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1.
Rev Bras Epidemiol ; 24: e210020, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33825776

RESUMEN

OBJECTIVE: To describe the entry of Dengue virus (DENV) serotypes in Brazil and its federative units. METHODS: A systematic review of studies published between 1980 and 2018 in databases and in the gray literature was performed using descriptors related to the years of entry of the DENV serotypes. Additionally, experts and official sources of information (Brazilian Ministry of Health) were consulted. RESULTS: From 100 publications selected for the systematic review, 26 addressed the entry of DENV serotypes in the North region of the country, 33 in the Northeast, 24 in the Southeast, 14 in the Central-West, and five in the South. DENV-1 and DENV-4 were introduced in the North region in 1981. DENV-2 was introduced in the Southeast in 1990. DENV-3 was introduced in the North in 1999. CONCLUSION: The rapid expansion of dengue throughout the Brazilian territory was verified from the second half of the 1980s, with the gradual entry of the four serotypes, which resulted in the emergence of epidemics of arbovirus, which are currently verified in the country. Considering the epidemiology of the disease, more information should be disseminated and published in the wide-ranging scientific literature for a better understanding of the spread and circulation of DENV serotypes.


Asunto(s)
Virus del Dengue , Dengue , Brasil/epidemiología , Dengue/epidemiología , Virus del Dengue/genética , Geografía , Humanos , Serogrupo
2.
PLoS Negl Trop Dis ; 15(3): e0009259, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33705409

RESUMEN

Dengue, Zika and chikungunya are diseases of global health significance caused by arboviruses and transmitted by the mosquito Aedes aegypti, which is of worldwide circulation. The arrival of the Zika and chikungunya viruses to South America increased the complexity of transmission and morbidity caused by these viruses co-circulating in the same vector mosquito species. Here we present an integrated analysis of the reported arbovirus cases between 2007 and 2017 and local climate and socio-economic profiles of three distinct Colombian municipalities (Bello, Cúcuta and Moniquirá). These locations were confirmed as three different ecosystems given their contrasted geographic, climatic and socio-economic profiles. Correlational analyses were conducted with both generalised linear models and generalised additive models for the geographical data. Average temperature, minimum temperature and wind speed were strongly correlated with disease incidence. The transmission of Zika during the 2016 epidemic appeared to decrease circulation of dengue in Cúcuta, an area of sustained high incidence of dengue. Socio-economic factors such as barriers to health and childhood services, inadequate sanitation and poor water supply suggested an unfavourable impact on the transmission of dengue, Zika and chikungunya in all three ecosystems. Socio-demographic influencers were also discussed including the influx of people to Cúcuta, fleeing political and economic instability from neighbouring Venezuela. Aedes aegypti is expanding its range and increasing the global threat of these diseases. It is therefore vital that we learn from the epidemiology of these arboviruses and translate it into an actionable local knowledge base. This is even more acute given the recent historical high of dengue cases in the Americas in 2019, preceding the COVID-19 pandemic, which is itself hampering mosquito control efforts.


Asunto(s)
Fiebre Chikungunya/epidemiología , Dengue/epidemiología , Infección por el Virus Zika/epidemiología , Aedes/fisiología , Aedes/virología , Animales , Fiebre Chikungunya/economía , Fiebre Chikungunya/virología , Virus Chikungunya/fisiología , Clima , Colombia/epidemiología , Dengue/economía , Dengue/virología , Virus del Dengue/fisiología , Ecosistema , Humanos , Mosquitos Vectores/fisiología , Mosquitos Vectores/virología , América del Sur , Temperatura , Virus Zika/fisiología , Infección por el Virus Zika/economía , Infección por el Virus Zika/virología
3.
Nat Commun ; 12(1): 1810, 2021 03 22.
Artículo en Inglés | MEDLINE | ID: mdl-33753725

RESUMEN

For most pathogens, transmission is driven by interactions between the behaviours of infectious individuals, the behaviours of the wider population, the local environment, and immunity. Phylogeographic approaches are currently unable to disentangle the relative effects of these competing factors. We develop a spatiotemporally structured phylogenetic framework that addresses these limitations by considering individual transmission events, reconstructed across spatial scales. We apply it to geocoded dengue virus sequences from Thailand (N = 726 over 18 years). We find infected individuals spend 96% of their time in their home community compared to 76% for the susceptible population (mainly children) and 42% for adults. Dynamic pockets of local immunity make transmission more likely in places with high heterotypic immunity and less likely where high homotypic immunity exists. Age-dependent mixing of individuals and vector distributions are not important in determining spread. This approach provides previously unknown insights into one of the most complex disease systems known and will be applicable to other pathogens.


