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1.
Rev Soc Bras Med Trop ; 54: e0891 2020, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33950132

RESUMEN

INTRODUCTION: Cerebrospinal fluid analysis contributes to the diagnosis and neuropathogenesis of neuroinvasive arboviruses. Neurological complications caused by dengue, Zika, and chikungunya infections have high clinical relevance because of their high potential to cause death or neurological deficits. We aimed to evaluate the use of cerebrospinal fluid assays for diagnostic support in neurological disorders associated with dengue, chikungunya, and Zika infections. METHODS: A systematic review was carried out by searching the electronic databases LILACS, PubMed, Scopus, and Embase for articles written in English, Portuguese, or Spanish in the last 19 years. Published studies were reviewed using the terms "dengue," "Zika", "chikungunya", alone or in combination with "cerebrospinal fluid" in the period from 2000 to 2019. RESULTS: A total of 98,060 studies were identified; of these, 1.1% (1,041 studies, 58,478 cases) used cerebrospinal fluid assays for neurological investigations. The most frequent neurological disorders included encephalitis (41.4%), congenital syndromes (17%), and microcephaly associated with Zika virus infections (8.9%). Neuroinvasive disorders were confirmed in 8.03% of 58,478 cases by specific cerebrospinal fluid analyses. The main methods used were IgM-specific antibodies (66%) and reverse transcription-polymerase chain reaction (10%). The largest number of scientific papers (29%) originated from Brazil, followed by India (18.4%) and the United States (14.4%). CONCLUSIONS: Although cerebrospinal fluid analysis is of great importance for increasing neurological diagnostic accuracy and contributes to the early diagnosis of neuroinvasive dengue, chikungunya, and Zika infections, it is underused in routine laboratory investigations worldwide.


Asunto(s)
Fiebre Chikungunya , Virus Chikungunya , Virus del Dengue , Dengue , Infección por el Virus Zika , Virus Zika , Brasil , Fiebre Chikungunya/diagnóstico , Dengue/diagnóstico , Humanos , Infección por el Virus Zika/diagnóstico
2.
Rev Soc Bras Med Trop ; 54: e0855, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33886823

RESUMEN

The persistence of serum-specific anti-chikungunya IgM antibodies (CHIKV-IgM) can vary after chikungunya fever (CHIK) infection. However, the factors related to its production are not yet known. We described a case series drawn up from data collected from 57 patients between 12 and 36 months after the acute phase of CHIK infection in Northeastern Brazil. CHIKV-IgM was detectable in 7/57 (12.3%) patients after 28.3 months of infection. No frequency differences in chronic musculoskeletal manifestations and underlying conditions were detected between patients with or without CHIKV-IgM. CHIKV-IgM was detected for up to 35 months in Brazilian patients after CHIK infection.


Asunto(s)
Fiebre Chikungunya , Virus Chikungunya , Anticuerpos Antivirales , Brasil , Fiebre Chikungunya/diagnóstico , Humanos , Inmunoglobulina M
3.
Medicine (Baltimore) ; 100(17): e25695, 2021 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-33907147

RESUMEN

RATIONALE: The chikungunya virus (CHIKV) was first isolated in a Tanzanian epidemic area between 1952 and 1953. The best description of the CHIKV transmission during pregnancy can be found in a well-documented epidemic in 2005, in the "La Reunion" island, a French territory located in the Indian Ocean, in which about one-third of the population was infected. Reports of arbovirus infections in pregnancy are increasing over time, but the spectrum of clinical findings remains an incognita among researchers, including CHIKV. PATIENT CONCERNS: In this report, it was possible to verify 2 cases exposed to CHIKV during foetal period and the possible implications of the infection on gestational structures and exposed children after the birth. DIAGNOSIS: In both cases, the mothers were positive by laboratory tests in serologic analysis for CHIKV, as ezyme-linked immunossorbent assay (ELISA), plaque reduction neutralisation testing (PRNT) and immunofluorescence (IF); but there were no positive tests in quantitative polymerase chain reaction (qPCR) for mothers or children. INTERVENTIONS: The exposed children were followed up in a paediatrics clinic in order not only to provide the medical assistance, but also to verify child development and the possible implications and neurocognitive changes caused by gestational infection. OUTCOMES: There were neurological and developmental changes in one of the children followed up on an outpatient basis. There was an improvement in the neurological situation and symptoms only 3 years and 1 month after birth. LESSONS: Based on the cases presented, we can conclude that clinical symptoms of CHIKV maternal infection may occur late in new-borns and can affect their development.


