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Background: The incidence of Dengue Haemoragic Fever (DHF) in the Pamekasan District is still high. Mortality of DHF was always happening in Pamekasan District from 2016 to 2020. Purpose: This study aims to analyze the risk factors of DHF mortality in the Pamekasan District (2018-2020). Methods: The study was conducted from October 2020-June 2021 with a case-control study. Total population was 293 cases. The sample was 54 respondents (1:2) with proportional random sampling. The inclusion criteria were families living under the same roof for a minimum of 17 years. The variables were dengue mortality, age, sex, education, history of DHF, comorbidities, access to health services, delay in treatment, family income, residence, and family knowledge. Data were collected through interviews and documentation study. The analysis in this study used univariate (frequency) and bivariate (crosstabs use OR). Results: Risk factors of DHF mortality in Pamekasan District are children (OR = 2.05; 95% CI=0.59-7.04), low education (OR=1.16; 95% CI=0.30-4.46), history of dengue (OR=3.57;95%CI=1.09-11.66), comorbidities(OR=17.50; 95% CI=4.25-72.05), difficult access to health services (OR=3.10; 95% CI=0.79-12.09), delay in treatment (OR=5.20;95% CI=1.50-18.0), low income family (OR=1.16; 95% CI = 0.30-4.46) and low of family knowledge about dengue (OR = 7.00; 95% CI = 1.99-24.58). Meanwhile, protective factors are female (OR = 0.70; 95% CI = 0.22-2.23) and rural (OR = 0.48 ; 95% CI = 0.13-1.73). Conclusion: Risk factors of DHF mortality in Pamekasan District (2018-2020) are the history of DHF, comorbidities, delay in treatment, and low family knowledge about DHF.

Background: Dengue has emerged as a rapidly escalating health issue in low- and middle-income countries, with its burden and geographic spread increasing over the years. Malaysia, in particular, has witnessed a significant rise in dengue cases, accompanied by a spike in mortality rates. Several studies have identified various factors, primarily focusing on the 27 clinical aspects of severe dengue infection and the development of dengue-related fatalities. Expanding on this focus, this study aims to identify the demographic, clinical, and environmental factors contributing to dengue mortality, providing a more comprehensive understanding of the variables influencing dengue-related fatalities., Methods: This study utilized a 1:2 case-control design, analyzing data from the E-dengue system database and medical records from January 2015 to December 2022, involving 219 participants (73 dengue fatalities as cases and 146 recovered patients as controls). Dengue deaths were confirmed by the Penang State Mortality Review Committee, and controls were randomly selected from laboratory-confirmed dengue cases. Statistical analyses were performed using SPSS software, including descriptive statistics, chi-square tests, and multivariable logistic regression to identify predictors of dengue mortality, with variables included in the multivariable model if p < 0.05., Results: Several significant predictors of dengue-related mortality, including clinical and environmental factors were identified. Key predictors were a platelet count below 50,000/µL (OR 15.70; 95% CI: 5.65-43.53), presence of one comorbid condition (OR 2.90; 95% CI: 1.22-6.90), more than two comorbid conditions (OR 10.15; 95% CI: 3.53-29.23), bronchial asthma (OR 12.00; 95% CI: 1.08-132.13), and outbreak locality status (OR 2.3; 95% CI: 1.11-4.79). An interaction was also found between locality status and platelet levels., Conclusion: The study emphasizes the need for developing risk profiles for dengue patients by integrating factors such as platelet levels, comorbidities, and locality status to improve clinical care. Nuanced protocols are needed to address the specific challenges of single-case and outbreak areas. In single-case localities, patients with low platelet counts (below 100,000/µL) should be prioritized for rapid intervention to mitigate severe outcomes. In outbreak areas, healthcare systems should bolster resources and apply comprehensive triage approaches considering platelet levels and other risk factors. Implementing predictive models that account for geographical factors can enhance resource allocation and preparedness for dengue outbreaks. These recommendations aim to empower public health personnel, healthcare providers, and communities to collectively reduce dengue-related mortality rates., (© 2024. The Author(s).)

Background: Haemophagocytic lymphohistiocytosis (HLH) is a rare complication of dengue fever with potentially life-threatening consequences and high mortality. Therefore, this study aims to investigate the prevalence, management and outcome of HLH in dengue fever., Methods: The major electronic databases, including PubMed, ScienceDirect and Ovid SP, were searched from inception until 31 January 2024 to identify relevant studies. Pooled prevalence and mortality were calculated using the random-effects generic inverse variance model with a 95% CI. All the statistical analysis was conducted using R programming., Results: A total of nine studies with 157 patients with HLH, 576 patients with severe dengue and 5081 patients with dengue fever were included in this meta-analysis. The prevalence of HLH in severe dengue (22.1%, 95% CI 8.07 to 48.0%) was significantly higher than the prevalence in dengue fever (3.12%, 95% CI 0.37 to 21.9%). The prevalence of HLH in severe dengue was higher in the paediatric population (22.8%, 95% CI 3.9 to 68.4%) compared with the adult population (19.0%, 95% CI 3.0 to 63.9%). The overall mortality rate was 20.2% (95% CI 9.7 to 37.2%)., Conclusion: The prevalence of dengue-associated HLH was low in patients with dengue fever but is significantly higher in patients with severe dengue and a high mortality rate., (© The Author(s) 2024. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Objectives: To compare the number of suspected cases, severe cases, and deaths of dengue in 2023 and 2024 in Brazil and Latin America; and to describe its epidemiological profile., Design: Observational study., Methods: The data regarding dengue was retrieved from the Brazilian Ministry of Health website. The Chi-square test was used to compare the proportion of dengue cases in 2023 and 2024 according to gender, race, and age range. The odds ratio and the 95% confidence intervals were used to describe the data. The Spearman correlation test was used to compare the number of suspected cases, severe cases, and deaths of dengue with the number of distributed vaccines against dengue., Results: Dengue is one of the most common zoonoses in Latin America. In 2023, Brazil registered a total of 1,658,814 suspected cases of dengue with 1094 deaths. For 2024, a total of 1,978,372 suspected cases of dengue were reported only until the 11th epidemiological week, with 656 deaths. When comparing dengue cases reported in 2024 and 2023, there is an increase in suspected cases, with 20% more cases reported during the first 11 epidemiological weeks of 2024 than in the entire 52 epidemiological weeks of 2023. At the same time, in 2024, the Pan American Health Organization reported suspected cases in 20 Latin American countries, with 3073 cases of severe dengue and 1187 deaths. In Brazil, a different racial profile for dengue was described since Black people [OR = 1.56 (95% CI = 1.54-1.57)], Mixed individuals [OR = 1.36 (95% CI = 1.35-1.37), and Indigenous peoples [OR = 1.77 (95% CI = 1.70-1.85)] were more likely to be suspected cases of dengue in 2024 compared to 2023. Also, a positive correlation between the distributed vaccines with deaths due to dengue and the number of severe cases was described., Conclusion: Brazil was responsible for more than 50% of suspected cases and deaths from dengue compared to the other Latin American countries in 2024. Furthermore, there is a different racial profile for dengue in Brazil, as Black people, Mixed individuals, and Indigenous peoples were more likely to be suspected cases of dengue in 2024 compared to 2023., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The incidence of Dengue Haemoragic Fever (DHF) in the Pamekasan District is still high. Mortality of DHF was always happening in Pamekasan District from 2016 to 2020. Purpose: This study aims to analyze the risk factors of DHF mortality in the Pamekasan District (2018-2020). Methods: The study was conducted from October 2020-June 2021 with a case-control study. Total population was 293 cases. The sample was 54 respondents (1:2) with proportional random sampling. The inclusion criteria were families living under the same roof for a minimum of 17 years. The variables were dengue mortality, age, sex, education, history of DHF, comorbidities, access to health services, delay in treatment, family income, residence, and family knowledge. Data were collected through interviews and documentation study. The analysis in this study used univariate (frequency) and bivariate (crosstabs use OR). Results: Risk factors of DHF mortality in Pamekasan District are children (OR = 2.05; 95% CI=0.59-7.04), low education (OR=1.16; 95% CI=0.30-4.46), history of dengue (OR=3.57;95%CI=1.09-11.66), comorbidities(OR=17.50; 95% CI=4.25-72.05), difficult access to health services (OR=3.10; 95% CI=0.79-12.09), delay in treatment (OR=5.20;95% CI=1.50-18.0), low income family (OR=1.16; 95% CI = 0.30-4.46) and low of family knowledge about dengue (OR = 7.00; 95% CI = 1.99-24.58). Meanwhile, protective factors are female (OR = 0.70; 95% CI = 0.22-2.23) and rural (OR = 0.48; 95% CI = 0.13-1.73). Conclusion: Risk factors of DHF mortality in Pamekasan District (2018-2020) are the history of DHF, comorbidities, delay in treatment, and low family knowledge about DHF. [ABSTRACT FROM AUTHOR]

