Dengue Type Research Articles

Diagnostic accuracy of Dengue NS1 lateral flow immunoassay in comparison to reverse transcriptase polymerase chain reaction and enzyme linked Immunosorbent Assay

The most widely used invitro diagnostic qualitative screening method for dengue virus infection is the lateral flow immunoassay technique. Testing of dengue non-structural antigen NS1 offers specificity in determining the active infection while testing of IgM and IgG helps in differentiating the primary and secondary dengue infections. The ELISA functions as the golden standard for dengue testing and PCR credits for the most accurate determination tool at the genetic level. The RT-PCR endorsed NS1 gene and in ELISA or LFIA NS1 antigen is used as the marker owing to the specificity and lesser chances of mutation effects. This study evaluated the performance of AG-Q Dengue NS1 LFIA kit in comparison with RT-PCR quantification cycle (Cq) Values and ELISA NS1 quantitation. The study also focused on differentiating the samples among dengue serotypes using the RealStar Dengue Type RT-PCR Kit 1.0. Dengue serotype 2 is the prominent viral strain in Kerala region succeeded by serotype 3 and 1 with a prevalence rate of 64 %, 20 % and 6 % respectively. Dengue serotype 4 was not reported during this study period. 10 % co-infection with DENV 1 & DENV 2 was also reported. The AG-Q Dengue NS1 kit stood as efficient in screening by providing positive results with samples having RT-PCR Cq values up to 43 and ELISA NS1 quantification minimum of 14 Panbio units.

Structural relationship of regioselectively-sulfonated botryosphaeran derivatives on activity against herpes simplex virus type 1

The bioactivities of sulfonated polysaccharides are frequently related to their substitution pattern. In this study, the regioselective sulfonation of an exocellular fungal (1→3)(1→6)-β-D-glucan (botryosphaeran) was performed by two different methods: mild sulfonation (MS) and via pivaloyl ester (PS), in order to study the influence of the sulfonation pattern on the antiviral activity of the respective derivatives. Two sulfonated derivatives with substitution degrees of 0.82 (MS) and 0.49 (PS) were obtained, with substitution patterns at positions C-6, and C-2/C-4 of the glucose units, respectively. All derivatives were chemically characterized and evaluated for antiviral activity against Herpes simplex virus type 1 (HSV-1) KOS strain, and dengue type 2 (DENV-2). The sample sulfonated at positions C-6 (MS) showed a remarkable antiviral effect on HSV-1 (IC50 of 5.38 μg mL1), while PS remained inactive. The investigation of the mode of action of sample MS pointed to the inhibition of HSV-1 adsorption to the host cells. Both samples were inactive towards the dengue virus strain. This study demonstrated that the presence of sulfate groups at the C-6 positions of botryosphaeran is the preferred substitution pattern that enables the antiviral activity towards HSV-1.

Assessment of the importance of platelet transfusion in patients with severe dengue: a systematic review

Introduction: Dengue is one of the most important vector-borne viral diseases in subtropical and tropical regions. The World Health Organization (WHO) 2009 classified dengue into three groups: dengue without alarm signs, dengue with alarm signs, and severe dengue. According to the type of dengue, various managements have been proposed. The authors suggest that a predictive factor to avoid a poor prognosis in this disease is to keep platelet levels stable in the patient to prevent a fatal outcome. The aim of this paper is to analyze the efficacy of transfusion of platelet agents in the outcome of patients with severe dengue and thrombocytopenia. Material and methods: A bibliographic search was carried out in the Medline, OVID, and Scielo databases from January 1, 2008, to April 31, 2023, using the MeSH terms. Results: 7 articles were included in the systematic review. A wide range in age was found (18 to 79 years). A minimal number of studies detail the comorbidities of patients in their enrollment. Regarding platelet transfusion, the average number of platelet units used in the transfusion case was 5 (2 - 14). Transfusions of ABO identical and compatible pooled platelets transfusion were found to be more successful in increasing platelets. Almost all of the patients included in the studies had platelets <20,000 at enrollment. One study found a significant increase in platelets after transfusion, while the rest did not find it compelling. No mortality associated with platelet transfusion was recorded. Conclusions: Prophylactic platelet transfusion is not recommended as a routine measure in patients with severe dengue and thrombocytopenia. The uncertainty highlights need to reach a specific consensus establishing the appropriate indications for platelet transfusion and what type of patients with dengue virus would be beneficial.

