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.

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.

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.

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.

Economic burden of dengue in urban Bangladesh: A societal perspective.

BACKGROUND: Dengue, a vector-borne disease, is a major public health problem in many tropical and subtropical countries including Bangladesh. The objective of this study is to estimate the societal cost of illness of dengue infections among the urban population in Dhaka, Bangladesh. METHODS: A cost-of-illness study was conducted using a prevalence-based approach from a societal perspective. Costs attributable to dengue were estimated from a bottom-up strategy using the guideline proposed by the World Health Organization for estimating the economic burden of infectious diseases. RESULTS: A total of 302 hospitalized confirmed dengue patients were enrolled in this study. The average cost to society for a person with a dengue episode was US$ 479.02. This amount was ranged between US$ 341.67 and US$ 567.12 for those patients who were treated at public and private hospitals, respectively. The households out-of-pocket cost contributed to a larger portion of the total costs of illness (66%) while the cost burden was significantly higher for the poorest households than the richest quintile. CONCLUSIONS: Dengue disease imposes a substantial financial burden on households and society. Therefore, decision-makers should consider the treatment cost of dengue infections, particularly among the poor in the population while balancing the benefits of introducing potentially effective dengue preventive programs in Bangladesh.

Burden of dengue, leishmaniasis and lymphatic filariasis in India and its states from 1990-2019: Analysis from the Global Burden of Disease study (GBD 2019).

Vector-borne diseases such as dengue, leishmaniasis, and lymphatic filariasis, constitute significant sources of illness, disability, and mortality among the poor and vulnerable in many countries around the world, including India. Based on the global burden of diseases, injuries, and risk factors study 2019, we analyse the burden of dengue, leishmaniasis, and lymphatic filariasis, in India from 1990 to 2019. Over this period, there was a reduction in the burden of lymphatic filariasis and leishmaniasis. Notably, dengue emerged as the most common vector-borne disease, exhibiting high fatality rate above 15 years of age and the highest DALY within 15-49 age group. Additionally, dengue cases surged substantially between 1990 and 2019. Leishmaniasis related mortality and DALY declined in the year 2019 compared to the year 1990, with high mortality and DALY in the 0-49-year-old age group. For lymphatic filariasis, DALY was more pronounce among those in the 15-49-year age group, which underwent reduction in 2019. Males had a higher burden in other vector-borne diseases than females, although females had a slightly elevated dengue burden. These findings highlight the evolving epidemiological trends related to vector-borne diseases in India, over the last three decades and underline the critical significance of sustained efforts for the elimination and control of vector-borne diseases.

Enhancing Community Participation in Dengue Control Through Digital Crowdsourcing: An Analysis of a World Mosquito Program Digital Open Call in Sri Lanka.

BACKGROUND: Two crowdsourcing open calls were created to enhance community engagement in dengue control in Sri Lanka. We analyzed the process and outcomes of these digital crowdsourcing open calls. METHODS: We used standard World Health Organization methods to organize the open calls, which used exclusively digital methods because of coronavirus disease 2019 (COVID-19). We collected and analyzed sociodemographic information and digital engagement metrics from each submission. Submissions in the form of textual data describing community-led strategies for mosquito release were coded using grounded theory. RESULTS: The open calls received 73 submissions. Most people who submitted ideas spoke English, lived in Sri Lanka, and were 18 to 34 years old. The total Facebook reach was initially limited (16 161 impressions), prompting expansion to a global campaign, which reached 346 810 impressions over 14 days. Diverse strategies for the distribution of Wolbachia-infected mosquito boxes were identified, including leveraging traditional festivals, schools, and community networks. Fifteen submissions (21%) suggested the use of digital tools for monitoring and evaluation, sharing instructions, or creating networks. Thirteen submissions (18%) focused on social and economic incentives to prompt community engagement and catalyze community-led distribution. CONCLUSIONS: Our project demonstrates that digital crowdsourcing open calls are an effective way to solicit creative and innovative ideas in a resource-limited setting.

Socio-economic factors and its influence on the association between temperature and dengue incidence in 61 Provinces of the Philippines, 2010-2019.

