Febrile Phase Research Articles

Cutaneous manifestations and sequelae of Chikungunya fever: a single centre experience

Background: Chikungunya fever is a common viral illness in the tropical and subtropical areas. Various cutaneous manifestations can develop during the acute phase and post-febrile convalescent phase. Objective: To determine the frequency and types of cutaneous manifestations associated with chikungunya fever in acute and post-febrile phase. Methods: We conducted a prospective, observational study including 20 patients with laboratory-confirmed chikungunya fever. All the patients were followed up for 1 year to detect any cutaneous sequelae. Results: Pruritic maculopapular rash was the most common cutaneous manifestation during the acute febrile phase, noted in 60% of the patients. The rash usually appeared within 1–3 days of fever onset and spread in cephalo-caudal direction. Cutaneous hyperpigmentation was the most common dermatologic sequelae in the post-febrile period, occurring in 3 (15%) patients. In all patients, pigmentation appeared 3–4 weeks after resolution of fever, and started on the nose, gradually spreading to the forehead. The pigmentation improved significantly with topical hydroquinone after 4 weeks. Other additional manifestations of chikungunya fever included joint pain and joint swelling. None of our patients presented with mucosal or systemic involvement. Conclusion: Maculopapular skin rash was the most common manifestation during acute febrile phase of chikungunya fever, while cutaneous hyperpigmentation was the most common dermatologic sequelae after resolution of fever.

Are viral loads in the febrile phase a predictive factor of dengue disease severity?

As many studies have shown conflicting results regarding the extent of viraemia and clinical disease severity, we sought to investigate if viraemia during early dengue illness is associated with subsequent clinical disease severity. Realtime PCR was carried out to identify the dengue virus (DENV serotype), in 362 patients, presenting within the first 4 days of illness, from 2017 to 2022, in Colombo Sri Lanka. To characterize subsequent clinical disease severity, all patients were followed throughout their illness daily and disease severity classified according to WHO 1997 and 2009 disease classification. 263 patients had DF, 99 progressed to develop DHF, and 15/99 with DHF developed shock (DSS). Although the viral loads were higher in the febrile phase in patients who progressed to develop DHF than in patients with DF this was not significant (p = 0.5). Significant differences were observed in viral loads in patients infected with different DENV serotypes (p = 0.0009), with lowest viral loads detected in DENV2 and the highest viral loads in DENV3. Sub-analysis for association of viraemia with disease severity for each DENV serotype was again not significant. Although those infected with DENV2 had lower viral loads, infection with DENV2 was significantly associated with a higher risk of developing DHF (p = 0.011, Odds ratio 1.9; 95% CI 1.164 to 3.078). Based on the WHO 2009 disease classification, 233 had dengue with warning signs (DWW), 114 dengue without warning signs (DWoWS), and 15 had severe dengue (SD). No significant difference was observed in the viral loads between those with SD, DWW and DWoWS (p = 0.27). Viral loads were significantly different in the febrile phase between different DENV serotypes, and do not appear to significantly associate with subsequent clinical disease severity in a large Sri Lankan cohort.

Immune Thrombocytopenia Following Dengue Fever

Introduction: Dengue is an endemic mosquito-borne infection in tropical countries. The manifestations vary from asymptomatic infection to classic dengue fever, to more critical forms like dengue hemorrhagic fever and dengue shock syndrome. The critical phase occurs typically within the timeline of 4-7 days from the onset of symptoms. Case Report: We, hereby, report the case of a 7-year-old girl child who initially recovered from classic dengue fever. However, she was readmitted 18 days after the onset of initial symptoms with major bleeding manifestations due to immune thrombocytopenia responding to intravenous immunoglobulin. Discussion: Dengue fever may be associated with mild to moderate thrombocytopenia in the febrile phase and moderate to severe thrombocytopenia in the critical phase. Here, the index case developed thrombocytopenia much after the expected critical phase was over. Conclusion: Awareness of this possibility and continued monitoring, even after apparent recovery from dengue, is important for detecting and managing late-onset thrombocytopenia.

Secondary Dengue Infection Elicits Earlier Elevations in IL-6 and IL-10 Levels.

