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1.
Sci Total Environ ; 700: 134443, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31655455

RESUMO

Worldwide, billions of people are at risk from viruses, parasites and bacteria transmitted by mosquitoes, ticks, fleas and other vectors. Over exploitation of chemical pesticides to overcome the mosquito borne diseases led to detrimental effects on environment and human health. The present research aims to explore bio-fabrication of metal silver nanomaterials using Rhazya stricta extract against deadly mosquito vectors and microbial pathogens. The phytochemical profile of the R. stricta extracts was studied by HPLC-MS and 1H NMR. Further, confirmation of the bio-fabricated silver nanoparticles (AgNPs) was carried out by UV-vis spectroscopy and characterization through FTIR, TEM, EDX, and XRD analyses. The R. stricta-fabricated AgNPs showed acute toxicity on key mosquito vectors from two different country (India and Kingdom of Saudi Arabia, KSA) strains, notably, with LC50 values of 10.57, 11.89 and 12.78 µg/ml on malarial, dengue and filarial key Indian strains of mosquito vectors, respectively, and 30.66 and 38.39 µg/ml on KSA strains of Aedes aegypti and Culex pipiens, respectively. In mosquito adulticidal activity, R. stricta extract alone exhibited LC50 values ranging from 304.34 to 382.45 µg/ml against Indian strains and from 738.733 to 886.886 against Saudi Arabian strains, while AgNPs LC50 boosted from 9.52 to 12.16 µg/ml and from 30.66 to 38.39 µg/ml, respectively. Moreover, it was noticed that at low concentration the tested AgNPs showed high growth retardation of important pathogenic bacteria such as Bacillus subtilis, Klebsiella pneumoniae and Salmonella typhi with inhibition zone diameters from 11.86 to 22.92 mm. In conclusion, the present study highlighted that R. stricta-fabricated AgNPs could be a lead material for the management of mosquito vector and microbial pathogens control.

2.
Pac Symp Biocomput ; 25: 487-498, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31797621

RESUMO

Flaviviruses such as dengue encode a protease that is essential for viral replication. The protease functions by cleaving well-conserved positions in the viral polyprotein. In addition to the viral polyprotein, the dengue protease cleaves at least one host protein involved in immune response. This raises the question, what other host proteins are targeted and cleaved? Here we present a new computational method for identifying putative host protein targets of the dengue virus protease. Our method relies on biochemical and secondary structure features at the known cleavage sites in the viral polyprotein in a two-stage classification process to identify putative cleavage targets. The accuracy of our predictions scaled inversely with evolutionary distance when we applied it to the known cleavage sites of several other flaviviruses-a good indication of the validity of our predictions. Ultimately, our classifier identified 257 human protein sites possessing both a similar target motif and accessible local structure. These proteins are promising candidates for further investigation. As the number of viral sequences expands, our method could be adopted to predict host targets of other flaviviruses.

3.
J Environ Manage ; 253: 109748, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31678687

RESUMO

On November 2015, the Fundão Tailings Dam, located at Mariana municipality in Brazil, failed. Besides the deaths and injuries, economic losses, pollution and health problems associated to heavy metals in the water, Brazilian municipalities near the accident experienced an increase in the incidence of dengue. Since dengue fever is an insect-borne disease and the mosquito develops where there is stored water, there must be a relationship between the dam accident and the incidence of the disease. The purpose of this study is to test whether there is a causal relationship between the dam accident in Mariana and the number of dengue cases, number of hospitalizations due to dengue, and dengue outbreak in the municipalities affected by the accident. We find evidence that the accident had a positive and statistically significant impact on dengue indicators (for example, the probability of a dengue outbreak increased in 19%), what makes us call attention to another negative externality of tailings dam accidents.