BACKGROUND: Temperature has a significant impact on dengue incidence, however, changes on the temperature-dengue relationship across axes of socio-economic vulnerability is not well described. This study sought to determine the association between dengue and temperature in multiple locations in the Philippines and explore the effect modification by socio-economic factors. METHOD: Nationwide dengue cases per province from 2010 to 2019 and data on temperature were obtained from the Philippines' Department of Health-Epidemiological Bureau and ERA5-land, respectively. A generalized additive mixed model (GAMM) with a distributed lag non-linear model was utilized to examine the association between temperature and dengue incidence. We further implemented an interaction analysis in determining how socio-economic factors modify the association. All analyses were implemented using R programming. RESULTS: Nationwide temperature-dengue risk function was noted to depict an inverted U-shaped pattern. Dengue risk increased linearly alongside increasing mean temperature from 15.8 degrees Celsius and peaking at 27.5 degrees Celsius before declining. However, province-specific analyses revealed significant heterogeneity. Socio-economic factors had varying impact on the temperature-dengue association. Provinces with high population density, less people in urban areas with larger household size, high poverty incidence, higher health spending per capita, and in lower latitudes were noted to exhibit statistically higher dengue risk compared to their counterparts at the upper temperature range. CONCLUSIONS: This observational study found that temperature was associated with dengue incidence, and that this association is more apparent in locations with high population density, less people in urban areas with larger household size, high poverty incidence, higher health spending per capita, and in lower latitudes. Differences with socio-economic conditions is linked with dengue risk. This highlights the need to develop interventions tailor-fit to local conditions.

Assessment of the readiness and response toward the dengue fever outbreak (2019) in Sudan: a qualitative exploration.

BACKGROUND: Dengue fever (DF) is a mosquito-borne viral disease transmitted by Aedes mosquito species and has been considered a major public health problem in Kassala State for tens of years. This study aimed to assess the level of readiness and response toward the 2019 dengue fever outbreak in Kassala at the state and community levels. METHODS: This exploratory cross-sectional study was conducted in Kassala State, Sudan, from January to March 2020. The researcher conducted interviews with the key respondents at the state level to assess the level of readiness and response and to reflect the capacity of institutions-public health authorities, health systems, and emergency response bodies. RESULTS: The surveillance system reported 3961 DF cases in Kassala State, representing 93.5% of the total cases in Sudan between August 2019 and January 2020. This outbreak was identified by passive surveillance, 51 samples were tested during the outbreak period, and private clinics and labs were not included in the surveillance system. According to the WHO checklist of outbreak readiness and response, Kassala's surveillance system and public health laboratory received the lowest scores. CONCLUSIONS: The study concludes that outbreak readiness and response could be considered below standards, mainly in the surveillance system and laboratory diagnostic facilities, due to the absence of intersectoral collaboration with a regulatory framework in terms of financial and operational participation.

Economic Evaluation of Novel Models of Care for Patients With Acute Medical Problems.

Importance: During COVID-19, Singapore simultaneously experienced a dengue outbreak, and acute hospitals were under pressure to lower bed occupancy rates. This led to new models of care to treat patients with acute, low-severity medical conditions either at home, in a hospital-at-home (HaH) model, or in a clinic-style setting sited at the emergency department in an ambulatory care team (ACT) model, but a reliable cost analysis for these models is lacking. Objective: To compare personnel costs of HaH and ACT with inpatient care. Design, Setting, and Participants: In this economic evaluation study, time-driven activity-based costing was used to compare the personnel cost of inpatient care with treating dengue via HaH and treating chest pain via ACT. Participants were patients with nonsevere dengue and chest pain unrelated to a coronary event admitted via the emergency department to the internal medicine service of a tertiary hospital in Singapore. Exposures: HaH for dengue and ACT for chest pain. Main Outcomes and Measures: A process map was created for the patient journey for a typical patient with each condition. The amount of time personnel spent on delivering care was estimated and the cost per minute determined based on their wages in 2022. The total cost of care was calculated by multiplying the time spent by the per-minute cost of the personnel resource and summing all costs. Results: Compared with inpatient care, HaH used 50% less nursing time (418 minutes, 95% uncertainty interval [UI], 370 to 465 minutes) but 80% more medical time (303 minutes, 95% UI, 270 to 338 minutes) per case of dengue. If implemented nationally, HaH would save an estimated 56 828 SGD per year (95% UI, -169 497 to 281 412 SGD [US $41 856; 95% UI, -$124 839 to $207 268]). The probability that HaH is cost saving was 69.2%. Compared with inpatient care, ACT used 15% less nursing time (296 minutes, 95% UI, 257 to 335 minutes) and 50% less medical time (57 minutes, 95% UI, 46 to 69 minutes) per case of chest pain. If implemented nationally, ACT would save an estimated 1 561 185 SGD per year (95% UI, 1 040 666 to 2 086 518 SGD [US $1 149 862; 95% UI, $766 483 to $1 536 786]). The probability that ACT is cost saving was 100%. Conclusions and Relevance: This economic evaluation found that the HaH and ACT models decreased the overall personnel cost of care. Reorganizing hospital resources may help hospitals reap the benefits of reduced hospital-acquired infections, improved patient recovery, and reduced hospital bed occupancy rates.

