The impact of certain underlying comorbidities on the risk of developing hospitalised pneumonia in England.

BACKGROUND: UK specific data on the risk of developing hospitalised CAP for patients with underlying comorbidities is lacking. This study compared the likelihood of hospitalised all-cause community acquired pneumonia (CAP) in patients with certain high-risk comorbidities and a comparator group with no known risk factors for pneumococcal disease. METHODS: This retrospective cohort study interrogated data in the Hospital Episodes Statistics (HES) dataset between financial years 2012/13 and 2016/17. In total 3,078,623 patients in England (aged ≥18 years) were linked to their hospitalisation records. This included 2,950,910 individuals with defined risk groups and a comparator group of 127,713 people who had undergone tooth extraction with none of the risk group diagnoses. Risk groups studied were chronic respiratory disease (CRD), chronic heart disease (CHD), chronic liver disease (CLD), chronic kidney disease (CKD), diabetes (DM) and post bone marrow transplant (BMT). The patients were tracked forward from year 0 (2012/13) to Year 3 (2016/17) and all diagnoses of hospitalised CAP were recorded. A Logistic regression model compared odds of developing hospitalised CAP for patients in risk groups compared to healthy controls. The model was simultaneously adjusted for age, sex, strategic heath authority (SHA), index of multiple deprivation (IMD), ethnicity, and comorbidity. To account for differing comorbidity profiles between populations the Charlson Comorbidity Index (CCI) was applied. The model estimated odds ratios (OR) with 95% confidence intervals of developing hospitalised CAP for each specified clinical risk group. RESULTS: Patients within all the risk groups studied were more likely to develop hospitalised CAP than patients in the comparator group. The odds ratios varied between underlying conditions ranging from 1.18 (95% CI 1.13, 1.23) for those with DM to 5.48 (95% CI 5.28, 5.70) for those with CRD. CONCLUSIONS: Individuals with any of 6 pre-defined underlying comorbidities are at significantly increased risk of developing hospitalised CAP compared to those with no underlying comorbid condition. Since the likelihood varies by risk group it should be possible to target patients with each of these underlying comorbidities with the most appropriate preventative measures, including immunisations.

Dynamic transmission modelling to address infant pneumococcal conjugate vaccine schedule modifications in the UK.

The 13-valent pneumococcal conjugate vaccine (PCV) has been part of routine immunisation in a 2 + 1 schedule (two primary infant doses and one booster during the second year of life) in the UK since 2010. Recently, the UK's Joint Committee on Vaccination and Immunisation recommended changing to a 1 + 1 schedule while conceding that this will increase disease burden; however, uncertainty remains on how much pneumococcal burden - including invasive pneumococcal disease (IPD) and non-invasive disease - will increase. We built a dynamic transmission model to investigate this question. The model predicted that a 1 + 1 schedule would incur 8777-27 807 additional cases of disease and 241-743 more deaths over 5 years. Serotype 19A caused 55-71% of incremental IPD cases. Scenario analyses showed that booster dose adherence, effectiveness against carriage and waning in a 1 + 1 schedule had the most influence on resurgence of disease. Based on the model assumptions, switching to a 1 + 1 schedule will substantially increase disease burden. The results likely are conservative since they are based on relatively low vaccine-type pneumococcal transmission, a paradigm that has been called into question by data demonstrating an increase of IPD due to several vaccine serotypes during the last surveillance year available.

Meningococcal carriage in children and young adults in the Philippines: a single group, cross-sectional study.

This cross-sectional prevalence study investigates meningococcal carriage for the first time in a Southeast Asian population. Posterior pharyngeal swabs were collected between August 2013 and March 2014 from 937 healthy Filipinos aged 5-24 years attending school or university in Manila. Of these, 35 were found to be carriers giving an overall carriage prevalence of 3·7% [95% confidence interval (CI) 2·6-5·2]. Carriage was associated with age (P < 0·001) and was highest (9·0%, 95% CI 5·5-13·8) in subjects aged 10-14 years, but was comparatively low (<3%) in all other age groups considered. This suggests that an immunization programme in the Philippines designed to reduce carriage acquisition and induce herd immunity may require a vaccine dose before the age of 10 years. Serogroup B was most commonly carried (65·7%, 95% CI 47·8-80·9), with a small number of carriers for serogroups C, Y and W also present. Two individuals (5·7%, 95% CI 0·7-19·2) who were simultaneously carrying multiple serogroups were identified. This exploratory study provides valuable insight into the asymptomatic carriage of Neisseria meningitidis in a healthy subset of the Filipino population and illustrates the importance of generating local carriage data.

