Journal Article > ResearchFull Text
Lancet Infect Dis. 2017 July 1; Volume 17 (Issue 7); 754-762.; DOI:10.1016/S1473-3099(17)30170-6
Parikh S, Newbold L, Slater S, Moschioni M, Lucidarme J, et al.
Lancet Infect Dis. 2017 July 1; Volume 17 (Issue 7); 754-762.; DOI:10.1016/S1473-3099(17)30170-6
BACKGROUND
The UK introduced 4CMenB-a multicomponent vaccine against serogroup B meningococcal disease-into the national infant immunisation programme in September, 2015. The Meningococcal Antigen Typing System (MATS) was used to estimate coverage by 4CMenB of invasive meningococcal group B isolates obtained during 2007-08 in England and Wales (MATS coverage). We aimed to repeat the MATS survey for invasive meningococcal group B isolates obtained during 2014-15, before 4CMenB introduction; compare strain coverage between 2007-08 and 2014-15; and investigate associations between MATS coverage, age, region, and disease outcomes.
METHODS
Invasive serogroup B meningococcal isolates from cases in England, Wales, and Northern Ireland during 2014-15 were assayed using MATS and compared with 2007-08 data. MATS coverage was assessed by geographical region and age group. Clinical characteristics, risk factors, and outcomes were assessed according to MATS coverage for 2014-15 English cases.
FINDINGS
In 2014-15, 165 of 251 (66%; 95% CI 52-80) meningococcal group B isolates were estimated by MATS to be covered by 4CMenB, compared with 391 of 535 (73%; 95% CI 57-87) in 2007-08. The proportion of MATS-positive isolates with one vaccine antigen increased from 23% (122 of 535) in 2007-08 to 31% (78 of 251) in 2014-15, whereas the proportion with more than one antigen fell from 50% (269 of 535) to 35% (87 of 251). This effect reflected changes in circulating strains, particularly ST-269 clonal complex strains. MATS coverage increased with age, varied by geographical region, and was associated with more severe disease.
INTERPRETATION
In 2014-15, two-thirds of meningococcal group B isolates were predicted to be covered by 4CMenB. Temporal changes in MATS coverage underscore the need for continued monitoring of antigen expression and diversity, particularly in countries with 4CMenB programmes.
FUNDING
Public Health England, GlaxoSmithKline.
The UK introduced 4CMenB-a multicomponent vaccine against serogroup B meningococcal disease-into the national infant immunisation programme in September, 2015. The Meningococcal Antigen Typing System (MATS) was used to estimate coverage by 4CMenB of invasive meningococcal group B isolates obtained during 2007-08 in England and Wales (MATS coverage). We aimed to repeat the MATS survey for invasive meningococcal group B isolates obtained during 2014-15, before 4CMenB introduction; compare strain coverage between 2007-08 and 2014-15; and investigate associations between MATS coverage, age, region, and disease outcomes.
METHODS
Invasive serogroup B meningococcal isolates from cases in England, Wales, and Northern Ireland during 2014-15 were assayed using MATS and compared with 2007-08 data. MATS coverage was assessed by geographical region and age group. Clinical characteristics, risk factors, and outcomes were assessed according to MATS coverage for 2014-15 English cases.
FINDINGS
In 2014-15, 165 of 251 (66%; 95% CI 52-80) meningococcal group B isolates were estimated by MATS to be covered by 4CMenB, compared with 391 of 535 (73%; 95% CI 57-87) in 2007-08. The proportion of MATS-positive isolates with one vaccine antigen increased from 23% (122 of 535) in 2007-08 to 31% (78 of 251) in 2014-15, whereas the proportion with more than one antigen fell from 50% (269 of 535) to 35% (87 of 251). This effect reflected changes in circulating strains, particularly ST-269 clonal complex strains. MATS coverage increased with age, varied by geographical region, and was associated with more severe disease.
INTERPRETATION
In 2014-15, two-thirds of meningococcal group B isolates were predicted to be covered by 4CMenB. Temporal changes in MATS coverage underscore the need for continued monitoring of antigen expression and diversity, particularly in countries with 4CMenB programmes.
FUNDING
Public Health England, GlaxoSmithKline.