ABSTRACT Since the reintroduction of dengue viruses in 1987, Sao Paulo State (SP), Brazil, has experienced recurrent epidemics in a growing number of municipalities, each time with more cases and deaths. In the present study, we investigated the spatio-temporal dynamics of dengue-related deaths and associated factors in SP. This was an ecological study with spatial and temporal components, based on notified dengue-related deaths in the municipalities of SP between 2007 and 2017. A latent Gaussian Bayesian model with Poisson probability distribution was used to estimate the standardized mortality ratios (SMR) for dengue and relative risks (RR) for the socioeconomic, demographic, healthcare-related, and epidemiological factors considered. Epidemiological factors included the annual information on the number of circulating serotypes. A total of 1,019 dengue-related deaths (0.22 per 100,000 inhabitant-years) between 2007 and 2017 were confirmed in SP by laboratory testing. Mortality increased with age, peaking at 70 years or older (1.41 deaths per 100,000 inhabitant-years). Mortality was highest in 2015, and the highest SMR values were found in the North, Northwest, West, and coastal regions of SP. An increase of one circulating serotype, one standard deviation in the number of years with cases, and one standard deviation in the degree of urbanization were associated with increases of 75, 35, and 45% in the risk of death from dengue, respectively. The risk of death from dengue increased with age, and the distribution of deaths was heterogeneous in space and time. The positive relationship found between the number of dengue serotypes circulating and years with cases at the municipality/micro-region level indicates that this information can be used to identify risk areas, intensify surveillance and control measures, and organize healthcare to better respond to this disease.

Since the reintroduction of dengue viruses in 1987, Sao Paulo State (SP), Brazil, has experienced recurrent epidemics in a growing number of municipalities, each time with more cases and deaths. In the present study, we investigated the spatio-temporal dynamics of dengue-related deaths and associated factors in SP. This was an ecological study with spatial and temporal components, based on notified dengue-related deaths in the municipalities of SP between 2007 and 2017. A latent Gaussian Bayesian model with Poisson probability distribution was used to estimate the standardized mortality ratios (SMR) for dengue and relative risks (RR) for the socioeconomic, demographic, healthcare-related, and epidemiological factors considered. Epidemiological factors included the annual information on the number of circulating serotypes. A total of 1,019 dengue-related deaths (0.22 per 100,000 inhabitant-years) between 2007 and 2017 were confirmed in SP by laboratory testing. Mortality increased with age, peaking at 70 years or older (1.41 deaths per 100,000 inhabitant-years). Mortality was highest in 2015, and the highest SMR values were found in the North, Northwest, West, and coastal regions of SP. An increase of one circulating serotype, one standard deviation in the number of years with cases, and one standard deviation in the degree of urbanization were associated with increases of 75, 35, and 45% in the risk of death from dengue, respectively. The risk of death from dengue increased with age, and the distribution of deaths was heterogeneous in space and time. The positive relationship found between the number of dengue serotypes circulating and years with cases at the municipality/micro-region level indicates that this information can be used to identify risk areas, intensify surveillance and control measures, and organize healthcare to better respond to this disease. [ABSTRACT FROM AUTHOR]

Acute liver failure (ALF) is a devastating consequence of dengue infection. This systematic review and meta-analysis assessed the incidence of ALF in dengue infection and its associated mortality. We systematically searched the EMBASE and MEDLINE databases from inception to December 2023 for observational studies reporting ALF incidence and mortality in dengue patients. Twenty-one studies encompassing 26,839 dengue-infected patients were included. Meta-analysis revealed a pooled incidence of ALF in cases of general dengue infection of 2.0 % (95 % CI, 1.2-3.0 %), with 1.2 % (95 % CI, 0.6-2.1 %) in adults and 5.0 % (95 % CI, 1.5-10.2 %) in children. ALF incidence was 17.3 % (95 % CI, 6.5 %-31.5 %) in severe dengue and 7.4 % (95 % CI, 0.8-18.5 %) in dengue shock syndrome. The pooled mortality rate of dengue-associated ALF was 47.0 % (95 % CI, 32.9-61.2 %). These findings underscore the detrimental impact of dengue infection on the development of the relatively uncommon, albeit life-threatening, condition of ALF., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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.

Abstract Background Over the last 30 years, extensive dengue epidemics have occurred in Brazil, characterized by emergences and re-emergences of different serotypes, a change in the epidemiological profile and an increase in the number of severe and fatal cases. Here, we present a review on the dengue fatal cases that occurred in Brazil in 30 years (1986–2015). Methods We performed an ecological study by using secondary data on dengue fatal cases obtained in the National System of Reported Diseases (Sistema de Informação de Agravos de Notificação -SINAN) and in the Mortality Information System (SIM), both maintained by the Brazilian Ministry of Health. Cases were analyzed by region, demographic variables, clinical classification and complications based on the data available. Results In 30 years (1986–2015), the Southeast region reported 43% (n = 2225) of all dengue deaths in the country. The Midwest region was responsible for 18% of the fatal cases. After 2000, deaths occurred in almost all states, with the exception of Santa Catarina and Rio Grande do Sul, South region. From 2006 to 2010, the number of deaths increased, with higher rates of mortality, especially in Goiás and Mato Grosso. From 2011 to 2015, Goiás became the state with the highest mortality rate in the country, and Rio Grande do Sul reported its first dengue deaths. In 30 years, a total of 2682 dengue deaths occurred in males and 2455 in females, and an equal distribution between the sexes was observed. From 1986 to 2006, dengue deaths occurred predominantly in individuals over 15 years old, but this scenario changed in 2007–2008. After 2009, fatal cases on individuals above 15 years old became more frequent, with peaks in the years of 2010, 2013 and 2015. Conclusions The Brazil is experiencing a hyperendemic scenario, which has resulted in the co-circulation of the four DENV serotypes and with the increasing occurrence of severe and fatal cases. The disease surveillance and studies characterizing what has been reported overtime, are still important tools to better understand the factors involved in the disease outcome.

