Assessing dengue risk globally using non-Markovian models.

Dengue is a vector-borne disease transmitted by Aedes mosquitoes. The worldwide spread of these mosquitoes and the increasing disease burden have emphasized the need for a spatio-temporal risk map capable of assessing dengue outbreak conditions and quantifying the outbreak risk. Given that the life cycle of Aedes mosquitoes is strongly influenced by habitat temperature, numerous studies have utilized temperature-dependent development rates of these mosquitoes to construct virus transmission and outbreak risk models. In this study, we contribute to existing research by developing a mechanistic model for the mosquito life cycle that accurately captures its non-Markovian nature. Beginning with integral equations to track the mosquito population across different life cycle stages, we demonstrate how to derive the corresponding differential equations using phase-type distributions. This approach can be further applied to similar non-Markovian processes that are currently described with less accurate Markovian models. By fitting the model to data on human dengue cases, we estimate several model parameters, allowing the development of a global spatiotemporal dengue risk map. This risk model employs temperature and precipitation data to assess the environmental suitability for dengue outbreaks in a given area.

The epidemiologic and economic burden of dengue in Singapore: A systematic review.

BACKGROUND: Despite its well-regarded vector control program, Singapore remains susceptible to dengue epidemics. To assist evaluation of dengue interventions, we aimed to synthesize current data on the epidemiologic and economic burden of dengue in Singapore. METHODOLOGY: We used multiple databases (PubMed, Embase, Cochrane, international/national repositories, surveillance) to search for published and gray literature (2000-2022). We included observational and cost studies, and two interventional studies, reporting Singapore-specific data on our co-primary outcomes, dengue incidence and dengue-related costs. Quality was assessed using the Newcastle-Ottawa Scale and an adapted cost-of-illness evaluation checklist. We performed a narrative synthesis and grouped studies according to reported outcomes and available stratified analyses. FINDINGS: In total, 333 reports (330 epidemiological, 3 economic) were included. Most published epidemiological studies (89%) and all economic studies were of good quality. All gray literature reports were from the Ministry of Health or National Environment Agency. Based predominantly on surveillance data, Singapore experienced multiple outbreaks in 2000-2021, attaining peak incidence rate in 2020 (621.1 cases/100,000 person-years). Stratified analyses revealed the highest incidence rates in DENV-2 and DENV-3 serotypes and the 15-44 age group. Among dengue cases, the risk of hospitalization has been highest in the ≥45-year-old age groups while the risks of dengue hemorrhagic fever and death have generally been low (both <1%) for the last decade. Our search yielded limited data on deaths by age, severity, and infection type (primary, secondary, post-secondary). Seroprevalence (dengue immunoglobulin G) increases with age but has remained <50% in the general population. Comprising 21-63% indirect costs, dengue-related total costs were higher in 2010-2020 (SGD 148 million) versus the preceding decade (SGD 58-110 million). CONCLUSION: Despite abundant passive surveillance data, more stratified and up-to-date data on the epidemiologic and economic burden of dengue are warranted in Singapore to continuously assess prevention and management strategies.

The macroeconomic impact of a dengue outbreak: Case studies from Thailand and Brazil.

