Global burden and economic impact of vaccine-preventable cancer mortality.

BackgroundInfections are responsible for approximately 13% of cancer cases worldwide and many of these infections can be prevented by vaccination. Human papillomavirus (HPV) and hepatitis B virus (HBV) are among the most common infections that cause cancer deaths globally, despite effective prophylactic vaccines being available. This analysis aims to estimate the global burden and economic impact of vaccine-preventable cancer mortality across World Health Organization (WHO) regions.MethodsThe number of deaths and years of life lost (YLL) due to five different vaccine-preventable cancer forms (oral cavity, liver, laryngeal, cervical and oropharyngeal cancer) in each of the WHO regions (African, Eastern Mediterranean, European, the Americas, South-East Asia Pacific and Western Pacific) were obtained from the Institute for Health Metrics Evaluation global burden of disease dataset. Vaccine-preventable mortality was estimated considering the fraction attributable to infection, to estimate the number of deaths and YLL potentially preventable through vaccination. Data from the World Bank on GDP per capita were used to estimate the value of YLL (VYLL). The robustness of these results was explored with sensitivity analysis. Given that several Epstein-Barr virus (EBV) vaccines are in development, but not yet available, the impact of a potential vaccine for EBV was evaluated in a scenario analysis.ResultsIn 2019, there were 465,740 potentially vaccine-preventable cancer deaths and 14,171,397 YLL across all WHO regions. The estimated economic impact due to this mortality was $106.3 billion globally. The sensitivity analysis calculated a range of 403,025-582,773 deaths and a range in productivity cost of $78.8-129.0 billion. In the scenario analysis EBV-related cancer mortality increased the global burden by 159,723 deaths and $32.4 billion.ConclusionOverall, the findings from this analysis illustrated high economic impact of premature cancer mortality that could be potentially preventable by vaccination which may assist decision-makers in allocating limited resources among competing priorities. Improved implementation and increased vaccination coverage of HPV and HBV should be prioritized to decrease this burden.

The indirect costs of human papillomavirus-related cancer in Central and Eastern Europe: years of life lost and productivity costs.

BACKGROUND: Human papilloma virus (HPV) is a common cause of several types of cancer, including head and neck (oral cavity, pharynx, oropharynx, hypopharynx, nasopharynx, and larynx), cervical, vulval, vaginal, anal, and penile cancers. As HPV vaccines are available, there is potential to prevent HPV-related disease burden and related costs. METHOD: A model was developed for nine Central Eastern European (CEE) countries (Bulgaria, Croatia, Czechia, Hungary, Poland, Romania, Serbia, Slovakia, Slovenia). This model considered cancer patients who died from 11 HPV-related cancers (oropharynx, oral cavity, nasopharynx, hypopharynx, pharynx, anal, larynx, vulval, vaginal, cervical, and penile) in 2019. Due to data limitations, Bulgaria only included four cancer types. The model estimated the number of HPV-related deaths and years of life lost (YLL) based on published HPV-attributable fractions. YLL was adjusted with labor force participation, retirement age and then multiplied by mean annual earnings, discounted at a 3% annual rate to calculate the present value of future lost productivity (PVFLP). RESULTS: In 2019, there were 6,832 deaths attributable to HPV cancers resulting in 107,846 YLL in the nine CEE countries. PVFLP related to HPV cancers was estimated to be €46 M in Romania, €37 M in Poland, €19 M in Hungary, €15 M in Czechia, €12 M in Croatia, €10 M in Serbia, €9 M in Slovakia, €7 M in Bulgaria and €4 M in Slovenia. CONCLUSIONS: There is a high disease burden of HPV-related cancer-related deaths in the CEE region, with a large economic impact to society due to substantial productivity losses. It is critical to implement and reinforce public health measures with the aim to reduce the incidence of HPV-related diseases, and the subsequent premature cancer deaths. Improving HPV screening and increasing vaccination programs, in both male and female populations, could help reduce this burden.

An economic evaluation of two cervical screening algorithms in Belgium: HR-HPV primary compared to HR-HPV and liquid-based cytology co-testing.