Background: Dengue has emerged as an unprecedented epidemic in Peru, and it is anticipated that this issue will escalate further owing to climate change. This study aimed to determine the risk factors associated with death from dengue in patients treated at Hospital II in Pucallpa, Peru., Methodology: This retrospective cohort study collected information from the medical records of patients with a diagnosis of dengue treated at Hospital II Pucallpa-Peru between January 2019 and March 2023. The primary outcome was death, and the secondary outcome was death, development of severe dengue, or Intensive Care Unit (ICU) admission. Cox regression models were used to determine risk factors., Findings: The clinical records of 152 patients were evaluated, with a median age of 27.5 years (interquartile range, 11-45). Among all patients, 29 (19.1%) developed severe dengue, 31 (20.4%) were admitted to the ICU, and 13 (8.6%) died during follow-up. In the survival analysis, bilirubin >1.2 mg/dL was associated with a higher risk of death aHR: 11.38 (95% CI: 1.2 106.8). Additionally, factors associated with poor prognosis included having 1 to 3 comorbidities aRR: 1.92 (1.2 to 3.2), AST ≥251 U/L aRR: 6.79 (2.2 to 21.4), history of previous dengue aRR: 1.84 (1.0 to 3.3), and fibrinogen ≥400 mg/dL aRR: 2.23 (1.2 to 4.1)., Significance: Elevated bilirubin was associated with death from dengue, whereas an increase in comorbidities and a history of previous dengue were related to a poor prognosis of the disease. Early identification of severe dengue would be more feasible with improved access to laboratory testing, particularly in tropical areas with a high dengue incidence., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Copaja-Corzo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Dengue Viral Infection (DVI) has become endemic in Pakistan since the first major outbreak in Karachi in 1996. Despite aggressive measures taken by relevant authorities, Pakistan has been dealing with a worsening dengue crisis for the past two decades. DHF is severe form of dengue infection which is linked with significant morbidity and mortality. Early identification of severe dengue infections can reduce the morbidity and mortality. In this context we planned current study in which we find out the different factors related with DHF as well as clinical laboratory features of DHF and compare them to DF so that patients can be best evaluated for DHF and managed accordingly at admission., Methods: Retrospective study conducted over a period of 6 years (2013-2018) in two tertiary care hospitals in Pakistan. Data were collected by using a pre-structured data collection form. Data were statistically analyzed to determine the clinical and laboratory characteristics of DVI and risk factors of dengue hemorrhagic fever (DHF)., Results: A total 512 dengue cases (34.05 ± 15.08 years; Male 69.53%) were reviewed. Most common clinical manifestations of DVI were fever (99.60%), headache (89.1%), chills (86.5%), rigors (86.5%), myalgia (72.3%). Less common clinical manifestations were vomiting (52.5%), arthralgia (50.2%) and skin rashes (47.5%). Furthermore, nasal bleeding (44.1%), gum bleeding (32.6%), pleural effusion (13.9%) and hematuria (13.1%) were more profound clinical presentations among DHF patients. Mortality rate was 1.5% in this study. Logistic regression analysis indicated that delayed hospitalization (OR: 2.30) and diabetes mellitus (OR:2.71), shortness of breath (OR:2.21), association with risk groups i.e., living near stagnant water, travelling to endemic areas, living in endemic regions (OR:1.95), and presence of warning signs (OR:2.18) were identified as risk factors of DHF. Statistically we found that there is strong association of diabetes mellitus (DM) with DHF while the patient suffering from DM individually had higher odds (2.71) of developing DHF than patients without disease., Conclusions: The current study demonstrated that the clinical and laboratory profiles of DF and DHF are significantly distinct. Significant predictors of DHF were advanced age, diabetes mellitus, ascites, pleural effusion, thick gallbladder and delayed hospitalization. The identification of these factors at early stage provides opportunities for the clinicians to identify high risk patients and to reduce dengue-related morbidity and mortality., (© 2024. The Author(s).)

Dengue is the most important arthropod-borne viral infection of humans. However, its viral pathogenesis is still unknown. The information collected from dengue fatal cases is crucial for understanding the complex interactions between virulence and host factors. This study aimed to establish possible associations between the clinical characteristics, histopathological changes, replication, and tissue location of viral serotypes in dengue fatal cases. Clinical and histopathological characterizations, antigen localization in tissue, and detection of the infecting serotype and replication using real-time polymerase chain reaction were all performed on the dengue fatal cases. The majority of the cases involved people under the age of 20. Bleeding (48.3%), abdominal pain (44.8%), myalgia (52.9%), and headache (48.3%) were the most common clinical manifestations in the cases. There was multiorgan pathology, with histopathological changes primarily in the liver, spleen, and lung. Similarly, the viral antigen was found primarily in these organs; however, there were no associations between tissue changes, viral location, infecting serotypes, and replication processes. Dengue infection should be considered a multiorgan disease, the outcome of which is possibly not associated with the infecting viral serotype.

This article presents a space-time scan statistic, useful for evaluating space-time cluster alarms, and illustrates the method to investigate a recent dengue mortality alarm in Indonesia. Space-time scan statistics account for multiple testing inherent in a cluster alarm. The baseline process may be any inhomogeneous Poisson process with intensity proportional to some known function. Confounders in a particular time can be adjusted for. Three cluster alarms of dengue mortality in Indonesia in 2005 were statistically significant. Space-time scan statistics are useful as screening tools for evaluating which cluster alarms merit further investigation and which clusters are probably chance occurrences.

Background: Dengue is a viral disease whose clinical spectrum ranges from unapparent to severe forms and fatal outcomes. Although dengue death is 99 % avoidable, every year around 20,000 deaths are estimated to occur in more than 100 countries. We consider that, along with biological factors, social determinants of health (SDHs) are related to dengue deaths as well. Methods: A scoping review was conducted to explore what has been written about the role of SDHs in dengue mortality. The inclusion criteria were that documents (grey or peer-reviewed) had to include information about dengue fatal cases in humans and be published between 1997 and 2013 and written in English, Spanish, Portuguese or French. The search was conducted using a set of key words related to dengue mortality in several electronic databases: PubMed, LILACS, COCHRANE, Scielo, Science Direct, WHOLIS, OpenGrey, OpenSingle and Google Scholar. Information on SDHs was categorized under individual, social and environmental, and health systems dimensions. A summative content analysis using QDA Miner was conducted to assess the frequency of information on SDHs and its contextual meaning in the reviewed literature. The role of each SDH in dengue mortality was assessed using content analysis results. Results: From a total of 971 documents retrieved, 78 met the criteria. Those documents were published in the Americas region (50.0 %), Asia (38.4 %), Europe (9.0 %) and Africa (2.6 %). The described SDHs related to dengue deaths included, in the individual dimension: age, ethnicity, education, type of infection and immunological status; and in the social dimension: poverty and care-seeking behavior. The health systems dimension included access, opportunity, and quality of care, as well as health staff knowledge. Ethnicity was considered a determinant that depends on cultural and socioeconomic conditions. Conclusions: Along with biological factors, there are several SDHs related to dengue mortality. However, only a few of these have been systematically analyzed, suggesting the need for more studies on this subject to inform the design and implementation of sustainable interventions to decrease dengue mortality. These findings nevertheless provide a better understanding of the non-biological factors involved in dengue mortality. [ABSTRACT FROM AUTHOR]

Epidemics are among the most costly and destructive natural hazards globally. To reduce the impacts of infectious disease outbreaks, the development of a risk index for infectious diseases can be effective, by shifting infectious disease control from emergency response to early detection and prevention. In this study, we introduce a methodology to construct and validate an epidemic risk index using only open data, with a specific focus on scalability. The external validation of our risk index makes use of distance sampling to correct for underreporting of infections, which is often a major source of biases, based on geographical accessibility to health facilities. We apply this methodology to assess the risk of dengue in the Philippines. The results show that the computed dengue risk correlates well with standard epidemiological metrics, i.e. dengue incidence (p = 0.002). Here, dengue risk constitutes of the two dimensions susceptibility and exposure. Susceptibility was particularly associated with dengue incidence (p = 0.048) and dengue case fatality rate (CFR) (p = 0.029). Exposure had lower correlations to dengue incidence (p = 0.193) and CFR (p = 0.162). Highest risk indices were seen in the south of the country, mainly among regions with relatively high susceptibility to dengue outbreaks. Our findings reflect that the modelled epidemic risk index is a strong indication of sub-national dengue disease patterns and has therefore proven suitability for disease risk assessments in the absence of timely epidemiological data. The presented methodology enables the construction of a practical, evidence-based tool to support public health and humanitarian decision-making processes with simple, understandable metrics. The index overcomes the main limitations of existing indices in terms of construction and actionability., Competing Interests: The authors have declared that no competing interests exist.

Background: Chikungunya and dengue are emerging diseases that have caused large outbreaks in various regions of the world. Both are both spread by Aedes aegypti and Aedes albopictus mosquitos. We developed a dynamic transmission model of chikungunya and dengue, calibrated to data from Colombia (June 2014 -December 2017)., Methodology/principal Findings: We evaluated the health benefits and cost-effectiveness of residual insecticide treatment, long-lasting insecticide-treated nets, routine dengue vaccination for children aged 9, catchup vaccination for individuals aged 10-19 or 10-29, and portfolios of these interventions. Model calibration resulted in 300 realistic transmission parameters sets that produced close matches to disease-specific incidence and deaths. Insecticide was the preferred intervention and was cost-effective. Insecticide averted an estimated 95 chikungunya cases and 114 dengue cases per 100,000 people, 61 deaths, and 4,523 disability-adjusted life years (DALYs). In sensitivity analysis, strategies that included dengue vaccination were cost-effective only when the vaccine cost was 14% of the current price., Conclusions/significance: Insecticide to prevent chikungunya and dengue in Colombia could generate significant health benefits and be cost-effective. Because of limits on diagnostic accuracy and vaccine efficacy, the cost of dengue testing and vaccination must decrease dramatically for such vaccination to be cost-effective in Colombia. The vectors for chikungunya and dengue have recently spread to new regions, highlighting the importance of understanding the effectiveness and cost-effectiveness of policies aimed at preventing these diseases., Competing Interests: The authors have declared that no competing interests exist.

