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OBJECTIVE: To describe cases of invasive meningococcal disease (IMD) in women of childbearing age and to estimate the disease incidence and relative risk of IMD in pregnant compared with non-pregnant women. DESIGN: Prospective enhanced national surveillance for IMD. SETTING: England. POPULATION: Women of reproductive age (15-44 years) with laboratory-confirmed IMD. METHODS: Public Health England conducts enhanced national surveillance for IMD in England. Laboratory-confirmed cases are followed up with postal questionnaires to general practitioners. All cases confirmed in women of reproductive age from 1 January 2011 to 31 December 2014 were included. MAIN OUTCOME MEASURES: Annual IMD incidence and relative risk of IMD in pregnant compared with non-pregnant women of reproductive age. RESULTS: During the 4-year surveillance period, there were 1502 cases of IMD in females across England; of these, 310 (20.6%) cases were in women of reproductive age, including four women who were pregnant at the time of IMD confirmation (1.3%). Serogroup distribution of IMD cases in women of childbearing age was similar to the overall distribution. The four cases in otherwise healthy pregnant women were confirmed across all trimesters and all survived; one case in the first trimester had a septic miscarriage. The incidence of IMD was lower in pregnant than in non-pregnant women (0.16 compared with 0.76 per 100 000 pregnant and non-pregnant years, respectively), giving a lower risk of IMD in pregnant women (incidence rate ratio, IRR, 0.21; 95% confidence interval, 0.06-0.54). CONCLUSIONS: Pregnant women are nearly five times less likely to develop IMD compared with non-pregnant women, but the infection can be severe. TWEETABLE ABSTRACT: The risk of meningococcal disease is lower in pregnant women compared with non-pregnant women; the infection can occur across all trimesters and can be severe.

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Public Health England conducts enhanced national surveillance of tetanus, a potentially life-threatening vaccine-preventable disease. A standardized questionnaire was used to ascertain clinical and demographic details of individuals reported with clinically suspected tetanus. The 96 cases identified between 2001 and 2014 were analysed. The average annual incidence was 0·13/million (95% confidence interval 0·10-0·16) of which 50·0% were male. Where reported, 70·3% of injuries occurred in the home/garden (45/64). Overall, 40·3% (31/77) cases were in people who inject drugs (PWID), including a cluster of 22 cases during 2003-2004. Where known (n = 68), only 8·8% were age-appropriately immunized. The overall case-fatality rate was 11·0% (9/82). All tetanus-associated deaths occurred in adults aged >45 years, none of whom were fully immunized. Due to the success of the childhood immunization programme, tetanus remains a rare disease in England with the majority of cases occurring in older unimmunized or partially immunized adults. Minor injuries in the home/garden were the most commonly reported likely sources of infection, although cases in PWID increased during this period. It is essential that high routine vaccine coverage is maintained and that susceptible individuals, particularly older adults, are protected through vaccination and are offered timely post-exposure management following a tetanus-prone wound.

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New direct-acting antivirals have the potential to transform the hepatitis C (HCV) treatment landscape, with rates of sustained viral response in excess of 90%. As these new agents are expensive, an important question is whether to focus on minimizing the consequences of severe liver disease, or reducing transmission via 'treatment as prevention'. A back-calculation model was used to estimate the impact of treatment of mild, moderate and compensated cirrhosis on incident cases of HCV-related end-stage liver disease/hepatocellular carcinoma (ESLD/HCC). In addition, a dynamic model was used to determine the impact on incidence and prevalence of chronic infection in people who inject drugs (PWID), the main risk group in England. Treating 3500 cirrhotics per year was predicted to reduce ESLD/HCC incidence from 1100 (95% CrI 970-1240) cases per year in 2015 to 630 (95% CrI 530-770) in 2020, around half that currently expected, although treating moderate-stage disease will also be needed to sustain this reduction. Treating mild-stage PWID was required to make a substantial impact on transmission: with 2500 treated per year, chronic prevalence/annual incidence in PWID was reduced from 34%/4.8% in 2015 to 11%/1.4% in 2030. There was little overlap between the two goals: treating mild stage had virtually no impact on ESLD/HCC within 15 years, but the long timescale of liver disease means relatively few PWID reach cirrhosis before cessation of injecting. Strategies focussing on treating advanced disease have the potential for dramatic reductions in severe morbidity, but virtually no preventative impact.

