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Biomedical subjects

M Zambon

Publications and source records attributed to M Zambon.

At least 19 recordsLinked to original sources
PubMed2006

SARS transmission in Vietnam outside of the health-care setting.

To evaluate the risk of transmission of SARS coronavirus outside of the health-care setting, close household and community contacts of laboratory-confirmed SARS cases were identified and followed up for clinical and laboratory evidence of SARS infection. Individual- and household-level risk factors for transmission were investigated. Nine persons with serological evidence of SARS infection were identified amongst 212 close contacts of 45 laboratory-confirmed SARS cases (secondary attack rate 4.2%, 95% CI 1.5-7). In this cohort, the average number of secondary infections caused by a single infectious case was 0.2. Two community contacts with laboratory evidence of SARS coronavirus infection had mild or sub-clinical infection, representing 3% (2/65) of Vietnamese SARS cases. There was no evidence of transmission of infection before symptom onset. Physically caring for a symptomatic laboratory-confirmed SARS case was the only independent risk factor for SARS transmission (OR 5.78, 95% CI 1.23-24.24).

Adolescent↗
PubMed2005

Influenza immunisation in children with solid tumours.

We assessed response to immunisation with trivalent split virus influenza vaccine in children with non-leukaemic malignant disease. Children with solid tumours and lymphoma received one or two doses of influenza vaccine, according to current UK guidelines, in autumn 2001 and/or 2002. Children were currently receiving chemotherapy or were within 6 months of completing chemotherapy. Pre and post vaccination sera were assessed for antibodies to the prevalent influenza strains by haemagglutination inhibition (HI). Sixty six children were assessed prior to 69 episodes of vaccination. In 30% episodes, children were susceptible to all three circulating influenza viruses (65% to H1N1, 42% to H3N2 and 90% to B) and only one patient showed protective titres (HI32) against all three strains. Seroresponse rates (4-fold rise in HI) for H1N1, H3N2 and B were 52%, 33% and 51% in 65 episodes. Following immunisation protective titres to all three viruses were seen in 25 episodes (38%) and protective responses to one or two viruses were seen in a further 12 (19%) episodes. There was no significant difference in response rates among children on treatment and off treatment and by intensity of chemotherapy. Children with solid tumours and lymphoma are highly susceptible to influenza infection. Influenza vaccine was well tolerated in this patient group and children showed a significant response to immunisation. These findings support the recommendation for annual influenza vaccination in these children.

Adolescent↗
PubMed2004

Epidemiological features of a new strain of the influenza A virus--influenza A (H1N2) circulating in England and its public health implications.

The UK influenza season of 2001/2002 was characterized by widespread geographic circulation of a new subtype of influenza A (H1N2) virus throughout the duration of the season. Younger children were predominantly infected, suggesting primary infection. Despite this, the public health impact of this new virus was minimal. It remains to be seen whether influenza A (H1N2) virus will persist and co-circulate with the previously circulating subtypes of influenza A (H1N1 and H3N2), or whether it was a sporadic recombination event that will disappear. Ultimately, the emergence of a new strain highlights the importance of continual surveillance of circulating viruses.

Adolescent↗
PubMed2004

Outbreak of influenza A (H3N2) in a highly-vaccinated religious community: a retrospective cohort study.

An outbreak of influenza occurred at the end of the 2001-2 winter season in a highly-vaccinated, semi-enclosed, religious community. On the basis of retrospective self reporting, 43% met the case definition (151/350) and 81% (25/31) of throat swabs from cases were polymerase chain reaction (PCR) -positive for influenza A (H3N2). The risk of developing influenza in people aged 65 or more was lower than that of children aged 2 years and under (odds ratio 0.1, 95% confidence interval 0.02 to 0.38). The risk of developing symptoms of influenza was not significantly different between people who had been vaccinated in the United Kingdom and those who had not been vaccinated (OR 1.14, CI 0.41 to 3.14). Chronic disease was an independent risk factor for developing symptoms of influenza (OR 1.9, CI 1 to 3.63). Timing of the outbreak, the age structure and mode of communal living may have influenced the efficacy of the influenza vaccine, which was well matched to circulating strains at the time of the outbreak. It is important to consider the diagnosis of influenza even in a highly-vaccinated community.