The global burden of dengue is increasing against a background of rising global prevalence of chronic noncommunicable diseases (NCDs) and an epidemiological shift of dengue toward older age groups. The contribution of NCDs toward risk for adverse clinical and healthcare utilization outcomes was assessed in a national linked-database study. About 51,433 adult dengue cases between 2014 and 2015 were assessed for outpatient and inpatient claims data in Taiwan's National Health Insurance Research Database for the 30 days after their dengue diagnosis. A multivariable logistic regression with generalized estimating equations was used to estimate the probability of adverse dengue outcomes in patients with NCDs compared with dengue patients without underlying diseases. Rheumatoid arthritis and related disease were associated with the highest risk of hospitalization after dengue diagnosis (odds ratio: 1.78; 95% CI: 1.37-2.30), followed by stroke, chronic kidney disease (CKD), liver cirrhosis, asthma, coronary artery disease, chronic obstructive pulmonary disease, diabetes, congestive heart failure, hypertension, and malignancy. Chronic kidney disease and diabetes were associated with higher risks of hospitalization, intensive care unit (ICU) use, and all-cause mortality. After adjusting for socioeconomic status and other variables, the number of coexisting chronic diseases was associated with increasing risk of adverse dengue outcomes. Specific NCDs were associated with longer hospitalizations, ICU admission, and higher healthcare costs. Quantifying the risks of adverse dengue outcomes and health expenditures among dengue patients with preexisting NCDs provides insights for improved clinical management and essential inputs for health economic analyses on the cost-benefit of risk-based routine or catch-up immunization programs.

Dengue patients with comorbidities may be at higher risk of death. In this cross-sectional study, healthcare databases from Mexico (2008-2014), Brazil (2008-2015), and Colombia (2009-2017) were used to identify hospitalized dengue cases and their comorbidities. Case fatality rates (CFRs), relative risk, and odds ratios (OR) for in-hospital mortality were determined. Overall, 678,836 hospitalized dengue cases were identified: 68,194 from Mexico, 532,821 from Brazil, and 77,821 from Colombia. Of these, 35%, 5%, and 18% were severe dengue, respectively. Severe dengue and age ≥ 46 years were associated with increased risk of in-hospital mortality. Comorbidities were identified in 8%, 1%, and 4% of cases in Mexico, Brazil, and Colombia, respectively. Comorbidities increased hospitalized dengue CFRs 3- to 17-fold; CFRs were higher with comorbidities regardless of dengue severity or age. The odds of in-hospital mortality were significantly higher in those with pulmonary disorders (11.6 [95% CI 7.4-18.2], 12.7 [95% CI 9.3-17.5], and 8.0 [95% CI 4.9-13.1] in Mexico, Brazil, and Colombia, respectively), ischemic heart disease (23.0 [95% CI 6.6-79.6], 5.9 [95% CI 1.4-24.6], and 7.0 [95% CI 1.9-25.5]), and renal disease/failure (8.3 [95% CI 4.8-14.2], 8.0 [95% CI 4.5-14.4], and 9.3 [95% CI 3.1-28.0]) across the three countries; the odds of in-hospital mortality from dengue with comorbidities was at least equivalent or higher than severe dengue alone (4.5 [95% CI 3.4-6.1], 9.6 [95% CI 8.6-10.6], and 9.0 [95% CI 6.8-12.0). In conclusion, the risk of death because of dengue increases with comorbidities independently of age and/or disease severity.

Objective: To assess the presence, pattern and magnitude of socioeconomic inequalities on dengue, chikungunya and Zika in Latin America, accounting for their spatiotemporal distribution., Methods: Using longitudinal surveillance data (reported arboviruses) from Fortaleza, Brazil and Medellin, Colombia (2007-2017), we fit Bayesian hierarchical models with structured random effects to estimate: (i) spatiotemporally adjusted incidence rates; (ii) Relative Concentration Index and Absolute Concentration Index of inequality; (iii) temporal trends in RCIs; and (iv) socioeconomic-specific estimates of disease distribution. The spatial analysis was conducted at the neighbourhood level (urban settings). The socioeconomic measures were the median monthly household income (MMHI) for Brazil and the Socio-Economic Strata index (SES) in Colombia., Results: There were 281 426 notified arboviral cases in Fortaleza and 40 887 in Medellin. We observed greater concentration of dengue among residents of low socioeconomic neighbourhoods in both cities: Relative Concentration Index = -0.12 (95% CI = -0.13, -0.10) in Fortaleza and Relative Concentration Index = -0.04 (95% CI = -0.05, -0.03) in Medellin. The magnitude of inequalities varied over time across sites and was larger during outbreaks. We identified a non-monotonic association between disease rates and socioeconomic measures, especially for chikungunya, that changed over time. The Relative Concentration Index and Absolute Concentration Index showed few if any inequalities for Zika. The socioeconomic-specific model showed increased disease rates at MMHI below US$400 in Brazil and at SES-index below level four, in Colombia., Conclusions: We provide robust quantitative estimates of socioeconomic inequalities in arboviruses for two Latin American cities. Our findings could inform policymaking by identifying spatial hotspots for arboviruses and targeting strategies to decrease disparities at the local level., (© 2020 John Wiley & Sons Ltd.)

Background: Chikungunya, dengue, and Zika are three different arboviruses which have similar symptoms and are a major public health issue in Colombia. Despite the mandatory reporting of these arboviruses to the National Surveillance System in Colombia (SIVIGILA), it has been reported that the system captures less than 10% of diagnosed cases in some cities., Methodology/principal Findings: To assess the scope and degree of arboviruses reporting in Colombia between 2014-2017, we conducted an observational study of surveillance data using the capture-recapture approach in three Colombian cities. Using healthcare facility registries (capture data) and surveillance-notified cases (recapture data), we estimated the degree of reporting by clinical diagnosis. We fit robust Poisson regressions to identify predictors of reporting and estimated the predicted probability of reporting by disease and year. To account for the potential misclassification of the clinical diagnosis, we used the simulation extrapolation for misclassification (MC-SIMEX) method. A total of 266,549 registries were examined. Overall arboviruses' reporting ranged from 5.3% to 14.7% and varied in magnitude according to age and year of diagnosis. Dengue was the most notified disease (21-70%) followed by Zika (6-45%). The highest reporting rate was seen in 2016, an epidemic year. The MC-SIMEX corrected rates indicated underestimation of the reporting due to the potential misclassification bias., Conclusions: These findings reflect challenges on arboviruses' reporting, and therefore, potential challenges on the estimation of arboviral burden in Colombia and other endemic settings with similar surveillance systems., Competing Interests: The authors have declared that no competing interests exist.

