Climate-driven dengue fever outbreaks in Nepal:Trends,challenges,and strategies

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.

Dengue induced acute liver failure:A meta summary of case reports

BACKGROUND Dengue fever is the most common cause of viral hemorrhagic fever,with more than 400 million cases being reported annually,worldwide.Even though hepatic involvement is common,acute liver failure(ALF)is a rare complication of dengue fever.AIM To analyze the demographic profile,symptomology,hospital course and outcomes of patients presenting with ALF secondary to dengue infection by reviewing the published case reports.METHODS A systematic search was performed from multiple databases including PubMed,Reference Citation Analysis,Science Direct,and Google Scholar.The search terms used were"dengue"OR"severe dengue"OR"dengue shock syndrome"OR"dengue haemorrhagic syndrome"OR"dengue fever"AND"acute liver failure"OR"hepatic failure"OR"liver injury".The inclusion criteria were:(1)Case reports or case series with individual patient details;(2)Reported acute liver failure secondary to dengue infection;and(3)Published in English language and on adult humans.The data were extracted for patient demographics,clinical sympto-matology,clinical interventions,hospital and intensive care unit course,need for organ support and clinical outcomes.RESULTS Data from 19 case reports fulfilling the predefined inclusion criteria were included.The median age of patients was 38 years(inter quartile range:Q3-Q126.5 years)with a female preponderance(52.6%).The median days from diagnosis of dengue to development of ALF was 4.5 d.The increase in aspartate aminotransferase was higher than that in alanine aminotransferase(median 4625 U/L vs 3100 U/L).All the patients had one or more organ failure,with neurological failure present in 73.7%cases.42.1%patients required vasopressor support and hepatic enceph-alopathy was the most reported complication in 13(68.4%)cases.Most of the patients were managed conser-vatively and 2 patients were taken up for liver transplantation.Only 1 death was reported(5.3%).CONCLUSION Dengue infection may rarely lead to ALF.These patients may frequently require intensive care and organ support.Even though most of these patients may improve with supportive care,liver transplantation may be a therapeutic option in refractory cases.

Resurgence of dengue in the Philippines

The coronavirus disease 2019(COVID-19)pandemic has significantly influenced the epidemiological landscape of various infectious diseases such as dengue.Dengue is an endemic disease in the Philippines,which showed a significant de-cline in the number of cases beginning in March 2020 due to the stringent public health measures implemented to curb COVID-19 cases.However,the easing of these restrictions subsequently led to a resurgence in dengue cases,as reported by the World Health Organization,with a notable increase compared to previous years.As the country navigates towards a post-pandemic phase,addressing the resurgence of dengue requires sustained efforts in vector control,surveillance,and healthcare preparedness.This article underscores the critical need for collab-orative efforts among stakeholders to mitigate the resurgence of dengue while managing the ongoing recovery from the COVID-19 pandemic.

Dengue outbreaks in northern Nigeria: Evaluating the recommended Takeda vaccine and future prevention strategies

Dengue fever,caused by the dengue virus(DENV),poses a significant public health challenge globally,with Nigeria experiencing sporadic outbreaks.A clear understanding of the dengue burden has not been achieved in Nigeria,just as in other African countries.Understanding the epidemiology and burden of dengue fever is essential for effective prevention and control strategies.This paper examines the recent dengue outbreaks in northern Nigeria,particularly in Sokoto state,and evaluates the recommended Takeda dengue vaccine(TDV)along with future prevention strategies.Despite limited surveillance and underreporting,dengue fever is endemic in Nigeria(with over 5 million cases and 5000 dengue-related deaths in 2023),with recent outbreaks indicating a growing concern.The TDV,a live attenuated tetravalent vaccine,has shown promise in preventing dengue fever,but challenges such as vaccine acceptance and access-ibility need to be addressed.Global urbanization contributes to the disease's spread,which is influenced by factors such as population density,cultural beliefs,water storage practices,hygiene,and water supply accessibility.Future prevention strategies must focus on government intervention,community practices,and innovative vector control measures to mitigate the spread of DENV in Nigeria.This study will serve as a valuable reference for policy-makers,researchers,and clinicians in the management and control of DENV in Nigeria and Africa as a whole.

