31 results found
Lalvani A, Hakki S, Singanayagam A, et al., 2022, Transmissibility of SARS-CoV-2 among fully vaccinated individuals - Authors' reply., Lancet Infect Dis, Vol: 22, Pages: 18-19
Houston H, Hakki S, Pillay TD, et al., 2021, Broadening symptom criteria improves early case identification in SARS-CoV-2 contacts., Eur Respir J
INTRODUCTION: The success of case isolation and contact tracing for the control of 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) - fever; cough; 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-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 AUC-ROC. Improvements in sensitivity and time-to-detection were compared to 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 2 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.
Singanayagam A, Hakki S, Dunning J, et al., 2021, 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, ISSN: 1473-3099
BackgroundThe 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.MethodsBetween 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.FindingsThe 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 (median 101 days [IQR 74–120]) than for unin
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
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
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 Streptococcus pneumoniae 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
Villafuerte D, Aliberti S, Soni NJ, et al., 2019, Prevalence and risk factors for Enterobacteriaceae in patients hospitalized with community-acquired pneumonia, RESPIROLOGY, Vol: 25, Pages: 543-551, ISSN: 1323-7799
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 Pseudomonas aeruginosa 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 Staphylococcus aureus 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 (R) 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, European Respiratory Monograph, Vol: 63, Pages: 1-12, ISSN: 1025-448X
This article describes the epidemiology of community-acquired pneumonia(CAP)inEurope.Lower respiratory tract infections arethe fifth leading cause of death worldwide with the bulk of the mortality attributable to CAP. Pneumonia disproportionately affects elderly populations and demographic changes within Europe are leading to an older, more comorbid populationat high risk of pneumonia. Consequently, recent data suggests a progressive rise in hospitalisations for pneumonia throughout Europe over the past 10 years. CAP places a substantial burden on healthcare with costs largely attributable to inpatient care. Antibiotic resistance, particularlyStreptococcus pneumoniaeresistance to penicillin and macrolides, is rapidly increasing in Europe and poses a seriousthreattofutureeffective treatment. Prevention of pneumonia requires an understanding of the population risk factors, which will be discussed in this chapter. © 2014.
Singanayagam A, Singanayagam A, Chalmers JD, 2013, Obesity is associated with improved survival in community-acquired pneumonia, EUROPEAN RESPIRATORY JOURNAL, Vol: 42, Pages: 180-187, ISSN: 0903-1936
Schembri S, Williamson PA, Short PM, et al., 2013, Cardiovascular events after clarithromycin use in lower respiratory tract infections: analysis of two prospective cohort studies, BMJ-BRITISH MEDICAL JOURNAL, Vol: 346, ISSN: 1756-1833
Singanayagam A, Short P, Williamson P, et al., 2012, CARDIOVASCULAR EVENTS FOLLOWING CLARITHROMYCIN USE IN LOWER RESPIRATORY TRACT INFECTIONS: ANALYSIS OF TWO PROSPECTIVE COHORT STUDIES, Winter Meeting of the British-Thoracic-Society 2012, Publisher: BMJ PUBLISHING GROUP, Pages: A15-A16, ISSN: 0040-6376
Singanayagam A, Singanayagam A, Elder DHJ, et al., 2012, Is community-acquired pneumonia an independent risk factor for cardiovascular disease?, EUROPEAN RESPIRATORY JOURNAL, Vol: 39, Pages: 187-196, ISSN: 0903-1936
Singanayagam A, Singanayagam A, Wood V, et al., 2011, Factors associated with severe illness in pandemic 2009 influenza a (H1N1) infection: Implications for triage in primary and secondary care, JOURNAL OF INFECTION, Vol: 63, Pages: 243-251, ISSN: 0163-4453
Singanayagam A, 2009, WISP-1, a novel target for treatment of pulmonary fibrosis, Thorax, Vol: 64, ISSN: 0040-6376
Singanayagam A, Gange N, Singanayagam A, et al., 2008, Folate deficiency presenting as pyrexia: a case report., Cases J, Vol: 1
Folate deficiency is an uncommon cause of pyrexia. We describe the case of a 29-year-old male who presented with a pyrexial illness subsequently attributed to megaloblastic anaemia secondary to severe folate deficiency, after exclusion of other infective or inflammatory causes. A temperature chart documenting the course of the patient's pyrexia is presented and potential pathophysiological mechanisms are proposed. Folate deficiency is a reversible cause of pyrexia that should be considered in any patient who presents with a pyrexial illness of unknown cause.
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