Quality of life impacts from rotavirus gastroenteritis on children and their families in the UK.

AIMS: Rotavirus vaccines (RV) are safe and effective but demand significant investment of healthcare resource. In countries with low mortality due to rotavirus, a key component to assessing cost-effectiveness is quantifying the Health Related Quality of Life (HRQoL) lost due to rotavirus acute gastroenteritis (RVAGE). METHODS: Families with children less than six years old with gastroenteritis were recruited from attendees to Bristol Children's Hospital Emergency Department. Stools were tested for viral causes of gastroenteritis. Children's HRQoL was assessed at presentation using Health Utilities Index 2 (HUI2) with visual analogue scale (VAS). The effect of the child's illness on the HRQoL of up to two adult carers was assessed using EQ-5D-5L. Families completed a daily symptom diary to assess time to recovery and within-family transmission. RESULTS: 127 families consented to take part, 84(65%) had rotavirus as the cause of illness. At the time of attendance, mean paediatric HRQoL with RVAGE was 0.74(HUI2) and 0.42(VAS). Primary/secondary carer's HRQoL was 0.68/0.80 (EQ5D) or 0.70/0.79 (VAS). The mean number of QALYs lost due to RVAGE was 3.1-3.5 per thousand children and 7.7-8.7 per thousand family units. In 52% of RVAGE families at least one other member developed a secondary case of gastroenteritis. For working parents, 69% missed work, for a mean of 2.8 days (95% CI 2.3-3.4). CONCLUSIONS: We have found the HRQoL loss associated with RVAGE in children and their carers to be significantly higher than estimates used for all RV medical attendances in UK cost-effectiveness calculations.The study was supported by the NIHR Health Protection Research Unit in Evaluation of Interventions. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, the Department of Health or Public Health EnglandThis is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.vaccine.2015.07.01

Understanding the Role of Duration of Vaccine Protection with MenAfriVac: Simulating Alternative Vaccination Strategies.

We previously developed a transmission dynamic model of Neisseria meningitidis serogroup A (NmA) with the aim of forecasting the relative benefits of different immunisation strategies with MenAfriVac. Our findings suggested that the most effective strategy in maintaining disease control was the introduction of MenAfriVac into the Expanded Programme on Immunisation (EPI). This strategy is currently being followed by the countries of the meningitis belt. Since then, the persistence of vaccine-induced antibodies has been further studied and new data suggest that immune response is influenced by the age at vaccination. Here, we aim to investigate the influence of both the duration and age-specificity of vaccine-induced protection on our model predictions and explore how the optimal vaccination strategy may change in the long-term. We adapted our previous model and considered plausible alternative immunization strategies, including the addition of a booster dose to the current schedule, as well as the routine vaccination of school-aged children for a range of different assumptions regarding the duration of protection. To allow for a comparison between the different strategies, we use several metrics, including the median age of infection, the number of people needed to vaccinate (NNV) to prevent one case, the age distribution of cases for each strategy, as well as the time it takes for the number of cases to start increasing after the honeymoon period (resurgence). None of the strategies explored in this work is superior in all respects. This is especially true when vaccine-induced protection is the same regardless of the age at vaccination. Uncertainty in the duration of protection is important. For duration of protection lasting for an average of 18 years or longer, the model predicts elimination of NmA cases. Assuming that vaccine protection is more durable for individuals vaccinated after the age of 5 years, routine immunization of older children would be more efficient in reducing disease incidence and would also result in a fewer number of doses necessary to prevent one case. Assuming that elimination does not occur, adding a booster dose is likely to prevent most cases but the caveat will be a more costly intervention. These results can be used to understand important sources of uncertainty around MenAfriVac and support decisions by policymakers

Increasing Hospital Admissions for Pneumonia, England

This rise in recorded incidence from 2001 to 2005 was particularly marked among the elderly

Barriers and facilitators to uptake of the school-based HPV vaccination programme in an ethnically diverse group of young women.