Epidemiological trends for hospital admissions for acute rotavirus gastroenteritis in Belgium following the introduction of routine rotavirus vaccination and the subsequent switch from lyophilized to liquid formulation of Rotarix™.

This study describes epidemiological trends for acute rotavirus gastroenteritis (RVGE) in Belgium in children aged ⩽5 years during the period June 2007 to May 2014 after the introduction of routine rotavirus (RV) vaccination. This period encompassed the switch from lyophilized to the liquid formulation of Rotarix™ (GlaxoSmithKline, Belgium) in August 2011. Uptake of RV vaccine remained consistently high throughout the study period with Rotarix the brand most often used. RV was present in 9% (1139/12 511) of hospitalized cases with acute gastroenteritis included in the study. Epidemiological trends for hospital admissions for RVGE remained consistent throughout the study period, with no evidence of any change associated with the switch from lyophilized to liquid formulation of Rotarix. This suggests both formulations perform similarly, with the liquid formulation not inferior regarding ability to reduce hospital admissions for acute RVGE in children aged ⩽5 years. A strong seasonal effect was observed with most RVGE occurring in the winter months but with some variability in intensity, with highest incidence found in those aged 6-24 months. The main observation was the decreased number of hospital admissions for RVGE in Belgium that occurred during winter 2013/2014.

The epidemiology of meningococcal disease in Latin America 1945-2010: an unpredictable and changing landscape.

Meningococcal disease is mostly endemic in Latin America, with periodic occurrences of outbreaks and epidemics over the last few decades. This literature review summarizes the available epidemiological data for this region between 1945 and 2010. Incidence rates and serogroup distribution differ from country to country and over time. Serogroups A, B, and C have all been major causes of meningococcal disease since the 1970s. In the last decade serogroups W135 and Y may now be emerging in certain countries, with serogroup A virtually disappearing. Although progress has been made in improving and coordinating the surveillance of invasive disease, the uniformity and quality of reported data reflect the fact that the current surveillance systems focus on passive rather than active reporting, hence the reliability of data may vary between countries. Consideration of vaccination policies to control meningococcal disease can only be made with a sufficient understanding of the changing epidemiology in the region.

Meningococcal disease in Asia: an under-recognized public health burden.

A literature search traced existing information on meningococcal disease in Asia. Reviewed data describing the epidemiology of meningococcal disease in Asia are incomplete, due in part to absence of surveillance in many countries, poor bacterial detection methods and social and healthcare barriers to disease reporting. This suggests that meningococcal disease in some Asian countries may be under-recognized, with a need to introduce/improve existing surveillance and case identification systems. Nevertheless, in some developing Asian countries, the disease burden may be significant. Serogroup A meningococcal epidemics are responsible for high morbidity and mortality in some countries and continue to be an ongoing threat, particularly in developing countries. There is an increasing role played by serogroups C, Y, and W-135 in invasive disease, indicating evolving meningococcal disease epidemiology in some countries. Multivalent meningococcal conjugate vaccines offer new opportunities in the region for reducing the meningococcal disease burden.

Estimating hepatitis C infection acquired in England, 1986-2000.

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.

Evaluation of a measles vaccine campaign by oral-fluid surveys in a rural Kenyan district: interpretation of antibody prevalence data using mixture models.

We evaluated the effectiveness of a measles vaccine campaign in rural Kenya, based on oral-fluid surveys and mixture-modelling analysis. Specimens were collected from 886 children aged 9 months to 14 years pre-campaign and from a comparison sample of 598 children aged 6 months post-campaign. Quantitative measles-specific antibody data were obtained by commercial kit. The estimated proportions of measles-specific antibody negative in children aged 0-4, 5-9 and 10-14 years were 51%, 42% and 27%, respectively, pre- campaign and 18%, 14% and 6%, respectively, post-campaign. We estimate a reduction in the proportion susceptible of 65-78%, with approximately 85% of the population recorded to have received vaccine. The proportion of 'weak' positive individuals rose from 35% pre-campaign to 54% post-campaign. Our results confirm the effectiveness of the campaign in reducing susceptibility to measles and demonstrate the potential of oral-fluid studies to monitor the impact of measles vaccination campaigns.

The burden of infection with cytomegalovirus in England and Wales: how many women are infected in pregnancy?

