Maria Zambon

Public Health England, Londinium, England, United Kingdom

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Publications (197)1337.96 Total impact

  • [show abstract] [hide abstract]
    ABSTRACT: Assessment of the effect of influenza on populations, including risk of infection, illness if infected, illness severity, and consultation rates, is essential to inform future control and prevention. We aimed to compare the community burden and severity of seasonal and pandemic influenza across different age groups and study years and gain insight into the extent to which traditional surveillance underestimates this burden. Using preseason and postseason serology, weekly illness reporting, and RT-PCR identification of influenza from nasal swabs, we tracked the course of seasonal and pandemic influenza over five successive cohorts (England 2006-11; 5448 person-seasons' follow-up). We compared burden and severity of seasonal and pandemic strains. We weighted analyses to the age and regional structure of England to give nationally representative estimates. We compared symptom profiles over the first week of illness for different strains of PCR-confirmed influenza and non-influenza viruses using ordinal logistic regression with symptom severity grade as the outcome variable. Based on four-fold titre rises in strain-specific serology, on average influenza infected 18% (95% CI 16-22) of unvaccinated people each winter. Of those infected there were 69 respiratory illnesses per 100 person-influenza-seasons compared with 44 per 100 in those not infected with influenza. The age-adjusted attributable rate of illness if infected was 23 illnesses per 100 person-seasons (13-34), suggesting most influenza infections are asymptomatic. 25% (18-35) of all people with serologically confirmed infections had PCR-confirmed disease. 17% (10-26) of people with PCR-confirmed influenza had medically attended illness. These figures did not differ significantly when comparing pandemic with seasonal influenza. Of PCR-confirmed cases, people infected with the 2009 pandemic strain had markedly less severe symptoms than those infected with seasonal H3N2. Seasonal influenza and the 2009 pandemic strain were characterised by similar high rates of mainly asymptomatic infection with most symptomatic cases self-managing without medical consultation. In the community the 2009 pandemic strain caused milder symptoms than seasonal H3N2. Medical Research Council and the Wellcome Trust.
    The lancet. Respiratory medicine. 03/2014;
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    ABSTRACT: ABSTRACT Cross-species transmission of zoonotic coronaviruses (CoVs) can result in pandemic disease outbreaks. Middle East respiratory syndrome CoV (MERS-CoV), identified in 2012, has caused 182 cases to date, with ~43% mortality, and no small animal model has been reported. MERS-CoV and Pipistrellus bat coronavirus (BtCoV) strain HKU5 of Betacoronavirus (β-CoV) subgroup 2c share >65% identity at the amino acid level in several regions, including nonstructural protein 5 (nsp5) and the nucleocapsid (N) protein, which are significant drug and vaccine targets. BtCoV HKU5 has been described in silico but has not been shown to replicate in culture, thus hampering drug and vaccine studies against subgroup 2c β-CoVs. We report the synthetic reconstruction and testing of BtCoV HKU5 containing the severe acute respiratory syndrome (SARS)-CoV spike (S) glycoprotein ectodomain (BtCoV HKU5-SE). This virus replicates efficiently in cell culture and in young and aged mice, where the virus targets airway and alveolar epithelial cells. Unlike some subgroup 2b SARS-CoV vaccines that elicit a strong eosinophilia following challenge, we demonstrate that BtCoV HKU5 and MERS-CoV N-expressing Venezuelan equine encephalitis virus replicon particle (VRP) vaccines do not cause extensive eosinophilia following BtCoV HKU5-SE challenge. Passage of BtCoV HKU5-SE in young mice resulted in enhanced virulence, causing 20% weight loss, diffuse alveolar damage, and hyaline membrane formation in aged mice. Passaged virus was characterized by mutations in the nsp13, nsp14, open reading frame 5 (ORF5) and M genes. Finally, we identified an inhibitor active against the nsp5 proteases of subgroup 2c β-CoVs. Synthetic-genome platforms capable of reconstituting emerging zoonotic viral pathogens or their phylogenetic relatives provide new strategies for identifying broad-based therapeutics, evaluating vaccine outcomes, and studying viral pathogenesis. IMPORTANCE The 2012 outbreak of MERS-CoV raises the specter of another global epidemic, similar to the 2003 SARS-CoV epidemic. MERS-CoV is related to BtCoV HKU5 in target regions that are essential for drug and vaccine testing. Because no small animal model exists to evaluate MERS-CoV pathogenesis or to test vaccines, we constructed a recombinant BtCoV HKU5 that expressed a region of the SARS-CoV spike (S) glycoprotein, thereby allowing the recombinant virus to grow in cell culture and in mice. We show that this recombinant virus targets airway epithelial cells and causes disease in aged mice. We use this platform to (i) identify a broad-spectrum antiviral that can potentially inhibit viruses closely related to MERS-CoV, (ii) demonstrate the absence of increased eosinophilic immune pathology for MERS-CoV N protein-based vaccines, and (iii) mouse adapt this virus to identify viral genetic determinants of cross-species transmission and virulence. This study holds significance as a strategy to control newly emerging viruses.
