Mary Ramsay

Effectiveness of maternal pertussis vaccination in England: an observational study

BACKGROUND In October, 2012, a pertussis vaccination programme for pregnant women was introduced in response to an outbreak across England. We aimed to assess the vaccine effectiveness and the overall effect of the vaccine programme in preventing pertussis in infants. METHODS We undertook an analysis of laboratory-confirmed cases and hospital admissions for pertussis in infants between Jan 1, 2008, and Sept 30, 2013, using data submitted to Public Health England as part of its enhanced surveillance of pertussis in England, to investigate the effect of the vaccination programme. We calculated vaccine effectiveness by comparing vaccination status for mothers in confirmed cases with estimates of vaccine coverage for the national population of pregnant women, based on data from the Clinical Practice Research Datalink. FINDINGS The monthly total of confirmed cases peaked in October, 2012 (1565 cases), and subsequently fell across all age groups. For the first 9 months of 2013 compared with the same period in 2012, the greatest proportionate fall in confirmed cases (328 cases in 2012 vs 72 cases in 2013, -78%, 95% CI -72 to -83) and in hospitalisation admissions (440 admissions in 2012 vs 140 admissions in 2013, -68%, -61 to -74) occurred in infants younger than 3 months, although the incidence remained highest in this age group. Infants younger than 3 months were also the only age group in which there were fewer cases in 2013 than in 2011 (118 cases in 2011 vs 72 cases in 2013), before the resurgence. 26?684 women included in the Clinical Practice Research Datalink had a livebirth between Oct 1, 2012 and Sept 3, 2013; the average vaccine coverage before delivery based on this cohort was 64%. Vaccine effectiveness based on 82 confirmed cases in infants born from Oct 1, 2012, and younger than 3 months at onset was 91% (95% CI 84 to 95). Vaccine effectiveness was 90% (95% CI 82 to 95) when the analysis was restricted to cases in children younger than 2 months. INTERPRETATION Our assessment of the programme of pertussis vaccination in pregnancy in England is consistent with high vaccine effectiveness. This effectiveness probably results from protection of infants by both passive antibodies and reduced maternal exposure, and will provide valuable information to international policy makers. FUNDING Public Health England.

Increase in Endemic Neisseria meningitidis Capsular Group W Sequence Type 11 Complex Associated With Severe Invasive Disease in England and Wales

BACKGROUND In England and Wales, the incidence of invasive meningococcal disease has been declining for more than a decade, but meningococcal group W (MenW) cases have been increasing since 2009. METHODS Public Health England conducts enhanced national surveillance of invasive meningococcal disease in England and Wales. Detailed clinical information was obtained for all laboratory-confirmed MenW cases diagnosed during 3 epidemiologic years (2010-2011 to 2012-2013), alongside whole-genome sequencing analysis of the clinical isolates. RESULTS The year-on-year increase in invasive MenW disease across all age groups since 2009-2010 was due to rapid endemic expansion of a single clone belonging to the sequence type 11 complex (cc11). In 2013-2014, MenW was responsible for 15% of all invasive meningococcal disease. All but 1 of the recent MenW:cc11 isolates were very closely related, consistent with recent clonal expansion. Clinical follow-up of all 129 MenW cases diagnosed during 2010-2011 to 2012-2013 revealed that most patients were previously healthy (n = 105 [81%]), had not travelled abroad prior to illness and the majority presented with septicemia (n = 63 [49%]), meningitis (n = 16 [12%]) or both (n = 21 [16%]); however, one-quarter had atypical presentations including pneumonia (n = 15 [12%]), septic arthritis (n = 9 [7%]), and epiglottitis/supraglottitis (n = 5 [4%]). Forty-eight (37%) required intensive care and 15 (12%) died. There was no association between infecting strain, clinical disease, or outcome. CONCLUSIONS The recent increase in invasive MenW disease in England and Wales is due to rapid endemic expansion of a single clone belonging to cc11 and is associated with severe disease with unusual clinical presentations. This increase will require careful monitoring in the coming years.

Prioritization of HCV treatment in the direct-acting antiviral era: An economic evaluation

Graphical abstract

How should HCV treatment be prioritized in the direct-acting antiviral era? An economic evaluation including population prevention benefits.

Graphical abstract

HCV treatment rates and sustained viral response among people who inject drugs in seven UK sites: real world results and modelling of treatment impact.