A serological survey was used to investigate the epidemiology of cytomegalovirus (CMV) infection in England and Wales. A total of 5237 sera representing the complete age range were used reflecting the general population. The sera were collected in 1991 and 2002, and screened for CMV-specific IgG by ELISA. Antibody prevalence increased with age from approximately 15% in those aged 1-4 years to approximately 80% in those aged > or = 65 years with no association with gender or region. Analysing by common birth cohort demonstrated that between 1991 and 2002 incidence was highest in children born 1985-1989 (1.62% per year, 95% CI 0.86-2.35), lower in older children and younger adults born 1950-1984 (0.75% per year, 95% CI 0.29-1.19) with little evidence of infection in older adults born pre-1950 (0% per year, 95% CI 0-0.64). Application to population and live-birth estimates for England and Wales suggested that between 1991 and 2002, 159 996 (95% CI 67922-278277) CMV infections occurred annually with an annual average of 2133 (95% CI 816-3435) infections affecting pregnant females.

Parvovirus B19 infection in five European countries: seroepidemiology, force of infection and maternal risk of infection.

We conducted a seroprevalence survey in Belgium, Finland, England & Wales, Italy and Poland on 13 449 serum samples broadly representative in terms of geography and age. Samples were tested for the presence of immunoglobulin G antibody using an enzyme immunoassay. The age-specific risk of infection was estimated using parametric and non-parametric statistical modelling. The age-specific risk in all five countries was highest in children aged 7-9 years and lower in adults. The average proportion of women of child-bearing age susceptible to parvovirus B19 infection and the risk of a pregnant women acquiring B19 infection during pregnancy was estimated to be 26% and 0.61% in Belgium, 38% and 0.69% in England & Wales, 43.5% and 1.24% in Finland, 39.9% and 0.92% in Italy and 36.8% and 1.58% in Poland, respectively. Our study indicates substantial epidemiological differences in Europe regarding parvovirus B19 infection.

Prevalence of human papillomavirus antibodies in young female subjects in England.

Sera from 1483 female subjects in England aged 10-29 years were tested. The age-standardised seroprevalence was 10.7% (95% confidence intervals 9.0-12.3) for human papillomavirus (HPV) 6, 2.7% (1.8-3.6) for HPV 11, 11.9% (10.2-13.6) for HPV 16, 4.7% (3.5-5.8) for HPV 18, and 20.7% (18.6-22.7) for any of the four types.

The burden of parvovirus B19 infection in women of childbearing age in England and Wales.

A serological survey has been used to investigate the epidemiology of parvovirus B19 infection in England and Wales. A total of 2835 sera representing the complete age range were selected from a convenience collection obtained in 1996 that reflects the general population and screened for parvovirus B19-specific IgG. Antibody prevalence rose nonlinearly with age from 21% in those aged 1-4 years to >75% in adults aged > or = 45 years. Force-of-infection estimates were similar to those previously made in 1991, being highest in those aged <15 years. There was no association between evidence of previous infection and sex or region. Quantitatively strongest antibody responses were found in those aged 15-34 years and IgG levels in females were 28.5% higher than those found in males (P=0.004, 95% CI 8.2-52.6). Applying the upper 95% confidence interval for the force of infection to maternity estimates for England and Wales in 1996, parvovirus infection in pregnancy was estimated to occur on average in up to 1 in every 512 pregnancies each year. This represents 1257 maternal infections, causing up to an estimated 59 fetal deaths and 11 cases of hydrops fetalis annually. An analysis of all available laboratory-confirmed parvovirus infections found a mean of 944 infections per year in women aged 15-44 years highlighting a need for enhanced surveillance of maternal parvovirus B19 infection in England and Wales, including information on both pregnancy and outcome of pregnancy.

Interpreting serological surveys using mixture models: the seroepidemiology of measles, mumps and rubella in England and Wales at the beginning of the 21st century.

A mixture modelling technique is applied to age-specific frequency distributions of quantitative results from serological surveys for measles, mumps and rubella using samples collected across the age range in England and Wales in 2000. In accordance with previous studies the analysis suggests that the antibody response to natural infection is stronger than that produced by vaccination, that vaccine-induced antibody levels wane with time and that levels of vaccine-induced antibody response vary for each virus infection being strongest for rubella and weakest for mumps. The current mumps epidemic in the United Kingdom is focused in cohorts born during 1982-1987 who were too old to have received routine MMR vaccination. In the cohort born in 1981-1985 the model estimates that 7.5% have no evidence of mumps specific IgG and 24.9% have the lowest level of detectable antibody. The similar proportions of mumps antibody in these categories among cohorts with opportunity for 1 or 2 doses of vaccine is a concern, as the degree to which these individuals are protected is unclear. Investigations into the efficacy of two doses of a mumps containing vaccine should be a priority during the current epidemic.