Adolescent↗
PubMed2003

Neuraminidase sequence analysis and susceptibilities of influenza virus clinical isolates to zanamivir and oseltamivir.

The influenza virus neuraminidase (NA) inhibitors zanamivir and oseltamivir were introduced into clinical practice in various parts of the world between 1999 and 2002. In order to monitor the potential development of resistance, the Neuraminidase Inhibitor Susceptibility Network was established to coordinate testing of clinical isolates collected through the World Health Organization influenza surveillance network from different regions of the world (M. Zambon and F. G. Hayden, Antivir. Res. 49:147-156, 2001). The present study establishes the baseline susceptibilities prior to and shortly after the introduction of the NA inhibitors. Over 1000 clinical influenza isolates recovered from 1996 to 1999 were tested. Susceptibilities were determined by enzyme inhibition assays with chemiluminescent or fluorescent substrates with known NA inhibitor-resistant viruses as controls. The 50% inhibitory concentrations (IC(50)s) depended upon the assay method, the drug tested, and the influenza virus subtype. By both assays, the mean zanamivir IC(50)s were 0.76, 1.82, and 2.28 nM for the subtype H1N1 (N1), H3N2 (N2), and B NAs, respectively, and the oseltamivir IC(50)s were 1.2, 0.5, and 8.8 nM for the N1, N2, and B NAs, respectively. The drug susceptibilities of known zanamivir- and oseltamivir-resistant viruses with the NA mutations E119V, R292K, H274Y, and R152K fell well outside the 95% confidence limits of the IC(50)s for all natural isolates. Sequence analysis of the NAs of viruses for which the IC(50)s were above the 95% confidence limits and several control isolates for which the IC(50)s were in the normal range revealed variations in some previously conserved residues, including D151, A203, T225, and E375 (N2 numbering). Known resistance mutations are both influenza virus subtype and drug specific, but there was no evidence of naturally occurring resistance to either drug in any of the isolates.

Acetamides↗
PubMed2003

Evaluation of neuraminidase enzyme assays using different substrates to measure susceptibility of influenza virus clinical isolates to neuraminidase inhibitors: report of the neuraminidase inhibitor susceptibility network.

The increasing use of influenza virus neuraminidase (NA) inhibitors (NIs) necessitates the development of reliable methods for assessing the NI susceptibility of clinical isolates. We evaluated three NA inhibition assays against a panel of five clinical isolates each of influenza virus A/H1N1, A/H3N2, and B strains and four viruses with a defined resistance genotype (R292K, H274Y, R152K, and E119V). For fluorometric enzyme assay (FA) 1 (FA-1), 2'-(4-methylumbelliferyl)-alpha-D-N-acetylneuraminic acid (MUNANA) at 100 microM was used as the substrate, with pretitration of the virus input. For FA-2, MUNANA at 200 microM was used as the substrate, with a fixed 1:10 dilution of input virus. For the chemiluminescence (CL) assay, the 1,2-dioxetane derivative of sialic acid at 100 microM was used as the substrate, with pretitration of the virus. Four different operators repeated the assays several times in a blinded fashion with both zanamivir and oseltamivir carboxylate (GS4071) to determine intra- and interassay variations. Mean 50% inhibitory concentration (IC(50)) values were lower and generally less variable with the CL assay. FA-1 displayed greater variation than the CL assay or FA-2 and the highest IC(50) values with zanamivir; FA-2 showed the highest values with oseltamivir, particularly for influenza virus B, and was more variable with zanamivir than was the CL assay. All three assays detected 40-fold or greater changes in IC(50) values for the resistant viruses with at least one drug. Mixing experiments, whereby increasing fractions (0, 20, 40, 60, 80, and 100%) of NA from a known NI-resistant virus were mixed with the corresponding NI-sensitive parental NA, indicated that the resolution of IC(50) values was clearer with the CL assay than with FA-2 for two of the resistant variants (R152K and E119V). The FA and CL methods were reliable for the detection of NI resistance, but all assays have certain limitations. Based on reproducibility, ease of automation, time required for the assay, and greater sensitivity, the CL assay was selected for future susceptibility testing of influenza virus isolates circulating globally.

