Publications
265 results found
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
Philip K, Owles H, McVey S, et al., 2022, Impact of an online breathing and wellbeing programme (ENO Breathe) in people with persistent symptoms following COVID-19: a randomised controlled trial, The Lancet Respiratory Medicine, Vol: 60, ISSN: 2213-2600
Aims: ENO Breathe is an online breathing and wellbeing programme for people with Long COVID focusing on breathing re-training using singing techniques.Aim: to assess whether ENO Breathe improves health related quality-of-life (HRQoL) in people with persistent breathlessness following COVID-19.Method:A parallel-group, single-blind, RCT, comparing ENO Breathe(6 weeks) with usual care in adults, with persisting breathlessness +/− anxiety, following assessment at an NHS Long COVID clinic.Primary outcome: change in HRQoL using the RAND SF-36 Mental(MHC) and Physical(PHC) Health Composite Scores.Secondary outcomes: CAT, VAS for breathlessness (rest, walking, stairs, and running), Dysp-12, GAD-7. Participant experience was assessed using focus groups and free-text responses.Results: 150 participants (mean(SD) 49(12)years, 81% female, 320(127) days symptomatic; ENO Breathe(n=74), Control(n=76). ENO Breathe was associated with improvement in MHC of 2.42 points (95%CI 0.03 to 4.80, p=0.045), but not PHC 0.6 (-1.33 to 2.52, p=0.541). VAS breathlessness (running) favoured ENO Breathe -10.48(-17.23 to -3.73, p=0.003). Three participant experience themes were identified 1) improvements in symptoms; 2) feeling that the programme was complementary to standard care; 3) the particular suitability of singing and music to address their needs.Conclusion: An online breathing and wellbeing programme can improve the mental component of HRQoL and elements of breathlessness in people with persisting symptoms after COVID-19. Mind-body and music-based approaches, including practical, enjoyable symptom-management techniques may have a role supporting recovery.
Woodcock T, Greenfield G, Lalvani A, et al., 2022, Patient outcomes following emergency admission to hospital for COVID-19 compared with influenza: retrospective cohort study, Thorax, ISSN: 0040-6376
Background We examine differences in posthospitalisation outcomes, and health system resource use, for patients hospitalised with COVID-19 during the UK’s first pandemic wave in 2020, and influenza during 2018 and 2019.Methods This retrospective cohort study used routinely collected primary and secondary care data. Outcomes, measured for 90 days follow-up after discharge were length of stay in hospital, mortality, emergency readmission and primary care activity.Results The study included 5132 patients admitted to hospital as an emergency, with COVID-19 and influenza cohorts comprising 3799 and 1333 patients respectively. Patients in the COVID-19 cohort were more likely to stay in hospital longer than 10 days (OR 3.91, 95% CI 3.14 to 4.65); and more likely to die in hospital (OR 11.85, 95% CI 8.58 to 16.86) and within 90 days of discharge (OR 7.92, 95% CI 6.20 to 10.25). For those who survived, rates of emergency readmission within 90 days were comparable between COVID-19 and influenza cohorts (OR 1.07, 95% CI 0.89 to 1.29), while primary care activity was greater among the COVID-19 cohort (incidence rate ratio 1.30, 95% CI 1.23 to 1.37).Conclusions Patients admitted for COVID-19 were more likely to die, more likely to stay in hospital for over 10 days and interact more with primary care after discharge, than patients admitted for influenza. However, readmission rates were similar for both groups. These findings, while situated in the context of the first wave of COVID-19, with the associated pressures on the health system, can inform health service planning for subsequent waves of COVID-19, and show that patients with COVID-19 interact more with healthcare services as well as having poorer outcomes than those with influenza.