Journal Article > ResearchAbstract
Eur J Prev Cardiol. 2019 December 18; Volume 27; DOI:10.1177/2047487319876228
Munyombwe T, Lovelace R, Green M, Norman P, Walpole S, et al.
Eur J Prev Cardiol. 2019 December 18; Volume 27; DOI:10.1177/2047487319876228
Background
There is a paucity of population-based geospatial data about the association between active transport and myocardial infarction. We investigated the association between active transport to work and incidence of myocardial infarction.
Design
This ecological study of 325 local authorities in England included 43,077,039 employed individuals aged 25–74 years (UK Census, 2011), and 117,521 individuals with myocardial infarction (Myocardial Ischaemia National Audit Project, 2011–2013).
Methods
Bayesian negative binomial regression models were used to investigate the association of active transport to work and incidence of myocardial infarction adjusting for local levels of deprivation, obesity, smoking, diabetes and physical activity.
Results
In 2011, the prevalence of active transportation to work for people in employment in England aged 25–74 years was 11.4% (4,531,182 active transporters; 8.6% walking and 2.8% cycling). Active transport in 2011 was associated with a reduced incidence of myocardial infarction in 2012 amongst men cycling to work (incidence rate ratio (95% credible interval) 0.983 (0.967–0.999); and women walking to work (0.983 (0.967–0.999)) after full adjustments. However, the prevalence of active transport for men and women was not significantly associated with the combined incidence of myocardial infarction between 2011–2013 after adjusting for physical activity, smoking and diabetes.
Conclusions
In England, the prevalence of active transportation was associated with a reduced incidence of myocardial infarction for women walking and men cycling to work in corresponding local geographic areas. The overall association of active transport with myocardial infarction was, however, explained by local area levels of smoking, diabetes and physical activity.
There is a paucity of population-based geospatial data about the association between active transport and myocardial infarction. We investigated the association between active transport to work and incidence of myocardial infarction.
Design
This ecological study of 325 local authorities in England included 43,077,039 employed individuals aged 25–74 years (UK Census, 2011), and 117,521 individuals with myocardial infarction (Myocardial Ischaemia National Audit Project, 2011–2013).
Methods
Bayesian negative binomial regression models were used to investigate the association of active transport to work and incidence of myocardial infarction adjusting for local levels of deprivation, obesity, smoking, diabetes and physical activity.
Results
In 2011, the prevalence of active transportation to work for people in employment in England aged 25–74 years was 11.4% (4,531,182 active transporters; 8.6% walking and 2.8% cycling). Active transport in 2011 was associated with a reduced incidence of myocardial infarction in 2012 amongst men cycling to work (incidence rate ratio (95% credible interval) 0.983 (0.967–0.999); and women walking to work (0.983 (0.967–0.999)) after full adjustments. However, the prevalence of active transport for men and women was not significantly associated with the combined incidence of myocardial infarction between 2011–2013 after adjusting for physical activity, smoking and diabetes.
Conclusions
In England, the prevalence of active transportation was associated with a reduced incidence of myocardial infarction for women walking and men cycling to work in corresponding local geographic areas. The overall association of active transport with myocardial infarction was, however, explained by local area levels of smoking, diabetes and physical activity.
Journal Article > Meta-AnalysisFull Text
PLOS Med. 2012 August 28; Volume 9 (Issue 8); DOI:10.1371/journal.pmed.1001300
Ahuja SD, Ashkin D, Avendano M, Banerjee R, Bayona J, et al.
PLOS Med. 2012 August 28; Volume 9 (Issue 8); DOI:10.1371/journal.pmed.1001300
Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB.
Journal Article > ResearchFull Text
J Viral Hepat. 2022 March 12; Online ahead of print; DOI: 10.1111/jvh.13672
Morgan JR, Marsh E, Savinkina A, Shilton S, Shadaker S, et al.
