Dengue is an arboviral disease caused by the dengue virus,with 390 million infections reported annually worldwide.It is classified into two categories:dengue without or with warning signs and severe dengue.[1]Given th...Dengue is an arboviral disease caused by the dengue virus,with 390 million infections reported annually worldwide.It is classified into two categories:dengue without or with warning signs and severe dengue.[1]Given the moderate efficacy of the dengue vaccine,[2]there is an urgent necessity to design host-directed therapeutic strategies,such as the repurposing of FDA-approved drugs,to combat dengue virus infection.展开更多
BACKGROUND Severe dengue children with critical complications have been attributed to high mortality rates,varying from approximately 1%to over 20%.To date,there is a lack of data on machine-learning-based algorithms ...BACKGROUND Severe dengue children with critical complications have been attributed to high mortality rates,varying from approximately 1%to over 20%.To date,there is a lack of data on machine-learning-based algorithms for predicting the risk of inhospital mortality in children with dengue shock syndrome(DSS).AIM To develop machine-learning models to estimate the risk of death in hospitalized children with DSS.METHODS This single-center retrospective study was conducted at tertiary Children’s Hospital No.2 in Viet Nam,between 2013 and 2022.The primary outcome was the in-hospital mortality rate in children with DSS admitted to the pediatric intensive care unit(PICU).Nine significant features were predetermined for further analysis using machine learning models.An oversampling method was used to enhance the model performance.Supervised models,including logistic regression,Naïve Bayes,Random Forest(RF),K-nearest neighbors,Decision Tree and Extreme Gradient Boosting(XGBoost),were employed to develop predictive models.The Shapley Additive Explanation was used to determine the degree of contribution of the features.RESULTS In total,1278 PICU-admitted children with complete data were included in the analysis.The median patient age was 8.1 years(interquartile range:5.4-10.7).Thirty-nine patients(3%)died.The RF and XGboost models demonstrated the highest performance.The Shapley Addictive Explanations model revealed that the most important predictive features included younger age,female patients,presence of underlying diseases,severe transaminitis,severe bleeding,low platelet counts requiring platelet transfusion,elevated levels of international normalized ratio,blood lactate and serum creatinine,large volume of resuscitation fluid and a high vasoactive inotropic score(>30).CONCLUSION We developed robust machine learning-based models to estimate the risk of death in hospitalized children with DSS.The study findings are applicable to the design of management schemes to enhance survival outcomes of patients with DSS.展开更多
Dengue virus(DENV)is a positive-sense single-stranded RNA virus belonging to the genus Flavivirus within the Flaviviridae family.Four serotypes,DENV 1-4,are distributed globally[1].Hanoi metropolitan city is an endemi...Dengue virus(DENV)is a positive-sense single-stranded RNA virus belonging to the genus Flavivirus within the Flaviviridae family.Four serotypes,DENV 1-4,are distributed globally[1].Hanoi metropolitan city is an endemic hotspot for DENV transmission in Vietnam[2,3].The largest outbreak occurred in 2017,with more than 36000 cases and 7 deaths reported,causing by all four serotypes with the predominance of DENV1,following by DENV2[4,5].During the following dengue season,we collected 390 blood and serum samples from 197 hospitalized patients in a national hospital in Hanoi city,Northern Vietnam to identify the circulating DENV serotypes responsible for the 2018-2019 outbreak.展开更多
In this editorial,we comment on the article by Teerasarntipan et al published in a recent issue of the World Journal of Gastroenterology.Dengue infection is a major mosquito-borne disease with global significance.Deng...In this editorial,we comment on the article by Teerasarntipan et al published in a recent issue of the World Journal of Gastroenterology.Dengue infection is a major mosquito-borne disease with global significance.Dengue-induced severe hepatitis(DISH)is a rare complication though severe,as it can lead to acute liver failure(ALF)with an incidence rate between 0.7%and 2.0%and mortality rates from 47.0%to 58.8%.In this context,the identification of patients at risk of ALF could improve prognosis in DISH patients.Teerasarntipan et al retrospectively enrolled 2532 dengue patients,counting 193 DISH and 20 ALF.The authors explored the prognostic role of liver-specific scores,as the model for end-stage liver disease(MELD)score,albumin-bilirubin(ALBI)score,easy(EZ)-ALBI score,and platelet-ALBI(PALBI)score.Univariate analysis identified international normalized ratio(INR),total bilirubin,albumin,and creatinine as independent laboratory factors associated with ALF,while age,gender,and liver comorbidities were not linked to in-hospital mortality.The presence of dengue shock syndrome significantly increased mortality,with an odds ratio(OR)of 28.05(95%CI:7.21-109.18,P<0.001).High INR and low albumin were laboratory markers associated with death from DISH,with ORs of 5.83(95%CI:2.59-13.12,P<0.001)and 0.15(95%CI:0.05-0.44,P<0.001),respectively.Multivariate analysis confirmed that INR remained the only significant predictor of both ALF and death,with adjusted ORs of 19.54(95%CI:3.37-113.38,P<0.001)and 3.86(95%CI:1.13-13.18,P=0.031),respectively.Among prognostic models,the MELD score performed best in predicting ALF,with a very high accuracy[area under the receiver operating characteristic curve(AUROC)of 0.929,87.5%sensitivity,89.3%specificity at a cutoff of 16],followed by the EZ-ALBI,ALBI,and PALBI scores,with AUROCs of 0.865,0.832,and 0.797,respectively.As MELD remains the best scoring system for predicting poor outcomes in DISH-related ALF,EZ-ALBI is a valid adjunct tool that could improve medical care in these patients.展开更多
Dengue fever remains a significant public health challenge in Malaysia,with its incidence continuing to rise despite existing control measures.Dengue,a disease caused by the dengue virus and transmitted by Aedes mosqu...Dengue fever remains a significant public health challenge in Malaysia,with its incidence continuing to rise despite existing control measures.Dengue,a disease caused by the dengue virus and transmitted by Aedes mosquitoes,places a substantial burden on healthcare systems and economic productivity.Despite efforts by the Malaysian government,including the release of Wolbachia-carrying Aedes aegypti mosquitoes in dengue hotspot areas since 2017,the problem persists.In 2023,Malaysia reported 123133 dengue cases,an 86.3%increase compared to 2022[1].This highlights the urgent need for more effective interventions,including the potential integration of dengue vaccines into routine immunization programs.Currently,two dengue vaccines have been licensed:Dengvaxia(CYD-TDV)by Sanofi Pasteur and Qdenga(TAK-003)by Takeda.Dengvaxia,the first licensed dengue vaccine,has significant limitations,as it increases the risk of hospitalization in dengue-naïve individuals due to antibody-dependent enhancement[2,3].As a result,it is only licensed for individuals with prior dengue infections,necessitating pre-vaccination screening.These constraints make it unsuitable for inclusion in Malaysia’s routine immunization programs.展开更多
