Evaluation of the continuing effectiveness of the United Kingdom's Haemophilus influenzae type b national immunisation programme

Haemophilus influenzae (Hi) is a gram negative bacillus that commonly colonises the upper respiratory tract of humans. While the serotype b capsular form (Hib) of this organism accounts for less than 5% of carriage episodes, it is responsible for more than 95% of all invasive Hi infections. The capsular polysaccharide of Hib, polyribosylribitol phosphate (PRP), is an important virulence determinant. Serum antibodies specific for PRP correlate with bactericidal activity against the organism, and their acquisition with age in populations has an inverse relationship with the experience of invasive disease. The first vaccines to be developed against Hib were based on the capsular polysaccharide, but were limited in their application due to the T cell independent nature of the antigen, which was not immunogenic in children less than two years of age. Chemical conjugation of PRP with a carrier protein such as diphtheria or tetanus toxoid converted it into a T cell dependent antigen, capable of eliciting antibody production in infants only a few months old, and resulting in the formation of populations of ‘memory’ B lymphocytes believed to provide long term protection from infection. Efficacy of these conjugate vaccines against both acquisition of the organism and progression to invasive disease was subsequently demonstrated. Hib was a significant cause of morbidity and mortality among British children before inclusion of Hib conjugate vaccines in the routine UK infant immunisation schedule in October 1992. In contrast to other developed countries, it was scheduled as a three dose accelerated primary course at 2, 3 and 4 months of age without a booster dose in the second year of life. Vaccine introduction was accompanied by a catch-up immunisation campaign in which a single dose was given to children under four years of age. Despite an initial rapid and dramatic fall in Hib disease reports, a resurgence of cases occurred from 1999 onwards, predominantly in vaccinated children. This rise has since been attributed to a number of factors related to vaccine use. Wearing off of the initial catch-up campaign’s effect, rapid waning of immunity induced by the accelerated infant schedule and the use of less immunogenic acellular pertussis containing Hib combination vaccines in 2000/2001 have all resulted in a reduction in protective antibody titres in the population at risk. In keeping with the notion that this should correspond with greater likelihood of disease, infants bom prematurely, whose response to immunisation is less than term-delivered counterparts, have been shown to have a four fold increase in risk of invasive Hib infection. Hib vaccines have further been demonstrated to delay acquisition of carriage, thereby reducing transmission in populations. This indirect effect of immunisation, or ‘herd immunity’ was hailed as a major contribution to disease reduction. It may also impair the maintenance of long term immunity at a population level, however. Following an initial decline in Hib reports associated with vaccine introduction among older unimmunised cohorts, adult case numbers in the UK have now returned to prevaccination levels. This rise has occurred in association with a reduction in specific antibody titres to Hib in adult age groups which was observed within only two years of vaccine introduction. In a surprising finding, a national case-control study of invasive Hib infections found a reduced risk of invasive disease among children attending day nurseries, or exposed to cigarette smoke. Prior to vaccine use, both of these exposures were associated with higher rates of disease, presumed to be mediated through higher carriage prevalence. It is possible that repeated antigenic challenge through colonisation may result in improved persistence of antibodies elicited by immunisation. The anticipated medium to long term effects of Hib conjugate vaccine as used in the UK on transmission and maintenance of population immunity were simulated using a mathematical model. The model further provided a framework in which to investigate key assumptions regarding the mechanism of vaccine protection. Good correlation of outputs with seroepidemiologic data from the UK was achieved. Exploratory analysis of the protective efficacy of immunologic memory within this system reinforced individual and population level observations of relatively poor protection against invasive disease in individuals whose post-immunisation Hib antibody titres had waned to undetectable levels. The anticipated effects of a range of potential vaccination strategies which may be employed in the UK to raise antibody titres in the age groups at greatest risk and thereby reduce disease incidence were investigated

Haemophilus influenzae type b reemergence after combination immunization

An increase in Haemophilus influenzae type b (Hib) in British children has been linked to the widespread use of a diphtheria/tetanus/acellular pertussis combination vaccine (DTaP-Hib). We measured anti-polyribosyl-ribitol phos- phate antibody concentration and avidity before and after a Hib booster in 176 children 2–4 years of age who had received 3 doses of DTP-Hib (either DT whole cell pertus- sis-Hib or DTaP-Hib) combination vaccine in infancy. We also measured pharyngeal carriage of Hib. Antibody con- centrations before and avidity indices after vaccination were low (geometric mean concentration 0.46μg/mL, 95% confidence interval [CI] 0.36–0.58; geometric mean avidity index 0.16, 95% CI 0.14–0.18) and inversely related to the number of previous doses of DTaP-Hib (p = 0.02 and p<0.001, respectively). Hib was found in 2.1% (95% CI 0.7%–6.0%) of study participants. Our data support an association between DTaP-Hib vaccine combinations and clinical Hib disease through an effect on antibody concen- tration and avidit