Asunto(s)
Fiebre Chikungunya , Virus Chikungunya , Complicaciones Infecciosas del Embarazo , Efectos Tardíos de la Exposición Prenatal , Trastornos Psicomotores , Tiempo , Anticuerpos Antivirales/sangre , Fiebre Chikungunya/diagnóstico , Fiebre Chikungunya/inmunología , Fiebre Chikungunya/transmisión , Virus Chikungunya/inmunología , Virus Chikungunya/aislamiento & purificación , Desarrollo Infantil , Preescolar , Continuidad de la Atención al Paciente , Femenino , Humanos , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa , Pruebas de Estado Mental y Demencia , Embarazo , Complicaciones Infecciosas del Embarazo/diagnóstico , Complicaciones Infecciosas del Embarazo/inmunología , Efectos Tardíos de la Exposición Prenatal/diagnóstico , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Trastornos Psicomotores/diagnóstico , Trastornos Psicomotores/etiología , Pruebas Serológicas/métodos
4.
Arch Virol ; 166(5): 1455-1462, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33704558

RESUMEN

During the dengue epidemic in Yunnan Province, China, during 2019, a concurrent outbreak of chikungunya occurred in the city of Ruili, which is located in the southwest of the province, adjacent to Myanmar. As part of this outbreak, three neonatal cases of infection with indigenous chikungunya virus from mother-to-child (vertical) transmission were observed. Isolates of chikungunya virus were obtained from 37 serum samples of patients with chikungunya during this outbreak, and a phylogenetic analysis of these isolates revealed that they belong to the Indian Ocean subclade of the East/Central/South African genotype. The E1 genes of these viruses did not harbor the A226V mutation.


Asunto(s)
Fiebre Chikungunya/virología , Virus Chikungunya/aislamiento & purificación , Enfermedades Transmisibles Emergentes/virología , Transmisión Vertical de Enfermedad Infecciosa , Fiebre Chikungunya/epidemiología , Fiebre Chikungunya/transmisión , Virus Chikungunya/clasificación , Virus Chikungunya/genética , China/epidemiología , Enfermedades Transmisibles Emergentes/epidemiología , Enfermedades Transmisibles Emergentes/transmisión , Brotes de Enfermedades , Femenino , Genoma Viral/genética , Genotipo , Humanos , Masculino , Mutación , Filogenia , ARN Viral/genética , Proteínas Virales/genética
5.
RECIIS (Online) ; 15(1): 187-200, jan.-mar. 2021. ilus
Artículo en Portugués | LILACS | ID: biblio-1177392

RESUMEN

A mobilização social para o enfrentamento da dengue, zika, chikungunya e controle do Aedes aegypti tem sido um desafio no país. Esse artigo apresenta o processo de elaboração de uma plataforma virtual, incluindo a composição do seu acervo e a análise exploratória do seu uso, como ferramenta, numa proposta de mobilização social que envolve a criação de comitês populares nos territórios para o enfrentamento das três doenças e vetor. A construção da plataforma considerou: facilidade para usuário; acesso; armazenamento de material; interatividade e banco para monitoramento de dados. A seleção do acervo baseou-se em critérios: técnico, referente à fonte e autoria; acurácia, concordância entre informação e evidência em saúde; e legibilidade, garantindo a compreensão por diferentes grupos. A análise exploratória utilizou o banco de dados da plataforma. Os resultados apontaram a plataforma como uma ferramenta que pode contribuir com a comunicação e informação em saúde nessa proposta de mobilização social.


