COVID-19 inequalities in England: a mathematical modelling study of transmission risk and clinical vulnerability by socioeconomic status.

BACKGROUND: The COVID-19 pandemic resulted in major inequalities in infection and disease burden between areas of varying socioeconomic deprivation in many countries, including England. Areas of higher deprivation tend to have a different population structure-generally younger-which can increase viral transmission due to higher contact rates in school-going children and working-age adults. Higher deprivation is also associated with a higher presence of chronic comorbidities, which were convincingly demonstrated to be risk factors for severe COVID-19 disease. These two major factors need to be combined to better understand and quantify their relative importance in the observed COVID-19 inequalities. METHODS: We used UK Census data on health status and demography stratified by decile of the Index of Multiple Deprivation (IMD), which is a measure of socioeconomic deprivation. We calculated epidemiological impact using an age-stratified COVID-19 transmission model, which incorporated different contact patterns and clinical health profiles by decile. To separate the contribution of each factor, we considered a scenario where the clinical health profile of all deciles was at the level of the least deprived. We also considered the effectiveness of school closures and vaccination of over 65-year-olds in each decile. RESULTS: In the modelled epidemics in urban areas, the most deprived decile experienced 9% more infections, 13% more clinical cases, and a 97% larger peak clinical size than the least deprived; we found similar inequalities in rural areas. Twenty-one per cent of clinical cases and 16% of deaths in England observed under the model assumptions would not occur if all deciles experienced the clinical health profile of the least deprived decile. We found that more deaths were prevented in more affluent areas during school closures and vaccination rollouts. CONCLUSIONS: This study demonstrates that both clinical and demographic factors synergise to generate health inequalities in COVID-19, that improving the clinical health profile of populations would increase health equity, and that some interventions can increase health inequalities.

Scoring epidemiological forecasts on transformed scales.

Forecast evaluation is essential for the development of predictive epidemic models and can inform their use for public health decision-making. Common scores to evaluate epidemiological forecasts are the Continuous Ranked Probability Score (CRPS) and the Weighted Interval Score (WIS), which can be seen as measures of the absolute distance between the forecast distribution and the observation. However, applying these scores directly to predicted and observed incidence counts may not be the most appropriate due to the exponential nature of epidemic processes and the varying magnitudes of observed values across space and time. In this paper, we argue that transforming counts before applying scores such as the CRPS or WIS can effectively mitigate these difficulties and yield epidemiologically meaningful and easily interpretable results. Using the CRPS on log-transformed values as an example, we list three attractive properties: Firstly, it can be interpreted as a probabilistic version of a relative error. Secondly, it reflects how well models predicted the time-varying epidemic growth rate. And lastly, using arguments on variance-stabilizing transformations, it can be shown that under the assumption of a quadratic mean-variance relationship, the logarithmic transformation leads to expected CRPS values which are independent of the order of magnitude of the predicted quantity. Applying a transformation of log(x + 1) to data and forecasts from the European COVID-19 Forecast Hub, we find that it changes model rankings regardless of stratification by forecast date, location or target types. Situations in which models missed the beginning of upward swings are more strongly emphasised while failing to predict a downturn following a peak is less severely penalised when scoring transformed forecasts as opposed to untransformed ones. We conclude that appropriate transformations, of which the natural logarithm is only one particularly attractive option, should be considered when assessing the performance of different models in the context of infectious disease incidence.

How immunity from and interaction with seasonal coronaviruses can shape SARS-CoV-2 epidemiology.

We hypothesized that cross-protection from seasonal epidemics of human coronaviruses (HCoVs) could have affected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, including generating reduced susceptibility in children. To determine what the prepandemic distribution of immunity to HCoVs was, we fitted a mathematical model to 6 y of seasonal coronavirus surveillance data from England and Wales. We estimated a duration of immunity to seasonal HCoVs of 7.8 y (95% CI 6.3 to 8.1) and show that, while cross-protection between HCoV and SARS-CoV-2 may contribute to the age distribution, it is insufficient to explain the age pattern of SARS-CoV-2 infections in the first wave of the pandemic in England and Wales. Projections from our model illustrate how different strengths of cross-protection between circulating coronaviruses could determine the frequency and magnitude of SARS-CoV-2 epidemics over the coming decade, as well as the potential impact of cross-protection on future seasonal coronavirus transmission.