Formalin-fixed paraffin-embedded (FFPE) tissues are an important source for investigation of dengue virus (DENV) infection, particularly when blood or fresh frozen (FF) samples are unavailable. Histopathologic features and immunohistochemistry may have poor sensitivity and serotype determination is not always possible. Viral RNA genome detection tests are faster and considered the most sensitive technique for this kind of analysis, however, the use of molecular methods applied to FFPE tissues is still limited. The authors applied a single-step multiplex reverse transcription-quantitative polymerase chain reaction (RT-qPCR) for the investigation of DENV infection and typing to FFPE samples of 32 fatal cases received during the 2019 outbreak that occurred in São Paulo state, Brazil. The authors compared the results with those obtained using FF tissues. Of the 24 cases with both FF and FFPE samples, 22 (91.67%) of the FF and 19 (76.20%) of the FFPE specimens were positive. Two cases (8.33%) tested negative in both types of samples. All 8 cases with only FFPE samples available were positive. The accuracy (87.5%) of the RT-qPCR for DENV in FFPE samples were satisfactory. Although the cycle quantification (Cq) values were significantly higher in these materials (P<0.0001, Wilcoxon signed-rank test) when compared with FF tissues, Spearman's rank coefficient indicated a good correlation between the Cq values from both sample types (P=0.0063; rho=0.576). RT-qPCR applied to FFPE samples improved detection of DENV in fatal cases and represents a useful tool for diagnosis and epidemiologic studies., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

The clinical profile and risk factors for mortality in dengue fever have evolved over the years. The all-cause mortality in admitted dengue patients is around 6%. We aimed to evaluate the recent change in trends of the clinical characteristics and risk factors for in-hospital mortality in adults with dengue fever. This is a retrospective study on adults with confirmed dengue fever admitted in a medical unit of a tertiary care center in North India. Medical records of confirmed dengue fever patients admitted between January 2011, and December 2016 were reviewed. Chi-squared tests with Bonferroni correction for multiple testing were used to identify risk factors for mortality. 232 records were included, of which 66.8% were males. The mean age was 31.6 ± 14 years. There were 17 deaths with an all-cause mortality rate of 7.3% with 76.5% being classified as severe dengue at admission. Among the 17 mortality cases, dyspnea (47%), tachypnea (86.7%), leucocytosis (58.8%), raised urea (80%), and elevated serum creatinine (52.9%) at presentation were significantly associated with mortality (p < 0.001). Shock at any time during the hospital stay (58.8%) was also found to be significantly associated with mortality (p < 0.001). We found that dyspnea, tachypnea, acute kidney injury, and leucocytosis at presentation was significantly associated with in-hospital mortality. Based on our results, we recommend aggressive management of patients with severe dengue and those with mild/moderate disease with the above risk factors.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread throughout Latin America, a region swept by multiple previous and ongoing epidemics. There are significant concerns that the arrival of COVID-19 is currently overlapping with other viruses, particularly dengue, in various endo-epidemic regions across South America. In this report, we analyzed trends for both viral infections in Colombia during the first 20 epidemiological weeks (EWs) of 2020. From 1st January to 16th May 2020 (EWs, 1-20), a total of 52 679 cases of dengue and 14 943 cases of COVID-19 have been confirmed in Colombia. As both conditions may potentially lead to fatal outcomes, especially in patients with chronic co-morbidities, overlapping infections, and co-occurrence may increase the number of patients requiring intensive care and mechanical ventilation. In regions, such as Valle del Cauca, intensified preparation for such scenarios should be pondered, and further studies should be performed to address this critical issue in a timely matter., (© 2020 Wiley Periodicals LLC.)

Introduction: Clinical distinction between arbovirus infections and those caused by rickettsia is crucial to initiate appropriate medical treatment., Objective: To compare the differences between Rocky Mountain spotted fever (RMSF) and other vector-borne diseases (dengue and chikungunya) with similar clinical presentation, and to identify data that could aid rapid diagnosis of these diseases., Methods: We evaluated sociodemographic, clinical and laboratory data of 399 patients from five hospitals and clinics of Sonora, Mexico, between 2004 and 2016, with laboratory-confirmed diagnosis of RMSF, dengue, or chikungunya., Results: The RMSF group had the highest lethality (49/63 deaths, 77.8 %), followed by the chikungunya group (3/161, 1.9 %) and the dengue group (3/161, 1.9 %). Clinical differences included the presence of rash, edema, and pruritus; in addition, differences in multiple biomarkers such as platelets, hemoglobin, indirect bilirubin, and serum sodium levels were documented., Conclusion: Rash on the palms and soles, edema and absence of pruritus, together with high levels of direct bilirubin and severe thrombocytopenia could be useful indicators to differentiate patients at RMSF advanced stages from those with dengue and chikungunya., (Copyright: © 2020 Permanyer.)

Objetivo. Identificar factores demográficos y clínicos asociados con la mortalidad por dengue grave en cinco de-partamentos de Colombia. Material y métodos. Análisis secundario de un estudio de casos y controles basado en pa-cientes admitidos de 2009 a 2013. Los casos fueron pacientes que murieron por dengue y los controles fueron pacientes con dengue grave sobrevivientes a la enfermedad. Se utilizó el procedimiento de Mantel-Haenszel para identificar los factores. Resultados. Analizando 58 casos y 121 controles, cuatro factores fueron asociados con la mortalidad por den-gue: administración hospitalaria de dipirona (RMa=6.38 IC95% 2.41-16.86) y de acetaminofén (RMa=0.25 IC95% 0.10-0.61), presencia de comorbilidad (RMa=3.52 IC95% 1.51-8.18) y consulta previa por el mismo padecimiento (RMa=3.99 IC95% 1.63-9.77). Conclusiones. La administración de dipirona en pacientes con dengue grave se asoció con un aumento del riesgo de mortalidad. Si se considera que la dipirona fue retirada del mercado en 20 países por sus efectos secunda-rios, se puede desaconsejar su uso en el manejo del dengue.

Objective: During the 2013-2016 period, Dengue, Chikungunya, and Zika affected more than 1 million people in Colombia. These arboviruses and their chronic manifestations pose a public health challenge. Therefore, we estimated the burden of disease by Dengue, Chikungunya, and Zika in Colombia between 2013 and 2016., Methods: An exploratory ecological study was carried out using the disability-adjusted life years (DALYs) as a unit of measure. The mortality databases of the National Administrative Department of Statistics (DANE) and the morbidity databases of the National Public Health Surveillance System (SIVIGILA) were used. Deaths and cases for each arbovirus were grouped and then adjusted to control biases. Subsequently, we performed a sensitivity analysis., Results: In the 2013-2016 period, 491,629.2 DALYs were lost due to arboviruses in Colombia. By disease, 26.6% of the total DALYs were caused by Dengue, 71.3% by Chikungunya, and the remaining 2.2%, by Zika. The majority of DALYs (68.2%) were caused by chronic complications. Five out of 32 departments (Valle del Cauca, Tolima, Norte de Santander, Huila, and Bolívar) contributed 50.5% of total DALYs., Conclusion: The burden of disease by arboviruses in the 2013-2016 period exceeded the burden of other infectious diseases such as HIV/AIDS and tuberculosis in Colombia. Public health efforts must be made to mitigate new epidemics of these arboviruses., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Hepatitis infection from non-hepatotropic viruses such as dengue virus (DENV) is increasing worldwide. There is increasing recognition of the changing epidemiology and atypical presentations of DENV infection including acute liver failure (ALF). There is paucity of data regarding incidence, disease characteristics, and markers of prognosis in patients who develop DENV-related ALF., Methods: We aimed to study the incidence, clinical features, laboratory characteristics, and determinants of outcome in patients of DENV presenting with ALF. We reviewed all patients with DENV infection and focused on DENV-related ALF from 2014 to 2017. Diagnosis of DENV and ALF was confirmed by serological tests and standard criteria, respectively., Results: Thirty-six patients (20 men, mean age 32.3) developed ALF among 10 108 patients with DENV infection (0.35%). Twenty-one patients died (58.3%). Although bilirubin, aspartate and alanine aminotransferase, and international normalized ratio were markedly elevated in all patients with DENV ALF, there was no statistically significant difference between survivors and non-survivors. Lactate levels, pH at admission, and model for end-stage liver disease (MELD) score were the only predictors of mortality. Lactate levels were significantly higher in non-survivors (11.5 ± 4.2 mmol/L) than survivors (6.3 ± 3.6 mmol/L) (P < 0.001). MELD score in non-survivors (26.7 ± 10.2) was significantly higher than in survivors (20 ± 7.2) (P = 0.039). Receiver operator characteristic curve showed lactate or pH to be a superior prognostic marker than MELD with an area under the curve of 0.80, 0.79, and 0.70, respectively., Conclusion: Dengue hepatitis progressed to ALF in 0.35%. Development of ALF was associated with a high mortality (> 50%). Lactate level, pH, and MELD score at admission were significant determinants of outcome., (© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Dengue is an arboviral disease caused by dengue virus (DENV), which is transmitted to humans by Aedes aegypti mosquitoes. Infection by DENV most commonly results in a mild flu-like illness; however, the disease has been increasingly associated with neurological symptomatology. This association draws attention to further investigations on the impact of DENV infection in the host's central nervous system. Here, we analyzed brain samples of three fatal dengue cases that occurred in 2002 during an outbreak in Rio de Janeiro, Brazil. Brain tissues of these cases were marked by histopathological alterations, such as degenerated neurons, demyelination, hemorrhage, edema, and increased numbers of astrocytes and microglial cells. Samples were also characterized by lymphocytic infiltrates mainly composed of CD8 T cells. DENV replication was evidenced in neurons, microglia and endothelial cells through immunohistochemistry and in situ hybridization techniques. Pro-inflammatory cytokines, such as TNF-α and IFN-γ were detected in microglia, while endothelial cells were marked by the expression of RANTES/CCL5. Cytoplasmic HMGB1 and the production of nitric oxide were also found in neurons and microglial cells. This work highlights the possible participation of several local pro-inflammatory mediators in the establishment of dengue neuropathogenesis., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