A Novel Fractional Dengue Transmission Model in the Presence of Wolbachia Using Stochastic Based Artificial Neural Network

The purpose of this research work is to investigate the numerical solutions of the fractional dengue transmission model(FDTM)in the presence of Wolbachia using the stochastic-based Levenberg-Marquardt neural network(LM-NN)technique.The fractional dengue transmission model(FDTM)consists of 12 compartments.The human population is divided into four compartments;susceptible humans(S_(h)),exposed humans(E_(h)),infectious humans(I_(h)),and recovered humans(R_(h)).Wolbachia-infected and Wolbachia-uninfected mosquito population is also divided into four compartments:aquatic(eggs,larvae,pupae),susceptible,exposed,and infectious.We investigated three different cases of vertical transmission probability(η),namely when Wolbachia-free mosquitoes persist only(η=0.6),when both types of mosquitoes persist(η=0.8),and when Wolbachia-carrying mosquitoes persist only(η=1).The objective of this study is to investigate the effectiveness of Wolbachia in reducing dengue and presenting the numerical results by using the stochastic structure LM-NN approach with 10 hidden layers of neurons for three different cases of the fractional order derivatives(α=0.4,0.6,0.8).LM-NN approach includes a training,validation,and testing procedure to minimize the mean square error(MSE)values using the reference dataset(obtained by solving the model using the Adams-Bashforth-Moulton method(ABM).The distribution of data is 80% data for training,10% for validation,and,10% for testing purpose)results.A comprehensive investigation is accessible to observe the competence,precision,capacity,and efficiency of the suggested LM-NN approach by executing the MSE,state transitions findings,and regression analysis.The effectiveness of the LM-NN approach for solving the FDTM is demonstrated by the overlap of the findings with trustworthy measures,which achieves a precision of up to 10^(-4).

Role of doxycycline in the treatment of dengue infection: An open-label, randomized, controlled, pilot trial

Objective:To measure the effect of doxycycline on inflammatory marker[IL-6,TNF-α,ferritin and C reactive protein(CRP)]levels in patients with dengue infection.Methods:A single-centre,open-label,parallel-group randomized controlled trial was done in PGIMER Chandigarh from June 2021 to October 2022.Patients were randomized using a simple randomization process into two groups:the doxycycline treatment group(n=35)and the control group(n=34).Patients in the treatment group were given oral doxycycline 100 mg twice daily for five days along with standard treatment,whereas patients in the control group received only standard treatment.The objective was to measure the effect of doxycycline on inflammatory markers in dengue infection.Results:On comparative analysis at day 5,there was a statistically significant reduction in the median values of ferritin and CRP in cases compared to the control group(ferritin:P=0.006 and CRP:P=0.006).No significant reduction was noted in the levels of IL-6 and TNF-α.Conclusions:Doxycycline treatment led to a reduction of inflammatory markers in dengue infection.

Assessment of public perspectives and barriers towards dengue preventive practices using the Health Belief Model in Puducherry,India:A cross-sectional study