This study investigates the kinetics of interleukine-6 (IL-6) and interleukine-10 (IL-10) levels in dengue virus (DENV) infections during the febrile stage. Viremic patients were categorized into two phases based on anti-DENV IgM presence. Among 259 patients, 71% were in Phase I and 29% in Phase II. Secondary infections, accounting for 38.2% of cases, exhibited earlier elevations of IL-6 and IL-10 than primary infections, suggesting that pre-existing immune memory primes faster cytokine release. Thrombocytopenia and elevated aspartate transaminase (AST) levels were associated with Phase II, secondary infections, and hospitalization. Elevated IL-6 and IL-10 levels correlated with low platelet counts, linking them to clinical manifestations. The key finding is that IL-6 and IL-10 levels rise earlier in secondary infections compared to primary infections, whereas elevated cytokine levels typically occur later in the febrile phase. This study highlights the importance of cytokine dynamics in DENV infections, particularly during the early stages. The observation of cytokine concentration changes, especially in viremic samples, provides insights into the progression of dengue disease. Further research with broader cytokine panels is warranted to validate and expand these findings.

Are viral loads in the febrile phase a predictive factor of dengue disease severity?

As many studies have shown conflicting results regarding the extent of viraemia and clinical disease severity, we sought to investigate if viraemia during early dengue illness is associated with subsequent clinical disease severity. Realtime PCR was carried out to identify the dengue virus (DENV serotype), in 362 patients, presenting within the first 4 days of illness, from 2017 to 2022, in Colombo Sri Lanka. To characterize subsequent clinical disease severity, all patients were followed throughout their illness daily and disease severity classified according to WHO 1997 and 2009 disease classification. 263 patients had DF, 99 progressed to develop DHF, and 15/99 with DHF developed shock (DSS). Although the viral loads were higher in the febrile phase in patients who progressed to develop DHF than in patients with DF this was not significant (p=0.5). Significant differences were observed in viral loads in patients infected with different DENV serotypes (p=0.0009), with lowest viral loads detected in DENV2 and the highest viral loads in DENV3. Sub-analysis for association of viraemia with disease severity for each DENV serotyped was again not significant. Although those infected with DENV2 had lower viral loads, infection with DENV2 was significantly associated with a higher risk of developing DHF (p=0.011, Odds ratio 1.9; 95% CI 1.164 to 3.078). Based on the WHO 2009 disease classification, 233 had dengue with warning signs (DWW), 114 dengue without warning signs (DWoWS), and 15 had severe dengue (SD). No significant difference was observed in the viral loads between those with SD, DWW and DWoWS (p=0.27). Viral loads were significantly different in the febrile phase between different DENV serotypes, and do not appear to significantly associate with subsequent clinical disease severity in a large Sri Lankan cohort.

Antipyretic activity of the anti-Dengue herbal formula on yeast-induced pyrexia mice

Dengue hemorrhagic fever is characterised by fever, hemorrhage, and plasma leakage, which can lead to hypovolemic shock, coagulation disorders, and organ failure. If not diagnosed early and treated promptly, Dengue hemorrhagic fever can easily lead to death. Through many years of practice, traditional medicine has been shown to be effective in treating Dengue fever at the level of Dengue hemorrhagic fever (according to the World Health Organization - 2020 classification). The anti-Dengue herbal formula (bamboo leaves, spica prunellae, false daisy, cogongrass, cacumen platycladi, and honeysuckle flowers) was recommended by Professor Bui Chi Hieu for treatment of the febrile phase of Dengue hemorrhagic fever. Both ethanol and water extracts exhibited significant antipyretic effects on yeast-induced pyrexia mice at all tested dose levels. The aqueous extract (at 2.8 and 1.4 g/kg body weight dose), the ethanolic extract (at 2.45 and 4.9 g/kg body weight dose), and the reference drug paracetamol (150 mg/kg) significantly (p<0.05) reduced the increased rectal temperature as compared to the control.