Asunto(s)
Algoritmos , Virus del Dengue/genética , Dengue/transmisión , Modelos Teóricos , Adulto , Aedes/virología , Animales , Niño , Dengue/epidemiología , Dengue/virología , Virus del Dengue/clasificación , Virus del Dengue/fisiología , Genoma Viral/genética , Interacciones Huésped-Patógeno , Humanos , Mosquitos Vectores/virología , Filogenia , Filogeografía/métodos , Filogeografía/estadística & datos numéricos , Dinámica Poblacional , Tailandia/epidemiología
4.
Nat Commun ; 12(1): 1671, 2021 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-33723237

RESUMEN

Zika virus (ZIKV) has caused large, brief outbreaks in isolated populations, however ZIKV can also persist at low levels over multiple years. The reasons for these diverse transmission dynamics remain poorly understood. In Fiji, which has experienced multiple large single-season dengue epidemics, there was evidence of multi-year transmission of ZIKV between 2013 and 2017. To identify factors that could explain these differences in dynamics between closely related mosquito-borne flaviviruses, we jointly fit a transmission dynamic model to surveillance, serological and molecular data. We estimate that the observed dynamics of ZIKV were the result of two key factors: strong seasonal effects, which created an ecologically optimal time of year for outbreaks; and introduction of ZIKV after this optimal time, which allowed ZIKV transmission to persist over multiple seasons. The ability to jointly fit to multiple data sources could help identify a similar range of possible outbreak dynamics in other settings.


Asunto(s)
Infecciones por Flavivirus/epidemiología , Infecciones por Flavivirus/transmisión , Animales , Culicidae , Dengue/transmisión , Virus del Dengue , Brotes de Enfermedades , Epidemias , Fiji/epidemiología , Flavivirus , Humanos , Mosquitos Vectores/virología , Estaciones del Año , Virus Zika , Infección por el Virus Zika/epidemiología , Infección por el Virus Zika/transmisión
5.
Molecules ; 26(4)2021 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-33670247

RESUMEN

Dengue fever is one of the most common viral infections affecting humans. It is an expanding public health problem, particularly in tropical and subtropical regions. No effective vaccine or antiviral therapies against Dengue virus (DENV) infection are available. Therefore, there is a strong need to develop safe and effective therapeutic strategies that can reduce the burden and duration of hospitalizations due to this life-threatening disease. Oligonucleotide-based strategies are considered as an attractive means of inhibiting viral replication since oligonucleotides can be designed to interact with any viral RNA, provided its sequence is known. The resultant targeted destruction of viral RNA interferes with viral replication without inducing any adverse effects on cellular processes. In this review, we elaborate the ribozymes, RNA interference, CRISPR, aptamer and morpholino strategies for the inhibition of DENV replication and discuss the challenges involved in utilizing such approaches.


Asunto(s)
Virus del Dengue/efectos de los fármacos , Dengue/tratamiento farmacológico , Oligonucleótidos/uso terapéutico , Replicación Viral/efectos de los fármacos , Antivirales/química , Antivirales/uso terapéutico , Dengue/genética , Dengue/virología , Virus del Dengue/patogenicidad , Humanos , Oligonucleótidos/química , Oligonucleótidos/genética , Interferencia de ARN
6.
Infez Med ; 29(1): 114-116, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33664180

RESUMEN

Dengue fever should be included in the differential diagnosis of febrile illness even if another infection such as COVID-19 has been found in returning travellers from tropical and sub-tropical area where dengue virus circulates epidemically. We describe a 40-year-old man diagnosed with laboratory-confirmed COVID-19 and dengue fever during the COVID-19 outbreak in Milan, Italy.


Asunto(s)
/diagnóstico , Coinfección/diagnóstico , Dengue/diagnóstico , Anamnesis , Adulto , Coinfección/virología , Enfermedades Transmisibles Importadas/diagnóstico , Enfermedades Transmisibles Importadas/virología , Virus del Dengue , Diagnóstico Diferencial , Humanos , Masculino , Viaje
7.
Virol J ; 18(1): 54, 2021 03 11.
Artículo en Inglés | MEDLINE | ID: mdl-33706767

RESUMEN

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic remains ongoing around the world, including in areas where dengue is endemic. Dengue and COVID-19, to some extent, have similar clinical and laboratory features, which can lead to misdiagnosis, delayed treatment and patient's isolation. The use of rapid diagnostic tests (RDT) is easy and convenient for fast diagnosis, however there may be issues with cross-reactivity with antibodies for other pathogens. METHODS: We assessed the possibility of cross-reactivity between SARS-CoV-2 and dengue antibodies by: (1) testing five brands of COVID-19 IgG / IgM RDTs on 60 RT-PCR-confirmed dengue samples; (2) testing 95 RT-PCR-confirmed COVID-19 samples on dengue RDT; and (3) testing samples positive for COVID-19 IgG and/or IgM on dengue RDT. RESULTS: We observed a high specificity across all five brands of COVID-19 RDTs, ranging from 98.3 to 100%. Out of the confirmed COVID-19 samples, one patient tested positive for dengue IgM only, another tested positive for dengue IgG only. One patient tested positive for dengue IgG, IgM, and NS1, suggesting a co-infection. In COVID-19 IgG and/or IgM samples, 6.3% of COVID-19 IgG-positive samples also tested positive for dengue IgG, while 21.1% of COVID-19 IgM-positive samples also tested positive for dengue IgG. CONCLUSION: Despite the high specificity of the COVID-19 RDT, we observed cross-reactions and false-positive results between dengue and COVID-19. Dengue and COVID-19 co-infection was also found. Health practitioners in dengue endemic areas should be careful when using antibody RDT for the diagnosis of dengue during the COVID-19 pandemic to avoid misdiagnosis.


