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Nucleotide sequences of the nonstructural protein NS1 gene of three dengue-2 viruses, M1, M2 and M3, isolated in Malaysia from patients with dengue haemorrhagic fever, dengue shock syndrome and dengue fever, respectively

Fong MY, Koh CL, Samuel S, Pang T, Lam SK

Nucleic Acids Res, 1990 Mar 25;18(6):1642.
PMID: 2139210
Matched MeSH terms: Dengue Virus/genetics*
Pathogenesis of dengue haemorrhagic fever: current perspectives

Pang T

Adv Exp Med Biol, 1989;257:155-68.
PMID: 2694815 DOI: 10.1007/978-1-4684-5712-4_15
Matched MeSH terms: Dengue Virus/genetics
Fulltext Nucleotide and encoded amino acid sequences of the capsid protein gene of three dengue-2 viruses isolated in Malaysia from patients with dengue haemorrhagic fever, dengue shock syndrome or dengue fever

Samuel S, Koh CL, Pang T, Lam SK

Nucleic Acids Res, 1990 Apr 11;18(7):1904.
PMID: 2336373
Matched MeSH terms: Dengue Virus/genetics*
Complete genome sequence analysis of dengue virus type 2 isolated in Brunei

Osman O, Fong MY, Devi S

Virus Res, 2008 Jul;135(1):48-52.
PMID: 18406488 DOI: 10.1016/j.virusres.2008.02.006

In a previous study, we have reported the detection and isolation of dengue virus in Brunei (Osman, O., Fong, M.Y., Devi, S., 2007. A preliminary study of dengue infection in Brunei. JJID 60 (4), 205-208). DEN-2 was the predominant serotype followed by DEN-1. The full genomic sequences of 3 DEN-2 viruses isolated during the 2005-2006 dengue incident in Brunei were determined. Twenty-five primer sets were designed to amplify contiguous overlapping fragments of approximately 500-600 base pairs spanning the entire sequence of the viral genome. The amplified PCR products were sent for sequencing and their nucleotides and the deduced amino acids were determined. All three DEN-2 virus isolated were clustered in the Cosmopolitan genotype of the DEN-2 classification by Twiddy et al. This work constitutes the first complete genetic characterization of three Brunei DEN-2 virus strains.

Matched MeSH terms: Dengue Virus/genetics*
Fulltext Emergence of the Asian lineage dengue virus type 3 genotype III in Malaysia

Tan KK, Zulkifle NI, Sulaiman S, Pang SP, NorAmdan N, MatRahim N, et al.

BMC Evol. Biol., 2018 04 24;18(1):58.
PMID: 29699483 DOI: 10.1186/s12862-018-1175-4

BACKGROUND: Dengue virus type 3 genotype III (DENV3/III) is associated with increased number of severe infections when it emerged in the Americas and Asia. We had previously demonstrated that the DENV3/III was introduced into Malaysia in the late 2000s. We investigated the genetic diversity of DENV3/III strains recovered from Malaysia and examined their phylogenetic relationships against other DENV3/III strains isolated globally.
RESULTS: Phylogenetic analysis revealed at least four distinct DENV3/III lineages. Two of the lineages (DENV3/III-B and DENV3/III-C) are current actively circulating whereas the DENV3/III-A and DENV3/III-D were no longer recovered since the 1980s. Selection pressure analysis revealed strong evidence of positive selection on a number of amino acid sites in PrM, E, NS1, NS2a, NS2b, NS3, NS4a, and NS5. The Malaysian DENV3/III isolates recovered in the 1980s (MY.59538/1987) clustered into DENV3/III-B, which was the lineage with cosmopolitan distribution consisting of strains actively circulating in the Americas, Africa, and Asia. The Malaysian isolates recovered after the 2000s clustered within DENV3/III-C. This DENV3/III-C lineage displayed a more restricted geographical distribution and consisted of isolates recovered from Asia, denoted as the Asian lineage. Amino acid variation sites in NS5 (NS5-553I/M, NS5-629 T, and NS5-820E) differentiated the DENV3/III-C from other DENV3 viruses. The codon 629 of NS5 was identified as a positively selected site. While the NS5-698R was identified as unique to the genome of DENV3/III-C3. Phylogeographic results suggested that the recent Malaysian DENV3/III-C was likely to have been introduced from Singapore in 2008 and became endemic. From Malaysia, the virus subsequently spread into Taiwan and Thailand in the early part of the 2010s and later reintroduced into Singapore in 2013.
CONCLUSIONS: Distinct clustering of the Malaysian old and new DENV3/III isolates suggests that the currently circulating DENV3/III in Malaysia did not descend directly from the strains recovered during the 1980s. Phylogenetic analyses and common genetic traits in the genome of the strains and those from the neighboring countries suggest that the Malaysian DENV3/III is likely to have been introduced from the neighboring regions. Malaysia, however, serves as one of the sources of the recent regional spread of DENV3/III-C3 within the Asia region.

