Richard Pebody

Mortality from pandemic A/H1N1 2009 influenza in England: public health surveillance study

Objective To establish mortality from pandemic A/H1N1 2009 influenza up to 8 November 2009. Design Investigation of all reported deaths related to pandemic A/H1N1 in England. Setting Mandatory reporting systems established in acute hospitals and primary care. Participants Physicians responsible for the patient. Main outcome measures Numbers of deaths from influenza combined with mid-range estimates of numbers of cases of influenza to calculate age specific case fatality rates. Underlying conditions, time course of illness, and antiviral treatment. Results With the official mid-range estimate for incidence of pandemic A/H1N1, the overall estimated case fatality rate was 26 (range 11-66) per 100 000. It was lowest for children aged 5-14 (11 (range 3-36) per 100 000) and highest for those aged ≥65 (980 (range 300-3200) per 100 000). In the 138 people in whom the confirmed cause of death was pandemic A/H1N1, the median age was 39 (interquartile range 17-57). Two thirds of patients who died (92, 67%) would now be eligible for the first phase of vaccination in England. Fifty (36%) had no, or only mild, pre-existing illness. Most patients (108, 78%) had been prescribed antiviral drugs, but of these, 82 (76%) did not receive them within the first 48 hours of illness. Conclusions Viewed statistically, mortality in this pandemic compares favourably with 20th century influenza pandemics. A lower population impact than previous pandemics, however, is not a justification for public health inaction. Our data support the priority vaccination of high risk groups. We observed delayed antiviral use in most fatal cases, which suggests an opportunity to reduce deaths by making timely antiviral treatment available, although the lack of a control group limits the ability to extrapolate from this observation. Given that a substantial minority of deaths occur in previously healthy people, there is a case for extending the vaccination programme and for continuing to make early antiviral treatment widely available.

Risk Factors for Severe Outcomes following 2009 Influenza A (H1N1) Infection: A Global Pooled Analysis

This study analyzes data from 19 countries (from April 2009 to Jan 2010), comprising some 70,000 hospitalized patients with severe H1N1 infection, to reveal risk factors for severe pandemic influenza, which include chronic illness, cardiac disease, chronic respiratory disease, and diabetes.

RECENT DEVELOPMENTS IN PERTUSSIS

Pertussis causes nearly 300,000 deaths in children every year. Most deaths take place in developing countries, but the infection remains a priority everywhere. Pertussis vaccination protects infants and children against death and admission to hospital, but breakthrough disease in vaccinated people can happen. In high-mortality countries, the challenge is to improve timeliness and coverage of childhood vaccination and surveillance. In regions with low mortality and highest coverage, pertussis is frequently the least well-controlled disease in childhood vaccination programmes. Some countries have reported a rise in pertussis in adolescents, adults, and pre-vaccination infants, but how much these changes are real or a result of improved recognition and surveillance remains uncertain. In response, several countries have introduced adolescent and adult acellular pertussis vaccine boosters. The effect so far is unknown; assessment is impeded by poor data. Uncertainties still persist about key variables needed to model and design vaccination programmes, such as risk of transmission from adults and adolescents to infants. New vaccination strategies under investigation include vaccination of neonates, family members, and pregnant women.

Antibody Responses to Nasopharyngeal Carriage of Streptococcus pneumoniae in Adults: A Longitudinal Household Study