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BACKGROUND: Liver transplantation is an important and established treatment option for chronic hepatitis C virus (HCV) related end-stage liver disease (HCV-related ESLD). This study describes trends in elective liver transplantation among persons with HCV-related ESLD. STUDY DESIGN: Retrospective cohort. METHODS: Analyses of United Kingdom (UK) Transplant Registry data for the period 1994 to 2010, with follow-up information extending to 2011. RESULTS: Annual registrations for liver transplantation increased linearly and alcoholic liver cirrhosis (2075, 24%) and HCV-related ESLD (1213, 14%) were the most common indications. HCV-related ESLD patients were mainly aged 40-49 years (32%) and 50-59 years (43%); males (76%); and of white ethnicity (74%). Overall, 75% (956/1213) received a liver transplant with a linear increase over the period (OR 1.11, 95% CI 1.08, 1.13). Pre transplant mortality was unchanged (adjusted OR 1.0, 95% CI 0.96, 1.05) and post-transplant mortality decreased in both HCV-related (adjusted OR 0.77, 95% CI 0.68, 0.88) and non-HCV-related ESLD (adjusted OR 0.82, 95% CI 0.75, 0.89) patients. CONCLUSION: The increase in demand for and receipt of liver transplants among persons with HCV-related ESLD requires coordinated efforts to increase not only organ donation, but investment in HCV prevention programmes and improved access to hepatitis C treatment services.

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The aim of this study was to estimate the amount of childhood hepatitis B virus transmission in children born in the UK, a very low-prevalence country, that is preventable only by universal hepatitis B immunization of infants. Oral fluid specimens were collected from schoolchildren aged 7-11 years in four inner city multi-ethnic areas and tested for the presence of antibody to hepatitis B core antigen (anti-HBc). Those found positive or indeterminate were followed up with testing on serum to confirm their hepatitis B status. The overall prevalence of anti-HBc in children was low [0.26%, 95% confidence interval (CI) 0.14-0.44]. The estimated average annual incidence of hepatitis B was estimated to be 29.26/100 000 children (95% CI 16.00-49.08). The total incidence that is preventable only by a universal infant immunization programme in the UK was estimated to be between 5.00 and 12.49/100 000. The study demonstrates that the extent of horizontal childhood hepatitis B virus transmission is low in children born in the UK and suggests that schools in the UK are an uncommon setting for the transmission of the virus. Targeted hepatitis B testing and immunization of migrants from intermediate- and high-prevalence countries is likely to be a more effective measure to reduce childhood transmission than a universal infant immunization programme.

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Surveillance of acute hepatitis B in England is necessary to estimate incidence, determine routes of transmission and inform public health actions. Here we describe an automated process to extract information on testing for markers of hepatitis B infection in English sentinel laboratories between 2002 and 2008. The resulting data were used to identify individuals with acute infections, describe their characteristics and estimate the incidence of infection. Two-thirds of acute infections were in males. Heterosexual exposure and injecting drug use were the main risks reported. Annual incidence was estimated at 1.3/100 000 person-years overall (1.7 and 0.6 for males and females, respectively) and declined each year. Automated extraction of hepatitis B markers, including quantitative results where available, can help to classify HBV status more accurately for surveillance. HBV incidence in England is at its lowest level in recent years.

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In a cohort of 272 treatment-naive individuals with chronic hepatitis C infection acquired on a known date who were enrolled in the UK HCV National Register, a progressive improvement in response to treatment was found with the evolution of antiviral therapies from 20% (25/122) for interferon monotherapy to 63% (55/88) for pegylated interferon+ribavirin therapy. Multivariable analysis results showed increasing age to be associated with poorer response to therapy [odds ratio (OR) 0·84, 95% confidence interval (CI) 0·72-0·99, P=0·03] whereas time since infection was not associated with response (OR 0·93, 95% CI 0·44-1·98, P=0·85). Other factors significantly associated with a positive response were non-type 1 genotype (P<0·0001) and combination therapies (P<0·0001). During the first two decades of chronic HCV infection, treatment at a younger age was found to be more influential in achieving a sustained viral response than treating earlier in the course of infection.