Matched MeSH terms: Dengue Virus/genetics*
Disruption of predicted dengue virus type 3 major outbreak cycle coincided with switching of the dominant circulating virus genotype

Tan KK, Zulkifle NI, Abd-Jamil J, Sulaiman S, Yaacob CN, Azizan NS, et al.

Infect Genet Evol, 2017 Oct;54:271-275.
PMID: 28698156 DOI: 10.1016/j.meegid.2017.07.008

Dengue is hyperendemic in most of Southeast Asia. In this region, all four dengue virus serotypes are persistently present. Major dengue outbreak cycle occurs in a cyclical pattern involving the different dengue virus serotypes. In Malaysia, since the 1980s, the major outbreak cycles have involved dengue virus type 3 (DENV3), dengue virus type 1 (DENV1) and dengue virus type 2 (DENV2), occurring in that order (DENV3/DENV1/DENV2). Only limited information on the DENV3 cycles, however, have been described. In the current study, we examined the major outbreak cycle involving DENV3 using data from 1985 to 2016. We examined the genetic diversity of DENV3 isolates obtained during the period when DENV3 was the dominant serotype and during the inter-dominant transmission period. Results obtained suggest that the typical DENV3/DENV1/DENV2 cyclical outbreak cycle in Malaysia has recently been disrupted. The last recorded major outbreak cycle involving DENV3 occurred in 2002, and the expected major outbreak cycle involving DENV3 in 2006-2012 did not materialize. DENV genome analyses revealed that DENV3 genotype II (DENV3/II) was the predominant DENV3 genotype (67%-100%) recovered between 1987 and 2002. DENV3 genotype I (DENV3/I) emerged in 2002 followed by the introduction of DENV3 genotype III (DENV3/III) in 2008. These newly emerged DENV3 genotypes replaced DENV3/II, but there was no major upsurge of DENV3 cases that accompanied the emergence of these viruses. DENV3 remained in the background of DENV1 and DENV2 until now. Virus genome sequence analysis suggested that intrinsic differences within the different dengue virus genotypes could have influenced the transmission efficiency of DENV3. Further studies and continuous monitoring of the virus are needed for better understanding of the DENV transmission dynamics in hyperendemic regions.

Matched MeSH terms: Dengue Virus/genetics*
Fulltext Global Epidemiology of Dengue Outbreaks in 1990-2015: A Systematic Review and Meta-Analysis

Guo C, Zhou Z, Wen Z, Liu Y, Zeng C, Xiao D, et al.