Asunto(s)
Anticuerpos Antivirales/inmunología , Reacciones Cruzadas/inmunología , Virus del Dengue/inmunología , Dengue/diagnóstico , /inmunología , Adolescente , Adulto , Niño , Diagnóstico Diferencial , Pruebas Diagnósticas de Rutina , Reacciones Falso Positivas , Femenino , Humanos , Inmunoglobulina A/inmunología , Inmunoglobulina G/inmunología , Inmunoglobulina M/inmunología , Indonesia , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Proteínas no Estructurales Virales/inmunología , Adulto Joven
8.
Public Health ; 192: 21-29, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33607517

RESUMEN

OBJECTIVES: The primary aim of this study was to evaluate the temporal correlation between Wikitrends and conventional surveillance data generated for Chikungunya, Dengue, Zika, and West Nile Virus infection reported by bulletin of Italian National Institute of Health (Istituto Superiore di Sanità in italian, ISS). STUDY DESIGN: A cross-sectional study design was used. METHODS: The reported cases of Dengue and Chikungunya were selected from July 2015 to December 2019. For West Nile Virus, the bulletins are issued in the period June-November (6 months) of the years 2015-2019, and for Zika virus, the data reported in the ISS bulletin start from January 2016. From Wikipedia Trends, we extracted the number of monthly views by users from the July 2015 to December 2019 of the pages Chikungunya, Dengue, Zika virus, and West Nile Virus. RESULTS: A correlation was observed between the bulletin of ISS and Wikipedia Wikitrends, the correlation was strong for Chikungunya and West Nile Virus (r = 0.9605; r = 0.9556, respectively), and highly statistically significant with P-values <0.001. The correlation was moderate for Dengue and Zika virus (r = 0.6053; r = 0.5888, respectively), but highly statistically significant with P-values <0.001. CONCLUSIONS: Classical surveillance system should be integrated with the tools of digital epidemiology that have potential role in public health for the dynamic information and provide near real-time indicators of the spread of infectious disease.


Asunto(s)
Arbovirus , Fiebre Chikungunya/epidemiología , Culicidae/virología , Dengue/epidemiología , Internet , Fiebre del Nilo Occidental/epidemiología , Infección por el Virus Zika/epidemiología , Animales , Arbovirus/clasificación , Arbovirus/aislamiento & purificación , Virus Chikungunya , Estudios Transversales , Dengue/virología , Virus del Dengue , Monitoreo Epidemiológico , Humanos , Italia/epidemiología , Masculino , Salud Pública , Virus del Nilo Occidental , Virus Zika
9.
Arch Virol ; 166(4): 1103-1112, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33575893

RESUMEN

Dengue virus (DV) is a mosquito-borne virus that is endemic to many tropical and subtropical areas. Recently, the annual incidence of DV infection has increased worldwide, including in Korea, due to global warming and increased global travel. We therefore sought to characterize the molecular and evolutionary features of DV-1 and DV-4 isolated from Korean overseas travelers. We used phylogenetic analysis based on the full coding region to classify isolates of DV-1 in Korea into genotype I (43251, KP406802), genotype IV (KP406803), and genotype V (KP406801). In addition, we found that strains of DV-4 belonged to genotype I (KP406806) and genotype II (43257). Evidence of positive selection in DV-1 strains was identified in the C, prM, NS2A, and NS5 proteins, whereas DV-4 showed positive selection only in the non-structural proteins NS2A, NS3, and NS5. The substitution rates per site per year were 5.58 × 10-4 and 6.72 × 10-4 for DV-1 and DV-4, respectively, and the time of the most recent common ancestor was determined using the Bayesian skyline coalescent method. In this study, the molecular, phylogenetic, and evolutionary characteristics of Korean DV-1 and DV-4 isolates were evaluated for the first time.