One of the most promising vector control strategies for controlling dengue fever is the stable introduction of the obligate intracellular Wolbachia bacteria strain into Aedes aegypti mosquitoes. This method reduces th...One of the most promising vector control strategies for controlling dengue fever is the stable introduction of the obligate intracellular Wolbachia bacteria strain into Aedes aegypti mosquitoes. This method reduces the mosquito’s ability to transmit dengue through reproductive strategies associated with Wolbachia infection, such as parthenogenesis, male elimination or feminization, sex ratio distortions and cytoplasmic incompatibility. Expert knowledge and a risk assessment framework were used to identify the risks associated with the release of Wolbachia-bearing mosquitoes. Then, consultations with individual participants were organized and a Bayesian network (BN) was developed to capture the relationship between the hazards as well as the likelihood of these adverse events occurring. Finally, risk was calculated from the probability and consequence estimates obtained from our Burkina Faso participants, using a questionnaire based on the identified risks. Our “Cause More Harm” study yielded 46.15% negligible risk, 44.23% very low risk and 9.62% low risk. The “socio-cultural change” parameter had the greatest influence, with the perception that the dissemination project would be poorly received by the local population. This parameter alone accounted for 80% of the most significant risks. This explains the fact that hazard RA 49 “negative messages in social media” is ranked as the highest individual risk (although the risk is low) with a calculated risk of 0.261. The risk assessment was designed to integrate the interdependent complexity of hazards likely to affect the dissemination of technology in the environment. It represents an important implementation phase in the success of this innovative research, introducing a new technology to combat the transmission of dengue fever.展开更多
Over the last few decades, dengue fever epidemics have increased in frequency and intensity worldwide, making it a major global concern for public health. Its prevention, which is essentially vector-based control, is ...Over the last few decades, dengue fever epidemics have increased in frequency and intensity worldwide, making it a major global concern for public health. Its prevention, which is essentially vector-based control, is already being compromised by reports of resistance of the main vector Aedes aegypti to insecticides. To tackle the rapid increase in insecticide resistance and outbreaks, the biological vector control is a promising approach. One of the strategies of this approach is the use of entomopathogenic fungi because of their great efficacy and their eco-friendly aspects. However, some aspects of their use, such as the low efficiency, the high cost of production and the sensitivity to various adverse conditions, need to be addressed for their successful large-scale application. Therefore, innovative technologies based on strains of transgenic fungi with improved biocontrol potentials by genetic engineering are actively pursued. Although these modified mycoinsecticides are acclaimed for their better effectiveness against target insects, the main concern remains their potential adverse effects on the environment and human health. The present review is dedicated to giving an update on recent developments in transgenic entomopathogenic fungi (TEF) for Aedes mosquito control. Future perspectives are also proposed to address the safety concerns related to the release of transgenic entomopathogenic fungi into the environment.展开更多
The current recommendation to avoid non-steroidal anti-inflammatory drugs(NSAIDs)in the management of dengue virus disease(DVD)is scientifically considered of very low to low certainty,despite being widely adopted wor...The current recommendation to avoid non-steroidal anti-inflammatory drugs(NSAIDs)in the management of dengue virus disease(DVD)is scientifically considered of very low to low certainty,despite being widely adopted worldwide.The same recommendation,initially made during the coronavirus disease 2019(COVID-19)pandemic,was subsequently proven incorrect.In this clinical report,we present evidence,for the first time globally,from a real-life practice that NSAIDs may actually be lifesaving in the early management of DVD as they have proved to be in COVID-19.Moreover,we propose that the personalized immunemodulatory Kelleni’s protocol,which includes nitazoxanide as a key component,can be safely and effectively used to manage various separate or concomitant viral infections and co-infections,including DVD.Importantly,this article contributes to the current medical knowledge in the global pursuit of a safe and effective broad-spectrum antiviral protocol that can be used to early manage multiple highly infectious viruses.However,it’s crucial that sufficiently powered controlled randomized clinical trials be conducted to thoroughly assess and evaluate the safety of NSAIDs in the early management of DVD as well as the efficacy of nitazoxanide with or without NSAIDs in its management.展开更多
Objective:Children below 14 years of age are highly vulnerable to dengue infection and are at a greater risk of developing severe dengue illness.This study aimed to investigate the trends in the burden of dengue fever...Objective:Children below 14 years of age are highly vulnerable to dengue infection and are at a greater risk of developing severe dengue illness.This study aimed to investigate the trends in the burden of dengue fever among children below 14 years of age in China from 1990 to 2021 and to project the disease burden from 2022 to 2035.Methods:Based on the datasets derived from the Global Burden of Disease Study 2021,the following data were collected from dengue-affected children aged ≤14 years in China from 1990 to 2021:number and rate of incident dengue cases,number of prevalent dengue cases,number of deaths due to dengue,and disability-adjusted life years(DALYs) lost due to dengue.The trends in disease burden were examined based on average annual percent change(AAPC) and annual percent change,and the burdens were proj ected from 2022 to 2035 by using a Bayesian age-period-cohort model.Results:The incidence and prevalence of dengue fever were increased in children aged ≤ 14 years in China from1990 to 2021(AAPC=5.42 % and 5.44 %,respectively,P <0.001),while the mortality and DALYs rates were reduced(AAPC=-8.21 % and-7.55 %,respectively,P <0.001).The burden was comparable between genders,with numerically lower incidence and prevalence in boys than in girls.The lowest incidence and prevalence and the highest mortality and DALYs rates were observed in children aged <5 years.The incidence and prevalence rates were projected to increase from 2022 to 2035;in contrast,the mortality and DALYs rates were projected to decrease during this period.Conclusions:Although the mortality and DALYs rates of dengue fever decreased significantly in children aged0-14 years in China from 1990 to 2021,the incidence and prevalence increased remarkably.Enhanced surveillance and ample health education programs and preventive interventions are recommended for targeting this high-risk population.展开更多
A study published by Teerasarntipan et al in the World Journal of Gastroenterology provides valuable insights into prognostic scoring for acute liver failure and inhospital mortality in patients with dengue-induced se...A study published by Teerasarntipan et al in the World Journal of Gastroenterology provides valuable insights into prognostic scoring for acute liver failure and inhospital mortality in patients with dengue-induced severe hepatitis.Their findings validate the model for end-stage liver disease score as the most reliable predictor while demonstrating the utility of the simpler Easy Albumin-Bilirubin score.Despite these findings,current prognostic models face limitations in realworld clinical applications.This letter discusses the strengths and weaknesses of current prognostic models,proposes future directions for improving prognostic accuracy and clinical implementations.This letter also broadens the horizons of prognostic models for liver dysfunction caused by other viral infections.展开更多