OBJECTIVE: To assess the costs and benefits of two algorithms for cervical cancer screening in Belgium (1) high-risk human papillomavirus (HR-HPV) primary screening and (2) HR-HPV and liquid-based cytology (LBC) co-testing. METHODS: A decision tree was adapted from published work and parameterised using HORIZON study data and Belgian cost and population data. The theoretical model represents two different screening algorithms for a cohort of 577 846 women aged 25-64 attending routine cervical screening. Scenario analyses were used to explore the impact of including vaccinated women and alternative pricing approaches. Uncertainty analyses were conducted. RESULTS: The cost per woman screened was €113.50 for HR-HPV primary screening and €101.70 for co-testing, representing a total cost of €65 588 573 and €58 775 083, respectively, for the cohort; a 10% difference. For one screening cycle, compared to HR-HPV primary, co-testing resulted in 13 173 more colposcopies, 67 731 more HR-HPV tests and 477 020 more LBC tests. Co-testing identified 2351 more CIN2+ cases per year (27% more than HR-HPV primary) and 1602 more CIN3+ cases (24% more than HR-HPV primary) than HR-HPV primary. CONCLUSION: In Belgium, a co-testing algorithm could increase cervical pre-cancer detection rates compared to HR-HPV primary. Co-testing would cost less than HR-HPV primary if the cost of the HPV test and LBC were cost-neutral compared to the current cost of LBC screening but would cost more if the cost per HPV test and LBC were the same in both co-testing and HR-HPV primary strategies.

Global Prevalence of Varicella-Associated Complications: A Systematic Review and Meta-Analysis.

INTRODUCTION: Varicella (chickenpox) is an infectious disease caused by the varicella zoster virus affecting children, adolescents, and adults. Varicella symptoms are usually self-limiting; however, different complications with widespread and systemic manifestations can occur. This systematic literature review aims to explore and quantify varicella-associated complication rates. METHODS: Two databases (Embase and MEDLINE), congress abstracts, and reference lists of systematic reviews were screened to identify evidence on varicella complications. Complications were identified and grouped into 14 clinically relevant categories. Proportional meta-analyses were conducted using a random-effects model and tests for heterogeneity and publication bias were performed. Subgroup, sensitivity, and meta-regression analyses were also conducted. A total of 78 studies, spanning 30 countries, were included in the meta-analysis. RESULTS: Pooled prevalence was highest in severe varicella (22.42%; 95% confidence interval [CI] 10.13-37.77), skin-related complications (20.12%; 95% CI 15.48-25.20), and infection-related complications (10.03%; 95% CI 7.47-12.90). Cardiovascular (0.55%; 95% CI 0.08-1.33), genitourinary (1.17%; 95% CI 0.55-1.99), and musculoskeletal (1.54%; 95% CI 1.06-2.11) complications had the lowest pooled prevalence. The remaining complication categories ranged between 1% and 10%. Subgroup analysis showed that complications were more prevalent in children versus adults and in hospitalized patients versus outpatients. Meta-regression analysis found that no ecological level covariates were accurate predictors for the overall prevalence of varicella-associated complications. There was substantial heterogeneity and publication bias across all meta-analyses. CONCLUSION: Results suggest that different types of varicella-associated complications could be frequent, impacting quality of life, and healthcare resource utilisation and budgets. These findings are crucial to raise awareness of the health and economic burden of varicella disease.

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The cost-effectiveness of unilateral magnetic resonance-guided focused ultrasound in comparison with unilateral deep brain stimulation for the treatment of medically refractory essential tremor in England.