J Viral Hepat. 2022 March 12; Online ahead of print; DOI: 10.1111/jvh.13672
Achieving global elimination of hepatitis C virus requires a substantial scale-up of testing. Point-of-care HCV viral load assays are available as an alternative to laboratory-based assays to promote access in hard to reach or marginalized populations. The diagnostic performance and lower limit of detection are important attributes of these new assays for both diagnosis and test of cure. Therefore, our objective was to determine an acceptable LLoD for detectable HCV viraemia as a test for cure, 12-weeks post-treatment (SVR12). We assembled a global dataset of patients with detectable viraemia at SVR12 from observational databases from 9 countries (Egypt, the United States, United Kingdom, Georgia, Ukraine, Myanmar, Cambodia, Pakistan, Mozambique), and two pharmaceutical-sponsored clinical trial registries. We examined the distribution of HCV viral load at SVR12 and presented the 90th , 95th, 97th, and 99th percentiles. We used logistic regression to assess characteristics associated with low-level virological treatment failure (defined as <1000 IU/mL). There were 5,973 cases of detectable viremia at SVR12 from the combined dataset. Median detectable HCV RNA at SVR12 was 287,986 IU/mL. The level of detection for the 95th percentile was 227 IU/mL (95% CI 170-276). Females and those with minimal fibrosis were more likely to experience low-level viremia at SVR12 compared to men (adjusted odds ratio AOR = 1.60 95% confidence interval [CI] 1.30-1.97 and those with cirrhosis (AOR=1.49 95% CI 1.15-1.93). In conclusion, an assay with a level of detection of 1000 IU/mL or greater may miss a proportion of those with low-level treatment failure
Journal Article > LetterFull Text
BMJ. 2024 September 12; Volume 386; q2002.; DOI:10.1136/bmj.q2002
Burnett A, Katona C, McCann S, Mostafanejad R, Yfantis A
BMJ. 2024 September 12; Volume 386; q2002.; DOI:10.1136/bmj.q2002
Journal Article > ResearchFull Text
J Clin Microbiol. 2014 July 16; Volume 52 (Issue 9); DOI:10.1128/JCM.00593-14
Ritchie AV, Ushiro-Lumb I, Edemaga D, Joshi HA, De Ruiter A, et al.
J Clin Microbiol. 2014 July 16; Volume 52 (Issue 9); DOI:10.1128/JCM.00593-14
Routine viral load (VL) testing of HIV-infected individuals on antiretroviral therapy (ART) is used to monitor treatment efficacy. However, due to logistical challenges, implementation of VL has been difficult in resource-limited settings. The aim of this study was to evaluate the performance of the SAMBA Semi-Q Test in London, Malawi, and Uganda. The SAMBA HIV-1 Semi-Q Test can distinguish between patients with VL above or below 1000 copies/ml. The SAMBA Semi-Q was validated with diluted clinical samples and blinded plasma samples collected from HIV-1-positive individuals. SAMBA Semi-Q results were compared with results from the Roche COBAS AmpliPrep/COBAS TaqMan HIV-1 Test v2.0. Testing of 96 2-10 fold dilutions of four samples containing HIV-1 subtype C as well as 488 samples from patients in the United Kingdom, Malawi, and Uganda, respectively, yielded an overall accuracy for SAMBA Semi-Q of 99% (95% CI 93.8 - 99.9%) and 96.9% (95% CI 94.9 - 98.3%) respectively compared to Roche. Analysis of VL data from patients in Malawi and Uganda showed that the SAMBA cut-off of 1000 copies/ml appropriately distinguished treated from untreated individuals. Furthermore, analysis of the viral load of 232 patients on ART in Malawi and Uganda revealed similar patterns for virological control defined as either <1000 copies/ml (SAMBA cut-off) or <5000 copies/ml (WHO 2010 criterion). This study suggests that SAMBA Semi-Q has adequate concurrency with the gold standard measurements for viral load measurement. This test can allow VL monitoring of patients on ART at the point of care in resource-limited settings.
Journal Article > ResearchFull Text
Epidemiol Infect. 2018 May 24; Volume 146 (Issue 12); DOI:10.1017/S0950268818001097
Azman AS, Ciglenecki I, Oeser C, Said B, Tedder IRS, et al.