A functionalized Sup35NM nanofibril-assisted oriented antibody capture in lateral flow immunoassay for sensitive detection of dengue type II NS1.

Rapid and sensitive dengue non-structural protein 1 (NS1) detection assay is essential for the treatment of disease and currentlyreleases high medical cost burdens. To address the limitations of conventional LFIA strips, we have developed an improved Sup35NM-Z-based LFIA that immobilizes antibodies on cellulose membranes in an orientated manner to increase the sensitivity of LFIA strips. A dual-functional Sup35NM nanofibril was fabricated by fusion with the antibody binding domain; resultant nanofibril from the amyloid Sup35NM was sprayed on the T-line to orientate the capture antibody and produces fluorescence signals. Antibody binding analysis showed that self-assembly of the Sup35NM monomer does not affect the binding activity of the Z-domain with the antibody. The NS1 for DENV-2 infection was chosen as a model target antigen to assess the feasibility of the Sup35NM-Z-domain-based LFIA platform. Under optimal conditions, the Sup35NM-Z-domain-based LFIA detected NS1 within 15 min with a detection limit of 1.29 ng/ml, while the detection limit of traditional LFIA with the same concentration of anti-NS1-Ab1 on the T-line by conventional physical adsorption was 2.20 ng/ml, 1.7 times higher than that of Sup35NM-Z-domain-based LFIA. As compared to traditional LFIAs, the Sup35NM-Z-based LFIA had a wide detection range of 1.29-625 ng/mL. The LFIA's clinical performance in identifying NS1 was also assessed using 15 clinical samples. The LFIA accurately recognized positive and negative samples, equal to 86.7% accuracy. The developed Sup35NM-Z-domain-based LFIA in this study offers great potential for the identification of target markers because of its greatly improved sensitivity and wider detection range.

Dengue Types 1 and 3 Identified in Travelers Returning from Kathmandu, Nepal, during the October 2022 Outbreak Are Related to Strains Recently Identified in India.

Phylogenetic analysis of dengue serotypes 1 and 3, which were diagnosed in travelers and Nepalese infected in Kathmandu during the October 2022 outbreak, revealed that both serotypes were clustered closest to the sequences sampled in India. This suggests both serotypes may have originated in India.

Novel insights into the structure and function of dengue virus NS1 protein.

The dengue flavivirus is responsible for dengue fever. While generally mild, a proportion of cases develop into life-threatening dengue haemorrhagic fever. Flaviviruses produce a non-structural protein, NS1, that is essential to flavivirus genome replication, though it has no known catalytic function. Early in infection, dimeric NS1 localises on the endoplasmic reticulum membrane at the site of viral RNA replication and may be involved in the replication complexs formation. Later on NS1 is secreted as a hexameric lipoprotein that interacts with components of the complement-mediated immune system. In 2014, crystal structures of full-length, glycosylated, and truncated West Nile Virus and Dengue Type 2 Virus (DENV2) NS1 dimers were obtained, which have aided interpretation of low-resolution cryo-electron microscopy reconstructions of the hexameric structure of secreted NS1. This along with biochemical and NMR analyses of the NS1 lipid cargo was used to build and simulate models of the DENV2 NS1 hexamer with and without a lipid cargo. Coarse-grained molecular dynamics simulations showed that the glycosylation of NS1 is essential for hexamer stability, with the glycans compensating for the paucity of protein-protein contacts between dimers. Lipid loaded NS1 hexamers can pick up lipids from their environment and deposit lipids into membranes but are not able to pick up lipids from membranes, whereas NS1 hexamers without a lipid cargo are not effective at picking up environmental lipids. The lipid cargo forms a dumbbell shape, with polar lipids towards the outside of the bulbs and non-polar lipids in the centre of the bulbs and bar of the dumbbell. These results add to our somewhat scarce understanding of the otherwise enigmatic function of a protein whose presence is an important biomarker for dengue fever, but whose role in infection has been controversial and not well understood.

Quercetin: A Functional Food-Flavonoid Incredibly Attenuates Emerging and Re-Emerging Viral Infections through Immunomodulatory Actions.

