Dengue Illness Research Articles

Early diagnostic indicators of dengue versus other febrile illnesses in Asia and Latin America (IDAMS study): a multicentre, prospective, observational study

Improvements in the early diagnosis of dengue are urgently needed, especially in resource-limited settings where the distinction between dengue and other febrile illnesses is crucial for patient management. In this prospective, observational study (IDAMS), we included patients aged 5 years and older with undifferentiated fever at presentation from 26 outpatient facilities in eight countries (Bangladesh, Brazil, Cambodia, El Salvador, Indonesia, Malaysia, Venezuela, and Viet Nam). We used multivariable logistic regression to investigate the association between clinical symptoms and laboratory tests with dengue versus other febrile illnesses between day 2 and day 5 after onset of fever (ie, illness days). We built a set of candidate regression models including clinical and laboratory variables to reflect the need of a comprehensive versus parsimonious approach. We assessed performance of these models via standard measures of diagnostic values. Between Oct 18, 2011, and Aug 4, 2016, we recruited 7428 patients, of whom 2694 (36%) were diagnosed with laboratory-confirmed dengue and 2495 (34%) with (non-dengue) other febrile illnesses and met inclusion criteria, and were included in the analysis. 2703 (52%) of 5189 included patients were younger than 15 years, 2486 (48%) were aged 15 years or older, 2179 (42%) were female and 3010 (58%) were male. Platelet count, white blood cell count, and the change in these variables from the previous day of illness had a strong association with dengue. Cough and rhinitis had strong associations with other febrile illnesses, whereas bleeding, anorexia, and skin flush were generally associated with dengue. Model performance increased between day 2 and 5 of illness. The comprehensive model (18 clinical and laboratory predictors) had sensitivities of 0·80 to 0·87 and specificities of 0·80 to 0·91, whereas the parsimonious model (eight clinical and laboratory predictors) had sensitivities of 0·80 to 0·88 and specificities of 0·81 to 0·89. A model that includes laboratory markers that are easy to measure (eg, platelet count or white blood cell count) outperformed the models based on clinical variables only. Our results confirm the important role of platelet and white blood cell counts in diagnosing dengue, and the importance of serial measurements over subsequent days. We successfully quantified the performance of clinical and laboratory markers covering the early period of dengue. Resulting algorithms performed better than published schemes for distinction of dengue from other febrile illnesses, and take into account the dynamic changes over time. Our results provide crucial information needed for the update of guidelines, including the Integrated Management of Childhood Illness handbook. EU's Seventh Framework Programme. For the Bangla, Bahasa Indonesia, Portuguese, Khmer, Spanish and Vietnamese translations of the abstract see Supplementary Materials section.

Diagnostic Performance of Dengue NS1 and Antibodies by Serum Concentration Technique

Dengue infection has been a public health problem worldwide, especially in tropical areas. A lack of sensitive diagnostic methods in the early phase of the illness is one of the challenging problems in clinical practices. We, herein, analyzed 86 sera of acute febrile patients, from both dengue and non-dengue febrile illness, to study the diagnostic performance of dengue diagnostics. When compared with detection by Polymerase Chain Reaction (PCR), dengue NS1 detection by enzyme-linked immunosorbent assay (ELISA) had the highest sensitivity of 82.4% (with 94.3% specificity), while NS1 by rapid diagnostic test (RDT) had 76.5% sensitivity. IgM detection by ELISA and RDT showed only 27.5% and 17.9% sensitivity, respectively. The combination of NS1 and IgM in RDT yielded a sensitivity of 78.4%, with 97.1% specificity. One of the essential steps in making a diagnosis from patient samples is the preparation process. At present, a variety of techniques have been used to increase the number of analytes in clinical samples. In this study, we focused on the sample concentration method. The sera were concentrated three times with the ultrafiltration method using a 10 kDa molecular weight cut-off membrane. The results showed an increase in the sensitivity of RDT-NS1 detection at 80.4%, with 100% specificity. When combining NS1 and IgM detection, the concentration method granted RDT an 82.4% sensitivity, with 100% specificity. In conclusion, serum concentration by the ultrafiltration method is a simple and applicable technique. It could increase the diagnostic performance of point-of-care dengue diagnostics.