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The present study describes the clinical and immunological features of children with Hib vaccine failure, who were identified through national surveillance between 1996 and 2001 in Europe, Israel and Australia. True vaccine failure was defined as invasive Hib disease occurring ≥2 weeks after one dose, given after the first birthday, or ≥1 week after ≥2 doses, given at <1 year of age. Of the 423 cases (representing 0.2 cases per 100,000 child-years at risk) reported, 330 (78%) had received three doses in the first year of life and developed disease at a median age of 28 months. Of the remaining 93, 48 had received two doses in infancy, 34 had received four doses including a booster, and 11 had received a single dose after 12 months of age. These children developed disease at a median age of 12, 33 and 71 months, respectively. In total, 47 out of 258 children (18%) with available information had an underlying medical problem (including prematurity) and 53 out of 161 (33%) had immunoglobulin deficiency. Convalescent Hib antibody concentrations were above the putative protective concentration of 1.0 mg/L in 147/194 (76%) children; low concentrations were associated with both the presence of an underlying medical problem and young age at the time of Hib disease. Almost all children who received an additional vaccine dose developed antibodies at protective concentrations. Thus, Hib vaccine failure is rare, but can occur with any immunization schedule. Children with Hib vaccine failure should have immunoglobulin and convalescent Hib antibody concentrations measured after infection and receive additional vaccination, if required.

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Hepatitis C is a global health problem and in the UK seroprevalence studies have mainly concentrated on specific high-risk groups. The aim of this study was to determine changes in the prevalence of antibody to hepatitis C virus in England using residual specimens collected between 1986 and 2000 reflecting the general population. A cross-sectional study design using a convenience collection of serum specimens from adult patients submitted to laboratories in the years 1986, 1991, 1996 and 2000 from a total of 19 laboratories around England were investigated. The main outcome was to determine anti-HCV prevalence and the average incidence occurring between 1986 and 2000 and factors associated with infection. Multivariable analysis of results from all years showed there was a significant difference in prevalence between males and females (P < 0.001), birth cohort (P < 0.001) and by health region (P < 0.001). An average of 0.72% (95% CI 0-1.65%) of those susceptible to HCV born between 1950 and 1970 were estimated to have acquired the infection between 1986 and 2000. Analysis of this convenience serum collection suggests that HCV prevalence is low in the general population, and is associated with period of birth, gender and health region. There was evidence to support a low incidence of HCV infection in those born between 1950 and 1970 over the period 1986-2000 which, at the population level, equated to a substantial burden of infection (approximately 106,000 persons). Continued surveillance and prevention targeted at injecting drug users are essential for the control of hepatitis C in the UK.

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Surveillance reports and prevalence studies have indicated that injecting drug users (IDUs) contribute more to the hepatitis C epidemic in the United Kingdom than any other risk group. Information on both the prevalence and incidence of hepatitis C in IDUs is therefore essential to understanding the epidemiology of this infection. The prevalence of hepatitis C in specimens from the Unlinked Anonymous Prevalence Monitoring Programme collected in 1995, 1996, 1998, 1999, 2000, and 2001 was determined using residual syphilis serology specimens from IDUs attending 15 genitourinary medicine (GUM) clinics in and outside London. These specimens were tested for antibodies to hepatitis C virus (anti-HCV). Using this cross-sectional design, anti-HCV-negative specimens were tested for HCV RNA to identify incident infections during the 'window' period of infection, and thus to estimate HCV incidence. Results of the multivariable analysis showed that there was marked variation in prevalence by clinic (P<0.0001) and age (P<0.0001). Overall the majority of infections were in males and the overall prevalence in injectors declined over the study period from 36.9% to 28.7%. The annual incidence in these injectors was estimated as being 3.01% (95% CI 1.25-6.73). Over the study period HCV incidence decreased by 1.2% per year. Genotyping of the incident infections identified the most common genotype as type 1 with type 3 being more frequently seen after 1998. Of the prevalent infections, genotype 1 was the most common. The study has confirmed a higher prevalence of anti-HCV in IDUs in the London area compared to those outside London. How representative of the current injecting drug user population are IDUs attending GUM clinics is unclear. Even so, such studies allow prevalence and incidence to be estimated in individuals who have ever injected drugs and inform ongoing public health surveillance.

