Dengue is a systemic viral infection transmitted between humans by Aedes mosquitoes. For some patients, dengue is a life-threatening illness. There are currently no licensed vaccines or specific therapeutics, and substantial vector control efforts have not stopped its rapid emergence and global spread. The contemporary worldwide distribution of the risk of dengue virus infection and its public health burden are poorly known. Here we undertake an exhaustive assembly of known records of dengue occurrence worldwide, and use a formal modelling framework to map the global distribution of dengue risk. We then pair the resulting risk map with detailed longitudinal information from dengue cohort studies and population surfaces to infer the public health burden of dengue in 2010. We predict dengue to be ubiquitous throughout the tropics, with local spatial variations in risk influenced strongly by rainfall, temperature and the degree of urbanization. Using cartographic approaches, we estimate there to be 390 million (95% credible interval 284-528) dengue infections per year, of which 96 million (67-136) manifest apparently (any level of disease severity). This infection total is more than three times the dengue burden estimate of the World Health Organization. Stratification of our estimates by country allows comparison with national dengue reporting, after taking into account the probability of an apparent infection being formally reported. The most notable differences are discussed. These new risk maps and infection estimates provide novel insights into the global, regional and national public health burden imposed by dengue. We anticipate that they will provide a starting point for a wider discussion about the global impact of this disease and will help to guide improvements in disease control strategies using vaccine, drug and vector control methods, and in their economic evaluation.

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The global distribution and burden of dengue

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(16)00562-6.pdf

Guillain-Barré Syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study

Dengue fever and dengue haemorrhagic fever are important arthropod-borne viral diseases. Each year, there are ∼50 million dengue infections and ∼500,000 individuals are hospitalized with dengue haemorrhagic fever, mainly in Southeast Asia, the Pacific and the Americas. Illness is produced by any of the four dengue virus serotypes. A global strategy aimed at increasing the capacity for surveillance and outbreak response, changing behaviours and reducing the disease burden using integrated vector management in conjunction with early and accurate diagnosis has been advocated. Antiviral drugs and vaccines that are currently under development could also make an important contribution to dengue control in the future.

Dengue: a continuing global threat

Statistical Analysis With Missing Data (2nd ed.) (Book)

Background: Dengue is a growing problem both in its geographical spread and in its intensity, and yet current global distribution remains highly uncertain. Challenges in diagnosis and diagnostic methods as well as highly variable national health systems mean no single data source can reliably estimate the distribution of this disease. As such, there is a lack of agreement on national dengue status among international health organisations. Here we bring together all available information on dengue occurrence using a novel approach to produce an evidence consensus map of the disease range that highlights nations with an uncertain dengue status. Methods/Principal Findings: A baseline methodology was used to assess a range of evidence for each country. In regions where dengue status was uncertain, additional evidence types were included to either clarify dengue status or confirm that it is unknown at this time. An algorithm was developed that assesses evidence quality and consistency, giving each country an evidence consensus score. Using this approach, we were able to generate a contemporary global map of national-level dengue status that assigns a relative measure of certainty and identifies gaps in the available evidence. Conclusion: The map produced here provides a list of 128 countries for which there is good evidence of dengue occurrence, including 36 countries that have previously been classified as dengue-free by the World Health Organization and/or the US Centers for Disease Control. It also identifies disease surveillance needs, which we list in full. The disease extents and limits determined here using evidence consensus, marks the beginning of a five-year study to advance the mapping of dengue virus transmission and disease risk. Completion of this first step has allowed us to produce a preliminary estimate of population at risk with an upper bound of 3.97 billion people. This figure will be refined in future work.