Dengue determinants: Necessities and challenges for universal dengue vaccine development.

Dengue illness can range from mild illness to life-threatening haemorrhage. It is an Aedes-borne infectious disease caused by the dengue virus, which has four serotypes. Each serotype acts as an independent infectious agent. The antibodies against one serotype confer homotypic immunity but temporary protection against heterotypic infection. Dengue has become a growing health concern for up to one third of the world's population. Currently, there is no potent anti-dengue medicine, and treatment for severe dengue relies on intravenous fluid management and pain medications. The burden of dengue dramatically increases despite advances in vector control measures. These factors underscore the need for a vaccine. Various dengue vaccine strategies have been demonstrated, that is, live attenuated vaccine, inactivated vaccine, DNA vaccine, subunit vaccine, and viral-vector vaccines, some of which are at the stage of clinical testing. Unfortunately, the forefront candidate vaccine is less than satisfactory, and its performance depends on serostatus and age factors. The lessons from clinical studies depicted ambiguity concerning the efficacy of dengue vaccine. Our study highlighted that viral structural heterogeneity, epitope accessibility, autoimmune complications, genetic variants, genetic diversities, antigen competition, virulence variation, host-pathogen specific interaction, antibody-dependent enhancement, cross-reactive immunity among Flaviviruses, and host-susceptibility determinants not only influence infection outcomes but also hampered successful vaccine development. This review integrates dengue determinants allocated necessities and challenges, which would provide insight for universal dengue vaccine development.

A Critical Analysis of Intracranial Hemorrhage as a Fatal Complication of Dengue Fever.

Dengue fever is the most rapidly spreading mosquito-borne virus in the world, infecting about 100 million individuals. A rare but possibly dangerous consequence of dengue illness is intracranial hemorrhage (ICH). Currently, the pathogenesis of ICH is unknown. A number of studies have found a variety of risk factors for ICH in dengue. In addition, studies have reported the use of emergency surgery while monitoring thrombocytopenia in the therapy of dengue ICH. This review enumerates the potential predictors of ICH in dengue, discusses the use of brain imaging, and mentions the possibility of emergency surgery.

Vitamin D Deficiency (VDD) and Susceptibility towards Severe Dengue Fever-A Prospective Cross-Sectional Study of Hospitalized Dengue Fever Patients from Lahore, Pakistan.

Dengue is a mosquito-borne flaviviral serious febrile illness, most common in the tropical and subtropical regions including Pakistan. Vitamin D is a strong immunomodulator affecting both the innate and adaptive immune responses and plays a pivotal role in pathogen-defense mechanisms. There has been considerable interest in the possible role of vitamin D in dengue viral (DENV) infection. In the present prospective cross-sectional study, we assessed a possible association between serum vitamin D deficiency (VDD) and susceptibility towards severe dengue fever (DF) illness. Serum vitamin D levels were measured at the time of hospitalization in 97 patients diagnosed with dengue fever (DF), dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS) at Mayo Hospital, King Edward Medical University, Lahore, PK, from 16 November 2021 to 15 January 2022. In terms of disease severity, 37 (38.1%) patients were DF, 52 (53.6%) were DHF grade 1 and 2, and 8 (8.2%) were DSS. The results revealed that most patients (75 (77.3%)) were vitamin-D-deficient (i.e., serum level < 20 ng/mL), including 27 (73.0%) in DF, 41 (78.8%) in DHF grade 1 and 2, and 7 (87.5%) in DSS. The degree of VDD was somewhat higher in DSS patients as compared to DF and DHF grade 1 and 2 patients. Overall, serum vitamin D levels ranged from 4.2 to 109.7 ng/mL, and the median (IQR) was in the VDD range, i.e., 12.2 (9.1, 17.8) ng/mL. Our results suggest that there may be a possible association between VDD and susceptibility towards severe dengue illness. Hence, maintaining sufficient vitamin D levels in the body either through diet or supplementation may help provide adequate immune protection against severe dengue fever illness. Further research is warranted.

