Dengue Virus Type Research Articles

Inhibitory Activities of Methanolic Extracts of Carica papaya, Mentha piperita and Citrullus colocynthis Against Dengue Viruses-2 viability

This study targets the methanolic extracts from the leaves of Carica papaya (Papaya) and Mentha piperita (Mint), as well as the leaves and fruit extracts of Citrullus colocynthis (Tumma plant) for their antiviral activity against dengue virus type 2 (DENV-2) in vitro, utilizing the HepG2 cell line. The antiviral activity of the plant extracts mentioned above was assessed through a plaque formation assay on the HepG2 cell line. The methanolic extracts from the leaves of C. papaya and M. piperita demonstrated lower toxicity than the fruit extract of C. colocynthis. Notably, the fruit extract of C. colocynthis maintained the normal morphology of DENV-2- infected HepG2 cells with minimal cell mortality. The cell survival rates were found to be 80-100% for 0.30mg/ml and 0.20mg/ml of C. papaya and M. piperita leaves extracts and 0.08mg/ml of C. colocynthis fruit extract. The most effective inhibition of DENV-2 was attributed to the fruit extract of C. colocynthis, exhibiting 46.55% inhibition at 0.08mg/ml. In comparison, M. Piperita and C. papaya leaf extracts demonstrated 24.14% and 23.33% inhibition against 0.20mg/ml and 0.30mg/ml, respectively. The plaque forming unit (PFU/ml) at the highest concentration ensuring 100% cell survival was calculated as 1.5×106, 1.4×106, and 1.0×106 PFU/ml for C. papaya and M. piperita leaves extracts and C. colocynthis fruit extract, respectively. The study infers that the methanolic fruit extract of C. colocynthis exhibits a high potential for inhibiting DENV-2 compared to the other two extracts.

Dengue virus infection induces selective expansion of Vγ4 and Vγ6TCR γδ T cells in the small intestine and a cytokine storm driving vascular leakage in mice.

Dengue is a major health problem in tropical and subtropical regions. Some patients develop a severe form of dengue, called dengue hemorrhagic fever, which can be fatal. Severe dengue is associated with a transient increase in vascular permeability. A cytokine storm is thought to be the cause of the vascular leakage. Although there are various research reports on the pathogenic mechanism, the complete pathological process remains poorly understood. We previously reported that dengue virus (DENV) type 3 P12/08 strain caused a lethal systemic infection and severe vascular leakage in interferon (IFN)-α/β and γ receptor knockout mice (IFN-α/β/γRKO mice), and that blockade of TNF-α signaling protected mice. Here, we performed transcriptome analysis of liver and small intestine samples collected chronologically from P12/08-infected IFN-α/β/γRKO mice in the presence/absence of blockade of TNF-α signaling and evaluated the cytokine and effector-level events. Blockade of TNF-α signaling mainly protected the small intestine but not the liver. Infection induced the selective expansion of IL-17A-producing Vγ4 and Vγ6 T cell receptor (TCR) γδ T cells in the small intestine, and IL-17A, together with TNF-α, played a critical role in the transition to severe disease via the induction of inflammatory cytokines such as TNF-α, IL-1β, and particularly the excess production of IL-6. Infection also induced the infiltration of neutrophils, as well as neutrophil collagenase/matrix metalloprotease 8 production. Blockade of IL-17A signaling reduced mortality and suppressed the expression of most of these cytokines, including TNF-α, indicating that IL-17A and TNF-α synergistically enhance cytokine expression. Blockade of IL-17A prevented nuclear translocation of NF-κB p65 in stroma-like cells and epithelial cells in the small intestine but only partially prevented recruitment of immune cells to the small intestine. This study provides an overall picture of the pathogenesis of infection in individual mice at the cytokine and effector levels.

Putting the pieces together: Chimeric virus strategy decode Dengue virus 3 antibody responses

In this issue of Cell Host & Microbe, Munt etal. shed light on variability in human immune responses after natural infection compared to vaccination by using a recombinant virus platform that expresses chimeric Dengue virus type 1 and type 3 envelope proteins to identify and characterize type-specific neutralizing antibodies.