Potential health and economic impact of paediatric vaccination using next-generation influenza vaccines in Kenya: a modelling study.

BACKGROUND: Influenza is a major year-round cause of respiratory illness in Kenya, particularly in children under 5. Current influenza vaccines result in short-term, strain-specific immunity and were found in a previous study not to be cost-effective in Kenya. However, next-generation vaccines are in development that may have a greater impact and cost-effectiveness profile. METHODS: We expanded a model previously used to evaluate the cost-effectiveness of seasonal influenza vaccines in Kenya to include next-generation vaccines by allowing for enhanced vaccine characteristics and multi-annual immunity. We specifically examined vaccinating children under 5 years of age with improved vaccines, evaluating vaccines with combinations of increased vaccine effectiveness, cross-protection between strains (breadth) and duration of immunity. We evaluated cost-effectiveness using incremental cost-effectiveness ratios (ICERs) and incremental net monetary benefits (INMBs) for a range of values for the willingness-to-pay (WTP) per DALY averted. Finally, we estimated threshold per-dose vaccine prices at which vaccination becomes cost-effective. RESULTS: Next-generation vaccines can be cost-effective, dependent on the vaccine characteristics and assumed WTP thresholds. Universal vaccines (assumed to provide long-term and broad immunity) are most cost-effective in Kenya across three of four WTP thresholds evaluated, with the lowest median value of ICER per DALY averted ($263, 95% Credible Interval (CrI): $ - 1698, $1061) and the highest median INMBs. At a WTP of $623, universal vaccines are cost-effective at or below a median price of $5.16 per dose (95% CrI: $0.94, $18.57). We also show that the assumed mechanism underlying infection-derived immunity strongly impacts vaccine outcomes. CONCLUSIONS: This evaluation provides evidence for country-level decision makers about future next-generation vaccine introduction, as well as global research funders about the potential market for these vaccines. Next-generation vaccines may offer a cost-effective intervention to reduce influenza burden in low-income countries with year-round seasonality like Kenya.

Chimpanzees communicate to coordinate a cultural practice.

Human culture thrives by virtue of communication, yet whether communication plays an influential role in the cultural lives of other animals remains understudied. Here, we investigated whether chimpanzees use communication to engage in a cultural practice by analysing grooming handclasp (GHC) interactions-a socio-cultural behaviour requiring interindividual coordination for successful execution. Previous accounts attributed GHC initiations to behavioural shaping, whereby the initiator physically moulds the partner's arm into the desired GHC posture. Using frame-by-frame analysis and matched-control methodology, we find that chimpanzees do not only shape their partner's posture (22%), but also use gestural communication to initiate GHC (44%), which requires an active and synchronized response from the partner. Moreover, in a third (34%) of the GHC initiations, the requisite coordination was achieved by seemingly effortless synchrony. Lastly, using a longitudinal approach, we find that for GHC initiations, communication occurs more frequently than shaping in experienced dyads and less in mother-offspring dyads. These findings are consistent with ontogenetic ritualization, thereby reflecting first documentation of chimpanzees communicating to coordinate a cultural practice. We conclude that chimpanzees show interactional flexibility in the socio-cultural domain, opening the possibility that the interplay between communication and culture is rooted in our deep evolutionary history.

Evidence for influenza and RSV interaction from 10 years of enhanced surveillance in Nha Trang, Vietnam, a modelling study.