Fractional dynamics of the transmission phenomena of dengue infection with vaccination

&lt;p style='text-indent:20px;'&gt;Dengue infection brings unimaginable damage in low-income countries across the world to public health, social, and economical fields. Scientists rely on modeling to preferable understand the transmission phenomena of dengue in order to forecast some preventive measures and to give better data for the development of vaccines and medications. In present work, we construct a compartmental model for dengue infection via fractional derivatives to show the influence of memory. The suggested system's solution is investigated for existence as well as uniqueness with the help of fractional calculus fundamental characteristics. The model is analyzed and the reproduction number is obtained through Next-generation Matrix technique, moreover, the sensitivity of the reproduction number is determined using the partial rank correlation coefficient (PRCC) method. We have shown that if &lt;inline-formula&gt;&lt;tex-math id="M1"&gt;\begin{document}$ R_0&amp;lt;1 $\end{document}&lt;/tex-math&gt;&lt;/inline-formula&gt;, the disease-free steady-state of the dengue model is locally asymptotically stable (LAS) and globally asymptotically stable (GAS) in the absence of vaccine. In particular case, we have shown that the infection of dengue persists uniformly in the system for &lt;inline-formula&gt;&lt;tex-math id="M2"&gt;\begin{document}$ R_0 $\end{document}&lt;/tex-math&gt;&lt;/inline-formula&gt; greater than one. Furthermore, we quantitatively showed memory's impact on &lt;inline-formula&gt;&lt;tex-math id="M3"&gt;\begin{document}$ R_0 $\end{document}&lt;/tex-math&gt;&lt;/inline-formula&gt; by fluctuation of different factors. Our result predicted that the biting frequency, mosquito recruiting rate, and memory index are the most sensitive aspects in efficiently controlling new dengue illnesses, according to our findings. The effect of vaccination on the suggested system's threshold is also investigated. Novel numerical schemes are presented to conceptualize the time series of the system in different scenarios. The findings suggested that more accurate and precious results are obtained through non-integer derivative and that memory plays a beneficial role in the management of dengue disease. We demonstrated that manipulating the index of memory in the system may manage the system reproduction number and endemic level of dengue infection.&lt;/p&gt;

Burden of Postinfectious Symptoms after Acute Dengue, Vietnam

We assessed predominantly pediatric patients in Vietnam with dengue and other febrile illness 3 months after acute illness. Among dengue patients, 47% reported >1 postacute symptom. Most resolved by 3 months, but alopecia and vision problems often persisted. Our findings provide additional evidence on postacute dengue burden and confirm children are affected.

A facile microfluidic chip design for DNA detection using dengue serotypes as a proof-of-concept case study

Dengue fever is caused by any of the four serotypes of dengue viruses, DENV-1, DENV-2, DENV-3 and DENV-4 spread by mosquito bites and is important to distinguish between them due to lack of cross-protective neutralizing antibodies for each serotype. Secondary infections also put individuals at higher risk for severe dengue illness than those who have not been previously infected. Current preferred assays include reverse transcription-PCR (RT-PCR) and ELISA. To enable on-field diagnosis of dengue serotypes, the detection process would need to be simplified or at least semi-automated. A downstream detection module was conceptualized and fabricated to detect the amplified DNA from the provided PCR mix (product) of previously developed modular microfluidic chips involving sample loading, cell lysis, RNA extraction and RT-PCR. Further, to ensure accuracy, each serotype assay necessitates a positive control, negative control and test sample, which constitutes 3 separate channels for the diagnosis of just 1 serotype. In this study, a 6-channel bi-assay microfluidic chip was designed with pre-loaded diluent and cyanine dye, sample chamber for loading, sequential fluidic sample mixing, and integrated membranes for simultaneous (6-channel) fluidic manipulation from a single actuation source. Positive samples will turn the dye from blue to violet while the negative controls will remain blue. The integrated membranes provided color contrast and facilitated the manipulation of the samples to the same line of sight for simultaneous analysis, paving the way for automated color analysis via smartphone.