Flavivirus genome recoding by codon optimisation confers genetically stable in vivo attenuation in both mice and mosquitoes.

Virus genome recoding is an attenuation method that confers genetically stable attenuation by rewriting a virus genome with numerous silent mutations. Prior flavivirus genome recoding attempts utilised codon deoptimisation approaches. However, these codon deoptimisation approaches act in a species dependent manner and were unable to confer flavivirus attenuation in mosquito cells or in mosquito animal models. To overcome these limitations, we performed flavivirus genome recoding using the contrary approach of codon optimisation. The genomes of flaviviruses such as dengue virus type 2 (DENV2) and Zika virus (ZIKV) contain functional RNA elements that regulate viral replication. We hypothesised that flavivirus genome recoding by codon optimisation would introduce silent mutations that disrupt these RNA elements, leading to decreased replication efficiency and attenuation. We chose DENV2 and ZIKV as representative flaviviruses and recoded them by codon optimising their genomes for human expression. Our study confirms that this recoding approach of codon optimisation does translate into reduced replication efficiency in mammalian, human, and mosquito cells as well as in vivo attenuation in both mice and mosquitoes. In silico modelling and RNA SHAPE analysis confirmed that DENV2 recoding resulted in the extensive disruption of genomic structural elements. Serial passaging of recoded DENV2 resulted in the emergence of rescue or adaptation mutations, but no reversion mutations. These rescue mutations were unable to rescue the delayed replication kinetics and in vivo attenuation of recoded DENV2, demonstrating that recoding confers genetically stable attenuation. Therefore, our recoding approach is a reliable attenuation method with potential applications for developing flavivirus vaccines.

Development of flavivirus subviral particles with low cross-reactivity by mutations of a distinct antigenic domain

The most conserved fusion loop (FL) domain present in the flavivirus envelope protein has been reported as a dominant epitope for cross-reactive antibodies to mosquito-borne flaviviruses (MBFVs). As a result, establishing accurate serodiagnosis for MBFV infections has been difficult as anti-FL antibodies are induced by both natural infection and following vaccination. In this study, we modified the most conserved FL domain to overcome this cross-reactivity. We showed that the FL domain of lineage I insect-specific flavivirus (ISFV) has differences in antigenicity from those of MBFVs and lineage II ISFV and determined the key amino acid residues (G106, L107, or F108), which contribute to the antigenic difference. These mutations were subsequently introduced into subviral particles (SVPs) of dengue virus type 2 (DENV2), Zika virus (ZIKV), Japanese encephalitis virus (JEV), and West Nile virus (WNV). In indirect enzyme-linked immunosorbent assays (ELISAs), these SVP mutants when used as antigens reduced the binding of cross-reactive IgG and total Ig induced by infection of ZIKV, JEV, and WNV in mice and enabled the sensitive detection of virus-specific antibodies. Furthermore, immunization of ZIKV or JEV SVP mutants provoked the production of antibodies with lower cross-reactivity to heterologous MBFV antigens compared to immunization with the wild-type SVPs in mice. This study highlights the effectiveness of introducing mutations in the FL domain in MBFV SVPs with lineage I ISFV-derived amino acids to produce SVP antigens with low cross-reactivity and demonstrates an improvement in the accuracy of indirect ELISA-based serodiagnosis for MBFV infections.Key points• The FL domain of Lineage I ISFV has a different antigenicity from that of MBFVs.• Mutated SVPs reduce the binding of cross-reactive antibodies in indirect ELISAs.• Inoculation of mutated SVPs induces antibodies with low cross-reactivity.