Front Cell Infect Microbiol, 2017;7:317.
PMID: 28748176 DOI: 10.3389/fcimb.2017.00317

Dengue is an arthropod-borne infectious disease caused by dengue virus (DENV) infection and transmitted byAedesmosquitoes. Approximately 50-100 million people are infected with DENV each year, resulting in a high economic burden on both governments and individuals. Here, we conducted a systematic review and meta-analysis to summarize information regarding the epidemiology, clinical characteristics, and serotype distribution and risk factors for global dengue outbreaks occurring from 1990 to 2015. We searched the PubMed, Embase and Web of Science databases through December 2016 using the term "dengue outbreak." In total, 3,853 studies were identified, of which 243 studies describing 262 dengue outbreaks met our inclusion criteria. The majority of outbreak-associated dengue cases were reported in the Western Pacific Region, particularly after the year 2010; these cases were primarily identified in China, Singapore and Malaysia. The pooled mean age of dengue-infected individuals was 30.1 years; of the included patients, 54.5% were male, 23.2% had DHF, 62.0% had secondary infections, and 1.3% died. The mean age of dengue patients reported after 2010 was older than that of patients reported before 2010 (34.0 vs. 27.2 years); however, the proportions of patients who had DHF, had secondary infections and died significantly decreased after 2010. Fever, malaise, headache, and asthenia were the most frequently reported clinical symptoms and signs among dengue patients. In addition, among the identified clinical symptoms and signs, positive tourniquet test (OR= 4.86), ascites (OR= 13.91) and shock (OR= 308.09) were identified as the best predictors of dengue infection, DHF and mortality, respectively (bothP< 0.05). The main risk factors for dengue infection, DHF and mortality were living with uncovered water container (OR= 1.65), suffering from hypotension (OR= 6.18) and suffering from diabetes mellitus (OR= 2.53), respectively (allP< 0.05). The serotype distribution varied with time and across WHO regions. Overall, co-infections were reported in 47.7% of the evaluated outbreaks, and the highest pooled mortality rate (2.0%) was identified in DENV-2 dominated outbreaks. Our study emphasizes the necessity of implementing programs focused on targeted prevention, early identification, and effective treatment.

Matched MeSH terms: Dengue Virus/genetics
Fulltext The epidemiological characteristics and molecular phylogeny of the dengue virus in Guangdong, China, 2015

Sun J, Zhang H, Tan Q, Zhou H, Guan D, Zhang X, et al.

Sci Rep, 2018 07 02;8(1):9976.
PMID: 29967414 DOI: 10.1038/s41598-018-28349-2

In 2015, an unexpected multiple outbreak of dengue occurred in Guangdong, China. In total, 1,699 cases were reported, of which 1,627 cases were verified to have DENV infections by nucleic acid or NS1 protein, including 44 DENV-1, 1126 DENV-2, 18 DENV-3 and 6 DENV-4, and the other cases were confirmed by NS1 ELISA. Phylogenetic analyses of DENV-1 isolates identified two genotypes (I and V). The predominant DENV-2 outbreak isolates were the Cosmopolitan genotypes, which likely originated from Malaysia. The DENV-3 isolates were assigned into genotype I and genotype III. All 6 DENV-4 isolates from imported cases were likely originally from Cambodia, Thailand and the Philippines. The entomological surveillance showed a moderate risk for the BI index in Chaozhou and Foshan and a low risk in Guangzhou. The imported cases were mostly detected in Guangzhou and Foshan. Surprisingly, the most serious outbreak occurred in Chaozhou, but not in Guangzhou or Foshan. A combined analyses demonstrated the multiple geographical origins of this outbreak, and highlight the detection of suspected cases after the alerting of imported cases, early implementation of control policies and reinforce the vector surveillance strategies were the key points in the chain of prevention and control of dengue epidemics.

Matched MeSH terms: Dengue Virus/genetics*
Fulltext A broadly neutralizing germline-like human monoclonal antibody against dengue virus envelope domain III

Hu D, Zhu Z, Li S, Deng Y, Wu Y, Zhang N, et al.