Assuntos
Dengue , Acidentes , Animais , Brasil , Cidades , Incidência
4.
Acta Trop ; 201: 105201, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31562846

RESUMO

Zika virus (ZIKV) is a mosquito-borne flavivirus that has caused recent large outbreaks in the Americas. Given its association with severe congenital defects including microcephaly, distinguishing infections caused by ZIKV from those caused by dengue virus (DENV) is of primordial importance. The objectives of this study were to evaluate the recombinant proteins rEIII-ZIKV (Envelope protein domain III) and rNS1ß-leader-ZIKV (non-structural protein 1) for the serological diagnosis of ZIKV in the Mexican population. We also evaluated potential cross-reactivity in commercial enzyme-linked immunosorbent assays (ELISA) based on the ZIKV NS1 and DENV NS1 proteins. rEIII-ZIKV and rNS1ß-leader-ZIKV proteins were tested with sera from 30 PCR-confirmed ZIKV cases, 50 ZIKV-naive, DENV-exposed subjects with no acute febrile disease, (asymptomatic subjects, AS), and 50 ZIKV-naive and DENV naive AS. Commercial ELISA tests were evaluated with sera from 57 ZIKV and 20 DENV PCR-confirmed cases, and 50 ZIKV-naive, DENV-exposed AS. In-house ELISA assays showed that IgM antibody levels against rEIII-ZIKV and rNS1ß-ZIKV were higher in ZIKV naive, DENV-exposed AS than in acutely infected ZIKV individuals. IgG reactivity was highest for rEIII-ZIKV, and indistinguishable between acutely infected ZIKV cases and DENV exposed AS. Positivity for the Euroimmun Zika IgM assay at 7-10 days was considerably higher in DENV-naive ZIKV patients (86%) than in DENV-exposed ZIKV patients (33%), while 39% of the latter had false-negative anti-ZIKV IgG before 7 days of onset. DENV-exposed ZIKV patients presented lower anti-ZIKV IgM and higher IgG responses similar to a secondary dengue response. Forty-four percent of DENV- exposed acute ZIKV patients were DENV IgM positive with the Panbio Dengue assay, and two (15%) of the DENV-naive ZIKV patients presented false DENV IgG conversion. Given the extensive cross-reactivity to both the NS1 and EDIII proteins in current serological methods, the development of sensitive and specific serological tests to distinguish ZIKV from DENV infections is an urgent priority.

5.
Dev Comp Immunol ; 103: 103514, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31585195

RESUMO

One of the defining features of mosquito vectors of arboviruses such as Dengue and Zika is their ability to tolerate high levels of virus proliferation without suffering significant pathology. This adaptation is central to vector competence and disease spread. The molecular mechanisms, pathways, cellular and metabolic adaptations responsible for mosquito disease tolerance are still largely unknown and may represent effective ways to control mosquito populations and prevent arboviral diseases. In this review article, we describe the key link between disease tolerance and pathogen transmission, and how vector control methods may benefit by focusing efforts on dissecting the mechanisms underlying mosquito tolerance of arboviral infections. We briefly review recent work investigating tolerance mechanisms in other insects, describe the state of the art regarding the mechanisms of disease tolerance in mosquitos, and highlight the emerging role of gut microbiota in mosquito immunity and disease tolerance.

6.
J Theor Biol ; 484: 110014, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31557473

RESUMO

Superinfection exclusion is a phenomenon whereby the co-infection of a host with a secondary pathogen is prevented due to a current infection by another closely-related pathogenic strain. We construct a novel vector-host mathematical model for two pathogens that exhibit superinfection exclusion and simultaneously account for vaccination strategies against them. We then derive the conditions under which an endemic disease will prevent the establishment of another through the action of superinfection exclusion and show that vaccination against the endemic strain can enable the previously suppressed strain to invade the population. Through appropriate parameterisation of the model for dengue and yellow fever we find that superinfection exclusion alone is unlikely to explain the absence of yellow fever in many regions where dengue is endemic, and that the rollout of the recently licensed dengue vaccine, Dengvaxia, is unlikely to enable the establishment of Yellow Fever in regions where it has previously been absent.

7.
J Virol Methods ; : 113793, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31794781

RESUMO

Dengue fever is a highly endemic arthropod-borne viral disease in the tropical and sub-tropical countries and is rapidly becoming a global threaten. Diagnosis has been conducted by either traditional serological methods or molecular biological techniques. However, these methods are either labor-intensive, time-consuming or with multiple steps, which are not suitable for high throughput detection of large quantity of samples. In the current study, a novel, rapid, no-wash one-step amplified luminescent proximity homogenous assay-linked immunosorbent assay (AlphaLISA) was developed and optimized for the diagnosis of dengue fever through the detection of dengue virus non-structural protein 1 (NS1). The linear range of the assay was determined to be 60,000 pg/mL to 200 pg/mL, with a lower detection limit of 127.45 pg/mL for NS1 protein. The precision of the assay was 8.24% and 4.93% for the high and low concentration. Clinical evaluation indicated that the sensitivity and specificity of the assay was 91.49% and 81.54%, respectively. This novel, rapid, no-wash one-step AlphaLISA assay is convenient and sensitive, which could be a good alternative for the screening of dengue fever in a high throughput format.

