38 results found
Zhou J, Singanayagam A, Barclay WS, 2023, Is it possible to generalise superspreading individuals or events of SARS-CoV-2? - Authors' reply., Lancet Microbe, Vol: 4
Singanayagam A, Moore C, Froude S, et al., 2023, Increased reports of severe myocarditis associated with enterovirus infection in neonates, United Kingdom, 27 June 2022 to 26 April 2023, Eurosurveillance, Vol: 28, ISSN: 1025-496X
Enteroviruses are a common cause of seasonal childhood infections. The vast majority of enterovirus infections are mild and self-limiting, although neonates can sometimes develop severe disease. Myocarditis is a rare complication of enterovirus infection. Between June 2022 and April 2023, twenty cases of severe neonatal enteroviral myocarditis caused by coxsackie B viruses were reported in the United Kingdom. Sixteen required critical care support and two died. Enterovirus PCR on whole blood was the most sensitive diagnostic test. We describe the initial public health investigation into this cluster and aim to raise awareness among paediatricians, laboratories and public health specialists.
Zhou J, Singanayagam A, Goonawardane N, et al., 2023, Viral emissions into the air and environment after SARS-CoV-2 human challenge: a phase 1, open label, first-in-human study, The Lancet Microbe, Vol: 4, Pages: e579-e590, ISSN: 2666-5247
BackgroundEffectively implementing strategies to curb SARS-CoV-2 transmission requires understanding who is contagious and when. Although viral load on upper respiratory swabs has commonly been used to infer contagiousness, measuring viral emissions might be more accurate to indicate the chance of onward transmission and identify likely routes. We aimed to correlate viral emissions, viral load in the upper respiratory tract, and symptoms, longitudinally, in participants who were experimentally infected with SARS-CoV-2.MethodsIn this phase 1, open label, first-in-human SARS-CoV-2 experimental infection study at quarantine unit at the Royal Free London NHS Foundation Trust, London, UK, healthy adults aged 18–30 years who were unvaccinated for SARS-CoV-2, not previously known to have been infected with SARS-CoV-2, and seronegative at screening were recruited. Participants were inoculated with 10 50% tissue culture infectious dose of pre-alpha wild-type SARS-CoV-2 (Asp614Gly) by intranasal drops and remained in individual negative pressure rooms for a minimum of 14 days. Nose and throat swabs were collected daily. Emissions were collected daily from the air (using a Coriolis μ air sampler and directly into facemasks) and the surrounding environment (via surface and hand swabs). All samples were collected by researchers, and tested by using PCR, plaque assay, or lateral flow antigen test. Symptom scores were collected using self-reported symptom diaries three times daily. The study is registered with ClinicalTrials.gov, NCT04865237.FindingsBetween March 6 and July 8, 2021, 36 participants (ten female and 26 male) were recruited and 18 (53%) of 34 participants became infected, resulting in protracted high viral loads in the nose and throat following a short incubation period, with mild-to-moderate symptoms. Two participants were excluded from the per-protocol analysis owing to seroconversion between screening and inoculation, identified post hoc. Viral RNA was de
Singanayagam A, Klapsa D, Burton-Fanning S, et al., 2023, Asymptomatic immunodeficiency-associated vaccine-derived poliovirus infections in two UK children, Nature Communications, Vol: 14, ISSN: 2041-1723
Increasing detections of vaccine-derived poliovirus (VDPV) globally, including in countries previously declared polio free, is a public health emergency of international concern. Individuals with primary immunodeficiency (PID) can excrete polioviruses for prolonged periods, which could act as a source of cryptic transmission of viruses with potential to cause neurological disease. Here, we report on the detection of immunodeficiency-associated VDPVs (iVDPV) from two asymptomatic male PID children in the UK in 2019. The first child cleared poliovirus with increased doses of intravenous immunoglobulin, the second child following haematopoetic stem cell transplantation. We perform genetic and phenotypic characterisation of the infecting strains, demonstrating intra-host evolution and a neurovirulent phenotype in transgenic mice. Our findings highlight a pressing need to strengthen polio surveillance. Systematic collection of stool from asymptomatic PID patients who are at high risk for poliovirus excretion could improve the ability to detect and contain iVDPVs.