Currently, no clinically approved therapeutic drugs specifically target dengue virus infections. This study aims to evaluate the potential of antiviral drugs originally developed for other purposes as viable candidate...Currently, no clinically approved therapeutic drugs specifically target dengue virus infections. This study aims to evaluate the potential of antiviral drugs originally developed for other purposes as viable candidates for combating dengue virus. The RNA-elongating NS5-NS3 complex is a critical molecular structure responsible for dengue virus replication. Using the cryo-electron microscopy (Cryo-EM) structures available in the Protein Data Bank and AlphaFold 3 predictions, this study simulated the replication complexes of dengue virus serotypes 1, 2, 3, and 4. The RNA-dependent RNA polymerase (RdRp) domain of the NS5 protein within the NS5-NS3 complex was selected as the molecular docking template. Molecular docking simulations were conducted using AutoDock4. Seven small molecules—AT-9010, RK-0404678, Oseltamivir, Remdesivir, Favipiravir-RTP, Abacavir, and Ribavirin—were assessed for binding affinity by calculating their binding energies, where lower values indicate stronger molecular interactions. Based on published data, antiviral replication assays were conducted for the four dengue virus serotypes. AT-9010 and RK-0404678 were used as benchmarks for antiviral replication efficacy, while Oseltamivir served as the control group. The Mann-Whitney U test was employed to classify the clinical antiviral candidates—Remdesivir, Favipiravir-RTP, Abacavir, and Ribavirin. Results demonstrated that among the four small molecules, Favipiravir-RTP exhibited the highest binding affinity with the RdRp domain of the NS5-NS3 complex across all four dengue virus serotypes. Statistical classification revealed that in five simulated scenarios—including the four virus serotypes and Cryo-EM structural data—Favipiravir-RTP shared three classifications with the benchmark molecule AT-9010. Based on these findings, Favipiravir-RTP, a broad-spectrum antiviral agent, shows potential as a therapeutic option for inhibiting dengue virus replication. However, further clinical trials are necessary to validate their efficacy in humans.展开更多
Objective:To predict the distribution of dengue vector Aedes(Ae.)albopictus and identify high-risk areas for dengue fever transmission.Methods:Data on Ae.albopictus occurrences were collected from electronic databases...Objective:To predict the distribution of dengue vector Aedes(Ae.)albopictus and identify high-risk areas for dengue fever transmission.Methods:Data on Ae.albopictus occurrences were collected from electronic databases.Ensemble models were developed to assess the impacts of climate,vegetation,and human activity on Ae.albopictus.The optimal ensemble model was then used to identify the distribution of suitable areas for Ae.albopictus.Results:After removing duplicate sites and retaining only one location per 100 m×100 m grid,189 Ae.albopictus breeding sites were identified.The optimal ensemble model revealed that Ae.albopictus exhibited higher breeding suitability in Shanghai under specific conditions:a normalized difference vegetation index of 0.1 to 0.6,maximum precipitation in the warmest month ranging from 400 mm to 470 mm,maximum temperature in the warmest month between 30.0℃and 31.0℃,and proximity to waterways within 0.5 km.The most suitable habitats for Ae.albopictus were primarily concentrated in Shanghai’s central urban areas and scattered across the inner suburban districts.Conclusions:The high-risk areas of Ae.albopictus are widely distributed throughout the central urban area and scattered across the inner suburban district of Shanghai,creating conditions conducive to the outbreak of dengue fever.It is essential to enhance targeted control measures for Ae.albopictus in the identified risk areas.展开更多
Dengue fever presents a significant and persistent public health challenge in Sri Lanka.The disease,transmitted by Aedes aegypti and Aedes albopictus mosquitoes,affects individuals across all age groups,with working p...Dengue fever presents a significant and persistent public health challenge in Sri Lanka.The disease,transmitted by Aedes aegypti and Aedes albopictus mosquitoes,affects individuals across all age groups,with working populations and school-aged children at higher risk due to increased outdoor exposure[1].Dengue transmission in Sri Lanka is seasonal with two high transmission waves corresponding with the two monsoon rains every year.The estimated average annual incidence is 175/100000 population,and it was 407.5/100000 in 2023 with a case fatality rate of 0.07%[2].展开更多
In Burkina Faso, recent dengue outbreaks were exacerbated by Aedes aegypti mosquitoes, which have developed resistance to conventional insecticides. This study investigates the potential of Metarhizium pingshaense Met...In Burkina Faso, recent dengue outbreaks were exacerbated by Aedes aegypti mosquitoes, which have developed resistance to conventional insecticides. This study investigates the potential of Metarhizium pingshaense Met_S26, a fungus from Burkina Faso, for controlling both endophilic and exophilic Aedes mosquitoes. Traditional interventions are less effective against mosquitoes resting outdoors, and the ability of the fungus to be sexually transmitted could enhance its efficacy. Aedes mosquitoes were reared and exposed to various concentrations of Metarhizium pingshaense to assess its virulence. The fungus showed significant efficacy, with lethal times (LT80) ranging from 8.67 to 11.83 days depending on the concentration. Furthermore, bioassays demonstrated effective sexual auto-dissemination, with substantial transmission of fungal spores between infected and uninfected mosquitoes, leading to lower survival rates in uninfected mates. This study highlights Metarhizium pingshaense Met_S26 as a promising tool for controlling both indoor and outdoor Aedes populations, complementing existing vector control strategies such as the Sterile Insect Technique (SIT) and Wolbachia-based approaches. Future research should explore integrating this fungus with other control methods for a comprehensive vector management strategy.展开更多
In this paper,we establish an ShIhAhSvIvW model to investigate the impact of media communication on the transmission mechanism of dengue fever.Firstly,the basic reproduction number R0of the model is obtained by using ...In this paper,we establish an ShIhAhSvIvW model to investigate the impact of media communication on the transmission mechanism of dengue fever.Firstly,the basic reproduction number R0of the model is obtained by using the method of the next generation matrix.It shows that disease-free equilibrium is globally asymptotically stable when R0<1;the disease is uniformly persistent when R_(0)>1.Secondly,we select dengue fever case data from Guangdong Province from 2006 to 2019 for numerical simulations and predict its development trend.Finally,we conduct parameter sensitivity analysis,and the results show that increasing media publicity can to some extent reduce the number of patients.展开更多