Age and socio-economic status affect dengue and COVID-19 incidence: spatio-temporal analysis of the 2020 syndemic in Buenos Aires City.

In early 2020, Argentina experienced the worst dengue outbreak in its history, concomitant with first-to-date increasing COVID-19 cases. Dengue epidemics in temperate Argentina have already been described as spatially heterogeneous; in the previous 2016 outbreak, transmission occurred 7.3 times more frequently in slums compared to the rest of Buenos Aires City (CABA). These informal settlements have deficient sanitary conditions, precarious housing and high incidence of social vulnerabilities. The purpose of this work was to study the spatio-temporal patterns of the 2020 dengue epidemic in CABA in relation to socio-economic living conditions of its inhabitants and its interaction with the onset of COVID-19. The study considered the period between Jan 1st and May 30th 2020. Dengue and COVID-19 databases were obtained from the National Health Surveillance System; each record was anonymized and geo-localized. The city was divided according to census tracts and grouped in four socio-economic strata: slums, high, mid and low residential. An aligned-rank transform ANOVA was performed to test for differences in the incidence of dengue and COVID-19, and age at death due to COVID-19, among socio-economic strata, four age categories and their interaction. The incidence by cluster was calculated with a distance matrix up to 600 m from the centroid. Spatial joint dengue and COVID-19 risk was estimated by multiplying the nominal risk for each disease, defined from 1 (low) to 5 (high) according to their quantiles. During the study period, 7,175 dengue cases were registered in CABA (incidence rate 23.3 cases per 10,000 inh), 29.2% of which occurred in slums. During the same period, 8,809 cases of COVID-19 were registered (28.6 cases per 10,000 inh); over half (51.4%) occurred in slums, where the median age of cases (29 years old) was lower than in residential areas (42 years old). The mean age of the deceased was 58 years old in slums compared to 79 years old outside. The percentage of deaths in patients under 60 years old was 56% in slums compared to 8% in the rest of the city. The incidence of both diseases was higher in slums than in residential areas for most age categories. Spatial patterns were heterogeneous: dengue presented higher incidence values in the southern sector of the city and the west, and low values in highly urbanized quarters, whereas COVID-19 presented higher values in the east, south, high populated areas and slums. The lowest joint risk clusters were located mainly in high residential areas, whereas high joint risk was observed mainly in the south, some western clusters, the historical part of the city and center north. The social epidemiological perspective of dengue and COVID-19 differed, given that socio environmental heterogeneity influenced the burden of both viruses in a different manner. Despite the overwhelming effect of the COVID-19 pandemic, health care towards other diseases, especially in territories with pre-existing vulnerabilities, should not be unattended.

Epidemiological Characteristics and Economic Burden of Dengue in Zhejiang Province, China.