BACKGROUND Natural immunity to Streptococcus pneumoniae is thought to be induced by exposure to S. pneumoniae or cross-reactive antigens. No longitudinal studies of carriage of and immune responses to S. pneumoniae have been conducted using sophisticated immunological laboratory techniques. METHODS We enrolled 121 families with young children into this study. Nasopharyngeal (NP) swabs were collected monthly for 10 months from all family members and were cultured in a standard fashion. Cultured S. pneumoniae isolates were serotyped. At the beginning (month 0) and end (month 10) of the study, venous blood was collected from family members >18 years old. Serotype-specific antipolysaccharide immunoglobulin G (IgG) and functional antibody and antibodies to pneumolysin, pneumococcal surface protein A (PspA), and pneumococcal surface antigen A (PsaA) were measured in paired serum samples. RESULTS Levels of anticapsular IgG increased significantly after carriage of serotypes 9V, 14, 18C, 19F, and 23F by an individual or family member. For serotype 14, a higher level of anticapsular IgG at the beginning of the study was associated with reduced odds of carriage (P = .006). There was a small (approximately 20%) but significant increase in titers of antibodies to PsaA and pneumolysin but no change in titers of antibody to PspA. CONCLUSIONS Adults respond to NP carriage by mounting anticapsular and weak antiprotein antibody responses, and naturally induced anticapsular IgG can prevent carriage.

The seroepidemiology of herpes simplex virus type 1 and 2 in Europe

Objectives: To describe the seroepidemiology of herpes simplex virus (HSV) types 1 and 2 in the general populations of eight European countries to better understand recent reported changes in disease epidemiology. Methods: Belgium, Bulgaria, Czech Republic, England and Wales, Finland, Germany, Netherlands, and Slovenia conducted national cross sectional serological surveys for HSV-1 and HSV-2 between 1989 and 2000. Survey sizes ranged from 3000 to 7166 sera. External quality control was ensured through reference panel testing. Results: Large intercountry and intracountry differences in HSV-1 and HSV-2 seroprevalence were observed. Age standardised HSV-1 seroprevalence ranged from 52% in Finland, to 57% in the Netherlands, 67% in Belgium, 81% in Czech Republic, and 84% in Bulgaria. Age standardised (>12 years) HSV-2 seroprevalence ranged from 24% in Bulgaria, to 14% in Germany, 13% in Finland, 11% in Belgium, 9% in Netherlands, 6% in Czech Republic, and 4% in England and Wales. In all countries, probability of seropositivity for both infections increased with age. A large proportion of teenagers and young adults remain HSV-1 susceptible particularly in northern Europe. Women were significantly more likely to be HSV-2 seropositive in six of seven (p<0.05) countries and HSV-1 seropositive in four of seven (p<0.05) countries, particularly in northern Europe. No significant evidence of a protective role of HSV-1 for HSV-2 infection was found adjusting for age and sex (p<0.05). Conclusions: There is large variation in the seroepidemiology of HSV-1 and HSV-2 across Europe. The observation that a significant proportion of adolescents are now HSV-1 susceptible may have implications for transmission and clinical presentation of HSV-1 and HSV-2.

A longitudinal household study of Streptococcus pneumoniae nasopharyngeal carriage in a UK setting

A 10-month longitudinal household study of pre-school children and their families was undertaken with monthly visits collecting epidemiological data and nasopharyngeal swabs in Hertfordshire, England from 2001 to 2002. Pneumococcal culture was with standard methods. In total, 121 families (489 individuals) took part. Mean prevalence of carriage ranged from 52% for age groups 0-2 years, 45% for 3-4 years, 21% for 5-17 years and 8% for >or=18 years. Carriage occurred more than once in 86% of children aged 0-2 years compared to 36% of those aged >or=18 years. The most prevalent serotypes in the 0-2 years age group were 6B followed by 19F, 23F, 6A and 14. Young children were responsible for the majority of introductions of new serotypes into a household. Erythromycin resistance (alone or in combination) occurred in 10% of samples and penicillin non-susceptibility in 3.7%. Overall the recently licensed 7-valent conjugate vaccine (PCV) would protect against 64% of serotypes with no intra-serogroup cross protection and 82% with such protection. Nasopharyngeal carriage of S. pneumoniae is common in a UK setting in the pre-conjugate vaccine era. PCV would protect against a large proportion of carriage isolates. However, the impact of vaccination on non-vaccine serotypes will need to be monitored.