Early-phase factors associated with pediatric severe dengue in the Thai–Myanmar cross-border region

BackgroundDengue disease is caused by dengue virus, which is transmitted by Aedes mosquitoes in tropical and subtropical regions worldwide. Although most infected individuals have benign febrile illness or no apparent symptoms, a small percentage develop severe dengue, a potentially fatal condition that occurs after a febrile stage. Many studies have identified factors predicting dengue severity among different populations and time courses. To help find practical approaches applicable in remote settings, we focused on the investigation of early factors associated with severe dengue in Thai–Myanmar cross-border region.MethodsThis retrospective case-control study was performed to determine factors contributing to severe dengue in the pediatric population. We reviewed the hospital records of patients with dengue infection aged 0–19 years who were admitted to Maesot General Hospital, situated near the Thai–Myanmar cross-border region, between 2017 and 2022. Medical data during the first 5 days of illness and outcomes were collected and analyzed.ResultsThis study included 144 patients with a serologically confirmed diagnosis of dengue infection, with 43 severe and 101 non-severe cases. Among biological factors, being an infant and belonging to an ethnic group in Myanmar showed a significant association with severe dengue in the univariable analysis. Multivariable logistic regression revealed that the presence of mucosal bleeding (adjusted OR 5.39, 95% CI 1.06–27.52, P = 0.043), a change in hematocrit ≥ 10% (adjusted OR 3.68, 95% CI 1.15–11.74, P = 0.028), and serum albumin < 35 g/L (adjusted OR 8.10, 95% CI 2.55–25.72, P < 0.001) during the first 5 days of illness were significantly associated with developing severe dengue.ConclusionsThis study supports the use of certain WHO warning signs and hematocrit change during febrile phase to predict pediatric severe dengue in low-resource settings. Potential factors such as very young age and ethnic groups warrant further exploration to identify risks contributing to severe dengue infection.

Dengue viremia kinetics and effects on platelet count and clinical outcomes: An analysis of 2340 patients from Vietnam.

Viremia is a critical factor in understanding the pathogenesis of dengue infection, but limited data exist on viremia kinetics. This study aimed to investigate the kinetics of viremia and its effects on subsequent platelet count, severe dengue, and plasma leakage. We pooled data from three studies conducted in Vietnam between 2000 and 2016, involving 2340 dengue patients with daily viremia measurements and platelet counts after symptom onset. Viremia kinetics were assessed using a random effects model that accounted for left-censored data. The effects of viremia on subsequent platelet count and clinical outcomes were examined using a landmark approach with a random effects model and logistic regression model with generalized estimating equations, respectively. The rate of viremia decline was derived from the model of viremia kinetics. Its effect on the clinical outcomes was assessed by logistic regression models. Viremia levels rapidly decreased following symptom onset, with variations observed depending on the infecting serotype. DENV-1 exhibited the highest mean viremia levels during the first 5-6 days, while DENV-4 demonstrated the shortest clearance time. Higher viremia levels were associated with decreased subsequent platelet counts from day 6 onwards. Elevated viremia levels on each illness day increased the risk of developing severe dengue and plasma leakage. However, the effect size decreased with later illness days. A more rapid decline in viremia is associated with a reduced risk of the clinical outcomes. This study provides comprehensive insights into viremia kinetics and its effect on subsequent platelet count and clinical outcomes in dengue patients. Our findings underscore the importance of measuring viremia levels during the early febrile phase for dengue studies and support the use of viremia kinetics as outcome for phase-2 dengue therapeutic trials. Wellcome Trust and European Union Seventh Framework Programme.

Dengue NS1 antibodies are associated with clearance of viral NS1.

Dengue vascular permeability syndrome is the primary cause of death in severe dengue infections. The protective versus potentially pathogenic role of dengue NS1 antibodies are not well understood. The main goal of this analysis was to characterize the relationship between free NS1 concentration and NS1 antibody titers in primary and secondary dengue infection in order to better understand the presence and duration of NS1 antibody complexes in clinical dengue infections. Hospitalized participants with acute dengue infection were recruited from Northern Colombia between 2018 to 2020. Symptom assessment including dengue signs and symptoms, chart review and blood collection was performed. Primary versus secondary Dengue was assessed serologically. NS1 titers and anti-NS1 antibodies were measured daily. Patients with secondary infection have higher antibody titers than those in primary infection, and we find a negative correlation between anti-NS1 antibody titer and NS1 protein. We demonstrate that in a subset of secondary infection, there are indeed NS1 antibody-antigen complexes at the admission day during the febrile phase that are not detectable by the recovery phase. Furthermore, dengue infection status is associated with higher circulating sialidases. The negative correlation between antibody and protein suggests that antibodies may play a role in clearing this viral protein.