OBJECTIVES: This study aims to ascertain the cost-effectiveness of magnetic resonance-guided focused ultrasound (MRgFUS) for the treatment of medically refractory Essential Tremor (mrET) in England. Essential Tremor (ET) is the most common movement disorder affecting approximately 1 million in the UK causing considerable societal impact affecting patients, carers and the wider healthservice. Medical treatment has mixed efficacy, with approximately 25-55% of ET medication refractory. Deep brain stimulation (DBS) is a proven neurosurgical treatment; however, the risks of surgery and anaesthesia mean some patients are ineligible. MRgFUS is an emerging noninvasive technique that causes tremor suppression by thermal ablation of tremor-sensitive brain tissue. Several international clinical trials have demonstrated MRgFUS is safe and clinically effective; however, to-date no cost-effectiveness study has been performed in Europe. METHODS: A Markov model was used to assess two subpopulations of mrET - those eligible and those ineligible for neurosurgery - in the context specific to England and its healthcare system. For those eligible for neurosurgery, MRgFUS was compared to DBS, the current standard treatment. For those ineligible for neurosurgery, MRgFUS was compared to treatment with medication alone. The model calculated the Incremental cost-effectiveness ratio (ICER) with appropriate sensitivity and scenario analyses. RESULTS: For those eligible for neurosurgery: In the model base case, the MRgFUS was economically dominant compared to DBS; MRgFUS was less costly (£19,779 vs £62,348) and more effective generating 0.03 additional quality-adjusted life-years (QALYs) per patient (3.71 vs 3.68) over the 5-year time horizon.For those ineligible for neurosurgery: In the model base case, MRgFUS cost over £16,000 per patient more than medication alone (£19,779 vs £62,348) but yielded 0.77 additional QALYs per patient(3.71 vs 2.95), producing an incremental cost-effectiveness ratio (ICER) of £20,851 per QALY. This ICER of £20,851 per QALY falls within the National Institute for Clinical Excellence's (NICE) willingness to pay threshold (WTP) of 20,000-30,000 demonstrating the cost-effectiveness profile of MRgFUS. CONCLUSION: This study demonstrates the favourable cost-effectiveness profile of MRgFUS for the treatment of mrET in England; in both patients suitable and not suitable for neurosurgery. ADVANCES IN KNOWLEDGE: The introduction of MRgFUS as a widely available ET treatment in UK is currently undergoing the necessary stages of regulatory approval. As the first European study, these favourable cost-effectiveness outcomes (notably the model base case ICER falling within NICE's WTP) can provide a basis for future commissioning of brain MRgFUS treatments in the UK, Europe and globally.

High-throughput barcoding method for the genetic surveillance of insecticide resistance and species identification in Anopheles gambiae complex malaria vectors.

Surveillance of malaria vector species and the monitoring of insecticide resistance are essential to inform malaria control strategies and support the reduction of infections and disease. Genetic barcoding of mosquitoes is a useful tool to assist the high-throughput surveillance of insecticide resistance, discriminate between sibling species and to detect the presence of Plasmodium infections. In this study, we combined multiplex PCR, custom designed dual indexing, and Illumina next generation sequencing for high throughput single nucleotide polymorphism (SNP)-profiling of four species from the Anopheles (An.) gambiae complex (An. gambiae sensu stricto, An. coluzzii, An. arabiensis and An. melas). By amplifying and sequencing only 14 genetic fragments (500 bp each), we were able to simultaneously detect Plasmodium infection; insecticide resistance-conferring SNPs in ace1, gste2, vgsc and rdl genes; the partial sequences of nuclear ribosomal internal transcribed spacers (ITS1 and ITS2) and intergenic spacers (IGS), Short INterspersed Elements (SINE), as well as mitochondrial genes (cox1 and nd4) for species identification and genetic diversity. Using this amplicon sequencing approach with the four selected An. gambiae complex species, we identified a total of 15 non-synonymous mutations in the insecticide target genes, including previously described mutations associated with resistance and two new mutations (F1525L in vgsc and D148E in gste2). Overall, we present a reliable and cost-effective high-throughput panel for surveillance of An. gambiae complex mosquitoes in malaria endemic regions.

Qualitative Validation of COPD Evidenced Care Pathways in Japan, Canada, England, and Germany: Common Barriers to Optimal COPD Care.

Background: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. A comprehensive and detailed understanding of COPD care pathways from pre-diagnosis to acute care is required to understand the common barriers to optimal COPD care across diverse health systems. Methods: Country-specific COPD care pathways were created for four high-income countries using international recommendations and country-specific guidelines, then populated with published epidemiological, clinical, and economic data. To refine and validate the pathways, semi-structured interviews using pre-prepared discussion guides and country-specific pathway maps were held with twenty-four primary and secondary care respiratory healthcare professionals. Thematic analysis was then performed on the interview transcripts. Results: The COPD care pathway showed broad consistency across the countries. Three key themes relating to barriers in optimal COPD management were identified across the countries: journey to diagnosis, treatment, and the impact of COVID-19. Common barriers included presentation to healthcare with advanced COPD, low COPD consideration, and sub-optimal acute and chronic disease management. COVID-19 has negatively impacted disease management across the pathway but presents opportunities to retain virtual consultations. Structural factors such as insurance and short duration of appointments also impacted the diagnosis and management of COPD. Conclusion: COPD is an important public health issue that needs urgent prioritization. The use of Evidenced Care Pathways with decision-makers can facilitate evidence-based decision making on interventions and policies to improve care and outcomes for patients and reduce unnecessary resource use and associated costs for the healthcare provider/payer.