Derqui N, Koycheva A, Zhou J, et al., 2023, Risk factors and vectors for SARS-CoV-2 household transmission: a prospective, longitudinal cohort study, The Lancet Microbe, Vol: 4, Pages: e397-e408, ISSN: 2666-5247
BACKGROUND: Despite circumstantial evidence for aerosol and fomite spread of SARS-CoV-2, empirical data linking either pathway with transmission are scarce. Here we aimed to assess whether the presence of SARS-CoV-2 on frequently-touched surfaces and residents' hands was a predictor of SARS-CoV-2 household transmission. METHODS: In this longitudinal cohort study, during the pre-alpha (September to December, 2020) and alpha (B.1.1.7; December, 2020, to April, 2021) SARS-CoV-2 variant waves, we prospectively recruited contacts from households exposed to newly diagnosed COVID-19 primary cases, in London, UK. To maximally capture transmission events, contacts were recruited regardless of symptom status and serially tested for SARS-CoV-2 infection by RT-PCR on upper respiratory tract (URT) samples and, in a subcohort, by serial serology. Contacts' hands, primary cases' hands, and frequently-touched surface-samples from communal areas were tested for SARS-CoV-2 RNA. SARS-CoV-2 URT isolates from 25 primary case-contact pairs underwent whole-genome sequencing (WGS). FINDINGS: From Aug 1, 2020, until March 31, 2021, 620 contacts of PCR-confirmed SARS-CoV-2-infected primary cases were recruited. 414 household contacts (from 279 households) with available serial URT PCR results were analysed in the full household contacts' cohort, and of those, 134 contacts with available longitudinal serology data and not vaccinated pre-enrolment were analysed in the serology subcohort. Household infection rate was 28·4% (95% CI 20·8-37·5) for pre-alpha-exposed contacts and 51·8% (42·5-61·0) for alpha-exposed contacts (p=0·0047). Primary cases' URT RNA viral load did not correlate with transmission, but was associated with detection of SARS-CoV-2 RNA on their hands (p=0·031). SARS-CoV-2 detected on primary cases' hands, in turn, predicted contacts' risk of infection (adjusted relative risk [aRR]=1·70 [95% CI 1·24-2·3
Hakki S, Zhou J, Jonnerby J, et al., 2022, Onset and window of SARS-CoV-2 infectiousness and temporal correlation with symptom onset: a prospective, longitudinal, community cohort study, The Lancet Respiratory Medicine, Vol: 10, Pages: 1061-1073, ISSN: 2213-2600
BACKGROUND: Knowledge of the window of SARS-CoV-2 infectiousness is crucial in developing policies to curb transmission. Mathematical modelling based on scarce empirical evidence and key assumptions has driven isolation and testing policy, but real-world data are needed. We aimed to characterise infectiousness across the full course of infection in a real-world community setting. METHODS: The Assessment of Transmission and Contagiousness of COVID-19 in Contacts (ATACCC) study was a UK prospective, longitudinal, community cohort of contacts of newly diagnosed, PCR-confirmed SARS-CoV-2 index cases. Household and non-household exposed contacts aged 5 years or older were eligible for recruitment if they could provide informed consent and agree to self-swabbing of the upper respiratory tract. The primary objective was to define the window of SARS-CoV-2 infectiousness and its temporal correlation with symptom onset. We quantified viral RNA load by RT-PCR and infectious viral shedding by enumerating cultivable virus daily across the course of infection. Participants completed a daily diary to track the emergence of symptoms. Outcomes were assessed with empirical data and a phenomenological Bayesian hierarchical model. FINDINGS: Between Sept 13, 2020, and March 31, 2021, we enrolled 393 contacts from 327 households (the SARS-CoV-2 pre-alpha and alpha variant waves); and between May 24, 2021, and Oct 28, 2021, we enrolled 345 contacts from 215 households (the delta variant wave). 173 of these 738 contacts were PCR positive for more than one timepoint, 57 of which were at the start of infection and comprised the final study population. The onset and end of infectious viral shedding were captured in 42 cases and the median duration of infectiousness was 5 (IQR 3-7) days. Although 24 (63%) of 38 cases had PCR-detectable virus before symptom onset, only seven (20%) of 35 shed infectious virus presymptomatically. Symptom onset was a median of 3 days before both peak viral RNA and