BACKGROUND: Dengue is spreading in (sub)tropical areas, and half of the global population is at risk. The macroeconomic impact of dengue extends beyond healthcare costs. This study evaluated the impact of dengue on gross domestic product (GDP) based on approaches tailored to two dengue-endemic countries, Thailand and Brazil, from the tourism and workforce perspectives, respectively. FINDINGS: Because the tourism industry is a critical economic sector for Thailand, lost tourism revenues were estimated to analyze the impact of a dengue outbreak. An input-output model estimated that the direct effects (on international tourism) and indirect effects (on suppliers) of dengue on tourism reduced overall GDP by 1.43 billion US dollars (USD) (0.26%) in the outbreak year 2019. The induced effect (reduced employee income/spending) reduced Thailand's GDP by 375 million USD (0.07%). Overall, lost tourism revenues reduced Thailand's GDP by an estimated 1.81 billion USD (0.33%) in 2019 (3% of annual tourism revenue). An inoperability input-output model was used to analyze the effect of workforce absenteeism on GDP due to a dengue outbreak in Brazil. This model calculates the number of lost workdays associated with ambulatory and hospitalized dengue. Input was collected from state-level epidemiological and economic data for 2019. An estimated 22.4 million workdays were lost in the employed population; 39% associated with the informal sector. Lost workdays due to dengue reduced Brazil's GDP by 876 million USD (0.05%). CONCLUSIONS: The economic costs of dengue outbreaks far surpass the direct medical costs. Dengue reduces overall GDP and inflicts national economic losses. With a high proportion of the population lacking formal employment in both countries and low income being a barrier to seeking care, dengue also poses an equity challenge. A combination of public health measures, like vector control and vaccination, against dengue is recommended to mitigate the broader economic impact of dengue.

Development and assessment of a multiepitope synthetic antigen for the diagnosis of Dengue virus infection.

Immunodiagnostic tests for detecting dengue virus infections encounter challenges related to cross-reactivity with other related flaviviruses. Our research focuses on the development of a synthetic multiepitope antigen tailored for dengue immunodiagnostics. Selected dengue epitopes involved structural linearity and dissimilarity from the proteomes of Zika and Yellow fever viruses which served for computationally modeling the three-dimensional protein structure, resulting in the design of two proteins: rDME-C and rDME-BR. Both proteins consist of seven epitopes, separated by the GPGPG linker, and a carboxy-terminal 6 × -histidine tag. The molecular weights of the final proteins rDME-C and rDME-BR are 16.83 kDa and 16.80 kDa, respectively, both with an isoelectric point of 6.35. The distinguishing factor between the two proteins lies in the origin of their epitope sequences, where rDME-C is based on the reference dengue proteome, while rDME-BR utilizes sequences from prevalent Dengue genotypes in Brazil from 2008 to 2019. PyMol analysis revealed exposure of epitopes in the secondary structure. Successful expression of the antigens was achieved in soluble form and fluorescence experiments indicated a disordered structure. In subsequent testing, rDME-BR and rDME-C antigens were assessed using an indirect Elisa protocol against Dengue infected serum, previously examined with a commercial diagnostic test. Optimal concentrations for antigens were determined at 10 µg/mL for rDME-BR and 30 µg/mL for rDME-C, with serum dilutions ranging from 1:50 to 1:100. Both antigens effectively detected IgM and IgG antibodies in Dengue fever patients, with rDME-BR exhibiting higher sensitivity. Our in-house test showed a sensitivity of 77.3 % and 82.6 % and a specificity of 89.4 % and 71.4 % for rDME-C and rDEM-BR antigens. No cross-reactivity was observed with serum from Zika-infected mice but with COVID-19 serum samples. Our findings underscore the utility of synthetic biology in crafting Dengue-specific multiepitope proteins and hold promise for precise clinical diagnosis and monitoring responses to emerging Dengue vaccines.

Cost of controlling the dengue vector Aedes aegypti in the Peruvian amazon. / Costo del control de Aedes aegypti en la Amazonía peruana.

OBJECTIVE.: Motivation for the study. Dengue prevention and control is based on the control of its vector. This study was conducted because of the need to know the costs associated with Aedes aegypti control in a region that carries out planned vector control activities. Main findings. The costs incurred in dengue vector control in the Loreto region in 2017 and 2018 amounted to PEN 4,066,380.25 and PEN 3,807,858.73, respectively. Implications. Knowing the cost of vector control activities will allow us to better plan these activities and have a basis for cost-effectiveness studies with other methods of prevention and control of dengue. To estimate the costs incurred in the control of Aedes aegypti in the Loreto region, during the years 2017 and 2018. MATERIALS AND METHODS.: We conducted a partial retrospective economic evaluation of the costs of Aedes aegypti control of the Regional Health Directorate Loreto, during the implementation of the Regional Plan for Surveillance and Control of Aedes aegypti. Documentation such as plans, intervention reports and payment slips were reviewed, and interviews were conducted with professional personnel involved in vector control, on the costs of control interventions. RESULTS.: We found that the costs incurred in dengue vector control in the Loreto Region in the two years were: PEN 3,807,858 and PEN 4,066,380 during 2017 and 2018, respectively (USD 1,175,264 and USD 1,1210,232 at the 2017 and 2018 exchange rate). However, the effect of control activities is short-lived. CONCLUSIONS.: The high cost involved in vector control with the methods currently used and the short duration of its effect make it unsustainable. Studies should be conducted in order to find other more efficient methods for dengue control.

