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1.
Health Secur ; 18(S1): S14-S22, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32004129

RESUMEN

Global spread of Zika virus in 2015 and 2016 highlighted the importance of surveillance to rapidly detect, report, and respond to emerging infections. We describe the lessons learned from the development and deployment of a web-based surveillance reporting system for Zika virus and other acute febrile illnesses (AFI) in Guangdong and Yunnan provinces, China. In less than 2 months, we customized the China Epidemiologic Dynamic Data Collection (EDDC) platform to collect, manage, and visualize data in close to real time. According to provincial and sentinel hospital staff requirements, the customized platform provided specific user authorization management, online/offline data collection, data quality control, and secure data transmission and protection and visualization tools. AFI case data and laboratory test results were entered through a web-based interface by hospital and provincial-level staff and saved on a China CDC server in Beijing. The dashboard visualized aggregate data by hospital, age, onset date, and laboratory test results. From June 2017 to December 2018, data from 768 patients with AFI were entered into the web-based surveillance system and visualized by hospital and provincial-level decision makers. Input from provincial and hospital staff was essential for developing the AFI case-reporting and feedback tools appropriate for specific settings and decision-making requirements. Web-based systems (eg, EDDC, data collection, and visualization tools that can be easily adapted to meet local surveillance needs) can help shorten time for system deployment, thereby strengthening global health security to rapidly detect and respond to emerging infections and outbreaks.

2.
PLoS One ; 15(1): e0227998, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32004323

RESUMEN

Arboviruses cause diseases of significant global health concerns. Interactions between mosquitoes and their microbiota as well as the important role of this interaction in the mosquito's capacity to harbor and transmit pathogens have emerged as important fields of research. Aedes aegypti is one of the most abundant mosquitoes in many geographic locations, a vector capable of transmitting a number of arboviruses such as dengue and Zika. Currently, there are few studies on the metavirome of this mosquito particularly in the Americas. This study analyzes the metavirome of A. aegypti from Grenada, a Caribbean nation with tropical weather, abundant A. aegypti, and both endemic and arboviral pathogens transmitted by this mosquito. Between January and December 2018, 1152 mosquitoes were collected from six semi-rural locations near houses in St. George Parish, Grenada, by weekly trapping using BG-Sentinel traps. From these, 300 A. aegypti were selected for analysis. The metavirome was analyzed using the Illumina HiSeq 1500 for deep sequencing. The generation sequencing library construction protocol used was NuGEN Universal RNA with an average read length of 125 bp. Reads were mapped to the A. aegypti assembly. Non-mosquito reads were analyzed using the tools FastViromeExplorer. The NCBI total virus, RNA virus, and eukaryotic virus databases were used as references. The metagenomic comparison analysis showed that the most abundant virus-related reads among all databases and assemblies was Phasi Charoen-like virus. The Phasi Charoen-like virus results are in agreement to other studies in America, Asia and Australia. Further studies using wild-caught mosquitoes is needed to assess the impact of this insect-specific virus on the A. aegypti lifecycle and vector capacity.