8.
PLoS Negl Trop Dis ; 13(12): e0007883, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31790395

RESUMO

BACKGROUND: Symbiotic bacteria are pervasive in mosquitoes and their presence can influence many host phenotypes that affect vectoral capacity. While it is evident that environmental and host genetic factors contribute in shaping the microbiome of mosquitoes, we have a poor understanding regarding how bacterial genetics affects colonization of the mosquito gut. The CRISPR/Cas9 gene editing system is a powerful tool to alter bacterial genomes facilitating investigations into host-microbe interactions but has yet to be applied to insect symbionts. METHODOLOGY/PRINCIPAL FINDINGS: To investigate the role of bacterial genetic factors in mosquito biology and in colonization of mosquitoes we used CRISPR/Cas9 gene editing system to mutate the outer membrane protein A (ompA) gene of a Cedecea neteri symbiont isolated from Aedes mosquitoes. The ompA mutant had an impaired ability to form biofilms and poorly infected Ae. aegypti when reared in a mono-association under gnotobiotic conditions. In adult mosquitoes, the mutant had a significantly reduced infection prevalence compared to the wild type or complement strains, while no differences in prevalence were seen in larvae, suggesting genetic factors are particularly important for adult gut colonization. We also used the CRISPR/Cas9 system to integrate genes (antibiotic resistance and fluorescent markers) into the symbionts genome and demonstrated that these genes were functional in vitro and in vivo. CONCLUSIONS/SIGNIFICANCE: Our results shed insights into the role of ompA gene in host-microbe interactions in Ae. aegypti and confirm that CRISPR/Cas9 gene editing can be employed for genetic manipulation of non-model gut microbes. The ability to use this technology for site-specific integration of genes into the symbiont will facilitate the development of paratransgenic control strategies to interfere with arboviral pathogens such Chikungunya, dengue, Zika and Yellow fever viruses transmitted by Aedes mosquitoes.

9.
PLoS Negl Trop Dis ; 13(12): e0007919, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31790401

RESUMO

Current knowledge of the piRNA pathway is based mainly on studies on Drosophila melanogaster where three proteins of the Piwi subclade of the Argonaute family interact with PIWI-interacting RNAs to silence transposable elements in gonadal tissues. In mosquito species that transmit epidemic arboviruses such as dengue and chikungunya viruses, Piwi clade genes underwent expansion, are also expressed in the soma and cross-talk with proteins of recognized antiviral function cannot be excluded for some Piwi proteins. These observations underscore the importance of expanding our knowledge of the piRNA pathway beyond the model organism D. melanogaster. Here we focus on the emerging arboviral vector Aedes albopictus and we couple traditional approaches of expression and adaptive evolution analyses with most current computational predictions of protein structure to study evolutionary divergence among Piwi clade proteins. Superposition of protein homology models indicate possible high structure similarity among all Piwi proteins, with high levels of amino acid conservation in the inner regions devoted to RNA binding. On the contrary, solvent-exposed surfaces showed low conservation, with several sites under positive selection. Analysis of the expression profiles of Piwi transcripts during mosquito development and following infection with Dengue serotype 1 or Chikungunya viruses showed a concerted elicitation of all Piwi transcripts during viral dissemination of dengue viruses while maintenance of infection relied on expression of primarily Piwi5. Opposite, establishment of persistent infection by Chikungunya virus is accompanied by increased expression of all Piwi genes, particularly Piwi4 and, again, Piwi5. Overall these results are consistent with functional specialization and a general antiviral role for Piwi5. Experimental evidences of sites under positive selection in Piwi1-3, Piwi4 and Piwi6, that have complex expression profiles, provide useful knowledge to design tailored functional experiments.