OBJETIVO.: Motivación para realizar el estudio. La prevención y control del dengue se basa en el control de su vector. Este estudio se realizó por la necesidad de conocer los costos asociados al control Aedes aegypti en una región que realiza actividades planificadas de control vectorial. Principales hallazgos. Los costos incurridos en el control del vector del dengue en la región Loreto en los años 2017 y 2018, ascienden a 4,066,380.25 y 3,807,858.73 PEN, respectivamente. Implicancias. Conocer el costo de las actividades de control vectorial nos permitirá planificar mejor estas actividades y tener una base para estudios de costo efectividad con otros métodos de prevención y control del dengue. Estimar los costos incurridos en el control del Aedes aegypti en la región Loreto, en los años 2017 y 2018. MATERIALES Y MÉTODOS.: Se realizó una evaluación económica retrospectiva parcial de los costos del control del Aedes aegypti de la Dirección Regional de Salud Loreto, durante la ejecución del Plan Regional de Vigilancia y Control de Aedes aegypti. Se revisó documentación como planes, informes de intervenciones y planillas de pago y se realizaron entrevistas al personal profesional implicado en el control vectorial, sobre los costos de las intervenciones de control. RESULTADOS.: Se halló, que los costos incurridos en el control del vector del dengue en la Región Loreto en los dos años estudiados ascienden a: 3,807,858 PEN y 4,066,380 PEN durante el 2017 y 2018, respectivamente (1´175,264 USD y 1´1210,232 USD al tipo de cambio del 2017 y 2018). Sin embargo, el efecto de las actividades de control es de corta duración. CONCLUSIONES.: El alto costo que implica el control vectorial con los métodos usados actualmente y la corta duración de su efecto lo hace insostenible. Se deben realizar estudios para hallar otros métodos más eficientes para el control del dengue.

Discrepancies in dengue burden estimates: a comparative analysis of reported cases and global burden of disease study, 2010-2019.

BACKGROUND: Dengue is a significant mosquito-borne disease. Several studies have utilized estimates from the Global Burden of Disease (GBD) study to assess the global, regional or national burden of dengue over time. However, our recent investigation suggests that GBD's estimates for dengue cases in Taiwan are unrealistically high. The current study extends the scope to compare reported dengue cases with GBD estimates across 30 high-burden countries and territories, aiming to assess the accuracy and interpretability of the GBD's dengue estimates. METHODS: Data for this study were sourced from the GBD 2019 study and various national and international databases documenting reported dengue cases. The analysis targeted the top 30 countries and territories with the highest 10-year average of reported cases from 2010 to 2019. Discrepancies were quantified by computing absolute differences and ratios between the 10-year average of reported cases and GBD estimates. Coefficients of variation (CV) and estimated annual percentage changes (EAPCs) were calculated to assess variations and trends in the two data sources. RESULTS: Significant discrepancies were noted between reported data and GBD estimates in the number of dengue cases, incidence rates, and EAPCs. GBD estimates were substantially higher than reported cases for many entities, with the most notable differences found in China (570.0-fold), India (303.0-fold), Bangladesh (115.4-fold), Taiwan (85.5-fold) and Indonesia (23.2-fold). Furthermore, the GBD's estimates did not accurately reflect the extensive yearly fluctuations in dengue outbreaks, particularly in non-endemic regions such as Taiwan, China and Argentina, as evidenced by high CVs. CONCLUSIONS: This study reveals substantial discrepancies between GBD estimates and reported dengue cases, underscoring the imperative for comprehensive analysis in areas with pronounced disparities. The failure of GBD estimates to represent the considerable annual fluctuations in dengue outbreaks highlights the critical need for improvement in disease burden estimation methodologies for dengue.