Development of a complex intervention package for dengue prevention

Introduction: Complex interventions are widely used in public health practices with noteworthy health impacts. Communication for Behavioural Impact (COMBI) plan is an effective method directed at enacting behaviour change to benefit health and social development which encourage precise behavioural outcomes and is effective in planning a behavioural change for dengue control. The aim of this study was to develop an intervention package to change the behaviour to prevent dengue in one of the highest dengue-endemic areas of Sri Lanka.Methods: The development of the intervention package was formulated according to the two phases, the ‘Theoretical phase’ and ‘Modelling phase’ of the framework for ‘Developing and Evaluating Complex Interventions’. World Health Organization’s 10 key steps in planning COMBI strategies were followed in order to develop the present intervention package. A situational market analysis was conducted in the highest dengue-endemic area in Kurunegala district to identify the Specific Behavioural Objectives (SBOO) for the COMBI plan. The development of the COMBI plan was conducted using the mixed methodological approach including quantitative and qualitative designs.Results: The overall goal of the COMBI plan was to decrease the morbidity and mortality due to dengue illness by improving the dengue prevention behaviours among householders. The SBOO for the plan were to improve the proper waste management practices according to the ‘3R concept’ (Reduce, Reuse and Re-cycling) and to improve the dengue prevention practices by 30 minutes of weekly cleaning. The strategies of intervention package were to conduct a community empowerment program to improve household waste management and weekly practices on dengue prevention by conducting administrative mobilization and public relationship, public advocacy, community mobilization, personal selling, advertising, and point of service promotion during follow-up.Conclusion: Developing a COMBI plan for an area after the identification of SBOO would be feasible to implement in order to empower the community to prevent dengue and improve community health services.

Respiratory sequelae of dengue fever.

Dengue viral illness is endemic in many tropical countries with temperate climates. The haematological and cardiovascular sequelae of dengue are well known; however, respiratory manifestations are still an area of active medical research. We conducted a literature search on PubMed, Medline CINAHIL, EMBASE and found 64 articles on respiratory sequelae of dengue. All relevant original articles and case reports were included and the relevant information regarding the respiratory manifestations of dengue was retrieved from the relevant eligible articles. Respiratory manifestations of dengue range from mild pleural effusion to acute respiratory distress syndrome. The former was the most common complication, seen in 5.1% of patients, followed by acute respiratory distress syndrome (ARDS) in 1.7%, pneumonia in 0.5%, respiratory distress in 0.3%, pulmonary hemorrhage in 0.1%, and haemothorax in 0.01%. Involvement of the respiratory system indicates severe disease and is difficult to manage. Therefore its early detection is important.

A rare case of acute liver failure with intrahepatic cholestasis due to dengue hemorrhagic fever: CytoSorb® and plasma exchange aided in the recovery: case report

BackgroundDengue haemorrhagic fever is a severe form of acute dengue infection characterized by leakage of plasma through capillaries into body spaces resulting in circulatory insufficiency leading to shock. Despite varying degrees of liver involvement occurring in acute dengue infection, intrahepatic cholestasis is very rare in the literature with only two cases reported so far. We report a challenging case of a middle-aged woman with DHF complicated by acute liver failure, coagulopathy, acute renal failure and prolonged intrahepatic cholestasis. She was successfully managed in the intensive care unit with supportive therapy, Cytosorb® and therapeutic plasma exchange.Case presentationA 54-year-old Sri Lankan obese woman with multiple comorbidities presented with fever, headache, vomiting and generalized malaise for 3 days and was diagnosed with dengue haemorrhagic fever. Despite the standard dengue management, she clinically deteriorated due to development of complications such as, acute liver injury, intrahepatic cholestasis and acute renal injury. Acute liver failure was evidenced by transaminitis, lactic acidosis, coagulopathy with pervaginal bleeding and severe encephalopathy necessitating elective intubation and mechanical ventilation. She was immediately transferred to intensive care facilities where she underwent supportive management for liver failure, continuous renal replacement therapy coupled with cytosorb and therapeutic plasma exchange with which she made a remarkable recovery.ConclusionAcute liver failure with a prolonged phase of intrahepatic cholestasis is a very rare complication of acute dengue illness which is sparsely documented in medical literature so far. This patient was managed successfully with supportive therapy, aided by cytoSorb hemo-adsorption and therapeutic plasma exchange.