10.
PLoS Pathog ; 15(12): e1008218, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31790509

RESUMO

Dengue virus (DENV) transmission by mosquitoes is a time-dependent process that begins with the consumption of an infectious blood-meal. DENV infection then proceeds stepwise through the mosquito from the midgut to the carcass, and ultimately to the salivary glands, where it is secreted into saliva and then transmitted anew on a subsequent bite. We examined viral kinetics in tissues of the Aedes aegypti mosquito over a finely graded time course, and as per previous studies, found that initial viral dose and serotype strain diversity control infectivity. We also found that a threshold level of virus is required to establish body-wide infections and that replication kinetics in the early and intermediate tissues do not predict those of the salivary glands. Our findings have implications for mosquito GMO design, modeling the contribution of transmission to vector competence and the role of mosquito kinetics in the overall DENV epidemiological landscape.

11.
PLoS One ; 14(12): e0225193, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31800583

RESUMO

With approximately half of the world's population at risk of contracting dengue, this mosquito-borne disease is of global concern. International travellers significantly contribute to dengue's rapid and large-scale spread by importing the disease from endemic into non-endemic countries. To prevent future outbreaks and dengue from establishing in non-endemic countries, knowledge about the arrival time and location of infected travellers is crucial. We propose a network model that predicts the monthly number of dengue-infected air passengers arriving at any given airport. We consider international air travel volumes to construct weighted networks, representing passenger flows between airports. We further calculate the probability of passengers, who travel through the international air transport network, being infected with dengue. The probability of being infected depends on the destination, duration and timing of travel. Our findings shed light onto dengue importation routes and reveal country-specific reporting rates that have been until now largely unknown. This paper provides important new knowledge about the spreading dynamics of dengue that is highly beneficial for public health authorities to strategically allocate the often limited resources to more efficiently prevent the spread of dengue.

12.
J Med Entomol ; 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31799614

RESUMO

Aedes aegypti (Linnaeus), the primary vectors of the arboviruses dengue virus and Zika virus, continue to expand their global distributions. In efforts to better control such species, several mosquito control programs are investigating the efficacy of rearing and releasing millions of altered male Aedes throughout landscapes to reduce populations and disease transmission risk. Unfortunately, little is known about Ae. aegypti, especially male, dispersal behaviors within urban habitats. We deployed Sound-producing Gravid Aedes Traps (SGATs) in Cairns, northern Australia, to investigate male Ae. aegypti attraction to various oviposition container configurations. The traps were arranged to include: 1) water only, 2) organically infused water, 3) infused water and L3 larvae, 4) infused water and a human-scented lure, and lastly 5) no water or olfactory attractant (dry). Our data suggest that males were more attracted to SGATs representing active larval sites than potential larval sites, but were equally attracted to dry SGATs relative to those containing water and/or infusion. Additionally, we found that female Ae. aegypti were equally attracted to wet SGATs, with or without infusion, but not dry ones. These results suggest that male Ae. aegypti within northern Australia are more attracted to active larval sites and equally attracted to dry containers as wet or infused ones. Additionally, female Ae. aegypti are unlikely to enter dry containers. Such findings contribute to our understanding of potentially attractive features for local and released Ae. aegypti throughout the northern Australian urban landscape.

13.
An. Fac. Cienc. Méd. (Asunción) ; 52(3): 97-100, 20191201.
Artigo em Espanhol | LILACS-Express | ID: biblio-1026777

RESUMO

El Dengue es una infección por arbovirus, con baja incidencia de asociación con síntomas neurológicos. Las presentaciones incluyen encefalopatía, síndrome de Guillain-Barré (SGB), debilidad motora aguda, convulsiones, entre otras (1). En el 2018, en Paraguay, se registraron un total de 33.258 casos compatibles con dengue (9), pero no existen datos estadísticos de afectación neurológica. Por lo que consideramos reconocer esta afectación, como marcador de gravedad de la enfermedad. Se relaciona con alta tasa de mortalidad y/o secuelas. A continuación, tres casos masculinos con este padecimiento, de los cuales, recibieron Inmunoglulina con recuperación total en dos de los tres casos, por lo que es muy importante establecer el tratamiento de forma oportuna.


Dengue is an arbovirus infection, with a low incidence of association with neurological symptoms. Presentations include encephalopathy, Guillain-Barré syndrome (GBS), acute motor weakness, seizures, among others (1). In 2018, in Paraguay, a total of 33,258 cases consistent with dengue (9) were registered, but there are no statistical data on involvement neurological. For what, we consider to recognize this affectation, as a marker of severity of the disease. It is related to high mortality rate and / or sequelae. Then, three male cases with this condition, of which, they received Immunoglulin with total recovery in two of the three cases. It is very important to establish the treatment in a timely manner.