Hepatitis C virus (HCV) antiviral treatment for people who inject drugs (PWID) could prevent onwards transmission and reduce chronic prevalence. We assessed current PWID treatment rates in seven UK settings and projected the potential impact of current and scaled‐up treatment on HCV chronic prevalence. Data on number of PWID treated and sustained viral response rates (SVR) were collected from seven UK settings: Bristol (37–48% HCV chronic prevalence among PWID), East London (37–48%), Manchester (48–56%), Nottingham (37–44%), Plymouth (30–37%), Dundee (20–27%) and North Wales (27–33%). A model of HCV transmission among PWID projected the 10‐year impact of (i) current treatment rates and SVR (ii) scale‐up with interferon‐free direct acting antivirals (IFN‐free DAAs) with 90% SVR. Treatment rates varied from <5 to over 25 per 1000 PWID. Pooled intention‐to‐treat SVR for PWID were 45% genotypes 1/4 [95%CI 33–57%] and 61% genotypes 2/3 [95%CI 47–76%]. Projections of chronic HCV prevalence among PWID after 10 years of current levels of treatment overlapped substantially with current HCV prevalence estimates. Scaling‐up treatment to 26/1000 PWID annually (achieved already in two sites) with IFN‐free DAAs could achieve an observable absolute reduction in HCV chronic prevalence of at least 15% among PWID in all sites and greater than a halving in chronic HCV in Plymouth, Dundee and North Wales within a decade. Current treatment rates among PWID are unlikely to achieve observable reductions in HCV chronic prevalence over the next 10 years. Achievable scale‐up, however, could lead to substantial reductions in HCV chronic prevalence.

Trends in bacterial, mycobacterial, and fungal meningitis in England and Wales 2004–11: an observational study

BACKGROUND Meningitis remains one of the most feared infectious diseases worldwide, yet there are few population-based studies on the epidemiology, causes, or trends over time in meningitis, especially in industrialised countries. Our aim was to do such a study using routinely reported data available in England and Wales. METHODS In England and Wales, UK National Health Service hospitals routinely report laboratory-confirmed pathogens electronically to Public Health England. Records of all positive bacterial, mycobacterial, and fungal results from cerebrospinal fluid or from blood cultures in patients with clinical meningitis were extracted for analysis. The percentage change in annual incidence was estimated using linear regression analysis of the log of the annual incidence. FINDINGS During 2004-11, 7061 cases of meningitis were reported (mean annual incidence 1·62 per 100,000 people, 95% CI 1·58-1·66), including 2594 cases in children (37%). The incidence of bacterial (1·44 per 100,000 people, 1·41-1·48), fungal (0·09, 0·08-0·10), and mycobacterial (0·09, 0·08-0·09) meningitis remained stable overall and across the age groups, apart from significant year-on-year increases in children younger than 3 months (978 cases; incidence 72·2 per 100,000 people; annual increase 7·4%, 5·1-9·8; p<0·0001) driven mainly by group B streptococci (GBS), and in adults aged 65 years or older (752 cases; incidence 1·2 per 100,000 people; annual increase 3·0%, 1·4-4·8; p<0·0001) primarily because of Escherichia coli. By contrast, meningococcal meningitis rates declined steadily, but remained the most common cause of meningitis in children. Overall, five groups of bacteria accounted for 60% (3790/6286) of bacterial meningitis cases: Neisseria meningitidis (1350 cases, 22%), Streptococcus pneumoniae (1143, 18%), Staphylococcus aureus (652, 10%), GBS (326, 5%), and E coli (319, 5%). INTERPRETATION In England and Wales, laboratory-based surveillance shows a remarkably stable incidence of bacterial, fungal, and mycobacterial meningitis in recent years, although there were differences in individual trends among the main pathogens causing meningitis in different age groups. FUNDING None.

