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Viruses ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 99
Author(s):  
Harapan Harapan ◽  
Alice Michie ◽  
Timo Ernst ◽  
Kritu Panta ◽  
Mudatsir Mudatsir ◽  
...  

Dengue is a mosquito-borne disease of public health concern affecting tropical and subtropical countries, including Indonesia. Although studies on dengue epidemiology have been undertaken in Indonesia, data are lacking in many areas of the country. The aim of this study was to determine dengue virus (DENV) and chikungunya virus (CHIKV) molecular epidemiology in western regions of the Indonesian archipelago. A one-year prospective study was conducted in Aceh and Jambi in 2015 and 2016, respectively, where patients with dengue-like illness were enrolled. Of 205 patients recruited, 29 and 27 were confirmed with dengue in Aceh and Jambi, respectively, and three from Jambi were confirmed with chikungunya. DENV-1 was the predominant serotype identified in Aceh while DENV-2 was predominant in Jambi. All DENV-1 and DENV-2 from both regions were classified as Genotype I and Cosmopolitan genotype, respectively, and all DENV-3 viruses from Jambi were Genotype I. Some viruses, in particular DENV-1, displayed a distinct lineage distribution, where two DENV-1 lineages from Aceh were more closely related to viruses from China instead of Jambi highlighting the role of travel and flight patterns on DENV transmission in the region. DENV-2 from both Aceh and Jambi and DENV-3 from Jambi were all closely related to Indonesian local strains. All three CHIKV belonged to Asian genotype and clustered closely with Indonesian CHIKV strains including those previously circulating in Jambi in 2015, confirming continuous and sustainable transmission of CHIKV in the region. The study results emphasize the importance of continuous epidemiological surveillance of arboviruses in Indonesia and simultaneous testing for CHIKV among dengue-suspected patients.


2021 ◽  
Vol 8 (1) ◽  
pp. 1042-1048
Author(s):  
Moushumi Ghosh Roy ◽  
Kutub Uddin ◽  
Din Islam ◽  
Anjuvan Singh ◽  
Mohammad Monirul Islam

Purposes: Dengue fever, a mosquito-borne viral disease, is a global public health burden affecting millions of people each year and over 40% of world populations are at risk of dengue. Therefore, prompt and accurate dengue diagnosis is inevitable for disease surveillance and for aiding disease management. In this study we report dengue virus (DENV) seroprevalence in Chittagong, Bangladesh along with clinical manifestation of dengue infections. Methods: All samples included in this study were selected based on dengue NS1-based diagnosis, clinical sign and symptoms were judged by expert clinical physicians and infecting DENV serotyping was done by RT-PCR. The blood cells (Platelet, Haematocrit, WBC etc) were analyzed using Haematology cell counter. Results: First, among the 112 DENV infected serum samples tested by RT-PCR, 42 were DENV positive where 76% samples had single DENV serotype infection and 24% were concurrently infected with two or more DENV serotypes, indicating that all four DENVs were present in a single dengue session in Chittagong, Bangladesh. Then, DENV4 was the most prevailed serotype, followed by DENV2, DENV1 and DENV3 in single DENV serotype infections. However, in almost 90% cases of concurrent multiple DENV infections DENV1 serotype was present. A detail analysis of clinical data clearly indicated that DENV1 and DENV2 resulted very similar patterns of clinical symptoms which were quite different from those caused by DENV3 and DENV4. For example, ache and pain were absent in DENV3 infection and diarrhea was absent in DENV4 infections. Furthermore, DENV3, both in single and concurrent multiple DENV infections, might increase dengue disease severity as observed highly reduced platelet counts along with increased WBC in patients infected with DENV3 serotype. Conclusion: All four DENV serotypes, both as single and concurrent multiple DENV infections, were present in single dengue session in Bangladesh. Despite having very similar sequences and structures all four DENVs might produce different disease spectra, ranging from classical dengue fever to dengue hemorrhagic fever. Concurrent multiple DENV infections could contribute increased dengue disease severity in dengue outbreaks in Bangladesh. Bioresearch Commu. 8(1): 1042-1048, 2022 (January)


Viruses ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 20
Author(s):  
Bárbara Aparecida Chaves ◽  
Raquel Soares Maia Godoy ◽  
Thaís Bonifácio Campolina ◽  
Ademir Bentes Vieira Júnior ◽  
Andréia da Costa Paz ◽  
...  