Many of the medicinally active molecules in the flavonoid class of phytochemicals are being researched for their potential antiviral activity against various DNA and RNA viruses. Quercetin is a flavonoid that can be found in a variety of foods, including fruits and vegetables. It has been reported to be effective against a variety of viruses. This review, therefore, deciphered the mechanistic of how Quercetin works against some of the deadliest viruses, such as influenza A, Hepatitis C, Dengue type 2 and Ebola virus, which cause frequent outbreaks worldwide and result in significant morbidity and mortality in humans through epidemics or pandemics. All those have an alarming impact on both human health and the global and national economies. The review extended computing the Quercetin-contained natural recourse and its modes of action in different experimental approaches leading to antiviral actions. The gap in effective treatment emphasizes the necessity of a search for new effective antiviral compounds. Quercetin shows potential antiviral activity and inhibits it by targeting viral infections at multiple stages. The suppression of viral neuraminidase, proteases and DNA/RNA polymerases and the alteration of many viral proteins as well as their immunomodulation are the main molecular mechanisms of Quercetin's antiviral activities. Nonetheless, the huge potential of Quercetin and its extensive use is inadequately approached as a therapeutic for emerging and re-emerging viral infections. Therefore, this review enumerated the food-functioned Quercetin source, the modes of action of Quercetin for antiviral effects and made insights on the mechanism-based antiviral action of Quercetin.

Monkey Business – Host Viral Load and Vector Infection Reveals Heterogeneity of Dengue Type 2 and Zika Virus Transmission in Native and Novel Non-Human Primate Hosts

Monkey Business – Host Viral Load and Vector Infection Reveals Heterogeneity of Dengue Type 2 and Zika Virus Transmission in Native and Novel Non-Human Primate Hosts

Risk of Viral Infectious Diseases from Live Bats, Primates, Rodents and Carnivores for Sale in Indonesian Wildlife Markets.

Southeast Asia is considered a global hotspot of emerging zoonotic diseases. There, wildlife is commonly traded under poor sanitary conditions in open markets; these markets have been considered 'the perfect storm' for zoonotic disease transmission. We assessed the potential of wildlife trade in spreading viral diseases by quantifying the number of wild animals of four mammalian orders (Rodentia, Chiroptera, Carnivora and Primates) on sale in 14 Indonesian wildlife markets and identifying zoonotic viruses potentially hosted by these animals. We constructed a network analysis to visualize the animals that are traded alongside each other that may carry similar viruses. We recorded 6725 wild animals of at least 15 species on sale. Cities and markets with larger human population and number of stalls, respectively, offered more individuals for sale. Eight out of 15 animal taxa recorded are hosts of 17 zoonotic virus species, nine of which can infect more than one species as a host. The network analysis showed that long-tailed macaque has the greatest potential for spreading viral diseases, since it is simultaneously the most traded species, sold in 13/14 markets, and a potential host for nine viruses. It is traded alongside pig-tailed macaques in three markets, with which it shares six viruses in common (Cowpox, Dengue, Hepatitis E, Herpes B, Simian foamy, and Simian retrovirus type D). Short-nosed fruit bats and large flying foxes are potential hosts of Nipah virus and are also sold in large quantities in 10/14 markets. This study highlights the need for better surveillance and sanitary conditions to avoid the negative health impacts of unregulated wildlife markets.

Dengue classification method using support vector machines and cross-validation techniques

Dengue is a dangerous disease that can lead to death if the diagnosis and treatment are inappropriate. The common symptoms that occur, including headache, muscle aches, fever, and rash. Dengue is a disease that causes endemics in several countries in South Asia and Southeast Asia. There are three varieties of dengue, such as dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS). This disease can currently be classified using a machine learning approach with the input data being the dengue symptoms. This study aims to classify dengue types consisting of three classes: DF, DHF, and DSS using five classification methods including C.45, decision tree (DT), k-nearest neighbor (KNN), random forest (RF), and support vector machine (SVM). The dataset used consists of 21 attributes, which are the dengue symptoms. It was collected from 110 patients. The evaluation method was conducted using cross-validation with k-folds of 3, 5, and 10. The dengue classification method was evaluated using three parameters: precision, recall, and accuracy, which were most optimally achieved. The most optimal evaluation results were obtained using SVM with k-fold 3 and 10 with precision, recall, and accuracy values reaching 99.1%, 99.1%, and 99.1%, respectively.