    mBio 01/2014; 5(2). · 5.62 Impact Factor
  • Euro surveillance: bulletin europeen sur les maladies transmissibles = European communicable disease bulletin 01/2014; 19(3). · 5.49 Impact Factor
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    ABSTRACT: Following human infections with novel avian influenza A(H7N9) viruses in China, the European Centre for Disease Prevention and Control, the World Health Organization (WHO) Regional Office for Europe and the European Reference Laboratory Network for Human Influenza (ERLI-Net) rapidly posted relevant information, including real-time RT-PCR protocols. An influenza RNA sequence-based computational assessment of detection capabilities for this virus was conducted in 32 national influenza reference laboratories in 29 countries, mostly WHO National Influenza Centres participating in the WHO Global Influenza Surveillance and Response System (GISRS). Twentyseven countries considered their generic influenza A virus detection assay to be appropriate for the novel A(H7N9) viruses. Twenty-two countries reported having containment facilities suitable for its isolation and propagation. Laboratories in 27 countries had applied specific H7 real-time RT-PCR assays and 20 countries had N9 assays in place. Positive control virus RNA was provided by the WHO Collaborating Centre in London to 34 laboratories in 22 countries to allow evaluation of their assays. Performance of the generic influenza A virus detection and H7 and N9 subtyping assays was good in 24 laboratories in 19 countries. The survey showed that ERLI-Net laboratories had rapidly developed and verified good capability to detect the novel A(H7N9) influenza viruses.
    Euro surveillance: bulletin europeen sur les maladies transmissibles = European communicable disease bulletin 01/2014; 19(4). · 5.49 Impact Factor
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    The Lancet Infectious Diseases 01/2014; 14(1):8. · 19.97 Impact Factor
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    ABSTRACT: Background. Middle East Respiratory Syndrome Coronavirus (MERS-CoV) emerged in 2012 causing Severe Acute Respiratory Disease and pneumonia, with ∼44% mortality in 136 cases till date. Design of vaccines to limit the virus spread or diagnostics to track newly emerging strains requires knowledge of antigenic and serological relationships of MERS-CoV to other coronaviruses.Methods. Using synthetic genomics and Venezuelan Equine Encephalitis Virus replicons (VRPs) expressing S and N proteins from MERS-CoV and other human and bat CoV`s, we characterize the antigenic (using western blots and ELISA) and serological responses (using Neutralization Assays) against two MERS-CoV isolates in comparison with other human and bat coronaviruses.Results. Serologic and neutralization responses against the S glycoprotein were primarily strain specific with very low level cross reactivity within, or across subgroups. Coronaviruses N proteins within, but not across subgroups, share cross-reactive epitopes with MERS-CoV isolates. Our findings were validated using MERS-CoV patient (NA 01) convalescent serum, and human serum to SARS-CoV, NL63 and OC43.Conclusions. Vaccine design for emerging coronaviruses should involve chimeric S protein containing neutralizing epitopes from multiple virus strains across subgroups, to reduce immune pathology, and diagnostic platform should include a panel of N and S proteins from phylogenetically distinct coronaviruses.