Background:Dengue fever,an acute insect-borne infectious disease caused by the dengue virus(DENV),poses a great challenge to global public health.Hepatic involve-ment is the most common complication of severe dengue a...Background:Dengue fever,an acute insect-borne infectious disease caused by the dengue virus(DENV),poses a great challenge to global public health.Hepatic involve-ment is the most common complication of severe dengue and is closely related to the occurrence and development of disease.However,the features of adaptive immune responses associated with liver injury in severe dengue are not clear.Methods:We used single-cell sequencing to examine the liver tissues of mild or se-vere dengue mice model to analyze the changes in immune response of T cells in the liver after dengue virus infection,and the immune interaction between macrophages and T cells.Flow cytometry was used to detect T cells and macrophages in mouse liver and blood to verify the single-cell sequencing results.Results:Our result showed CTLs were significantly activated in the severe liver injury group but the immune function-related signal pathway was down-regulated.The rea-son may be that the excessive immune response in the severe group at the late stage of DENV infection induces the polarization of macrophages into M2 type,and the macrophages then inhibit T cell immunity through the TGF-βsignaling pathway.In ad-dition,the increased proportion of Treg cells suggested that Th17/Treg homeostasis was disrupted in the livers of severe liver injury mice.Conclusions:In this study,single-cell sequencing and flow cytometry revealed the characteristic changes of T cell immune response and the role of macrophages in the liver of severe dengue fever mice.Our study provides a better understanding of the pathogenesis of liver injury in dengue fever patients.展开更多
Dengue viruses(DENV)have spread throughout the world and pose a huge threat to human life.The most widespread serotype is type 2 DENV(DENV 2),which has no specific treatment.NS2B-NS3 protease plays a pivotal role in D...Dengue viruses(DENV)have spread throughout the world and pose a huge threat to human life.The most widespread serotype is type 2 DENV(DENV 2),which has no specific treatment.NS2B-NS3 protease plays a pivotal role in DENV replication because of its function in cleavage of the viral polyprotein;thus,it is considered a promising target for antiviral discovery.In this study,we developed a high-throughput screening system based on the NS2B-NS3 protease to identify candidates from an FDA-approved drug library.Eltrombopag was screened out of 3273 drugs,and demonstrated inhibition on DENV 2 at the micromolar level in vitro,significantly reducing viral loads in the targeted organs of challenged mice following intraperitoneal injection.Further mechanistic analysis showed that eltrombopag allosterically binds to the DENV 2 NS2B-NS3 protease in a reversible,noncompetitive manner,therefore inhibiting DENV 2 at the post-infection stage.In addition,eltrombopag inhibited the NS2B-NS3 proteases of DENV 4 and Zika virus,suggesting its potential as a broadspectrum antiviral agent.This study repurposed eltrombopag as a promising antiviral agent against DENV,providing an alternative for antiviral development against flaviviruses.展开更多
Rationale:Dengue fever is a mosquito-borne viral infection,which commonly presents as an acute febrile illness.As the number of cases increases,rare manifestations including neurological manifestations are occasionall...Rationale:Dengue fever is a mosquito-borne viral infection,which commonly presents as an acute febrile illness.As the number of cases increases,rare manifestations including neurological manifestations are occasionally encountered.Patient concerns:A 20-year-old female presented with fever for 3 days with slurring of speech and unsteady gait,which were developed from the third day of illness.On examination,she had bilateral cerebellar signs.Dengue non-structural protein 1 antigen and dengue IgM in serum were positive.Her cerebrospinal fluid analysis and magnetic resonance image brain were normal.Diagnosis:Dengue cerebellitis.Intervention:Supportive management with fluids including oral rehydration solutions and intravenous fluids and paracetamol.Outcome:Cerebellar symptoms and signs completely resolved by the 20th day of illness.Lesson:Dengue cerebellitis is an unusual neurological manifestation of dengue infection.展开更多
BACKGROUND Dengue-associated acute liver failure(PALF)accounts for a high mortality rate in children admitted to the pediatric intensive care unit(PICU).To date,there is a lack of data on clinical algorithms for estim...BACKGROUND Dengue-associated acute liver failure(PALF)accounts for a high mortality rate in children admitted to the pediatric intensive care unit(PICU).To date,there is a lack of data on clinical algorithms for estimating the risk of mortality in pediatric patients with dengue-induced severe hepatitis(DISH).AIM To determine the prevalence of PALF and identify the predictors of mortality among patients with DISH.METHODS This single-institution retrospective study was performed at a tertiary pediatric hospital in Vietnam between 2013 and 2022.The primary outcome was in-hospital mortality in pediatric patients with DISH,which was defined as either aspartate aminotransferase>350 IU/L or alanine aminotransferase>400 IU/L.Prognostic models for estimating the risk of death among patients with DISH were developed using a predefined set of clinical covariables and hepatic biomarkers on PICU admission and during the first 72 hours of admission.Area under the curve,multivariable logistic regression,and multiple imputation using the chained equation for missing values were performed.Backward stepwise model selection based on the Akaike information criterion was employed.Bootstrapping,calibration slope,and Brier score were used to assess the final models.RESULTS A total of 459 children with DISH were included in the analysis.The median patient age was 7.7 years(interquartile range:4.3-10.1 years).The prevalence of dengue-associated PALF in children with DISH was 18.3%.Thirty-nine DISH patients developing PALF(8.5%)died.Hepatic biomarkers,including the international normalized ratio(INR)≥2.11 and total serum bilirubin(≥1.7 mg/dL),showed high predictive values for mortality(all P values<0.001).Multivariable models showed the significant clinical predictors of death from dengue-induced PALF in patients with DISH,including reduced level of consciousness(pain and unresponsive levels on the Alert,Verbal,Pain,Unresponsive scale),high vasoactive-inotropic score(>30),and elevated levels of blood lactate,INR,and serum bilirubin.The final prognostic model demonstrated high discrimination,Brier score,and an acceptable calibration slope.CONCLUSION The prevalence of PALF in children with DISH is 18.3%.We developed robust prognostic models to estimate the risk of death in hospitalized children with severe dengue-induced hepatitis.展开更多
Dengue fever(DF)has become a major public health concern in Nepal,with increasing outbreaks in recent years.Transmitted by Aedes mosquitoes,this climate-sensitive viral disease presents a significant challenge for hea...Dengue fever(DF)has become a major public health concern in Nepal,with increasing outbreaks in recent years.Transmitted by Aedes mosquitoes,this climate-sensitive viral disease presents a significant challenge for healthcare providers and policymakers.Since 2004,Nepal has experienced a sharp increase in DF cases,peaking in 2022 with 54784 cases and 88 deaths.The surge,driven mainly by serotypes 1,2,and 3,is exacerbated by climate change,which prolongs mosquito breeding seasons due to warmer temperatures and increased rainfall.This trend has even impacted previously unaffected hilly regions.Effective dengue control strategies must focus on climate change adaptation,strengthening healthcare system reinforcement,raising public awareness,and enhancing vector control measures.Government initiatives,like the national dengue control program,play a critical role,but research and community engagement are also vital for prevention and early detection.Integrating climate resilience into public health efforts is essential to reducing the dengue burden in Nepal.展开更多
基金funded by grants Pronaii 302979A1-S-9005 CONACyT (México) from RMDA。
文摘Dengue is an arboviral disease caused by the dengue virus,with 390 million infections reported annually worldwide.It is classified into two categories:dengue without or with warning signs and severe dengue.[1]Given the moderate efficacy of the dengue vaccine,[2]there is an urgent necessity to design host-directed therapeutic strategies,such as the repurposing of FDA-approved drugs,to combat dengue virus infection.