Incorporating population dynamics into household models of infectious disease transmission

Most household models of disease transmission assume static household distributions. Although this is a reasonable simplification for assessing vaccination strategies at a single point in time or over the course of an outbreak, it has considerable drawbacks for assessing long term vaccination policies or for predicting future changes in immunity. We demonstrate that household models that include births, deaths and movement between households can show dramatically different patterns of infection and immunity to static population models. When immunity is assumed to be life-long, the pattern of births by household size is the key driver of infection, suggesting that the influx of susceptibles has most impact on infection risk in the household. In a comparison of 12 countries, we show that both the crude birth rate and the mean household size affect the risk of infection in households

Diagnosis and Antiviral Intervention Strategies for Mitigating an Influenza Epidemic

BACKGROUND: Many countries have amassed antiviral stockpiles for pandemic preparedness. Despite extensive trial data and modelling studies, it remains unclear how to make optimal use of antiviral stockpiles within the constraints of healthcare infrastructure. Modelling studies informed recommendations for liberal antiviral distribution in the pandemic phase, primarily to prevent infection, but failed to account for logistical constraints clearly evident during the 2009 H1N1 outbreaks. Here we identify optimal delivery strategies for antiviral interventions accounting for logistical constraints, and so determine how to improve a strategy's impact. METHODS AND FINDINGS: We extend an existing SEIR model to incorporate finite diagnostic and antiviral distribution capacities. We evaluate the impact of using different diagnostic strategies to decide to whom antivirals are delivered. We then determine what additional capacity is required to achieve optimal impact. We identify the importance of sensitive and specific case ascertainment in the early phase of a pandemic response, when the proportion of false-positive presentations may be high. Once a substantial percentage of ILI presentations are caused by the pandemic strain, identification of cases for treatment on syndromic grounds alone results in a greater potential impact than a laboratory-dependent strategy. Our findings reinforce the need for a decentralised system capable of providing timely prophylaxis. CONCLUSIONS: We address specific real-world issues that must be considered in order to improve pandemic preparedness policy in a practical and methodologically sound way. Provision of antivirals on the scale proposed for an effective response is infeasible using traditional public health outbreak management and contact tracing approaches. The results indicate to change the transmission dynamics of an influenza epidemic with an antiviral intervention, a decentralised system is required for contact identification and prophylaxis delivery, utilising a range of existing services and infrastructure in a "whole of society" response

Characterising pandemic severity and transmissibility from data collected during first few hundred studies

Early estimation of the probable impact of a pandemic influenza outbreak can assist public health authorities to ensure that response measures are proportionate to the scale of the threat. Recently, frameworks based on transmissibility and severity have been proposed for initial characterization of pandemic impact. Data requirements to inform this assessment may be provided by "First Few Hundred" (FF100) studies, which involve surveillance-possibly in person, or via telephone-of household members of confirmed cases. This process of enhanced case finding enables detection of cases across the full spectrum of clinical severity, including the date of symptom onset. Such surveillance is continued until data for a few hundred cases, or satisfactory characterization of the pandemic strain, has been achieved. We present a method for analysing these data, at the household level, to provide a posterior distribution for the parameters of a model that can be interpreted in terms of severity and transmissibility of a pandemic strain. We account for imperfect case detection, where individuals are only observed with some probability that can increase after a first case is detected. Furthermore, we test this methodology using simulated data generated by an independent model, developed for a different purpose and incorporating more complex disease and social dynamics. Our method recovers transmissibility and severity parameters to a high degree of accuracy and provides a computationally efficient approach to estimating the impact of an outbreak in its early stages.Andrew J. Black, Nicholas Gear, James M. McCaw, Jodie McVernon, Joshua V. Ros

Actividades deportivas en el medio natural: su representación en libros de texto de Educación Física en Primaria

The objective of this research is to analyze the sport activities carried out in the natural environment represented in the textbooks of Physical Education (PE) in Primary Education (EP), published according to Organic Law of Education 2/2006, of May 3rd, (LOE). 4339 images have been analyzed, from 44 different textbooks, belonging to eight Spanish publishers. The SAIMEF (Physical Analysis Images Analysis System) tool, elaborated ad hoc, was used to analyze the content of the images. The pilot test, panel of experts and triangulation with several observers were some of the scientific criteria that endorsed this tool. The results show that the presence of images related to sport activities in the natural environment continues to be very scarce in PE textbooks. The editorial Teide represents in greater proportion this type of activities compared to the rest of publishers. In the third cycle appears a greater number of images, predominating drawings over pictures. The most represented sport activity is the orientation, with a 25.6%, included within the multidisciplinary sports, prevailing the terrestrial environment. The representation of sports in the natural environment varies according to the analyzed publishers. Thus, in Anaya and Bruño predominates the orientation, in Edelvives, Paidotribo and Serbal predominates the ski, and in the publishers Santillana and Teide prevails the escalation. It is necessary to reflect on the low representation of these activities in EF textbooks