Hematological Indicators Assessing Severity in Dengue Patients

Background: Dengue is viral disease of human transmitted by Aedes aegypti mosquito. The clinical signs and symptoms of dengue infection range significantly, from mild dengue fever to a severe illness. Objective: Our study aims to describe the potential predictive hematological parameters which are associated with severity in dengue patients. Methodology: This study was descriptive study conducted at the department of Pathology (Hematology), Maqsood Medical Complex and General Hospital, Peshawar, for duration of six months from 1st May 2022 to 31st October 2022. Blood samples were taken aseptically from all the included patients and were sent to the hospital diagnostic laboratory where the hematological parameters were determined. All the data was collected in a pre-designed proforma. The data analysis was done by using IBM SPSS version 23. Results: In the current study, a total of 160 patients were enrolled. There were 102 (63.75%) male patients while female patients were 56 (36.25%). Based on the hematological parameters, the mean (±SD) Hematocrit (%), Hemoglobin (g/dl), White cell count (/µL), Lymphocytes(/µL), Neutrophils (%) and Platelets (/µL) in non severe dengue cases vs severe dengue cases were 39.2 (±5.1)% vs 42.3 (±4.3)%, 12.5 (±0.9) g/dl vs 13.9 (±1.8) g/dl, 3290 (±1.4) /µL vs 4750 (±1.6) /µL, 40.6 (±12.19)/µL vs 46.1 (±9.96) /µL, 44.4 (±16.56)% vs 49.4 (±12.44) % and 10,5000 (±1.12) /µL vs 56,000 (±2.36)/µL respectively. Conclusion: Our study concludes that some common hematological markers have a substantial correlation with the severity of dengue illness. Keywords: Hematological indicators; severe dengue; Non-severe dengue

Are we contented with achieving universal health coverage in treating dengue patients in Sri Lanka?

Background: The preventive and curative services for dengue illness cause a significant financial burden on the state health sector. Household costs and out-of-pocket expenditure (OOPE) too are important cost components embedded with dengue illness. The objective was to estimate the household costs and out-of-pocket expenses incurred due to dengue infection among adults who received institutional care in Colombo district, Sri Lanka.Methods: A longitudinal study was conducted from July to December 2018. Fifty patients recruited from dengue fever (DF) and dengue hemorrhagic fever (DHF) categories. Adults residing in the Colombo district for more than six months prior to dengue illness were recruited based on systematic sampling. Data was collected via an interviewer-administered questionnaire on the day of discharge from the hospital and followed up for two weeks. Unit cost per patient was calculated. Household costs were calculated for 3 phases: ambulatory, during, and post-hospitalization. These components were described using mean, median, standard deviation and inter-quartile range, and OOPE.Results: The median age in the DF group was 38.5 years and in the DHF group was 28.5 years. The average household cost was US$ 127.69 (SD=93.32) and US$ 134.71 (SD=94.31) for DF and DHF patients respectively. Among DF patients 98.03% were borne using OOPE and among DHF patients it was 95.57%.Conclusions: If an adult member is hospitalized with dengue infection the OOPE is high, which is nearly 25% of a family’s monthly income. Strengthening dengue control programme is the key to universal health coverage (UHC).