Expert System of Dengue Disease Using Artificial Neural Network Classifier

Abstract – Expert systems can be applied to the classification of dengue fever. Dengue is a serious disease that can be fatal if not diagnosed and treated properly. Headache, muscle aches, fever, and rash are some of the most prevalent symptoms. Dengue fever is a disease that is endemic in various South Asian and Southeast Asian nations. Dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome are the three types of dengue (DSS). Currently, these diseases may be classified using a machine learning approach with dengue symptoms as the input data. This study proposes implementing an Artificial Neural Network (ANN) with the Backpropagation (BPNN) algorithm as the classifier to categorize dengue types, divided into three categories: DF, DHF, and DSS. The dengue symptoms are represented by 21 attributes in the dataset. It was gathered from 110 patients. Cross-validation with k-fold 3, 5, and 10 were applied as the evaluation method. Three parameters were obtained to evaluate the ANN classification method: precision, recall, and accuracy. These were used to justify the most optimal performance. Cross-validation using k-fold 3 produced the best evaluation results, with precision, recall, and accuracy values of 97.3%, 97.3%, and 97.27%, respectively.

Hit-to-Lead Short Peptides against Dengue Type 2 Envelope Protein: Computational and Experimental Investigations.

Data from the World Health Organisation show that the global incidence of dengue infection has risen drastically, with an estimated 400 million cases of dengue infection occurring annually. Despite this worrying trend, there is still no therapeutic treatment available. Herein, we investigated short peptide fragments with a varying total number of amino acid residues (peptide fragments) from previously reported dengue virus type 2 (DENV2) peptide-based inhibitors, DN58wt (GDSYIIIGVEPGQLKENWFKKGSSIGQMF), DN58opt (TWWCFYFCRRHHPFWFFYRHN), DS36wt (LITVNPIVTEKDSPVNIEAE), and DS36opt (RHWEQFYFRRRERKFWLFFW), aided by in silico approaches: peptide–protein molecular docking and 100 ns of molecular dynamics (MD) simulation via molecular mechanics using Poisson–Boltzmann surface area (MMPBSA) and molecular mechanics generalised Born surface area (MMGBSA) methods. A library of 11,699 peptide fragments was generated, subjected to in silico calculation, and the candidates with the excellent binding affinity and shown to be stable in the DI-DIII binding pocket of DENV2 envelope (E) protein were determined. Selected peptides were synthesised using conventional Fmoc solid-phase peptide chemistry, purified by RP-HPLC, and characterised using LCMS. In vitro studies followed, to test for the peptides’ toxicity and efficacy in inhibiting the DENV2 growth cycle. Our studies identified the electrostatic interaction (from free energy calculation) to be the driving stabilising force for the E protein–peptide interactions. Five key E protein residues were also identified that had the most interactions with the peptides: (polar) LYS36, ASN37, and ARG350, and (nonpolar) LEU351 and VAL354; these residues might play crucial roles in the effective binding interactions. One of the peptide fragments, DN58opt_8-13 (PFWFFYRH), showed the best inhibitory activity, at about 63% DENV2 plague reduction, compared with no treatment. This correlates well with the in silico studies in which the peptide possessed the lowest binding energy (−9.0 kcal/mol) and was maintained steadily within the binding pocket of DENV2 E protein during the MD simulations. This study demonstrates the use of computational studies to expand research on lead optimisation of antiviral peptides, thus explaining the inhibitory potential of the designed peptides.