Social mobilization for dengue, zika and chikungunya prevention and control of Aedes aegypti has been a challenge in the country. This paper presents the process of elaboration of a virtual platform, including the composition of its collection and the exploratory analysis of its use, as a tool in a social mobilization proposal that encompasses the creation of popular committees in the territories for the confrontation of the three diseases and vector. The construction of the platform considered: ease of use; access; material storage; interactivity and database for data monitoring. The selection of the collection was based on the following criteria: technical, considering source and authorship; accuracy, regarding the agreement between health information and evidence; legibility, ensuring the understanding by different groups. The exploratory analysis used the platform database. The results showed the platform as a tool which can contribute to health communication and information in this proposal of social mobilization.


La movilización social para combatir el dengue, zika, chikungunya y control de Aedes ha sido un desafío. Este artículo presenta el proceso de elaboración de una plataforma virtual, que incluye la composición de su acervo y el análisis exploratorio de su uso, como herramienta en una propuesta de movilización social que implica la creación de comités populares en los territorios para enfrentar las enfermedades y el vector. La construcción de la plataforma consideró: facilidad para usuario; acceso; almacenamiento de material; interactividad y bases de datos para el monitoreo. La selección del acervo se basó en criterios: técnico, con fuente y autoría; precisión, concordancia entre información y evidencia en salud; legibilidad, para garantizar la comprensión por diferentes grupos. El análisis utilizó datos de la plataforma. Los resultados mostraron que la plataforma puede ser una herramienta para contribuir a la comunicación e información de salud en esta propuesta de movilización social.


Asunto(s)
Humanos , Infecciones por Arbovirus , Participación de la Comunidad , Comunicación en Salud , Medios de Comunicación Sociales , Promoción de la Salud , Virus Chikungunya , Epidemiología Descriptiva , Aedes , Dengue , Virus Zika
6.
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
7.
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
8.
BMC Infect Dis ; 21(1): 186, 2021 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-33602147

RESUMEN

BACKGROUND: Chikungunya fever (CHIKF) was first described in Tanzania in 1952. Several epidemics including East Africa have occurred, but there are no descriptions of longitudinal surveillance of endemic disease. Here, we estimate the incidence of CHIKF in coastal Kenya and describe the associated viral phylogeny. METHODS: We monitored acute febrile illnesses among 3500 children visiting two primary healthcare facilities in coastal Kenya over a 5-year period (2014-2018). Episodes were linked to a demographic surveillance system and blood samples obtained. Cross-sectional sampling in a community survey of a different group of 435 asymptomatic children in the same study location was done in 2016. Reverse-transcriptase PCR was used for chikungunya virus (CHIKV) screening, and viral genomes sequenced for phylogenetic analyses. RESULTS: We found CHIKF to be endemic in this setting, associated with 12.7% (95% CI 11.60, 13.80) of all febrile presentations to primary healthcare. The prevalence of CHIKV infections among asymptomatic children in the community survey was 0.7% (95% CI 0.22, 2.12). CHIKF incidence among children < 1 year of age was 1190 cases/100,000-person years and 63 cases/100,000-person years among children aged ≥10 years. Recurrent CHIKF episodes, associated with fever and viraemia, were observed among 19 of 170 children with multiple febrile episodes during the study period. All sequenced viral genomes mapped to the ECSA genotype albeit distinct from CHIKV strains associated with the 2004 East African epidemic. CONCLUSIONS: CHIKF may be a substantial public health burden in primary healthcare on the East African coast outside epidemic years, and recurrent infections are common.