Drug Resistance, Viral↗
PubMed2003

Severe and unrecognised: pertussis in UK infants.

AIMS: To diagnose pertussis using culture, polymerase chain reaction, and serology, in children admitted to intensive care units (PICUs) and some paediatric wards in London, and in their household contacts to determine the source of infection. METHODS: Infants <5 months old admitted to London PICUs between 1998 and 2000 with respiratory failure, apnoea and/or bradycardia, or acute life threatening episodes (ALTE), and children <15 years admitted to paediatric wards at St Mary's and St George's Hospitals between 1999 and 2000 with lower respiratory tract infection, apnoea, or ALTE were studied. RESULTS: Sixty seven per cent of eligible children (142/212) were recruited; 23% (33/142) had pertussis, 19.8% (25/126) on the PICU and 50% (8/16) on wards. Two died. Only 4% (6/142) were culture positive. Pertussis was clinically suspected on admission in 28% of infants (7/25) on the PICU and 75% (6/8) on the wards. Infants on PICU with pertussis coughed for longer, had apnoeas and whooped more often, and a higher lymphocyte count than infants without pertussis. Pertussis and respiratory syncytial virus (RSV) co-infection was frequent (11/33, 33%). Pertussis was confirmed in 22/33 (67%) of those who were first to become ill in the family. For 14/33 children the source of infection was a parent; for 9/33 the source of pertussis was an older fully vaccinated child in the household. CONCLUSIONS: Severe pertussis is under diagnosed. An RSV diagnosis does not exclude pertussis. Future changes to the UK vaccination programme should aim to reduce pertussis transmission to young infants by their parents and older siblings.

Anti-Bacterial Agents↗
PubMed2002

Experience with the clinical development of influenza vaccines for potential pandemics.

During normal interpandemic influenza seasons, immune responses to vaccines are quite predictable and meet the licensing criteria of the European Union (EU) Committee for Proprietary Medicinal Products (CPMP). In a pandemic situation, large sections, if not all of the community will be immunologically naïve and therefore new immunisation strategies will be needed. In 1976 and 1977 H1N1 vaccines were prepared and tested clinically. To stimulate 'protective' antibody responses, two doses of vaccine were needed in people below the age of 24 years (no previous experience of H1N1 virus), whereas one conventional dose was adequate in older people. In 1997, the highly pathogenic avian influenza H5N1 virus caused widespread concern when it infected man, with lethal effects. Due to safety concerns it was necessary to adopt new strategies for vaccine development and one such strategy was to produce vaccine from an avirulent H5N3 virus, A/Duck/Singapore-Q/F119-2/97. Clinical trials of a subunit vaccine prepared from A/Duck/Sing/97 virus revealed that even two doses of twice the normal vaccine concentration (i.e. 30 micro g haemagglutinin) were poorly immunogenic, whereas an H5N3 vaccine adjuvanted with microfluidised emulsion (MF) 59 stimulated antibody levels that complied with CPMP criteria after two half strength doses (i.e. 7.5 micro g haemagglutinin).

Clinical Trials as Topic↗
PubMed2002

Emergence of influenza A H1N2 reassortant viruses in the human population during 2001.