3.
PLoS One ; 15(2): e0220753, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32027652

RESUMEN

BACKGROUND: Three arthropod-borne viruses (arboviruses) causing human disease have been the focus of a large number of studies in the Americas since 2013 due to their global spread and epidemiological impacts: Zika, dengue, and chikungunya viruses. A large proportion of infections by these viruses are asymptomatic. However, all three viruses are associated with moderate to severe health consequences in a small proportion of cases. Two mosquito species, Aedes aegypti and Aedes albopictus, are among the world's most prominent arboviral vectors, and are known vectors for all three viruses in the Americas. OBJECTIVES: This review summarizes the state of the entomological literature surrounding the mosquito vectors of Zika, dengue and chikungunya viruses and factors affecting virus transmission. The rationale of the review was to identify and characterize entomological studies that have been conducted in the Americas since the introduction of chikungunya virus in 2013, encompassing a period of arbovirus co-circulation, and guide future research based on identified knowledge gaps. METHODS: The preliminary search for this review was conducted on PubMed (National Library of Health, Bethesda, MD, United States). The search included the terms 'zika' OR 'dengue' OR 'chikungunya' AND 'vector' OR 'Aedes aegypti' OR 'Aedes albopictus'. The search was conducted on March 1st of 2018, and included all studies since January 1st of 2013. RESULTS: A total of 96 studies were included in the scoping review after initial screening and subsequent exclusion of out-of-scope studies, secondary data publications, and studies unavailable in English language. KEY FINDINGS: We observed a steady increase in number of publications, from 2013 to 2018, with half of all studies published from January 2017 to March 2018. Interestingly, information on Zika virus vector species composition was abundant, but sparse on Zika virus transmission dynamics. Few studies examined natural infection rates of Zika virus, vertical transmission, or co-infection with other viruses. This is in contrast to the wealth of research available on natural infection and co-infection for dengue and chikungunya viruses, although vertical transmission research was sparse for all three viruses.

4.
PLoS Pathog ; 16(2): e1008102, 2020 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-32027727

RESUMEN

Understanding the circumstances under which arboviruses emerge is critical for the development of targeted control and prevention strategies. This is highlighted by the emergence of chikungunya and Zika viruses in the New World. However, to comprehensively understand the ways in which viruses emerge and persist, factors influencing reductions in virus activity must also be understood. Western equine encephalitis virus (WEEV), which declined during the late 20th century in apparent enzootic circulation as well as equine and human disease incidence, provides a unique case study on how reductions in virus activity can be understood by studying evolutionary trends and mechanisms. Previously, we showed using phylogenetics that during this period of decline, six amino acid residues appeared to be positively selected. To assess more directly the effect of these mutations, we utilized reverse genetics and competition fitness assays in the enzootic host and vector (house sparrows and Culex tarsalis mosquitoes). We observed that the mutations contemporary with reductions in WEEV circulation and disease that were non-conserved with respect to amino acid properties had a positive effect on enzootic fitness. We also assessed the effects of these mutations on virulence in the Syrian-Golden hamster model in relation to a general trend of increased virulence in older isolates. However, no change effect on virulence was observed based on these mutations. Thus, while WEEV apparently underwent positive selection for infection of enzootic hosts, residues associated with mammalian virulence were likely eliminated from the population by genetic drift or negative selection. These findings suggest that ecologic factors rather than fitness for natural transmission likely caused decreased levels of enzootic WEEV circulation during the late 20th century.

5.
PLoS Negl Trop Dis ; 14(2): e0008027, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32049958

RESUMEN

Zika virus (ZIKV) has spread in many countries or territories causing severe neurologic complications with potential fatal outcomes. The small primate common marmosets are susceptible to ZIKV, mimicking key features of human infection. Here, a novel simian adenovirus type 23 vector-based vaccine expressing ZIKV pre-membrane-envelope proteins (Sad23L-prM-E) was produced in high infectious titer. Due to determination of immunogenicity in mice, a single-dose of 3×108 PFU Sad23L-prM-E vaccine was intramuscularly inoculated to marmosets. This vaccine raised antibody titers of 104.07 E-specific and 103.13 neutralizing antibody (NAb), as well as robust specific IFN-γ secreting T-cell response (1,219 SFCs/106 cells) to E peptides. The vaccinated marmosets, upon challenge with a high dose of ZIKV (105 PFU) six weeks post prime immunization, reduced viremia by more than 100 folds, and the low level of detectable viral RNA (<103 copies/ml) in blood, saliva, urine and feces was promptly eliminated when the secondary NAb (titer >103.66) and T-cell response (>726 SFCs/106 PBMCs) were acquired 1-2 weeks post exposure to ZIKV, while non-vaccinated control marmosets developed long-term high titer of ZIKV (105.73 copies/ml) (P<0.05). No significant pathological lesions were observed in marmoset tissues. Sad23L-prM-E vaccine was detectable in spleen, liver and PBMCs at least 4 months post challenge. In conclusion, a prime immunization with Sad23L-prM-E vaccine was able to protect marmosets against ZIKV infection when exposed to a high dose of ZIKV. This Sad23L-prM-E vaccine is a promising vaccine candidate for prevention of ZIKV infection in humans.