Houston H, Hakki S, Pillay TD, et al., 2022, Broadening symptom criteria improves early case identification in SARS-CoV-2 contacts, European Respiratory Journal, Vol: 60, Pages: 1-13, ISSN: 0903-1936
Background The success of case isolation and contact tracing for the control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission depends on the accuracy and speed of case identification. We assessed whether inclusion of additional symptoms alongside three canonical symptoms (CS), i.e. fever, cough and loss or change in smell or taste, could improve case definitions and accelerate case identification in SARS-CoV-2 contacts.Methods Two prospective longitudinal London (UK)-based cohorts of community SARS-CoV-2 contacts, recruited within 5 days of exposure, provided independent training and test datasets. Infected and uninfected contacts completed daily symptom diaries from the earliest possible time-points. Diagnostic information gained by adding symptoms to the CS was quantified using likelihood ratios and area under the receiver operating characteristic curve. Improvements in sensitivity and time to detection were compared with penalties in terms of specificity and number needed to test.Results Of 529 contacts within two cohorts, 164 (31%) developed PCR-confirmed infection and 365 (69%) remained uninfected. In the training dataset (n=168), 29% of infected contacts did not report the CS. Four symptoms (sore throat, muscle aches, headache and appetite loss) were identified as early-predictors (EP) which added diagnostic value to the CS. The broadened symptom criterion “≥1 of the CS, or ≥2 of the EP” identified PCR-positive contacts in the test dataset on average 2 days earlier after exposure (p=0.07) than “≥1 of the CS”, with only modest reduction in specificity (5.7%).Conclusions Broadening symptom criteria to include individuals with at least two of muscle aches, headache, appetite loss and sore throat identifies more infections and reduces time to detection, providing greater opportunities to prevent SARS-CoV-2 transmission.Tweetable abstract @ERSpublications
Deeks JJ, Singanayagam A, Houston H, et al., 2022, SARS-CoV-2 antigen lateral flow tests for detecting infectious people: linked data analysis, BMJ-BRITISH MEDICAL JOURNAL, Vol: 376, ISSN: 0959-535X
Singanayagam A, Hakki S, Dunning J, et al., 2022, Community transmission and viral load kinetics of the SARS-CoV-2 delta (B.1.617.2) variant in vaccinated and unvaccinated individuals in the UK: a prospective, longitudinal, cohort study., The Lancet. Infectious diseases, Vol: 22, Pages: 183-195, ISSN: 1473-3099
<h4>Background</h4>The SARS-CoV-2 delta (B.1.617.2) variant is highly transmissible and spreading globally, including in populations with high vaccination rates. We aimed to investigate transmission and viral load kinetics in vaccinated and unvaccinated individuals with mild delta variant infection in the community.<h4>Methods</h4>Between Sept 13, 2020, and Sept 15, 2021, 602 community contacts (identified via the UK contract-tracing system) of 471 UK COVID-19 index cases were recruited to the Assessment of Transmission and Contagiousness of COVID-19 in Contacts cohort study and contributed 8145 upper respiratory tract samples from daily sampling for up to 20 days. Household and non-household exposed contacts aged 5 years or older were eligible for recruitment if they could provide informed consent and agree to self-swabbing of the upper respiratory tract. We analysed transmission risk by vaccination status for 231 contacts exposed to 162 epidemiologically linked delta variant-infected index cases. We compared viral load trajectories from fully vaccinated individuals with delta infection (n=29) with unvaccinated individuals with delta (n=16), alpha (B.1.1.7; n=39), and pre-alpha (n=49) infections. Primary outcomes for the epidemiological analysis were to assess the secondary attack rate (SAR) in household contacts stratified by contact vaccination status and the index cases' vaccination status. Primary outcomes for the viral load kinetics analysis were to detect differences in the peak viral load, viral growth rate, and viral decline rate between participants according to SARS-CoV-2 variant and vaccination status.<h4>Findings</h4>The SAR in household contacts exposed to the delta variant was 25% (95% CI 18-33) for fully vaccinated individuals compared with 38% (24-53) in unvaccinated individuals. The median time between second vaccine dose and study recruitment in fully vaccinated contacts was longer for infected individuals (medi