In South East Asia, dengue epidemics have increased in size and geographical distribution in recent years. We examined the spatiotemporal distribution and epidemiological characteristics of reported dengue cases in the predominantly rural state of Sabah, in Malaysian Borneo-an area where sylvatic and urban circulation of pathogens are known to intersect. Using a public health data set of routinely notified dengue cases in Sabah between 2010 and 2016, we described demographic and entomological risk factors, both before and after a 2014 change in the clinical case definition for the disease. Annual dengue incidence rates were spatially variable over the 7-year study period from 2010-2016 (state-wide mean annual incidence of 21 cases/100,000 people; range 5-42/100,000), but were highest in rural localities in the western districts of the state (Kuala Penyu, Nabawan, Tenom and Kota Marudu). Eastern districts exhibited lower overall dengue rates, although a high proportion of severe (haemorrhagic) dengue cases (44%) were focused in Sandakan and Tawau. Dengue incidence was highest for those aged between 10 and 29 years (24/100,000), and was slightly higher for males compared to females. Available vector surveillance data indicated that during large outbreaks in 2015 and 2016 the mosquito Aedes albopictus was more prevalent in both urban and rural households (House Index of 64%) than Ae. aegypti (15%). Demographic patterns remained unchanged both before and after the dengue case definition was changed; however, in the years following the change, reported case numbers increased substantially. Overall, these findings suggest that dengue outbreaks in Sabah are increasing in both urban and rural settings. Future studies to better understand the drivers of risk in specific age groups, genders and geographic locations, and to test the potential role of Ae. albopictus in transmission, may help target dengue prevention and control efforts., Competing Interests: The authors declare no conflict of interest in conducting this study.

Background: Sri Lanka experienced its largest dengue outbreak in 2017 with more than 185,000 dengue cases including at least 250 fatalities., Objectives: Our study aimed to characterize the clinical, immunological and virological features of confirmed dengue patients in Sri Lanka during the outbreak in 2017 when unusual manifestations of severe dengue were observed., Study Design: Sera from 295 patients who were admitted to Teaching Hospital Kandy, Kandy, Sri Lanka between March 2017- January 2018 were subjected to NS1 antigen, IgM and IgG ELISAs, virus isolation, conventional and real time RT-PCR and next generation sequencing., Results: Primary and secondary infections were detected in 48.5 % and 51.5 % of the study population, respectively. Two hundred twenty five DENV strains were isolated (219 DENV-2, one DENV-3, two DENV-4, two mixed infections of DENV-2 and -3 and one mixed infection of DENV-2 and -4). Unusual and severe manifestations such as encephalitis, encephalopathy, liver failure, kidney failure, myocarditis, Guillain-Barré syndrome and multi-organ failure were noted in 44 dengue patients with 11 deaths. The viraemia levels in patients with primary infection and unusual manifestations were significantly higher compared to those in patients with secondary infection. A new clade of DENV-2 Cosmopolitan genotype strains was observed with the strains closely related to those from China, Malaysia, Indonesia, Singapore and Taiwan., Conclusions: The new clade of DENV-2 cosmopolitan genotype observed in Sri Lanka in 2017 caused an unprecedented, severe dengue outbreak. The emergence of DENV-3 and DENV-4 in the 2017 outbreak might cause future outbreaks in Sri Lanka., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The study aimed to develop dengue severity score to assess severe manifestations among hospitalized patients with dengue infection., Method: Children and adolescents with serologically confirmed dengue infection admitted at Ramathibodi Hospital from 2004 to 2018 and treated by an expert multidisciplinary team were recruited. Medical records were retrospectively reviewed and 14 items, related to clinical parameters and managements during hospitalization, were obtained daily as dengue severity score., Results: A total of 191 patients with a mean age of 10.7 years from 2004 to 2013 were recruited. They were classified as dengue fever (35), dengue hemorrhagic fever (DHF) I (53), II (50), III (37) and IV (16). The analysis of 593 daily records revealed the range of daily severity score among patients with DHF grades III (10-20) and IV (31-47) were significantly higher than those of other groups (dengue fever, 5-13; DHF I, 2-10; DHF II, 6-11) with P-values of 0.0001. Using a validity test, a total daily score of ≥12 was an assessment tool for dengue shock syndrome with sensitivity, 86% and specificity, 84%. An additional 51 hospitalized patients with DHF grades II, III and IV with similar ages from 2014 to 2018 were recruited. The number of patients with severe manifestations, having daily score of ≥12, was significantly higher than those without severe manifestations starting from Day -3 to Day +1 of illness., Conclusions: Daily dengue severity score of ≥12 was an accurate assessment tool for severe manifestations.

Dengue viral infection (DVI) has emerged as one of the most common arthropod borne diseases and is more prevalent in the tropical countries. It has varied clinical spectrum ranging from undifferentiated fever to severe hemorrhagic fever and shock with multi-organ dysfunction. Acute kidney injury (AKI) is lesser known complication in DVI. Although studies report varying reports of AKI in DVI among children, exact incidence is not known as most of the studies are retrospective. Hospital-based observational study in 105 children with DVI requiring admission was studied for the occurrence of AKI along with clinical course and outcome. AKI Network (AKIN) criteria were used to define AKI. The IBM SPSS Statistics software version 21.0 was used for the statistical analysis. Of 105 children with dengue, six (5.71%) cases developed AKI. All six cases had urine output <0.5 mL/kg/h for ≥12 h. Out of six cases with AKI, four had raised serum creatinine (SCr) ≥0.3 mg/dL at admission. One child had normal SCr level at admission which got deranged over the next 12 h, one child had oliguria ( <0.5 mL/kg/h) for about 24 h though the renal function was not deranged. Out of six children with AKI, three (50%) in Stage III and three had AKI Stage II as per the AKIN criteria. Children with AKI (Group A) differed significantly from those without AKI (Group B) in having blood pressure <3 rd centile (P = 0.0023), tachycardia P = 0.008), hyponatremia and hypokalemia (P <0.001 and P = 0.029, respectively) and poor outcome 6% mortality in Group B compared to 66.67% in Group A) with P = 0.001. AKI is not a common complication of DVI but if develops it may lead to significant morbidity and mortality among pediatric age group.