Dengue imposes a heavy economic burden on families and society. We used surveillance data reported in 2019 to characterize the dengue epidemic in Zhejiang Province, China, which provided guidance for dengue prevention and control. Dengue epidemics mostly occurred in July to October. People aged 30-44 years, males, and commercial service workers were more likely to suffer from dengue. The epidemic areas were mainly in Hangzhou and Wenzhou. Meanwhile, we assessed the economic cost of dengue in the province from both family and organizational perspectives. The direct economic burden of dengue patients was estimated to be USD 405,038.25, and the indirect economic burden was USD 140,364.90, for a total economic burden of USD 543,213.00. The direct economic burden of dengue patients should be reduced by increasing the coverage and reimbursement of health insurance. Additionally, the total annual cost of dengue prevention and control for the government and organizational sectors was estimated to be USD 7075,654.83. Quantifying the dengue burden is critical for developing disease control strategies, allocating public health resources, and setting health policy priorities.

An ecological assessment of the potential pandemic threat of Dengue Virus in Zhejiang province of China.

BACKGROUND AND AIM: Dengue fever, transmitted by Aedes mosquitoes, is a significant public health concern in tropical and subtropical regions. With the end of the COVID-19 pandemic and the reopening of the borders, dengue fever remains a threat to mainland China, Zhejiang province of China is facing a huge risk of importing the dengue virus. This study aims to analyze and predict the current and future potential risk regions for Aedes vectors distribution and dengue prevalence in Zhejiang province of China. METHOD: We collected occurrence records of DENV and DENV vectors globally from 2010 to 2022, along with historical and future climate data and human population density data. In order to predict the probability of DENV distribution in Zhejiang province of China under future conditions, the ecological niche of Ae. aegypti and Ae. albopictus was first performed with historical climate data based on MaxEnt. Then, predicted results along with a set of bioclimatic variables, elevation and human population density were included in MaxEnt model to analyze the risk region of DENV in Zhejiang province. Finally, the established model was utilized to predict the spatial pattern of DENV risk in the current and future scenarios in Zhejiang province of China. RESULTS: Our findings indicated that approximately 89.2% (90,805.6 KM2) of Zhejiang province of China is under risk, within about 8.0% (8,144 KM2) classified as high risk area for DENV prevalence. Ae. albopictus were identified as the primary factor influencing the distribution of DENV. Future predictions suggest that sustainable and "green" development pathways may increase the risk of DENV prevalence in Zhejiang province of China. Conversely, Fossil-fueled development pathways may reduce the risk due to the unsuitable environment for vectors. CONCLUSIONS: The implications of this research highlight the need for effective vector control measures, community engagement, health education, and environmental initiatives to mitigate the potential spread of dengue fever in high-risk regions of Zhejiang province of China.

Dengue virus infection during window period of consecutive outbreaks in Nepal and assessment of clinical parameters.

Nepal is an endemic country for dengue infection with rolling of every 3 year's clear cyclic outbreaks with exponential growth since 2019 outbreak and the virus gearing towards the non-foci temperate hill regions. However, the information regarding circulating serotype and genotype is not frequent. This research discusses on the clinical features, diagnosis, epidemiology, circulating serotype and genotype among 61 dengue suspected cases from different hospitals of Nepal during the window period 2017-2018 between the two outbreaks of 2016 and 2019. E-gene sequences from PCR positive samples were subjected to phylogenetic analysis under time to most recent common ancestor tree using Markov Chain Monte Carlo (MCMC) and BEAST v2.5.1. Both evolution and genotypes were determined based on the phylogenetic tree. Serotyping by Real-time PCR and Nested PCR showed the co-circulation of all the 3 serotypes of dengue in the year 2017 and only DENV-2 in 2018. Genotype V for DENV-1 and Cosmopolitan Genotype IVa for DENV-2 were detected. The detected Genotype V of DENV-1 in Terai was found close to Indian genotype while Cosmopolitan IVa of DENV-2 found spreading to geographically safe hilly region (now gripped to 9 districts) was close to South-East Asia. The genetic drift of DENV-2 is probably due to climate change and rapid viral evolution which could be a representative model for high altitude shift of the infection. Further, the increased primary infection indicates dengue venturing to new populations. Platelets count together with Aspartate transaminase and Aalanine transaminase could serve as important clinical markers to support clinical diagnosis. The study will support future dengue virology and epidemiology in Nepal.