The successful spread and maintenance of the dengue virus (DENV) in mosquito vectors depends on their viral infection susceptibility, and parameters related to vector competence are the most valuable for measuring the risk of viral transmission by mosquitoes. These parameters may vary according to the viral serotype in circulation and in accordance with the geographic origin of the mosquito population that is being assessed. In this study, we investigated the effect of DENV serotypes (1–4) with regards to the infection susceptibility of five Brazilian Ae. aegypti populations from Manaus, the capital of the state of Amazonas, Brazil. Mosquitoes were challenged by oral infection with the DENV serotypes and then tested for the presence of the arbovirus using quantitative PCR at 14 days post-infection, which is the time point that corresponds to the extrinsic incubation period of Ae. aegypti when reared at 28 °C. Thus, we were able to determine the infection patterns for DENV-1, -2, -3 and -4 in the mosquito populations. The mosquitoes had both interpopulation and inter-serotype variation in their viral susceptibilities. All DENV serotypes showed a similar tendency to accumulate in the body in a greater amount than in the head/salivary gland (head/SG), which does not occur with other flaviviruses. For DENV-1, DENV-3, and DENV-4, the body viral load varied among populations, but the head/SG viral loads were similar. Differently for DENV-2, both body and head/SG viral loads varied among populations. As the lack of phenotypic homogeneity represents one of the most important reasons for the long-term fight against dengue incidence, we expect that this study will help us to understand the dynamics of the infection patterns that are triggered by the distinct serotypes of DENV in mosquitoes.


2021 ◽  
Vol 948 (1) ◽  
pp. 012080
Author(s):  
S Pambudi ◽  
D Irawan ◽  
A Danny ◽  
T Widayanti ◽  
Tarwadi

Abstract The identification of human Non-Structural-1 (NS1) protein epitopes will help us better understand Dengue virus (DENV) immunopathogenesis. In this study, several online and offline bioinformatic prediction tools were exploited to predict and analyze T-cell and B-cell epitopes of DENV NS1 consensus sequences originated from Indonesian clinical isolates. We identified a potential peptide at NS1155--163 (VEDYGFGIF) which interact with MHC-I allele HLA-B*40:01 and showed high binding affinity (IC50) scores ranging between 63.8 nM to 183.9 nM for all Indonesian DENV serotypes. Furthermore, we have succeeded identified a region at the C-terminal of Indonesian DENV NS1 protein between 325--344 as part of discontinuous antigenic epitope which conserved for all serotypes. Our analyses showed this region could induce strong and persistent antibody against all DENV serotypes by interacting with MHC-I molecule and also recognized by B-cell receptor. The identification of DENV NS1 T-cell and B-cell epitopes may help in the development of a new vaccine, drug discovery, and diagnostic system to help eradicate dengue infection.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wei-Liang Liu ◽  
Chia-Wei Hsu ◽  
Shih-Peng Chan ◽  
Pei-Shi Yen ◽  
Matthew P. Su ◽  
...  

AbstractThe areas where dengue virus (DENV) is endemic have expanded rapidly, driven in part by the global spread of Aedes species, which act as disease vectors. DENV replicates in the mosquito midgut and is disseminated to the mosquito’s salivary glands for amplification. Thus, blocking virus infection or replication in the tissues of the mosquito may be a viable strategy for reducing the incidence of DENV transmission to humans. Here we used the mariner Mos1 transposase to create an Aedes aegypti line that expresses virus-specific miRNA hairpins capable of blocking DENV replication. These microRNA are driven by the blood-meal-inducible carboxypeptidase A promoter or by the polyubiquitin promoter. The transgenic mosquitoes exhibited significantly lower infection rates and viral titers for most DENV serotypes 7 days after receiving an infectious blood meal. The treatment was also effective at day 14 post infection after a second blood meal had been administered. In viral transmission assay, we found there was significantly reduced transmission in these lines. These transgenic mosquitoes were effective in silencing most of the DENV genome; such an approach may be employed to control a dengue fever epidemic.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Chandana Wijesinghe ◽  
Jagath Gunatilake ◽  
P. H. D. Kusumawathie ◽  
P. D. N. N. Sirisena ◽  
S. W. P. L. Daulagala ◽  
...  