Asunto(s)
Fiebre Chikungunya/epidemiología , Fiebre Chikungunya/virología , Adolescente , Fiebre Chikungunya/diagnóstico , Virus Chikungunya/clasificación , Virus Chikungunya/genética , Virus Chikungunya/aislamiento & purificación , Niño , Preescolar , Estudios Transversales , Femenino , Fiebre/diagnóstico , Fiebre/epidemiología , Fiebre/virología , Genotipo , Humanos , Incidencia , Lactante , Kenia/epidemiología , Masculino , Filogenia , Prevalencia , Estudios Prospectivos , Recurrencia
9.
PLoS Negl Trop Dis ; 15(1): e0009005, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33465098

RESUMEN

BACKGROUND: The integration of house-screening and long-lasting insecticidal nets, known as insecticide-treated screening (ITS), can provide simple, safe, and low-tech Aedes aegypti control. Cluster randomised controlled trials in two endemic localities for Ae. aegypti of south Mexico, showed that ITS conferred both, immediate and sustained (~2 yr) impact on indoor-female Ae. aegypti infestations. Such encouraging results require further validation with studies quantifying more epidemiologically-related endpoints, including arbovirus infection in Ae. aegypti. We evaluated the efficacy of protecting houses with ITS on Ae. aegypti infestation and arbovirus infection during a Zika outbreak in Merida, Yucatan, Mexico. METHODOLOGY/PRINCIPAL FINDINGS: A two-arm cluster-randomised controlled trial evaluated the entomological efficacy of ITS compared to the absence of ITS (with both arms able to receive routine arbovirus vector control) in the neighbourhood Juan Pablo II of Merida. Cross-sectional entomological surveys quantified indoor adult mosquito infestation and arbovirus infection at baseline (pre-ITS installation) and throughout two post-intervention (PI) surveys spaced at 6-month intervals corresponding to dry/rainy seasons over one year (2016-2017). Household-surveys assessed the social reception of the intervention. Houses with ITS were 79-85% less infested with Aedes females than control houses up to one-year PI. A similar significant trend was observed for blood-fed Ae. aegypti females (76-82%). Houses with ITS had significantly less infected female Ae. aegypti than controls during the peak of the epidemic (OR = 0.15, 95%CI: 0.08-0.29), an effect that was significant up to a year PI (OR = 0.24, 0.15-0.39). Communities strongly accepted the intervention, due to its perceived mode of action, the prevalent risk for Aedes-borne diseases in the area, and the positive feedback from neighbours receiving ITS. CONCLUSIONS/SIGNIFICANCE: We show evidence of the protective efficacy of ITS against an arboviral disease of major relevance, and discuss the relevance of our findings for intervention adoption.


Asunto(s)
Aedes/virología , Control de Mosquitos/métodos , Mosquiteros/estadística & datos numéricos , Infección por el Virus Zika/prevención & control , Animales , Virus Chikungunya/aislamiento & purificación , Virus del Dengue , Femenino , Vivienda , Humanos , Mordeduras y Picaduras de Insectos/prevención & control , Insecticidas , México , Mosquitos Vectores , Virus Zika/aislamiento & purificación , Infección por el Virus Zika/epidemiología
10.
Acta Trop ; 215: 105819, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33406443

RESUMEN

The outbreaks caused by the Aedes aegypti-transmitted dengue virus (DENV), zakat virus (ZIKV), and chikungunya virus (CHIKV) result in a significant impact to the health systems of tropical countries. Furthermore, the occurrence of patients coinfected by at least two of these arboviruses is an aggravating factor in that scenario. On this basis, surveillance tools such as the Rapid Index Survey for Aedes aegypti (LIRAa) are used to estimate vector infestation in order to improve the prediction of human outbreaks. Ae. aegypti eggs were collected in the city of Vitória da Conquista, in Bahia State, Brazil, and subsequently hatched into larvae, which were analyzed in pools or individually for the presence of DENV, ZIKV, and CHIKV by molecular biology methods. The detection data for arboviruses were crossed with the LIRAa obtained in each region of the study city. Thirty larvae pools were analyzed, and fourteen (46.6%) of them were detected positive for DENV, ZIKV, and/or CHIKV. Among the individually analyzed larvae (n = 30), nine (30%) were positive for any of these arboviruses, and four (13.3%) were simultaneously coinfected by DENV and ZIKV. Furthermore, there was a positive correlation between the detection of circulating arboviruses and LIRAa. The simultaneous Ae. aegypti larvae infection by two different arboviruses is an unprecedented finding. This result suggests the occurrence of a vertical arboviruses co-transmission from the female mosquito to its offspring in nature. The occurrence of concomitant circulation of DENV, ZIKV, and CHIKV in Ae. aegypti from a single study region is another finding of this article. Finally, LIRAa seems to not only estimate vector infestation but also to predict circulation of arboviruses.