Lalvani A, Hakki S, Singanayagam A, et al., 2022, Transmissibility of SARS-CoV-2 among fully vaccinated individuals reply, LANCET INFECTIOUS DISEASES, Vol: 22, Pages: 18-19, ISSN: 1473-3099
Hall JA, Harris RJ, Emmett HE, et al., 2021, On the sensitivity and specificity of postmortem upper respiratory tract testing for SARS-CoV-2, Journal of Infectious Diseases, Vol: 224, Pages: 389-394, ISSN: 0022-1899
BackgroundPostmortem testing can improve our understanding of the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) if sufficiently sensitive and specific.MethodsWe investigated the postmortem sensitivity and specificity of reverse transcriptase polymerase chain reaction (PCR) testing on upper respiratory swabs using a dataset of everyone tested for SARS-CoV-2 before and after death in England, 1 March to 29 October 2020. We analyzed sensitivity in those with a positive test before death by time to postmortem test. We developed a multivariate model and conducted time-to-negativity survival analysis. For specificity, we analyzed those with a negative test in the week before death.ResultsPostmortem testing within a week after death had a sensitivity of 96.8% if the person had tested positive within a week before death. There was no effect of age, sex, or specimen type on sensitivity, but individuals with coronavirus disease 2019 (COVID-19)–related codes on their death certificate were 5.65 times more likely to test positive after death (95% confidence interval, 2.31–13.9). Specificity was 94.2%, increasing to 97.5% in individuals without COVID-19 on the death certificate.ConclusionPostmortem testing has high sensitivity (96.8%) and specificity (94.2%) if performed within a week after death and could be a useful diagnostic tool.
Marin-Corral J, Pascual-Guardia S, Amati F, et al., 2021, Aspiration Risk Factors, Microbiology, and Empiric Antibiotics for Patients Hospitalized With Community-Acquired Pneumonia, CHEST, Vol: 159, Pages: 58-72, ISSN: 0012-3692
Singanayagam A, Patel M, Charlett A, et al., 2020, Duration of infectiousness and correlation with RT-PCR cycle threshold values in cases of COVID-19, England, January to May 2020, EUROSURVEILLANCE, Vol: 25, Pages: 2-6, ISSN: 1025-496X
Villafuerte D, Aliberti S, Soni NJ, et al., 2020, Prevalence and risk factors for <i>Enterobacteriaceae</i> in patients hospitalized with community-acquired pneumonia, RESPIROLOGY, Vol: 25, Pages: 543-551, ISSN: 1323-7799
Singanayagam A, Zhou J, Elderfield RA, et al., 2020, Characterising viable virus from air exhaled by H1N1 influenza-infected ferrets reveals the importance of haemagglutinin stability for airborne infectivity, PLoS Pathogens, Vol: 16, Pages: 1-21, ISSN: 1553-7366
The transmissibility and pandemic potential of influenza viruses depends on their ability to efficiently replicate and be released from an infected host, retain viability as they pass through the environment, and then initiate infection in the next host. There is a significant gap in knowledge about viral properties that enable survival of influenza viruses between hosts, due to a lack of experimental methods to reliably isolate viable virus from the air. Using a novel technique, we isolate and characterise infectious virus from droplets emitted by 2009 pandemic H1N1-infected ferrets. We demonstrate that infectious virus is predominantly released early after infection. A virus containing a mutation destabilising the haemagglutinin (HA) surface protein displayed reduced survival in air. Infectious virus recovered from droplets exhaled by ferrets inoculated with this virus contained mutations that conferred restabilisation of HA, indicating the importance of influenza HA stability for between-host survival. Using this unique approach can improve knowledge about the determinants and mechanisms of influenza transmissibility and ultimately could be applied to studies of airborne virus exhaled from infected people.