Abstract Background Spatial and temporal changes in the dengue incidence are associated with multiple factors, such as climate, immunity among a population against dengue viruses (DENV), circulating DENV serotypes and vertical transmission (VT) of DENV in an area at a given time. The level of VT in a specific location has epidemiological implications in terms of viral maintenance in vectors. Identification of the circulating DENV serotypes in both patients and Aedes mosquito larvae in an area may be useful for the early detection of outbreaks. We report here the results of a prospective descriptive study that was conducted to detect the levels of VT in Aedes mosquito larvae and circulating DENV serotypes in patients and Aedes mosquito larvae from December 2015 to March 2017 in an area of Sri Lanka at high risk for dengue. Methods A total of 200 patients with clinically suspected dengue who had been admitted to a tertiary care hospital during a dengue outbreak (3 study periods: December 2015–January 2016, June–August 2016, December 2016–January 2017) and in the inter-outbreak periods (February–May 2016 and September–November 2016) were investigated. Blood samples were drawn from the study participants to test for DENV. The houses of the study participants were visited within 7 days of admission to the hospital, and Aedes larvae were also collected within a radius of 400 m from the houses. The larvae were separately identified to species and then pooled according to each patient’s identification number. Patients’ sera and the Aedes larvae were tested to identify the infecting DENV serotypes using a reverse transcription PCR (RT-PCR) method. Levels of VT in Aedes mosquito larvae were also identified. Results All four DENV serotypes (DENV-1 to -4) were identified in the study area. In the early part of the study (December 2015–February 2016), DENV-3 was predominant and from April 2016 to March 2017, DENV-2 became the most predominant type. Four cases of DENV co-infections were noted during the study period in patients. Interestingly, all four DENV serotypes were detected in Aedes albopictus larvae, which was the prominent immature vectorial form identified throughout the study period in the area, showing 9.8% VT of DENV. With the exception of DENV-4, the other three DENV serotypes were identified in Aedes aegypti larvae with a VT of 8.1%. Conclusion Comparatively high rates of VT of DENV was detected in Ae. albopictus and Ae. aegypti larvae. A shift in the predominant DENV serotype with simultaneous circulation of all four DENV serotypes was identified in the study area from December 2015 to March 2017. Graphical Abstract


Sensors ◽  
2021 ◽  
Vol 21 (23) ◽  
pp. 7809
Author(s):  
Kanaporn Poltep ◽  
Emi E. Nakayama ◽  
Tadahiro Sasaki ◽  
Takeshi Kurosu ◽  
Yoshiki Takashima ◽  
...  

Four serotypes of dengue virus (DENV), type 1 to 4 (DENV-1 to DENV-4), exhibit approximately 25–40% of the difference in the encoded amino acid residues of viral proteins. Reverse transcription of RNA extracted from specimens followed by PCR amplification is the current standard method of DENV serotype determination. However, since this method is time-consuming, rapid detection systems are desirable. We established several mouse monoclonal antibodies directed against DENV non-structural protein 1 and integrated them into rapid DENV detection systems. We successfully developed serotype-specific immunochromatography systems for all four DENV serotypes. Each system can detect 104 copies/mL in 15 min using laboratory and clinical isolates of DENV. No cross-reaction between DENV serotypes was observed in these DENV isolates. We also confirmed that there was no cross-reaction with chikungunya, Japanese encephalitis, Sindbis, and Zika viruses. Evaluation of these systems using serum from DENV-infected individuals indicated a serotype specificity of almost 100%. These assay systems could accelerate both DENV infection diagnosis and epidemiologic studies in DENV-endemic areas.


Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2232
Author(s):  
Caroline J. Stephenson ◽  
Heather Coatsworth ◽  
Christy M. Waits ◽  
Nicole M. Nazario-Maldonado ◽  
Derrick K. Mathias ◽  
...  

Dengue viruses (DENVs) cause the greatest public health burden globally among the arthropod-borne viruses. DENV transmission risk has also expanded from tropical to subtropical regions due to the increasing range of its principal mosquito vector, Aedes aegypti. Focal outbreaks of dengue fever (dengue) in the state of Florida (FL) in the USA have increased since 2009. However, little is known about the competence of Ae. aegypti populations across different regions of FL to transmit DENVs. To understand the effects of DENV genotype and serotype variations on vector susceptibility and transmission potential in FL, we orally infected a colony of Ae. aegypti (Orlando/ORL) with low passage or laboratory DENV-1 through -4. Low passage DENVs were more infectious to and had higher transmission potential by ORL mosquitoes. We used these same DENVs to examine natural Ae. aegypti populations to determine whether spatial distributions correlated with differential vector competence. Vector competence across all DENV serotypes was greater for mosquitoes from areas with the highest dengue incidence in south FL compared to north FL. Vector competence for low passage DENVs was significantly higher, revealing that transmission risk is influenced by virus/vector combinations. These data support a targeted mosquito-plus-pathogen screening approach to more accurately estimate DENV transmission risk.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Mahesha N. Nadugala ◽  
Chandima Jeewandara ◽  
Ramesh S. Jadi ◽  
Gathsaurie N. Malavige ◽  
Aravinda M. de Silva ◽  
...  