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Matching individuals reported to a sentinel surveillance scheme for hepatitis C between 2000 and 2005 to individuals with a hospital episode for hepatitis C-related liver disease in the same hospitals, we estimated that the number of cases of hepatitis C-related end-stage liver disease in these English hospitals was 42% (597/419) higher than Hospital Episode Statistics (HES) would indicate. Further, matching records of hepatitis C-related deaths in HES to death certificates, we estimated that, between 2000 and 2005, the true number of deaths from hepatitis C-related end-stage liver disease was between 185% (353/124) and 257% (378/106) higher than the number recorded in routine mortality statistics. We provide estimates of under-recording that can be used to modify existing models of disease burden due to hepatitis C and provide a simple approach to improve the monitoring of trends in severe hepatitis C-related morbidity over time.

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The diagnosis of acute hepatitis C virus (HCV) infection is not straightforward; few people exhibit clinical symptoms and genome/antigen detection techniques do not indicate when infection had occurred. Here, a strategy to detect HCV RNA in the absence of antibody ('window-period') for diagnosis of acute infection is assessed. The sentinel surveillance of hepatitis testing study was used to retrospectively identify anti-HCV negative samples from high-risk individuals (2002-2003), for testing singly for HCV RNA. Additional samples were identified prospectively (2005) and tested in pools for HCV RNA. Positive samples were genotyped. Incidence and costs of adopting the pooling strategy were estimated. In the retrospective study, 8/390 (2.1%) samples were confirmed HCV RNA positive, anti-HCV negative. Prospectively, 3237 samples were tested in 325 pools. Five positive pools identified four confirmed HCV RNA positive patients (one false positive). Estimated incidence was 12.9 per 100 person-years in injecting drug users (IDUs) (retrospective study) and 3.7 per 100 person-years among drug/alcohol services and prison attendees (prospective study). Estimated costs were pound 850 per positive sample, in areas of higher risk. The yield from a window-period strategy depends upon the population tested. Pooled HCV RNA testing of anti-HCV negative samples from the current IDUs is realistic and relatively inexpensive to identify recently infected individuals.

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SUMMARY: Many people infected with hepatitis C virus (HCV) are unaware of their infection and are, therefore. potentially infectious to others. To enable effective case-finding policies to be developed, an understanding of where people, and injecting drug users (IDUs) in particular, are accessing HCV antibody testing is needed. HCV antibody testing data were collected electronically from 21 sentinel laboratories in England between 2002 and 2006 in this cross-sectional study. Service types of the physician requesting the HCV test were identified and classified. Differences in people being tested in each service type and over time were investigated. Over half a million people were tested in 5 years. Whilst most testing took place in hospital, a large proportion of people were tested in community care, particularly in general practice surgeries and genito-urinary medicine clinics. Younger people were more likely to be tested in community care, and there was evidence that testing differed according to ethnic status. IDUs were tested in all parts of the health services, although the highest proportion positive were from prisons and specialist services for drug users. Testing increased between 2002 and 2005 whilst the proportion of people testing positive declined. Routine laboratory data can provide valuable information on where people are being tested for HCV. Risk exposures should be investigated and testing targeted to people at higher risk for infection. Local laboratories should review data on testing locations and proportion positive to inform local initiatives to improve testing and yield.

