sampling of cases, indicating its usefulness in surveillance of human and non-human influenza viruses. During two outbreaks of influenza in schools, Directigen Flu-A, a near patient test, the cell-EIA, and tissue culture were compared. The cell-EIA gave higher sensitivity and specificity (74% and 90%) than Directigen Flu-A (65% and 84.6%) in comparison with cell culture.

Animals↗
PubMed2000

Different diagnostic methods for detection of influenza epidemics.

Linking continuous community-based morbidity recording of influenza-like illness (ILI) with virological sampling has consistently proved its value as one of the earliest indicators of circulating influenza activity. The clinical morbidity recording in the Portuguese national surveillance network, during a 7-year period, and the contribution of different diagnostic techniques, including virus isolation, multiplex RT-PCR, immunocapture enzyme linked immunoassay (EIA) and complement fixation tests (CFTs) for the detection of influenza in such a community-based setting is described and evaluated in this study. There was good correlation between the increase of morbidity, total samples taken and the detection of influenza virus by all the methods although this was less evident for virus isolation and EIA than for RT-PCR or serology. From a total of 1685 throat swabs collected from cases of ILI, 43.6% were RT-PCR positive, 17.5% were positive by capture EIA and in 5% virus isolates were made. The detection of influenza by RT-PCR occurred earlier than by any other method and showed the best correlation with epidemic patterns of morbidity registration. We conclude that in surveillance systems where virus culture is sub-optimal, RT-PCR provides a rapid, sensitive, specific method for detecting influenza viruses from community-based sampling.

Complement Fixation Tests↗
PubMed2000

Influenza virus infection in the second and third trimesters of pregnancy: a clinical and seroepidemiological study.

OBJECTIVE: To determine whether maternal influenza virus infection in the second and third trimesters of pregnancy results in transplacental transmission of infection, maternal auto-antibody production or an increase in complications of pregnancy. DESIGN: Case-control cohort study. POPULATION: Study and control cohorts were derived from 3,975 women who were consecutively delivered at two Nottingham teaching hospitals between May 1993 and July 1994. A complete set of three sera was available for 1,659 women. METHODS: Paired maternal ante- and postnatal sera were screened for a rise in anti-influenza virus antibody titre by single radial haemolysis and haemagglutination inhibition. Routine obstetric data collected during and after pregnancy were retrieved from the Nottingham obstetric database. Cord samples were tested for the presence of IgM anti-influenza antibodies, and postnatal infant sera were tested for the persistence of influenza-virus specific IgG. Paired antenatal and postnatal sera were tested against a standard range of auto-antigens by immunofluorescence. MAIN OUTCOME MEASURES: Classification of women as having definite serological evidence of an influenza virus infection in pregnancy (cases) or as controls. RESULTS: Intercurrent influenza virus infections were identified in 182/1,659 (11.0%) pregnancies. None of 138 cord sera from maternal influenza cases was positive for influenza A virus specific IgM. IgG anti-influenza antibodies did not persist in any of 12 infant sera taken at age 6-12 months. Six of 172 postnatal maternal sera from cases of influenza were positive for auto-antibodies. In all cases the corresponding antenatal serum was also positive for the same auto-antibody. There were no significant differences in pregnancy outcome measures between cases and controls. Overall, there were significantly more complications of pregnancy in the cases versus the controls, but no single type of complication achieved statistical significance. CONCLUSIONS: Influenza infection in the second and third trimesters of pregnancy is a relatively common event. We found no evidence for transplacental transmission of influenza virus or auto-antibody production in pregnancies complicated by influenza infections. There was an increase in the complications of pregnancy in our influenza cohort.

Adolescent↗
PubMed1999

Epidemiological features of parainfluenza virus infections: laboratory surveillance in England and Wales, 1975-1997.