The rising global economic costs of invasive Aedes mosquitoes and Aedes-borne diseases.

Invasive Aedes aegypti and Aedes albopictus mosquitoes transmit viruses such as dengue, chikungunya and Zika, posing a huge public health burden as well as having a less well understood economic impact. We present a comprehensive, global-scale synthesis of studies reporting these economic costs, spanning 166 countries and territories over 45 years. The minimum cumulative reported cost estimate expressed in 2022 US$ was 94.7 billion, although this figure reflects considerable underreporting and underestimation. The analysis suggests a 14-fold increase in costs, with an average annual expenditure of US$ 3.1 billion, and a maximum of US$ 20.3 billion in 2013. Damage and losses were an order of magnitude higher than investment in management, with only a modest portion allocated to prevention. Effective control measures are urgently needed to safeguard global health and well-being, and to reduce the economic burden on human societies. This study fills a critical gap by addressing the increasing economic costs of Aedes and Aedes-borne diseases and offers insights to inform evidence-based policy.

Dengue hospitalizations and in-hospital mortality changes in trend in Ecuador: a nationwide study from 2015 to 2022.

OBJECTIVE: This study aimed to analyze dengue hospitalizations and in-hospital mortality trends in Ecuador, along with sociodemographic factors influencing adverse outcomes. METHODS: This study included 31,616 dengue hospitalizations in Ecuador during 2015-2022, of which 115 (0.36%) died. Data were extracted from national hospital registries. Age adjusted rates were calculated, and for the analysis of changes in trend, a Joinpoint regression was performed. Multivariate binary and multinomial logistic regressions were performed for assessing sociodemographic factors influencing dengue adverse outcomes. RESULTS: During 2015-2022, the mean age adjusted dengue hospitalization rate was 22.3 per 100,000 inhabitants with 49.41% annual decrease during 2015-2017 and 31.73% annual increase during 2017-2022 with higher rates in 2020 with 31.61, 2021 with 34.42, and 2022 with 25.81. The mean dengue in-hospital mortality rate was 0.08, mortality rates did not show significant changes during 2015-2022. Higher probability of death was observed in ages ≥50 years and ethnic minorities. People living in rural areas exhibited a 64% higher risk for complicated dengue hospitalization. CONCLUSIONS: It was observed as an important accomplishment in Ecuador's ongoing efforts to improve healthcare regarding dengue. 0.36% of dengue hospitalizations ended in death which is below the recommended 1%. The increase in dengue hospitalizations in Ecuador during recent years remains a concern. The COVID-19 pandemic might have influenced dengue prevention and vector control to be neglected leading to an increase in cases.

Assessment of larval and pupal indices of dengue mosquito vectors in a North-Eastern state of Tripura, India.

BACKGROUND OBJECTIVES: Dengue is a major vector-borne disease having public health importance. It is caused by Dengue Virus (DENV) and is transmitted by mosquitoes of Aedes species. With the unavailability of a vaccine, vector control remains the only preventive measure for dengue. Studies have already been conducted to establish the presence of dengue vectors in the north-eastern states of India. However, limited studies have been conducted in Tripura state. In the present study we aimed to identify the preferred breeding habitats of dengue vectors in the state. METHODS: Clinical case data of dengue since the last five years was studied and the areas with the highest case numbers were identified. Entomological investigation was carried out in areas reporting the highest number of cases. Larvae were collected from the breeding habitats using standard protocol followed by morphological and molecular identification. Further, House index (HI), Container index (CI) and Pupal index (PI) were determined. The positive pools were then processed for incrimination for the presence of dengue virus. Calculation of entomological indices was done. RESULTS: Of the total 815 containers searched, 36.80% containers were positive for mosquito larvae. Among the immature mosquito collection, 836 adults emerged and were identified as Aedes albopictus using standard taxonomic keys followed by molecular methods. HI, CI and PI, varied from 15.38% to 100%, 21% to 31.04 %, and 2.93% to 110.53% respectively. However, none of the pools was positive for dengue virus. INTERPRETATION CONCLUSION: The present study identified Ae. albopictus as a potential vector of dengue in Tripura. The study gave important insights on the preferred larval habitats and provides information on the indication of displacement of Ae. albopictus from rural to urban and semi-urban areas. However, longitudinal studies for longer time frame are necessary for any conclusive remarks.