Modelling testing and response strategies for COVID-19 outbreaks in remote Australian Aboriginal communities

Background: Remote Australian Aboriginal and Torres Strait Islander communities have potential to be severely impacted by COVID-19, with multiple factors predisposing to increased transmission and disease severity. Our modelling aims to inform optimal public health responses. Methods: An individual-based simulation model represented SARS-CoV2 transmission in communities ranging from 100 to 3500 people, comprised of large, interconnected households. A range of strategies for case finding, quarantining of contacts, testing, and lockdown were examined, following the silent introduction of a case. Results: Multiple secondary infections are likely present by the time the first case is identified. Quarantine of close contacts, defined by extended household membership, can reduce peak infection prevalence from 60 to 70% to around 10%, but subsequent waves may occur when community mixing resumes. Exit testing significantly reduces ongoing transmission. Concurrent lockdown of non-quarantined households for 14 days is highly effective for epidemic control and reduces overall testing requirements; peak prevalence of the initial outbreak can be constrained to less than 5%, and the final community attack rate to less than 10% in modelled scenarios. Lockdown also mitigates the effect of a delay in the initial response. Compliance with lockdown must be at least 80–90%, however, or epidemic control will be lost. Conclusions: A SARS-CoV-2 outbreak will spread rapidly in remote communities. Prompt case detection with quarantining of extended-household contacts and a 14 day lockdown for all other residents, combined with exit testing for all, is the most effective strategy for rapid containment. Compliance is crucial, underscoring the need for community supported, culturally sensitive responses

A Small Community Model for the Transmission of Infectious Diseases: Comparison of School Closure as an Intervention in Individual-Based Models of an Influenza Pandemic

BACKGROUND: In the absence of other evidence, modelling has been used extensively to help policy makers plan for a potential future influenza pandemic. METHOD: We have constructed an individual based model of a small community in the developed world with detail down to exact household structure obtained from census collection datasets and precise simulation of household demographics, movement within the community and individual contact patterns. We modelled the spread of pandemic influenza in this community and the effect on daily and final attack rates of four social distancing measures: school closure, increased case isolation, workplace non-attendance and community contact reduction. We compared the modelled results of final attack rates in the absence of any interventions and the effect of school closure as a single intervention with other published individual based models of pandemic influenza in the developed world. RESULTS: We showed that published individual based models estimate similar final attack rates over a range of values for R(0) in a pandemic where no interventions have been implemented; that multiple social distancing measures applied early and continuously can be very effective in interrupting transmission of the pandemic virus for R(0) values up to 2.5; and that different conclusions reached on the simulated benefit of school closure in published models appear to result from differences in assumptions about the timing and duration of school closure and flow-on effects on other social contacts resulting from school closure. CONCLUSION: Models of the spread and control of pandemic influenza have the potential to assist policy makers with decisions about which control strategies to adopt. However, attention needs to be given by policy makers to the assumptions underpinning both the models and the control strategies examined

Evaluation of the Australian first few X household transmission project for COVID-19

Background: The Australian First Few X (FFX) Household Transmission Project for COVID-19 was the first prospective, multi-jurisdictional study of its kind in Australia. The project was undertaken as a partnership between federal and state health departments and the Australian Partnership for Preparedness Research on Infectious Disease Emergencies (APPRISE) and was active from April to October 2020. Methods: We aimed to identify and explore the challenges and strengths of the Australian FFX Project to inform future FFX study development and integration into pandemic preparedness plans. We asked key stakeholders and partners involved with implementation to identify and rank factors relating to the strengths and challenges of project implementation in two rounds of modified Delphi surveys. Key representatives from jurisdictional health departments were then interviewed to contextualise findings within public health processes and information needs to develop a final set of recommendations for FFX study development in Australia. Results: Four clear recommendations emerged from the evaluation. Future preparedness planning should aim to formalise and embed partnerships between health departments and researchers to help better integrate project data collection into core public health surveillance activities. The development of functional, adaptable protocols with pre-established ethics and governance approvals and investment in national data infrastructure were additional priority areas noted by evaluation participants. Conclusion: The evaluation provided a great opportunity to consolidate lessons learnt from the Australian FFX Household Transmission Project. The developed recommendations should be incorporated into future pandemic preparedness plans in Australia to enable effective implementation and increase local utility and value of the FFX platform within emergency public health response

The ongoing value of first few X studies for COVID-19 in the Western Pacific Region

First few ‘X’ (FFX) studies for COVID-19 involve data collection from confirmed cases and their close contacts. They remain relevant especially as many remain susceptible to infection, and as they can provide detailed insight into vaccine effectiveness and the epidemiology of variants of concern, helping to inform a proportionate health response