Application of multiplex realtime PCR detection for hemorrhagic fever syndrome viruses

BackgroundMultiplex real-time PCR is a quick and cost effective method for detection of various gene simultaneously. HFSV (Hemorrhagic Fever Syndrome Virus) is a newly emerging infectious disease because of globalization and climate change. We tried to develop a molecular diagnostic technique for various causative viruses and evaluate its usefulness for improving public health. MethodsMolecular diagnostic test method that qualitatively detects viruses causing viral hemorrhagic fevers hired Taq-Man Real-time RT-PCR technique. The Ct value was experimentally observed three or more times at the RNA concentration before and after the detection limit. After designing a multiplex real-time RT-PCR test for target gene of selected 17 viruses, the detection limit for each target and the presence or absence of cross-reaction and interference reaction were evaluated to determine its availability. ResultsSix kinds of viruses, including Crimean-Congo hemorrhagic fever virus, Omsk hemorrhagic fever virus, Sabia virus, Chapare virus, Yellow fever virus, and Variola virus (A4L gene, B12R gene), were able to confirm the detection limit of 0.5 copies/μl, and other Ebola virus, Marburg virus, Rift Valley fever virus, Kyasanur Forest disease virus, Junin virus, Guanarito virus, Machupo virus, Chikungunya virus, Hantavirus, Dengue virus types 1–4, and Lassa virus (L gene, GPC gene), and 11 kinds of viruses, the detection limit was confirmed at 5 copies/μl. No cross-reaction or interference between detected genes was observed. ConclusionThe virus test method developed through this study using multiplex is expected to be used for public health and quarantine as a test method that can be used when a hemorrhagic fever virus of unknown cause is introduced.

The dynamics of deltamethrin resistance evolution in Aedes albopictus has an impact on fitness and dengue virus type-2 vectorial capacity

BackgroundWorldwide invasion and expansion of Aedes albopictus, an important vector of dengue, chikungunya, and Zika viruses, has become a serious concern in global public health. Chemical insecticides are the primary means currently available to control the mosquito populations. However, long-term and large-scale use of insecticides has selected for resistance in the mosquito that is accompanied by a genetic load that impacts fitness.ResultsA number of laboratory strains representing different resistance mechanisms were isolated and identified from laboratory-derived, deltamethrin-resistant Ae. albopictus recovered in previous work. Resistance levels and fitness costs of the strains were evaluated and compared to characterize the evolution of the resistance genotypes and phenotypes. The heterozygous F1534S mutation (1534F/S) in the voltage gated sodium channel (vgsc) gene product (VGSC), first detected in early stages of resistance evolution, not only confers high-level resistance, but also produces no significant fitness costs, leading to the rapid spread of resistance in the population. This is followed by the increase in frequency of homozygous F1534S (1534S/S) mosquitoes that have significant fitness disadvantages, prompting the emergence of an unlinked I1532T mutation with fewer side effects and a mating advantage better adapted to the selection and reproductive pressures imposed in the experiments. Metabolic resistance with no significant fitness cost and mediating a high-tolerance resistance phenotype may play a dominant role in the subsequent evolution of resistance. The different resistant strains had similar vector competence for dengue virus type-2 (DENV-2). Furthermore, a comparative analysis of vectorial capacity revealed that increased survival due to deltamethrin resistance balanced the negative fitness cost effects and contributed to the risk of dengue virus (DENV) transmission by resistant populations. The progressive evolution of resistance results in mosquitoes with both target-site insensitivity and metabolic resistance with lower fitness costs, which further leads to resistant populations with both high resistance levels and vectorial capacity.ConclusionsThis study reveals a possible mechanism for the evolution of deltamethrin resistance in Aedes albopictus. These findings will help guide practical strategies for insecticide use, resistance management and the prevention and control of mosquito-borne disease.

Genetic Characterization of the Dengue Virus Type 3 Genotype I Prevailing in Dhaka, Bangladesh, 2021.

Background: In Bangladesh, dengue has been prevalent since its resurgence in 2018, and the dominant causative virus in 2019 was considered dengue virus serotype 3 (DENV-3). However, limited information is available for DENV serotype/genotype circulating after 2020. Materials and Methods: Viral RNA was extracted from NS1 antigen-positive blood samples of febrile patients in Dhaka, in 2021. DENV gene was detected by semi-nested RT-PCR, and sequences of envelope (E) gene and C-prM gene were determined by direct sequencing of RT-PCR products for genetic analysis. Results: Among 172 NS1-positive samples collected, 91 samples were assigned to DENV-3 and DENV-2 (88 and 3 samples, respectively) by RT-PCR targeting the C-prM gene. Phylogenetic analysis of the E gene for the 17 representative DENV-3 samples showed that all the viruses belonged to genotype I, forming a cluster (B-cluster) with those of DENV-3 reported in Bangladesh in 2017. Analysis of the deduced amino acid sequences of E protein revealed 16 amino acid substitutions, including two novel ones (G221W, L285P), and a substitution T223I that was specifically found in DENV-3 B-cluster. Conclusion: This study showed the persistent predominance of DENV-3 genotype I in Bangladesh having unique genetic traits in the E gene. (Approval number: MMC/IRB/2022/468).