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The aim of the study was to investigate the differing epidemiology of hepatitis C-related end-stage liver disease in ethnic minorities in England. We used Hospital Episode Statistics from 1997/98 to 2004/05 to directly age-standardize numbers of episodes and deaths from hepatitis C-related end-stage liver disease in ethnic groups using the white English population as standard and the age-structured population by ethnic group from the 2001 Census. We estimated the odds of having a diagnosis of end-stage liver disease amongst hepatitis C-infected individuals in each ethnic group compared with whites using logistic regression. The main outcome measures were age-standardized morbidity and mortality ratios and morbidity and mortality odds ratios. Standardized ratios (95% confidence interval) for hepatitis C-related end-stage liver disease ranged from 73 (38-140) in Chinese people to 1063 (952-1186) for those from an 'Other' ethnic group. Amongst individuals with a diagnosis of hepatitis C infection, the odds ratios (95% CI) of severe liver disease were 1.42 (1.13-1.79), 1.57 (1.36-1.81), 2.44 (1.85-3.22), 1.73 (1.36-2.19) and 1.83 (1.08-3.10) comparing individuals of Black African, Pakistani, Bangladeshi, Indian and Chinese origin with whites, respectively. Ethnic minority populations in England are more likely than whites to experience an admission or to die from severe liver disease as a result of hepatitis C infection. Ethnic minority populations may have a higher prevalence of hepatitis C or they may experience a poorer prognosis because of differential access to health services, longer duration of infection or the prevalence of co-morbidities.

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A rise in invasive Haemophilus influenzae type b (Hib) infections occurred 8 years after vaccine introduction in the United Kingdom. Aspects of Hib vaccine delivery unique to the United Kingdom have been implicated. The authors developed a fully age-structured deterministic susceptible-infected-resistant-susceptible mathematical model, expressed as a set of partial differential equations, to better understand the causes of declining vaccine effectiveness. We also investigated the consequences of the vaccine's impact on reducing Hib transmission for maintenance of immunity. Our findings emphasized the importance of maintaining high post-immunization antibody titres among age groups at greatest risk of invasive infections. In keeping with UK population-based estimates, low direct efficacy of immunological memory against disease was found, cautioning against over-reliance on evidence of priming alone as a correlate of population protection. The contribution of herd immunity to disease control was reinforced. Possible intervention strategies will be explored in subsequent work.

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OBJECTIVE: To assess the impact of a Hib vaccination booster campaign targeting children aged 6 months to 4 years between May and September 2003, following a nationwide increase in the number of invasive Haemophilus influenzae serotype b (Hib) cases in all age groups after 1999. DESIGN: The Health Protection Agency Centre for Infections prospectively monitors all cases of H influenzae disease in England and Wales and collects data from primary care trusts (PCTs) on coverage for vaccines in the childhood programme. POPULATION: Adults and children in England and Wales (January 1991 to December 2006) RESULTS: Data on vaccine coverage during the Hib booster campaign were available for 288/303 (95%) PCTs in England and revealed coverage of 71.8% for the 6-12-month age group and 63.2% for the 13-48-month age group. The Hib booster campaign resulted in a dramatic reduction in cases within 12 months in the age groups targeted for the booster. This decline was followed by a reduction in the number of cases reported among older children and adults. Since the campaign, however, there has been an increase in the number of cases reported among 1-3-year-old children (13 cases in 2004, 26 cases in 2005 and 32 cases in 2006), primarily in children who were too young to be vaccinated in the booster campaign. This group of children will be targeted in the pre-school catch-up programme that began in September 2007. CONCLUSIONS: The Hib booster campaign has helped to re-establish herd immunity in the UK. The increase in Hib disease among toddlers after 2004 supports the decision to introduce routine boosting for Hib at 12 months of age.

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In England, a large number of individuals are infected with the hepatitis C virus (HCV) and may develop future liver complications, such as decompensated cirrhosis and hepatocellular carcinoma (HCC). Estimates of the magnitude of this future burden are required to plan healthcare resources. We have estimated past incidence of HCV infection in England and predict future burden of end-stage liver disease in the HCV-infected population. A model of the natural history of HCV as a series of disease stages was constructed. A back-calculation approach was performed, using the natural history model and data on annual HCC deaths in England from 1996 to 2004 with mention of HCV and hospital episode statistics for end-stage liver disease with HCV. The number of HCV-infected people living with compensated cirrhosis is predicted to rise from 3705 [95% credible interval (CrI): 2820-4975] in 2005 to 7550 (95% CrI: 5120-11,640) in 2015. The number of decompensated cirrhosis and/or HCC cases is also predicted to rise, to 2540 (95% CrI: 2035-3310) by 2015. HCV incidence increased during the 1980s, with an annual incidence of 12 650 (95% CrI: 6150-26,450) by 1989. HCV-related cirrhosis and deaths from HCC in England are likely to increase dramatically within the next decade. If patients are left undiagnosed and untreated, the future burden of the disease on healthcare resources will be substantial.