Bilateral Abducens Nerve Paresis: A Rare Manifestation of Dengue Fever

Dengue fever is endemic in over 100 countries, with the majority of cases reported in the World Health Organization (WHO) regions of the Americas, Southeast Asia and the Western Pacific. Dengue fever is endemic in almost every state in India, and it is the leading cause of hospitalisation. The presentation may vary from being asymptomatic to having mild syndrome. Among other neuro-ophthalmological manifestations, oculomotor neuropathy, optic neuropathy and unilateral abducens nerve palsy has been reported but to the best of authors' knowledge this is the first reported case of dengue virus related type three internuclear Ophthalmoplegia. A 47-year-old male patient presented with complaints of fever on and off for the last 3 days along with speech defects. At admission his blood pressure was 120/86 mmHg, pulse rate was 96 per minute. Oxygen saturation (SpO2 ) was 94%. He was thoroughly investigated for various viral and bacterial infections, none of which was detected in Polymerase Chain Reaction (PCR) serum test. Hepatitis B virus surface antigen (HBsAg), antibody against Hepatitis C Virus (anti-HCV), antibody against Human Immunodeficiency Virus type 1/2 (anti-HIV 1/2) were all negative. Anti-dengue virus Immunoglobulin M (IgM) antibody was found to be positive. The patient complained of double vision and on examination diplopia in both lateral gaze with maximum separation of images in right gaze. Due to the wider range of possible presentations, it is imperative to consistently follow-up with all dengue patients to check for any neurological sequalae.

1051. Characterization of Immune Responses to a Live-Attenuated Tetravalent Dengue Vaccine

BackgroundA safe and effective vaccine against dengue is needed to address an unmet medical need that affects a large portion of the world’s population. Takeda’s live attenuated tetravalent dengue vaccine candidate (TAK-003) has shown protection in an ongoing Phase 3 efficacy trial. TAK-003 contains an attenuated dengue type 2 virus (DENV-2), and 3 genetically modified viruses in which the structural proteins from each of the serotypes 1, 3 and 4 have been placed into the DENV-2 backbone. Exploratory immunological assessments have been a part of the TAK-003 clinical development plan to better understand the mechanisms of action of TAK-003, and to identify immune response signatures that may correlate with protection. MethodsCellular and humoral immune responses elicited by vaccination in dengue-naïve and dengue-exposed individuals were measured across several clinical trials. For the humoral response, several methods were used to measure the magnitude and characteristics of the antibodies following vaccination with TAK-003 including studies of neutralizing antibodies, antibodies that bind to the viral components of the vaccine, the affinity and complement fixing capabilities of antibodies specific to structural proteins, and additionally the level of antibodies specific to nonstructural protein 1 (NS1).ResultsA multifunctional cellular immune response was found following vaccination that primarily targeted nonstructural proteins in the DENV-2 backbone and was cross reactive to epitopes found in the other serotypes. The vaccine elicited neutralizing antibodies with high tetravalent seropositivity rates among participants. Further assessment of this response revealed that it consists of serotype-specific and cross-reactive neutralizing antibodies against all four serotypes. In addition, sera from vaccinated individuals neutralized genotypically diverse dengue strains. In addition to antibodies specific to structural components, antibodies to DENV-2 NS1 that were cross reactive to the NS1 proteins of the other serotypes were found.ConclusionThe breadth of the cellular and humoral immune responses elicited by TAK-003 in vaccine recipients across a wide age range living in different endemicities aligns with the response profile expected of a multivalent live vaccine.Disclosures Ralph Braun, PhD, Takeda Pharmaceuticals (Employee) Mayuri Sharma, PhD, Takeda Pharmaceuticals (Employee) Christina DeMaso, n/a, Takeda Pharmaceuticals (Employee) Allan Parker, n/a, Takeda Pharmaceuticals (Employee) David Dominguez, n/a, Takeda Pharmaceuticals (Employee) Heather Watkins, n/a, Takeda Pharmaceuticals (Employee) Hansi Dean, PhD, Takeda Pharmaceuticals (Consultant) Lovkesh Karwal, n/a, Takeda Pharmaceuticals (Employee) Eduardo Nascimento, n/a, Takeda Pharmaceuticals (Employee) Nicole Messere, n/a, Takeda Pharmaceuticals (Employee) Isamu Tsuji, n/a, Takeda Pharmaceuticals (Employee) Melissa Zahralban-Steele, n/a, Takeda Pharmaceuticals (Employee) Jeffrey R. Currier, PhD, Takeda Pharmaceuticals (Scientific Research Study Investigator) Heather Friberg-Robertson, PhD, Takeda Pharmaceuticals (Scientific Research Study Investigator)

Detection of Antibodies to Lokern, Main Drain, St. Louis Encephalitis, and West Nile Viruses in Vertebrate Animals in Chihuahua, Guerrero, and Michoacán, Mexico.