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Refining the global spatial limits of dengue virus transmission by evidence-based consensus

Abstract Purpose Despite being vaccine-preventable, tick-borne encephalitis (TBE) continues to cause considerable morbidity in Germany. Limited insight into potentially debilitating consequences of TBE may partially underly low (~ 20%) TBE vaccine uptake. We aimed to systematically assess TBE sequelae and other consequences. Methods Routinely notified TBE patients from 2018 to 2020 from Southern Germany were invited to telephone interviews acutely and again after 18 months. Duration of acute symptoms was prospectively assessed. Recovery was defined as score 0 on the modified RANKIN scale. Determinants of time to recovery were analysed with cox regression, adjusted for covariates identified using directed acyclic graphs, yielding hazard ratios (HR) and 95% confidence intervals (CI). Results Of 558 cases, 523 (93.7%) completed follow-up. Full recovery was reported by 67.3% (children: 94.9%, adults: 63.8%). Sequelae included fatigue (17.0%), weakness (13.4%), concentration deficit (13.0%), and impaired balance (12.0%). Compared with 18–39-year-olds, recovery rates were 44% lower in ≥ 50-year-olds (HR: 0.56, 95%CI 0.42–0.75) and 79% higher in children (HR: 1.79, 95%CI 1.25–2.56). The recovery rate was 64% lower after severe TBE (compared to mild; HR: 0.36, 95%CI 0.25–0.52) and 22% lower with comorbidities (HR: 0.78, 95%CI 0.62–0.99). Substantial health-care use was reported (90.1% hospitalisation, 39.8% rehabilitation). Of employed cases, 88.4% required sick leave; 10.3% planned/reported premature retirement due to sequelae. Conclusion Half the adult and 5% of paediatric patients reported persisting sequelae after 18 months. Improved prevention could alleviate both individual (morbidity) and societal TBE burden (health-care costs, productivity losses). Insights into sequelae can help guide at-risk populations towards tick-avoidant strategies and encourage TBE vaccination. 

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Recovery and sequelae in 523 adults and children with tick-borne encephalitis in Germany

Abstract Background Control of the 2019 coronavirus disease (COVID-19) pandemic in Germany and return to pre-pandemic behaviour can only be achieved through natural or vaccine-induced immunity. Sufficient vaccine capacity promotes interest in the necessary and feasible target vaccination coverage. Methods An age and risk group stratified SEIR transmission model was used to assess the impact of vaccination coverage ranging 65%-95% for 12-59-year-olds and 90%-95% for ≥ 60-year-olds on COVID-19 incidence and intensive care unit (ICU) utilization between 01.07.2021-31.03.2022. Separate implementation of licensed vaccines allows to consider different efficacies, delivery rates and age-specific national vaccination recommendations. The analysis was conducted under different assumptions about contact behaviour during summer, reduction of daily contacts with increasing number of cases, daily vaccination uptake and the dominant variant. Data from the COVIMO study (N = 3004, data collection: 17.05.-09.06.2021) were used to define the population percentage willing to be vaccinated. Results The COVIMO study indicates an achievable vaccination compliance rate of 83.9% among 12-59-year-olds and 94.8% among those ≥ 60-year-olds. Maximum incidence or ICU utilization during observation period decreases from 385 to 61 and 6220 to 2800, respectively, with an increase in vaccination coverage from 65% to 95% of 12-59-year-olds, 90% vaccination rate among ≥ 60-year-olds, compared to pre-pandemic reduced contact behaviour in summer and reduction of contacts as case numbers increase. Conclusions The vaccination campaign should be continued at high intensity until at least 85% of 12-59-year-olds or 90% of ≥ 60-year-olds are fully vaccinated against COVID-19. Based on the population's willingness to be vaccinated, this goal seemed feasible. Key messages • Mathematical modeling was used to determine an evidence-based target vaccination coverage of ≥ 85%. • Expertise in modeling should be further strengthened.