Review on microbially synthesized nanoparticles: a potent biocontrol agent against Aedes species of mosquito

Aedes aegypti is a principal vector of dengue, chikungunya and Zika illnesses worldwide. Because effective vaccinations or medications for the prevention and/or treatment for these illnesses are not available, vector management has been embraced as the primary method of reducing their transmission. The strategy that is often used for controlling Aedes populations is chemical insecticides; however, despite their efficiency, extensive usage of these pesticides has resulted in high operating costs, the establishment of resistant populations and undesirable non-target impacts. Therefore, the use of nanoparticles derived from multiple synthesis processes as new insecticides has recently attracted the interest of researchers. This study provides an overview of the current understanding concerning the method of action of nanoparticles against mosquitoes. Metal nanoparticles strongly influence antioxidant and detoxifying enzymes in insects, causing oxidative stress and cell death. These nanoparticles similarly inhibited acetylcholinesterase activity. Metal-based nanoparticles can potentially bind to S and P units in proteins and nucleic acids respectively resulting in decreased membrane permeability, organelle and enzyme denaturation which leads to cell death. Furthermore, they upregulate and downregulate critical insect genes, lower protein synthesis and gonadotrophin release, resulting in developmental and reproductive failure. This review critically examines insect nanotoxicology research trends and highlights the ecotoxicological effects of practical usage of nanoparticles as insecticides.

Dengue algorithms integrated into the IMCI guidelines: An updated assessment in five Southeast-Asian countries.

BackgroundDengue is not included explicitly in the WHO Integrated Management of Childhood Illness (IMCI) algorithm. However, the assessment, classification and management of dengue has been incorporated into several IMCI country adaptations. We aimed to evaluate the dengue algorithms incorporated into IMCI guidelines and discuss the need for harmonization, including an extension of the age range for IMCI.MethodsThis study included three steps. First, we investigated dengue algorithms incorporated into five Southeast-Asian (Myanmar, Philippines, Vietnam, Indonesia, Cambodia) country IMCI guidelines through a desk-based analysis. Second, we conducted an expert survey to elicit opinions regarding the integration of dengue and extension of the age range in IMCI. Third, we compared our findings with data from a large multicentric prospective study on acute febrile illness.ResultsWe found considerable heterogeneity between the country specific IMCI guidelines in the dengue algorithms as well as classification schemes. Most guidelines did not differentiate between diagnostic algorithms for the detection of dengue versus other febrile illness, and warning signs for progression to severe dengue. Our expert survey resulted in a consensus to further integrate dengue in IMCI and extend the age range for IMCI guidelines beyond 5 years of age. Most of the interviewees responded that their country had a stand-alone clinical guideline for dengue, which was not integrated into the IMCI approach and considered laboratory testing for dengue necessary on day three of consecutive fever. Using data from a large multicentric study of children 5–15 years of age, we could confirm that the likelihood of dengue increased with consecutive fever days. However, a significant proportion of children (36%) would be missed if laboratory testing was only offered on the third consecutive day of fever.ConclusionsThis study supports the extension of the IMCI age range beyond 5 years of age as well as the inclusion of dengue relevant content in the algorithm. Because of the challenge of distinguishing dengue from other febrile illnesses, simple laboratory testing (e.g., full blood count) should be offered at an early stage during the course of the illness. Testing only children with consecutive fever over 3 days may lead to an underdiagnosis of dengue among those with acute febrile illness in children 5–15 years of age. In addition, specific laboratory testing for dengue should be made available to peripheral health facilities.

Dengue Transmission From Donor to Recipient After Deceased Donor Liver Transplant; Report of a Case and Review of Literature: Is Liver a Privileged Organ?

Nonvector transmission of dengue virus via organ transplantis rare.We report a probable case of dengue virus transmission via deceased donorlivertransplant. The donor was asymptomatic for dengue infection, and the liver recipient developed fever and thrombocytopenia 8 days after transplant. The recipient's testresults were positive forthe antigen for nonstructural protein 1 and for immunoglobulin M; however, donor serum samples were not available. Other transplant recipients (renal allograft) also showed dengue-positive test results during the same period, and these patients eventually died. Dengue illness in the liver recipient was severe and associated with shock and cardiomyopathy that required mechanical ventilation, intensive care, and cessation of immunosuppression; however, the patient subsequently improved and was discharged. This case highlights the importance of a high index of suspicion for dengue infection in the presence of graft dysfunction in dengue-endemic areas like India, as well as the importance of the test for the nonstructural protein 1 antigen during dengue outbreaks. These considerations should be included on the standard evaluation of solid-organ transplant donors.