14.
Infectio ; 23(4): 352-356, Dec. 2019. tab, graf
Artigo em Espanhol | LILACS-Express | ID: biblio-1040005

RESUMO

Resumen Objetivo: describir la distribución espacial y temporal de los virus del dengue, zika y Chikungunya en Colombia e identificar si existe agregación espacial, temporal y espacio-temporal. Métodos: se desarrolló un estudio descriptivo de la distribución espacial y temporal de los virus del Dengue (2006-2017), Zika (2015-2017) y Chikungunya (2014-2017) en Colombia, utilizando los principios de la estadística espacial, específicamente en el análisis exploratorio de datos espaciales. Resultados: se identificaron zonas de Colombia donde se presenta una mayor densidad y prevalencia de casos. A partir de los 1124 municipios analizados para cada evento (casos de Dengue, Zika y Chikungunya), se comprobó con significancia estadística (p<0.05) la existencia de dos conglomerados espacio-temporales, en la zona sur-occidental de la región andina y en la región de la Orinoquia. Conclusiones: Se demostró la existencia de dos conglomerados para los eventos Dengue, Zika y Chikungunya que podría establecerse como zonas de mayor riesgo de co-infección.


Abstract Objective: to describe the spatial and temporal distribution of dengue, zika and Chikungunya viruses in Colombia and to identify clusters at spatial, temporal and space-temporal levels. Methods: A descriptive study was developed about the space and time distribution of the Dengue virus (2006-2017), Zika (2015-2017) and Chikungunya (2014-2017) in Colombia, using principles of spatial statistics, namely the spatial data exploratory analysis. Results: Areas of Colombia were identified where there is a higher density and prevalence of cases and were analyzed 1124 municipalities for each event (cases of Dengue, Zika and Chikungunya). Significant clusters (P<0.05) were proven in spatial, temporal and space-temporal analysis, in the south-western zone of the Andean region and in the Orinoquia region. Conclusions: Two conglomerates were confirmed for the Dengue, Zika and Chikungunya events, that could be established as areas of higher risk of co-infection.

15.
Bol. venez. infectol ; 30(2): 86-96, jul-dic 2019.
Artigo em Espanhol | LILACS-Express | ID: biblio-1024091

RESUMO

Introducción: La malaria continúa siendo un importante problema de salud pública en todo el mundo. Las coinfecciones son un factor de riesgo que incrementa la mortalidad de esta enfermedad. En Venezuela no existen estudios que describan la presencia de coinfecciones en pacientes con malaria. Nosotros determinamos las características clínicas y epidemiológicas de los pacientes con malaria y la presencia de coinfecciones en Ciudad Bolívar, Estado Bolívar, Venezuela. Metodología: Se realizó un estudio descriptivo, correlacional y transversal, que incluyó pacientes diagnosticados con malaria por prueba rápida y/o gota gruesa y extendido de sangre periférica que consultaron en tres centros médicos de Ciudad Bolívar, estado Bolívar, entre junio y noviembre de 2018. Se realizó una evaluación clínica y de laboratorio de cada paciente, las coinfecciones con Dengue (VD), Hepatitis viral (HV) (A, B y C), Leptospirosis (LP), y Chikungunya (VCHIK) fueron evaluadas mediante la técnica de ELISA. Resultados: Un total de 161 pacientes fueron estudiados, 106 (65,8 %) presentaron infección por P. vivax, 43 (26,7 %) por P. falciparum y 12 (7,4 %) tenían malaria mixta (Pf/Pv). La media de edad fue 33,8 (±13,43) años; 103 (63,9 %) fueron hombres, la raza más frecuente fue mestiza (94,4 %); la mayoría de los pacientes (37,3 %) practicaban la minería ilegal. Los síntomas más frecuentes fueron fiebre, escalofríos y cefalea. Anemia leve, trombocitopenia moderada, y compromiso de la función hepática fueron los hallazgos de laboratorio más relevantes en todas las especies parasitarias. Se encontró coinfección en 55/161 (34,2 %) pacientes, siendo más frecuente entre los pacientes con P. falciparum (48,8 %). La coinfección más frecuente fue con VD (14,9 %), seguida de VHA (11,8 %)VHB (6,2 %), VCHIK (5,5 %) y LP (3,7 %). En el grupo de coinfectados fue más frecuente la malaria complicada (56,36 %) que la no complicada (43,63 %) con una diferencia estadísticamente significativa (P=0,018). Conclusión: Se encontró una alta prevalencia de coinfecciones en los pacientes con malaria, y su asociación con la severidad de la Malaria, estos datos epidemiológicos influyen de manera directa en el curso clínico, así como en la mortalidad de la enfermedad. Estos hallazgos deben darse a conocer al personal de salud para la identificación oportuna de coinfecciones en estos pacientes.