    The Journal of Infectious Diseases 11/2013; · 5.85 Impact Factor
  • Deeva Berera, Maria Zambon
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    ABSTRACT: The World Health Organization's declaration of an imminent swine-origin influenza A pandemic in April 2009 triggered the global launch of national pandemic preparedness plans. An integral component of pandemic preparedness in many countries was the targeted use of antiviral therapy for containment, disease mitigation, and treatment. The 2009 pandemic marked the first pandemic during which influenza antivirals were available for global use. Although most national pandemic plans included provisions for antiviral treatment, these pre-determined protocols required frequent updating as more information became available about the virus, and its susceptibility to antiviral agents, the epidemiology of infection, and the population groups that were most susceptible to severe disease. National public health agencies in countries with both plans for use of antivirals and pre-existing stockpiles, including those in Japan, the United Kingdom, and the United States, operated distinctly different antiviral distribution and treatment programs from one another. In the 3 years following the pandemic, there is still little comparison of the diversity of national antiviral treatment policies and drug distribution mechanisms that were implemented, whether they had any mitigating effects and which might be most efficient. The purpose of this study is to outline roles of antiviral medicines in a pandemic period, provide insights into the diversity of antiviral treatment and distribution policies applied by selected countries between April 2009-July 2010, and to stimulate discussion on whether these policies remain appropriate for implementation in future pandemics.
    Influenza and Other Respiratory Viruses 11/2013; 7 Suppl 3:72-9. · 1.47 Impact Factor
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    ABSTRACT: Background. We report a follow up clinical and serological investigation of 274 children receiving seasonal influenza vaccine (TIV) one year after receipt of either AS03B-adjuvanted subunit or whole virus monovalent A(H1N1)pdm09 vaccine and describe the antibody responses to the H3N2 A/Perth/16/2009 and B/Brisbane/60/2008 components of TIV. Method and Findings. Vaccine responses were analysed using Haemagglutination Inhibition (HAI) assays. In individuals under 3 years of age, previous receipt of adjuvanted vaccine resulted in higher HAI antibody responses to H3N2 and B strains compared to non-adjuvanted vaccine (fold change 16.8 vs 4.3 for H3N2 and 7.0 vs 1.6 for B). In older children, responses to the H3 and B components of TIV were similar between vaccine groups. Sera taken pre- and post pandemic vaccine were also analysed by HAI with A/Perth/16/2009 virus. This analysis showed that 11.1% of children receiving the AS03B-adjuvanted vaccine but only 1.4% in the non-adjuvanted group had a 4-fold rise to A/Perth/16/2009. Conculsion. AS03B-adjuvanted A(H1N1)pdm09 influenza vaccine generates a cross-reactive antibody response to H3N2 in children and enhances responses to heterologous subtypes in <3-year-old children one year later.
    Clinical Infectious Diseases 10/2013; · 9.37 Impact Factor
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    ABSTRACT: Current seasonal influenza vaccines have reduced immunogenicity and are of suboptimal efficacy in older adults. We have previously shown that the novel candidate vaccineMVA-NP+M1 is able to boost memory T cell responses in adultsaged 50-85 years. Pre-clinical studies have demonstrated that viral vectored vaccines can act as adjuvants when co-administered with protein-based vaccines.We have conducted a phase I clinical trial to compare co-administration of seasonal influenza vaccine and MVA-NP+M1, to seasonal influenza vaccine alone in adults aged 50 years and over. This combination of vaccines was safe and well tolerated. T cell responses to internal influenza proteins were boosted to significantly higher levels in the group receiving MVA-NP+M1 compared to the group receiving seasonal influenza vaccine alone. Rates of seroprotection and seroconversionagainst the three vaccine strains were similar in both groups however there was a significant increase in the geometric mean titre ratio for the H3N2 component of seasonal influenza vaccine in the co-administration group. While some vaccine combinations result in immune interference, the co-administration of MVA-NP+M1 alongside seasonal influenza vaccine is shown here to increase some influenza strain-specific antibody responses and boost memory T cells capable of recognising a range of influenza A subtypes.Molecular Therapy (2013); doi:10.1038/mt.2013.162.