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Injection drug use is a common route of infection for the hepatitis B virus (HBV) in the UK. The aim of this study was to establish the prevalence and force of infection for HBV among injecting drug users (IDUs) recruited from multiple community and drug agency settings in England and Wales between 1990 and 2004. Cross-sectional studies of IDUs in and out of contact with drug agencies were conducted throughout the 15-year period. Oral fluid samples were tested for antibodies to the hepatitis B core antigen (anti-HBc). Logistic regression was used to investigate associations between risk factors and anti-HBc positivity and force of infection models were explored. In total, 2527 injectors were recruited from community settings, and 29 386 from drug agencies. Anti-HBc prevalence was 31% (95% CI 30.7-31.8%). It declined in the early 1990s from around 50% in 1992 to 25% in 1999, after which it increased slightly. It was also higher in those who had injected for longer, older IDUs, those recruited in London and North West England, and those reporting having a previous voluntary confidential HIV test. The force of infection models suggested that the incidence of infection increased in 1999-2004 compared with 1993-1998, and was higher in new injectors compared with those injecting for > or =1 year. In conclusion, findings suggest ongoing HBV transmission in recent years despite an overall decline in prevalence in the early and mid-1990s, and highlight the importance of targeting vaccination programmes at new IDUs who have high incidence rates of infection.

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Whether differences in the natural history of hepatitis C virus (HCV) can be explained by differences in the infecting HCV type is unknown. The aim of this study was to investigate whether the HCV type might influence the clinical outcome of infection. Study serum samples were assembled from 749 individuals enrolled into the UK HCV National Register from which data on clinical outcomes were extracted. HCV-RNA-positive specimens were genotyped and HCV-RNA-negative specimens serotyped. Logistic regression analysis was used to investigate the independent effect of HCV type on viral clearance by comparing patients who were HCV RNA negative (n = 86) with those who were HCV RNA positive (n = 508). The same method was used to investigate whether HCV type was associated with histological stage of liver disease. The prevalence of HCV type 1 among those who cleared infection was 69% and among those who remained HCV RNA positive was 51%: Type 1 infections were more likely to be HCV RNA negative than non-1 types (OR 0.47, 95% CI 0.29-0.78, P = 0.003). Type 1 infections were also more likely to be associated with histological stage scores above the median when compared with non-1 types (OR 2.03, 95% CI 1.07-3.83, P = 0.03). In conclusion, HCV type 1 infection was more often HCV RNA negative, suggesting that spontaneous clearance may occur more commonly with this type. Among the RNA-positive infections, type 1 infection may be more aggressive than types 2/3.

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Enhanced surveillance for Hib infection, initially covering Wales and five English regions, began in 1990 and in 1995 was extended to the whole of England and Wales. To determine whether changes in the ascertainment of Haemophilus influenzae may have affected estimates of Hib disease incidence, data from January 1990 to December 2003 were analysed. A total of 8887 and 4020 (45%) cases of H. influenzae and Hib respectively were reported. The proportion of isolates that were serotyped increased over time, and therefore reported incidence may have underestimated the true incidence in the early years of the study. Adjusting for this under-ascertainment, the incidence in children aged <5 years declined from a peak of 28.3/100,000 in 1991 to 0.97/100,000 in 1998 and increased to 3.8/100,000 in 2003. Following the implementation of universal vaccination a dramatic decline in the true incidence of invasive Hib disease occurred. The observation of the subsequent resurgence was real but the highest incidence reached was 85% below the corrected incidence in the pre-vaccine era. Continued high-quality surveillance is needed in order to accurately monitor and detect changes in disease incidence.

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