Asunto(s)
Virus del Dengue/genética , Dengue/virología , Evolución Molecular , Viaje , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Secuencia de Bases , Dengue/epidemiología , Virus del Dengue/clasificación , Virus del Dengue/aislamiento & purificación , Genotipo , Humanos , Filogenia , ARN Viral/genética , República de Corea/epidemiología , Selección Genética , Serogrupo , Proteínas Virales/genética
10.
Mem Inst Oswaldo Cruz ; 115: e200287, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33533869

RESUMEN

BACKGROUND: The heat-labile nature of Dengue virus (DENV) in serum samples must be considered when applying routine diagnostic tests to avoid issues that could impact the accuracy of test results with direct implications for case management and disease reporting. OBJECTIVES: To check if pre-analytical variables, such as storage time and temperature, have an impact on the accuracy of the main routine diagnostic tests for dengue. METHODS: Virus isolation, reverse transcription real-time polymerase chain reaction (RT-PCR) and NS1 enzyme-linked immunosorbent assay (ELISA) were evaluated using 84 samples submitted to different pre-analytical conditions. FINDINGS: Sensitivity and negative predictive value were directly affected by sample storage conditions. RT-PCR and virus isolation showed greater dependence on well-conserved samples for an accurate diagnosis. Interestingly, even storage at -30ºC for a relatively short time (15 days) was not adequate for accurate results using virus isolation and RT-PCR tests. On the other hand, NS1 ELISA showed no significant reduction in positivity for aliquots tested under the same conditions as in the previous tests. MAIN CONCLUSIONS: Our results support the stability of the NS1 marker in ELISA diagnosis and indicate that the accuracy of routine tests such as virus isolation and RT-PCR is significantly affected by inadequate transport and storage conditions of serum samples.


Asunto(s)
Antígenos Virales/sangre , Virus del Dengue/aislamiento & purificación , Dengue/diagnóstico , Ensayo de Inmunoadsorción Enzimática/métodos , Pruebas Inmunológicas/métodos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Proteínas no Estructurales Virales/inmunología , Anticuerpos Antivirales/sangre , Antígenos Virales/inmunología , Dengue/sangre , Dengue/virología , Virus del Dengue/genética , Virus del Dengue/inmunología , Humanos , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad , Proteínas no Estructurales Virales/genética
11.
Nat Commun ; 12(1): 1102, 2021 02 17.
Artículo en Inglés | MEDLINE | ID: mdl-33597521

RESUMEN

The four-dengue virus (DENV) serotypes infect several hundred million people annually. For the greatest safety and efficacy, tetravalent DENV vaccines are designed to stimulate balanced protective immunity to all four serotypes. However, this has been difficult to achieve. Clinical trials with a leading vaccine demonstrated that unbalanced replication and immunodominance of one vaccine component over others can lead to low efficacy and vaccine enhanced severe disease. The Laboratory of Infectious Diseases at the National Institutes of Health has developed a live attenuated tetravalent DENV vaccine (TV003), which is currently being tested in phase 3 clinical trials. Here we report, our study to determine if TV003 stimulate balanced and serotype-specific (TS) neutralizing antibody (nAb) responses to each serotype. Serum samples from twenty-one dengue-naive individuals participated under study protocol CIR287 (ClinicalTrials.gov NCT02021968) are analyzed 6 months after vaccination. Most subjects (76%) develop TS nAbs to 3 or 4 DENV serotypes, indicating immunity is induced by each vaccine component. Vaccine-induced TS nAbs map to epitopes known to be targets of nAbs in people infected with wild type DENVs. Following challenge with a partially attenuated strain of DENV2, all 21 subjects are protected from the efficacy endpoints. However, some vaccinated individuals develop post challenge nAb boost, while others mount post-challenge antibody responses that are consistent with sterilizing immunity. TV003 vaccine induced DENV2 TS nAbs are associated with sterilizing immunity. Our results indicate that nAbs to TS epitopes on each serotype may be a better correlate than total levels of nAbs currently used for guiding DENV vaccine development.


Asunto(s)
Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Vacunas contra el Dengue/inmunología , Virus del Dengue/inmunología , Dengue/inmunología , Formación de Anticuerpos/inmunología , Especificidad de Anticuerpos/inmunología , Dengue/prevención & control , Dengue/virología , Vacunas contra el Dengue/administración & dosificación , Virus del Dengue/clasificación , Epítopos/inmunología , Humanos , Serotipificación , Especificidad de la Especie , Resultado del Tratamiento , Vacunación/métodos , Vacunas Atenuadas/administración & dosificación , Vacunas Atenuadas/inmunología
12.
BMC Infect Dis ; 21(1): 166, 2021 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-33568111