Association of Reduced Long-Lasting Insecticidal Net Efficacy and Pyrethroid Insecticide Resistance With Overexpression of CYP6P4, CYP6P3, and CYP6Z1 in Populations of Anopheles coluzzii From Southeast Côte d'Ivoire.

BACKGROUND: Resistance to major public health insecticides in Côte d'Ivoire has intensified and now threatens the long-term effectiveness of malaria vector control interventions. METHODS: This study evaluated the bioefficacy of conventional and next-generation long-lasting insecticidal nets (LLINs), determined resistance profiles, and characterized molecular and metabolic mechanisms in wild Anopheles coluzzii from Southeast Côte d'Ivoire in 2019. RESULTS: Phenotypic resistance was intense: >25% of mosquitoes survived exposure to 10 times the doses of pyrethroids required to kill susceptible populations. Similarly, the 24-hour mortality rate with deltamethrin-only LLINs was very low and not significantly different from that with an untreated net. Sublethal pyrethroid exposure did not induce significant delayed vector mortality effects 72 hours later. In contrast, LLINs containing the synergist piperonyl butoxide, or new insecticides clothianidin and chlorfenapyr, were highly toxic to A. coluzzii. Pyrethroid-susceptible A. coluzzii were significantly more likely to be infected with malaria, compared with those that survived insecticidal exposure. Pyrethroid resistance was associated with significant overexpression of CYP6P4, CYP6P3, and CYP6Z1. CONCLUSIONS: Study findings raise concerns regarding the operational failure of standard LLINs and support the urgent deployment of vector control interventions incorporating piperonyl butoxide, chlorfenapyr, or clothianidin in areas of high resistance intensity in Côte d'Ivoire.

Overabundance of Asaia and Serratia Bacteria Is Associated with Deltamethrin Insecticide Susceptibility in Anopheles coluzzii from Agboville, Côte d'Ivoire.

Insecticide resistance among mosquito species is now a pervasive phenomenon that threatens to jeopardize global malaria vector control efforts. Evidence of links between the mosquito microbiota and insecticide resistance is emerging, with significant enrichment of insecticide degrading bacteria and enzymes in resistant populations. Using 16S rRNA amplicon sequencing, we characterized and compared the microbiota of Anopheles coluzzii in relation to their deltamethrin resistance and exposure profiles. Comparisons between 2- and 3-day-old deltamethrin-resistant and -susceptible mosquitoes demonstrated significant differences in microbiota diversity. Ochrobactrum, Lysinibacillus, and Stenotrophomonas genera, each of which comprised insecticide-degrading species, were significantly enriched in resistant mosquitoes. Susceptible mosquitoes had a significant reduction in alpha diversity compared to resistant individuals, with Asaia and Serratia dominating microbial profiles. There was no significant difference in deltamethrin-exposed and -unexposed 5- to 6-day-old individuals, suggesting that insecticide exposure had minimal impact on microbial composition. Serratia and Asaia were also dominant in 5- to 6-day-old mosquitoes, which had reduced microbial diversity compared to 2- to 3-day-old mosquitoes. Our findings revealed significant alterations of Anopheles coluzzii microbiota associated with deltamethrin resistance, highlighting the potential for identification of novel microbial markers for insecticide resistance surveillance. qPCR detection of Serratia and Asaia was consistent with 16S rRNA sequencing, suggesting that population-level field screening of bacterial microbiota may be feasibly integrated into wider resistance monitoring, if reliable and reproducible markers associated with phenotype can be identified. IMPORTANCE Control of insecticide-resistant vector populations remains a significant challenge to global malaria control and while substantial progress has been made elucidating key target site mutations, overexpressed detoxification enzymes and alternate gene families, the contribution of the mosquito microbiota to phenotypic insecticide resistance has been largely overlooked. We focused on determining the effects of deltamethrin resistance intensity on Anopheles coluzzii microbiota and identifying any microbial taxa associated with phenotype. We demonstrated a significant reduction in microbial diversity between deltamethrin-resistant and -susceptible mosquitoes. Insecticide degrading bacterial species belonging to Ochrobactrum, Lysinibacillus, and Stenotrophomonas genera were significantly enriched in resistant mosquitoes, while Asaia and Serratia dominated microbial profiles of susceptible individuals. Our results revealed significant alterations of Anopheles coluzzii microbiota associated with deltamethrin resistance, highlighting the potential for identification of novel microbial markers for surveillance and opportunities for designing innovative control techniques to prevent the further evolution and spread of insecticide resistance.