Antiviral Activities of Streptomyces KSF 103 Methanolic Extracts against Dengue Virus Type-2.

Dengue has long been a serious health burden to the global community, especially for those living in the tropics. Despite the availability of vaccines, effective treatment for the infection is still needed and currently remains absent. In the present study, the antiviral properties of the Streptomyces sp. KSF 103 methanolic extract (Streptomyces KSF 103 ME), which consists of a number of potential antiviral compounds, were investigated against dengue virus serotype 2 (DENV-2). The effects of this extract against DENV-2 replication were determined using the quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Findings from the study suggested that the Streptomyces KSF 103 ME showed maximum inhibitory properties toward the virus during the virus entry stage at concentrations of more than 12.5 µg/mL. Minimal antiviral activities were observed at other virus replication stages; adsorption (42% reduction at 50 µg/mL), post-adsorption (67.6% reduction at 50 µg/mL), prophylactic treatment (68.4% and 87.7% reductions at 50 µg/mL and 25 µg/mL, respectively), and direct virucidal assay (48% and 56.8% reductions at 50 µg/mL and 25 µg/mL, respectively). The Streptomyces KSF 103 ME inhibited dengue virus replication with a 50% inhibitory concentration (IC50) value of 20.3 µg/mL and an International System of Units (SI) value of 38.9. The Streptomyces KSF 103 ME showed potent antiviral properties against dengue virus (DENV) during the entry stage. Further studies will be needed to deduce the antiviral mechanisms of the Streptomyces KSF 103 ME against DENV.

Expression of recombinant dengue virus type 1 non-structural protein 1 in mammalian cells and preliminary assessment of its suitability to detect human IgG antibodies elicited by viral infection

In recent years dengue has become a rapidly growing public health problem worldwide, however, the availability of accurate and affordable diagnostic immunoassays is limited, partly due to the difficulty of producing large quantities of purified antigen. Non-structural protein 1 (NS1) has shown to be a good candidate for inclusion in diagnostic assays and for serosurveys, particularly in endemic countries as a prerequisite for vaccination. In this work the NS1 antigen derived from dengue virus type-1 (DENV1) was expressed in HEK293-T cells and purified by affinity chromatography. The recombinant protein was recovered properly folded as dimers, highly purified and with good yield (1.5 mg/L). It was applied as a serological probe in an indirect ELISA developed in this work to detect human IgG antibodies. Preliminary comparative performance values of 81.1% sensitivity and 83.0% specificity of the developed and preliminary validated iELISA, relative to a commercial kit were obtained, suggesting that the purified recombinant DENV1 NS1 antigen is suitable to detect IgG antibodies, indicative of past DENV infection.

NS1 Protein N-Linked Glycosylation Site Affects the Virulence and Pathogenesis of Dengue Virus.

Live attenuated vaccine is one of the most effective vaccines against flavivirus. Recently, site-directed mutation of the flavivirus genome using reverse genetics techniques has been used for the rapid development of attenuated vaccines. However, this technique relies on basic research of critical virulence loci of the virus. To screen the attenuated sites in dengue virus, a total of eleven dengue virus type four mutant strains with deletion of N-glycosylation sites in the NS1 protein were designed and constructed. Ten of them (except for the N207-del mutant strain) were successfully rescued. Out of the ten strains, one mutant strain (N130del+207-209QQA) was found to have significantly reduced virulence through neurovirulence assay in suckling mice, but was genetically unstable. Further purification using the plaque purification assay yielded a genetically stable attenuated strain #11-puri9 with mutations of K129T, N130K, N207Q, and T209A in the NS1 protein and E99D in the NS2A protein. Identifying the virulence loci by constructing revertant mutant and chimeric viruses revealed that five amino acid adaptive mutations in the dengue virus type four non-structural proteins NS1 and NS2A dramatically affected its neurovirulence and could be used in constructing attenuated dengue chimeric viruses. Our study is the first to obtain an attenuated dengue virus strain through the deletion of amino acid residues at the N-glycosylation site, providing a theoretical basis for understanding the pathogenesis of the dengue virus and developing its live attenuated vaccines.