Aliberti S, Cook GS, Babu BL, et al., 2019, International prevalence and risk factors evaluation for drug-resistant <i>Streptococcus pneumoniae</i> pneumonia, JOURNAL OF INFECTION, Vol: 79, Pages: 300-311, ISSN: 0163-4453
Singanayagam A, Zambon M, Barclay W, 2019, Influenza virus with increased pH of HA activation has improved replication in cell culture but at the cost of infectivity in human airway epithelium., Journal of Virology, Vol: 98, ISSN: 0022-538X
Pandemic H1N1 (pH1N1) influenza virus emerged from swine in 2009 with adequate capability to infect and transmit between people. In subsequent years it has circulated as a seasonal virus and evolved further human-adapting mutations. Mutations in the haemagglutinin (HA) stalk that increase pH stability have been associated with human adaptation and airborne transmission of pH1N1 virus. Yet, our understanding of how pH stability impacts virus/host interactions is incomplete. Here, using recombinant viruses with point mutations that alter the pH stability of pH1N1 HA, we found distinct effects on virus phenotypes in different experimental models. Increased pH sensitivity enabled virus to uncoat in endosomes more efficiently, manifesting as increased replication rate in typical continuous cell cultures under single-cycle conditions. A more acid labile HA also conferred a small reduction in sensitivity to antiviral therapeutics that act at the pH-sensitive HA fusion step. Conversely, in primary human airway epithelium cultured at air-liquid interface, increased pH sensitivity attenuated multicycle viral replication, by compromising virus survival in the extracellular microenvironment. In a mouse model of influenza pathogenicity, there was an optimum HA activation pH and viruses with either more or less pH stable HA were less virulent. Opposing pressures inside and outside the host cell that determine pH stability may influence zoonotic potential. The distinct effects that changes in pH stability exert on viral phenotypes underscore the importance of using the most appropriate systems for assessing virus titre and fitness, which has implications for vaccine manufacture, antiviral drug development and pandemic risk assessment.ImportanceThe pH stability of the haemagglutinin surface protein varies between different influenza strains and subtypes and can affect the virus' ability to replicate and transmit. Here, we demonstrate a delicate balance the virus strikes within and
Lindsey BB, Jagne YJ, Armitage EP, et al., 2019, Effect of a Russian-backbone live-attenuated influenza vaccine with an updated pandemic H1N1 strain on shedding and immunogenicity among children in The Gambia: an open-label, observational, phase 4 study, Lancet Respiratory Medicine, Vol: 7, Pages: 665-676, ISSN: 2213-2600
BACKGROUND: The efficacy and effectiveness of the pandemic H1N1 (pH1N1) component in live attenuated influenza vaccine (LAIV) is poor. The reasons for this paucity are unclear but could be due to impaired replicative fitness of pH1N1 A/California/07/2009-like (Cal09) strains. We assessed whether an updated pH1N1 strain in the Russian-backbone trivalent LAIV resulted in greater shedding and immunogenicity compared with LAIV with Cal09. METHODS: We did an open-label, prospective, observational, phase 4 study in Sukuta, a periurban area in The Gambia. We enrolled children aged 24-59 months who were clinically well. Children received one dose of the WHO prequalified Russian-backbone trivalent LAIV containing either A/17/California/2009/38 (Cal09) or A/17/New York/15/5364 (NY15) based on their year of enrolment. Primary outcomes were the percentage of children with LAIV strain shedding at day 2 and day 7, haemagglutinin inhibition seroconversion, and an increase in influenza haemagglutinin-specific IgA and T-cell responses at day 21 after LAIV. This study is nested within a randomised controlled trial investigating LAIV-microbiome interactions (NCT02972957). FINDINGS: Between Feb 8, 2017, and April 12, 2017, 118 children were enrolled and received one dose of the Cal09 LAIV from 2016-17. Between Jan 15, 2018, and March 28, 2018, a separate cohort of 135 children were enrolled and received one dose of the NY15 LAIV from 2017-18, of whom 126 children completed the study. Cal09 showed impaired pH1N1 nasopharyngeal shedding (16 of 118 children [14%, 95% CI 8·0-21·1] with shedding at day 2 after administration of LAIV) compared with H3N2 (54 of 118 [46%, 36·6-55·2]; p<0·0001) and influenza B (95 of 118 [81%, 72·2-87·2]; p<0·0001), along with suboptimal serum antibody (seroconversion in six of 118 [5%, 1·9-10·7]) and T-cell responses (CD4+ interferon γ-positive and/or CD4+ interleukin 2-positive
