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.

Estimating adult accident and emergency attendances in English hospitals attributed to respiratory syncytial virus.

In this short communication, we describe annual accident and emergency (A&E) respiratory illness attendances in English hospitals for the years 2017-2019 estimated to be attributed to respiratory syncytial virus (RSV) in adults aged ≥18 years. Results suggest RSV caused an overall annual average of 23,440 adult A&E respiratory attendances in England across this period, equating to 53 A&E adult respiratory attendances per 100,000 population per year. Adult respiratory A&E attendance due to RSV increased with age and was highest in older adults, especially those aged ≥75 years where RSV was estimated to cause an average of 238 respiratory attendances per 100,000 population per year. However, this may be under an under ascertainment as respiratory attendances only were included. A further proportion of adult A&E attendances due to cardiac events such as myocardial infarction (MI), arrhythmias and ischemic stroke (IS) may be attributed to an RSV infection, particularly in older adults.

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.

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.

Detection of IgG antibody to Epstein-Barr virus viral capsid antigen in saliva by antibody capture radioimmunoassay.

A 'G' antibody capture radioimmunoassay (GACRIA) to detect IgG to Epstein-Barr virus (EBV) viral capsid antigen (VCA) in saliva is described. The monoclonal antibody to EBV VCA used in the GACRIA bound non-specifically when testing saliva samples having a total IgG content of less than 2.0 mg/l, so giving false positive results. This problem was overcome by including 0.5% EBV-negative human serum in the monoclonal antibody diluent. The performance of the assay was then evaluated by comparing the GACRIA test on serum and saliva samples to indirect immunofluorescence assay (IFA) results on sera using a panel of paired serum/saliva samples. Compared to the corresponding serum IFA the saliva GACRIA had a sensitivity and specificity of 93.5 and 100%, respectively. Although less sensitive than IFA on serum samples, the saliva GACRIA is sufficiently sensitive to be used for epidemiological screening and will enable testing for anti-EBV VCA to be carried out easily and on a wide scale.

A monoclonal blocking EIA for herpes simplex virus type 2 antibody: validation for seroepidemiological studies in Africa.

A competitive type-specific enzyme-linked immunosorbent assay (ELISA) for herpes simplex virus type 2 (HSV-2) antibody was developed using an infected cell antigen and a monoclonal antibody to glycoprotein G-2. This assay has been validated for use for epidemiological studies using a large panel of sera collected in rural Uganda and a panel of 143 sera characterised previously by Western blotting, the 'gold standard' for HSV type-specific serology. This evaluation was found to have a sensitivity of 96% and a specificity of 91% in comparison with Western blot on 143 sera from clinic patients. The ELISA had a sensitivity of 93% and a specificity of 91% in comparison with Western blot on 495 sera collected in Uganda. The assay showed good reproducibility and a low percentage of sera gave equivocal results, indicating its suitability for epidemiological studies.

Detection of measles specific IgG in oral fluid using an FITC/anti-FITC IgG capture enzyme linked immunosorbent assay (GACELISA).

An IgG antibody capture enzyme linked immunosorbent assay (GACELISA) for the detection of measles specific IgG in oral fluid was developed using an FITC/anti-FITC amplification system. The GACELISA was evaluated by testing paired oral fluid and serum samples from 787 subjects in an epidemiological study of measles in rural Ethiopia. Oral fluids were tested by GACELISA and corresponding serum samples by a sensitive indirect ELISA for measles IgG (Behring Enzygnost). By comparison with the serum measles IgG assay, the oral fluid GACELISA had a sensitivity of 97.4% (95% confidence intervals: 95.9, 98.2) and a specificity of 90.0% (81.9, 94.3), with no significant differences observed by age group. Total IgG concentrations were measured on a subset of 160 oral fluids by an in-house ELISA. This showed that false negative GACELISA results tended to occur in samples with low concentrations of total IgG, although the trend was not statistically significant. It is concluded that the overall performance of the GACELISA was satisfactory, showing close agreement to the serum ELISA, and has potential to serve as an easily transferable tool for large scale epidemiological studies as required for the World Health Organisation's programme for the global control of measles.