The acute effects of nonstructural-1 protein dengue virus type 2 on wet liver weight, zonulin expression and serum zonulin.

Intestinal leakage commonly occurs in severe dengue infection with zonulin as a biomarker. The aim of this study was to determine the effects of NS1 on liver weight, zonulin expression and serum zonulin levels. This laboratory experiment used 18 ddY mice, which were randomly divided into control (C), PBS (T1), and PBS + NS1 (T2) groups. Mice in the T1 and T2 groups were intravenously injected with 500 μl PBS only and 50 μg NS1 respectively. Mice blood samples were collected before and after three-day treatment for measurement of zonulin level. The fresh liver was weighted directly and were then used for immunostaining. The C group had lower wet liver weight compared to the T groups (p=0.001). Increased expression of liver zonulin was found in the T2 group, significant different from the C (p=0.014) and T1 groups (p=0.020). After treatment, serum zonulin levels in the T1 group was higher than that of the T1 group before treatment (p=0.035) but not in control (p=0.753) and T2 groups (p=0.869). Administration of 50 μg NS 1 increases wet liver weight and zonulin expression in hepatocytes, but did not increase serum zonulin levels in ddY mice.

PENERAPAN METODE MULTIPLICATIVE DECOMPOSITION DALAM MEMPREDIKSI JUMLAH KASUS DBD DI RSU. HAJI MEDAN

DHF case are diseases caused by four types of dengue virus, where each type has its own characteristics and pattern of spread. The purpose of this study is to make predictions on DHF cases in the future. This study uses the Multiplicative Decomposition method, in which this method breaks down time series data into four patterns, namely trend, seasonality, cycles and error. This research was conducted at RSU Haji Medan using DHF case data from January 2017 to December 2021. The results showed that the Multiplicative Decomposition method has an MSE value of 0,0012 and a MAPE value of 0,23%, which means it has a very good accuracy value because less than 10%. The conclusion of the study is that the Multiplicative Decomposition method is a method in the good category in predicting future DHF cases

Tizoxanide Antiviral Activity on Dengue Virus Replication.

Dengue virus is an important circulating arbovirus in Brazil responsible for high morbidity and mortality worldwide, representing a huge economic and social burden, in addition to affecting public health. In this study, the biological activity, toxicity, and antiviral activity against dengue virus type 2 (DENV-2) of tizoxanide (TIZ) was evaluated in Vero cell culture. TIZ has a broad spectrum of action in inhibiting different pathogens, including bacteria, protozoa, and viruses. Cells were infected for 1 h with DENV-2 and then treated for 24 h with different concentrations of the drug. The quantification of viral production indicated the antiviral activity of TIZ. The protein profiles in infected Vero cells treated and not treated with TIZ were analyzed using the label-free quantitative proteomic approach. TIZ was able to inhibit virus replication mainly intracellularly after DENV-2 penetration and before the complete replication of the viral genome. Additionally, the study of the protein profile of infected not-treated and infected-treated Vero cells showed that TIZ interferes with cellular processes such as intracellular trafficking and vesicle-mediated transport and post-translational modifications when added after infection. Our results also point to the activation of immune response genes that would eventually lead to a decrease of DENV-2 production. TIZ is a promising therapeutic molecule for the treatment of DENV-2 infections.

Serum biomarkers and anti-flavivirus antibodies at presentation as indicators of severe dengue.