6.
8.
BMC Res Notes ; 13(1): 67, 2020 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-32041646

RESUMEN

OBJECTIVE: To evaluate the frequency of infection caused by the Oropouche virus (OROV) in 496 patients with acute febrile disease (AFI), whose samples were obtained for the analysis of endemic arboviruses in a previous investigation carried out in 2016. RESULTS: OROV was detected in 26.4% (131/496) of serum samples from patients with AFI. Co-infections with Dengue virus (7.3%), Zika virus (1.8%) and Chikungunya (0.2%) were observed. The most common clinical symptoms reported among the patients with OROV infections were headache 85.5% (112/131), myalgia 80.9% (106/131), arthralgia 72.5% (95/131) and loss of appetite 67.9% (89/131). Headache and myalgia were predominant in all age groups. Both OROV infections and co-infections were more frequent in May, June and July corresponding to the dry season of the region.

9.
Artículo en Inglés | MEDLINE | ID: mdl-32053906

RESUMEN

Land use boundaries represent human-physical interfaces where risk of vector-borne disease transmission is elevated. Land development practices, coupled with rural and urban land fragmentation, increases the likelihood that immunologically naïve humans will encounter infectious vectors at land use interfaces. This research consolidated land use classes from the GLC-SHARE dataset; calculated landscape metrics in linear (edge) density, proportion abundance, and patch density; and derived the incidence rate ratios of the Zika virus occurrence in Colombia, South America during 2016. Negative binomial regression was used to evaluate vector-borne disease occurrence counts in relation to Population Density, Average Elevation, Per Capita Gross Domestic Product, and each of three landscape metrics. Each kilometer of border length per square kilometer of area increase in the linear density of the Cropland and Grassland classes is associated with an increase in Zika virus risk. These spatial associations inform a risk reduction approach to rural and urban morphology and land development that emphasizes simple and compact land use geometry that decreases habitat availability for mosquito vectors of Zika virus.

10.
J Insect Physiol ; 121: 104019, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32032591

RESUMEN

Aedes aegypti is the primary vector of several arboviruses that impact human health including the dengue, Zika, and yellow fever viruses. The potential of Ae. aegypti females to transmit viruses is enhanced by mating-induced behavioral and physiological changes that increase female host-seeking behaviors, blood-feeding frequency and longevity. The mating-induced changes are due to female receipt of male seminal fluid proteins (SFPs) during copulation. SFPs also inhibit female re-mating-re-mating incidence is significantly reduced in the initial hours after mating and nearly absent after 24 h. Males, however, are not limited in the number of females they can inseminate and are able to mate with multiple females in succession. As successive mating depletes SFPs, we examined parameters of fertility and re-mating incidence in females after mating with recently mated males. Males of two Ae. aegypti strains (Colombian and Thai) were mated five consecutive times and fecundity, resulting larvae and hatch percentage in each female of the mating sequence was assessed. In both strains, we found that males can mate three times in succession without impacting fertility in their mates. However, significant declines in fecundity, resulting larvae, and hatch percentage were observed after a third mating. Male size influenced female fecundity and fertility as mates of small males showed further reductions compared to mates of big males after mating consecutively. Seven days after the consecutive mating assays, the re-mating rate of females mated fifth in succession was significantly increased (Colombian strain: 33%; Thai strain: 48%) compared to females mated first (0% in both strains). Re-mating incidence was further increased in small, Thai strain males where 82% of fifth mated females re-mated compared to 0% of first mated females. Finally, we show that regardless of male size, mates of experimental males were similarly fertile to mates of control males when mated for a sixth time 48 h after the consecutive mating assays, showing that males recover fertility after 2 d. Our results show that male sexual history influences fertility and re-mating incidence of Ae. aegypti females.