Di Pasquale MF, Sotgiu G, Gramegna A, et al., 2019, Prevalence and Etiology of Community-acquired Pneumonia in Immunocompromised Patients, CLINICAL INFECTIOUS DISEASES, Vol: 68, Pages: 1482-1493, ISSN: 1058-4838
Lindsey BB, Singanayagam A, Tregoning JS, et al., 2019, The impact of an updated pandemic H1N1 strain on shedding and immunogenicity to Russian-backbone live attenuated influenza vaccine among children in The Gambia: an open-label, observational, phase 4 study, Lancet Respiratory Medicine, ISSN: 2213-2600
Background: Poor efficacy and effectiveness of thepandemic H1N1 (pH1N1) component inlive attenuated influenza vaccine (LAIV)has been demonstrated in several studies.The reasons for this are unclear, butmay be due toimpairedreplicative fitness of pH1N1 A/California/07/2009-like (Cal09) strains. The aim of this study was to establish whether an updated pH1N1 strain in the Russian-backbone trivalent LAIV resulted in greater shedding and immunogenicitycompared to Cal09.Methods: In an open-label, prospective,observational,phase 4study, we evaluated the impact of updating the pH1N1 component in the WHO prequalified Russian-backbone trivalent LAIV from Cal09in 2016-17(n=118) to an A/Michigan/45/2015-like strain (A/17/New York/15/5364, NY15) in 2017-18(n=126),on shedding and immunogenicity in Gambian children aged 2-4 years old.The study was nested within a randomised controlled trial investigating LAIV-microbiome interactions (ClinicalTrials.gov NCT02972957). Findings: Cal09 showed impairednasopharyngeal shedding(13.6%children shedding at day 2 post-LAIV)compared to H3N2(45.8%)and influenza B(80.5%), along with sub-optimal serum antibody(5.1%seroconversion)and T-cell responses(40.5% CD4+IFN-g+ and/or CD4+IL-2+responders). Following the switch to NY15, a significant increase in pH1N1 shedding(63.5%)was seen, along with improvements in seroconversion(19.1%)and influenza-specific CD4+ T-3cell responses(65.7%). The improvement in pH1N1 seroconversion with NY15 was even greater in children seronegative at baseline(37.5% vs. 7.6%). Persistent shedding today 7was independently associated with both seroconversionand CD4+ T cell responsein multivariable logistic regression. Interpretation:The pH1N1 component switch may have overcome problems in prior LAIV formulations.LAIV effectiveness against pH1N1 shouldtherefore improve in upcoming influenza seasons. Our dataalso highlightthe importance of evaluat
Radovanovic D, Sotgiu G, Jankovic M, et al., 2019, An international perspective on hospitalized patients with viral community-acquired pneumonia, EUROPEAN JOURNAL OF INTERNAL MEDICINE, Vol: 60, Pages: 54-70, ISSN: 0953-6205
Carugati M, Aliberti S, Felipe Reyes L, et al., 2018, Microbiological testing of adults hospitalised with community-acquired pneumonia: an international study, ERJ Open Research, Vol: 4, Pages: 1-13, ISSN: 2312-0541
This study aimed to describe real-life microbiological testing of adults hospitalised with community-acquired pneumonia (CAP) and to assess concordance with the 2007 Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) and 2011 European Respiratory Society (ERS) CAP guidelines.This was a cohort study based on the Global Initiative for Methicillin-resistant Staphylococcus aureus Pneumonia (GLIMP) database, which contains point-prevalence data on adults hospitalised with CAP across 54 countries during 2015.In total, 3702 patients were included. Testing was performed in 3217 patients, and included blood culture (71.1%), sputum culture (61.8%), Legionella urinary antigen test (30.1%), pneumococcal urinary antigen test (30.0%), viral testing (14.9%), acute-phase serology (8.8%), bronchoalveolar lavage culture (8.4%) and pleural fluid culture (3.2%). A pathogen was detected in 1173 (36.5%) patients. Testing attitudes varied significantly according to geography and disease severity. Testing was concordant with IDSA/ATS and ERS guidelines in 16.7% and 23.9% of patients, respectively. IDSA/ATS concordance was higher in Europe than in North America (21.5% versus 9.8%; p<0.01), while ERS concordance was higher in North America than in Europe (33.5% versus 19.5%; p<0.01).Testing practices of adults hospitalised with CAP varied significantly by geography and disease severity. There was a wide discordance between real-life testing practices and IDSA/ATS/ERS guideline recommendations.