Dengue is the most common vector-borne viral disease worldwide. Most cases are mild, but some evolve into severe dengue (SD), with high lethality. Therefore, it is important to identify biomarkers of severe disease to improve outcomes and judiciously utilize resources. One hundred forty-five confirmed dengue cases (median age, 42; range <1-91 years), enrolled from February 2018 to March 2020, were selected from an ongoing study of suspected arboviral infections in metropolitan Asunción, Paraguay. Cases included dengue virus types 1, 2, and 4, and severity was categorized according to the 2009 World Health Organization guidelines. Testing for anti-dengue virus IgM and IgG and serum biomarkers (lipopolysaccharide binding protein and chymase) was performed on acute-phase sera in plate-based ELISAs; in addition, a multiplex ELISA platform was used to measure anti-dengue virus and anti-Zika virus IgM and IgG. Complete blood counts and chemistries were performed at the discretion of the care team. Age, gender, and pre-existing comorbidities were associated with SD vs. dengue with/without warning signs in logistic regression with odds ratios (ORs) of 1.07 (per year; 95% confidence interval, 1.03, 1.11), 0.20 (female; 0.05,0.77), and 2.09 (presence; 1.26, 3.48) respectively. In binary logistic regression, for every unit increase in anti-DENV IgG in the multiplex platform, odds of SD increased by 2.54 (1.19-5.42). Platelet count, lymphocyte percent, and elevated chymase were associated with SD in a combined logistic regression model with ORs of 0.99 (1,000/μL; 0.98,0.999), 0.92 (%; 0.86,0.98), and 1.17 (mg/mL; 1.03,1.33) respectively. Multiple, readily available factors were associated with SD in this population. These findings will aid in the early detection of potentially severe dengue cases and inform the development of new prognostics for use in acute-phase and serial samples from dengue cases.

In Vitro Dengue Virus Inhibition by Aqueous Extracts of Aegle marmelos, Munronia pinnata and Psidium guajava.

Dengue is an arboviral (insect-transmitted) infection of global concern. Currently, there are still no specific dengue antiviral agents to treat the disease. Plant extracts have been used in traditional medicine for treating various viral infections - thus, in the present study, aqueous extracts of dried flowers of Aegle marmelos (AM), whole plant of Munronia pinnata (MP) and leaves of Psidium guajava (PG) were investigated for their potential capacity to inhibit dengue virus infection of Vero cells. The maximum non-toxic dose (MNTD) and the 50% cytotoxic concentration (CC50) were determined by using the MTT assay. A plaque reduction antiviral assay was carried out with dengue virus types 1 (DV1), 2 (DV2), 3 (DV3) and 4 (DV4), in order to calculate the half-maximum inhibitory concentration (IC50). AM extract inhibited all four virus serotypes tested; MP extract inhibited DV1, DV2 and DV4, but not DV3; PG extract inhibited DV1, DV2 and DV4, but not DV3. Thus, the results suggest that AM is a promising candidate for the pan-serotype inhibition of dengue viral activity.

Primary infection of BALB/c mice with a dengue virus type 4 strain leads to kidney injury

Dengue is a disease caused by dengue virus (DENV-1 through -4). Among the four serotypes, DENV-4 remains the least studied. Acute kidney injury is a potential complication of dengue generally associated with severe dengue infection.The goal of this study was to investigate the alterations caused by experimental dengue infection in the kidney of adult BALB/c mice.In this study, BALB/c mice were infected through the intravenous route with a DENV-4 strain, isolated from a human patient. The kidneys of the mice were procured and subject to histopathological and ultrastructural analysis.The presence of the viral antigen was confirmed through immunohistochemistry. Analysis of tissue sections revealed the presence of inflammatory cell infiltrate throughout the parenchyma. Glomerular enlargement was a common find. Necrosis of tubular cells and haemorrhage were also observed. Analysis of the kidney on a transmission electron microscope allowed a closer look into the necrotic tubular cells, which presented nuclei with condensed chromatin, and loss of cytoplasm.Even though the kidney is probably not a primary target of dengue infection in mice, the inoculation of the virus in the blood appears to damage the renal tissue through local inflammation.