11.
Virology ; 543: 1-6, 2020 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-32056841

RESUMEN

Arboviruses are an emerging threat to public health. Arbovirus transmission to vertebrates hinges on dissemination from the arthropod gastrointestinal tract, and ultimately infection of the arthropod salivary glands. Therefore, salivary gland immunity impacts arbovirus transmission; however, these immune responses are poorly understood. Here, we describe the utility of Drosophila melanogaster as a salivary gland infection model. First, we describe the use of a salivary gland-specific driver to launch RNA interference or virus replicon transgenes. Next, we infect flies with an arbovirus panel and find multiple viruses that infect Drosophila salivary glands, albeit inefficiently. We find that this infection is not controlled by antiviral RNA silencing; thus, we silence a panel of immune genes in the salivary glands, but do not observe changes in infection. These data suggest that Drosophila may be used to study salivary gland infection, and that there are likely unexplored pathways controlling infection of this tissue.

12.
Virology ; 543: 34-42, 2020 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-32056845

RESUMEN

Zika Virus (ZIKV) is a Flavivirus transmitted primarily via the bite of infected Aedes aegypti mosquitoes. Globally, 87 countries and territories have recorded autochthonous mosquito-borne transmission of ZIKV as at July 2019 and distributed across four of the six WHO Regions. Outbreaks of ZIKV infection peaked in 2016 and declined substantially throughout 2017 and 2018 in the Americas region. There is the likely risk for ZIKV to spread to more countries. There is also the potential for the re-emergence of ZIKV in all places with prior reports of the virus transmission. The current status of ZIKV transmission and spread is, however, a global health threat, and from the aforementioned, has the potential to re-emerge as an epidemic. This review summarizes the past and present spread of ZIKV outbreak-2007-2019, the genome, transmission cycle, clinical manifestations, vaccine and antiviral drug advancement.

13.
Int J Infect Dis ; 2020 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-32062059

RESUMEN

Toscana virus (TOSV) is a common cause of meningitis in Mediterranean area. However, rare publications reported extra-meningeal signs. We report the third case of testicular pain associated with TOSV meningitis despite there is no evidence of semen involvement in other well-known arboviruses, excepted in Zika virus.

14.
Sci Adv ; 6(5): eaaw7449, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32064329

RESUMEN

Disease epidemics and outbreaks often generate conspiracy theories and misperceptions that mislead people about the risks they face and how best to protect themselves. We investigate the effectiveness of interventions aimed at combating false and unsupported information about the Zika epidemic and subsequent yellow fever outbreak in Brazil. Results from a nationally representative survey show that conspiracy theories and other misperceptions about Zika are widely believed. Moreover, results from three preregistered survey experiments suggest that efforts to counter misperceptions about diseases during epidemics and outbreaks may not always be effective. We find that corrective information not only fails to reduce targeted Zika misperceptions but also reduces the accuracy of other beliefs about the disease. In addition, although corrective information about the better-known threat from yellow fever was more effective, none of these corrections affected support for vector control policies or intentions to engage in preventive behavior.

15.
Sci Adv ; 6(5): eaax9318, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32064341

RESUMEN

Viral infections kill millions of people and new antivirals are needed. Nontoxic drugs that irreversibly inhibit viruses (virucidal) are postulated to be ideal. Unfortunately, all virucidal molecules described to date are cytotoxic. We recently developed nontoxic, broad-spectrum virucidal gold nanoparticles. Here, we develop further the concept and describe cyclodextrins, modified with mercaptoundecane sulfonic acids, to mimic heparan sulfates and to provide the key nontoxic virucidal action. We show that the resulting macromolecules are broad-spectrum, biocompatible, and virucidal at micromolar concentrations in vitro against many viruses [including herpes simplex virus (HSV), respiratory syncytial virus (RSV), dengue virus, and Zika virus]. They are effective ex vivo against both laboratory and clinical strains of RSV and HSV-2 in respiratory and vaginal tissue culture models, respectively. Additionally, they are effective when administrated in mice before intravaginal HSV-2 inoculation. Lastly, they pass a mutation resistance test that the currently available anti-HSV drug (acyclovir) fails.