Hospital laboratory reports of parainfluenza virus (PIV) infections from England and Wales between 1975 and 1997 were analysed with regard to PIV type and seasonality, and in addition, those between 1985 1997 with regard to age, sex and clinical features. Laboratory-based surveillance data highlight striking differences in the seasonality of different PIV types. PIV-3 reports demonstrated a clear annual epidemic cycle, with a peak usually occurring in late spring or summer, whereas peaks of PIV-1 and PIV-2 occurred at one or two year intervals, in the late autumn or early winter. PIV-4 also occurred most frequently in the late autumn or early winter, but a clear epidemic cycle could not be identified. Laboratory surveillance data also provide insight into the age and disease distribution of PIV infection in children and indicate severity of PIV infection in immunosuppressed adults. Of 8221 PIV reports received between 1985-1997, PIV-3 accounted for 70.8%, PIV-1 for 17.2%, PIV-2 for 7.5%, and PIV-4 for 1.1%; 64.1% of reports came from infants under one year, 24.4% from children aged 1-4 years and 7.2% from individuals aged 5 years or older, with an excess of males in all age groups. Bronchiolitis, croup and pneumonia occurred in association with all PIV types. In children under 1 year, PIV-2 infections were more likely to be associated with bronchiolitis than infections with other PIV types. In children under 15 years, croup was more frequently associated with PIV-1 and PIV-2 than with PIV-3 or PIV-4. In 392 (7.2%) of the reported PIV infections between 1989 and 1997 an underlying condition was implicated, which included immunosuppression or chronic cardiac or pulmonary disease. Considerable morbidity is associated with PIV infections in infants and young children and would make the widescale use of a vaccine a valuable public health intervention. Surveillance information is essential to guide the development and use of preventive measures as well as to monitor their effectiveness.

Adolescent↗
PubMed1999

Epidemiology and pathogenesis of influenza.

Influenza A, B and C all have a segmented genome, although only certain influenza A subtypes and influenza B cause severe disease in humans. The two major proteins of influenza are the surface glycoproteins-haemagglutinin (HA) and neuraminidase (NA). HA is the major antigen for neutralizing antibodies and is involved in the binding of virus particles to receptors on host cells. Pandemics are a result of novel virus subtypes of influenza A, created by reassortment of the segmented genome (antigenic shift), whereas annual epidemics are a result of evolution of the surface antigens of influenza A and B virus (antigenic drift). The rapid evolution of influenza viruses highlights the importance of surveillance in identifying novel circulating strains. Infectivity of influenza depends on the cleavage of HA by specific host proteases, whereas NA is involved in the release of progeny virions from the cell surface and prevents clumping of newly formed virus. In birds, the natural hosts of influenza, the virus causes gastrointestinal infection and is transmitted via the faeco-oral route. Virulent avian influenza strains, which cause systemic disease, have an HA that is cleaved by proteases present in all cells of the body, rather than by proteases restricted to the intestinal tract. In mammals, replication of influenza subtypes appears restricted to respiratory epithelial cells. Most symptoms and complications, therefore, involve the respiratory tract. However, systemic complications are sometimes observed and other viral genes besides the HA, including the NA, may be involved in determination of virulence of influenza strains in mammals.

Animals↗
PubMed1999

The influenza virus.

Influenza is a severe cause of morbidity and mortality throughout the world, resulting in annual outbreaks in all age ranges of the population. With an extensive animal reservoir the threat of emergence of a novel influenza virus, capable of causing a pandemic, has spurred research into novel therapies with which to fight the virus.

Animals↗
PubMed1999

Respiratory syncytial virus: an underestimated cause of respiratory infection, with prospects for a vaccine.

Respiratory syncytial virus (RSV) infects most people by the time they are 2 years old and reinfects throughout life. RSV is best recognised for causing bronchiolitis in infants--it is one of the most important respiratory pathogens in childhood in industrialised countries. The clinical manifestations of RSV infection in adults and elderly people, from upper respiratory tract infection to pneumonia, are less well known. Part of the burden of winter mortality in elderly people is attributable to RSV infection and it may be as important a cause of death as influenza. Recent advances in RSV vaccines have made RSV a more important topic for epidemiological research and surveillance. Basic research required before vaccine programmes can be developed includes describing the natural history of RSV infection in adults, quantifying the burden of disease attributable to RSV, and defining the best surveillance methods with which to evaluate different vaccination strategies.

Adult↗
PubMed1998

Multiplex PCR for typing and subtyping influenza and respiratory syncytial viruses.