BACKGROUND: To identify the barriers and facilitators to uptake of the HPV vaccine in an ethnically diverse group of young women in the south west of England. METHODS: Three school-based vaccination sessions were observed. Twenty-three young women aged 12 to 13 years, and six key informants, were interviewed between October 2012 and July 2013. Data were analysed using thematic analysis and the Framework method for data management. RESULTS: The priority given to preventing cervical cancer in this age group influenced whether young women received the HPV vaccine. Access could be affected by differing levels of commitment by school staff, school nurses, parents and young women to ensure parental consent forms were returned. Beliefs and values, particularly relevant to minority ethnic groups, in relation to adolescent sexual activity may affect uptake. Literacy and language difficulties undermine informed consent and may prevent vaccination. CONCLUSIONS: The school-based HPV vaccination programme successfully reaches the majority of young women. However, responsibility for key aspects remain unresolved which can affect delivery and prevent uptake for some groups. A multi-faceted approach, targeting appropriate levels of the socio-ecological model, is required to address procedures for consent and cultural and literacy barriers faced by minority ethnic groups, increase uptake and reduce inequalities

Assessing the impacts of the first year of rotavirus vaccination in the United Kingdom

The United Kingdom (UK) added rotavirus (RV) vaccine (Rotarix GlaxoSmithKline) to the national vaccine schedule in July 2013. During the 2012–2014 rotavirus seasons, children presenting to the Bristol Royal Hospital for Children Emergency Department with gastroenteritis symptoms had stool virology analysis (real-time PCR) and clinical outcome recorded. Nosocomial cases were identified as patients with non-gastroenteritis diagnosis testing positive for rotavirus > 48h after admission. In comparison to average pre-vaccine seasons, in the first year after vaccine introduction there were 48% fewer attendances diagnosed with gastroenteritis, 53% reduction in gastroenteritis admissions and a total saving of 330 bed-days occupancy. There was an overall reduction in number of rotavirus-positive stool samples with 94% reduction in children aged under one year and a 65% reduction in those too old to have been vaccinated. In the first year after the introduction of universal vaccination against rotavirus we observed a profound reduction in gastroenteritis presentations and admissions with a substantial possible herd effect seen in older children. Extrapolating these findings to the UK population we estimate secondary healthcare savings in the first year of ca £7.5 (€10.5) million. Ongoing surveillance will be required to determine the long-term impact of the RV immunisation programme

The cost-effectiveness of alternative vaccination strategies for polyvalent meningococcal vaccines in Burkina Faso: A transmission dynamic modeling study.

BACKGROUND: The introduction of a conjugate vaccine for serogroup A Neisseria meningitidis has dramatically reduced disease in the African meningitis belt. In this context, important questions remain about the performance of different vaccine policies that target remaining serogroups. Here, we estimate the health impact and cost associated with several alternative vaccination policies in Burkina Faso. METHODS AND FINDINGS: We developed and calibrated a mathematical model of meningococcal transmission to project the disability-adjusted life years (DALYs) averted and costs associated with the current Base policy (serogroup A conjugate vaccination at 9 months, as part of the Expanded Program on Immunization [EPI], plus district-specific reactive vaccination campaigns using polyvalent meningococcal polysaccharide [PMP] vaccine in response to outbreaks) and three alternative policies: (1) Base Prime: novel polyvalent meningococcal conjugate (PMC) vaccine replaces the serogroup A conjugate in EPI and is also used in reactive campaigns; (2) Prevention 1: PMC used in EPI and in a nationwide catch-up campaign for 1-18-year-olds; and (3) Prevention 2: Prevention 1, except the nationwide campaign includes individuals up to 29 years old. Over a 30-year simulation period, Prevention 2 would avert 78% of the meningococcal cases (95% prediction interval: 63%-90%) expected under the Base policy if serogroup A is not replaced by remaining serogroups after elimination, and would avert 87% (77%-93%) of meningococcal cases if complete strain replacement occurs. Compared to the Base policy and at the PMC vaccine price of US$4 per dose, strategies that use PMC vaccine (i.e., Base Prime and Preventions 1 and 2) are expected to be cost saving if strain replacement occurs, and would cost US$51 (-US$236, US$490), US$188 (-US$97, US$626), and US$246 (-US$53, US$703) per DALY averted, respectively, if strain replacement does not occur. An important potential limitation of our study is the simplifying assumption that all circulating meningococcal serogroups can be aggregated into a single group; while this assumption is critical for model tractability, it would compromise the insights derived from our model if the effectiveness of the vaccine differs markedly between serogroups or if there are complex between-serogroup interactions that influence the frequency and magnitude of future meningitis epidemics. CONCLUSIONS: Our results suggest that a vaccination strategy that includes a catch-up nationwide immunization campaign in young adults with a PMC vaccine and the addition of this new vaccine into EPI is cost-effective and would avert a substantial portion of meningococcal cases expected under the current World Health Organization-recommended strategy of reactive vaccination. This analysis is limited to Burkina Faso and assumes that polyvalent vaccines offer equal protection against all meningococcal serogroups; further studies are needed to evaluate the robustness of this assumption and applicability for other countries in the meningitis belt

Minimum Incidence of Adult Invasive Pneumococcal Disease in Blantyre, Malawi an Urban African Setting: A Hospital Based Prospective Cohort Study