Asunto(s)
Aedes/virología , Virus Chikungunya/aislamiento & purificación , Coinfección/transmisión , Virus del Dengue/aislamiento & purificación , Transmisión Vertical de Enfermedad Infecciosa , Mosquitos Vectores/virología , Virus Zika/aislamiento & purificación , Animales , Femenino , Humanos , Larva/virología
11.
PLoS Pathog ; 17(1): e1009033, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33411764

RESUMEN

The p53 transcription factor plays a key role both in cancer and in the cell-intrinsic response to infections. The ORFEOME project hypothesized that novel p53-virus interactions reside in hitherto uncharacterized, unknown, or hypothetical open reading frames (orfs) of human viruses. Hence, 172 orfs of unknown function from the emerging viruses SARS-Coronavirus, MERS-Coronavirus, influenza, Ebola, Zika (ZIKV), Chikungunya and Kaposi Sarcoma-associated herpesvirus (KSHV) were de novo synthesized, validated and tested in a functional screen of p53 signaling. This screen revealed novel mechanisms of p53 virus interactions and two viral proteins KSHV orf10 and ZIKV NS2A binding to p53. Originally identified as the target of small DNA tumor viruses, these experiments reinforce the notion that all viruses, including RNA viruses, interfere with p53 functions. These results validate this resource for analogous systems biology approaches to identify functional properties of uncharacterized viral proteins, long non-coding RNAs and micro RNAs.


Asunto(s)
Enfermedades Transmisibles Emergentes/virología , Virus ARN/metabolismo , Transducción de Señal/genética , Proteína p53 Supresora de Tumor/metabolismo , Virus Chikungunya/genética , Virus Chikungunya/metabolismo , Coronavirus/genética , Coronavirus/metabolismo , Ebolavirus/genética , Ebolavirus/metabolismo , Herpesvirus Humano 8/genética , Herpesvirus Humano 8/metabolismo , Humanos , Virus de la Influenza A/genética , Virus de la Influenza A/metabolismo , Sistemas de Lectura Abierta , Virus ARN/genética , Proteína p53 Supresora de Tumor/genética , Proteínas no Estructurales Virales/metabolismo , Virus Zika/genética , Virus Zika/metabolismo
12.
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
13.
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.
J Virol ; 95(6)2021 02 24.
Artículo en Inglés | MEDLINE | ID: mdl-33328310