We conducted serologic surveillance for flaviviruses and orthobunyaviruses in vertebrate animals in Mexico in 2018-2019. Sera were collected from 856 vertebrate animals, including 323 dogs, 223 horses, and 121 cows, from 16 species. The animals were from 3 states: Chihuahua in northwest Mexico (704 animals) and Guerrero and Michoacán on the Pacific Coast (27 and 125 animals, respectively). Sera were assayed by plaque reduction neutralization test using four flaviviruses (dengue type 2, St. Louis encephalitis, West Nile, and Zika viruses) and six orthobunyaviruses from the Bunyamwera (BUN) serogroup (Cache Valley, Lokern, Main Drain, Northway, Potosi, and Tensaw viruses). Antibodies to West Nile virus (WNV) were detected in 154 animals of 9 species, including 89 (39.9%) horses, 3 (21.4%) Indian peafowl, and 41 (12.7%) dogs. Antibodies to St. Louis encephalitis virus (SLEV) were detected in seven animals, including three (0.9%) dogs. Antibodies to Lokern virus (LOKV) were detected in 22 animals: 19 (8.5%) horses, 2 (1.7%) cows, and a dog (0.3%). Antibodies to Main Drain virus (MDV) were detected in three (1.3%) horses. WNV and LOKV activity was detected in all three states, SLEV activity was detected in Chihuahua and Michoacán, and MDV activity was detected in Chihuahua. None of the animals was seropositive for Cache Valley virus, the most common and widely distributed BUN serogroup virus in North America. In conclusion, we provide serologic evidence that select flaviviruses and BUN serogroup viruses infect vertebrate animals in Chihuahua, Guerrero, and Michoacán. We also provide the first evidence of LOKV and MDV activity in Mexico.

Viral metagenomic sequencing in a cohort of international travellers returning with febrile illness.

Diagnosis of infections in returning international travellers can be challenging because of the broad spectrum of potential infectious etiologies potentially involved. Viral metagenomic next-generation sequencing (mNGS) has the potential to detect any virus present in a patient sample and is increasingly being used for difficult to diagnose cases. The aim of this study was to analyze the performance of mNGS for viral pathogen detection in the clinical setting of international travellers returning with febrile illness. Thirty-eight serum samples from international travellers returning with febrile illness and presenting at the outpatient clinic of the Leiden University Medical Center in the Netherlands in the time period 2015-2016 were selected retrospectively. Samples were processed for viral metagenomic sequencing using a probe panel capturing all known vertebrate viruses. Bioinformatic analysis was performed using Genome Detective software for metagenomic virus detection. Metagenomic virus findings were compared with viral pathogen detection using conventional methods. In 8 out of the 38 patients (21%), a pathogenic virus was detected by mNGS. All viral pathogens detected by conventional assays were also detected by mNGS: dengue virus (n=4 patients), Epstein-Barr virus (n=2), hepatitis B virus (n=1). In addition, mNGS resulted in additional pathogenic findings in 2 patients (5%): dengue virus (n=1), and hepatitis C virus (n=1). Non-pathogenic viruses detected were: GB virus C (n=1) and torque teno viruses (n=3). High genome coverage and depth using capture probes enabled typing of the dengue viruses detected. Viral metagenomics has the potential to assist the detection of viral pathogens and co-infections in one step in international travellers with a febrile syndrome. Furthermore, viral enrichment by probes resulted in high genome coverage and depth which enabled dengue virus typing.

Dengue fever outbreak in Cook Island: A rising concern, efforts, challenges, and future recommendations.

The Cook Island government has made several efforts to ensure zero confirmed cases and transmission of COVID-19, especially among visiting travelers. However, the Cook Island ministry of health has to deal with the new strain of dengue fever outbreak, known as dengue fever type 2 (DEN-2), by adopting several measures to control its spread, especially in the affected parts of the subtropical country. This paper aims to describe the dengue fever response taken in Cook Island and suggest recommendations to control the risk of transmission in endemic parts of the world.