Introduction: Malaria continues to be a major public health problem worldwide. Co-infections are a risk factor that increases the mortality of this disease. In Venezuela there are no studies describing the presence of coinfections in patients with malaria. We determine the clinical and epidemiological characteristics of patients with malaria and the presence of coinfections in Ciudad Bolívar, Bolívar state, Venezuela. Methodology: A descriptive, correlational and cross-sectional study was carried out, which included patients diagnosed with malaria by rapid test and / or thick and extended peripheral blood drop that they consulted in three medical centers in Ciudad Bolívar, Bolívar state, between June and November 2018 A clinical and laboratory evaluation of each patient was performed, coinfections with Dengue (DV), viral hepatitis (HV) (A, B and C), Leptospirosis (LP), and Chikungunya (VCHIK) were evaluated using the technique of ELISA Results: A total of 161 patients were studied, 106 (65.8 %) had P. vivax infection, 43 (26.7 %) due to P. falciparum and 12 (7.4 %) had mixed malaria (Pf / Pv ). The mean age was 33.8 (± 13.43) years; 103 (63.9 %) were men, the most frequent race was mestizo (94.4 %); the majority of patients (37.3 %) practiced illegal mining. The most frequent symptoms were fever, chills and headache. Mild anemia, moderate thrombocytopenia, and hepatic function impairment were the most relevant laboratory findings in all parasitic species. Coinfection was found in 55/161 (34.2 %) patients, being more frequent among patients with P. falciparum (48.8 %). The most frequent coinfection was with RV (14.9 %), followed by HAV (11.8 %) HBV (6.2 %), HCV (5.5 %) and LP (3.7 %). Complicated malaria (56.36 %) was more frequent than uncomplicated (43.63 %) with a statistically significant difference (P = 0.018). Conclusion: A high prevalence of coinfections was found in patients with malaria, and its association with the severity of Malaria, these epidemiological data directly influence the clinical course, as well as the mortality of the disease. These findings should be made known to health personnel for the timely identification of coinfections in these patients.

16.
Antiviral Res ; : 104668, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31786251

RESUMO

Arboviral diseases caused by dengue (DENV), Zika (ZIKV) and chikungunya (CHIKV) viruses represent a major public health problem worldwide, especially in tropical areas where millions of infections occur every year. The aim of this research was to identify candidate molecules for the treatment of these diseases among the drugs currently available in the market, through in silico screening and subsequent in vitro evaluation with cell culture models of DENV and ZIKV infections. Numerous pharmaceutical compounds from antibiotics to chemotherapeutic agents presented high in silico binding affinity for the viral proteins, including ergotamine, antrafenine, natamycin, pranlukast, nilotinib, itraconazole, conivaptan and novobiocin. These five last compounds were tested in vitro, being pranlukast the one that exhibited the best antiviral activity. Further In vitro assays for this compound showed a significant inhibitory effect on DENV and ZIKV infection of human monocytic cells and human hepatocytes (Huh-7 cells) with potential abrogation of virus entry. Finally, intrinsic fluorescence analyses suggest that pranlukast may have some level of interaction with three viral proteins of DENV: envelope, capsid, and NS1. Due to its promising results, suitable accessibility in the market and reduced restrictions compared to other pharmaceuticals; the anti-asthmatic pranlukast is proposed as a drug candidate against DENV, ZIKV, and CHIKV, supporting further in vitro and in vivo assessment of the potential of this and other lead compounds that exhibited good affinity scores in silico as therapeutic agents or scaffolds for the development of new drugs against arboviral diseases.