Economic optimization of Wolbachia-infected Aedes aegypti release to prevent dengue.

BACKGROUND: Dengue virus, primarily transmitted by the Aedes aegypti mosquito, is a major public health concern affecting ≈3.83 billion people worldwide. Recent releases of Wolbachia-transinfected Ae. aegypti in several cities worldwide have shown that it can reduce dengue transmission. However, these releases are costly, and, to date, no framework has been proposed for determining economically optimal release strategies that account for both costs associated with disease risk and releases. RESULTS: We present a flexible stochastic dynamic programming framework for determining optimal release schedules for Wolbachia-transinfected mosquitoes that balances the cost of dengue infection with the costs of rearing and releasing transinfected mosquitoes. Using an ordinary differential equation model of Wolbachia and dengue in a hypothetical city loosely describing areas at risk of new dengue epidemics, we determined that an all-or-nothing release strategy that quickly brings Wolbachia to fixation is often the optimal solution. Based on this, we examined the optimal facility size, finding that it was inelastic with respect to the mosquito population size, with a 100% increase in population size resulting in a 50-67% increase in optimal facility size. Furthermore, we found that these results are robust to mosquito life-history parameters and are mostly determined by the mosquito population size and the fitness costs associated with Wolbachia. CONCLUSIONS: These results reinforce that Wolbachia-transinfected mosquitoes can reduce the cost of dengue epidemics. Furthermore, they emphasize the importance of determining the size of the target population and fitness costs associated with Wolbachia before releases occur. © 2024 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Global Patterns of Trends in Incidence and Mortality of Dengue, 1990-2019: An Analysis Based on the Global Burden of Disease Study.

Background and Objectives: Dengue is an important public health concern that warrants an examination of the longer-term global trends of its disease burden. The aim of this study was to assess the trends in dengue incidence and mortality worldwide over the last three decades. Materials and Methods: A descriptive epidemiological study was carried out, investigating the trends in the incidence and mortality of dengue from 1990 to 2019. The dengue incidence and mortality data were obtained from the Global Burden of Disease study database. Trends were examined using joinpoint regression analysis. Results: Globally, there were 56.7 million new cases of dengue reported in 2019: the disease was diagnosed in 27.4 million males and 29.3 million females. A total of 36,055 (18,993 males and 17,032 females) related deaths were reported worldwide in 2019. In both sexes, about 60% of new cases were recorded in the South-East Asia region (16.3 million in males and 17.4 million in females). Globally, the incidence of dengue exhibited an increasing tendency from 1990 to 2019 in both sexes (equally, by 1.2% per year). A significantly decreasing trend in the mortality of dengue was recorded only in females (by -0.5% per year), while an increasing trend was observed in males (by +0.6% per year). Conclusions: The rise in the number of new dengue cases and deaths in the world in the last several decades suggests a need for implementing more effective prevention and management measures.

Assessment of perceived dengue risk and prevention practices among youth in Bangladesh.