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
Halliday A, Masonou T, Tolosa-Wright MR, et al., 2022, Defining the role of cellular immune signatures in diagnostic evaluation of suspected tuberculosis, Journal of Infectious Diseases, Vol: 225, Pages: 1632-1641, ISSN: 0022-1899
BACKGROUND: Diagnosis of paucibacillary tuberculosis (TB) including extrapulmonary TB is a significant challenge, particularly in high-income, low-incidence settings. Measurement of Mycobacterium tuberculosis (Mtb)-specific cellular immune signatures by flow cytometry discriminates active TB from latent TB infection (LTBI) in case-control studies; however, their diagnostic accuracy and clinical utility in routine clinical practice is unknown. METHODS: Using a nested case-control study design within a prospective multicenter cohort of patients presenting with suspected TB in England, we assessed diagnostic accuracy of signatures in 134 patients who tested interferon-gamma release assay (IGRA)-positive and had final diagnoses of TB or non-TB diseases with coincident LTBI. Cellular signatures were measured using flow cytometry. RESULTS: All signatures performed less well than previously reported. Only signatures incorporating measurement of phenotypic markers on functional Mtb-specific CD4 T cells discriminated active TB from non-TB diseases with LTBI. The signatures measuring HLA-DR+IFNγ + CD4 T cells and CD45RA-CCR7-CD127- IFNγ -IL-2-TNFα + CD4 T cells performed best with 95% positive predictive value (95% confidence interval, 90-97) in the clinically challenging subpopulation of IGRA-positive but acid-fast bacillus (AFB) smear-negative TB suspects. CONCLUSIONS: Two cellular immune signatures could improve and accelerate diagnosis in the challenging group of patients who are IGRA-positive, AFB smear-negative, and have paucibacillary TB.
Park M, Lalvani A, Satta G, et al., 2022, Evaluating the clinical impact of routine whole genome sequencing in tuberculosis treatment decisions and the issue of isoniazid mono-resistance, BMC Infectious Diseases, Vol: 22, Pages: 1-10, ISSN: 1471-2334
BackgroundThe UK has implemented routine use of whole genome sequencing (WGS) in TB diagnostics. The WHO recommends addition of a fluoroquinolone for isoniazid mono-resistance, so early detection may be of use. The aim of this study was to describe the clinical utility and impact of WGS on treatment decisions for TB in a low incidence high resource clinical setting. The clinical turnaround time (TAT) for WGS was analysed in comparison to TB PCR using Xpert MTB/RIF (Cepheid, Sunnyvale, CA) results where available and subsequent phenotypic drug susceptibility testing (DST) when required.MethodsThis was a retrospective analysis of TB cases from January 2018 to March 2019 in London. Susceptibility and TAT by WGS, phenotypic DST, TB PCR using Xpert MTB/RIF were correlated to drug changes in order to describe the utility of WGS on treatment decisions on isoniazid mono-resistance in a low incidence high resource setting.Results189 TB cases were identified; median age 44 years (IQR 28–60), m:f ratio 112:77, 7 with HIV and 6 with previous TB. 80/189 cases had a positive culture and WGS result. 50/80 were fully sensitive to 1st line treatment on WGS, and the rest required additional DST. 20/80 cases required drug changes; 12 were defined by WGS: 8 cases had isoniazid mono-resistance, 2 had MDR-TB, 1 had isoniazid and pyrazinamide resistance and 1 had ethambutol resistance. The median TAT for positive culture was 16 days (IQR 12.5–20.5); for WGS was 35 days (IQR 29.5–38.75) and for subsequent DST was 86 days (IQR 69.5–96.75), resulting in non-WHO regimens for a median of 50.5 days (IQR 28.0–65.0). 9/12 has TB PCRs (Xpert MTB/RIF), with a median TAT of 1 day.ConclusionWGS clearly has a substantial role in our routine UK clinical settings with faster turnaround times in comparison to phenotypic DST. However, the majority of treatment changes defined by WGS were related to isoniazid resistance and given the 1 month TAT for WGS, it would be preferable
Walker TM, Miotto P, Köser CU, et al., 2022, The 2021 WHO catalogue of Mycobacterium tuberculosis complex mutations associated with drug resistance: a genotypic analysis., The Lancet Microbe, Vol: 3, Pages: e265-e273, ISSN: 2666-5247
