ResearchPad - dengue-virus https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Potency and breadth of human primary ZIKV immune sera shows that Zika viruses cluster antigenically as a single serotype]]> https://www.researchpad.co/article/elastic_article_7747 The recent emergence of Zika virus as an important human pathogen has raised questions about the durability and breadth of Zika virus immunity following natural infection in humans. While global epidemic patterns suggest that Zika infection elicits a protective immune response that is likely to offer long-term protection against repeat infection by other Zika viruses, only one study to date has formally examined the ability of human Zika immune sera to neutralize different Zika viruses. That study was limited because it evaluated human immune sera no more than 13 weeks after Zika virus infection and tested a relatively small number of Zika viruses. In this study, we examine twelve human Zika immune sera as far as 3 years after infection and test the sera against a total of eleven Zika virus isolates. Our results confirm the earlier study and epidemic patterns that suggest Zika virus exists in nature as a single serotype, and infection with one Zika virus can be expected to elicit protective immunity against repeat infection by any Zika virus for years to decades after the first infection.

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<![CDATA[Epidemiological and clinical characteristics of Dengue virus outbreaks in two regions of China, 2014 – 2015]]> https://www.researchpad.co/article/5c8823dcd5eed0c4846391a6

Dengue virus (DENV), a single-stranded RNA virus and Flaviviridae family member, is transmitted by Aedes aegypti and Aedes albopictus mosquitoes. DENV causes dengue fever, which may progress to severe dengue. Hospital-based surveillance was performed in two Chinese regions, Guangzhou and Xishuangbanna, during the dengue epidemics in 2014 and 2015, respectively. Acute-phase serum was obtained from 133 patients with suspected dengue infections during the peak season for dengue cases. Viremia levels, virus sero-positivity, serotype distribution, infection type, clinical manifestations and virus phylogenetics were investigated. Of the 112 DENV-confirmed cases, 92(82.14%) were IgM antibody-positive for DENV, and 69(51.88%) were positive for DENV RNA. From these cases, 47(41.96%) were classified as primary infections, 39(34.82%) as secondary infections and 26 (23.21%) as undetermined infections. The viremia levels were negatively correlated with IgM presence, but had no relationship with the infection type. DENV-1 genotype V dominated in Guangzhou, whereas the DENV-2 Cosmopolitan genotype dominated in Xishuangbanna, where fewer DENV-1 genotype I cases occurred. DENV-2 is associated with severe dengue illness with more serious clinical issues. The strains isolated during 2014–2015 are closely related to the isolates obtained from other Chinese regions and to those isolated recently in Southeast Asian countries. Our results indicate that DENV is no longer an imported virus and is now endemic in China. An extensive seroepidemiological study of DENV and the implementation of vector control measures against it are now warranted in China.

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<![CDATA[Accuracy of the SD BIOLINE Dengue Duo for rapid point-of-care diagnosis of dengue]]> https://www.researchpad.co/article/5c897732d5eed0c4847d268d

Background

Rapid diagnosis tests (RDTs) are easy to carry out, provide fast results, and could potentially guide medical treatment decisions. We investigated the performance of a commercially available RDT, which simultaneously detects the non-structural 1 (NS1) dengue virus (DENV) antigen, and IgM and IgG DENV antibodies, using representative serum samples from individuals in a dengue endemic area in Salvador, Brazil.

Methodology/Principal findings

We evaluated the accuracy of the SD BIOLINE Dengue Duo RDT (Abbott, Santa Clara, USA; former Alere Inc, Waltham, USA) in a random collection of sera. Samples included acute-phase sera from 246 laboratory-confirmed dengue cases and 108 non-dengue febrile patients enrolled in a surveillance study for dengue detection, 73 healthy controls living in the same surveillance community, and 73 blood donors. RDT accuracy was blindly assessed based on the combined results for the NS1 and the IgM test components. The RDT sensitivity was 46.8% (38.6% for the NS1 component and 13.8% for the IgM component). Sensitivity was greater for samples obtained from patients with secondary DENV infections (49.8%) compared to primary infections (31.1%) (P: 0.02) and was also influenced by the result in the confirmatory dengue diagnostic test, ranging from 39.7% for samples of cases confirmed by IgM-ELISA seroconversion between paired samples to 90.4% for samples of cases confirmed by a positive NS1-ELISA. The RDT specificity was 94.4% for non-dengue febrile patients, 87.7% for the community healthy controls, and 95.9% for the blood donors.