Gallbladder Wall Thickening for Early Detection of Plasma Leakage Among Children with Dengue Fever Admitted in a Tertiary Care Hospital

Background: Plasma leakage is defined as e”20% elevation of hematocrit from baseline or evidence of plasma leakages such as pleural effusion, ascites, or hypoalbuminemia. In the early phase, these signs of plasma leakage are usually difficult to ascertain by physical examination and laboratory tests. Objective: This study aimed to investigate whether gallbladder wall thickening (GBWT) in the febrile phase of the disease can be used to detect the occurrence of plasma leakage in dengue patients. Methods: A cross-sectional analytical study was conducted during a 4-month period in Dr. M R Khan Shishu Hospital and ICH from September 2021 to December 2021. Children from 6 months to 14 years who were admitted with acute onset of fever less than 3 days with NS1 positivity were included consecutively. Laboratory tests and abdominal Ultrasonography were also performed to confirm the occurrence of plasma leakage. Result: Out of 114 patients, the majority were male (64%), in the 5-&lt;10-year age group(48.25%). Common presentations include fever (100%), flushed appearance (66.7%), abdominal pain (66.7%), vomiting (44.7%), bodyache (39.5%), During the febrile phase, 56patients were presented with GBWT, 49 of which showed plasma leakage during treatment. The sensitivity and specificity of GBWT during fever were 89% and 88%. PPV and NPV were 87% and 90% respectively. In risk factor analysis, Gallbladder wall thickening was found statistically significant (&lt;.009) predictor of plasma leakage in dengue. Conclusion: Gallbladder wall thickening during the febrile phaseis a predictor of plasma leakage in Dengue. BANGLADESH J CHILD HEALTH 2022; VOL 46 (3) : 138-143

Interferon responses in monocytes at the febrile phase of PFAPA

Interferon responses in monocytes at the febrile phase of PFAPA

Longitudinal serum profiling in Dengue fever patients with different severities by using multiplex flavivirus antigen microarrays

Dengue fever is one of the most common arbovirus-infected diseases and typically progresses through the febrile, critical, and convalescent phases. While most Dengue Fever patients have mild symptoms, a few develop severe symptoms due to hyperimmune responses. However, the role of the humoral responses during the Dengue fever progression, especially in severe cases, is still unclear. Here, we developed multiplex Flavivirus Antigen Microarrays (FAMs) for profiling antibody specificities in different infection phases and Dengue fever severities. The FAMs comprised 17 nonstructural and envelope proteins from Flaviviruses that frequently infect humans, e.g., 4 serotypes of Dengue viruses, Zika virus, Japanese encephalitis virus, West Nile virus, Yellow fever virus, and Tick-borne encephalitis virus. We collected serum samples from Dengue fever patients with different degrees of severity, including mild (n = 17), hospitalized non-severe (n = 21), and severe (n = 19), during febrile (Day < 7) and convalescent (Day > 7) phases. We simultaneously profiled the serum IgG and IgM against multiple antigens on the FAMs to demonstrate the immunological signatures in Dengue fever patients with different severities and two infection stages. Compared to febrile phase, the convalescent phase of mild but not hospitalized cases exhibiting evoked Dengue-specific IgM. In IgG profiling, the convalescent phase showed generally higher immune responses compared to febrile phase. Moreover, in the febrile phase, the hospitalized patients displayed higher IgG levels against 4 serotypes of Dengue viruses, Zika virus, and West Nile virus compared to mild patients, suggesting early and strong humoral responses. This study provides a valuable tool for monitoring antibody specificities and advances our understanding of humoral responses along with Dengue fever severities.