文摘BACKGROUND Severe dengue children with critical complications have been attributed to high mortality rates,varying from approximately 1%to over 20%.To date,there is a lack of data on machine-learning-based algorithms for predicting the risk of inhospital mortality in children with dengue shock syndrome(DSS).AIM To develop machine-learning models to estimate the risk of death in hospitalized children with DSS.METHODS This single-center retrospective study was conducted at tertiary Children’s Hospital No.2 in Viet Nam,between 2013 and 2022.The primary outcome was the in-hospital mortality rate in children with DSS admitted to the pediatric intensive care unit(PICU).Nine significant features were predetermined for further analysis using machine learning models.An oversampling method was used to enhance the model performance.Supervised models,including logistic regression,Naïve Bayes,Random Forest(RF),K-nearest neighbors,Decision Tree and Extreme Gradient Boosting(XGBoost),were employed to develop predictive models.The Shapley Additive Explanation was used to determine the degree of contribution of the features.RESULTS In total,1278 PICU-admitted children with complete data were included in the analysis.The median patient age was 8.1 years(interquartile range:5.4-10.7).Thirty-nine patients(3%)died.The RF and XGboost models demonstrated the highest performance.The Shapley Addictive Explanations model revealed that the most important predictive features included younger age,female patients,presence of underlying diseases,severe transaminitis,severe bleeding,low platelet counts requiring platelet transfusion,elevated levels of international normalized ratio,blood lactate and serum creatinine,large volume of resuscitation fluid and a high vasoactive inotropic score(>30).CONCLUSION We developed robust machine learning-based models to estimate the risk of death in hospitalized children with DSS.The study findings are applicable to the design of management schemes to enhance survival outcomes of patients with DSS.
基金the“Metropolitan Mosquitoes Project”funded by the Swedish Research Council for Environment,Agricultural Sciences and Spatial Planning(Formas,grant number 2016-00364).
文摘Dengue virus(DENV)is a positive-sense single-stranded RNA virus belonging to the genus Flavivirus within the Flaviviridae family.Four serotypes,DENV 1-4,are distributed globally[1].Hanoi metropolitan city is an endemic hotspot for DENV transmission in Vietnam[2,3].The largest outbreak occurred in 2017,with more than 36000 cases and 7 deaths reported,causing by all four serotypes with the predominance of DENV1,following by DENV2[4,5].During the following dengue season,we collected 390 blood and serum samples from 197 hospitalized patients in a national hospital in Hanoi city,Northern Vietnam to identify the circulating DENV serotypes responsible for the 2018-2019 outbreak.
文摘In this editorial,we comment on the article by Teerasarntipan et al published in a recent issue of the World Journal of Gastroenterology.Dengue infection is a major mosquito-borne disease with global significance.Dengue-induced severe hepatitis(DISH)is a rare complication though severe,as it can lead to acute liver failure(ALF)with an incidence rate between 0.7%and 2.0%and mortality rates from 47.0%to 58.8%.In this context,the identification of patients at risk of ALF could improve prognosis in DISH patients.Teerasarntipan et al retrospectively enrolled 2532 dengue patients,counting 193 DISH and 20 ALF.The authors explored the prognostic role of liver-specific scores,as the model for end-stage liver disease(MELD)score,albumin-bilirubin(ALBI)score,easy(EZ)-ALBI score,and platelet-ALBI(PALBI)score.Univariate analysis identified international normalized ratio(INR),total bilirubin,albumin,and creatinine as independent laboratory factors associated with ALF,while age,gender,and liver comorbidities were not linked to in-hospital mortality.The presence of dengue shock syndrome significantly increased mortality,with an odds ratio(OR)of 28.05(95%CI:7.21-109.18,P<0.001).High INR and low albumin were laboratory markers associated with death from DISH,with ORs of 5.83(95%CI:2.59-13.12,P<0.001)and 0.15(95%CI:0.05-0.44,P<0.001),respectively.Multivariate analysis confirmed that INR remained the only significant predictor of both ALF and death,with adjusted ORs of 19.54(95%CI:3.37-113.38,P<0.001)and 3.86(95%CI:1.13-13.18,P=0.031),respectively.Among prognostic models,the MELD score performed best in predicting ALF,with a very high accuracy[area under the receiver operating characteristic curve(AUROC)of 0.929,87.5%sensitivity,89.3%specificity at a cutoff of 16],followed by the EZ-ALBI,ALBI,and PALBI scores,with AUROCs of 0.865,0.832,and 0.797,respectively.As MELD remains the best scoring system for predicting poor outcomes in DISH-related ALF,EZ-ALBI is a valid adjunct tool that could improve medical care in these patients.