Objective:To assess the perspectives and barriers towards dengue preventive practices among the residents of Puducherry,India.Methods:A cross-sectional survey was conducted in 300 households in Puducherry,using a population-proportionate(7:3)distribution from urban and rural areas by grid sampling.One adult interview per household was conducted and the participants were selected using a KISH grid.A semi-structured questionnaire based on the Health Belief Model(HBM)with additional questions on knowledge assessment was used.Knowledge was assessed based on the correctness of answers and the HBM scores were calculated on a 5-point Likert scale.Participants were categorized based on the median score under each domain.Logistic regression was used for adjusted analysis and models were built to predict the performances in each domain.Results:Four percent of the participants lacked basic knowledge regarding dengue transmission.While 208(69.3%)participants did not consider themselves at risk of contracting dengue within the next year,majority perceived dengue as a disease with low severity.Around 49.3%(148)were skeptical about the benefit of time and money spent on dengue prevention.Inadequate government efforts were stated as the major barrier(47.0%)and frequent reminders(142,47.3%)as the major cue to action.Age above 50 years(aOR 1.78,95%CI 1.04-3.06,P=0.037)and rural locality(aOR 2.68,95%CI 1.52-4.71,P=0.001)were found to be significantly associated with poor knowledge scores.Urban participants had a significantly higher chance to perceive low susceptibility as compared to the rural counterparts(aOR 1.74,95%CI 1.05-2.9,P=0.03).Participants with less than a high school education had low perceived benefits(aOR 2.46,95%CI 1.52-3.96,P<0.001)and low self-efficacy scores(aOR 2.66,95%CI 1.61-4.39,P<0.001).Conclusions:This study identifies key gaps in dengue prevention,including low perceived susceptibility,mild disease perception,limited knowledge of breeding sites,and overreliance on government efforts.Tailoring interventions to community needs,stratified to factors influencing the community perspectives can significantly improve dengue prevention efforts.

Prognostic value of N-terminal pro B-type natriuretic peptide and troponin Ⅰ in children with dengue shock syndrome

Objective:To investigate the contribution of N-terminal pro B-type natriuretic peptide(NT-pro BNP)and troponin Ⅰ to mortality in children with dengue shock syndrome.Methods:A longitudinal study was conducted on children with dengue shock syndrome in a hospital in southern Vietnam.Detailed clinical histories,physical examinations,and laboratory parameters,including NT-pro BNP and troponin Ⅰ,were recorded.A comparison between survival and non-survival was carried out to identify factors influencing mortality.Results:A total of 107 patients with a median age of 9 years were included in the study.Among them,63.6%(68/107)presented with compensated shock,36.4%(39/107)had hypotensive shock,23.4%(25/107)required mechanical ventilation,and 12.1%(13/107)died.The NT-pro BNP levels were 3.9 pmol/L(IQR:1.9,10.3)and 15.2 pmol/L(5.8,46.3),while the median high sensitivity troponin Ⅰ levels were 20 pg/L(6,95)and 62 pg/L(12,325)at the first and second measurements,respectively.The mortality group exhibited higher rates of hypotensive shock,prolonged shock,lactate levels,liver damage,NT-pro BNP,and troponin Ⅰ levels.Hypotensive shock(OR 12.96,95%CI 2.70-62.30,P=0.004),prolonged shock(OR 39.40,95%CI 6.68-232.70,P<0.001),AST>1000 IU/L(OR 9.50,95%CI 2.63-34.34,P=0.041),and NT-pro BNP>7 pmol/L(OR 44.40,95%CI 5.44-362.20,P=0.001)were identified as predictive factors for mortality in dengue shock syndrome.Conclusions:The NT-pro BNP level could serve as a potential biomarker for predicting mortality in children with dengue shock syndrome.

Dengue hemorrhagic fever with rectus sheath hematoma:A case report

Rationale:Acute pain is a medical emergency that requires prompt abdominal evaluation and management.Dengue,a mosquito-borne arboviral infection,can lead to complications such as acute abdominal pain.Patient concerns:A 72-year-old hypertensive female presented with high-grade intermittent fever with chills and rigors for four days.She was diagnosed with dengue fever(NS1Ag-reactive)the day before admission.A contrast-enhanced computed tomography of the abdomen showed a hematoma along the rectus sheath which was managed conservatively as per surgical opinion.Diagnosis:Dengue hemorrhagic fever with rectus sheath hematoma.Interventions:Blood transfusion and fluid therapy.Outcomes:Ten days after discharge,the patient reproted no pain in the right iliac fossa and the size of the hematoma was significantly reduced.Lessons:Although it is rarely seen as a cause of acute abdomen,complaints of adnominal pain should never be ignored in critical or convalescent phase of dengue fever.Radiological investigations should be promptly conducted as hematoma is often difficult to be diagnosed clinically.Delay in diagnosis of rectus sheath hematoma can be fatal.