RESUMEN

BACKGROUND: An unexpected dengue outbreak occurred in Hunan Province in 2018. This was the first dengue outbreak in this area of inland China, and 172 cases were reported. METHODS: To verify the causative agent of this outbreak and characterise the viral genes, the genes encoding the structural proteins C/prM/E of viruses isolated from local residents were sequenced followed by mutation and phylogenetic analysis. Recombination, selection pressure, potential secondary structure and three-dimensional structure analyses were also performed. RESULTS: Phylogenetic analysis revealed that all epidemic strains were of the cosmopolitan DENV-2 genotype and were most closely related to the Zhejiang strain (MH010629, 2017) and then the Malaysia strain (KJ806803, 2013). Compared with the sequence of DENV-2SS, 151 base substitutions were found in the sequences of 89 isolates; these substitutions resulted in 20 non-synonymous mutations, of which 17 mutations existed in all samples (two in the capsid protein, six in the prM/M proteins, and nine in the envelope proteins). Moreover, amino acid substitutions at the 602nd (E322:Q → H) and 670th (E390: N → S) amino acids may have enhanced the virulence of the epidemic strains. One new DNA binding site and five new protein binding sites were observed. Two polynucleotide binding sites and seven protein binding sites were lost in the epidemic strains compared with DENV-2SS. Meanwhile, five changes were found in helical regions. Minor changes were observed in helical transmembrane and disordered regions. The 429th amino acid of the E protein switched from a histamine (positively charged) to an asparagine (neutral) in all 89 isolated strains. No recombination events or positive selection pressure sites were observed. To our knowledge, this study is the first to analyse the genetic characteristics of epidemic strains in the first dengue outbreak in Hunan Province in inland China. CONCLUSIONS: The causative agent is likely to come from Zhejiang Province, a neighbouring province where dengue fever broke out in 2017. This study may help clarify the intrinsic geographical relatedness of DENV-2 and contribute to further research on pathogenicity and vaccine development.


Asunto(s)
Virus del Dengue/genética , Dengue/diagnóstico , Proteínas del Envoltorio Viral/genética , Sitios de Unión , Proteínas de la Cápside/química , Proteínas de la Cápside/genética , Proteínas de la Cápside/metabolismo , China/epidemiología , Dengue/epidemiología , Dengue/virología , Virus del Dengue/clasificación , Virus del Dengue/aislamiento & purificación , Brotes de Enfermedades , Genotipo , Humanos , Mutación , Filogenia , Estructura Terciaria de Proteína , ARN Viral/química , ARN Viral/metabolismo , Análisis de Secuencia de ARN , Proteínas del Envoltorio Viral/química , Proteínas no Estructurales Virales/genética , Proteínas no Estructurales Virales/metabolismo
13.
Parasit Vectors ; 14(1): 22, 2021 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-33407778

RESUMEN

BACKGROUND: Due to an increase in mosquito habitats and the lack facilities to carry out basic mosquito control, construction sites in China are more likely to experience secondary dengue fever infection after importation of an initial infection, which may then increase the number of infections in the neighboring communities and the chance of community transmission. The aim of this study was to investigate how to effectively reduce the transmission of dengue fever at construction sites and the neighboring communities. METHODS: The Susceptible-Exposed-Infectious/Asymptomatic-Recovered (SEIAR) model of human and SEI model of mosquitoes were developed to estimate the transmission of dengue virus between humans and mosquitoes within the construction site and within a neighboring community, as well between each of these. With the calibrated model, we further estimated the effectiveness of different intervention scenarios targeting at reducing the transmissibility at different locations (i.e. construction sites and community) with the total attack rate (TAR) and the duration of the outbreak (DO). RESULTS: A total of 102 construction site-related and 131 community-related cases of dengue fever were reported in our area of study. Without intervention, the number of cases related to the construction site and the community rose to 156 (TAR: 31.25%) and 10,796 (TAR: 21.59%), respectively. When the transmission route from mosquitoes to humans in the community was cut off, the number of community cases decreased to a minimum of 33 compared with other simulated scenarios (TAR: 0.068%, DO: 60 days). If the transmission route from infectious mosquitoes in the community and that from the construction site to susceptible people on the site were cut off at the same time, the number of cases on the construction site dropped to a minimum of 74 (TAR: 14.88%, DO: 66 days). CONCLUSIONS: To control the outbreak of dengue fever effectively on both the construction site and in the community, interventions needed to be made both within the community and from the community to the construction site. If interventions only took place within the construction site, the number of cases on the construction site would not be reduced. Also, interventions implemented only within the construction site or between the construction site and the community would not lead to a reduction in the number of cases in the community.