Influenza A H1N2 viruses, which emerged during 2001, are genetic reassortants between H1N1 and H3N2 subtype viruses which have cocirculated in the human population since 1977. They possess a H1 hemagglutinin antigenically and genetically similar to contemporary A/New Caledonia/20/99 (H1N1)-like viruses and seven genes closely related to those of recent A/Moscow/10/99 (H3N2)-like viruses. The viruses have spread to many regions of the world and have predominated over H1N1 viruses in several countries. Since half of the amino acid changes which accumulated in the HAs of H1N1 viruses since 1995 are in residues implicated in receptor binding, functional changes in the H1 HA may have facilitated its replacement of the H3 HA and may contribute to the future epidemiologic significance of these H1N2 viruses.

Geography↗
PubMed2002

The epidemiology of influenza.

Influenza remains a globally important cause of febrile respiratory illness. Influenza virus activity in the community results in significant mortality, morbidity and economic disruption, particularly in those at high risk of developing complications, such as the elderly and those with underlying chronic medical conditions, including pulmonary disease and diabetes mellitus. The occurrence in Hong Kong in 1997 of avian influenza H5N1 in man, which resulted in six deaths, served to remind us of the importance of continuing surveillance and preparation for the next pandemic.

Antigenic Variation↗
PubMed2001

Diagnosis of influenza in the community: relationship of clinical diagnosis to confirmed virological, serologic, or molecular detection of influenza.

BACKGROUND: Successful treatment of influenza depends on an accurate diagnosis of the illness and prompt intervention. However, there is a lack of data comparing clinical diagnosis vs laboratory diagnostic techniques. OBJECTIVE: To compare the clinical diagnosis of community cases of influenza with various laboratory diagnostic techniques including multiplex, reverse transcription polymerase chain reaction. METHODS: Clinical diagnosis, viral isolation, hemagglutinin inhibition serology, and multiplex, reverse transcription polymerase chain reaction were used to diagnose influenza in patients enrolled in international phase 3 studies designed to investigate the efficacy and safety of an anti-influenza drug (inhaled zanamivir). Patients clinically diagnosed with influenza were enrolled at centers across North America and Europe. RESULTS: A total of 791 (77%) of 1033 patients with laboratory results from all 3 methods were confirmed positive for influenza by 1 or more test results. For 692 patients (67%), the results of all 3 tests agreed. Total symptom scores at baseline showed a significant association toward greater severity of symptoms with an increasing number of positive test results (P<.001). An increasing number of positive test results also showed a significant correlation with a longer time to alleviation of symptoms of influenza in the placebo group (P =.001). CONCLUSIONS: During a time when influenza was known to be circulating and clinical diagnostic criteria were applied, diagnosis of influenza in these trials was accurate in approximately 77% of adults on clinical grounds alone. This highlights the need for primary care physicians to be alerted to circulating influenza and to be aware that presentation with cough and fever provide the most predictive symptoms.

Administration, Inhalation↗
PubMed2001

Flavonoids as chemotaxonomic markers for Asteraceae.

Flavonoids have been shown to be good taxonomic markers for Asteraceae. More than 800 compounds comprising 4700 flavonoid occurrences were included in a computational system specially made for chemotaxonomic purposes. Some implications of flavonols, flavones and other types as well as structural features of them are discussed for tribes and subtribes of Asteraceae.

Journal Article↗
PubMed2001

Antibody responses to vaccinations given within the first two years after transplant are similar between autologous peripheral blood stem cell and bone marrow transplant recipients.

As a consequence of the significantly larger inoculum of lymphoid cells present in peripheral blood stem cell (PBSC) harvests compared to bone marrow (BM), it is possible that autoPBSCT recipients may have an earlier and*or enhanced response to vaccines. Until data to confirm this become available, the European Blood and Marrow Transplantation Association (EBMT) recommend that all transplant recipients be immunized in the same way regardless of stem cell source. We performed a prospective study comparing serological responses to influenza, pneumococcal polysaccharide and tetanus toxoid vaccines between autoPBSCT with autoBMT recipients. Antibody responses in sibling HLA-matched allogeneic BMT (alloBMT) survivors were also evaluated. All vaccines were administered within the first 2 years after stem cell transplantation. Fifty patients were enrolled. The time of vaccination after transplant was similar between autoPBSCT (mean 11 months for each vaccine) and autoBMT recipients (mean 12 months except 13 months for tetanus toxoid) (P = NS). Serological responses were poor and no significant difference in response to any of the vaccines used was seen between the three transplant cohorts. We provide no evidence that current EBMT guidelines be modified. Large prospective vaccine studies are needed to address the issue more fully.