Geographically and Temporally Weighted Regression in Assessing Dengue Fever Spread Factors in Yunnan Border Regions

Objective This study employs the Geographically and Temporally Weighted Regression(GTWR)model to assess the impact of meteorological elements and imported cases on dengue fever outbreaks,emphasizing the spatial-temporal variability of these factors in border regions.Methods We conducted a descriptive analysis of dengue fever’s temporal-spatial distribution in Yunnan border areas.Utilizing annual data from 2013 to 2019,with each county in the Yunnan border serving as a spatial unit,we constructed a GTWR model to investigate the determinants of dengue fever and their spatio-temporal heterogeneity in this region.Results The GTWR model,proving more effective than Ordinary Least Squares(OLS)analysis,identified significant spatial and temporal heterogeneity in factors influencing dengue fever’s spread along the Yunnan border.Notably,the GTWR model revealed a substantial variation in the relationship between indigenous dengue fever incidence,meteorological variables,and imported cases across different counties.Conclusion In the Yunnan border areas,local dengue incidence is affected by temperature,humidity,precipitation,wind speed,and imported cases,with these factors’influence exhibiting notable spatial and temporal variation.

Acute paroxysmal cold hemoglobinuria upon dengue fever:A case report

Rationale:Dengue fever is capable of inciting the formation of transient polyclonal antibodies directed at red blood cell antigens,resulting in complement-mediated hemolysis,leading to intravascular hemolysis and hemoglobinuria.Patient’s concern:A 12-year-old male patient who recovered from dengue fever a week ago had red blood cell agglutination,spherocytes,and engulfment of red blood cells(erythrophagocytosis)by monocytes and neutrophils on routine hematological peripheral blood smear.The unexpected blood smear results prompted the lab physicians to investigate autoimmune hemolytic anemia,which revealed a monospecific positive direct antiglobulin test for complement(C3d,C3b)and the presence of Donath-Landsteiner antibody.Diagnosis:Paroxysmal cold hemoglobinuria(PCH),secondary to dengue fever.Interventions:Oxygen supplements,antibiotics,intravenous immunoglobulins,steroid therapy,and packed cell transfusions were administered.Outcomes:The patient’s condition was improved following the therapy.Lessons:Post-dengue PCH is a rare complication that requires a thorough peripheral smear examination for erythrophagocytosis,as advanced hematology analyzers fail to detect such findings.

Stochastic Model of Dengue: Analysing the Probability of Extinction and LLN

In this article, we develop and analyze a continuous-time Markov chain (CTMC) model to study the resurgence of dengue. We also explore the large population asymptotic behavior of probabilistic model of dengue using the law of large numbers (LLN). Initially, we calculate and estimate the probabilities of dengue extinction and major outbreak occurrence using multi-type Galton-Watson branching processes. Subsequently, we apply the LLN to examine the convergence of the stochastic model towards the deterministic model. Finally, theoretical numerical simulations are conducted exploration to validate our findings. Under identical conditions, our numerical results demonstrate that dengue could vanish in the stochastic model while persisting in the deterministic model. The highlighting of the law of large numbers through numerical simulations indicates from what population size a deterministic model should be considered preferable.

Transplacental transmission of dengue infection

We specifically addressed the persistent challenge of dengue in endemic regions,highlighting the potential seriousness of dengue infection through vertical trans-mission.Vertical dengue transmission has been well documented,particularly in hyper-endemic regions,including Ecuador.Herein,we present a neonate diagno-sed with congenital dengue and review similar cases from previously published reports.Although congenital dengue is commonly infected with severe serotypes of DENV(DENV-1 and DENV-2)infections,favorable outcomes are generally observed.