PLoS Pathog, 2019 06;15(6):e1007836.
PMID: 31242272 DOI: 10.1371/journal.ppat.1007836

Dengue is the most widespread vector-borne viral disease caused by dengue virus (DENV) for which there are no safe, effective drugs approved for clinical use. Here, by using sequential antigen panning of a yeast antibody library derived from healthy donors against the DENV envelop protein domain III (DIII) combined with depletion by an entry defective DIII mutant, we identified a cross-reactive human monoclonal antibody (mAb), m366.6, which bound with high affinity to DENV DIII from all four DENV serotypes. Immunogenetic analysis indicated that m366.6 is a germline-like mAb with very few somatic mutations from the closest VH and Vλ germline genes. Importantly, we demonstrated that it potently neutralized DENV both in vitro and in the mouse models of DENV infection without detectable antibody-dependent enhancement (ADE) effect. The epitope of m366.6 was mapped to the highly conserved regions on DIII, which may guide the design of effective dengue vaccine immunogens. Furthermore, as the first germline-like mAb derived from a naïve antibody library that could neutralize all four DENV serotypes, the m366.6 can be a tool for exploring mechanisms of DENV infection, and is a promising therapeutic candidate.

Matched MeSH terms: Dengue Virus/genetics
Detection of dengue virus serotype 2 (DENV-2) in population of Aedes mosquitoes from Sibu and Miri divisions of Sarawak using reverse transcription polymerase chain reaction (RT-PCR) and semi-nested PCR

Harvie S, Nor Aliza AR, Lela S, Razitasham S

Trop Biomed, 2020 Jun 01;37(2):258-272.
PMID: 33612796

Dengue has been a public health concern for many years in Malaysia. Having knowledge on the current circulating dengue serotypes and population of vector mosquitoes is key in controlling outbreaks and future outbreak predictions. The current study reports the first study on detecting dengue virus serotypes in the Aedes mosquito population in Sibu and Miri divisions of Sarawak. Mosquito samples were collected at selected localities from September 2016 to December 2017. Localities were selected mainly focussing on urban residential areas. The mosquitoes collected comprises of the field-caught adults and immatures collected from artificial and natural water containers. Collected mosquitoes were identified to species level and screened for the presence of dengue virus using conventional reverse transcription polymerase chain reaction (RT-PCR). Dengue virus serotype 2 (DENV-2) was identified in 3 pools of field-caught female Aedes albopictus adults collected from Jalan Tong Sang, Sibu, Sibu Lake Garden, and Taman Ceria, Permyjaya, Miri, respectively. DENV-2 was also detected in one pool of adult male Ae. albopictus emerged from immatures collected from Taman Ceria, Permyjaya, Miri. The findings in this study revealed that Ae. albopictus was the main species colonizing the study areas, and the current circulating dengue virus serotype was DENV-2. This study also reports the first natural evidence of transovarial transmission of dengue in the natural population of Ae. albopictus within the study area and provides information as reference for further vector-pathogen studies.

Matched MeSH terms: Dengue Virus/genetics
Fulltext The epidemiological characteristics of dengue in high-risk areas of China, 2013-2016

Sang S, Liu Q, Guo X, Wu D, Ke C, Liu-Helmersson J, et al.

PLoS Negl Trop Dis, 2021 12;15(12):e0009970.
PMID: 34928951 DOI: 10.1371/journal.pntd.0009970