Conclusions/Significance

The SD BIOLINE Dengue Duo RDT showed good specificities, but low sensitivity, suggesting that it may be more useful to rule in than to rule out a dengue diagnosis in dengue endemic regions.

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<![CDATA[Potential for sylvatic and urban Aedes mosquitoes from Senegal to transmit the new emerging dengue serotypes 1, 3 and 4 in West Africa]]> https://www.researchpad.co/article/5c6dc998d5eed0c484529ea3

Dengue fever (DEN) is the most common arboviral disease in the world and dengue virus (DENV) causes 390 million annual infections around the world, of which 240 million are inapparent and 96 million are symptomatic. During the past decade a changing epidemiological pattern has been observed in Africa, with DEN outbreaks reported in all regions. In Senegal, all DENV serotypes have been reported. These important changes in the epidemiological profile of DEN are occurring in a context where there is no qualified vaccine against DEN. Further there is significant gap of knowledge on the vector bionomics and transmission dynamics in the African region to effectively prevent and control epidemics. Except for DENV-2, few studies have been performed with serotypes 1, 3, and 4, so this study was undertaken to fill out this gap. We assessed the vector competence of Aedes (Diceromyia) furcifer, Ae. (Diceromyia) taylori, Ae. (Stegomyia) luteocephalus, sylvatic and urban Ae. (Stegomyia) aegypti populations from Senegal for DENV-1, DENV-3 and DENV-4 using experimental oral infection. Whole bodies and wings/legs were tested for DENV presence by cell culture assays and saliva samples were tested by real time RT-PCR to estimate infection, disseminated infection and transmission rates. Our results revealed a low capacity of sylvatic and urban Aedes mosquitoes from Senegal to transmit DENV-1, DENV-3 and DENV-4 and an impact of infection on their mortality. The highest potential transmission rate was 20% despite the high susceptibility and disseminated infection rates up to 93.7% for the 3 Ae. aegypti populations tested, and 84.6% for the sylvatic vectors Ae. furcifer, Ae. taylori and Ae. luteocephalus.

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<![CDATA[Serological evidence of infection with dengue and Zika viruses in horses on French Pacific Islands]]> https://www.researchpad.co/article/5c65dccdd5eed0c484dec265

New Caledonia and French Polynesia are areas in which arboviruses circulate extensively. A large serological survey among horses from New Caledonia and French Polynesia was carried out to investigate the seroprevalence of flaviviruses in the horse population. Here, 293 equine sera samples were screened for flaviviruses using a competitive enzyme-linked immunosorbent assay (cELISA). The positive sera were then confirmed using a flavivirus-specific microsphere immunoassay (MIA) and seroneutralization tests. This serosurvey showed that 16.6% (27/163) and 30.8% (40/130) of horses were positive for cELISA tests in New Caledonia and French Polynesia, respectively, but the MIA technique, targeting only flaviviruses causing neuro-invasive infections in humans and horses (i.e. West Nile virus [WNV], Japanese encephalitis virus [JEV] and tick-borne encephalitis virus [TBEV]), showed negative results for more than 85% (57/67) of the cELISA-positive animals. Seroneutralization tests with the main flaviviruses circulating in the South Pacific revealed that 6.1% (10/163; confidence interval [95% CI] 3.0%-11.0%) of sera in New Caledonia and 7.7% (10/130; 95% CI 3.8%-13.7%) in French Polynesia were positive for dengue virus serotype 1 (DENV1) and 4.3% (7/163; 95% CI 1.7%-8.6%) in New Caledonia and 15.4% (20/130, 95% CI 9.7%-22.8%) in French Polynesia were found positive for Zika virus (ZIKV). Seroprevalence of the JEV and WNV flaviviruses on the 293 samples from both island groups were comparatively much lower (less than 2%). This seroprevalence study in the horse population shows that horses can be infected with dengue and Zika viruses and that these infections lead to seroconversions in horses. The consequences of these infections in horses and their role in ZIKV and DENV epidemiological cycles are two issues that deserve further investigation.