Predictors of hemorrhagic manifestations in dengue:A prospective observational study from the Hadoti region of Rajasthan

Objective:To study the laboratory and clinical predictors of hemorrhagic manifestations in dengue virus-infected patients.Methods:This was a single-center hospital-based prospective observational study.200 Dengue seropositive patients were included in the study.A detailed clinical examination was done and comprehensive laboratory investigations were done.These parameters were compared between patients with and without hemorrhagic manifestations.Results:Out of the 200 patients,47(23.5%)had bleeding.64.5%Patients were males and 76.0%were under the age of 40 years.The most common presenting symptoms were fever(100.0%)followed by myalgia(77.0%),nausea and vomiting(56.0%).Leukocytosis,neutrophilia,thrombocytopenia,hyperbilirubinemia,transaminitis,decreased serum albumins,and raised D-dimer can serve as hematological,biochemical,and coagulation predictors of hemorrhagic manifestations for dengue.Conclusions:Dengue is a tropical infection with various complications.Bleeding complications are one of them.Laboratory parameters like white blood cells,platelets,bilirubin level,liver enzymes,and D-dimer can help to identify patients at risk for bleeding.Early identification and appropriate management can save a lot of resources and lives.

Emerging peril of post-dengue mucormycosis:A case report

Rationale:Dengue fever is a leading cause of death in tropical and subtropical countries.Although most patients have a self-limited febrile illness,the viral infection can induce virus-mediated host changes,making immunocompetent persons susceptible to deadly fungal infections.However,there are only a few reports of such an association.Here we present a case of this deadly co-infection.Patient’s Concern:A 17-year-old male patient was diagnosed with dengue fever.He presented to us with facial swelling,periorbital edema,and black discoloration over the palate during the second week of his illness.Diagnosis:Diagnostic tests confirmed the presence of fungal hyphae.A diagnosis of post-dengue mucormycosis was made.No other comorbidity or underlying immune deficit was detected.Interventions:The patient underwent surgical debridement and antifungal treatment.Outcomes:The patient recovered and showed signs of palatal healing with an advancing mucosal edge.Lessons:Dengue virus and mucor co-infection has brought to light a new pathogenic paradigm.Clinicians need to be aware of this emerging medical condition and maintain a high index of suspicion for mucor co-infections while treating dengue patients.

Association between serum albumin levels and disease severity in adult patients with dengue: A 7-year retrospective cohort study in China's Mainland

Objective:To identify the association between serum albumin levels and disease severity among adult patients with dengue in China's Mainland.Methods:This retrospective cohort study analyzed the data of adult patients(aged≥18 years)hospitalized with laboratory-confirmed dengue in a tertiary center for infectious diseases from 2013 to 2019 in China's Mainland.Serum albumin levels were estimated and compared between patients with severe dengue and non-severe dengue.Additionally,the association between serum albumin levels and severe dengue was evaluated using a generalized linear model[relative risks(RR)].Multivariate logistic regression analysis was performed to identify the potential predictors of severe dengue.Results:Overall,1568 patients were included in this study.Of these patients,34(2.17%)developed severe dengue.The median serum albumin levels were significantly lower in patients with severe dengue than that in those with non-severe dengue(33 g/L vs.37 g/L,P<0.001).After adjustment for age,sex,and comorbidities,hypoalbuminemia(RR 4.877,95%CI 2.193-11.461,P<0.001)was found to be a predictor of severe dengue.Serum albumin levels(OR 1.303,95%CI 1.161-1.462,P<0.001)and age(OR 1.038,95%CI 1.017-1.061,P<0.001)were significant risk factors for severe dengue.The area under the curve for serum albumin levels to distinguish severe dengue was 0.787.Conclusions:Lower serum albumin levels were significantly associated with disease severity in adult patients with dengue.Hypoalbuminemia on admission resulted in at least a four-fold increased risk of severe dengue.

