The potential cost-effectiveness of next generation influenza vaccines in England and Wales: A modelling analysis.

Next generation influenza vaccines are in development and have the potential for widespread health and economic benefits. Determining the potential health and economic impact for these vaccines is needed to drive investment in bringing these vaccines to the market, and to inform which groups public health policies on influenza vaccination should target. We used a mathematical modelling approach to estimate the epidemiological impact and cost-effectiveness of next generation influenza vaccines in England and Wales. We used data from an existing fitted model, and evaluated new vaccines with different characteristics ranging from improved vaccines with increased efficacy duration and breadth of protection, to universal vaccines, defined in line with the World Health Organisation (WHO) Preferred Product Characteristics (PPC). We calculated the cost effectiveness of new vaccines in comparison to the current seasonal vaccination programme. We calculated and compared the Incremental Cost-Effectiveness Ratio and Incremental Net Monetary Benefit for each new vaccine type. All analysis was conducted in R. We show that next generation influenza vaccines may result in a 21% to 77% reduction in influenza infections, dependent on vaccine characteristics. Our economic modelling shows that using any of these next generation vaccines at 2019 coverage levels would be highly cost-effective at a willingness to pay threshold of £20,000 for a range of vaccine prices. The vaccine threshold price for the best next generation vaccines in £-2019 is £230 (95%CrI £192 - £269) per dose, but even minimally-improved influenza vaccines could be priced at £18 (95%CrI £16 - £21) per dose and still remain cost-effective. This evaluation demonstrates the promise of next generation influenza vaccines for impact on influenza epidemics, and likely cost-effectiveness profiles. We have provided evidence towards a full value of vaccines assessment which bolsters the investment case for development and roll-out of next-generation influenza vaccines.

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.

The impact of the COVID-19 pandemic on patterns of attendance at emergency departments in two large London hospitals: an observational study.

BACKGROUND: Hospitals in England have undergone considerable change to address the surge in demand imposed by the COVID-19 pandemic. The impact of this on emergency department (ED) attendances is unknown, especially for non-COVID-19 related emergencies. METHODS: This analysis is an observational study of ED attendances at the Imperial College Healthcare NHS Trust (ICHNT). We calibrated auto-regressive integrated moving average time-series models of ED attendances using historic (2015-2019) data. Forecasted trends were compared to present year ICHNT data for the period between March 12, 2020 (when England implemented the first COVID-19 public health measure) and May 31, 2020. We compared ICHTN trends with publicly available regional and national data. Lastly, we compared hospital admissions made via the ED and in-hospital mortality at ICHNT during the present year to the historic 5-year average. RESULTS: ED attendances at ICHNT decreased by 35% during the period after the first lockdown was imposed on March 12, 2020 and before May 31, 2020, reflecting broader trends seen for ED attendances across all England regions, which fell by approximately 50% for the same time frame. For ICHNT, the decrease in attendances was mainly amongst those aged < 65 years and those arriving by their own means (e.g. personal or public transport) and not correlated with any of the spatial dependencies analysed such as increasing distance from postcode of residence to the hospital. Emergency admissions of patients without COVID-19 after March 12, 2020 fell by 48%; we did not observe a significant change to the crude mortality risk in patients without COVID-19 (RR 1.13, 95%CI 0.94-1.37, p = 0.19). CONCLUSIONS: Our study findings reflect broader trends seen across England and give an indication how emergency healthcare seeking has drastically changed. At ICHNT, we find that a larger proportion arrived by ambulance and that hospitalisation outcomes of patients without COVID-19 did not differ from previous years. The extent to which these findings relate to ED avoidance behaviours compared to having sought alternative emergency health services outside of hospital remains unknown. National analyses and strategies to streamline emergency services in England going forward are urgently needed.

Rabies as a Public Health Concern in India-A Historical Perspective.

India bears the highest burden of global dog-mediated human rabies deaths. Despite this, rabies is not notifiable in India and continues to be underprioritised in public health discussions. This review examines the historical treatment of rabies in British India, a disease which has received relatively less attention in the literature on Indian medical history. Human and animal rabies was widespread in British India, and treatment of bite victims imposed a major financial burden on the colonial Government of India. It subsequently became a driver of Pasteurism in India and globally and a key component of British colonial scientific enterprise. Efforts to combat rabies led to the establishment of a wide network of research institutes in India and important breakthroughs in development of rabies vaccines. As a result of these efforts, rabies no longer posed a significant threat to the British, and it declined in administrative and public health priorities in India towards the end of colonial rule-a decline that has yet to be reversed in modern-day India. The review also highlights features of the administrative, scientific and societal approaches to dealing with this disease in British India that persist to this day.

A note on wildlife poisoning cases from Kerala, South India.

Wildlife poisoning is an important conservation threat for endangered species in India. There are no publications in the scientific literature that identify the specific poisons or chemicals involved in wildlife poisoning cases from the state of Kerala. In this report, all cases of wildlife mortality recorded between 2011 and 2013 at the office of the Assistant Forest Veterinary Officer, Periyar Tiger Reserve in Kerala were reviewed and cases where poisoning was considered as a differential diagnosis were identified. Specific poisons or chemicals were identified in three cases, while in a fourth, poisoning was determined to have occurred based on physical traces of the poison in gut contents. The poisons identified include carbofuran (a carbamate pesticide) in a bonnet macaque (Macaca radiata), warfarin (a rodenticide) in a mortality event involving four wild boars (Sus scrofa), endosulfan (an organochlorine pesticide) toxicity in a gaur (Bos gaurus) and imidacloprid (a neonicotinoid pesticide) toxicity in a wild adult Asian elephant (Elephas maximus). This communication thus reports for the first time on the specific chemical compounds identified in wildlife poisoning cases from Kerala state and argues for greater regulation of the sale and use of such toxic compounds in India.

First record of Chrysomya albiceps Wiedemann, 1819 (Diptera: Calliphoridae) maggots from a sambar deer (Rusa unicolor) in Kerala, South India.

Fully grown third stage larvae (LIII) of Chrysomya albiceps were recovered from aberrant sites viz. trachea and rumen during necropsy of a free-range sambar deer that had been observed to bear an inflamed tongue infested with maggots and subsequently died due to starvation. Five dead maggots of C. bezziana were also recovered from rumen. The aberrant locations of the recovery of the maggots indicated that they might have reached these sites accidentally. This is the first report of LIII of C. albiceps from a sambar deer from Kerala, South India.