RESUMEN

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus responsible for chikungunya fever. Nonstructural protein 2 (nsP2), a multifunctional protein essential for viral replication, has an N-terminal helicase region (nsP2h), which has both nucleotide triphosphatase and RNA triphosphatase activities, as well as a C-terminal cysteine protease region (nsP2p), which is responsible for nonstructural polyprotein processing. The two functional units are connected through a linker of 14 residues. Although crystal structures of the helicase and protease regions of CHIKV nsP2 have been solved separately, the conformational arrangement of the full-length nsP2 and the biological role of the linker remain elusive. Using the small-angle X-ray scattering (SAXS) method, we demonstrated that the full-length nsP2 is elongated and partially folded in solution. The reconstructed model of the structure of nsP2 contains a flexible interdomain linker, and there is no direct interaction between the two structured regions. To examine the function of the interdomain linker, we constructed and characterized a set of CHIKV mutants. The deletion of three or five amino acid residues in the linker region resulted in a modest defect in viral RNA replication and transcription but completely abolished viral infectivity. In contrast, increasing the flexibility of nsP2 by lengthening the interdomain linker increased both genomic RNA replication and viral infectivity. The enzymatic activities of the corresponding mutant proteins were largely unaffected. This work suggests that increasing the interdomain flexibility of nsP2 could facilitate the assembly of the replication complex (RC) with increased efficiency and promote virus production.IMPORTANCE CHIKV nsP2 plays multiple roles in viral RNA replication and virus-host interactions. The helicase and protease regions of nsP2 are connected through a short linker. Here, we determined that the conformation of full-length CHIKV nsP2 is elongated and that the protein is flexible in solution. We also highlight the importance of the flexibility of the interdomain of nsP2 on viral RNA synthesis and infectivity. CHIKV mutants harboring shortened linkers fail to produce infectious virus particles despite showing only relatively mild defects in genomic and subgenomic RNA synthesis. Mutations increasing the length of the interdomain linker have only mild and generally beneficial impacts on virus replication. Thus, our findings link interdomain flexibility with the regulation of viral RNA replication and infectivity of the viral genome.


Asunto(s)
Virus Chikungunya/fisiología , Cisteína Endopeptidasas/química , ARN Helicasas/química , Replicación Viral , Secuencia de Aminoácidos , Animales , Línea Celular , Virus Chikungunya/química , Virus Chikungunya/genética , Cisteína Endopeptidasas/genética , Cisteína Endopeptidasas/metabolismo , Humanos , Mutación , Estructura Terciaria de Proteína , ARN Helicasas/genética , ARN Helicasas/metabolismo , ARN Viral/metabolismo , /metabolismo
16.
Nature ; 589(7843): 615-619, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33328629

RESUMEN

Positive-sense single-stranded RNA viruses, such as coronaviruses, flaviviruses and alphaviruses, carry out transcription and replication inside virus-induced membranous organelles within host cells1-7. The remodelling of the host-cell membranes for the formation of these organelles is coupled to the membrane association of viral replication complexes and to RNA synthesis. These viral niches allow for the concentration of metabolites and proteins for the synthesis of viral RNA, and prevent the detection of this RNA by the cellular innate immune system8. Here we present the cryo-electron microscopy structure of non-structural protein 1 (nsP1) of the alphavirus chikungunya virus, which is responsible for RNA capping and membrane binding of the viral replication machinery. The structure shows the enzyme in its active form, assembled in a monotopic membrane-associated dodecameric ring. The structure reveals the structural basis of the coupling between membrane binding, oligomerization and allosteric activation of the capping enzyme. The stoichiometry-with 12 active sites in a single complex-redefines viral replication complexes as RNA synthesis reactors. The ring shape of the complex implies it has a role in controlling access to the viral organelle and ensuring the exit of properly capped viral RNA. Our results provide high-resolution information about the membrane association of the replication machinery of positive-sense single-stranded RNA viruses, and open up avenues for the further characterization of viral replication on cell membranes and the generation of antiviral agents.


Asunto(s)
Membrana Celular/metabolismo , Virus Chikungunya/crecimiento & desarrollo , Virus Chikungunya/ultraestructura , Microscopía por Crioelectrón , Caperuzas de ARN/metabolismo , Proteínas no Estructurales Virales/química , Proteínas no Estructurales Virales/metabolismo , Replicación Viral , Animales , Dominio Catalítico , Línea Celular , Membrana Celular/química , Virus Chikungunya/química , Virus Chikungunya/genética , Modelos Moleculares , Caperuzas de ARN/química , ARN Viral/biosíntesis , ARN Viral/química , ARN Viral/metabolismo , Proteínas no Estructurales Virales/ultraestructura
17.
PLoS Negl Trop Dis ; 14(12): e0008934, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33347450