INTRODUCTION: Dengue has become a more serious human health concern in China, with increased incidence and expanded outbreak regions. The knowledge of the cross-sectional and longitudinal epidemiological characteristics and the evolutionary dynamics of dengue in high-risk areas of China is limited.
METHODS: Records of dengue cases from 2013 to 2016 were obtained from the China Notifiable Disease Surveillance System. Full envelope gene sequences of dengue viruses detected from the high-risk areas of China were collected. Maximum Likelihood tree and haplotype network analyses were conducted to explore the phylogenetic relationship of viruses from high-risk areas of China.
RESULTS: A total of 56,520 cases was reported in China from 2013 to 2016. During this time, Yunnan, Guangdong and Fujian provinces were the high-risk areas. Imported cases occurred almost year-round, and were mainly introduced from Southeast Asia. The first indigenous case usually occurred in June to August, and the last one occurred before December in Yunnan and Fujian provinces but in December in Guangdong Province. Seven genotypes of DENV 1-3 were detected in the high-risk areas, with DENV 1-I the main genotype and DENV 2-Cosmopolitan the secondary one. The Maximum Likelihood trees show that almost all the indigenous viruses separated into different clusters. DENV 1-I viruses were found to be clustered in Guangdong Province, but not in Fujian and Yunnan, from 2013 to 2015. The ancestors of the Guangdong viruses in the cluster in 2013 and 2014 were most closely related to strains from Thailand or Singapore, and the Guangdong virus in 2015 was most closely related to the Guangdong virus of 2014. Based on closest phylogenetic relationships, viruses from Myanmar possibly initiated further indigenous cases in Yunnan, those from Indonesia in Fujian, while viruses from Thailand, Malaysia, Singapore and Indonesia were predominant in Guangdong Province.
CONCLUSIONS: Dengue is still an imported disease in China, although some genotypes continued to circulate in successive years. Viral phylogenies based on the envelope gene suggested periodic introductions of dengue strains into China, primarily from Southeast Asia, with occasional sustained, multi-year transmission in some regions of China.

Matched MeSH terms: Dengue Virus/genetics
Fulltext Rapid detection and serotyping of dengue virus by multiplex RT-PCR and real-time SYBR green RT-PCR

Yong YK, Thayan R, Chong HT, Tan CT, Sekaran SD

Singapore Med J, 2007 Jul;48(7):662-8.
PMID: 17609830

Dengue fever and dengue haemorrhagic fever currently rank highly among the newly-emerging infectious diseases, and are considered to be the most important arboviral disease worldwide. The definitive diagnosis is culture analysis, but practical considerations limit its use. Also, the period for viral detection is limited. Within a day or two after fever subsides, rising levels of antibodies interfere with viral cultures. An alternative to this quandary is the use of viral RNA detection assays. In our laboratory, a reverse transcriptase polymerase chain reaction (RT-PCR) assay was developed using a set of degenerate primers.

Matched MeSH terms: Dengue Virus/genetics*
Fulltext Dengue vaccine design: issues and challenges

Cardosa MJ

Br Med Bull, 1998;54(2):395-405.
PMID: 9830205 DOI: 10.1093/oxfordjournals.bmb.a011696

Dengue virus infection is now a global problem affecting tens of millions of people. The spread of the four dengue virus serotypes had led to increased incidence of dengue haemorrhagic fever (DHF) reported and with 2.5 billion people at risk, efforts towards the development of safe and effective vaccines against dengue must be accelerated. This chapter reviews some of the important lessons of pathogenesis which may be learnt from classical studies in the field and place these in the context of current knowledge about the molecular biology of the virus. The issues which have to be addressed in designing a safe vaccine against dengue are raised and the problems of designing subunit as well as whole virus vaccines are pointed out, particularly with regard to the phenomenon of antibody dependent enhancement and, more generally, the problem of immune potentiation of disease. More efforts must be made to understand the basis of pathogenesis in DHF and in finding out what nature has to teach about protection against and recovery from dengue virus infection.

Matched MeSH terms: Dengue Virus/genetics
Fulltext Meta-Analysis of Dengue Severity during Infection by Different Dengue Virus Serotypes in Primary and Secondary Infections