Asunto(s)
Dengue/prevención & control , Dengue/transmisión , Infecciones Asintomáticas/epidemiología , China/epidemiología , Control de Enfermedades Transmisibles , Industria de la Construcción , Dengue/epidemiología , Dengue/virología , Virus del Dengue/fisiología , Brotes de Enfermedades/prevención & control , Susceptibilidad a Enfermedades/epidemiología , Susceptibilidad a Enfermedades/virología , Humanos , Incidencia , Modelos Teóricos , Control de Mosquitos , Mosquitos Vectores/crecimiento & desarrollo , Mosquitos Vectores/virología , Características de la Residencia , Lugar de Trabajo
14.
PLoS One ; 16(1): e0244937, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33406122

RESUMEN

BACKGROUND: The impact of SARS-CoV-2 in regions endemic for both Dengue and Chikungunya is still not fully understood. Considering that symptoms/clinical features displayed during Dengue, Chikungunya and SARS-CoV-2 acute infections are similar, undiagnosed cases of SARS-CoV-2 in co-endemic areas may be more prevalent than expected. This study was conducted to assess the prevalence of covert cases of SARS-CoV-2 among samples from patients with clinical symptoms compatible with either Dengue or Chikungunya viral infection in the state of Espírito Santo, Brazil. METHODS: Presence of immunoglobulin G (IgG) antibody specific to SARS-CoV-2 nucleoprotein was detected using a chemiluminescent microparticle immunoassay in samples from 7,370 patients, without previous history of COVID-19 diagnosis, suspected of having either Dengue (n = 1,700) or Chikungunya (n = 7,349) from December 1st, 2019 to June 30th, 2020. FINDINGS: Covert cases of SARS-CoV-2 were detected in 210 (2.85%) out of the 7,370 serum samples tested. The earliest undiagnosed missed case of COVID-19 dated back to a sample collected on December 18, 2019, also positive for Dengue Virus. Cross-reactivity with either Dengue virus or other common coronaviruses were not observed. INTERPRETATION: Our findings demonstrate that concomitant Dengue or Chikungunya outbreaks may difficult the diagnosis of SARS-CoV-2 infections. To our knowledge, this is the first study to demonstrate, with a robust sample size (n = 7,370) and using highly specific and sensitive chemiluminescent microparticle immunoassay method, that covert SARS-CoV-2 infections are more frequent than previously expected in Dengue and Chikungunya hyperendemic regions. Moreover, our results suggest that SAR-CoV-2 cases were occurring prior to February, 2020, and that these undiagnosed missed cases may have contributed to the fast expansion of SARS-CoV-2 outbreak in Brazil. Data presented here demonstrate that in arboviral endemic regions, SARS-CoV-2 infection must be always considered, regardless of the existence of a previous positive diagnosis for Dengue or Chikungunya.


Asunto(s)
/epidemiología , Fiebre Chikungunya/epidemiología , Dengue/epidemiología , Adulto , Anticuerpos Antivirales/sangre , Brasil/epidemiología , Virus Chikungunya/patogenicidad , Coinfección/epidemiología , Virus del Dengue/patogenicidad , Errores Diagnósticos/tendencias , Brotes de Enfermedades , Femenino , Humanos , Inmunoglobulina G/sangre , Masculino , Persona de Mediana Edad , Prevalencia , /patogenicidad
15.
Science ; 371(6525): 194-200, 2021 01 08.
Artículo en Inglés | MEDLINE | ID: mdl-33414220

RESUMEN

Medically important flaviviruses cause diverse disease pathologies and collectively are responsible for a major global disease burden. A contributing factor to pathogenesis is secreted flavivirus nonstructural protein 1 (NS1). Despite demonstrated protection by NS1-specific antibodies against lethal flavivirus challenge, the structural and mechanistic basis remains unknown. Here, we present three crystal structures of full-length dengue virus NS1 complexed with a flavivirus-cross-reactive, NS1-specific monoclonal antibody, 2B7, at resolutions between 2.89 and 3.96 angstroms. These structures reveal a protective mechanism by which two domains of NS1 are antagonized simultaneously. The NS1 wing domain mediates cell binding, whereas the ß-ladder triggers downstream events, both of which are required for dengue, Zika, and West Nile virus NS1-mediated endothelial dysfunction. These observations provide a mechanistic explanation for 2B7 protection against NS1-induced pathology and demonstrate the potential of one antibody to treat infections by multiple flaviviruses.


Asunto(s)
Anticuerpos Neutralizantes/química , Anticuerpos Antivirales/química , Virus del Dengue/inmunología , Proteínas no Estructurales Virales/inmunología , Virus del Nilo Occidental/inmunología , Virus Zika/inmunología , Animales , Anticuerpos Monoclonales/química , Anticuerpos Monoclonales/inmunología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Reacciones Cruzadas , Cristalografía por Rayos X , Dengue/prevención & control , Dengue/terapia , Endotelio/inmunología , Glicocálix/inmunología , Humanos , Ratones , Conformación Proteica en Lámina beta , Dominios Proteicos , Proteínas no Estructurales Virales/química , Fiebre del Nilo Occidental/prevención & control , Fiebre del Nilo Occidental/terapia , Infección por el Virus Zika/prevención & control , Infección por el Virus Zika/terapia
16.
Arch Virol ; 166(3): 863-870, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33495898