Host immune response against DENV and ZIKV infections.

Dengue is a major public health concern, affecting almost 400 million people worldwide, with about 70% of the global burden of disease in Asia. Despite revised clinical classifications of dengue infections by the World Health Organization, the wide spectrum of the manifestations of dengue illness continues to pose challenges in diagnosis and patient management for clinicians. When the Zika epidemic spread through the American continent and then later to Africa and Asia in 2015, researchers compared the characteristics of the Zika infection to Dengue, considering both these viruses were transmitted primarily through the same vector, the Aedes aegypti female mosquitoes. An important difference to note, however, was that the Zika epidemic diffused in a shorter time span compared to the persisting feature of Dengue infections, which is endemic in many Asian countries. As the pathogenesis of viral illnesses is affected by host immune responses, various immune modulators have been proposed as biomarkers to predict the risk of the disease progression to a severe form, at a much earlier stage of the illness. However, the findings for most biomarkers are highly discrepant between studies. Meanwhile, the cross-reactivity of CD8+ and CD4+ T cells response to Dengue and Zika viruses provide important clues for further development of potential treatments. This review discusses similarities between Dengue and Zika infections, comparing their disease transmissions and vectors involved, and both the innate and adaptive immune responses in these infections. Consideration of the genetic identity of both the Dengue and Zika flaviviruses as well as the cross-reactivity of relevant T cells along with the actions of CD4+ cytotoxic cells in these infections are also presented. Finally, a summary of the immune biomarkers that have been reported for dengue and Zika viral infections are discussed which may be useful indicators for future anti-viral targets or predictors for disease severity. Together, this information appraises the current understanding of both Zika and Dengue infections, providing insights for future vaccine design approaches against both viruses.

COVID-19 Antibodies as Predictor of Severe Dengue among Hospitalized Children with Dengue Illness in the Post-third-wave Period of COVID-19 Infection in India.

There were widespread unconfirmed reports about the increased severity of dengue post-second wave of the COVID-19 pandemic in India. It is known that a second dengue infection with a different strain in an individual can trigger antibody-dependent enhancement (ADE). A similar phenomenon is hypothesized for severe COVID-19 infection since both dengue and COVID-19 are viral diseases with different and varying strains. However, much research is needed to confirm this hypothesis. In this context, we intended to assess the severity of dengue illness in relation to previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, possibly the role of COVID-19 antibodies as an early predictor of severe dengue illness. To assess the utility of COVID-19 antibodies for early identification of severe dengue illness among children in the post-third-wave period of COVID-19 infection in India. All hospitalized children with dengue illness were categorized as severe (shock and/or hemorrhage and/or multi-organ dysfunction) and non-severe dengue illness (dengue with or without warning signs) as per WHO definition. COVID-19 antibody titers were estimated in both groups. Clinical features and seroprevalence of COVID-19 antibodies were compared in both groups. A total of 31 children were studied (13 severe and 18 non-severe dengue illnesses). The most common symptoms prior to presenting to the hospital included fever (100% in both groups), vomiting (85% in severe and 63% in non-severe), abdominal pain (85% in severe and 50% in non-severe), poor feeding (54% in severe and 28% in non-severe), and skin rashes (15% in severe and none in non-severe). The mean duration from the onset of fever to the first hospital visit was 4.6 days in severe illness and 5.3 days in non-severe dengue illness. The mean duration of hospitalization was 9.7 days in severe dengue illness and 4.1 days in non-severe dengue illness. While 92.3% of all severe dengue had significantly higher COVID-19 antibody titers, it was found elevated only in 44.4% of the children with non-severe dengue illness (p-value 0.0059; Yates' corrected p-value 0.0179). Clinical symptoms prior to presenting to the hospital were fever, vomiting, abdominal pain, poor oral feeding, and skin rashes. While fever, vomiting, and abdominal pain were seen commonly in both severe and non-severe dengue illnesses, the presence of skin rash during febrile phase is associated with severe dengue illness only. Hospitalized children having severe dengue had increased seroprevalence of COVID-19 antibodies (92.3%) compared to children with non-severe dengue (44.4%). However, there is no corelation of the severity of dengue illness with absolute values of COVID-19 antibody levels. Therefore, the presence of COVID-19 antibodies (previous COVID-19 infection) can be a predictor of severe illness in children with dengue especially if associated with poor oral feeding and skin rashes. The limitation of the study is its lesser sample size to conclude any definitive statement; nevertheless, the study paves way for a similar cohort of a larger sample size to draw conclusions.