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<![CDATA[Does prior dengue virus exposure worsen clinical outcomes of Zika virus infection? A systematic review, pooled analysis and lessons learned]]> https://www.researchpad.co/article/5c57e689d5eed0c484ef3602

Zika virus (ZIKV) recently caused a pandemic complicated by Guillain-Barre syndrome (GBS) and birth defects. ZIKV is structurally similar to the dengue viruses (DENV) and in vitro studies suggest antibody dependent enhancement occurs in ZIKV infections preceded by DENV; however, the clinical significance of this remains unclear. We undertook a PRISMA-adherent systematic review of all current human and non-human primate (NHP) data to determine if prior infection with DENV, compared to DENV-naïve hosts, is associated with a greater risk of ZIKV clinical complications or greater ZIKV peak viremia in vivo. We identified 1146 studies in MEDLINE, EMBASE and the grey literature, of which five studies were eligible. One human study indicated no increase in the risk of GBS in ZIKV infections with prior DENV exposure. Two additional human studies showed a small increase in ZIKV viremia in those with prior DENV exposure; however, this was not statistically significant nor was it associated with an increase in clinical severity or adverse pregnancy outcomes. While no meta-analysis was possible using human data, a pooled analysis of the two NHP studies leveraging extended data provided only weak evidence of a 0.39 log10 GE/mL rise in ZIKV viremia in DENV experienced rhesus macaques compared to those with no DENV exposure (p = 0.22). Using a customized quality grading criteria, we further show that no existing published human studies have offered high quality measurement of both acute ZIKV and antecedent DENV infections. In conclusion, limited human and NHP studies indicate a small and non-statistically significant increase in ZIKV viremia in DENV-experienced versus DENV-naïve hosts; however, there is no evidence that even a possible small increase in ZIKV viremia would correlate with a change in ZIKV clinical phenotype. More data derived from larger sample sizes and improved sero-assays are needed to resolve this question, which has major relevance for clinical prognosis and vaccine design.

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<![CDATA[Arbovirus coinfection and co-transmission: A neglected public health concern?]]> https://www.researchpad.co/article/5c50c455d5eed0c4845e8560

Epidemiological synergy between outbreaks of viruses transmitted by Aedes aegypti mosquitoes, such as chikungunya, dengue, and Zika viruses, has resulted in coinfection of humans with multiple viruses. Despite the potential impact on public health, we know only little about the occurrence and consequences of such coinfections. Here, we review the impact of coinfection on clinical disease in humans, discuss the possibility for co-transmission from mosquito to human, and describe a role for modeling transmission dynamics at various levels of co-transmission. Solving the mystery of virus coinfections will reveal whether they should be viewed as a serious concern for public health.

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<![CDATA[Thioguanine-based DENV-2 NS2B/NS3 protease inhibitors: Virtual screening, synthesis, biological evaluation and molecular modelling]]> https://www.researchpad.co/article/5c536b8fd5eed0c484a48cc8

Dengue virus Type 2 (DENV-2) is predominant serotype causing major dengue epidemics. There are a number of studies carried out to find its effective antiviral, however to date, there is still no molecule either from peptide or small molecules released as a drug. The present study aims to identify small molecules inhibitor from National Cancer Institute database through virtual screening. One of the hits, D0713 (IC50 = 62 μM) bearing thioguanine scaffold was derivatised into 21 compounds and evaluated for DENV-2 NS2B/NS3 protease inhibitory activity. Compounds 18 and 21 demonstrated the most potent activity with IC50 of 0.38 μM and 16 μM, respectively. Molecular dynamics and MM/PBSA free energy of binding calculation were conducted to study the interaction mechanism of these compounds with the protease. The free energy of binding of 18 calculated by MM/PBSA is -16.10 kcal/mol compared to the known inhibitor, panduratin A (-11.27 kcal/mol), which corroborates well with the experimental observation. Results from molecular dynamics simulations also showed that both 18 and 21 bind in the active site and stabilised by the formation of hydrogen bonds with Asn174.