Influenza and Respiratory Syncytial Virus (RSV) interact within their host posing the concern for impacts on heterologous viruses following vaccination. We aimed to estimate the population level impact of their interaction. We developed a dynamic age-stratified two-pathogen mathematical model that includes pathogen interaction through competition for infection and enhanced severity of dual infections. We used parallel tempering to fit its parameters to 11 years of enhanced hospital-based surveillance for acute respiratory illnesses (ARI) in children under 5 years old in Nha Trang, Vietnam. The data supported either a 41% (95%CrI: 36-54) reduction in susceptibility following infection and for 10.0 days (95%CrI 7.1-12.8) thereafter, or no change in susceptibility following infection. We estimate that co-infection increased the probability for an infection in <2y old children to be reported 7.2 fold (95%CrI 5.0-11.4); or 16.6 fold (95%CrI 14.5-18.4) in the moderate or low interaction scenarios. Absence of either pathogen was not to the detriment of the other. We find stronger evidence for severity enhancing than for acquisition limiting interaction. In this setting vaccination against either pathogen is unlikely to have a major detrimental effect on the burden of disease caused by the other.

Comparing human and model-based forecasts of COVID-19 in Germany and Poland.

Forecasts based on epidemiological modelling have played an important role in shaping public policy throughout the COVID-19 pandemic. This modelling combines knowledge about infectious disease dynamics with the subjective opinion of the researcher who develops and refines the model and often also adjusts model outputs. Developing a forecast model is difficult, resource- and time-consuming. It is therefore worth asking what modelling is able to add beyond the subjective opinion of the researcher alone. To investigate this, we analysed different real-time forecasts of cases of and deaths from COVID-19 in Germany and Poland over a 1-4 week horizon submitted to the German and Polish Forecast Hub. We compared crowd forecasts elicited from researchers and volunteers, against a) forecasts from two semi-mechanistic models based on common epidemiological assumptions and b) the ensemble of all other models submitted to the Forecast Hub. We found crowd forecasts, despite being overconfident, to outperform all other methods across all forecast horizons when forecasting cases (weighted interval score relative to the Hub ensemble 2 weeks ahead: 0.89). Forecasts based on computational models performed comparably better when predicting deaths (rel. WIS 1.26), suggesting that epidemiological modelling and human judgement can complement each other in important ways.

Chimpanzee communities differ in their inter- and intrasexual social relationships.

Male and female human social bonding strategies are culturally shaped, in addition to being genetically rooted. Investigating nonhuman primate bonding strategies across sex groups allows researchers to assess whether, as with humans, they are shaped by the social environment or whether they are genetically predisposed. Studies of wild chimpanzees show that in some communities males have strong bonds with other males, whereas in others, females form particularly strong intrasex bonds, potentially indicative of cultural differences across populations. However, excluding genetic or ecological explanations when comparing different wild populations is difficult. Here, we applied social network analysis to examine male and female social bonds in two neighbouring semiwild chimpanzee groups of comparable ecological conditions and subspecies compositions, but that differ in demographic makeup. Results showed differences in bonding strategies across the two groups. While female-female party co-residence patterns were significantly stronger in Group 1 (which had an even distribution of males and females) than in Group 2 (which had a higher proportion of females than males), there were no such differences for male-male or male-female associations. Conversely, female-female grooming bonds were stronger in Group 2 than in Group 1. We also found that, in line with captive studies but contrasting research with wild chimpanzees, maternal kinship strongly predicted proximity and grooming patterns across the groups. Our findings suggest that, as with humans, male and female chimpanzee social bonds are influenced by the specific social group they live in, rather than predisposed sex-based bonding strategies.

Long-Term Health-Related Quality of Life in Non-Hospitalized Coronavirus Disease 2019 (COVID-19) Cases With Confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in England: Longitudinal Analysis and Cross-Sectional Comparison With Controls.