Soo KM, Khalid B, Ching SM, Chee HY

PLoS One, 2016;11(5):e0154760.
PMID: 27213782 DOI: 10.1371/journal.pone.0154760

INTRODUCTION: Dengue virus (DENV) infection is currently a major cause of morbidity and mortality in the world; it has become more common and virulent over the past half-century and has gained much attention. Thus, this review compared the percentage of severe cases of both primary and secondary infections with different serotypes of dengue virus.
METHODS: Data related to the number of cases involving dengue fever (DF), dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS) or severe dengue infections caused by different serotypes of dengue virus were obtained by using the SCOPUS, the PUBMED and the OVID search engines with the keywords "(dengue* OR dengue virus*) AND (severe dengue* OR severity of illness index* OR severity* OR DF* OR DHF* OR DSS*) AND (serotypes* OR serogroup*)", according to the MESH terms suggested by PUBMED and OVID.
RESULTS: Approximately 31 studies encompassing 15,741 cases reporting on the dengue serotypes together with their severity were obtained, and meta-analysis was carried out to analyze the data. This study found that DENV-3 from the Southeast Asia (SEA) region displayed the greatest percentage of severe cases in primary infection (95% confidence interval (CI), 31.22-53.67, 9 studies, n = 598, I2 = 71.53%), whereas DENV-2, DENV-3, and DENV-4 from the SEA region, as well as DENV-2 and DENV-3 from non-SEA regions, exhibited the greatest percentage of severe cases in secondary infection (95% CI, 11.64-80.89, 4-14 studies, n = 668-3,149, I2 = 14.77-96.20%). Moreover, DENV-2 and DENV-4 from the SEA region had been found to be more highly associated with dengue shock syndrome (DSS) (95% CI, 10.47-40.24, 5-8 studies, n = 642-2,530, I2 = 76.93-97.70%), while DENV-3 and DENV-4 from the SEA region were found to be more highly associated with dengue hemorrhagic fever (DHF) (95% CI, 31.86-54.58, 9 studies, n = 674-2,278, I2 = 55.74-88.47%), according to the 1997 WHO dengue classification. Finally, DENV-2 and DENV-4 from the SEA region were discovered to be more highly associated with secondary infection compared to other serotypes (95% CI, 72.01-96.32, 9-12 studies, n = 671-2,863, I2 = 25.01-96.75%).
CONCLUSION: This study provides evidence that the presence of certain serotypes, including primary infection with DENV-3 from the SEA region and secondary infection with DENV-2, DENV-3, and DENV-4 also from the SEA region, as well as DENV-2 and DENV-3 from non SEA regions, increased the risk of severe dengue infections. Thus, these serotypes are worthy of special consideration when making clinical predictions upon the severity of the infection.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015026093 (http://www.crd.york.ac.uk/PROSPERO).

Matched MeSH terms: Dengue Virus/genetics
Fulltext Refractoriness of Aedes aegypti (Linnaeus) to dual infection with dengue and chikungunya virus

Rohani A, Potiwat R, Zamree I, Lee HL

Southeast Asian J Trop Med Public Health, 2009 May;40(3):443-8.
PMID: 19842428

In this study, artificial membrane feeding technique was used to orally feed Aedes aegypti with dengue and chikungunya viruses. Virus detection was carried out by reverse transcriptase polymerase chain reaction. The study did not detect dual infection of Ae. aegypti with dengue and chikungunya virus from the same pool or from individual mosquitoes. Oral receptivity of Ae. aegypti to chikungunya virus was higher than that of dengue virus.

Matched MeSH terms: Dengue Virus/genetics
Fulltext Dengue virus type 1 clade replacement in recurring homotypic outbreaks

Teoh BT, Sam SS, Tan KK, Johari J, Shu MH, Danlami MB, et al.

BMC Evol. Biol., 2013;13:213.
PMID: 24073945 DOI: 10.1186/1471-2148-13-213

Recurring dengue outbreaks occur in cyclical pattern in most endemic countries. The recurrences of dengue virus (DENV) infection predispose the population to increased risk of contracting the severe forms of dengue. Understanding the DENV evolutionary mechanism underlying the recurring dengue outbreaks has important implications for epidemic prediction and disease control.

Matched MeSH terms: Dengue Virus/genetics*
Molecular identification of the first local dengue fever outbreak in Shenzhen city, China: a potential imported vertical transmission from Southeast Asia?

Yang F, Guo GZ, Chen JQ, Ma HW, Liu T, Huang DN, et al.