Increased uptake and new therapies are needed to avert rising hepatitis C-related end stage liver disease in England: Modelling the predicted impact of treatment under different scenarios

BACKGROUND & AIMS Hepatitis C (HCV) related disease in England is predicted to rise, and it is unclear whether treatment at current levels will be able to avert this. The aim of this study was to estimate the number of people with chronic HCV infection in England that are treated and assess the impact and costs of increasing treatment uptake. METHODS Numbers treated were estimated using national data sources for pegylated interferon supplied, dispensed, or purchased from 2006 to 2011. A back-calculation approach was used to project disease burden over the next 30 years and determine outcomes under various scenarios of treatment uptake. RESULTS 5000 patients were estimated to have been treated in 2011 and 28,000 in total from 2006 to 2011; approximately 3.1% and 17% respectively of estimated chronic infections. Without treatment, incident cases of decompensated cirrhosis and hepatocellular carcinoma were predicted to increase until 2035 and reach 2290 cases per year. Treatment at current levels should reduce incidence by 600 cases per year, with a peak around 2030. Large increases in treatment are needed to halt the rise; and with more effective treatment the best case scenario predicts incidence of around 500 cases in 2030, although treatment uptake must still be increased considerably to achieve this. CONCLUSIONS If the infected population is left untreated, the number of patients with severe HCV-related disease will continue to increase and represent a substantial future burden on healthcare resources. This can be mitigated by increasing treatment uptake, which will have the greatest impact if implemented quickly.

Strengthening the Reporting of Molecular Epidemiology for Infectious Diseases (STROME-ID): an extension of the STROBE statement

Molecular data are now widely used in epidemiological studies to investigate the transmission, distribution, biology, and diversity of pathogens. Our objective was to establish recommendations to support good scientific reporting of molecular epidemiological studies to encourage authors to consider specific threats to valid inference. The statement Strengthening the Reporting of Molecular Epidemiology for Infectious Diseases (STROME-ID) builds upon the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) initiative. The STROME-ID statement was developed by a working group of epidemiologists, statisticians, bioinformaticians, virologists, and microbiologists with expertise in control of infection and communicable diseases. The statement focuses on issues relating to the reporting of epidemiological studies of infectious diseases using molecular data that were not addressed by STROBE. STROME-ID addresses terminology, measures of genetic diversity within pathogen populations, laboratory methods, sample collection, use of molecular markers, molecular clocks, timeframe, multiple-strain infections, non-independence of infectious-disease data, missing data, ascertainment bias, consistency between molecular and epidemiological data, and ethical considerations with respect to infectious-disease research. In total, 20 items were added to the 22 item STROBE checklist. When used, the STROME-ID recommendations should advance the quality and transparency of scientific reporting, with clear benefits for evidence reviews and health-policy decision making.

Hib vaccination in infants born prematurely

Aims: To document the immunogenicity and persistence of antibody to polyribosyl-ribitol phosphate (PRP) as well as the clinical protection against invasive Haemophilus influenzae type b (Hib) disease in premature infants immunised at the routine schedule. Methods: Blood was obtained at 2, 5, 12, and 64 months of age from a cohort of prematurely born infants (≤32 weeks gestation). Anti-PRP antibody concentrations were compared with those of a control cohort of infants born at full term and vaccinated at the same schedule. Hib vaccine failures occurring between October 1992 and October 2000 were reported by paediatricians through an active, prospective, national survey in the UK and Republic of Ireland. The number of prematurely born children with vaccine failure was compared with the corresponding number born at term. Results: Twenty seven prematurely born infants were followed to 5 years of age. Compared with term infants they had a significantly lower geometric mean concentration of anti-PRP antibody and/or a significantly lower proportion above one or both of the conventional protective antibody concentrations (0.15 and 1.0 μg/ml) at all ages. A total of 165 cases of invasive Hib disease were identified over eight years of national surveillance. Eighteen were premature (<37 weeks); approximately 12 would be expected. The relative risk of UK premature infants developing disease compared with term infants was 1.5 (95% CI 0.9 to 2.6). Conclusions: Premature infants develop lower antibody concentrations than term infants following Hib conjugate vaccination. Premature infants may also have an increased risk of clinical vaccine failure, but interpretation is limited by the small number of premature infants developing invasive Hib disease over eight years of national surveillance. Overall, vaccination with Hib conjugate vaccines affords a high level of protection to premature babies.

Targeted vaccination of teenagers following continued rapid endemic expansion of a single meningococcal group W clone (sequence type 11 clonal complex), United Kingdom 2015.

Since the epidemiological year 2009/10, the United Kingdom has experienced a year-on-year increase in meningococcal group W (MenW) disease due to rapid expansion of a single endemic hyper-virulent strain belonging to sequence type 11 clonal complex (cc). This strain was identified among cases diagnosed across all regions and was not linked to travel abroad. Consequently, an adolescent MenACWY conjugate vaccination programme for 13-18 year-olds will be introduced in August 2015, with priority given to 17-18 year-olds (school leavers).