BACKGROUND: We aimed to quantify the unknown losses in health-related quality of life of coronavirus disease 2019 (COVID-19) cases using quality-adjusted lifedays (QALDs) and the recommended EQ-5D instrument in England. METHODS: Prospective cohort study of nonhospitalized, polymerase chain reaction (PCR)-confirmed severe acute respiratory syndrome coronavirus 2-positive (SARS-CoV-2-positive) cases aged 12-85 years and followed up for 6 months from 1 December 2020, with cross-sectional comparison to SARS-CoV-2-negative controls. Main outcomes were QALD losses; physical symptoms; and COVID-19-related private expenditures. We analyzed results using multivariable regressions with post hoc weighting by age and sex, and conditional logistic regressions for the association of each symptom and EQ-5D limitation on cases and controls. RESULTS: Of 548 cases (mean age 41.1 years; 61.5% female), 16.8% reported physical symptoms at month 6 (most frequently extreme tiredness, headache, loss of taste and/or smell, and shortness of breath). Cases reported more limitations with doing usual activities than controls. Almost half of cases spent a mean of £18.1 on nonprescription drugs (median: £10.0), and 52.7% missed work or school for a mean of 12 days (median: 10). On average, all cases lost 13.7 (95% confidence interval [CI]: 9.7, 17.7) QALDs, whereas those reporting symptoms at month 6 lost 32.9 (95% CI: 24.5, 37.6) QALDs. Losses also increased with older age. Cumulatively, the health loss from morbidity contributes at least 18% of the total COVID-19-related disease burden in the England. CONCLUSIONS: One in 6 cases report ongoing symptoms at 6 months, and 10% report prolonged loss of function compared to pre-COVID-19 baselines. A marked health burden was observed among older COVID-19 cases and those with persistent physical symptoms.

What isn't social tolerance? The past, present, and possible future of an overused term in the field of primatology.

In the past four decades, the term social tolerance has been utilized to describe, explain, and predict many different aspects of primates' sociality and has been measured with a large range of traits and behaviors. To date, however, there has been little discussion on whether these different phenomena all reflect one and the same construct. This paper opens the discussion by presenting the historical development of the term social tolerance and a structured overview of its current, overextended use. We argue that social tolerance has developed to describe two distinct concepts: social tolerance as the social structure of a group and social tolerance as the dyadic or group-level manifestation of tolerant behaviors. We highlight how these two concepts are based on conflicting theoretical understandings and practical assessments. In conclusion, we present suggestions for future research on primate social tolerance, which will allow for a more systematic and comparable investigation of primate sociality.

The impact of COVID-19 vaccination in prisons in England and Wales: a metapopulation model.

BACKGROUND: High incidence of cases and deaths due to coronavirus disease 2019 (COVID-19) have been reported in prisons worldwide. This study aimed to evaluate the impact of different COVID-19 vaccination strategies in epidemiologically semi-enclosed settings such as prisons, where staff interact regularly with those incarcerated and the wider community. METHODS: We used a metapopulation transmission-dynamic model of a local prison in England and Wales. Two-dose vaccination strategies included no vaccination, vaccination of all individuals who are incarcerated and/or staff, and an age-based approach. Outcomes were quantified in terms of COVID-19-related symptomatic cases, losses in quality-adjusted life-years (QALYs), and deaths. RESULTS: Compared to no vaccination, vaccinating all people living and working in prison reduced cases, QALY loss and deaths over a one-year period by 41%, 32% and 36% respectively. However, if vaccine introduction was delayed until the start of an outbreak, the impact was negligible. Vaccinating individuals who are incarcerated and staff over 50 years old averted one death for every 104 vaccination courses administered. All-staff-only strategies reduced cases by up to 5%. Increasing coverage from 30 to 90% among those who are incarcerated reduced cases by around 30 percentage points. CONCLUSIONS: The impact of vaccination in prison settings was highly dependent on early and rapid vaccine delivery. If administered to both those living and working in prison prior to an outbreak occurring, vaccines could substantially reduce COVID-19-related morbidity and mortality in prison settings.

Temporal stability of chimpanzee social culture.