Background: Molecular diagnostics are considered the most promising route to achieving rapid, universal drug susceptibility testing for Mycobacterium tuberculosiscomplex (MTBC). We aimed to generate a WHO endorsed catalogue of mutations to serve as a global standard for interpreting molecular information for drug resistance prediction. Methods: A candidate gene approach was used to identify mutations as associated with resistance, or consistent with susceptibility, for 13 WHO endorsed anti-tuberculosis drugs. 38,215 MTBC isolates with paired whole-genome sequencing and phenotypic drug susceptibility testing data were amassed from 45 countries. For each mutation, a contingency table of binary phenotypes and presence or absence of the mutation computed positive predictive value, and Fisher's exact tests generated odds ratios and Benjamini-Hochberg corrected p-values. Mutations were graded as Associated with Resistance if present in at least 5 isolates, if the odds ratio was >1 with a statistically significant corrected p-value, and if the lower bound of the 95% confidence interval on the positive predictive value for phenotypic resistance was >25%. A series of expert rules were applied for final confidence grading of each mutation. Findings: 15,667 associations were computed for 13,211 unique mutations linked to one or more drugs. 1,149/15,667 (7·3%) mutations were classified as associated with phenotypic resistance and 107/15,667 (0·7%) were deemed consistent with susceptibility. For rifampicin, isoniazid, ethambutol, fluoroquinolones, and streptomycin, the mutations' pooled sensitivity was >80%. Specificity was over 95% for all drugs except ethionamide (91·4%), moxifloxacin (91·6%) and ethambutol (93·3%). Only two resistance mutations were classified for bedaquiline, delamanid, clofazimine, and linezolid as prevalence of phenotypic resistance was low for these drugs. Interpretation: This first WHO endorsed catalogue of mol
Berrocal-Almanza LC, Harris RJ, Collin SM, et al., 2022, Effectiveness of nationwide programmatic testing and treatment for latent tuberculosis infection in migrants in England: a retrospective, population-based cohort study, LANCET PUBLIC HEALTH, Vol: 7, Pages: E305-E315, ISSN: 2468-2667
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- Citations: 3
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
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- Citations: 5
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
Kundu R, Sam Narean J, Wang L, et al., 2022, Cross-reactive memory T cells associate with protection against SARS-CoV-2 infection in COVID-19 contacts, Nature Communications, Vol: 13, ISSN: 2041-1723
Cross-reactive immune responses to SARS-CoV-2 have been observed in pre-pandemic cohorts and proposed to contribute to host protection. Here we assess 52 COVID-19 household contacts to capture immune responses at the earliest timepoints after SARS-CoV-2 exposure. Using a dual cytokine FLISpot assay on peripheral blood mononuclear cells, we enumerate the frequency of T cells specific for spike, nucleocapsid, membrane, envelope and ORF1 SARS-CoV-2 epitopes that cross-react with human endemic coronaviruses. We observe higher frequencies of cross-reactive (p=0.0139), and nucleocapsid-specific (p=0.0355) IL-2-secreting memory T cells in contacts who remained PCR-negative despite exposure (n=26), when compared with those who convert to PCR-positive (n=26); no significant difference in the frequency of responses to spike is observed, hinting at a limited protective function of spike-cross-reactive T cells. Our results are thus consistent with pre-existing non-spike cross-reactive memory T cells protecting SARS-CoV-2-naïve contacts from infection, thereby supporting the inclusion of non-spike antigens in second-generation vaccines.
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
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Fries A, Mandagere V, Parker R, et al., 2021, EVALUATION OF MYCOBACTERIUM TUBERCULOSIS-SPECIFIC IFN-G, TNF-A, CXCL10, IL2, CCL2, CCL7 AND CCL4 LEVELS FOR ACTIVE TUBERCULOSIS DIAGNOSIS, Publisher: BMJ PUBLISHING GROUP, Pages: A27-A28, ISSN: 0040-6376
Sgalla G, Iovene B, Bruni T, et al., 2021, Telemedicine-enabled, Hotel-based Management of Patients with COVID-19: A Single-Center Feasibility Study, ANNALS OF THE AMERICAN THORACIC SOCIETY, Vol: 18, Pages: 1743-1746, ISSN: 1546-3222