文摘Dengue fever remains a significant public health challenge in Malaysia,with its incidence continuing to rise despite existing control measures.Dengue,a disease caused by the dengue virus and transmitted by Aedes mosquitoes,places a substantial burden on healthcare systems and economic productivity.Despite efforts by the Malaysian government,including the release of Wolbachia-carrying Aedes aegypti mosquitoes in dengue hotspot areas since 2017,the problem persists.In 2023,Malaysia reported 123133 dengue cases,an 86.3%increase compared to 2022[1].This highlights the urgent need for more effective interventions,including the potential integration of dengue vaccines into routine immunization programs.Currently,two dengue vaccines have been licensed:Dengvaxia(CYD-TDV)by Sanofi Pasteur and Qdenga(TAK-003)by Takeda.Dengvaxia,the first licensed dengue vaccine,has significant limitations,as it increases the risk of hospitalization in dengue-naïve individuals due to antibody-dependent enhancement[2,3].As a result,it is only licensed for individuals with prior dengue infections,necessitating pre-vaccination screening.These constraints make it unsuitable for inclusion in Malaysia’s routine immunization programs.
文摘One of the most promising vector control strategies for controlling dengue fever is the stable introduction of the obligate intracellular Wolbachia bacteria strain into Aedes aegypti mosquitoes. This method reduces the mosquito’s ability to transmit dengue through reproductive strategies associated with Wolbachia infection, such as parthenogenesis, male elimination or feminization, sex ratio distortions and cytoplasmic incompatibility. Expert knowledge and a risk assessment framework were used to identify the risks associated with the release of Wolbachia-bearing mosquitoes. Then, consultations with individual participants were organized and a Bayesian network (BN) was developed to capture the relationship between the hazards as well as the likelihood of these adverse events occurring. Finally, risk was calculated from the probability and consequence estimates obtained from our Burkina Faso participants, using a questionnaire based on the identified risks. Our “Cause More Harm” study yielded 46.15% negligible risk, 44.23% very low risk and 9.62% low risk. The “socio-cultural change” parameter had the greatest influence, with the perception that the dissemination project would be poorly received by the local population. This parameter alone accounted for 80% of the most significant risks. This explains the fact that hazard RA 49 “negative messages in social media” is ranked as the highest individual risk (although the risk is low) with a calculated risk of 0.261. The risk assessment was designed to integrate the interdependent complexity of hazards likely to affect the dissemination of technology in the environment. It represents an important implementation phase in the success of this innovative research, introducing a new technology to combat the transmission of dengue fever.
文摘Over the last few decades, dengue fever epidemics have increased in frequency and intensity worldwide, making it a major global concern for public health. Its prevention, which is essentially vector-based control, is already being compromised by reports of resistance of the main vector Aedes aegypti to insecticides. To tackle the rapid increase in insecticide resistance and outbreaks, the biological vector control is a promising approach. One of the strategies of this approach is the use of entomopathogenic fungi because of their great efficacy and their eco-friendly aspects. However, some aspects of their use, such as the low efficiency, the high cost of production and the sensitivity to various adverse conditions, need to be addressed for their successful large-scale application. Therefore, innovative technologies based on strains of transgenic fungi with improved biocontrol potentials by genetic engineering are actively pursued. Although these modified mycoinsecticides are acclaimed for their better effectiveness against target insects, the main concern remains their potential adverse effects on the environment and human health. The present review is dedicated to giving an update on recent developments in transgenic entomopathogenic fungi (TEF) for Aedes mosquito control. Future perspectives are also proposed to address the safety concerns related to the release of transgenic entomopathogenic fungi into the environment.
文摘The current recommendation to avoid non-steroidal anti-inflammatory drugs(NSAIDs)in the management of dengue virus disease(DVD)is scientifically considered of very low to low certainty,despite being widely adopted worldwide.The same recommendation,initially made during the coronavirus disease 2019(COVID-19)pandemic,was subsequently proven incorrect.In this clinical report,we present evidence,for the first time globally,from a real-life practice that NSAIDs may actually be lifesaving in the early management of DVD as they have proved to be in COVID-19.Moreover,we propose that the personalized immunemodulatory Kelleni’s protocol,which includes nitazoxanide as a key component,can be safely and effectively used to manage various separate or concomitant viral infections and co-infections,including DVD.Importantly,this article contributes to the current medical knowledge in the global pursuit of a safe and effective broad-spectrum antiviral protocol that can be used to early manage multiple highly infectious viruses.However,it’s crucial that sufficiently powered controlled randomized clinical trials be conducted to thoroughly assess and evaluate the safety of NSAIDs in the early management of DVD as well as the efficacy of nitazoxanide with or without NSAIDs in its management.
基金the Military Program for Clinical Cultivation Specialty and Chinese Preventive Medicine Association.
文摘Objective:Children below 14 years of age are highly vulnerable to dengue infection and are at a greater risk of developing severe dengue illness.This study aimed to investigate the trends in the burden of dengue fever among children below 14 years of age in China from 1990 to 2021 and to project the disease burden from 2022 to 2035.Methods:Based on the datasets derived from the Global Burden of Disease Study 2021,the following data were collected from dengue-affected children aged ≤14 years in China from 1990 to 2021:number and rate of incident dengue cases,number of prevalent dengue cases,number of deaths due to dengue,and disability-adjusted life years(DALYs) lost due to dengue.The trends in disease burden were examined based on average annual percent change(AAPC) and annual percent change,and the burdens were proj ected from 2022 to 2035 by using a Bayesian age-period-cohort model.Results:The incidence and prevalence of dengue fever were increased in children aged ≤ 14 years in China from1990 to 2021(AAPC=5.42 % and 5.44 %,respectively,P <0.001),while the mortality and DALYs rates were reduced(AAPC=-8.21 % and-7.55 %,respectively,P <0.001).The burden was comparable between genders,with numerically lower incidence and prevalence in boys than in girls.The lowest incidence and prevalence and the highest mortality and DALYs rates were observed in children aged <5 years.The incidence and prevalence rates were projected to increase from 2022 to 2035;in contrast,the mortality and DALYs rates were projected to decrease during this period.Conclusions:Although the mortality and DALYs rates of dengue fever decreased significantly in children aged0-14 years in China from 1990 to 2021,the incidence and prevalence increased remarkably.Enhanced surveillance and ample health education programs and preventive interventions are recommended for targeting this high-risk population.
基金Supported by The Natural Science Foundation of the Science and Technology Commission of Shanghai Municipality,No.23ZR1458300Key Discipline Project of Shanghai Municipal Health System,No.2024ZDXK0004+1 种基金Doctoral Innovation Talent Base Project for Diagnosis and Treatment of Chronic Liver Diseases,No.RCJD2021B02Pujiang Project of Shanghai Magnolia Talent Plan,No.24PJD098.