Coagulation abnormalities and their relationship with bleeding manifestations in patients with dengue-A single center observational study

Objective:To evaluate coagulation abnormalities and their relationship with bleeding manifestations among patients with dengue.Methods:This observational study was conducted on 292 adult dengue patients who were admitted to a tertiary care hospital of Western India from July 2021 to June 2022.Coagulation tests including prothrombin time(PT),international normalized ratio(INR),activated partial thromboplastin time(aPTT),fibrinogen,and D-dimer were performed.Patients were monitored for bleeding manifestations.Results:Coagulation abnormalities were reported in 42.8%of the patients.Overall,prolonged aPTT was the most common coagulation abnormality(40.8%),followed by low fibrinogen(38.7%),raised D-dimer(31.2%),raised INR(26.0%)and prolonged PT(19.2%).Bleeding manifestations were present in 19.9%patients.PT,INR,aPTT and D-dimer levels were significantly higher(P<0.01)and fibrinogen level was significantly lower(P<0.001)in patients with bleeding compared to patients without bleeding.Patients with bleeding had a significantly higher rate of all coagulation abnormalities than patients without bleeding(P<0.01).Conclusions:Patients with bleeding showed a significantly higher frequency of coagulation abnormalities compared to patients without bleeding.Patients with dengue should be assessed for coagulation abnormalities.

Recent advances on pathogenesis,diagnosis,prevention,immunological aspects,and vectors of dengue:A review

Dengue is a vector-borne disease caused by the dengue virus(DENV)of family Flaviviridae.Dengue fever is common in both developed and developing countries.Globally,approximately 400 million cases of dengue fever are reported annually,resulting in approximately 22000 fatalities.Dengue cases in India have progressively increased in the last decade.In recent years,substantial progress has been made in understanding various aspects of dengue,including its pathogenesis,diagnosis,prevention strategies,immunological responses,and the role of vectors in its transmission.The transmission of a positive RNA virus occurs through Aedes mosquitoes,specifically Aedes aegypti and Aedes albopictus.This virus is associated with a wide spectrum of symptoms,ranging from mild undifferentiated fever to severe hemorrhagic fever and shock,posing a potential threat to human health.There are 4 types of antigenically distinct dengue serotypes(DENV-1 to DENV-4)and among them,DENV-2 is more lethal and extremely severe.To overcome the severity of dengue,Dengvaxia is administered to children 9 to 16 years old with evidence of previous dengue infection.The diagnosis of dengue is carried out by ELISA-based non-structural protein(NS1)and immunoglobulin tests.However,there are no specific biomarkers to identify severe disease progression.Climatic factors and temperature play an important role in complex interaction among host,vector,and virus to manifest the severity of dengue.There is a need for the refinement of climate-based disease forecasting models in India to effectively control the spread of dengue.The mosquito repellent should be used periodically to kill or repel the Aedes mosquito to prevent the spread of dengue in humans.

Dengue and falciparum malaria co-infection in travelers returning from Burkina Faso:Report of two cases in Northeastern Italy

Rationale: Malaria and dengue are the most prevalent vector-borne diseases in tropical countries. Plasmodium parasite and dengue virus(DENV) concurrent infection is possible and often under-recognized in geographical areas where these infections are both endemic.Patients concern and diagnosis: We describe the first two cases of Plasmodium falciparum and DENV-3 co-infection in travelers returning to northeastern Italy from Burkina Faso during 2013-2014.Interventions: Malaria infection in both patients was treated with mefloquine. Due to the persistence of symptoms despite of the antimalaria treatment, dengue was also investigated;the treatment of dengue was symptomatic.Outcomes: The patients were discharged in good general condition.Lessons: The need for surveillance of potential malaria and dengue co-infection in travelers returning to Europe from endemic areas is highlighted, as infection with Plasmodium does not exclude arboviral co-infection.

Surveillance of arthropod-borne viruses in Benin,West Africa 2020–2021:detection of dengue virus 3 in Aedes aegypti(Diptera:Culicidae)

Dear Editor,Dengue virus(DENV,family Flaviviridae,genus Flavivirus)serotypes 1 to 4(DENV-1,-2,-3,and-4)are responsible for more than 100 million infections per year worldwide.Symptoms of DENV infection can be diverse,reaching from an acute febrile illness to the more severe,sometimes fatal dengue haemorrhagic fever/dengue shock syndrome.