Dengue is a potentially fatal acute febrile illness caused by any of four mosquito-transmitted dengue viruses (DENV-1 to DENV-4) belonging to the family Flaviviridae and endemic throughout the tropics. Competent mosquito vectors of DENV are present in approximately one half of all U.S. counties. To describe epidemiologic trends in travel-associated and locally acquired dengue cases in the United States, CDC analyzed cases reported from the 50 states and District of Columbia to the national arboviral surveillance system (ArboNET). Cases are confirmed by detection of 1) virus RNA by reverse transcription-polymerase chain reaction (RT-PCR) in any body fluid or tissue, 2) DENV antigen in tissue by a validated assay, 3) DENV nonstructural protein 1 (NS1) antigen, or 4) immunoglobulin M (IgM) anti-DENV antibody if the patient did not report travel to an area with other circulating flaviviruses. When travel to an area with other flaviviruses was reported, IgM-positive cases were defined as probable. During 2010-2017, totals of 5,009 (93%) travel-associated and 378 (7%) locally acquired confirmed or probable dengue cases were reported to ArboNET. Cases were equally distributed between males and females, and median age was 41 years. Eighteen (three per 1,000) fatal cases were reported, all among travelers. Travelers should review country-specific recommendations (https://wwwnc.cdc.gov/travel/notices/watch/dengue-asia) for reducing their risk for DENV infection, including using insect repellent and staying in residences with air conditioning or screens on windows and doors., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Background: To describe the characteristics of dengue in sickle cell children and try to identify risk factors of severity., Methods: In this retrospective study, we describe the evolution according to genotype (SS or SC and controls) and severity., Results and Conclusions: From 2005 to 2013, 106 hospitalizations for dengue fever were recorded, 35 SS genotype, 35 SC and 36 without SCD or any other chronic disease. The clinical evolution was quite different. During hospitalization, SC patients were more likely to develop multiorgan failure (31.4% versus 25.7% for SS, and 0% for controls, p=0.001), or acute pulmonary complications than patients without SC sickle cell disease (14.3% versus 8.6% for SS, and 0% for controls, p=0.03). Level 3 analgesic treatment was more frequent in SC patients (22.9% versus 3% for SS, and 0% for controls, p<0.001). Patients with SC sickle cell disease had a higher proportion of severe forms of dengue (57.1% versus 37.1% for SS, and 0% for controls, p<0.001) than patients without SC sickle cell disease. Transfer in intensive care unit was required for most SC patients (22.9% versus 3% for SS, and 0% for controls, p=0.005).Fatal episodes were more frequent in SC patients than in patients without SC sickle cell disease (5 deaths versus 1 for SS and 0 for controls, p=0.02). Thirty-three patients (47.1%) were diagnosed as having severe dengue (13 SS and 20 SC). On univariate analysis, age >10 years, acute pulmonary complications, multiorgan failure, severe anemia requiring transfusion, use of antibiotic treatment, need for treatment with morphine, and longer hospital stay were statistically more frequent in severe dengue-associated cases. Multiple logistic regression analysis showed that HbSC genotype and acute pulmonary complications, were significantly associated with severe dengue. In the multivariate model, the area of the ROC curve was 0.831. Children with SC genotype, typically thought to have less severe disease, actually had a higher rate of severe dengue and death than those with SS genotype., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Dengue has long been a public health problem in tropical and subtropical countries. In 2015, a dengue outbreak occurred in Taiwan, where 43,784 cases were reported. This study aims to assess the impact of dengue on Southern Taiwan's economic growth according to the economic growth model-based regression approach recommended by the World Health Organization (WHO). Herein, annual data from Southern Taiwan on the number of dengue cases, income growth, and demographics from 2010-2015 were analyzed. The percentage of reduction of the average income per capita in 2015 due to the dengue outbreak was estimated. Dengue was determined to have a negative linear economic impact on Southern Taiwan's economic growth. In particular, a reduction of 0.26% in the average income per capita was estimated in Southern Taiwan due to the 2015 outbreak. If the model is applied alongside other dengue outbreak forecast models, then the forecast for economic reduction due to a future dengue outbreak may also be estimated. Prevention and recovery policies may subsequently be decided upon based on not only the number of dengue cases but also the degree of economic burden resulting from an outbreak., Competing Interests: The authors declare no conflict of interest.

Introduction: Increasing number and the complexity of dengue cases pose a great challenge. The dengue outbreak preparedness and contingency plan is a series of collective intervention or polices put into place via collective agreement between administrative, Medical, Emergency Department and Intensive Care Unit (ICU). The aim of this paper is to evaluate the impact implementation of a dengue contingency plan on the clinical outcome of dengue cases. Methods: Implementation of the dengue outbreak preparedness and contingency plan was commenced in 2017. A pre-intervention (2017) and post-intervention (2018) retrospective review of mortality cases and referral to ICU were undertaken. The interventions included mandatory fast review by Emergency Physician, Medical Physician and Anaesthesist in Emergency Department for ill patients (Dengue Care Pathway), cohorting dengue patient to one ward with mandatory monitoring and review system, clinical management adhering to the Clinical Practice Guideline of Management of Dengue Infection in Adults (2015), referring ill patients to ICU, deployment of nurses and experienced doctors to the dengue ward based on ratio of staff to patients, increasing number of doctors on-call at the dengue ward and a dengue bed manager system led by the Matron and Sisters. The plan was activated by mutual agreement between the Head of Medical Department and the Hospital Director. Results: There was a marked increment of admission of dengue cases into intensive care unit by 59% either directly from emergency department or the dengue wards in 2018 compared to 2017. The mortality rates reduced significantly from 5.4 deaths for every 1000 admission in 2017 to 3.3 in 2018. This is a reduction 2.1 death for every 1000 dengue admission. Conclusion: The implementation of the dengue outbreak preparedness and contingency plan aided the team to provide best care and practice in dengue management especially in the severely ill. [ABSTRACT FROM AUTHOR]

Background: Hepatic dysfunction and coagulopathy are common in acute dengue illness. We analyzed the trajectories of the above parameters in the survivors and fatal patients in the outbreak in Tainan, 2015., Methods: A retrospective study was conducted using data from a tertiary hospital between January and December 2015. Multilevel modeling (MLM) was used to identify the changes in aminotransferase (AST), alanine aminotransferase (ALT), activated partial thromboplastin time (aPTT), and platelet counts from Day 0 to Day 7 of the onset of dengue infection. The machine-learning algorithm was used by purity measure assumption to calculate the accuracy of serum transaminases and coagulation variables to discriminate between the fatal and survival groups., Results: There were 4,069 dengue patients, of which 0.9% died in one week after illness onset (i.e., early mortality). Case fatality rate was the highest for those aged ≥70 years. Both AST and ALT values of the fatal group were significantly higher than those of the survivor group from Day 3 (AST median, 624 U/L vs. 60 U/L, p < 0.001; ALT median, 116 U/L vs. 29 U/L, p = 0.01) of illness onset and peaked on Day 6 (AST median, 9805 U/L vs. 90 U/L, p < 0.001; ALT median, 1504 U/L vs. 49 U/L, p < 0.001). AST ≥ 203 U/L, ALT ≥ 55 U/L, AST2/ALT criteria ≥337.35, or AST/platelet count ratio index (APRI) ≥ 19.18 on Day 3 of dengue infection had a high true positive rate, 90%, 78%, 100%, or 100%, respectively, of early mortality. The platelet counts of the fatal group declined significantly than those of the survivor group since Day 3 of illness onset (median, 19 x103/μl vs. 91 x103/μl, p < 0.01), and aPTT values of the fatal group significantly prolonged longer since Day 5 (median, 68.7 seconds vs. 40.1 seconds, p < 0.001)., Conclusions: AST, ALT, and platelet counts should be monitored closely from Day 0 to Day 3 of dengue infection, and aPTT be followed up on Day 5 of infection to identify the individuals at risk for early mortality., Competing Interests: The authors have declared that no competing interests exist.

Objective: to describe the experience and preliminary results of the Arbovirus Death Investigation Committee in Ceará, Brazil, in 2017., Methods: the Committee investigates and discusses all suspected cases of arbovirus deaths reported by the epidemiological surveillance service., Results: a total of 443 suspected arbovirus deaths were reported, 220 (49.7%) of which were confirmed; of these, 88.2% were from chikungunya and 11.8% from dengue; the median age of chikungunya deaths was higher when compared to dengue (77 versus 56 years) and the time until death was also longer when compared to dengue (38 versus 12 days); median time for case closure was 54.5 days; in 2017, Ceará confirmed 80.4% of Brazilian chikungunya deaths., Conclusion: the investigation of deaths showed that CHIK viruses were responsible for the majority of arboviral deaths in the state of Ceará, in 2017.