16.
Int J Dev Neurosci ; 2020 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-32065434

RESUMEN

OBJECTIVE: to characterize the spectrum of brain damages presented in children affected by Congenital Zika Syndrome (CZS), verify the existence of a co-occurrence pattern of these damages and discuss possible implications for the neuropsychological development. METHODS: descriptive, quantitative, individualized and cross-sectional study using secondary sources. We selected 136 children with CZS from the database of the Center of Strategic Information on Health Vigilance of the Municipal Office of Salvador, Brazil. We conducted descriptive and multiple correspondence analyses. RESULTS: Among the set of analyzed variables, microcephaly (51.5%), ventriculomegaly (57.4%) and brain calcifications (77.2%) were identified as the most frequent. The multiple correspondence analysis showed that the combination of these three variables (32.4%) was what better represented the spectrum of brain damages in the Central Nervous System. INTERPRETATION: Damage in the sensory-motor, cognitive and language development, as well as neurodevelopmental disorders, are described in the literature as impairments associated, either isolated or combined, with these damages, and it is worth highlighting that, in combined brain damages, impairments tend to be more severe. The findings of this study may contribute to understanding the repercussions of CZS on the neuropsychological development of children affected by the epidemic.

17.
Epilepsia ; 2020 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-32065676

RESUMEN

OBJECTIVE: To estimate the incidence of epilepsy in children with Zika-related microcephaly in the first 24 months of life; to characterize the associated clinical and electrographic findings; and to summarize the treatment responses. METHODS: We followed a cohort of children, born during the 2015-2016 Zika virus (ZIKV) epidemic in Brazil, with congenital microcephaly and evidence of congenital ZIKV infection on neuroimaging and/or laboratory testing. Neurological assessments were performed at ≤3, 6, 12, 15, 18, 21, and 24 months of life. Serial electroencephalograms were performed over the first 24 months. RESULTS: We evaluated 91 children, of whom 48 were female. In this study sample, the cumulative incidence of epilepsy was 71.4% in the first 24 months, and the main type of seizure was infantile spasms (83.1%). The highest incidence of seizures occurred between 3 and 9 months of age, and the risk remained high until 15 months of age. The incidence of infantile spasms peaked between 4 and 7 months and was followed by an increased incidence of focal epilepsy cases after 12 months of age. Neuroimaging results were available for all children, and 100% were abnormal. Cortical abnormalities were identified in 78.4% of the 74 children evaluated by computed tomography and 100% of the 53 children evaluated by magnetic resonance imaging. Overall, only 46.1% of the 65 children with epilepsy responded to treatment. The most commonly used medication was sodium valproate with or without benzodiazepines, levetiracetam, phenobarbital, and vigabatrin. SIGNIFICANCE: Zika-related microcephaly was associated with high risk of early epilepsy. Seizures typically began after the third month of life, usually as infantile spasms, with atypical electroencephalographic abnormalities. The seizure control rate was low. The onset of seizures in the second year was less frequent and, when it occurred, presented as focal epilepsy.