RESUMEN

BACKGROUND: Chikungunya virus (CHIKV) is an important emerging and re-emerging public health problem worldwide. In Indonesia, where the virus is endemic, epidemiological information from outside of the main islands of Java and Bali is limited. METHODOLOGY/PRINCIPAL FINDINGS: Four hundred and seventy nine acutely febrile patients presenting between September 2017-2019 were recruited from three city hospitals situated in Ambon, Maluku; Banjarmasin, Kalimantan; and Batam, Batam Island as part of a multi-site observational study. CHIKV RNA was detected in a single serum sample while a separate sample was IgM positive. IgG seroprevalence was also low across all three sites, ranging from 1.4-3.2%. The single RT-PCR positive sample from this study and 24 archived samples collected during other recent outbreaks throughout Indonesia were subjected to complete coding region sequencing to assess the genetic diversity of Indonesian strains. Phylogenetic analysis revealed all to be of a single clade, which was distinct from CHIKV strains recently reported from neighbouring regions including the Philippines and the Pacific Islands. CONCLUSIONS/SIGNIFICANCE: Chikungunya virus strains from recent outbreaks across Indonesia all belong to a single clade. However, low-level seroprevalence and molecular detection of CHIKV across the three study sites appears to contrast with the generally high seroprevalences that have been reported for non-outbreak settings in Java and Bali, and may account for the relative lack of CHIKV epidemiological data from other regions of Indonesia.


Asunto(s)
Fiebre Chikungunya/epidemiología , Virus Chikungunya/inmunología , Brotes de Enfermedades , Adolescente , Adulto , Fiebre Chikungunya/virología , Virus Chikungunya/genética , Niño , Preescolar , Femenino , Humanos , Indonesia/epidemiología , Lactante , Masculino , Persona de Mediana Edad , Filogenia , ARN Viral/genética , Estudios Seroepidemiológicos , Adulto Joven
18.
Viruses ; 12(12)2020 12 16.
Artículo en Inglés | MEDLINE | ID: mdl-33339324

RESUMEN

Baculovirus expression vectors are successfully used for the commercial production of complex (glyco)proteins in eukaryotic cells. The genome engineering of single-copy baculovirus infectious clones (bacmids) in E. coli has been valuable in the study of baculovirus biology, but bacmids are not yet widely applied as expression vectors. An important limitation of first-generation bacmids for large-scale protein production is the rapid loss of gene of interest (GOI) expression. The instability is caused by the mini-F replicon in the bacmid backbone, which is non-essential for baculovirus replication in insect cells, and carries the adjacent GOI in between attTn7 transposition sites. In this paper, we test the hypothesis that relocation of the attTn7 transgene insertion site away from the mini-F replicon prevents deletion of the GOI, thereby resulting in higher and prolonged recombinant protein expression levels. We applied lambda red genome engineering combined with SacB counterselection to generate a series of bacmids with relocated attTn7 sites and tested their performance by comparing the relative expression levels of different GOIs. We conclude that GOI expression from the odv-e56 (pif-5) locus results in higher overall expression levels and is more stable over serial passages compared to the original bacmid. Finally, we evaluated this improved next-generation bacmid during a bioreactor scale-up of Sf9 insect cells in suspension to produce enveloped chikungunya virus-like particles as a model vaccine.


Asunto(s)
Baculoviridae/genética , Genoma Viral , Inestabilidad Genómica , Recombinación Homóloga , Mutagénesis Insercional , Proteínas Recombinantes/genética , Transgenes , Animales , Reactores Biológicos , Línea Celular , Virus Chikungunya/inmunología , Ingeniería Genética , Vectores Genéticos/genética , Insectos , Células Sf9 , Vacunas de Partículas Similares a Virus/inmunología
19.
PLoS One ; 15(12): e0243239, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33332373