    Molecular Therapy 07/2013; · 7.04 Impact Factor
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    ABSTRACT: Booster vaccination against 2009 H1N1 influenza virus was recommended for rheumatologic patients under immunosuppressive therapy during the 2009/2010 H1N1 pandemic. In this study we assessed whether B cell depletion with Rituximab influences of the antiviral immune response in 2009 H1N1 influenza virus-vaccinated patients. Influenza virus-specific immune responses were analysed after the first and a booster vaccination with PandemrixTM in sixteen consecutive Rituximab-treated patients with different rheumatic autoimmune disorders. Antibody titers were determined by a haemagglutination-inhibition assay and virus-specific T cell responses were evaluated by a flow cytometry-based intracellular cytokine-secretion assay. Patients showing clinical symptoms of influenza infection were excluded from this study. Two out of seven patients with low (<10%) and four out of nine with normal (>10%) B cells developed significant antibody responses after the first vaccination. Booster vaccination led to an antibody response in one additional patient. After the first vaccination, virus-specific CD4+ and CD8+ T cell responses were significantly lower in patients with low B cells than in those with normal B cells. Of importance, the booster vaccination stimulated the antiviral T cell response only in patients with low B cells. In the absence of a significant effect of booster vaccinations against 2009 H1N1 influenza virus on the humoral immune response in B cell-depleted patients with autoimmune rheumatic diseases, enhanced antiviral T cell responses in patients with low B cells indicate that T cells, maybe, compensate for the impaired humoral immunity in these patients.
    Clinical and experimental rheumatology 06/2013; · 2.66 Impact Factor
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    ABSTRACT: OBJECTIVE: To perform antiviral susceptibility monitoring of treated individuals in the community during the 2009 influenza A(H1N1) pandemic in England. PATIENTS AND METHODS: Between 200 and 400 patients were enrolled daily through the National Pandemic Flu Service (NPFS) and issued with a self-sampling kit. Initially, only persons aged 16 and over were eligible, but from 12 November (week 45), self-sampling was extended to include school-age children (5 years and older). All samples received were screened for influenza A(H1N1)pdm09 as well as seasonal influenza [A(H1N1), A(H3N2) and influenza B] by a combination of RT-PCR and virus isolation methods. Influenza A(H1N1)pdm09 RT-PCR-positive samples were screened for the oseltamivir resistance-inducing H275Y substitution, and a subset of samples also underwent phenotypic antiviral susceptibility testing by enzyme inhibition assay. RESULTS: We were able to detect virus by RT-PCR in self-taken samples and recovered infectious virus enabling further virological characterization. The majority of influenza A(H1N1)pdm09 RT-PCR-positive NPFS samples (n = 1273) were taken after oseltamivir treatment had begun. No reduction in phenotypic susceptibility to neuraminidase inhibitors was detected, but five cases with minority quasi-species of oseltamivir-resistant virus (an H275Y amino acid substitution in neuraminidase) were detected. CONCLUSIONS: Self-sampling is a useful tool for community surveillance, particularly for the follow-up of drug-treated patients. The virological study of self-taken samples from the NPFS provided a unique opportunity to evaluate the emergence of oseltamivir resistance in treated individuals with mild illness in the community, a target population that may not be captured by traditional sentinel surveillance schemes.