Restrepo M, Babu BL, Reyes LF, et al., 2018, Burden and risk factors for <i>Pseudomonas aeruginosa</i> community-acquired pneumonia: a multinational point prevalence study of hospitalised patients, EUROPEAN RESPIRATORY JOURNAL, Vol: 52, ISSN: 0903-1936
Singanayagam A, Zambon M, Lalvani A, et al., 2017, Can defective interfering RNAs affect the live attenuated influenza vaccine? Reply, Lancet Infectious Diseases, Vol: 17, Pages: 1235-1236, ISSN: 1473-3099
Singanayagam A, Zambon M, Lalvani A, et al., 2017, Urgent challenges in implementing live attenuated influenza vaccine., Lancet Infectious Diseases, Vol: 18, Pages: e25-e32, ISSN: 1473-3099
Conflicting reports have emerged about the effectiveness of the live attenuated influenza vaccine. The live attenuated influenza vaccine appears to protect particularly poorly against currently circulating H1N1 viruses that are derived from the 2009 pandemic H1N1 viruses. During the 2015-16 influenza season, when pandemic H1N1 was the predominant virus, studies from the USA reported a complete lack of effectiveness of the live vaccine in children. This finding led to a crucial decision in the USA to recommend that the live vaccine not be used in 2016-17 and to switch to the inactivated influenza vaccine. Other countries, including the UK, Canada, and Finland, however, have continued to recommend the use of the live vaccine. This policy divergence and uncertainty has far reaching implications for the entire global community, given the importance of the production capabilities of the live attenuated influenza vaccine for pandemic preparedness. In this Personal View, we discuss possible explanations for the observed reduced effectiveness of the live attenuated influenza vaccine and highlight the underpinning scientific questions. Further research to understand the reasons for these observations is essential to enable informed public health policy and commercial decisions about vaccine production and development in coming years.
Aliberti S, Reyes LF, Faverio P, et al., 2016, Global initiative for meticillin-resistant <i>Staphylococcus aureus</i> pneumonia (GLIMP): an international, observational cohort study, LANCET INFECTIOUS DISEASES, Vol: 16, Pages: 1364-1376, ISSN: 1473-3099
Ho W, Connell DW, Singanayagam A, et al., 2015, PREDICTIVE ACCURACY AND CLINICAL IMPACT OF XPERT MTB/RIF FOR THE DIAGNOSIS OF SPUTUM SMEAR-NEGATIVE PULMONARY TUBERCULOSIS USING BRONCHOALVEOLAR LAVAGE FLUID, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A26-A26, ISSN: 0040-6376
Singanayagam A, Lamb L, Makinde JE, et al., 2015, Systemic cytokine storm in severe eosinophilic dermatitis, QJM-AN INTERNATIONAL JOURNAL OF MEDICINE, Vol: 108, Pages: 907-908, ISSN: 1460-2725
Singanayagam A, Donaldson H, Kon OM, 2014, GeneXpert® MTB/RIF in low prevalence settings: A UK laboratory perspective, JOURNAL OF INFECTION, Vol: 69, Pages: 199-200, ISSN: 0163-4453
Singanayagam A, Chalmers JD, Welte T, 2014, Epidemiology of CAP in Europe, COMMUNITY-ACQUIRED PNEUMONIA, Pages: 1-12, ISSN: 2075-6674
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