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<![CDATA[Biased efficacy estimates in phase-III dengue vaccine trials due to heterogeneous exposure and differential detectability of primary infections across trial arms]]> https://www.researchpad.co/article/5c57e697d5eed0c484ef38b1

Vaccine efficacy (VE) estimates are crucial for assessing the suitability of dengue vaccine candidates for public health implementation, but efficacy trials are subject to a known bias to estimate VE toward the null if heterogeneous exposure is not accounted for in the analysis of trial data. In light of many well-characterized sources of heterogeneity in dengue virus (DENV) transmission, our goal was to estimate the potential magnitude of this bias in VE estimates for a hypothetical dengue vaccine. To ensure that we realistically modeled heterogeneous exposure, we simulated city-wide DENV transmission and vaccine trial protocols using an agent-based model calibrated with entomological and epidemiological data from long-term field studies in Iquitos, Peru. By simulating a vaccine with a true VE of 0.8 in 1,000 replicate trials each designed to attain 90% power, we found that conventional methods underestimated VE by as much as 21% due to heterogeneous exposure. Accounting for the number of exposures in the vaccine and placebo arms eliminated this bias completely, and the more realistic option of including a frailty term to model exposure as a random effect reduced this bias partially. We also discovered a distinct bias in VE estimates away from the null due to lower detectability of primary DENV infections among seronegative individuals in the vaccinated group. This difference in detectability resulted from our assumption that primary infections in vaccinees who are seronegative at baseline resemble secondary infections, which experience a shorter window of detectable viremia due to a quicker immune response. This resulted in an artefactual finding that VE estimates for the seronegative group were approximately 1% greater than for the seropositive group. Simulation models of vaccine trials that account for these factors can be used to anticipate the extent of bias in field trials and to aid in their interpretation.

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<![CDATA[Protein refolding based on high hydrostatic pressure and alkaline pH: Application on a recombinant dengue virus NS1 protein]]> https://www.researchpad.co/article/5c6448dbd5eed0c484c2f04f

In this study we evaluated the association of high hydrostatic pressure (HHP) and alkaline pH as a minimally denaturing condition for the solubilization of inclusion bodies (IBs) generated by recombinant proteins expressed by Escherichia coli strains. The method was successfully applied to a recombinant form of the dengue virus (DENV) non-structural protein 1 (NS1). The minimal pH for IBs solubilization at 1 bar was 12 while a pH of 10 was sufficient for solubilization at HHP: 2.4 kbar for 90 min and 0.4 kbar for 14 h 30 min. An optimal refolding condition was achieved by compression of IBs at HHP and pH 10.5 in the presence of arginine, oxidized and reduced glutathiones, providing much higher yields (up to 8-fold) than association of HHP and GdnHCl via an established protocol. The refolded NS1, 109 ± 9.5 mg/L bacterial culture was recovered mainly as monomer and dimer, corresponding up to 90% of the total protein and remaining immunologically active. The proposed conditions represent an alternative for the refolding of immunologically active recombinant proteins expressed as IBs.

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<![CDATA[Prior dengue virus infection and risk of Zika: A pediatric cohort in Nicaragua]]> https://www.researchpad.co/article/5c50c4a2d5eed0c4845e8aa4

Background

Zika virus (ZIKV) emerged in northeast Brazil in 2015 and spread rapidly across the Americas, in populations that have been largely exposed to dengue virus (DENV). The impact of prior DENV infection on ZIKV infection outcome remains unclear. To study this potential impact, we analyzed the large 2016 Zika epidemic in Managua, Nicaragua, in a pediatric cohort with well-characterized DENV infection histories.

Methods and findings

Symptomatic ZIKV infections (Zika cases) were identified by real-time reverse transcription PCR and serology in a community-based cohort study that follows approximately 3,700 children aged 2–14 years old. Annual blood samples were used to identify clinically inapparent ZIKV infections using a novel, well-characterized serological assay. Multivariable Poisson regression was used to examine the relation between prior DENV infection and incidence of symptomatic and inapparent ZIKV infection. The generalized-growth method was used to estimate the effective reproduction number. From January 1, 2016, to February 28, 2017, 560 symptomatic ZIKV infections and 1,356 total ZIKV infections (symptomatic and inapparent) were identified, for an overall incidence of 14.0 symptomatic infections (95% CI: 12.9, 15.2) and 36.5 total infections (95% CI: 34.7, 38.6) per 100 person-years. Effective reproduction number estimates ranged from 3.3 to 3.4, depending on the ascending wave period. Incidence of symptomatic and total ZIKV infections was higher in females and older children. Analysis of the effect of prior DENV infection was performed on 3,027 participants with documented DENV infection histories, of which 743 (24.5%) had experienced at least 1 prior DENV infection during cohort follow-up. Prior DENV infection was inversely associated with risk of symptomatic ZIKV infection in the total cohort population (incidence rate ratio [IRR]: 0.63; 95% CI: 0.48, 0.81; p < 0.005) and with risk of symptomatic presentation given ZIKV infection (IRR: 0.62; 95% CI: 0.44, 0.86) when adjusted for age, sex, and recent DENV infection (1–2 years before ZIKV infection). Recent DENV infection was significantly associated with decreased risk of symptomatic ZIKV infection when adjusted for age and sex, but not when adjusted for prior DENV infection. Prior or recent DENV infection did not affect the rate of total ZIKV infections. Our findings are limited to a pediatric population and constrained by the epidemiology of the site.