Culture is a hallmark of the human species, both in terms of the transmission of material inventions (e.g. tool manufacturing) and the adherence to social conventions (e.g. greeting mannerisms). While material culture has been reported across the animal kingdom, indications of social culture in animals are limited. Moreover, there is a paucity of evidencing cultural stability in animals. Here, based on a large dataset spanning 12 years, I show that chimpanzees adhere to arbitrary group-specific handclasp preferences that cannot be explained by genetics or the ecological environment. Despite substantial changes in group compositions across the study period, and all chimpanzees having several behavioural variants in their repertoires, chimpanzees showed and maintained the within-group homogeneity and between-group heterogeneity that are so characteristic of the cultural phenomenon in the human species. These findings indicate that human culture, including its arbitrary social conventions and long-term stability, is rooted in our evolutionary history.

Foraging zebra finches (Taeniopygia guttata) are public information users rather than conformists.

Social learning enables adaptive information acquisition provided that it is not random but selective. To understand species typical decision-making and to trace the evolutionary origins of social learning, the heuristics social learners use need to be identified. Here, we experimentally tested the nature of majority influence in the zebra finch. Subjects simultaneously observed two demonstrator groups differing in relative and absolute numbers (ratios 1 : 2/2 : 4/3 : 3/1 : 5) foraging from two novel food sources (black and white feeders). We find that demonstrator groups influenced observers' feeder choices (social learning), but that zebra finches did not copy the majority of individuals. Instead, observers were influenced by the foraging activity (pecks) of the demonstrators and in an anti-conformist fashion. These results indicate that zebra finches are not conformist, but are public information users.

Population-specific social dynamics in chimpanzees.

Understanding intraspecific variation in sociality is essential for characterizing the flexibility and evolution of social systems, yet its study in nonhuman animals is rare. Here, we investigated whether chimpanzees exhibit population-level differences in sociality that cannot be easily explained by differences in genetics or ecology. We compared social proximity and grooming tendencies across four semiwild populations of chimpanzees living in the same ecological environment over three consecutive years, using both linear mixed models and social network analysis. Results indicated temporally stable, population-level differences in dyadic-level sociality. Moreover, group cohesion measures capturing network characteristics beyond dyadic interactions (clustering, modularity, and social differentiation) showed population-level differences consistent with the dyadic indices. Subsequently, we explored whether the observed intraspecific variation in sociality could be attributed to cultural processes by ruling out alternative sources of variation including the influences of ecology, genetics, and differences in population demographics. We conclude that substantial variation in social behavior exists across neighboring populations of chimpanzees and that this variation is in part shaped by cultural processes.

Seasonal influenza vaccination in Kenya: an economic evaluation using dynamic transmission modelling.

BACKGROUND: There is substantial burden of seasonal influenza in Kenya, which led the government to consider introducing a national influenza vaccination programme. Given the cost implications of a nationwide programme, local economic evaluation data are needed to inform policy on the design and benefits of influenza vaccination. We set out to estimate the cost-effectiveness of seasonal influenza vaccination in Kenya. METHODS: We fitted an age-stratified dynamic transmission model to active surveillance data from patients with influenza from 2010 to 2018. Using a societal perspective, we developed a decision tree cost-effectiveness model and estimated the incremental cost-effectiveness ratio (ICER) per disability-adjusted life year (DALY) averted for three vaccine target groups: children 6-23 months (strategy I), 2-5 years (strategy II) and 6-14 years (strategy III) with either the Southern Hemisphere influenza vaccine (Strategy A) or Northern Hemisphere vaccine (Strategy B) or both (Strategy C: twice yearly vaccination campaigns, or Strategy D: year-round vaccination campaigns). We assessed cost-effectiveness by calculating incremental net monetary benefits (INMB) using a willingness-to-pay (WTP) threshold of 1-51% of the annual gross domestic product per capita ($17-$872). RESULTS: The mean number of infections across all ages was 2-15 million per year. When vaccination was well timed to influenza activity, the annual mean ICER per DALY averted for vaccinating children 6-23 months ranged between $749 and $1385 for strategy IA, $442 and $1877 for strategy IB, $678 and $4106 for strategy IC and $1147 and $7933 for strategy ID. For children 2-5 years, it ranged between $945 and $1573 for strategy IIA, $563 and $1869 for strategy IIB, $662 and $4085 for strategy IIC, and $1169 and $7897 for strategy IID. For children 6-14 years, it ranged between $923 and $3116 for strategy IIIA, $1005 and $2223 for strategy IIIB, $883 and $4727 for strategy IIIC and $1467 and $6813 for strategy IIID. Overall, no vaccination strategy was cost-effective at the minimum ($17) and median ($445) WTP thresholds. Vaccinating children 6-23 months once a year had the highest mean INMB value at $872 (WTP threshold upper limit); however, this strategy had very low probability of the highest net benefit. CONCLUSION: Vaccinating children 6-23 months once a year was the most favourable vaccination option; however, the strategy is unlikely to be cost-effective given the current WTP thresholds.