Abstract Background The natural antibody responses to B-cell epitopes from dengue structural proteins were assessed using immune sera from people having well-defined past dengue infections with one of the four serotypes. Method Based on an immune-computational analysis previously conducted, nineteen epitopes from the envelope (E) and eight epitopes from pre-membrane (prM), which were more than 50% conserved across all the four DENV serotypes, were selected. Peptides to represent these B-cell epitopes were obtained from commercially available arrays, and were subjected to enzyme linked immunosorbent assay with sera obtained from dengue seropositive healthy volunteers (DENV1 n = 12: DENV2 n = 12: DENV3 n = 12 and DENV4 n = 12), and 10 dengue seronegative healthy volunteers from Sri Lanka. The cut-off value for the positive antibody response was set by taking the mean response of a peptide to the negative sera plus three standard deviations. The peptides (N = 7) showing the broad immune responses were used to generate antibodies in three mice (Balb/c) batches. The mice antisera were then subjected to microneutralization assays against all the four DENV serotypes. An EC50 viral neutralization ≥ 40 times the serum dilution was considered as neutralizing. Results Five of the E-peptide and two prM peptides were recognised by most individuls exposed to infections with each of the four serotypes, showing a serotype cross-reactive broad antibody response. The mice immune sera against the peptides representing the five E protein epitopes neutralized all the four DENV serotypes. Two of these five epitopes are from the Domain II, whereas one of them includes the whole bc-loop region. Conclusion The antibody responses of highly conserved epitopes across the serotypes, were broadly responsive with sera of all four DENV serotypes collected from individuals infected with only one DENV serotype. Weakly conserved epitopes showed rather specific antibody responses dominated by one or few serotypes.


2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S420-S421
Author(s):  
Kevin Russell ◽  
Richard E Rupp ◽  
Javier O Morales-Ramirez ◽  
Clemente Diaz-Perez ◽  
Charles P Andrews ◽  
...  

Abstract Background Dengue (DENV) is a mosquito-borne virus with four serotypes causing substantial morbidity in tropical and subtropical areas worldwide. A dengue vaccine that can be given to both seronegative and seropositive populations remains an important unmet medical need. V181 is an investigational live, attenuated, quadrivalent dengue vaccine. Methods In this phase 1 double-blind, placebo-controlled study, the safety, tolerability, and immunogenicity of V181 in healthy adults were evaluated in two formulations: TV003 and TV005. TV005 has a 10-fold higher DENV2 component as compared to TV003. Two-hundred participants [~ 50% baseline flavivirus-experienced (BFE) and 50% baseline flavivirus-naive (BFN)] were randomized 2:2:1 to receive TV003, TV005, or placebo on Days 1 and 180. Immunogenicity against each of the four DENV serotypes was measured using a Virus Reduction Neutralization Test (VRNT60) after each vaccination and out to 1 year after the second dose. Results There were no discontinuations due to adverse events (AEs) or vaccine-related serious AEs. The most common AEs Days 1-28 after any TV003 or TV005 vaccination were rash, headache, fatigue, and myalgia. DENV VRNT60 seropositivity to 3 or 4 serotypes (i.e. tri-or tetravalent) was demonstrated in 92.6% of BFN TV003 participants, 74.2% of BFN TV005 participants, and 100% of the BFE participants at 6 months postdose 1 (PD1). Vaccine viremia, a measure of vaccine infectivity, was transiently detected from all four DENV types after the first dose of TV003 and TV005. Tri- or tetravalent vaccine-viremia was detected in 63.9 % and 25.6 % of BFN TV003 and TV005 participants, respectively, PD1. Compared to baseline, robust increases in VRNT60 GMTs were observed after the first dose of TV003 and TV005 in both flavivirus subgroups for all DENV serotypes and minimal increases were observed PD2. GMTs in the TV003 and TV005 BFE and BFN subgroups remained above the respective baselines and placebo at 1-year PD2. Conclusion Both formulations of V181 were generally well tolerated in healthy adults. Overall, viremia and immunogenicity were higher after TV003 as compared to TV005. These data support the continued development of the V181 TV003 formulation as a single-dose vaccine for the prevention of DENV disease. Disclosures Kevin Russell, MD, MTM&H, Merck & Co., Inc. (Employee, Shareholder) Richard E. Rupp, MD, Merck & Co., Inc. (Research Grant or Support) Clemente Diaz-Perez, MD, Merck & Co., Inc. (Research Grant or Support) Charles P. Andrews, MD, Merck & Co., Inc. (Research Grant or Support) Andrew W. Lee, MD, Merck & Co., Inc. (Employee, Shareholder) Tyler S. Finn, BA, Merck & Co., Inc. (Employee, Shareholder) Kara Cox, MS, Merck & Co., Inc. (Employee, Shareholder) Amy Falk Russell, MS, Merck & Co., Inc. (Employee, Shareholder) Margaret M. Schaller, BS, Merck & Co., Inc. (Employee, Shareholder) Jason C. Martin, PhD, Merck & Co., Inc. (Employee, Shareholder) Donna M. Hyatt, BA, Merck & Co., Inc. (Employee, Shareholder) Sabrina Gozlan-Kelner, MS, Merck & Co., Inc. (Employee, Shareholder) Androniki Bili, MD, MPH, Merck & Co., Inc. (Employee, Shareholder) Beth-Ann Coller, PhD, Merck & Co., Inc. (Employee, Shareholder)


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