Conclusions

These findings support that prior DENV infection may protect individuals from symptomatic Zika. More research is needed to address the possible immunological mechanism(s) of cross-protection between ZIKV and DENV and whether DENV immunity also modulates other ZIKV infection outcomes such as neurological or congenital syndromes.

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<![CDATA[Molecular characterization of viruses associated with encephalitis in São Paulo, Brazil]]> https://www.researchpad.co/article/5c46657cd5eed0c48451968d

The objective of this study was to characterize the prevalence of viral encephalitis due to arbovirus infection of the Togaviridae and Flaviviridae families in São Paulo, Brazil. A total of 500 cerebrospinal fluid (CSF) samples collected between August 2012 and January 2013, from patients with symptoms of acute encephalitis were analyzed. Findings suggestive of viral encephalitis—elevations in cell concentration, glucose and total protein—were observed in 234 (46.8%) samples, designated as Group 1. The remaining 266 samples comprised Group 2. All samples were tested for Flaviviruses (dengue virus 1, 2, 3 and 4, yellow fever virus and West Nile virus), Alphavirus (NS5 region) and enterovirus by RT- PCR and for herpesviruses and enteroviruses using CLART-Entherpex. A presumptive viral etiological agent was detected in 26 samples (5.2%), 18 (8.0%) in Group 1 and 8 (3.0%) in Group 2. In Group 1 human herpesviruses were detected in 9 cases, enteroviruses in 7 cases, dengue viruses (DENV) in 2 CSFs and St. Louis encephalitis virus (SLEV) in one case. In Group 2 there were 3 CSFs positive for human herpesviruses, 2 for enteroviruses, 2 for DENV and 1 for SLEV. Detection of arboviruses, even though present in a minority of infected patients, identifies these viruses as a probable etiological agent of encephalitis. This is of special concern in regions where this class of viruses is endemic and has been linked to other recent epidemics.

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<![CDATA[A longitudinal systems immunologic investigation of acute Zika virus infection in an individual infected while traveling to Caracas, Venezuela]]> https://www.researchpad.co/article/5c33c3a3d5eed0c48459e586

Zika virus (ZIKV) is an emerging mosquito-borne flavivirus linked to devastating neurologic diseases. Immune responses to flaviviruses may be pathogenic or protective. Our understanding of human immune responses to ZIKV in vivo remains limited. Therefore, we performed a longitudinal molecular and phenotypic characterization of innate and adaptive immune responses during an acute ZIKV infection. We found that innate immune transcriptional and genomic responses were both cell type- and time-dependent. While interferon stimulated gene induction was common to all innate immune cells, the upregulation of important inflammatory cytokine genes was primarily limited to monocyte subsets. Additionally, genomic analysis revealed substantial chromatin remodeling at sites containing cell-type specific transcription factor binding motifs that may explain the observed changes in gene expression. In this dengue virus-experienced individual, adaptive immune responses were rapidly mobilized with T cell transcriptional activity and ZIKV neutralizing antibody responses peaking 6 days after the onset of symptoms. Collectively this study characterizes the development and resolution of an in vivo human immune response to acute ZIKV infection in an individual with pre-existing flavivirus immunity.