Soluble Endoglin and Syndecan-1 levels predicts the clinical outcome in COVID-19 patients

Endothelial instability is reported to be involved in the pathogenesis of COVID-19. The mechanism that regulates the endothelial dysfunction and disease virulence is not known. Studies on proteins that are released into circulation by activated endothelial cells may provide some means to understand the disease manifestation. The study investigated the circulating levels of two molecules Endoglin (Eng) and Syndecan-1 (SDC-1) that are presumed to be involved in the maintenance of endothelial integrity and their association with hypercoagulation marker in COVID-19 patients. The serum levels of Eng, SDC-1, D-mer were evaluated using ELISA at the time of admission (DOA) and day 7 post-admission among COVID-19 patients (N = 39 with 17 moderate and 22 severe cases). Compared to the time of admission, there was an increase in sEng and sSDC1 levels in all COVID-19 cases on day 7 post admission. The serum levels of sEng and sSDC-1 was significantly (P ≤ 0.001 & P ≤ 0.01 respectively) elevated in severe cases including the four deceased group compared to moderate cases on day 7 post admission. Further, the study molecules showed a strong positive association (P ≤ 0.001) with the hypercoagulation marker D-mer. The results show an early shedding of the endothelial proteins sEng and sSDC-1 into circulation as a host response to the viral infection during the febrile phase of infection. Increased levels of sEng and sSDC-1 along with D-mer could be beneficial in predicting COVID-19 disease severity.

Myositis : Rare Presentation of Dengue, not Uncommon in Children

Dengue myositis is a recently recognized category of idiopathic inflammatory myopathies manifested as symmetric proximal muscle weakness with severe limb pain and high serum creatine kinase (CK) levels, in dengue patient (NS1 positive or IgM positive). A total 4 cases of dengue myositis were admitted at Shaheed Suhrawardy Medical College during the period from August to October, 2023. All were male &amp; they presented mainly with severe limp pain with inability to walk they were diagnosed as dengue fever serologically. Two cases presented during febrile phase &amp; two following fever. Their S. CPK level were high with mildly low platelet count. None of them developed shock or hemorrhagic manifestation. They were treated supportively and all 4 cases recovered without any sequelae. Dengue myositis in children is usually benign and is differentiated from other causes of flaccid paralysis by tenderness of calf and thigh muscles and raised CPK levels with other normal neurological findings. But sometimes it may result in serious consequences, so all children with dengue infection should be followed up carefully with S.CPK level J Bangladesh Coll Phys Surg 2023; 41: 101-104

Inhibition of cellular activation induced by platelet factor 4 via the CXCR3 pathway ameliorates Japanese encephalitis and dengue viral infections

BackgroundActivated platelets secrete platelet factor 4 (PF4), which contributes to viral pathogenesis. Recently, we reported the proviral role of PF4 in replication of closely related flaviviruses, Japanese encephalitis virus (JEV) and dengue virus (DENV). ObjectivesThis study aimed to investigate the detailed mechanism of PF4-mediated virus replication. MethodsPF4−/− or wild-type (WT) mice were infected with JEV, and host defense mechanisms, including autophagic/interferon (IFN) responses, were assessed. WT mice were pretreated with the CXCR3 antagonist AMG487 that inhibits PF4:CXCR3 pathway. This pathway was tested in PF4−/− monocytes infected with DENV or in monocytes isolated from patients with DENV infection. ResultsPF4−/− mice infected with JEV showed reduced viral load and improved brain inflammation and survival. PF4−/− mice synthesized more IFN-α/β with higher expression of phosphorylated IRF3 in the brain. PF4 treatment decreased IRF-3/7/9 and IFN-α/β expression and suppressed autophagic LC3-II flux and lysosomal degradation of viral proteins in JEV-infected cells. PF4 increased the expression of P-mTOR, P-p38, and P-ULK1Ser757 and decreased expression of LC3-II. Decreased autophagosome-lysosome fusion in turn promoted DENV2 replication. The above processes were reversed by AMG487. Uninfected PF4−/− monocytes showed elevated LC3-II and autophagosome-lysosome fusion. Microglia of JEV-infected PF4−/− mice exhibited elevated LC3-II inversely related to viral load. Similarly, monocytes from PF4−/− mice showed reduced infection by DENV2. In patients with DENV infection, higher plasma PF4 and viral load were inversely correlated with LC3-II, LAMP-1, and lysosomal degradation of DENV-NS1 in monocytes during the febrile phase. ConclusionThese studies suggest that PF4 deficiency or inhibition of the PF4:CXCR3 pathway prevents JEV and DENV infection. The studies also highlight the PF4:CXCR3 axis as a potential target to develop treatment regimens against flaviviruses.