文摘A study published by Teerasarntipan et al in the World Journal of Gastroenterology provides valuable insights into prognostic scoring for acute liver failure and inhospital mortality in patients with dengue-induced severe hepatitis.Their findings validate the model for end-stage liver disease score as the most reliable predictor while demonstrating the utility of the simpler Easy Albumin-Bilirubin score.Despite these findings,current prognostic models face limitations in realworld clinical applications.This letter discusses the strengths and weaknesses of current prognostic models,proposes future directions for improving prognostic accuracy and clinical implementations.This letter also broadens the horizons of prognostic models for liver dysfunction caused by other viral infections.
文摘Currently, no clinically approved therapeutic drugs specifically target dengue virus infections. This study aims to evaluate the potential of antiviral drugs originally developed for other purposes as viable candidates for combating dengue virus. The RNA-elongating NS5-NS3 complex is a critical molecular structure responsible for dengue virus replication. Using the cryo-electron microscopy (Cryo-EM) structures available in the Protein Data Bank and AlphaFold 3 predictions, this study simulated the replication complexes of dengue virus serotypes 1, 2, 3, and 4. The RNA-dependent RNA polymerase (RdRp) domain of the NS5 protein within the NS5-NS3 complex was selected as the molecular docking template. Molecular docking simulations were conducted using AutoDock4. Seven small molecules—AT-9010, RK-0404678, Oseltamivir, Remdesivir, Favipiravir-RTP, Abacavir, and Ribavirin—were assessed for binding affinity by calculating their binding energies, where lower values indicate stronger molecular interactions. Based on published data, antiviral replication assays were conducted for the four dengue virus serotypes. AT-9010 and RK-0404678 were used as benchmarks for antiviral replication efficacy, while Oseltamivir served as the control group. The Mann-Whitney U test was employed to classify the clinical antiviral candidates—Remdesivir, Favipiravir-RTP, Abacavir, and Ribavirin. Results demonstrated that among the four small molecules, Favipiravir-RTP exhibited the highest binding affinity with the RdRp domain of the NS5-NS3 complex across all four dengue virus serotypes. Statistical classification revealed that in five simulated scenarios—including the four virus serotypes and Cryo-EM structural data—Favipiravir-RTP shared three classifications with the benchmark molecule AT-9010. Based on these findings, Favipiravir-RTP, a broad-spectrum antiviral agent, shows potential as a therapeutic option for inhibiting dengue virus replication. However, further clinical trials are necessary to validate their efficacy in humans.
基金supported by Three-Year Initiative Plan for Strengthening Public Health System Construction in Shanghai(2023-2025)Key Discipline Project(No.GWVI-11.1-12).
文摘Objective:To predict the distribution of dengue vector Aedes(Ae.)albopictus and identify high-risk areas for dengue fever transmission.Methods:Data on Ae.albopictus occurrences were collected from electronic databases.Ensemble models were developed to assess the impacts of climate,vegetation,and human activity on Ae.albopictus.The optimal ensemble model was then used to identify the distribution of suitable areas for Ae.albopictus.Results:After removing duplicate sites and retaining only one location per 100 m×100 m grid,189 Ae.albopictus breeding sites were identified.The optimal ensemble model revealed that Ae.albopictus exhibited higher breeding suitability in Shanghai under specific conditions:a normalized difference vegetation index of 0.1 to 0.6,maximum precipitation in the warmest month ranging from 400 mm to 470 mm,maximum temperature in the warmest month between 30.0℃and 31.0℃,and proximity to waterways within 0.5 km.The most suitable habitats for Ae.albopictus were primarily concentrated in Shanghai’s central urban areas and scattered across the inner suburban districts.Conclusions:The high-risk areas of Ae.albopictus are widely distributed throughout the central urban area and scattered across the inner suburban district of Shanghai,creating conditions conducive to the outbreak of dengue fever.It is essential to enhance targeted control measures for Ae.albopictus in the identified risk areas.
文摘Dengue fever presents a significant and persistent public health challenge in Sri Lanka.The disease,transmitted by Aedes aegypti and Aedes albopictus mosquitoes,affects individuals across all age groups,with working populations and school-aged children at higher risk due to increased outdoor exposure[1].Dengue transmission in Sri Lanka is seasonal with two high transmission waves corresponding with the two monsoon rains every year.The estimated average annual incidence is 175/100000 population,and it was 407.5/100000 in 2023 with a case fatality rate of 0.07%[2].
文摘In Burkina Faso, recent dengue outbreaks were exacerbated by Aedes aegypti mosquitoes, which have developed resistance to conventional insecticides. This study investigates the potential of Metarhizium pingshaense Met_S26, a fungus from Burkina Faso, for controlling both endophilic and exophilic Aedes mosquitoes. Traditional interventions are less effective against mosquitoes resting outdoors, and the ability of the fungus to be sexually transmitted could enhance its efficacy. Aedes mosquitoes were reared and exposed to various concentrations of Metarhizium pingshaense to assess its virulence. The fungus showed significant efficacy, with lethal times (LT80) ranging from 8.67 to 11.83 days depending on the concentration. Furthermore, bioassays demonstrated effective sexual auto-dissemination, with substantial transmission of fungal spores between infected and uninfected mosquitoes, leading to lower survival rates in uninfected mates. This study highlights Metarhizium pingshaense Met_S26 as a promising tool for controlling both indoor and outdoor Aedes populations, complementing existing vector control strategies such as the Sterile Insect Technique (SIT) and Wolbachia-based approaches. Future research should explore integrating this fungus with other control methods for a comprehensive vector management strategy.
基金Supported by the Natural Science Basic Research Plan in Shaanxi Province of China(2022JM-023)。
文摘In this paper,we establish an ShIhAhSvIvW model to investigate the impact of media communication on the transmission mechanism of dengue fever.Firstly,the basic reproduction number R0of the model is obtained by using the method of the next generation matrix.It shows that disease-free equilibrium is globally asymptotically stable when R0<1;the disease is uniformly persistent when R_(0)>1.Secondly,we select dengue fever case data from Guangdong Province from 2006 to 2019 for numerical simulations and predict its development trend.Finally,we conduct parameter sensitivity analysis,and the results show that increasing media publicity can to some extent reduce the number of patients.