RESUMEN

In the last 40 years, Latin America countries, including Brazil, have suffered from the emergence and reemergence of arboviruses, first Dengue (DENV) and recently Zika (ZIKV) and Chikungunya (CHIKV). All three arboviruses are currently endemic in Brazil and have caused major outbreaks in recent years. Rio de Janeiro city, host of the last Summer Olympic Games and the Football World Cup, has been specially affected by them. A surveillance system based on symptomatic reports is in place in Rio, but the true number of affected individuals is unknown due to the great number of Zika, Dengue and Chikungunya asymptomatic cases. Seroprevalence studies are more suitable to evaluate the real number of cases in a given population. We performed a populational seroprevalence survey in Rio, with recruitment of a sample of volunteers of all ages and gender from July to October 2018, within randomly selected census tracts and household. A total of 2,120 volunteers were interviewed and tested with rapid immunochromatographic test for ZIKV, DENV and CHIKV. Individuals with positive results for IgG and/or IgM from only one virus were classified accordingly, while those with test results positive for both ZIKV and DENV were classified as flaviviruses. We corrected for sample design and non-response in data analysis, and calculated point estimate prevalence and 95% confidence intervals for each virus. Arbovirus prevalence in the Rio's population (n = 6,688,927) was estimated at 48.6% [95% CI 44.8-52.4] (n = 3,254,121) for flaviviruses and at 18.0% [95% CI 14.8-21.2] (n = 1,204,765) for CHIKV. Approximately 17.0% [95% CI 14.1-20.1] (n = 1,145,674) of Rio´s population had no contact with any of the three arboviruses. The reported cases of Zika, Dengue and Chikungunya by the current surveillance system in place is insufficient to estimate their real numbers, and our data indicate that Zika seroprevalence could be at least five times and Chikungunya 45 times bigger. The high number of individuals having never been infected by any of the three arboviruses, may indicate a proper scenario for future outbreaks.


Asunto(s)
Fiebre Chikungunya/epidemiología , Dengue/epidemiología , Infección por el Virus Zika/epidemiología , Adolescente , Adulto , Brasil/epidemiología , Virus Chikungunya/aislamiento & purificación , Niño , Preescolar , Estudios Transversales , Virus del Dengue/aislamiento & purificación , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Seroepidemiológicos , Adulto Joven , Virus Zika/aislamiento & purificación
20.
Viruses ; 12(12)2020 12 17.
Artículo en Inglés | MEDLINE | ID: mdl-33348746

RESUMEN

Viral entry is the first stage in the virus replication cycle and, for enveloped viruses, is mediated by virally encoded glycoproteins. Viral glycoproteins have different receptor affinities and triggering mechanisms. We employed vesicular stomatitis virus (VSV), a BSL-2 enveloped virus that can incorporate non-native glycoproteins, to examine the entry efficiencies of diverse viral glycoproteins. To compare the glycoprotein-mediated entry efficiencies of VSV glycoprotein (G), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S), Ebola (EBOV) glycoprotein (GP), Lassa (LASV) GP, and Chikungunya (CHIKV) envelope (E) protein, we produced recombinant VSV (rVSV) viruses that produce the five glycoproteins. The rVSV virions encoded a nano luciferase (NLucP) reporter gene fused to a destabilization domain (PEST), which we used in combination with the live-cell substrate EndurazineTM to monitor viral entry kinetics in real time. Our data indicate that rVSV particles with glycoproteins that require more post-internalization priming typically demonstrate delayed entry in comparison to VSV G. In addition to determining the time required for each virus to complete entry, we also used our system to evaluate viral cell surface receptor preferences, monitor fusion, and elucidate endocytosis mechanisms. This system can be rapidly employed to examine diverse viral glycoproteins and their entry requirements.


Asunto(s)
Expresión Génica , Vectores Genéticos/genética , Glicoproteínas/genética , Virus de la Estomatitis Vesicular Indiana/genética , Proteínas del Envoltorio Viral/genética , Internalización del Virus , Animales , Línea Celular , Virus Chikungunya/genética , Chlorocebus aethiops , Clonación Molecular , Ebolavirus/genética , Orden Génico , Genes Reporteros , Humanos , Virus Lassa/genética , Factores de Tiempo , Células Vero , Replicación Viral
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