Invasive pneumococcal disease causes substantial morbidity and mortality in Africa. Evaluating population level indirect impact on adult disease of pneumococcal conjugate vaccine (PCV) programmes in infants requires baseline population incidence rates but these are often lacking in areas with limited disease surveillance. We used hospital based blood culture and cerebrospinal fluid surveillance to calculate minimal incidence of invasive pneumococcal disease in the adult (≥15 years old) population of Blantyre, a rapidly growing urban centre in southern Malawi, in the period preceding vaccine introduction. Invasive pneumococcal disease incidence in Blantyre district was high, mean 58.1 (95% confidence interval (CI): 53.7, 62.7) per 100,000 person years and peaking among 35 to 40 year olds at 108.8 (95%CI: 89.0, 131.7) mirroring the population age prevalence of HIV infection. For pneumococcal bacteraemia in urban Blantyre, mean incidence was 60.6 (95% CI: 55.2, 66.5) per 100,000 person years, peaking among 35 to 40 year olds at 114.8 (95%CI: 90.3, 143.9). We suspected that our surveillance may under-ascertain the true burden of disease, so we used location data from bacteraemic subjects and projected population estimates to calculate local sub-district incidence, then examined the impact of community level socio-demographic covariates as possible predictors of local sub-district incidence of pneumococcal and non-pneumococcal pathogenic bacteraemia. Geographic heterogeneity in incidence was marked with localised hotspots but ward level covariates apart from prison were not associated with pneumococcal bacteraemia incidence. Modelling suggests that the current sentinel surveillance system under-ascertains the true burden of disease. We outline a number of challenges to surveillance for pneumococcal disease in our low-resource setting. Subsequent surveillance in the vaccine era will have to account for geographic heterogeneity when evaluating population level indirect impact of PCV13 introduction to the childhood immunisation program

Health spillovers and economic evaluation

The health of carers and others close to the patient will often be relevant to economic evaluation, but it is very rarely considered in practice. This may reflect a lack of understanding of how the spillover effect of illness can be appropriately quantified. In this study we used three different approaches to quantify health spillovers resulting from meningitis. We conducted a survey of 1218 family networks affected by meningitis and used regression modelling to estimate spillover effects. The findings show that meningitis had long-term effects on family members' health, particularly affecting the likelihood of family members reporting anxiety and depression. These effects extended beyond a single close family member. These findings suggest that vaccinating against meningitis will bring significant health benefits not just to those that might have contracted the illness but also to their family networks. In methodological terms, different approaches for quantifying health spillovers provided broadly consistent results. The choice of method will be influenced by the ease of collecting primary data from family members in intervention contexts. © 2015 The Authors. Health Economics published by John Wiley & Sons Ltd.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/hec.325

Carriage of Neisseria Meningitidis in Low and Middle Income Countries of the Americas and Asia: A Review of the Literature.

Funder: Pfizer IncINTRODUCTION: Meningococcal colonization, or carriage, can progress to invasive meningococcal disease, a serious public health concern, with rapid progression of disease and severe consequences if left untreated. Information on meningococcal carriage and epidemiology in low/middle income American and Asian countries remains sparse. These data are crucial to ensure that appropriate preventive strategies such as vaccination can be implemented in these regions. The goal of this study was to summarize the Neisseria meningitidis carriage literature in low and middle income countries of the Americas and Asia. METHODS: Target countries were categorized as low and middle income according to the International Monetary Fund classification of low income/developing economies and middle income/emerging market economies, respectively. A PubMed search identified English-language publications that examined carriage in these countries. Studies reporting the epidemiology of N. meningitidis carriage or assessing risk factors for carriage were included. RESULTS: Fourteen studies from the Americas [Brazil (n = 7), Chile (n = 3), and Colombia, Cuba, Mexico, and Paraguay (n = 1 each)] and nine from Asia [China (n = 2), India (n = 3), and Malaysia, Nepal, Philippines, and Thailand (n = 1 each)] were identified; an additional Cuban study from the authors' files was also included. Studies were not identified in many target countries, and substantial diversity was observed among study methodologies, populations, and time periods, thereby limiting comparison between studies. The carriage rate in the Americas ranged from 1.6% to 9.9% and from 1.4% to 14.2% in Asia. Consistent risk factors for carriage were not identified. CONCLUSIONS: There is a lack of comprehensive and contemporary information on meningococcal carriage in low and medium income countries of the Americas and Asia. Future carriage studies should incorporate larger representative populations, a wider age range, and additional countries to improve our understanding of meningococcal epidemiology and disease control