基金Chinese Academy of Medical Sciences Initiative for Innovative Medicine,Grant/Award Number:2021-I2M-1-035 and 2022-I2M-1-011。
文摘Background:Dengue fever,an acute insect-borne infectious disease caused by the dengue virus(DENV),poses a great challenge to global public health.Hepatic involve-ment is the most common complication of severe dengue and is closely related to the occurrence and development of disease.However,the features of adaptive immune responses associated with liver injury in severe dengue are not clear.Methods:We used single-cell sequencing to examine the liver tissues of mild or se-vere dengue mice model to analyze the changes in immune response of T cells in the liver after dengue virus infection,and the immune interaction between macrophages and T cells.Flow cytometry was used to detect T cells and macrophages in mouse liver and blood to verify the single-cell sequencing results.Results:Our result showed CTLs were significantly activated in the severe liver injury group but the immune function-related signal pathway was down-regulated.The rea-son may be that the excessive immune response in the severe group at the late stage of DENV infection induces the polarization of macrophages into M2 type,and the macrophages then inhibit T cell immunity through the TGF-βsignaling pathway.In ad-dition,the increased proportion of Treg cells suggested that Th17/Treg homeostasis was disrupted in the livers of severe liver injury mice.Conclusions:In this study,single-cell sequencing and flow cytometry revealed the characteristic changes of T cell immune response and the role of macrophages in the liver of severe dengue fever mice.Our study provides a better understanding of the pathogenesis of liver injury in dengue fever patients.
基金supported by the National Natural Science Foundation of China(Grant No.82130101)the Youth Innovation Promotion Association of CAS(Grant No.2021333).
文摘Dengue viruses(DENV)have spread throughout the world and pose a huge threat to human life.The most widespread serotype is type 2 DENV(DENV 2),which has no specific treatment.NS2B-NS3 protease plays a pivotal role in DENV replication because of its function in cleavage of the viral polyprotein;thus,it is considered a promising target for antiviral discovery.In this study,we developed a high-throughput screening system based on the NS2B-NS3 protease to identify candidates from an FDA-approved drug library.Eltrombopag was screened out of 3273 drugs,and demonstrated inhibition on DENV 2 at the micromolar level in vitro,significantly reducing viral loads in the targeted organs of challenged mice following intraperitoneal injection.Further mechanistic analysis showed that eltrombopag allosterically binds to the DENV 2 NS2B-NS3 protease in a reversible,noncompetitive manner,therefore inhibiting DENV 2 at the post-infection stage.In addition,eltrombopag inhibited the NS2B-NS3 proteases of DENV 4 and Zika virus,suggesting its potential as a broadspectrum antiviral agent.This study repurposed eltrombopag as a promising antiviral agent against DENV,providing an alternative for antiviral development against flaviviruses.
文摘Rationale:Dengue fever is a mosquito-borne viral infection,which commonly presents as an acute febrile illness.As the number of cases increases,rare manifestations including neurological manifestations are occasionally encountered.Patient concerns:A 20-year-old female presented with fever for 3 days with slurring of speech and unsteady gait,which were developed from the third day of illness.On examination,she had bilateral cerebellar signs.Dengue non-structural protein 1 antigen and dengue IgM in serum were positive.Her cerebrospinal fluid analysis and magnetic resonance image brain were normal.Diagnosis:Dengue cerebellitis.Intervention:Supportive management with fluids including oral rehydration solutions and intravenous fluids and paracetamol.Outcome:Cerebellar symptoms and signs completely resolved by the 20th day of illness.Lesson:Dengue cerebellitis is an unusual neurological manifestation of dengue infection.
基金approved by the Scientific Committee and Institutional Review Board of the Children’s Hospital 2,Ho Chi Minh City,Vietnam(approval No.391/QD-BVND2,March 22,2022).
文摘BACKGROUND Dengue-associated acute liver failure(PALF)accounts for a high mortality rate in children admitted to the pediatric intensive care unit(PICU).To date,there is a lack of data on clinical algorithms for estimating the risk of mortality in pediatric patients with dengue-induced severe hepatitis(DISH).AIM To determine the prevalence of PALF and identify the predictors of mortality among patients with DISH.METHODS This single-institution retrospective study was performed at a tertiary pediatric hospital in Vietnam between 2013 and 2022.The primary outcome was in-hospital mortality in pediatric patients with DISH,which was defined as either aspartate aminotransferase>350 IU/L or alanine aminotransferase>400 IU/L.Prognostic models for estimating the risk of death among patients with DISH were developed using a predefined set of clinical covariables and hepatic biomarkers on PICU admission and during the first 72 hours of admission.Area under the curve,multivariable logistic regression,and multiple imputation using the chained equation for missing values were performed.Backward stepwise model selection based on the Akaike information criterion was employed.Bootstrapping,calibration slope,and Brier score were used to assess the final models.RESULTS A total of 459 children with DISH were included in the analysis.The median patient age was 7.7 years(interquartile range:4.3-10.1 years).The prevalence of dengue-associated PALF in children with DISH was 18.3%.Thirty-nine DISH patients developing PALF(8.5%)died.Hepatic biomarkers,including the international normalized ratio(INR)≥2.11 and total serum bilirubin(≥1.7 mg/dL),showed high predictive values for mortality(all P values<0.001).Multivariable models showed the significant clinical predictors of death from dengue-induced PALF in patients with DISH,including reduced level of consciousness(pain and unresponsive levels on the Alert,Verbal,Pain,Unresponsive scale),high vasoactive-inotropic score(>30),and elevated levels of blood lactate,INR,and serum bilirubin.The final prognostic model demonstrated high discrimination,Brier score,and an acceptable calibration slope.CONCLUSION The prevalence of PALF in children with DISH is 18.3%.We developed robust prognostic models to estimate the risk of death in hospitalized children with severe dengue-induced hepatitis.
文摘Dengue fever(DF)has become a major public health concern in Nepal,with increasing outbreaks in recent years.Transmitted by Aedes mosquitoes,this climate-sensitive viral disease presents a significant challenge for healthcare providers and policymakers.Since 2004,Nepal has experienced a sharp increase in DF cases,peaking in 2022 with 54784 cases and 88 deaths.The surge,driven mainly by serotypes 1,2,and 3,is exacerbated by climate change,which prolongs mosquito breeding seasons due to warmer temperatures and increased rainfall.This trend has even impacted previously unaffected hilly regions.Effective dengue control strategies must focus on climate change adaptation,strengthening healthcare system reinforcement,raising public awareness,and enhancing vector control measures.Government initiatives,like the national dengue control program,play a critical role,but research and community engagement are also vital for prevention and early detection.Integrating climate resilience into public health efforts is essential to reducing the dengue burden in Nepal.