Dengue is one of the most important mosquito-borne viral diseases. Over half of the world's population is living in dengue endemic countries, where 100 million cases are estimated to occur annually. Although one dengue vaccine is currently available commercially, unfortunately its safety and efficacy has not been demonstrated for seronegative populations. Therefore, other vaccine candidates as well as antivirals are urgently required to control dengue diseases. To contribute to the development of preventative measures, in the present study we established an immunocompetent-mouse infection model using dengue virus type 1 Mochizuki strain. Following intraperitoneal injection with K562 cells infected with Mochizuki strain, all mice injected with ≥1 × 10 6  cells were killed within 7-11 days. Mice injected with ≥1 × 10 7  cells showed viremia (~10 4 -10 5 FFU/ml) within 24 h of injection. Since a higher infective titer was detected in the mouse brain, this suggested that viruses were transmitted from the blood circulation into the brain. In further experiments, mice immunized with two types of DNA vaccines were challenged with virus. In contrast to the non-immunized control mice, all vaccinated mice survived after challenge. This immunocompetent-mouse infection model using dengue virus type 1 Mochizuki strain may be a useful tool to evaluate vaccines and preventive medicines against dengue virus., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Although epidemiological and molecular epidemiological (serotype, genotype, and lineage information) data are available for several major cities in Indonesia, there is yet to be a comprehensive national study of dengue in Indonesia over time. This study was conducted to provide a comprehensive epidemiology of circulating dengue viruses (DENV) in Indonesia between 1973 and 2016. This was conducted through a systematic review of the literature and phylogenetic analysis of available DENV sequences. Available data from National Disease Surveillance System have indicated an increasing trend of dengue incidence in Indonesia over the past 50 years. Incidence rates appear to be cyclic, peaking approximately every 6 to 8 years. In contrast, the case fatality rate has decreased approximately by half with each decade since 1980. Over this 50-year time span, serotype shifts, genotype displacement within DENV-1 and DENV-2, and introduction of DENV-1 and DENV-3 genotype from other countries occurred. These events were associated with increased incidence of dengue cases. Our study also provides a valuable national snapshot of DENV genetic diversity in Indonesia that may contribute to development of more effective dengue vaccine compositions for the region., (© 2019 John Wiley & Sons, Ltd.)

Objectives: This paper concerns a systematic analysis of dengue illness and costs in India from 2013 to 2016. A previous study for 2006-2012 found that that projected annual number of dengue cases (5.78 million) was 282 times the officially reported number (20,474), highlighting enormous uncertainty., Methods: This study updated primary data for India from 2012 to 2014 and synthesized the latest epidemiological and economic literature through 2018 using the country and global estimates., Results: The first empirically-based publication of dengue costs by country (in 2016) estimated India experienced 18,618,706 symptomatic dengue cases and 1602 deaths, and cost $1.51 billion in 2013. With a combination of increased incidence, more refined methods, and better data this 2018 study raised the latest estimates to 53,210,706 cases, 22,527 deaths, and $5.71 billion economic costs for 2016, representing increases over the previous publication of 186%, 1306%, and 278%, respectively. When consistent methods and data were used to compare 2013 to 2016, the corresponding changes were only +29%, -9%, and +12%, respectively over these 3 years., Conclusions: India's burden of dengue is substantially greater than previously estimated. Although uncertainty intervals remain wide, these latest estimates reinforce the health and economic benefits that India would realize if dengue were substantially controlled., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To provide a national incidence rate and case fatality rate of dengue hemorrhagic fever in Indonesia through an analysis of the National Disease Surveillance database from the Directorate General of Disease Prevention and Control of Ministry of Health., Results: Available data has indicated an increasing trend of dengue hemorrhagic fever incidence in Indonesia over the past 50 years. Incidence rates appear to be cyclic, peaking approximately every 6-8 years. In contrast, the case fatality rate has decreased approximately by half each decade, since 1980. Java Island contributed the highest average number of dengue hemorrhagic fever cases each year. In recent years, Bali and Borneo (Kalimantan) have had the highest incidence while Papua Island, the easternmost region of the Indonesian archipelago, has had the lowest incidence.

Introduction: Dengue virus serotype-3 caused a large community-level outbreak in Fiji in 2013 and 2014. We aimed to characterize the demographic features of affected individuals and to determine dengue mortality during the outbreak., Methods: All laboratory-confirmed dengue cases and deaths were included in this study. Incidence and mortality were calculated according to demographic variables., Results: A total of 5221 laboratory-confirmed cases of dengue were included in this analysis. The majority of patients were male (54.5%) and indigenous Fijians (iTaukei) (53.5%). The median age was 25 years old. The overall incidence was 603 per 100 000 population. The age-specific incidence was highest among people between 20 and 24 years of age (1057 per 100 000) for both sexes. The major urban and peri-urban areas of Suva and Rewa subdivisions reported the highest incidence of > 1000 cases per 100 000 population. ​: A total of 48 deaths were included in this analysis. The majority of dengue-related deaths occurred in males (62.5%) and in the iTaukei (60.4%) population. The median age at death was 35 years old. The overall dengue-related deaths was estimated to be 5.5 deaths per 100 000 population. Dengue mortality was higher for males (6.8 per 100 000) than females. The highest age- and sex-specific mortality of 18 per 100 000 population was among males aged 65 years and older., Discussion: Dengue morbidity and mortality were highest among males, indigenous people and residents of urban and peri-urban locations. Effective and integrated public health strategies are needed to ensure early detection and appropriate outbreak control measures., ((c) 2019 The authors; licensee World Health Organization.)

Background: State-specific disability-adjusted life years (DALYs) are seldom calculated. Understanding the health and disease trends in groups of states is useful for finding the heterogeneity of disease epidemiology in the country., Objective: The objective of the study was to assess dengue burden in Kerala state, using DALY., Methods: DALY was computed using the DALY package of R. Incidence was derived using reported and estimated dengue cases for 2006-2016. Mortality was calculated using reported deaths. We computed DALYs using the mortality estimates for the South-East Asia region (SEAR) also. Sensitivity and scenario analyses were done., Results: The highest estimated relative DALY for dengue is 7.22 (95% confidence interval [CI]: 6.66-7.72) per lakh population. The DALY obtained using the mortality rates of SEAR ranged from 19.89 (95% CI: 8.44-29.45) per lakh population to 28.56 (95% CI: 17.04-38.05). We observed a cyclical pattern of increase in DALY every 2-3 years. The DALY in lower age groups is lesser. DALY in females was higher than males., Conclusions: The dengue-related DALY for the state of Kerala is lower than that of the global burden of disease due to lower mortality rates. Mortality reduction becomes the key to reducing burden, especially in areas of low incidence. The study also forms the benchmark for evaluating and implementing cost-effective measures for dengue control in the state., Competing Interests: None

Background: Linking routinely-collected data provides an opportunity to measure the effects of exposures that occur before birth on maternal, fetal and infant outcomes. High quality linkage is a prerequisite for producing reliable results, and there are specific challenges in mother-baby linkage. Using population-based administrative databases from Brazil, this study aimed to estimate the accuracy of linkage between maternal deaths and birth outcomes and dengue notifications, and to identify potential sources of bias when assessing the risk of maternal death due to dengue in pregnancy., Methods: We identified women with dengue during pregnancy in a previously linked dataset of dengue notifications in women who had experienced a live birth or stillbirth during 2007-2012. We then linked this dataset with maternal death records probabilistically using maternal name, age and municipality. We estimated the accuracy of the linkage, and examined the characteristics of false-matches and missed-matches to identify any sources of bias., Results: Of the 10,259 maternal deaths recorded in 2007-2012, 6717 were linked: 5444 to a live birth record, 1306 to a stillbirth record, and 33 to both a live and stillbirth record. After identifying 2620 missed-matches and 124 false-matches, our estimated sensitivity was 72%, specificity was 88%, and positive predictive value was 98%. Linkage errors were associated with maternal education and self-identified race; women with more than 7 years of education or who self-declared as Caucasian were more likely to link. Dengue status was not associated with linkage error., Conclusion: Despite not having unique identifiers to link mothers and birth outcomes, we demonstrated a high standard of linkage, with sensitivity and specificity values comparable to previous literature. Although there were no differences in the characteristics of dengue cases missed or included in our linked dataset, linkage error occurred disproportionally by some social-demographic characteristics, which should be taken into account in future analyses., Competing Interests: The authors have declared that no competing interests exist.