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<![CDATA[Differential and convergent utilization of autophagy components by positive-strand RNA viruses]]> https://www.researchpad.co/article/5c390bb7d5eed0c48491df88

Many viruses interface with the autophagy pathway, a highly conserved process for recycling cellular components. For three viral infections in which autophagy constituents are proviral (poliovirus, dengue, and Zika), we developed a panel of knockouts (KOs) of autophagy-related genes to test which components of the canonical pathway are utilized. We discovered that each virus uses a distinct set of initiation components; however, all three viruses utilize autophagy-related gene 9 (ATG9), a lipid scavenging protein, and LC3 (light-chain 3), which is involved in membrane curvature. These results show that viruses use noncanonical routes for membrane sculpting and LC3 recruitment. By measuring viral RNA abundance, we also found that poliovirus utilizes these autophagy components for intracellular growth, while dengue and Zika virus only use autophagy components for post-RNA replication processes. Comparing how RNA viruses manipulate the autophagy pathway reveals new noncanonical autophagy routes, explains the exacerbation of disease by starvation, and uncovers common targets for antiviral drugs.

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<![CDATA[IgG1 and IgG4 antibodies against Aedes aegypti salivary proteins and risk for dengue infections]]> https://www.researchpad.co/article/5c36679fd5eed0c4841a5e0d

Dengue virus (DENV) is an arbovirus responsible for a significant number of deaths in Latin America. This virus is transmitted through the bite of Aedes aegypti, the main mosquito vector, and Ae. albopictus. During blood uptake, the mosquito injects its saliva into the host to facilitate the feeding process. Mosquito saliva contains potent immunogens capable of inducing antibody production directly related to mosquito bite exposure intensity and disease risk. In this study, we first determined the DENV infection status by two different DENV non-structural protein 1 (NS1) based rapid tests and qRT-PCR, then measured the levels of IgG1 and IgG4 antibodies against salivary proteins of Ae. aegypti female mosquitoes in volunteers living in a dengue endemic area. Our results show that people with a positive DENV diagnosis present higher levels of IgG4 antibodies than people with a negative diagnostic test, and that these antibody levels were higher in people with secondary DENV infections. With this study, we show that detection of IgG4 antibodies against mosquito saliva may be a reliable method to evaluate the risk of dengue infection.

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<![CDATA[Impact of glucose-6-phosphate dehydrogenase deficiency on dengue infection in Myanmar children]]> https://www.researchpad.co/article/5c3667d8d5eed0c4841a666f

Glucose-6-phosphate dehydrogenase (G6PD) deficiency may affect the clinical presentation of dengue due to the altered redox state in immune cells. We aimed to determine the association between G6PD deficiency and severity of dengue infection in paediatric patients in Myanmar. A cross-sectional study was conducted among paediatric patients aged 2–13 years with dengue in Yankin Children Hospital, Myanmar. One hundred and ninety-six patients positive for dengue infection, as determined via PCR or ELISA, were enrolled. Dengue severity was determined according to the 2009 WHO classification guidelines. Spectrophotometric assays determined G6PD levels. The adjusted median G6PD value of males in the study population was used to define various cut-off points according to the WHO classification guidelines. G6PD genotyping for Mahidol, Kaiping and Mediterranean mutations was performed for 128 out of 196 samples by real-time multiplex PCR. 51 of 196 (26.0%) patients had severe dengue. The prevalence of G6PD phenotype deficiency (< 60% activity) in paediatric patients was 14.8% (29/196), specifically, 13.6% (14/103) in males and 16.2% (15/93) in females. Severe deficiency (< 10% activity) accounted for 7.1% (14/196) of our cohort, occurring 11.7% (12/103) in males and 2.2% (2/93) in females. Among 128 samples genotyped, the G6PD gene mutations were detected in 19.5% (25/128) of patients, with 20.3% (13/ 64) in males and 18.8% (12/64) in females. The G6PD Mahidol mutation was 96.0% (24/25) while the G6PD Kaiping mutation was 4.0% (1/25). Severe dengue was not associated with G6PD enzyme deficiency or presence of the G6PD gene mutation. Thus, no association between G6PD deficiency and dengue severity could be detected.

Trial registration: The study was registered following the WHO International Clinical Trials Registry Platform (WHO-ICTRP) on Thai Clinical Trials Registry (TCTR) website, registration number # TCTR20180720001

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<![CDATA[Dengue Virus IgM Serotyping by ELISA with Recombinant Mutant Envelope Proteins]]> https://www.researchpad.co/article/5c354d13d5eed0c484dd3679

We developed an IgM-based ELISA that identifies the dengue virus serotype of recent infections. Dominant serotypes were detectable in 91.1% of samples from travelers and 86.5% of samples from residents of endemic regions; 97.1% corresponded to the serotype identified by PCR. This ELISA enables more accurate reporting of epidemiologic findings.