A multiplex reverse transcription (RT)-PCR method that has been developed is capable of detecting and subtyping influenza A (H1N1 and H3N2) and B viruses as well as respiratory syncytial virus (RSV) types A and B in respiratory clinical samples taken as part of a national community-based surveillance program of influenza-like illness in England and Wales. The detection of each different pathogen depended on distinguishing five amplification products of different sizes on agarose gels following RT-PCR with multiple primer sets. The multiplex RT-PCR was tested with 65 nasopharyngeal apirates from which RSV had been isolated and 237 combined nose and throat swabs from which influenza A (H1N1 and H3N2) or B virus had been detected by virus isolation, as well as 40 respiratory samples from which other viruses including cytomegalovirus, herpes simplex virus, enteroviruses, and parainfluenza viruses had been grown. For the typing and subtyping of influenza A and B viruses and RSV types A and B, the multiplex RT-PCR gave an excellent (100%) correlation with the results of conventional typing and subtyping with specific antisera. Multiplex RT-PCR can also be used to accurately detect more than one viral template in the same reaction mixture, allowing viral coinfections to be identified with the same respiratory specimen.

Child↗
PubMed1997

Molecular analysis of an outbreak of influenza in the United Kingdom.

The first outbreak of influenza virus in Europe in 1995/1996 occurred in a school in the south of England. RT-PCR-restriction analysis was performed on the HA1 portion of influenza haemagglutinin gene amplified directly from clinical samples. These were taken at the onset of the outbreak and indicated co-circulation of two distinct genetic variants of influenza virus which were antigenically identical. Investigations of this nature demonstrate the genetic diversity of circulating variants of influenza and have the potential to provide information on molecular evolution of strains within closed populations.

Adolescent↗
PubMed1997

Multiplex reverse transcription-PCR for surveillance of influenza A and B viruses in England and Wales in 1995 and 1996.

Multiple-target (multiplex) reverse transcription-PCR (RT-PCR) for detection, typing, and subtyping of the hemagglutinin gene of influenza type A (H3N2 and H1N1) and type B viruses was developed and applied prospectively to virological surveillance of influenza in England in the 1995-1996 winter season. During this season both influenza A H3N2 and H1N1 viruses were circulating, although at different times. Six hundred nineteen combined nose and throat swabs taken by general practitioners in sentinel practices from individuals presenting with "influenzalike illness" were analyzed by culture, multiplex RT-PCR, and immunofluorescence. Of the 619 samples, 246 (39.7%) were positive by multiplex RT-PCR compared with 200 (32.3%) which yielded influenza viruses on culture. There was 100% correlation between multiplex RT-PCR typing and subtyping and the influenza types and subtypes obtained from culture. There was also excellent correlation between the temporal detection of influenza A H3N2 and H1N1 viruses by multiplex RT-PCR and by culture. During the peak weeks of influenza virus activity, a total of 259 specimens were received, of which 101 (38.9%) yielded influenza viruses on culture while 149 (57.5%) were positive in multiplex RT-PCR, providing an increase in detection of influenza viruses of approximately 20%. The increased detection of influenza virus occurred in all the age groups sampled. Samples which were positive by multiplex RT-PCR but negative by culture were not detected significantly earlier or later in the winter of 1995-1996 but were detected during the peak weeks of clinical influenza virus activity. Multiplex RT-PCR was successfully used in surveillance of influenza to provide accurate, sensitive diagnosis directly on clinical specimens sent through the post.

Adolescent↗
PubMed1997

Analysis of influenza A H3N2 strains isolated in England during 1995-1996 using polymerase chain reaction restriction.

A polymerase chain reaction-restriction (PCR-restriction) endonuclease assay was developed to allow rapid analysis of influenza A H3N2 viruses circulating in England during 1995-1996. Restriction endonuclease digestion with two enzymes of amplicons derived from PCR of the HA1 portion of the influenza haemagglutinin (HA) gene was able to differentiate antigenically similar influenza strains into two groups. Group I variants were similar genetically to the 1995/96 vaccine strain, A/Johannesburg/33/94, whereas the HA sequences of Group II variants were similar genetically to the reference virus A/Thessaloniki/1/95. Of the 700 England A H3N2 strains isolated between February 1995 and the end of April 1996, 384 were analysed by this method. PCR-restriction analysis of sequential influenza isolates revealed a temporal alteration in prevalence of two variants. Groups I and II variants cocirculated with equal frequency during a period of sporadic influenza activity, but following the onset of epidemic influenza activity in 1995, only Group II variants were detected. PCR- restriction analysis was found to be a rapid method for studying genetic variation which could be applied to a large number of samples and provide information about the direction of genetic drift in the HA gene of influenza virus.

Animals↗