Seroprevalence of antibody to varicella zoster virus in England and Wales in children and young adults.

This is the first large-scale study to investigate the seroprevalence of varicella zoster (VZV) in the general population of England and Wales. The study focused on those aged 1-20 years, that age group in whom most infections occur. Prevalence rose rapidly with age, with 53% of children showing evidence of prior infection by the age of 5 years and most young adults having experienced infection. In addition to using a fixed cut-off recommended by the manufacturer, a mixture modelling technique was also used to define the proportion of the population seropositive in each age group. This was shown to be a more accurate approach to categorizing data from an epidemiological perspective.

Improving sensitivity of oral fluid testing in IgG prevalence studies: application of mixture models to a rubella antibody survey.

A method for the analysis of age-stratified antibody prevalence surveys is applied to a previously reported survey of antibody to rubella virus using oral fluid samples in which the sensitivity of the assay used was shown to be compromised. The age-specific distribution of the quantitative results of antibody tests using oral fluids is modelled as a mixture of strong positive, weak positive and negative components. This yields maximum likelihood estimates of the prevalence at each age and demonstrates that, when used in conjunction with mixture modelling techniques, the results of antibody prevalence studies using oral fluids accurately reflect those obtained using sera.

The burden of Helicobacter pylori infection in England and Wales.

The prevalence of active infection with Helicobacter pylori in the general population of England and Wales was estimated using high reactivity for specific IgG in serum ELISA as a marker. A total of 10,118 anonymized residues of serum samples collected in 1986 and 1996 from persons aged 1-84 years were used. Estimated prevalence of active infection varied by region and was highest in London. Prevalence was related to decade of birth and increased from 4-3% in those born during the 1980s to 30% in those born before 1940. An estimated total of 7.5 million people living in England and Wales have an active infection and analysis by decade of birth showed no significant difference between samples collected in 1986 and 1996. These data suggest H. pylori infection is becoming less common, is acquired at an early age and is unlikely to be resolved unless suitable antimicrobial treatment is sought.

An RT-PCR assay using oral fluid samples to detect rubella virus genome for epidemiological surveillance.

A reverse transcription nested polymerase chain reaction (RT-PCR) method was developed for detecting rubella virus (RV) RNA using primer pairs which targeted a variable region of the E1 gene. RV genome was detected in oral fluid, throat swabs, serum and tissue samples. This is the first report to show that RV genome can be detected in oral fluid samples, including acute cases < or = 2 days after onset of symptoms, which have previously only been used for antibody testing. This suggests that PCR is useful for assisting with early diagnosis when a sufficient IgM response may not have been mounted. The PCR amplicon of 553 nucleotides was also useful for molecular genotyping, which contributes to RV epidemiological surveillance.

Immunogenicity of second dose measles-mumps-rubella (MMR) vaccine and implications for serosurveillance.

Measles and mumps, but not rubella, outbreaks have been reported amongst populations highly vaccinated with a single dose of measles-mumps-rubella (MMR) vaccine. Repeated experience has shown that a two-dose regime of measles vaccine is required to eliminate measles. This paper reports the effect of the first and second MMR doses on specific antibody levels in a variety of populations.2-4 years after receiving a first dose of MMR vaccine at age 12-18 months, it was found that a large proportion of pre-school children had measles (19.5%) and mumps (23.4%) IgG antibody below the putative level of protection. Only a small proportion (4.6%) had rubella antibody below the putative protective level. A total of 41% had negative or equivocal levels to one or more antigens. The proportion measles antibody negative (but not rubella or mumps) was significantly higher in children vaccinated at 12 months of age than at 13-17 months. There was no evidence for correlation of seropositivity to each antigen, other than that produced by a small excess of children (1%) negative to all three antigens. After a second dose of MMR, the proportion negative to one or more antigens dropped to <4%. Examination of national serosurveillance data, found that following an MR vaccine campaign in cohorts that previously received MMR, both measles and rubella antibody levels were initially boosted but declined to pre-vaccination levels within 3 years. Our study supports the policy of administering a second dose of MMR vaccine to all children. However, continued monitoring of long-term population protection will be required and this study suggests that in highly vaccinated populations, total measles (and rubella) IgG antibody levels may not be an accurate reflection of protection. Further studies including qualitative measures, such as avidity, in different populations are merited and may contribute to the understanding of MMR population protection.