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<![CDATA[Molecular detection of dengue virus in patients suspected of Ebola virus disease in Ghana]]> https://www.researchpad.co/article/5c23f270d5eed0c484046ac0

Dengue fever is known to be one of the most common arthropod-borne viral infectious diseases of public health importance. The disease is now endemic in more than 100 countries in Africa, the Americas, the Eastern Mediterranean, Southeast Asia and the Western Pacific with an estimated two fifths of the world's population being at risk. The notable endemic viral hemorrhagic fevers (VHFs) found in West Africa, including yellow fever, Lassa fever, Rift Valley fever, dengue fever and until recently Ebola have been responsible for most outbreaks with fatal consequences. These VHFs usually produce unclear acute febrile illness, especially in the acute phase of infection. In this study we detected the presence of 2 different serotypes (DENV-2 and DENV-3) of Dengue virus in 4 sera of 150 patients clinically suspected of Ebola virus disease during the Ebola Virus Disease (EVD) outbreak in West Africa with the use of serological and molecular test assays. Sequence data was successfully generated for DENV-3 and phylogenetic analysis of the envelope gene showed that the DENV-3 sequences had close homology with DENV-3 sequences from Senegal and India. This study documents molecular evidence of an indigenous Dengue fever viral infection in Ghana and therefore necessitates the need to have an efficient surveillance system to rapidly detect and control the dissemination of the different serotypes in the population which has the potential to cause outbreaks of dengue hemorrhagic fevers.

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<![CDATA[Antibody responses to Zika virus proteins in pregnant and non-pregnant macaques]]> https://www.researchpad.co/article/5c06f04ad5eed0c484c6d62b

The specificity of the antibody response against Zika virus (ZIKV) is not well-characterized. This is due, in part, to the antigenic similarity between ZIKV and closely related dengue virus (DENV) serotypes. Since these and other similar viruses co-circulate, are spread by the same mosquito species, and can cause similar acute clinical syndromes, it is difficult to disentangle ZIKV-specific antibody responses from responses to closely-related arboviruses in humans. Here we use high-density peptide microarrays to profile anti-ZIKV antibody reactivity in pregnant and non-pregnant macaque monkeys with known exposure histories and compare these results to reactivity following DENV infection. We also compare cross-reactive binding of ZIKV-immune sera to the full proteomes of 28 arboviruses. We independently confirm a purported ZIKV-specific IgG antibody response targeting ZIKV nonstructural protein 2B (NS2B) that was recently reported in ZIKV-infected people and we show that antibody reactivity in pregnant animals can be detected as late as 127 days post-infection (dpi). However, we also show that these responses wane over time, sometimes rapidly, and in one case the response was elicited following DENV infection in a previously ZIKV-exposed animal. These results suggest epidemiologic studies assessing seroprevalence of ZIKV immunity using linear epitope-based strategies will remain challenging to interpret due to susceptibility to false positive results. However, the method used here demonstrates the potential for rapid profiling of proteome-wide antibody responses to a myriad of neglected diseases simultaneously and may be especially useful for distinguishing antibody reactivity among closely related pathogens.

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<![CDATA[Novel broad spectrum virucidal molecules against enveloped viruses]]> https://www.researchpad.co/article/5c141e85d5eed0c484d26fd8

Viral infections are an important cause of death worldwide. Unfortunately, there is still a lack of antiviral drugs or vaccines for a large number of viruses, and this represents a remarkable challenge particularly for emerging and re-emerging viruses. For this reason, the identification of broad spectrum antiviral compounds provides a valuable opportunity for developing efficient antiviral therapies. Here we report on a class of rhodanine and thiobarbituric derivatives displaying a broad spectrum antiviral activity against seven different enveloped viruses including an HSV-2 acyclovir resistant strain with favorable selectivity indexes. Due to their selective action on enveloped viruses and to their lipid oxidation ability, we hypothesize a mechanism on the viral envelope that affects the fluidity of the lipid bilayer, thus compromising the efficiency of virus-cell fusion and preventing viral entry.

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