Dengue fever is a global public health concern, especially in countries like Bangladesh. This study examines youth perceived dengue risk, and preventive practices, providing valuable insights into their behavior regarding this mosquito-borne disease. A cross-sectional survey was undertaken in various regions of the Dhaka district in Bangladesh. Face-to-face interviews were conducted with 1,358 participants using convenience sampling, spanning the period from September 2 to October 10, 2023. A semi-structured questionnaire covered informed consent, socio-demographic data, and questions about perceived dengue risk scale (12 items), and prevention practice (13 items). Participants' mean age was 22.02 ± 1.58 years. The average scores for perceived dengue risk, and prevention practices were found to be 51.39 ± 12.01 (out of 96), and 55.57 ± 14.55 (out of 104) respectively. Previous dengue history, history of other vector-borne diseases, gender, educational level, father's educational qualification, employment status, adequate sleep duration, father's occupation, etc. are factors associated with higher risk and prevention practices regarding dengue. The research underscores the importance of tailoring prevention strategies for different demographics, raising awareness, and promoting active engagement in preventive measures. These insights are crucial for developing effective public health policies and campaigns to combat dengue.

Eastern Mediterranean Health Journal [2024; Vol.30, Issue 1] / [المجلة الصحية لشرق المتوسط [2024; المجلد 30 , العدد 1

Eastern Mediterranean Health Journal is the official health journal published by the Eastern Mediterranean Regional Office of the World Health Organization. It is a forum for the presentation and promotion of new policies and initiatives in health services; and for the exchange of ideas concepts epidemiological data research findings and other information with special reference to the Eastern Mediterranean Region. It addresses all members of the health profession medical and other health educational institutes interested NGOs WHO Collaborating Centres and individuals within and outside the Region.

المجلة الصحية لشرق المتوسط هى المجلة الرسمية التى تصدرعن المكتب الاقليمى لشرق المتوسط بمنظمة الصحة العالمية. وهى منبر لتقديم السياسات والمبادرات الجديدة فى الصحة العامة والخدمات الصحية والترويج لها، و لتبادل الاراء و المفاهيم والمعطيات الوبائية ونتائج الابحاث وغير ذلك من المعلومات، و خاصة ما يتعلق منها باقليم شرق المتوسط. وهى موجهة الى كل اعضاء المهن الصحية، والكليات الطبية وسائر المعاهد التعليمية، و كذا المنظمات غير الحكومية المعنية، والمراكز المتعاونة مع منظمة الصحة العالمية والافراد المهتمين بالصحة فى الاقليم و خارجه

La Revue de Santé de la Méditerranée Orientale est une revue de santé officielle publiée par le Bureau régional de l’Organisation mondiale de la Santé pour la Méditerranée orientale. Elle offre une tribune pour la présentation et la promotion de nouvelles politiques et initiatives dans le domaine de la santé publique et des services de santé ainsi qu’à l’échange d’idées de concepts de données épidémiologiques de résultats de recherches et d’autres informations se rapportant plus particulièrement à la Région de la Méditerranée orientale. Elle s’adresse à tous les professionnels de la santé aux membres des instituts médicaux et autres instituts de formation médico-sanitaire aux ONG Centres collaborateurs de l’OMS et personnes concernés au sein et hors de la Région.

Rapid diagnostic tests for dengue would reduce hospitalizations, healthcare costs and antibiotic prescriptions in Spain: A cost-effectiveness analysis.

BACKGROUND: Current gold standard diagnostic techniques for dengue are expensive and time-consuming. Rapid diagnostic tests (RDTs) have been proposed as alternatives, although data about their potential impact in non-endemic areas is scarce. METHODS: We performed a cost-effectiveness analysis comparing the costs of dengue RDTs to the current standard of care for the management of febrile returning travelers in Spain. Effectiveness was measured in terms of potential averted hospital admissions and reduction of empirical antibiotics, based on 2015-2020 dengue admissions at Hospital Clinic Barcelona (Spain). RESULTS: Dengue RDTs were associated with 53.6% (95% CI: 33.9-72.5) reduction of hospital admissions and were estimated to save 289.08-389.31€ per traveler tested. Moreover, RDTs would have avoided the use of antibiotics in 46.4% (95% CI: 27.5-66.1) of dengue patients. DISCUSSION: Implementation of dengue RDTs for the management of febrile travelers is a cost-saving strategy that would lead to a reduction of half of dengue admissions and a reduction of inappropriate antibiotics in Spain.