Modelling canine rabies elimination in India through mass dog vaccination

The ‘Zero by 30’ campaign aims to globally eliminate dog-mediated human rabies deaths by 2030. Theoretical and empirical studies have shown that annual mass rabies vaccination (MRV) campaigns that vaccinate at least 70% of the dog population in an area can effectively control canine rabies outbreaks and eventually eliminate it. Achieving such coverages in free-ranging dog (FRD) populations, the main source of human infections in rabies-endemic regions, can be a major challenge where most FRDs are unowned and so not easily accessible for vaccination. Despite bearing the largest burden of human rabies deaths globally, few studies have explored the population characteristics of FRDs in India in the context of rabies elimination, particularly accessibility for vaccination. Similarly, there are limited studies of dog ownership practices (DOP) relevant to rabies control in India. We conducted a longitudinal field study over 16 months in a cohort of unowned dogs (UDs), semi-owned dogs (SODs) and ODs at an urban (human population of 240991 individuals) and a semi-urban (25861 individuals) site each in Kerala, south India. The study gathered data on dog population characteristics, DOP and pre- and post-vaccination rabies virus neutralizing antibody (RVNA) dynamics. In round 1 (R1) pre-vaccination blood samples were collected from all dogs, after which they were vaccinated against rabies, collared and microchipped where necessary and released. Data on demographic characteristics (sex, age, body condition etc.) and DOP were also collected. As many dogs as possible from this cohort were recaptured at approximately ~30 days (R2), ~150 – 180 days (R3) and ~365 days (R4) after first capture to collect post-vaccination blood samples. All serum samples were tested to assess post-vaccination RVNA titre dynamics and rates of decline. These data were used to parameterise an age-structured deterministic compartmental Susceptible-Exposed-Infectious-Vaccinated (SEIV) model incorporating assumptions about accessibility for vaccination. The model was used to assess the impacts of varying various demographic, immunological and MRV campaign parameters on prospects of rabies elimination within 20 years of campaign implementation. In R1, 577 dogs across all ownership categories were captured. Only 12% of FRDs were owned, with about 60% of ODs in R1 being free-ranging. Only 29% of ODs were vaccinated against rabies. Approximately 26% (95% CIs: 22 – 31%) of all dogs sampled in R1 had RVNA titres ≥ 0.23 IU/ml. Mixed-effects logistic regression models found higher recapture probabilities for sterilised dogs and lower probabilities for UDs, dogs from the semi-urban site and those with pre-vaccination RVNA titres ≤ 0.5 IU/ml or no detectable titres. Over 80% of dogs recaptured in R2 had titres > 0.5 IU/ml, irrespective of age or vaccination history. Mixed-effects linear regression models identified significant associations between post-vaccination RVNA titres and age at vaccination, sterilisation status and RVNA titre levels in R1. Titres were estimated to drop below 0.5 IU/ml approximately 200 days (95% CI: 167 – 256 days) after achieving post-vaccination peak levels. However, titres declined at a faster rate for ODs and completely/partially confined dogs compared to dogs without owners and completely FRDs. We also found evidence suggesting the occurrence of non-lethal rabies infections in FRDs. The SEIV model indicated that as accessibility for vaccination increased, rabies elimination was possible in a wider range of scenarios within shorter timeframes, generally within 10 years of implementation of vaccination campaigns, and required lower vaccination coverages. Where ≤ 20% of dogs were accessible, campaigns needed to consistently vaccinate > 95% of dogs for > 20 years to eliminate rabies. Rabies elimination was possible in most scenarios, typically with annual campaigns, even with < 70% effective vaccination coverages in the total dog population. The model also highlighted the complex interplay of demographic factors and disease transmission, with high birth rates resulting in higher rabies cases, irrespective of juvenile mortality or adult lifespan. Mass rabies vaccination continues to be the most effective rabies control method; however, the implementation and frequency of MRV campaigns must account for varying accessibility of FRD populations and consider variations in demography and immunological dynamics. Rabies control in India will require a multi-pronged approach incorporating more responsible dog ownership, access to veterinary care, effective MRV and dog population and waste management, while ensuring the use of properly stored, high-quality vaccines and where necessary, the use of alternative vaccination methods such as oral vaccines to access as many dogs as possible.Open Acces

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 ($263, 95$ - 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$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

Global dog and human rabies control efforts from ancient times to 2030 and beyond

Nowadays, rabies is mainly present in Africa and Asia, where every year it causes an estimated 59,000 human deaths and costs US$8.6 billion. A key date in the history of rabies control is 6 July 1885, when the first dose of rabies vaccine was successfully inoculated to an exposed individual in Paris. Yet, long before and after this event, many attempts at stopping rabies transmission, managing dog bites and preventing rabies symptoms have occurred throughout the world. Each step forwards – and backwards too – has been crucial to advance the scientific knowledge of rabies and how to control this disease at the interface of challenges of ecological, political and social nature. As the world starts to recover from the coronavirus 2019 (COVID-19) pandemic and move towards the 2030 goal of eliminating dog-mediated human rabies, learning from the past is vital for achieving a world with reduced rabies risk

Endoparasitism in captive wild-caught snakes indigenous to Kerala, India

In this preliminary survey, coprologic examination of six different captive snake species housed in three different herpetariums of Kerala state was conducted from July 2005 to January 2006, to study the prevalence of endoparasites. Of the 25 snakes examined, 22 (88%) were found infected. On the basis of morphology and morphometry, Capillaria spp. (72%), strongyle (28%), spirurid (20%), Strongyloides/Rhabdias spp. (16%), ascarid (12%), pseudophyllidean tapeworm (8%), acanthocephalan (4%) and pentastomid (12%) ova were identified. The occurrence of ova of Hymenolepis spp. as pseudoparasite was also noticed

First record in South Asia of deer throat bot fly larvae Pharyngomyia picta (Meigen, 1824) (Diptera: Oesteridae) from Sambar deer (Rusa unicolor), a new host record

The Bot fly larvae, identified to be the third instars of the deer throat bot fly Pharyngomyia picta were recovered from the lumen of trachea and secondary bronchi during the necropsy of a female sambar deer (Rusa unicolor) in Kerala, India. This forms the first report of P. picta from India and the whole of South Asia. Sambar deer is a new host record for the larvae of this fly. Morphological description of the third stage larvae with supporting figures are presented

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

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

Abstract 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