17.
World Neurosurg ; 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31786376

RESUMO

BACKGROUND: Spinal haematomas are very rarely associated with dengue syndrome and usually occur at the time of active dengue fever. Late presentation after recovery from dengue fever, intradural haematoma, presentation as a multiloculated cystic lesion with longitudinal extensive myelitis and recurrence after surgery are very rarely or not described. Due to the peculiar association of all these findings, we report this case to provide an insight into the existence of such a rare presentation. CASE DESCRIPTION: A 79-year-old-male developed sudden onset paraparesis after 1 week of recovery from dengue fever. The blood counts were normal. MRI of the thoracic spine was suggestive of intradural haematoma. The patient underwent emergency decompression and drainage of haematoma with recovery in the neurological status over the next few weeks. He presented to our emergency department after 5 weeks of the first surgery with deterioration in the neurological status to complete paraplegia. Repeat MRI showed posterior epidural collection bulging anteriorly causing cord compression and he was re-operated by decompression. There was no neurological recovery. Patient was managed with multi-disciplinary rehabilitation and he was independent in most of the activities at the time of discharge. CONCLUSION: Spinal hematoma should be kept in mind in patients who present with neurological complications after dengue fever. It can have an atypical radiological presentation and may present with recurrent haemorrhage after surgery. Attention should also be given to delayed presentation of neurological complications which may develop even after weeks of recovery from dengue fever.

18.
Ecohealth ; 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31786667

RESUMO

Knowledge of the interrelationship of mosquito communities and land use changes is of paramount importance to understand the potential risk of mosquito disease transmission. This study examined the effects of land use types in urban, peri-urban and natural landscapes on mosquito community structure to test whether the urban landscape is implicated in increased prevalence of potentially harmful mosquitoes. Three land use types (park, farm, and forest nested in urban, peri-urban and natural landscapes, respectively) in Klang Valley, Malaysia, were surveyed for mosquito larval habitat, mosquito abundance and diversity. We found that the nature of human activities in land use types can increase artificial larval habitats, supporting container-breeding vector specialists such as Aedes albopictus, a dengue vector. In addition, we observed a pattern of lower mosquito richness but higher mosquito abundance, characterised by the high prevalence of Ae. albopictus in the urban landscape. This was also reflected in the mosquito community structure whereby urban and peri-urban landscapes were composed of mainly vector species compared to a more diverse mosquito composition in natural landscape. This study suggested that good environmental management practices in the tropical urban landscape are of key importance for effective mosquito-borne disease management.

19.
Jpn J Infect Dis ; 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31787738

RESUMO

Dengue is one of the most serious mosquito-borne viral diseases occurring in humans. From their complexity of 4 serotypes, the ideal vaccine for dengue should be able to stimulate cross-neutralizing antibodies. Recently, genetic-based immune response have been studied for guiding of vaccine design for several viral pathogens. Despite a recent approval of dengue vaccine, the information of genetics-based immune response against dengue virus (DENV) are still limited. Consequently, we aimed to determine the profiles of immunoglobulin heavy chain gene from DENV2 infected patients. The immunoglobulin heavy chain variable region genes (IGHV) were amplified from peripheral blood mononuclear cells of DENV2 secondary infected patients over the acute, convalescence and recovery phases. Antibody heavy chain genes were sequenced by next-generation sequencing (NGS), and analyzed to identify correlations with neutralizing and enhancing activities of the serum samples. IGHV1-69, 3-23, and 3-30 were frequently discovered in our Thai DENV2 infected patients. Our findings provided the new data on the human B cell response during secondary DENV2 infections in Thai dengue patients that provide a supportive information for dengue vaccine design and therapeutics development.

20.
Jpn J Infect Dis ; 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31787741

RESUMO

Oropouche Virus (OROV) is a single-stranded negative-sense RNA arbovirus transmitted to humans by the midge Culicoides paraenesis causing a disease known as Oropouche fever. In Brazil, outbreaks of the virus have been reported to be restricted to the Central-Northern region of the country. However, its incidence is underestimated mainly due to the virus clinical similarities with other arbovirus diseases including dengue (DENV), chikungunya (CHIKV), and zika (ZIKV), and the lack of specific diagnostic tests. Here, we report for the first time OROV detection in saliva and urine samples and the first cases of OROV autochthone infections in Metropolitan region of Salvador, Bahia a Northeastern capital in the coast of Brazil. Serum, saliva and urine samples negative for DENV, CHIKV, and ZIKV were tested for OROV using a RT-nested-PCR protocol in which we found two positive samples of serum, two of saliva and one of urine. This report shows the need for an efficient surveillance system to control the spread of this virus in the population and suggests the use of saliva and urine samples as an alternative for the detection of OROV when serum samples are not available.

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