Enhancing sensitivity of QCM for dengue type 1 virus detection using graphene-based polymer composites

Graphene oxide-molecularly imprinted polymer composites (GO-MIP) have attracted significant attention as recognition materials in sensing due to their outstanding properties in terms of electrical and thermal conductivity, high mechanical modulus, and the comparably straightforward way to functionalize them. The aim of this study was to design a MIP-based sensor recognition material and enhance its sensitivity by blending it with GO for sensing a harmful dengue hemorrhagic fever pathogen, namely the dengue type 1 virus (DENV-1). Polymer composites comprising GO incorporated to an acrylamide (AAM)/methacrylic acid (MAA)/methyl methacrylate (MMA)/N-vinylpyrrolidone (VP) copolymer were synthesized and compared to the “pure” MIP, i.e., the copolymer without GO. The pure polymer revealed a zeta potential of + 9.9 ± 0.5 mV, whereas GO sheets prepared have a zeta potential of − 60.3 ± 2.7 mV. This results in an overall zeta potential of − 11.2 ± 0.2 mV of the composite. Such polymer composites seem appropriate to bind the positively charged DENV-1 particle (+ 42.2 ± 2.8 mV). GO-MIP coated onto 10-MHz quartz crystal microbalance (QCM) sensors indeed revealed two times sensitivity compared to sensors based on the pure MIP. Furthermore, GO-polymer composites revealed imprinting factors of up to 21, compared to 3 of the pure MIP. When plotting the sensor characteristic in a semilogarithmic way, the composite sensor shows the linear response to DENV-1 in the concentration range from 100 to 103 pfu mL−1. The corresponding limits of detection (S/N = 3) and quantification (S/N = 10) are 0.58 and 1.94 pfu mL−1, respectively. Furthermore, imprinted polymer composites selectively bind DENV-1 without significant interference: DENV-2, DENV-3, DENV-4, respectively, yield 13–16% of DENV-1 signal. The sensor requires only about 15–20 min to obtain a result.Graphical abstract

Systemic dengue infection associated with a new dengue virus type 2 introduction in Brazil \u2013 a case report

BackgroundDengue infection is caused by an arbovirus with a wide range of presentations, varying from asymptomatic disease to unspecific febrile illness and haemorrhagic syndrome with shock, which can evolve to death. In Brazil, the virus circulates since the 1980s with many introductions of new serotypes, genotypes, and lineages since then. Here we report a fatal case of dengue associated with a Dengue virus (DENV) lineage not detected in the country until now.Case presentationThe patient, a 58-year-old man arrived at the hospital complaining of fever and severe abdominal pain due to intense gallbladder edema, mimicking acute abdomen. After 48 h of hospital admission, he evolved to refractory shock and death. DENV RNA was detected in all tissues collected (heart, lung, brain, kidney, spleen, pancreas, liver, and testis). Viral sequencing has shown that the virus belongs to serotype 2, American/Asian genotype, in a new clade, which has never been identified in Brazil before. The virus was phylogenetically related to isolates from central America [Puerto Rico (2005–2007), Martinique (2005), and Guadeloupe (2006)], most likely arriving in Brazil from Puerto Rico.ConclusionIn summary, this was the first fatal documented case with systemic dengue infection associated with the new introduction of Dengue type 2 virus in Brazil during the 2019 outbreak.

Analysis of dengue cases and severity classifications in Cavite Province, Philippines

Dengue is considered endemic in many countries in the world including the Philippines, and factors associated with dengue infections have not been adequately explored in the Philippines. The aim of this study was to assess demographic and location-related factors associated with different classifications of dengue: mild dengue, dengue fever, and hemorrhage dengue fever. This study used consolidated dengue reports of 18482 individual cases from the Provincial Hospital (PH) of Cavite province from 2009-2014 and clinical classifications of dengue used by the Philippine Integrated Disease Surveillance and Response (PIDSR). Multinomial logistic regression and marginal effects were used to analyze factors associated with different dengue classifications. Living in densely populated cities and municipalities, individuals aged 19 years and below, and being female were closely associated with severe dengue (DHF) type, while being male and older (above 19 years old) decreased the risk of contracting severe dengue. Our study provides a preliminary assessment of association between demographic factors (gender and age-group), locations (municipalities and cities); and three classifications of dengue (mild, moderate, and severe) in Cavite province in the Philippines. To establish whether dengue is linked to populated areas, age and gender will require further assessments.