Functional and transcriptional heterogeneity within the massively expanding HLADR+CD38+ CD8 T cell population in acute febrile dengue patients.

CD8 T cells play a crucial role in protecting against intracellular pathogens such as viruses by eliminating infected cells and releasing anti-viral cytokines such as interferon gamma (IFNγ). Consequently, there is significant interest in comprehensively characterizing CD8 T cell responses in acute dengue febrile patients. Previous studies, including our own, have demonstrated that a discrete population of CD8 T cells with HLADR+ CD38+ phenotype undergoes massive expansion during the acute febrile phase of natural dengue virus infection. Although about a third of these massively expanding HLADR+ CD38+ CD8 T cells were also CD69high when examined ex vivo, only a small fraction of them produced IFNγ upon in vitro peptide stimulation. Therefore, to better understand such functional diversity of CD8 T cells responding to dengue virus infection, it is important to know the cytokines/chemokines expressed by these peptide-stimulated HLADR+CD38+ CD8 T cells and the transcriptional profiles that distinguish the CD69+IFNγ+, CD69+IFNγ-, and CD69-IFNγ- subsets.

Febrile Phase Soluble Urokinase Plasminogen Activator Receptor and Olfactomedin 4 as Prognostic Biomarkers for Severe Dengue in Adults.

Dengue cases continue to rise and can overwhelm healthcare systems during outbreaks. In dengue, neutrophil mediators, soluble urokinase plasminogen activator receptor (suPAR) and olfactomedin 4, and mast cell mediators, chymase and tryptase, have not been measured longitudinally across the dengue phases. The utility of these proteins as prognostic biomarkers for severe dengue has also not been assessed in an older adult population. We prospectively enrolled 99 adults with dengue-40 dengue fever, 46 dengue with warning signs and 13 severe dengue, along with 30 controls. Plasma levels of suPAR, olfactomedin 4, chymase and tryptase were measured at the febrile, critical and recovery phases in dengue patients. The suPAR levels were significantly elevated in severe dengue compared to the other dengue severities and controls in the febrile (P < .001), critical (P < .001), and recovery (P = .005) phases. In the febrile phase, suPAR was a prognostic biomarker of severe dengue, with an AUROC of 0.82. Using a cutoff derived from Youden's index (5.4 ng/mL) and an estimated prevalence of severe dengue (16.5%) in our healthcare institution, the sensitivity was 71.4% with a specificity of 87.9% in the febrile phase, and the positive and negative predictive values were 54.7% and 95.8%, respectively. Olfactomedin 4 was elevated in dengue patients but not in proportion to disease severity in the febrile phase (P = .04) There were no significant differences in chymase and tryptase levels between dengue patients and controls. In adult dengue, suPAR may be a reliable prognostic biomarker for severe dengue in the febrile phase.

Correlation between hematocrit and inferior vena cava collapsibility in adult patients with dengue fever: A prospective, observational study at a tertiary care setup in Eastern India