    Journal of Antimicrobial Chemotherapy 06/2013; · 5.34 Impact Factor
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    ABSTRACT: During the summer of 2012, in Jeddah, Saudi Arabia a hitherto unknown coronavirus was isolated from the sputum of a patient with acute pneumonia and renal failure (1, 2).…
    Journal of Virology 05/2013; · 5.08 Impact Factor
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    ABSTRACT: Very different influenza seasons have been observed from 2008/09-2011/12 in England and Wales, with the reported burden varying overall and by age group. The objective of this study was to estimate the impact of influenza on all-cause and cause-specific mortality during this period. Age-specific generalised linear regression models fitted with an identity link were developed, modelling weekly influenza activity through multiplying clinical influenza-like illness consultation rates with proportion of samples positive for influenza A or B. To adjust for confounding factors, a similar activity indicator was calculated for Respiratory Syncytial Virus. Extreme temperature and seasonal trend were controlled for. Following a severe influenza season in 2008/09 in 65+yr olds (estimated excess of 13,058 influenza A all-cause deaths), attributed all-cause mortality was not significant during the 2009 pandemic in this age group and comparatively low levels of influenza A mortality were seen in post-pandemic seasons. The age shift of the burden of seasonal influenza from the elderly to young adults during the pandemic continued into 2010/11; a comparatively larger impact was seen with the same circulating A(H1N1)pdm09 strain, with the burden of influenza A all-cause excess mortality in 15-64 yr olds the largest reported during 2008/09-2011/12 (436 deaths in 15-44 yr olds and 1,274 in 45-64 yr olds). On average, 76% of seasonal influenza A all-age attributable deaths had a cardiovascular or respiratory cause recorded (average of 5,849 influenza A deaths per season), with nearly a quarter reported for other causes (average of 1,770 influenza A deaths per season), highlighting the importance of all-cause as well as cause-specific estimates. No significant influenza B attributable mortality was detected by season, cause or age group. This analysis forms part of the preparatory work to establish a routine mortality monitoring system ahead of introduction of the UK universal childhood seasonal influenza vaccination programme in 2013/14.
    PLoS ONE 01/2013; 8(12):e79360. · 3.73 Impact Factor
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    ABSTRACT: INTRODUCTION: Illness and death from influenza increase during pregnancy. In the United Kingdom pregnant women were targeted in a national programme for vaccination during the H1N1 2009-10 pandemic. METHODS: In this study, pregnant women were recruited in labour from November 9, 2009 to March 10, 2010. Pandemic vaccination status was determined. Venous cord blood collected at delivery was evaluated for transplacental transfer of antibodies by measurement of haemagglutination inhibition and microneutralization titres. RESULTS: Samples were collected from 77 vaccinated and 27 unvaccinated women. Seroprotection (HI titre ≥1∶40) was detected in 58 (75.3%, 95% CI 64.2-84.4) cord blood samples from vaccinated women and 5 (18.5%, 95% CI 6.3-38.1) from unvaccinated women (P<0.0001). There was evidence of transplacental seroprotection 8 days after maternal immunization (77.9%, 95 CI 66.2-87.1), maintained in most cases for at least 16 weeks. DISCUSSION: Immunization of pregnant women with AS03(A)-adjuvanted vaccine is followed by transplacental transfer of passive immunity at titres consistent with clinical protection in three-quarters of new-born infants. The findings support national and international pandemic H1N1 2009 recommendations for immunization during pregnancy.
    PLoS ONE 01/2013; 8(1):e47448. · 3.73 Impact Factor
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    ABSTRACT: Following the discovery in September 2012 of 2 patients, both with links to the Eastern Mediterranean Region, with serious respiratory illness due to novel coronavirus, all countries have instigated surveillance and laboratory activities to detect further cases, with intensive case-contact investigations undertaken on laboratory confirmation of cases. A total of 30 cases, of whom 18 have died, and at least 3 clusters have been detected to date (1 cluster among health-care workers and another 2 clusters among family members). To date, transmission studies have shown a low risk of onward human transmission, with clinical presentation remaining severe for the majority. Many questions remain including the zoonotic source and geographical extent of infection. Surveillance has been extended to include clusters of cases or health-care workers with severe, undiagnosed respiratory illness regardless of travel history. Environmental studies, on-going surveillance and linked case-contact investigations will provide a critical role in answering some of these issues.
    Eastern Mediterranean health journal = La revue de santé de la Méditerranée orientale = al-Majallah al-ṣiḥḥīyah li-sharq al-mutawassiṭ 01/2013; 19 Suppl 1:S55-60.
  • Richard Pebody, Maria Zambon, John M Watson
    BMJ (Clinical research ed.). 01/2013; 346:f1301.