RESUMEN

A dengue virus serotype 1 (DENV-1) epidemic occurred from October to December 2018 in Xishuangbanna, Yunnan, Southwest China, neighboring Myanmar, Laos, and Vietnam. In this study, we investigated the molecular characteristics, evolution, and potential source of DENV from Xishuangbanna. The C (capsid), prM (premembrane), and E (envelope) genes of DENV isolated from 87 serum samples obtained from local patients were amplified and sequenced, and the sequences were evaluated by identification of mutations, phylogenetic and homologous recombination analysis, and secondary structure prediction. Phylogenetic analysis showed that all of the epidemic DENV strains from Xishuangbanna could be grouped in a branch with DENV-1 isolates, and were most similar to the Fujian 2005 (China, DQ193572) and Singapore 2016 (MF314188) strains. When compared with DENV-1SS (the standard strain), there were 31 non-synonymous mutations, but no obvious homologous recombination signal was found. Secondary structure prediction showed that some changes had occurred in a helical region in proteins of the MN123849 and MN123854 strains, but there were few changes in the disordered region. This study reveals the molecular characteristics of the structural genes of the Xishuangbanna epidemic strains in 2018 and provides a reference for molecular epidemiology, infection, and pathogenicity research and vaccine development.


Asunto(s)
Proteínas de la Cápside/genética , Virus del Dengue/genética , Dengue/epidemiología , Proteínas del Envoltorio Viral/genética , Secuencia de Aminoácidos , China/epidemiología , Virus del Dengue/clasificación , Virus del Dengue/aislamiento & purificación , Brotes de Enfermedades , Genotipo , Humanos , Epidemiología Molecular , Filogenia , ARN Viral/genética , Alineación de Secuencia , Análisis de Secuencia de ARN , Serogrupo
17.
Nat Commun ; 12(1): 151, 2021 01 08.
Artículo en Inglés | MEDLINE | ID: mdl-33420058

RESUMEN

Mosquito-borne viruses threaten the Caribbean due to the region's tropical climate and seasonal reception of international tourists. Outbreaks of chikungunya and Zika have demonstrated the rapidity with which these viruses can spread. Concurrently, dengue fever cases have climbed over the past decade. Sustainable disease control measures are urgently needed to quell virus transmission and prevent future outbreaks. Here, to improve upon current control methods, we analyze temporal and spatial patterns of chikungunya, Zika, and dengue outbreaks reported in the Dominican Republic between 2012 and 2018. The viruses that cause these outbreaks are transmitted by Aedes mosquitoes, which are sensitive to seasonal climatological variability. We evaluate whether climate and the spatio-temporal dynamics of dengue outbreaks could explain patterns of emerging disease outbreaks. We find that emerging disease outbreaks were robust to the climatological and spatio-temporal constraints defining seasonal dengue outbreak dynamics, indicating that constant surveillance is required to prevent future health crises.


Asunto(s)
Fiebre Chikungunya/epidemiología , Enfermedades Transmisibles Emergentes/epidemiología , Dengue/epidemiología , Brotes de Enfermedades/estadística & datos numéricos , Enfermedades Endémicas/estadística & datos numéricos , Infección por el Virus Zika/epidemiología , Adolescente , Aedes/virología , Animales , Fiebre Chikungunya/prevención & control , Fiebre Chikungunya/transmisión , Fiebre Chikungunya/virología , Virus Chikungunya/aislamiento & purificación , Niño , Preescolar , Enfermedades Transmisibles Emergentes/prevención & control , Enfermedades Transmisibles Emergentes/transmisión , Enfermedades Transmisibles Emergentes/virología , Dengue/prevención & control , Dengue/transmisión , Dengue/virología , Virus del Dengue/aislamiento & purificación , Brotes de Enfermedades/prevención & control , República Dominicana/epidemiología , Enfermedades Endémicas/prevención & control , Monitoreo Epidemiológico , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Control de Mosquitos , Mosquitos Vectores/virología , Análisis Espacio-Temporal , Adulto Joven , Virus Zika/aislamiento & purificación , Infección por el Virus Zika/prevención & control , Infección por el Virus Zika/transmisión , Infección por el Virus Zika/virología
18.
ACS Infect Dis ; 7(2): 471-478, 2021 02 12.
Artículo en Inglés | MEDLINE | ID: mdl-33395259

RESUMEN

A series of 7-deazaadenine ribonucleosides bearing alkyl, alkenyl, alkynyl, aryl, or hetaryl groups at position 7 as well as their 5'-O-triphosphates and two types of monophosphate prodrugs (phosphoramidates and S-acylthioethanol esters) were prepared and tested for antiviral activity against selected RNA viruses (Dengue, Zika, tick-borne encephalitis, West Nile, and SARS-CoV-2). The modified triphosphates inhibited the viral RNA-dependent RNA polymerases at micromolar concentrations through the incorporation of the modified nucleotide and stopping a further extension of the RNA chain. 7-Deazaadenosine nucleosides bearing ethynyl or small hetaryl groups at position 7 showed (sub)micromolar antiviral activities but significant cytotoxicity, whereas the nucleosides bearing bulkier heterocycles were still active but less toxic. Unexpectedly, the monophosphate prodrugs were similarly or less active than the corresponding nucleosides in the in vitro antiviral assays, although the bis(S-acylthioethanol) prodrug 14h was transported to the Huh7 cells and efficiently released the nucleoside monophosphate.


