Meningococcal carriage by age in the African meningitis belt: a systematic review and meta-analysis.

Meningococcal carriage dynamics drive patterns of invasive disease. The distribution of carriage by age has been well described in Europe, but not in the African meningitis belt, a region characterised by frequent epidemics of meningitis. We aimed to estimate the age-specific prevalence of meningococcal carriage by season in the African meningitis belt. We searched PubMed, Web of Science, the Cochrane Library and grey literature for papers reporting carriage of Neisseria meningitidis in defined age groups in the African meningitis belt. We used a mixed-effects logistic regression to model meningococcal carriage prevalence as a function of age, adjusting for season, location and year. Carriage prevalence increased from low prevalence in infants (0.595% in the rainy season, 95% CI 0.482-0.852%) to a broad peak at age 10 (1.94%, 95% CI 1.87-2.47%), then decreased in adolescence. The odds of carriage were significantly increased during the dry season (OR 1.5 95% CI 1.4-1.7) and during outbreaks (OR 6.7 95% CI 1.6-29). Meningococcal carriage in the African meningitis belt peaks at a younger age compared to Europe. This is consistent with contact studies in Africa, which show that children 10-14 years have the highest frequency of contacts. Targeting older children in Africa for conjugate vaccination may be effective in reducing meningococcal transmission.

Norovirus transmission dynamics: a modelling review.

Norovirus is one of the leading causes of viral gastroenteritis worldwide and responsible for substantial morbidity, mortality and healthcare costs. To further understanding of the epidemiology and control of norovirus, there has been much recent interest in describing the transmission dynamics of norovirus through mathematical models. In this study, we review the current modelling approaches for norovirus transmission. We examine the data and methods used to estimate these models that vary structurally and parametrically between different epidemiological contexts. Many of the existing studies at population level have focused on the same case notification dataset, whereas models from outbreak settings are highly specific and difficult to generalise. In this review, we explore the consistency in the description of norovirus transmission dynamics and the robustness of parameter estimates between studies. In particular, we find that there is considerable variability in estimates of key parameters such as the basic reproduction number, which may mean that the effort required to control norovirus at the population level may currently be underestimated.

Modelling meningococcal meningitis in the African meningitis belt.

SUMMARYMeningococcal meningitis is a major public health problem in a large area of sub-Saharan Africa known as the meningitis belt. Disease incidence increases every dry season, before dying out with the first rains of the year. Large epidemics, which can kill tens of thousands of people, occur frequently but unpredictably every 6-14 years. It has been suggested that these patterns may be attributable to complex interactions between the bacteria, human hosts and the environment. We used deterministic compartmental models to investigate how well simple model structures with seasonal forcing were able to qualitatively capture these patterns of disease. We showed that the complex and irregular timing of epidemics could be caused by the interaction of temporary immunity conferred by carriage of the bacteria together with seasonal changes in the transmissibility of infection. This suggests that population immunity is an important factor to include in models attempting to predict meningitis epidemics.

Understanding the role of peace of mind in childhood vaccination: A qualitative study with members of the general public.

BACKGROUND: Recent debates on the introduction of new childhood vaccines in the UK have suggested that 'peace of mind' (PoM) might influence decision making. The aim of this study is to ascertain the importance of 'PoM' in individuals' decision making. METHODS: Four focus groups were conducted in the UK. Participants were 22 females and 2 males, aged 18-74 years, with a selection of non-parents, parents, guardians and foster carers. Data were analysed using an inductive thematic framework approach and conceptualised using the Health Belief Model, which provided an overview of participants' perceptions and behaviours about childhood vaccinations. RESULTS: Vaccine associated PoM was associated with individuals' perceptions of disease severity, with individuals feeling more reassurance after obtaining vaccinations against diseases that they considered to be severe compared to relatively mild diseases. Conversely, concerns about vaccination side-effects reduced participants PoM, but the duration of this effect varied between individuals. Other factors, such as social pressure and the emotional anxiety related to children's feelings, or physical reactions, to vaccinations also negatively impacted on participants' vaccine associated PoM. CONCLUSION: Vaccine associated PoM was a consideration for some participants seeking vaccinations but was only a minor motivating factor for these individuals. These differences stemmed from whether participants received PoM from the uptake of a vaccination because they perceived some intrinsic benefit from it or, conversely, they considered vaccinations as a routine health intervention. Overall, vaccine related PoM varied between participants in magnitude and fluctuated over time, even in the same individuals.

Hepatitis C in ethnic minority populations in England.

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.

Modelling norovirus transmission and vaccination.

BACKGROUND: Norovirus is thought to be responsible for a fifth of all acute gastroenteritis cases globally each year. The population level transmission dynamics of this very common virus are still poorly understood, in part because illness is under-reported. With vaccines undergoing clinical trials, there is a growing need for appropriate, empirically grounded models, to predict the likely impact of vaccination. METHODS: We developed a dynamic age-specific mathematical model of norovirus transmission and vaccination, informed by available data, particularly age-stratified time series case notification data. We introduce the use of a self-reporting Markov model to account for variation by age and over time in the statutory reporting of norovirus in Germany. We estimated the model using a sequential Monte Carlo particle filter. We then extended and applied our estimated model to investigate the potential impact of a range of immunisation strategies. We performed sensitivity analyses on the mode of vaccine action and other vaccine-related parameters. RESULTS: We find that routine immunisation could reduce the incidence of norovirus by up to 70.5% even when those vaccines do not provide complete protection from disease. Furthermore, we find that the relative efficiency of alternative strategies targeting different age groups are dependant on the outcome we consider and are sensitive to assumptions on the mode of vaccine action. Strategies that target infants and toddler are more efficient in preventing infection but targeting older adults is preferable for preventing severe outcomes. CONCLUSIONS: Our model provides a robust estimate of a dynamic transmission model for norovirus at the population level. Vaccination may be an effective strategy in preventing disease but further work is required to ascertain norovirus vaccine efficacy, its mode of action and to estimate the cost-effectiveness of immunisation against norovirus.