Adolescent↗
PubMed2001

Influenza A antigen exposure selects dominant Vbeta17+ TCR in human CD8+ cytotoxic T cell responses.

During acute human viral infections, such as influenza A, specific cytotoxic T lymphocytes (CTL) are generated which aid virus clearance. We have observed that in HLA-A*0201+ subjects, CTL expressing Vbeta17+ TCR and recognizing a peptide from the influenza A matrix protein (M1(58-66)) dominate this response. In experimental models of infection such dominance can be due to inheritance of a restricted T cell repertoire or acquired consequent on expansion of CTL bearing an optimum TCR conformation against the MHC-peptide complex. To examine how influenza A infection might influence the development of TCR Vbeta17 expansion, we studied influenza A-specific CTL in a cross-sectional study of 82 HLA-A*0201+ individuals from birth (cord blood) to adulthood. Primary M1(58-66) -specific CTL were detected in cord blood, but their TCR were diverse and depletion of Vbeta17+ cells did not abrogate specific cytotoxicity. In contrast following natural influenza A infection, TCR Vbeta17+ CTL dominated to the extent that only one of nine adult CTL lines retained any functional activity after in vitro depletion of Vbeta17+ CTL. These results suggest that the dominance of Vbeta17+ TCR among adult M1(58-66)-specific CTL results from maturation and focussing of the response driven by exposure to influenza, and have implications for optimum immunization strategies.

Adolescent↗
PubMed2001

Update on influenza and other viral pneumonias.

Major developments during the past 5 years concerning influenza prevention by vaccination and treatment with neuraminidase inhibitors are reviewed. These have been accompanied by increased media interest in related issues: pressures on hospital admissions, ethical concerns and controls on prescribing limiting professional autonomy. The new live attenuated influenza vaccines, adjuvanted vaccines and the emerging recombinant DNA vaccines are discussed. Recent information on neuraminidase inhibitor antivirals, surveillance for resistant viruses, the prospects for near patient tests (i.e. tests that can be used near the patient to improve immediate patient management or in the laboratory to give rapid feedback for physicians) and the clinical significance of other respiratory viruses are highlighted. The benefits of recent advances provide challenges for health care delivery and public acceptance as great as those involved in their scientific development.

Animals↗
PubMed2001

Response to influenza immunisation during treatment for cancer.

AIMS: To assess the annual risk of influenza infection in children with cancer and the immunogenicity of a trivalent split virus influenza vaccine in these children. METHODS: Eighty four children with cancer were tested for susceptibility to the circulating strains of influenza virus in autumn 1995 and 1996. Non-immunised children were reassessed the following spring for serological evidence of natural infection. Forty two patients received two doses of influenza vaccine. These children were receiving continuing chemotherapy for acute lymphoblastic leukaemia or were within six months of completing chemotherapy. RESULTS: Among the 84 children tested for influenza virus susceptibility only 8% of patients were fully protected (antibody titres >/= 40) against all three of the prevalent influenza virus strains; 33% were susceptible to all three viruses. Evidence of acquired natural infection was seen in 30% of unimmunised patients. Among immunised susceptible patients, 66% made some protective response to the vaccine and 55% showed protective antibody titres to all three viral strains following vaccination. Older age was associated with increased response to the H1N1 and H3N2 vaccine components, but total white cell count or neutrophil count at immunisation, type of cancer, or length of time on treatment for acute lymphoblastic leukaemia did not affect response. CONCLUSIONS: Most children with cancer studied were at risk of influenza infection. A significant response to immunisation was seen, supporting annual influenza vaccination for children being treated for cancer.

Acute Disease↗