Epidemiol Infect, 2014 Feb;142(2):225-33.
PMID: 23587429 DOI: 10.1017/S0950268813000897

A suspected dengue fever outbreak occurred in 2010 at a solitary construction site in Shenzhen city, China. To investigate this epidemic, we used serological, molecular biological, and bioinformatics techniques. Of nine serum samples from suspected patients, we detected seven positive for dengue virus (DENV) antibodies, eight for DENV-1 RNA, and three containing live viruses. The isolated virus, SZ1029 strain, was sequenced and confirmed as DENV-1, showing the highest E-gene homology to D1/Malaysia/36000/05 and SG(EHI)DED142808 strains recently reported in Southeast Asia. Further phylogenetic tree analysis confirmed their close relationship. At the epidemic site, we also detected 14 asymptomatic co-workers (out of 291) positive for DENV antibody, and DENV-1-positive mosquitoes. Thus, we concluded that DENV-1 caused the first local dengue fever outbreak in Shenzhen. Because no imported case was identified, the molecular fingerprints of the SZ1029 strain suggest this outbreak may be due to vertical transmission imported from Southeast Asia.

Matched MeSH terms: Dengue Virus/genetics*
Fragment-based molecular design of new competitive dengue Den2 Ns2b/Ns3 inhibitors from the components of fingerroot (Boesenbergia rotunda)

Frimayanti N, Zain SM, Lee VS, Wahab HA, Yusof R, Abd Rahman N

In Silico Biol. (Gedrukt), 2011;11(1-2):29-37.
PMID: 22475750 DOI: 10.3233/ISB-2012-0442

Publication year=2011-2012

Matched MeSH terms: Dengue Virus/genetics*
Fulltext Dengue virus serotype 2 from a sylvatic lineage isolated from a patient with dengue hemorrhagic fever

Cardosa J, Ooi MH, Tio PH, Perera D, Holmes EC, Bibi K, et al.

PLoS Negl Trop Dis, 2009;3(4):e423.
PMID: 19399166 DOI: 10.1371/journal.pntd.0000423

Dengue viruses circulate in both human and sylvatic cycles. Although dengue viruses (DENV) infecting humans can cause major epidemics and severe disease, relatively little is known about the epidemiology and etiology of sylvatic dengue viruses. A 20-year-old male developed dengue hemorrhagic fever (DHF) with thrombocytopenia (12,000/ul) and a raised hematocrit (29.5% above baseline) in January 2008 in Malaysia. Dengue virus serotype 2 was isolated from his blood on day 4 of fever. A phylogenetic analysis of the complete genome sequence revealed that this virus was a member of a sylvatic lineage of DENV-2 and most closely related to a virus isolated from a sentinel monkey in Malaysia in 1970. This is the first identification of a sylvatic DENV circulating in Asia since 1975.

Matched MeSH terms: Dengue Virus/genetics
Emergence of dengue virus type 4 genotype IIA in Malaysia

AbuBakar S, Wong PF, Chan YF

J Gen Virol, 2002 Oct;83(Pt 10):2437-2442.
PMID: 12237425 DOI: 10.1099/0022-1317-83-10-2437

Phylogenetic analyses of the envelope (E) gene sequence of five recently isolated dengue virus type 4 (DENV-4) suggested the emergence of a distinct geographical and temporal DENV-4 subgenotype IIA in Malaysia. Four of the isolates had direct ancestral lineage with DENV-4 Indonesia 1973 and showed evidence of intra-serotypic recombination with the other recently isolated DENV-4, MY01-22713. The E gene of isolate MY01-22713 had strong evidence of an earlier recombination involving DENV-4 genotype II Indonesia 1976 and genotype I Malaysia 1969. These results suggest that intra-serotypic recombination amongst DENV-4 from independent ancestral lineages may have contributed to the emergence of DENV-4 subgenotype IIA in Malaysia.

Matched MeSH terms: Dengue Virus/genetics*

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