The natural history of meningococcal carriage and disease.

The prevalence of Neisseria meningitidis carriage is highest in teenagers and lowest in young children. In contrast, invasive meningococcal disease is most common in young children with a smaller secondary peak in teenagers. Data on carriage and disease were analysed to quantify the risks of infection and disease by age and serogroup. The forces of infection for serogroups B, C, other meningococci and Neisseria lactamica were modelled together with the risk of disease given infection for serogroups B and C, using maximum likelihood to fit the models to the available data. The risk of meningococcal disease given infection declines steeply through childhood and is higher for serogroup C than for serogroup B. The secondary peak in disease in teenagers appears to be explained mostly by increased transmission although there is a suggestion that other factors may also contribute. These analyses provide important insights and may be used to guide further data collection and modelling studies.

Analysis of longitudinal bacterial carriage studies accounting for sensitivity of swabbing: an application to Neisseria meningitidis.

Longitudinal carriage studies of colonizing bacteria such as Neisseria meningitidis can provide important insights into the transmission dynamics of these organisms. Carriage is detected by culturing from a nasopharyngeal swab, but the sensitivity of this technique is low and varies between studies. This paper applies a statistical method for estimating the sensitivity of swabbing, infection rate, recovery rate and initial prevalence of carriage to three longitudinal carriage studies of N. meningitidis. These parameters and 95% confidence intervals were estimated using maximum likelihood techniques. The sensitivity of swabbing was estimated to be 60-83% and this should be taken into account when interpreting carriage studies. The estimates of force of infection and recovery rates seem to be consistent with estimates from more traditional methods. Differences in the parameter estimates between datasets may be due to differences in study design. This method could be used to assist in the design of future carriage studies.

Meningococcal serogroup C conjugate vaccination in England and Wales: coverage and initial impact of the campaign.

The UK was the first country to introduce meningococcal serogroup C conjugate vaccination. The vaccine was incorporated into the routine infant immunisation schedule and was offered to all under 18 year olds in a catch-up campaign. The vaccine has been well accepted in infants receiving routine vaccination, with coverage around 89%. Coverage in older children targeted in the catch-up campaign was above 85% up to the age of 14, and was lowest (43%) in 15-17 year olds not in education. The winter of 2000-01 was the first meningococcal season following the offer of the vaccination to all children and adolescents. The incidence of serogroup C disease in the targeted age groups fell by 80%, and the number of deaths in laboratory confirmed cases in 0-19 year olds decreased from 78 to 8 between 1998-99 and 2000-01. The incidence of serogroup B disease in all age groups was slightly higher in 2000-01 than previous years, and there was an increase in the incidence of serogroup C disease in those aged over 20 during the study period, leading to the extension of the vaccination campaign to 20-24 year olds.

Rising incidence of Haemophilus influenzae type b disease in England and Wales indicates a need for a second catch-up vaccination campaign.

The incidence of invasive Haemophilus influenzae type b (Hib) disease in the UK fell rapidly following the introduction of routine vaccination in 1992 and the implementation of a catch-up campaign in children under 4 years old in 1992-93. However, since 1999 the number of cases of Hib has been increasing, and in 2002 there were 134 cases in 0-4 year olds (266 in all ages). While still much less than the prevaccine burden of disease (over 800 cases a year in 0-4 year olds), this increase in incidence is worrying and has sparked a range of detailed investigations. In February 2003, the Department of Health announced a second catch-up campaign offering all children between 6 months and 4 years a further dose of Hib vaccine. The epidemiology of Hib disease in England and Wales between 1990 and 2002 is reviewed here to provide a context for this public health response.

Antibody to Haemophilus influenzae type b after routine and catch-up vaccination.

Since 1999, the number of cases of Haemophilus influenzae type b (Hib) disease in the UK has risen. We investigated the role of population immunity in this change by testing more than 2600 serum samples from children aged 1-15 years. After the introduction of the routine Hib conjugate vaccination programme for infants, median antibody titres rose significantly in 1-year-olds. Individuals who received their first dose of vaccine at age 1-4 years in the original catch-up campaign initially had much higher concentrations of antibody than those who had been immunised in infancy. A second catch-up campaign in children aged 6 months to 4 years should be highly effective in boosting immunity and reducing disease in the short term.

Estimating the burden of serogroup C meningococcal disease in England and Wales.

In 1999 a new conjugate vaccine for serogroup C meningococcal disease was licensed for use in the UK. In order for an appropriate vaccination strategy to be developed the burden of serogroup C disease in England and Wales needed to be established. This was done using data from an enhanced surveillance scheme alongside routine laboratory reports and a total of 5,052 cases of serogroup C disease in England and Wales between 1993 and 1998 were estimated. Among these, an estimated 398 died and 1,767 were admitted to intensive care units (ITUs). The greatest burden of disease was in young children and teenagers. The current literature identified four studies reporting sequelae following serogroup C meningococcal disease. These provided estimates of sequelae in the range of 6.5% and 45% and presented some evidence of higher levels than occur following serogroup B meningococcal disease. This information was provided to the Joint Committee on Vaccination and Immunisation to inform policy to implement a serogroup C conjugate vaccination programme in the UK. The vaccination programme has since been justified by the dramatic reduction in serogroup C meningococcal cases.