Forecasting the 2017/2018 seasonal influenza epidemic in England using multiple dynamic transmission models: a case study.

BACKGROUND: Since the 2009 A/H1N1 pandemic, Public Health England have developed a suite of real-time statistical models utilising enhanced pandemic surveillance data to nowcast and forecast a future pandemic. Their ability to track seasonal influenza and predict heightened winter healthcare burden in the light of high activity in Australia in 2017 was untested. METHODS: Four transmission models were used in forecasting the 2017/2018 seasonal influenza epidemic in England: a stratified primary care model using daily, region-specific, counts and virological swab positivity of influenza-like illness consultations in general practice (GP); a strain-specific (SS) model using weekly, national GP ILI and virological data; an intensive care model (ICU) using reports of ICU influenza admissions; and a synthesis model that included all data sources. For the first 12 weeks of 2018, each model was applied to the latest data to provide estimates of epidemic parameters and short-term influenza forecasts. The added value of pre-season population susceptibility data was explored. RESULTS: The combined results provided valuable nowcasts of the state of the epidemic. Short-term predictions of burden on primary and secondary health services were initially highly variable before reaching consensus beyond the observed peaks in activity between weeks 3-4 of 2018. Estimates for R0 were consistent over time for three of the four models until week 12 of 2018, and there was consistency in the estimation of R0 across the SPC and SS models, and in the ICU attack rates estimated by the ICU and the synthesis model. Estimation and predictions varied according to the assumed levels of pre-season immunity. CONCLUSIONS: This exercise successfully applied a range of pandemic models to seasonal influenza. Forecasting early in the season remains challenging but represents a crucially important activity to inform planning. Improved knowledge of pre-existing levels of immunity would be valuable.

Are we prepared for the next influenza pandemic? Lessons from modelling different preparedness policies against four pandemic scenarios.

In the event of a novel influenza strain that is markedly different to the current strains circulating in humans, the population have little/no immunity and infection spreads quickly causing a global pandemic. Over the past century, there have been four major influenza pandemics: the 1918 pandemic ("Spanish Flu"), the 1957-58 pandemic (the "Asian Flu"), the 1967-68 pandemic (the "Hong Kong Flu") and the 2009 pandemic (the "Swine flu"). To inform planning against future pandemics, this paper investigates how different is the net-present value of employing pre-purchase and responsive- purchased vaccine programmes in presence and absence of anti-viral drugs to scenarios that resemble these historic influenza pandemics. Using the existing literature and in discussions with policy decision makers in the UK, we first characterised the four past influenza pandemics by their transmissibility and infection-severity. For these combinations of parameters, we then projected the net-present value of employing pre-purchase vaccine (PPV) and responsive-purchase vaccine (RPV) programmes in presence and absence of anti-viral drugs. To differentiate between PPV and RPV policies, we changed the vaccine effectiveness value and the time to when the vaccine is first available. Our results are "heat-map" graphs displaying the benefits of different strategies in pandemic scenarios that resemble historic influenza pandemics. Our results suggest that immunisation with either PPV or RPV in presence of a stockpile of effective antiviral drugs, does not have positive net-present value for all of the pandemic scenarios considered. In contrast, in the absence of effective antivirals, both PPV and RPV policies have positive net-present value across all the pandemic scenarios. Moreover, in all considered circumstances, vaccination was most beneficial if started sufficiently early and covered sufficiently large number of people. When comparing the two vaccine programmes, the RPV policy allowed a longer timeframe and lower coverage to attain the same benefit as the PPV policy. Our findings suggest that responsive-purchase vaccination policy has a bigger window of positive net-present value when employed against each of the historic influenza pandemic strains but needs to be rapidly available to maximise benefit. This is important for future planning as it suggests that future preparedness policies may wish to consider utilising timely (i.e. responsive-purchased) vaccines against emerging influenza pandemics.