Asunto(s)
Antivirales/farmacología , Profármacos/farmacología , Purinas/farmacología , Virus ARN/efectos de los fármacos , Ribonucleósidos/farmacología , /tratamiento farmacológico , Línea Celular Tumoral , Virus del Dengue/efectos de los fármacos , Virus de la Encefalitis Transmitidos por Garrapatas/efectos de los fármacos , Humanos , Fosfatos/farmacología , Nucleósidos de Purina , /efectos de los fármacos , Virus del Nilo Occidental/efectos de los fármacos , Virus Zika/efectos de los fármacos
19.
Science ; 371(6525): 190-194, 2021 01 08.
Artículo en Inglés | MEDLINE | ID: mdl-33414219

RESUMEN

There are no approved flaviviral therapies and the development of vaccines against flaviruses has the potential of being undermined by antibody-dependent enhancement (ADE). The flavivirus nonstructural protein 1 (NS1) is a promising vaccine antigen with low ADE risk but has yet to be explored as a broad-spectrum therapeutic antibody target. Here, we provide the structural basis of NS1 antibody cross-reactivity through cocrystallization of the antibody 1G5.3 with NS1 proteins from dengue and Zika viruses. The 1G5.3 antibody blocks multi-flavivirus NS1-mediated cell permeability in disease-relevant cell lines, and therapeutic application of 1G5.3 reduces viremia and improves survival in dengue, Zika, and West Nile virus murine models. Finally, we demonstrate that 1G5.3 protection is independent of effector function, identifying the 1G5.3 epitope as a key site for broad-spectrum antiviral development.


Asunto(s)
Anticuerpos Neutralizantes/química , Anticuerpos Antivirales/química , Virus del Dengue/inmunología , Proteínas no Estructurales Virales/inmunología , Virus del Nilo Occidental/inmunología , Virus Zika/inmunología , Animales , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/uso terapéutico , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/uso terapéutico , Células CHO , Línea Celular , Cricetulus , Reacciones Cruzadas , Dengue/prevención & control , Dengue/terapia , Modelos Animales de Enfermedad , Humanos , Ratones , Dominios Proteicos , Proteínas no Estructurales Virales/química , Viremia/terapia , Fiebre del Nilo Occidental/prevención & control , Fiebre del Nilo Occidental/terapia , Infección por el Virus Zika/prevención & control , Infección por el Virus Zika/terapia
20.
BMC Infect Dis ; 21(1): 96, 2021 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-33478432

RESUMEN

BACKGROUND: Dengue virus infection has been an important and serious public health concern in Taiwan, where local outbreaks of dengue fever occurred almost every year. To our knowledge, no nationwide investigation has been carried out to determine the actual extent of infection in the general population. METHODS: A total of 1308 random serum samples were collected from the general population in Taiwan in 2010. The antibody-captured enzyme-linked immunosorbent assays were used to detect DENV-specific IgM and IgG. Demographics data were used for risk analysis. RESULTS: The weighted overall seroprevalence was 1.96% for anti-DENV IgM, and 3.4% for anti-DENV IgG, respectively. A significant rise of DENV IgG seropositive rate had been noted since late adulthood stage, from 1.1% at the age group of 50-59 years to 7.6% at the age group of 60-69 years. For people aged over 70 years, the seropositive rate reached 19%. Age, nationality, and regions of residency were associated with the IgG seropositivity. There was no statistically significant difference in seroprevalence of anti-Dengue IgM, indicating recent infection, among univariate predictors we proposed, including gender, age, residency, nationality, and household size. CONCLUSIONS: Our results indicated that the majority of population in Taiwan born after 1940 is naive to dengue virus and the prevalence of IgG antibody against dengue virus rises with age. Nationality, and regions of residency are associated with the exposure of population to infection by dengue viruses. Further studies are needed to realize the current situation of seroprevalence of dengue fever in Taiwan.


Asunto(s)
Anticuerpos Antivirales/sangre , Virus del Dengue/inmunología , Dengue/epidemiología , Adolescente , Adulto , Anciano , Niño , Preescolar , Dengue/sangre , Virus del Dengue/aislamiento & purificación , Femenino , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Estudios Seroepidemiológicos , Taiwán/epidemiología , Adulto Joven
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