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A dynamic transmission model to calculate vaccination coverage needed to control COVID-19 in Germany

Abstract Issue/problem NITAGs are independent expert advisory committees that provide evidence-based recommendations to the Ministry of Health to guide the introduction of new vaccines and formulate national immunization plans. Description of the problem The evaluation of vaccines has become more and more complex. This is not only because the number of vaccines on the market and the diseases they target has increased, but also because a much wider range of population subgroups can be targeted, and for some diseases several vaccines are available and need to be compared. In addition, vaccines not only have an impact on individual well-being, but can also induce population-level effects and broader socioeconomic value. Results NITAGs consider to a large extent similar key factors in their evaluation processes. These can be divided into context-free and context-specific aspects. Context-free aspects include effectiveness and safety. Local disease epidemiology, potential vaccine impact at population-level, cost-effectiveness and societal or cultural values and preferences are context-specific aspects. Collaboration is possible when jointly assessing the evidence related to context-free aspects, since this is usually easily transferrable across countries. In 2019, a network of NITAGs in the European Union and Economic Area countries was established under the coordination of the European Centre for Disease Prevention and Control. Within this network, working groups have been established and either performed themselves or supported external contractors in conducting systematic reviews on vaccines effectiveness and safety. Lessons The increasing workload of NITAGs and the prospect of joint clinical assessments draw the attention to a number of practical issues to be solved, e.g., consensus on methodological guidelines for systematic reviews, processes to ensure that the products meet NITAGs expectations (content, quality, timing), and approaches how to consider unpublished data.

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Needs for a thorough Joint Clinical Assessment of vaccines within the HTAR: perspectives of NITAGs

Background: Patients with diabetes are at increased risk of severe influenza disease; influenza vaccination for these patients is therefore recommended by the World Health Organization and several National Immunization Technical Advisory Groups. However, no systematic review has evaluated the effects of influenza vaccines for patients with diabetes. Methods: We conducted a systematic review and meta-analysis by searching Medline, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from inception until November 2014. We included all types of studies reporting on the efficacy, effectiveness, and/or safety of influenza vaccination in patients with type 1 and type 2 diabetes of all ages. We used the Newcastle-Ottawa scale to assess risk of bias in observational studies. Residual confounding was addressed by comparing estimates of vaccine effectiveness (VE) during influenza seasons to those obtained during off-seasons. Quality of the evidence for each outcome was assessed using the GRADE methodology. Results: Following review of 1,444 articles, 11 observational studies with a total of 170,924 participants were included. In diabetic patients of working-age (18–64 years), influenza vaccination prevented all-cause hospitalization with a pooled VE of 58% (95% CI, 6–81%) and hospitalization due to influenza or pneumonia (VE 43%; 95% CI, 28–54%), whereas no effects on all-cause mortality and influenza-like illness (ILI) were observed. In the elderly (65+), influenza vaccination prevented all-cause mortality (VE 38%; 95% CI, 32–43%), all-cause hospitalization (VE 23%; 95% CI, 1–40%), hospitalization due to influenza or pneumonia (VE 45%; 95% CI, 34–53%), and ILI (VE 13%; 95% CI, 10–16%). However, significant off-season estimates for several outcomes indicated residual confounding, particularly in elderly patients. Quality of the evidence was low to very low for all outcomes. Laboratory-confirmed influenza infections were not reported. Conclusions: Due to strong residual confounding in most of the identified studies, the available evidence is insufficient to determine the magnitude of benefit that diabetic people derive from seasonal influenza vaccination. Adequately powered randomized controlled trials or quasi-experimental studies using laboratory-confirmed influenza-specific outcomes are urgently needed.

Vaccines for the prevention of seasonal influenza in patients with diabetes: systematic review and

https://doi.org/10.1016/j.vaccine.2023.02.027

Ole Wichmann

Papers

Recovery and sequelae in 523 adults and children with tick-borne encephalitis in Germany

A dynamic transmission model to calculate vaccination coverage needed to control COVID-19 in Germany

Needs for a thorough Joint Clinical Assessment of vaccines within the HTAR: perspectives of NITAGs

Vaccines for the prevention of seasonal influenza in patients with diabetes: systematic review and

Use of existing systematic reviews for the development of evidence-based vaccination recommendations: Guidance from the SYSVAC expert panel