Why intergroup variation matters for understanding behaviour.

Intergroup variation (IGV) refers to variation between different groups of the same species. While its existence in the behavioural realm has been expected and evidenced, the potential effects of IGV are rarely considered in studies that aim to shed light on the evolutionary origins of human socio-cognition, especially in our closest living relatives-the great apes. Here, by taking chimpanzees as a point of reference, we argue that (i) IGV could plausibly explain inconsistent research findings across numerous topics of inquiry (experimental/behavioural studies on chimpanzees), (ii) understanding the evolutionary origins of behaviour requires an accurate assessment of species' modes of behaving across different socio-ecological contexts, which necessitates a reliable estimation of variation across intraspecific groups, and (iii) IGV in the behavioural realm is increasingly likely to be expected owing to the progressive identification of non-human animal cultures. With these points, and by extrapolating from chimpanzees to generic guidelines, we aim to encourage researchers to explicitly consider IGV as an explanatory variable in future studies attempting to understand the socio-cognitive and evolutionary determinants of behaviour in group-living animals.

fluEvidenceSynthesis: An R package for evidence synthesis based analysis of epidemiological outbreaks.

Public health related decisions often have to balance the cost of intervention strategies with the benefit of the reduction in disease burden. While the cost can often be inferred, forward modelling of the effect of different intervention options is complicated and disease specific. Here we introduce a package that is aimed to simplify this process. The package allows one to infer parameters using a Bayesian approach, perform forward modelling of the likely results of the proposed intervention and finally perform cost effectiveness analysis of the results. The package is based on a method previously used in the United Kingdom to inform vaccination strategies for influenza, with extensions to make it easily adaptable to other diseases and data sources.

Cost-effectiveness analysis of quadrivalent seasonal influenza vaccines in England.

BACKGROUND: As part of the national seasonal influenza vaccination programme in England and Wales, children receive a quadrivalent vaccine offering protection against two influenza A strains and two influenza B strains. Healthy children receive a quadrivalent live attenuated influenza vaccine (QLAIV), whilst children with contraindications receive the quadrivalent inactivated influenza vaccine (QIIV). Individuals aged younger than 65 years in the clinical risk populations and elderly individuals aged 65+ years receive either a trivalent inactivated influenza vaccine (TIIV) offering protection from two A strains and one B strain or the QIIV at the choice of their general practitioner. The cost-effectiveness of quadrivalent vaccine programmes is an open question. The original analysis that supported the paediatric programme only considered a trivalent live attenuated vaccine (LAIV). The cost-effectiveness of the QIIV to other patients has not been established. We sought to estimate the cost-effectiveness of these programmes, establishing a maximum incremental total cost per dose of quadrivalent vaccines over trivalent vaccines. METHODS: We used the same mathematical model as the analysis that recommended the introduction of the paediatric influenza vaccination programme. The incremental cost of the quadrivalent vaccine is the additional cost over that of the existing trivalent vaccine currently in use. RESULTS: Introducing quadrivalent vaccines can be cost-effective for all targeted groups. However, the cost-effectiveness of the programme is dependent on the choice of target cohort and the cost of the vaccines: the paediatric programme is cost-effective with an increased cost of £6.36 per dose, though an extension to clinical risk individuals younger than 65 years old and further to all elderly individuals means the maximum incremental cost is £1.84 and £0.20 per dose respectively. CONCLUSIONS: Quadrivalent influenza vaccines will bring substantial health benefits, as they are cost-effective in particular target groups.