18.
Virology ; 541: 124-135, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32056710

RESUMEN

Zika virus (ZIKV) nonstructural protein 5 (NS5) is a multifunctional protein possessing methyltransferase and RNA-dependent RNA polymerase activities. In the present study, we have carried out an extensive mutagenesis analysis to determine the importance of nuclear localization sequences (NLS) of NS5 in its nuclear accumulation and ZIKV replication. Deletion mutagenesis analysis demonstrated that the bipartite NLS consisting of importin ß1 (ßNLS) and importin α/ß-recognized NLS (α/ßNLS) is required for NS5 nuclear accumulation. Deletion of ßNLS, α/ßNLS, or both as well as R393A and R393N mutations severely impaired NS5 nuclear import and consequently conferred NS5 degradation. The R393A and R393N mutations also ablated viral RNA replication and virus production. Treatment of ZIKV-infected cells with importin α/ß-NS5 interaction inhibitors ivermectin or 4-HPR resulted in a rapid degradation of NS5 similar to the R393 A/N mutations. Collectively, these findings suggest that NS5 nuclear accumulation protects NS5 from cytoplasmic degradation and therefore is required for viral RNA replication.

19.
Virology ; 541: 52-62, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32056715

RESUMEN

Zika virus (ZIKV) nonstructural protein 5 (NS5) plays a critical role in viral RNA replication and mediates key virus-host cell interactions. As with other flavivirus NS5 proteins, ZIKV NS5 is primarily found in the nucleus. We previously reported that the NS5 protein of dengue virus, another flavivirus, localized to centrosomes during cell division. Here we show that ZIKV NS5 also relocalizes from the nucleus to centrosomes during mitosis. In infected cells with supernumerary centrosomes, NS5 was present at all centrosomes. Transient expression of NS5 in uninfected cells confirmed that centrosomal localization was independent of other viral proteins. Live-cell imaging demonstrated that NS5-GFP accumulated at centrosomes shortly after break down of nuclear membrane and remained there through mitosis. Cells expressing NS5-GFP took longer to complete mitosis than control cells. Finally, an analysis of ZIKV NS5 binding partners revealed several centrosomal proteins, providing potential direct links between NS5 and centrosomes.

20.
PLoS Negl Trop Dis ; 14(2): e0008034, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32017766

RESUMEN

BACKGROUND: Zika virus has recently spread to South- and Central America, causing congenital birth defects and neurological complications. Many people at risk are flavivirus pre-immune due to prior infections with other flaviviruses (e.g. dengue virus) or flavivirus vaccinations. Since pre-existing cross-reactive immunity can potentially modulate antibody responses to Zika virus infection and may affect the outcome of disease, we analyzed fine-specificity as well as virus-neutralizing and infection-enhancing activities of antibodies induced by a primary Zika virus infection in flavivirus-naïve as well as yellow fever- and/or tick-borne encephalitis-vaccinated individuals. METHODOLOGY: Antibodies in sera from convalescent Zika patients with and without vaccine-induced immunity were assessed by ELISA with respect to Zika virus-specificity and flavivirus cross-reactivity. Functional analyses included virus neutralization and infection-enhancement. The contribution of IgM and cross-reactive antibodies to these properties was determined by depletion experiments. PRINCIPAL FINDINGS: Pre-existing flavivirus immunity had a strong influence on the antibody response in primary Zika virus infections, resulting in higher titers of broadly flavivirus cross-reactive antibodies and slightly lower levels of Zika virus-specific IgM. Antibody-dependent enhancement (ADE) of Zika virus was mediated by sub-neutralizing concentrations of specific IgG but not by cross-reactive antibodies. This effect was potently counteracted by the presence of neutralizing IgM. Broadly cross-reactive antibodies were able to both neutralize and enhance infection of dengue virus but not Zika virus, indicating a different exposure of conserved sequence elements in the two viruses. CONCLUSIONS: Our data point to an important role of flavivirus-specific IgM during the transient early stages of infection, by contributing substantially to neutralization and by counteracting ADE. In addition, our results highlight structural differences between strains of Zika and dengue viruses that are used for analyzing infection-enhancement by cross-reactive antibodies. These findings underscore the possible impact of specific antibody patterns on flavivirus disease and vaccination efficacy.

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