Background: Dengue fever (DF) is a vector-borne arboviral infection prevalent in tropical and sub-tropical countries. Early recognition of severity of the disease with appropriate fluid management is a challenge to the clinicians. Increase in capillary permeability is the pathophysiological hallmark of the disease which parallels with increase in hematocrit. This study aimed to evaluate the inferior vena cava (IVC) collapsibility and its relation to hematocrit. Methods: A prospective, observational study was conducted in the inpatient department of tropical medicine over a period of 1 year in a tertiary care set up in Eastern India. Clinical data and hematocrit of adult dengue cases were documented and their IVC collapsibility determined by bedside ultrasonography (USG) was recorded. Association was assessed between IVC collapsibility and hematocrit. Results were statistically analyzed. Results: Seventy dengue cases were included - 59 cases of DF with warning signs and 11 cases of dengue hemorrhagic fever (DHF). 85.7% of study population presented at febrile phase of their illness. Bedside USG was correlated with hematocrit on day 2 of admission. IVC was collapsible in 79.7% cases of DF and 90.9% cases of DHF. Of the 47 DF cases with collapsible IVC, 95.7% had high hematocrit, while all DHF cases with collapsible IVC had high hematocrit. A significant association between IVC collapsibility and hematocrit was noted (P = 0.000). Conclusion: The assessment of intravascular volume status by bedside USG-IVC collapsibility is a helpful noninvasive and better tool than hematocrit for determining fluid resuscitation in DF.

Updates in the Management of Dengue Shock Syndrome: A Comprehensive Review.

Dengue is a very serious public health problem that can manifest a wide range of symptoms from asymptomatic to fatal conditions, such as dengue shock syndrome (DSS). It is a life-threatening mosquito-borne viral infection widely spread in tropical areas. Dengue virus transmission occurs from an infected Aedes mosquito to humans. Various factors are responsible for the occurrence of the disease, such as viral load, age of the host, immune status of the host, and genetic variability. Dengue infection occurs in three phases: febrile, critical, and recovery. The febrile phase lasts for seven daysand manifests symptoms such as high-grade fever, headache, arthralgia, and backache, andin some cases, the upper respiratory tract and gastrointestinal tract are also involved. Severe dengue is characterized by endothelial dysfunction that causes vascular permeability and plasma leakage. The fundamental mechanisms of these immune pathologies are not yet known. Dengue manifests various complications such as dengue encephalopathy, encephalitis, stroke, ocular involvement, acute transverse myelitis, myalgia, and cerebellar syndrome, but the most commonly seen is liver involvement. Dengue is managed supportively because there are no proven curative treatments. The cornerstone of care during the critical period of dengue is prudent fluid resuscitation. The first fluid of preference is a crystalloid. Prophylactic transfusion of platelets is not advised. The occurrence of four antigenically different dengue virus serotypes, each able to elicit a cross-reactive and disease-enhancing antibody response against the other three serotypes, has made the creation of the dengue vaccine a difficult undertaking. The development of a dengue vaccine has faced significant challenges due to a lack of the best animal models and a variety of immunological conditions in people, particularly in endemic locations. Dengvaxia is a live attenuated vaccine, which was developed by Sanofi. It is made up of four chimeric vaccine viruses produced by Vero cells.

Clinical profile and early severity predictors of dengue fever: Current trends for the deadliest dengue infection in Bangladesh in 2022

ObjectivesIn 2022, Bangladesh had the highest dengue-related fatality (281). This study evaluated clinical profiles to detect early changes to predict dengue fever severity. MethodsThis prospective observational study was performed in four government hospitals from June to November 2022 in Dhaka. Febrile patients admitted within 4th day of illness were recruited if they had a confirmed dengue viral infection either by by positive dengue nonstructural protein antigen or anti-dengue immunoglobulin (Ig)M antibody. ResultsWe divided 308 patients with confirmed dengue into two groups: 232 (74.3%) in nonsevere dengue and 76 (24.7%) in severe dengue. Men were 205 (66.6%), and the most affected age group was 21-30 years (47.7%). Patients with severe dengue reported a higher number of nausea 80.3%, coughs 57.9%, abdominal pain 56.6%, persistent vomitting 53.9%, dyspnea 35.5%, diarrhea 28.9%, and skin rash at 27.6%. In addition, the disease's febrile phase (≤4 days) showed thrombocytopenia (odds ratio [OR] 6.409, 95% CI 2.855-14.386, p <0.001), hemoconcentration (OR 3.428, 95% CI 1.030-11.405, p 0.045), and hypotension (OR 5.896, 95% CI 1.203-28.897, p 0.029) were associated severe disease. ConclusionsHypotension, thrombocytopenia, and hemoconcentration during the febrile phase might indicate progression towards severe disease.