Lalvani A, Fenn J, Pillay TD, 2021, Probing the in-vivo reservoir of latent tuberculosis infection, LANCET MICROBE, Vol: 2, Pages: E226-E227
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- Citations: 1
Kondratiuk AL, Pillay TD, Kon OM, et al., 2021, A conceptual framework to accelerate the clinical impact of evolving research into long COVID, LANCET INFECTIOUS DISEASES, Vol: 21, Pages: 756-757, ISSN: 1473-3099
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- Citations: 8
Halliday A, Jain P, Hoang L, et al., 2021, New technologies for diagnosing active TB: the VANTDET diagnostic accuracy study, Efficacy and Mechanism Evaluation, Vol: 8, Pages: 1-160, ISSN: 2050-4365
<jats:sec id="abs1-1"> <jats:title>Background</jats:title> <jats:p>Tuberculosis (TB) is a devastating disease for which new diagnostic tests are desperately needed.</jats:p> </jats:sec> <jats:sec id="abs1-2"> <jats:title>Objective</jats:title> <jats:p>To validate promising new technologies [namely whole-blood transcriptomics, proteomics, flow cytometry and quantitative reverse transcription-polymerase chain reaction (qRT-PCR)] and existing signatures for the detection of active TB in samples obtained from individuals with suspected active TB.</jats:p> </jats:sec> <jats:sec id="abs1-3"> <jats:title>Design</jats:title> <jats:p>Four substudies, each of which used samples from the biobank collected as part of the interferon gamma release assay (IGRA) in the Diagnostic Evaluation of Active TB study, which was a prospective cohort of patients recruited with suspected TB.</jats:p> </jats:sec> <jats:sec id="abs1-4"> <jats:title>Setting</jats:title> <jats:p>Secondary care.</jats:p> </jats:sec> <jats:sec id="abs1-5"> <jats:title>Participants</jats:title> <jats:p>Adults aged ≥ 16 years presenting as inpatients or outpatients at 12 NHS hospital trusts in London, Slough, Oxford, Leicester and Birmingham, with suspected active TB.</jats:p> </jats:sec> <jats:sec id="abs1-6"> <jats:title>Interventions</jats:title> <jats:p>New tests using genome-wide gene expression microarray
Hoang LT, Jain P, Pillay TD, et al., 2021, Transcriptomic signatures for diagnosing tuberculosis in clinical practice: a prospective, multicentre cohort study, LANCET INFECTIOUS DISEASES, Vol: 21, Pages: 366-375, ISSN: 1473-3099
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- Citations: 15
Bruni T, Lalvani A, Richeldi L, 2020, Telemedicine-enabled Accelerated Discharge of Patients Hospitalized with COVID-19 to Isolation in Repurposed Hotel Rooms (vol 202, pg 508, 2020), AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 202, Pages: 1608-1609, ISSN: 1073-449X
Bruni T, Lalvani A, Richeldi L, 2020, An Expanded COVID-19 Telemedicine Intermediate Care Model Using Repurposed Hotel Rooms Reply, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 202, Pages: 1192-1193, ISSN: 1073-449X
Fenton ME, Wasko K, Behl V, et al., 2020, An Expanded COVID-19 Telemedicine Intermediate Care Model Using Repurposed Hotel Rooms, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 202, Pages: 1190-1192, ISSN: 1073-449X
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- Citations: 2
Bruni T, Lalvani A, Richeldi L, 2020, Telemedicine-enabled accelerated discharge of patients hospitalized with COVID-19 to isolation in repurposed hotel rooms., American Journal of Respiratory and Critical Care Medicine, Vol: 202, Pages: 508-510, ISSN: 1073-449X
de Lusignan S, Carlyon T, Lalvani A, 2020, COVID-19: REMOTE ASSESSMENT IN PRIMARY CARE Removing the handle of the Broad Street pump: measures to slow the spread of covid-19 in primary care teams, BMJ-BRITISH MEDICAL JOURNAL, Vol: 369, Pages: 1-1, ISSN: 1756-1833
Lalvani A, Seshadri C, 2020, Understanding how BCG vaccine protects against Mycobacterium tuberculosis infection: Lessons from household contact studies, Journal of Infectious Diseases, Vol: 221, Pages: 1229-1231, ISSN: 0022-1899
Jeon D, 2020, Latent tuberculosis infection: recent progress and challenges in South Korea, KOREAN JOURNAL OF INTERNAL MEDICINE, Vol: 35, Pages: 269-275, ISSN: 1226-3303
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- Citations: 9
Quijano-Campos JC, Williams L, Agarwal S, et al., 2020, CASPA (CArdiac Sarcoidosis in PApworth) improving the diagnosis of cardiac involvement in patients with pulmonary sarcoidosis: protocol for a prospective observational cohort study, BMJ OPEN RESPIRATORY RESEARCH, Vol: 7