Dengue Fever: A Case Study

Dengue is a pandemic that is brought on by the Dengue Virus (DENV), which is a single-stranded RNA (ribonucleic acid) virus. Dengue is also brought on by the bite of species in the Aedes family. Dengue, which is caused by the Dengue Virus, is the most common arboviral illness in the world and is a member of the Flaviviridae family. I present a study based on Dengue as a pandemic which outbreak on City Hospital of Delhi in the year 2010. Examining the clinical characteristics of dengue posi-tive cases, the prevalence of dengue diagnosis among patients with suspected dengue, and the effects of the aforemen-tioned on the environment and infectious illnesses. 4480 blood samples from clinically probable dengue fever patients were used in an enzyme-linked immunosorbent test (ELISA) to find dengue virus-specific IgM antibody protection. On 55 samples of C6/36 cell monolayers, virus isolation was carried out. The patient's application or the doctor might provide medical and public information about the patient. Results: Of the 4,480 blood samples tested, 1,800 blood samples (40.17%) were de-tected to be positive for the DENV with particular antibodies known as IgM antibodies. The most common group of single species of microorganism detected was DENV type 2. The conditions which were profusely detected were thrombocytopenia in which the blood platelet count observed is low and along with this Myalgia was also detected in which pain in the muscles is observed. In 32.4% and 17.9% of the 1,800-dengue fever IgM positive patients, respectively, low platelet count (thrombo-cytopenia) and muscle discomfort (myalgia) were noted. Together, these conditions accounted for 3% of the cases. Addition-ally, dengue hemorrhagic fever (DHF), which affects 10.3% of the 1,800 persons, has a fatality rate of 0.08%. Conclusions: Increased reporting due to changes in disease outbreaks, unprecedented rainfall, major infrastructure developments and improved medical facilities contributed to the shortage of dengue patients in 2010.

Neurological Manifestations of Perinatal Dengue.

Dengue viruses (DENVs) are single-stranded RNA viruses belonging to the family Flaviviridae. There are four distinct antigenically related serotypes, DENVs types 1, 2, 3, and 4. These are all mosquito-borne human pathogens. Congenital dengue disease occurs when there is mother-to-fetus transmission of the virus and should be suspected in endemic regions in neonates presenting with fever, maculopapular rash, and thrombocytopenia. Although most of the infected infants remain asymptomatic, some can develop clinical manifestations such as sepsis-like illness, gastric bleeding, circulatory failure, and death. Neurological manifestations include intracerebral hemorrhages, neurological malformations, and acute focal/disseminated encephalitis/encephalomyelitis. Dengue NS1Ag, a highly conserved glycoprotein, can help the detection of cases in the viremic stage. We do not have proven specific therapies yet; management is largely supportive and is focused on close monitoring and maintaining adequate intravascular volume.

Emergence Of Dengue Virus Type 4 During COVID-19 Pandemic In Patients Admitted to a Teaching Hospital In Malaysia

Prior to COVID-19, dengue was an important public health problem in Malaysia. Due to the movement control order imposed by the Malaysian government to curb the COVID-19 transmission, a study predicted that mosquito-borne diseases would increase during lockdown and partial lockdown seasons. Thus, this study aims to determine the current situation of dengue incidence during the pre-COVID-19 pandemic (2019) and during the COVID-19 pandemic (2020 and 2021). We compared the number of laboratory-confirmed cases in the pre-COVID19 year (2019) and during the COVID-19 pandemic (2020 and 2021). In addition to that, we characterized the clinical manifestation, dengue serotype and viremia levels of dengue patients that were admitted to the Hospital Cancelor Tuanku Muhriz. We found a significant decrease in the number of laboratory-confirmed cases between COVID-19 pandemic and the pre-covid period (p2020=0.064; p2021&lt;0.001). In this study, we found DENV 4 serotype was the most common serotype in dengue patients admitted to our hospital. There was no significant correlation between DENV serotype/viremia level with clinical manifestation of dengue fever and dengue with warning signs. However, patients infected with DENV4 had the highest viral load compared to patients infected with other serotypes. We also found high viremia levels were significantly associated with the febrile phase. Keywords dengue; clinical manifestation; dengue in Malaysia