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    ABSTRACT: Full text available at: Between September 2012 and 22 October 2013, 144 laboratory-confirmed and 17 probable MERS-CoV cases from nine countries were notified to WHO. We summarize what is known about the epidemiology, virology, phylogeny and emergence of MERS-CoV to inform public health policies. The median age of patients (n=161) was 50 years (range 14 months to 94 years), 64.5% were male and 63.4% experienced severe respiratory disease. 76.0% of patients were reported to have ≥1 underlying medical condition and fatal cases, compared to recovered or asymptomatic cases were more likely to have an underlying condition (86.8% vs. 42.4%, p<0.001). Analysis of genetic sequence data suggests multiple independent introductions into human populations and modelled estimates using epidemiologic and genetic data suggest R<sub>0</sub> is <1, though the upper range of estimates may exceed 1. Index/sporadic cases (cases with no epidemiologic-link to other cases) were more likely to be older (median 59.0 years vs. 43.0 years, p<0.001) compared to secondary cases, although these proportions have declined over time. 80.9% vs. 67.2% of index/sporadic and secondary cases, respectively, reported ≥1 underlying condition. Clinical presentation ranges from asymptomatic to severe pneumonia with acute respiratory distress syndrome and multi-organ failure. Nearly all symptomatic patients presented with respiratory symptoms and 1/3 of patients also had gastrointestinal symptoms. Sustained human-to-human transmission of MERS-CoV has not been observed. Outbreaks have been extinguished without overly aggressive isolation and quarantine suggesting that transmission of virus may be stopped with implementation of appropriate infection control measures.
    PLoS currents. 01/2013; 5.
  • Euro surveillance: bulletin europeen sur les maladies transmissibles = European communicable disease bulletin 01/2013; 18(36). · 5.49 Impact Factor
  • Euro surveillance: bulletin europeen sur les maladies transmissibles = European communicable disease bulletin 01/2013; 18(5). · 5.49 Impact Factor

Publication Stats

7k Citations
1,337.96 Total Impact Points


  • 2003–2014
    • Public Health England
      • • Respiratory Diseases Department
      • • Health Protection Agency - North East
      • • Immunisation, Hepatitis, and Blood Safety department
      Londinium, England, United Kingdom
    • University of Reading
      Reading, England, United Kingdom
    • The Commonwealth Scientific and Industrial Research Organisation
      Canberra, Australian Capital Territory, Australia
  • 2013
    • National Institutes of Health
      Maryland, United States
  • 2012
    • Wellcome Trust Sanger Institute
      Cambridge, England, United Kingdom
  • 2005–2011
    • Istituto Superiore di Sanità
      • • Department of Infectious, Parasitic and Immune-mediated Diseases
      • • Immuno-mediated Diseases Unit
      Roma, Latium, Italy
    • University of Virginia
      • Division of Infectious Diseases and International Health
      Charlottesville, VA, United States
    • Robert Koch Institut
      Berlín, Berlin, Germany
    • Great Ormond Street Hospital for Children NHS Foundation Trust
      Londinium, England, United Kingdom
  • 2004–2011
    • National Institute for Biological Standards and Control
      • Division of Virology
      Potters Bar, ENG, United Kingdom
    • International Society for Disease Surveillance
      Brighton, England, United Kingdom
    • University of Milan
      Milano, Lombardy, Italy
  • 2003–2011
    • University of Leicester
      • Department of Infection, Immunity and Inflammation
      Leicester, ENG, United Kingdom
  • 2010
    • National Institute of Health Dr. Ricardo Jorge
      • Department of Infectious Diseases
      Lisbon, Lisbon, Portugal
  • 2006–2009
    • Nederlands Instituut voor onderzoek van de Gezondheidszorg
      Utrecht, Utrecht, Netherlands
    • Centre D'Investigations Préventives Et Cliniques
      Lutetia Parisorum, Île-de-France, France
    • University of Michigan
      Ann Arbor, Michigan, United States
  • 1999–2009
    • Nottinghamshire Healthcare NHS Trust
      Nottigham, England, United Kingdom
  • 1996–2009
    • Royal College of General Practitioners
      Londinium, England, United Kingdom
  • 2008
    • Murdoch Childrens Research Institute
      Melbourne, Victoria, Australia
    • University of Melbourne
      • Melbourne School of Population Health
      Melbourne, Victoria, Australia
  • 1998
    • University of Birmingham
      • School of Immunity and Infection
      Birmingham, ENG, United Kingdom