Chronic sequelae complicate convalescence from both dengue and acute viral respiratory illness.

Long Covid has raised awareness of the potentially disabling chronic sequelae that afflicts patients after acute viral infection. Similar syndromes of post-infectious sequelae have also been observed after other viral infections such as dengue, but their true prevalence and functional impact remain poorly defined. We prospectively enrolled 209 patients with acute dengue (n = 48; one with severe dengue) and other acute viral respiratory infections (ARI) (n = 161), and followed them up for chronic sequelae up to one year post-enrolment, prior to the onset of the Covid-19 pandemic. Baseline demographics and co-morbidities were balanced between both groups except for gender, with more males in the dengue cohort (63% vs 29%, p<0.001). Except for the first visit, data on symptoms were collected remotely using a purpose-built mobile phone application. Mental health outcomes were evaluated using the validated SF-12v2 Health Survey. Almost all patients (95.8% of dengue and 94.4% of ARI patients) experienced at least one symptom of fatigue, somnolence, headache, concentration impairment or memory impairment within the first week of enrolment. Amongst patients with at least 3-months of follow-up, 18.0% in the dengue cohort and 14.6% in the ARI cohort experienced persistent symptoms. The median month-3 SF-12v2 Mental Component Summary Score was lower in patients who remained symptomatic at 3 months and beyond, compared to those whose symptoms fully resolved (47.7 vs. 56.0, p<0.001), indicating that patients who self-reported persistence of symptoms also experienced functionally worse mental health. No statistically significant difference in age, gender distribution or hospitalisation status was observed between those with and without chronic sequelae. Our findings reveal an under-appreciated burden of post-infection chronic sequelae in dengue and ARI patients. They call for studies to define the pathophysiology of this condition, and determine the efficacy of both vaccines as well as antiviral drugs in preventing such sequelae.

VALUE OF PERIPHERAL BLOOD COUNT FOR DENGUE SEVERITY PREDICTION

Objective: Dengue virus infection has diverse clinical manifestations often with unpredictableclinical evolution and outcome. This study was to evaluate the value of the peripheral blood cellin association with the severity of Dengue Infection. Method: This was an observational study on480 adult patients admitted to Bach Mai Hospital (Vietnam) with Dengue illness between Augustand October 2017. The diagnosis and classification of Dengue were based on WHO 2009 criteria.Blood samples were collected from patients during acute febrile phase time in hospital and theblood cell indices were analyzed. Results: A total 480 patients participated in the study including223 patients of Dengue without warning signs (A), 212 patients of Dengue with warning signs (B),and 45 patients of severe Dengue (C). B and C were considered as the severe group, and A wasclassified as the non-severe group. Compared to the non-severe group, the severe group hadsignificantly lowered hemoglobin, WBC, lymphocytes count and percentage of lymphocyte duringacute febrile phase on day 5 of illness. The percentagelymphocyte &lt;25% was associated with the severe group. Conclusion: The percentage oflymphocytes, percentage of neutrophil are likely to predict for severity.