Epidemiol Infect. 2018 May 24; Volume 146 (Issue 12); DOI:10.1017/S0950268818001097
Hepatitis E virus genotype 1 (HEV G1) is an important cause of morbidity and mortality in Africa and Asia. HEV G1's natural history, including the incubation period, remains poorly understood, hindering surveillance efforts and effective control. Using individual-level data from 85 travel-related HEV G1 cases in England and Wales, we estimate the incubation period distribution using survival analysis methods, which allow for appropriate inference when only time ranges, rather than exact times are known for the exposure to HEV and symptom onset. We estimated a 29.8-day (95% confidence interval (CI) 24.1-36.0) median incubation period with 5% of people expected to develop symptoms within 14.3 days (95% CI 10.1-21.7) and 95% within 61.9 days (95% CI 47.4-74.4) of exposure. These estimates can help refine clinical case definitions and inform the design of disease burden and intervention studies.
Journal Article > CommentaryFull Text
BMJ. 2021 November 30; Volume 375; n2962.; DOI:10.1136/bmj.n2962
McCann S
BMJ. 2021 November 30; Volume 375; n2962.; DOI:10.1136/bmj.n2962
Journal Article > ResearchFull Text
J. Infect.. 2021 July 1; Volume 83 (Issue 1); 84-91.; DOI:10.1016/j.jinf.2021.04.013
Farooq HZ, Davies E, Brown B, Whitfield T, Tilston P, et al.
J. Infect.. 2021 July 1; Volume 83 (Issue 1); 84-91.; DOI:10.1016/j.jinf.2021.04.013
OBJECTIVES
SARS-CoV-2 emerged in South Asia in 2019 and has resulted in a global pandemic. Public Health England (PHE) Manchester rapidly escalated testing for SARS-CoV-2 in the highest COVID-19 incidence location in England. The results of the PHE Manchester SARS-CoV-2 surveillance during the first wave are presented.
METHODS
Retrospective data were collected for patients fitting the PHE SARS-CoV-2 case definition from 11th February to 31st August 2020. Respiratory tract, tissue, faecal, fluid and cerebrospinal (CSF) samples were tested for SARS-CoV-2 by a semi-quantitative real-time reverse-transcription PCR.
RESULTS
Of the 204,083 tests for SARS-CoV-2, 18,011 were positive demonstrating a positivity of 8.90%. Highest positivity was in nasal swabs (20.99%) followed by broncheo-alveolar lavage samples (12.50%). None of the faecal, fluid or CSF samples received were positive for SARS-CoV-2.
CONCLUSIONS
There was a high incidence of SARS-CoV-2 patients in the North-West of England during the first UK wave of the Covid-19 pandemic. Highest positivity rate was in nasal specimens suggesting this is the optimum sample type within this dataset for detecting SARS-CoV-2. Further studies are warranted to assess the utility of testing faecal, fluid and CSF samples. Rapid escalation of testing via multiple platforms was required to ensure prompt diagnosis and isolate infected cases to reduce transmission of the virus.
SARS-CoV-2 emerged in South Asia in 2019 and has resulted in a global pandemic. Public Health England (PHE) Manchester rapidly escalated testing for SARS-CoV-2 in the highest COVID-19 incidence location in England. The results of the PHE Manchester SARS-CoV-2 surveillance during the first wave are presented.
METHODS
Retrospective data were collected for patients fitting the PHE SARS-CoV-2 case definition from 11th February to 31st August 2020. Respiratory tract, tissue, faecal, fluid and cerebrospinal (CSF) samples were tested for SARS-CoV-2 by a semi-quantitative real-time reverse-transcription PCR.
RESULTS
Of the 204,083 tests for SARS-CoV-2, 18,011 were positive demonstrating a positivity of 8.90%. Highest positivity was in nasal swabs (20.99%) followed by broncheo-alveolar lavage samples (12.50%). None of the faecal, fluid or CSF samples received were positive for SARS-CoV-2.
CONCLUSIONS
There was a high incidence of SARS-CoV-2 patients in the North-West of England during the first UK wave of the Covid-19 pandemic. Highest positivity rate was in nasal specimens suggesting this is the optimum sample type within this dataset for detecting SARS-CoV-2. Further studies are warranted to assess the utility of testing faecal, fluid and CSF samples. Rapid escalation of testing via multiple platforms was required to ensure prompt diagnosis and isolate infected cases to reduce transmission of the virus.