Deaths from Norovirus among the Elderly, England and Wales

Norovirus may be associated with ≈80 deaths/year.

The pre-vaccination epidemiology of measles, mumps and rubella in Europe: implications for modelling studies.

Data on the pre-vaccination patterns of infection for measles, mumps and rubella are collated from a number of European countries in order to compare the epidemiology of the three viruses. Key epidemiological parameters, such as the age-specific force of infection and the basic reproduction number (R0) are estimated from case notification or serological data using standard techniques. A method is described to compare force of infection estimates derived from serological data. Analysis suggests that the pre-vaccination patterns of measles and mumps infection in the different countries were similar. In contrast, the epidemiology of rubella was highly variable between countries. This suggests that it may be acceptable to use parameter values estimated from other countries to model measles and mumps transmission, but that this approach to modelling rubella transmission requires more caution. Estimates of R0 depend on underlying mixing assumptions. Constraints were placed on R0 estimates by utilising knowledge of likely mixing patterns. The estimates for R0 were highest for measles, intermediate for mumps, and generally lowest for rubella. Analysis of within- and between-age-group transmission rates suggested that mumps transmission tends to be more concentrated within young children than the other two viruses. The implications for the design of immunization programmes are that mumps may be the easiest to control via infant immunization since it is predominantly transmitted between the very young and the variability in rubella epidemiology requires that careful consideration of the possible effects of vaccination options should be made using local data when planning rubella immunization programmes.

Effectiveness of trivalent seasonal influenza vaccine in preventing laboratory-confirmed influenza in primary care in the United Kingdom: 2012/13 end of season results.

In 2015/16, the influenza season in the United Kingdom was dominated by influenza A(H1N1)pdm09 circulation. Virus characterisation indicated the emergence of genetic clusters, with the majority antigenically similar to the current influenza A(H1N1)pdm09 vaccine strain. Mid-season vaccine effectiveness (VE) estimates show an adjusted VE of 41.5% (95% confidence interval (CI): 3.0-64.7) against influenza-confirmed primary care consultations and of 49.1% (95% CI: 9.3-71.5) against influenza A(H1N1)pdm09. These estimates show levels of protection similar to the 2010/11 season, when this strain was first used in the seasonal vaccine.

The immunogenicity of 7-valent pneumococcal conjugate vaccine versus 23-valent polysaccharide vaccine in adults aged 50-80 years.

BACKGROUND Infections with pneumococci are a major cause of morbidity and mortality in the elderly population. Although 23-valent pneumococcal polysaccharide vaccine (PPV) is recommended for elderly persons, the potential benefits of conjugate vaccine use in this age group remain unclear. METHODS We performed an open-label, randomized study that compared 7-valent pneumococcal conjugate vaccine (7vPnC) with PPV in 599 adults aged 50-80 years. Vaccinees received either 1 dose of 7vPnC or PPV or 1 dose of 7vPnC followed by a dose of 7vPnC or PPV 6 months later. Groups were stratified so they contained similar numbers of individuals aged 50-59, 60-69, and 70-80 years. Concentrations of immunoglobulin G specific for the serotypes in 7vPnC were measured before and 4-6 weeks after each vaccination and 1 year after enrollment. RESULTS Although baseline antibody levels were slightly lower in the older age groups, responses (fold rises) to either vaccine did not depend on age. Single-dose 7vPnC was superior for only 3 serotypes. Administration of a second dose of PPV or 7vPnC was similarly immunogenic in adults primed with 7vPnC, and titers after a second dose were similar to the first. CONCLUSIONS Pneumococcal vaccines retain their immunogenicity when administered into the eighth decade of life, but a second dose, when assessed by antibody titers alone, has little utility. 7vPnC vaccines do not lead to subsequent hyporesponsiveness. CLINICAL TRIALS REGISTRATION http://www.clinicaltrials.gov/NCT00197821.