Katelaris AL, Jackson C, Southern J, et al., 2020, Effectiveness of BCG vaccination against Mycobacterium tuberculosis infection in adults: a cross-sectional analysis of a UK-based cohort, The Journal of Infectious Diseases, Vol: 221, Pages: 146-155, ISSN: 0022-1899
BackgroundBCG appears to reduce acquisition of Mycobacterium tuberculosis (Mtb) infection in children, measured using interferon-gamma release assays (IGRAs). We explored whether BCG vaccination continues to be associated with decreased prevalence of Mtb infection in adults.MethodsWe conducted a cross-sectional analysis of data from adult contacts of tuberculosis cases participating in a UK cohort study. Vaccine effectiveness (VE) of BCG, ascertained based on presence of a scar or vaccination history, against latent tuberculosis infection (LTBI), measured via IGRA, was assessed using multivariable logistic regression. The effects of age at BCG and time since vaccination were also explored.ResultsOf 3453 recent tuberculosis contacts, 27.5% had LTBI. There was strong evidence of an association between BCG and LTBI (aOR=0.70, 95% CI 0.56-0.87, p=0.0017) yielding a VE of 30%. VE declined with time since vaccination, but there was evidence that LTBI prevalence was lower amongst vaccinated individuals even >20 years after vaccination, compared with non-vaccinated participants.ConclusionBCG is associated with lower prevalence of LTBI in adult contacts of tuberculosis. These results contribute to growing evidence that suggests BCG may protect against Mtb infection as well as disease. This has implications for immunisation programmes, vaccine development and tuberculosis control efforts worldwide.
Gupta RK, Lipman M, Jackson C, et al., 2019, Quantitative interferon gamma release assay and tuberculin skin test Results to predict incident tuberculosis: a prospective cohort study., American Journal of Respiratory and Critical Care Medicine, Vol: 208, Pages: 984-991, ISSN: 1073-449X
RATIONALE: Development of diagnostic tools with improved predictive value for tuberculosis (TB) is a global research priority. OBJECTIVES: We evaluated whether implementing higher diagnostic thresholds than currently recommended for QuantiFERON Gold-in-Tube (QFT-GIT), T-SPOT.TB and the tuberculin skin test (TST) might improve prediction of incident TB. METHODS: Follow-up of a UK cohort of 9,610 adult TB contacts and recent migrants was extended by re-linkage to national TB surveillance records (median follow-up 4.7 years). Incidence rates and rate ratios, sensitivities, specificities and predictive values for incident TB were calculated according to ordinal strata for quantitative results of QFT-GIT, T-SPOT.TB and TST (with adjustment for prior BCG). MEASUREMENTS AND MAIN RESULTS: For all tests, incidence rates and rate ratios increased with the magnitude of the test result (p<0.0001). Over three years' follow-up, there was a modest increase in positive predictive value (PPV) with the higher thresholds (3.0% for QFT-GIT ≥0.35 IU/mL vs. 3.6% for ≥4.00 IU/mL; 3.4% for T-SPOT.TB ≥5 spots vs. 5.0% for ≥50 spots; and 3.1% for BCG-adjusted TST ≥5mm vs. 4.3% for ≥15mm). As thresholds increased, sensitivity to detect incident TB waned for all tests (61.0% for QFT-GIT ≥0.35 IU/mL vs. 23.2% for ≥4.00 IU/mL; 65.4% for T-SPOT.TB ≥5 spots vs. 27.2% for ≥50 spots; 69.7% for BCG-adjusted TST ≥5mm vs. 28.1% for ≥15mm). CONCLUSIONS: Implementation of higher thresholds for QFT-GIT, T-SPOT.TB and TST modestly increases PPV for incident TB, but markedly reduces sensitivity. Novel biomarkers or validated multivariable risk algorithms are required to improve prediction of incident TB. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Park M, Dave D, Russell G, et al., 2019, FDG-PET/CT APPEARANCES IN MDR-TB PATIENTS WITH RESIDUAL CT ABNORMALITIES, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A69-A70, ISSN: 0040-6376
Chaplin E, Rervitt O, Ward S, et al., 2019, S5 Changing the shape of rehabilitation: breathlessness rehabilitation, British Thoracic Society Winter Meeting 2019, QEII Centre, Broad Sanctuary, Westminster, London SW1P 3EE, 4 to 6 December 2019, Programme and Abstracts, Publisher: BMJ Publishing Group Ltd and British Thoracic Society
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