Epidemiology of Epstein-Barr virus infection in pre-adolescent children: application of a new salivary method in Edinburgh, Scotland.

STUDY OBJECTIVE: To describe the epidemiology of Epstein-Barr virus (EBV) among primary school children by testing saliva with a new EBV capsid antigen "G" antibody capture radioimmunoassay (GACRIA). DESIGN: A population based sample of 7 year old schoolchildren were followed up at age 11. SETTING: 30 randomly chosen primary schools in Edinburgh, Scotland. PARTICIPANTS: 552 schoolchildren. MEASUREMENTS: Data on risk factors for infection were collected by questionnaire at ages 7 and 11. Saliva samples collected at age 11 were examined by GACRIA for evidence of previous infection with EBV. For 102 subjects, a second salivary specimen collected approximately one month after the first sample was available for testing as a measure of the repeatability of the method. MAIN RESULTS: Unequivocal results were found in 91% of samples and the repeatability of the test was good (kappa = 0.71). Fifty six per cent of children had antibodies to EBV. In a logistic regression analysis, independent risk factors for infection were sharing a room (odds ratio 1.78, 1.14, 2.79), head of household's social class IV/V compared with I (odds ratio 2.87, 1.08, 7.34), and schools serving predominantly rented housing estates (odds ratio 2.3, 1.09, 4.84). CONCLUSION: This study is the first application of EBV viral capsid GACRIA to salivary samples. The method was successfully used to describe the epidemiology of EBV. In this study, characteristics of the home seemed to be more important than those of the school in determining the likelihood of infection with EBV.

An evaluation of oral-fluid collection devices for the determination of rubella antibody status in a rural Ethiopian community.

We compared 3 different oral-fluid collection devices to assess their suitability for use in community studies of rubella antibody. Of 58 individuals enrolled from 13 households from a southern Ethiopian village, 38 provided a blood sample and oral fluids by the 3 devices: 2 proprietary, Omni-SAL and OraSure, and a third a polystyrene sponge swab (Sponge). The Sponge swab, used like a toothbrush, was most acceptable to survey staff and to participants of all ages, although it proved ill-adapted for fluid extraction. The other devices more often caused participant discomfort or anxiety, particularly in the young. Statistical comparison of rubella-specific immunoglobulin (Ig) G in oral fluid, measured by antibody-capture radioimmunoassay, and in serum, by indirect enzyme-linked immunosorbent assay, showed no clear differences between the devices in oral-fluid performance. Specificity range was 75-100% and sensitivity 73-85%, relative to serum. Specific-antibody levels declined with increasing age, with concomitant decreases in sensitivity, as previously documented. The relationship between specific IgG and total IgG in oral fluid differed by device. Specific IgG levels were highly correlated between paired samples using the Sponge device. We consider the Sponge device to be the most suitable for community survey work, although the extraction method requires improvement. Further work is needed to improve the sensitivity of antibody status determination in adults.

Lumbosacral dysfunctions in elite cross-country skiers.

While the incidence of injury in cross-country skiing remains relatively low, overuse problems affecting the lumbosacral region may be on the rise, particularly among elite athletes. In this study, a certified "Part A" (Canadian Physiotherapy Association) manual therapist performed lumbosacral physical assessments on 18 elite cross-country skiers and 15 normal subjects. Results indicated sacroiliac (SI) joint dysfunction occurred significantly more often in the skier population (p < 0.007). Incidences of SI joint asymmetry and lumbar spine dysfunction did not differ between groups. The predominant use of asymmetrical ski-skating techniques may play an influential role in the pathogenesis of SI joint dysfunction in elite cross-country skiers.

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.

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.

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.