Journal Article > Meta-AnalysisFull Text
AIDS. 2010 June 19; Volume 24 (Issue 10); DOI:10.1097/QAD.0b013e32833a2a14
Ford NP, Mofenson L, Kranzer K, Medu L, Frigati L, et al.
AIDS. 2010 June 19; Volume 24 (Issue 10); DOI:10.1097/QAD.0b013e32833a2a14
INTRODUCTION
Primate studies and some observational human data have raised concern regarding an association of first-trimester efavirenz exposure with central nervous system congenital anomalies. The objective of this review is to update evidence on efavirenz safety in HIV-infected pregnant women to inform revision of the 2013 WHO guidelines for antiretroviral therapy in low and middle-income countries.
DESIGN
A systematic review and meta-analysis.
METHODS
We searched for studies reporting birth outcomes among women exposed to efavirenz during the first trimester of pregnancy up to 10 January 2014. Relative risks of congenital anomalies comparing women exposed to efavirenz and nonefavirenz-based antiretroviral regimens were pooled using random effects meta-analysis.
RESULTS
Twenty-three studies were included in this review, among which 21 reported the birth outcomes of 2026 live births among women exposed to efavirenz during the first trimester of pregnancy. Forty-four congenital anomalies were reported, giving a pooled proportion of 1.63% [95% confidence interval (95% CI) 0.78-2.48], with only one neural tube defect. Twelve studies reported birth outcomes of women exposed to efavirenz or nonefavirenz-containing regimens during the first trimester of pregnancy. Pooled analysis found no differences in overall risks congenital anomalies between these two groups (relative risk 0.78, 95% CI 0.56-1.08). The incidence of neural tube defects was low, 0.05% (95% CI <0.01-0.28), and similar to incidence in the general population.
DISCUSSION
This updated analysis found no evidence of an increased risk of overall or central nervous system congenital anomalies associated with first-trimester exposure to efavirenz, similar to previous systematic reviews. This review contributed to the evidence base for the revised 2013 WHO guidelines on antiretroviral therapy, which recommend that efavirenz can be included as part of first-line therapy in adults regardless of sex, and that it can be used throughout pregnancy, including during the first trimester. However, because of the low incidence of central nervous system anomalies in the overall population and relatively small number of exposures in the current literature, continued birth outcomes prospective surveillance is warranted.
Primate studies and some observational human data have raised concern regarding an association of first-trimester efavirenz exposure with central nervous system congenital anomalies. The objective of this review is to update evidence on efavirenz safety in HIV-infected pregnant women to inform revision of the 2013 WHO guidelines for antiretroviral therapy in low and middle-income countries.
DESIGN
A systematic review and meta-analysis.
METHODS
We searched for studies reporting birth outcomes among women exposed to efavirenz during the first trimester of pregnancy up to 10 January 2014. Relative risks of congenital anomalies comparing women exposed to efavirenz and nonefavirenz-based antiretroviral regimens were pooled using random effects meta-analysis.
RESULTS
Twenty-three studies were included in this review, among which 21 reported the birth outcomes of 2026 live births among women exposed to efavirenz during the first trimester of pregnancy. Forty-four congenital anomalies were reported, giving a pooled proportion of 1.63% [95% confidence interval (95% CI) 0.78-2.48], with only one neural tube defect. Twelve studies reported birth outcomes of women exposed to efavirenz or nonefavirenz-containing regimens during the first trimester of pregnancy. Pooled analysis found no differences in overall risks congenital anomalies between these two groups (relative risk 0.78, 95% CI 0.56-1.08). The incidence of neural tube defects was low, 0.05% (95% CI <0.01-0.28), and similar to incidence in the general population.
DISCUSSION
This updated analysis found no evidence of an increased risk of overall or central nervous system congenital anomalies associated with first-trimester exposure to efavirenz, similar to previous systematic reviews. This review contributed to the evidence base for the revised 2013 WHO guidelines on antiretroviral therapy, which recommend that efavirenz can be included as part of first-line therapy in adults regardless of sex, and that it can be used throughout pregnancy, including during the first trimester. However, because of the low incidence of central nervous system anomalies in the overall population and relatively small number of exposures in the current literature, continued birth outcomes prospective surveillance is warranted.