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Background Evidence indicates a strong link between Zika virus (ZikV) and neurological complications. Acute myelitis, optic neuritis, polyneuropathy, and encephalomyelitis that mimic inflammatory idiopathic demyelination disorders (HDD) after ZikV infection have been reported in Brazil. Objective The present study aims to investigate the possible occurrence of molecular mimicry between ZikV antigens and Multiple Sclerosis (MS) autoantigens, the most frequent HDD of the central nervous system (CNS). Methods A retrospective cohort study with 305 patients admitted due to suspected arbovirus infection in Rio de Janeiro was performed, all subjects were submitted to neurological examination, and a biological sample was collected for serologic and molecular diagnostic. Bioinformatics tools were used to analyze the peptides shared between ZikV antigens and MS autoantigens. Results Of 305 patients, twenty-six were positive for ZikV and 4 presented IDD patterns found in MS cases. Sequence homology comparisons by bioinformatics approach between NS5 ZikV and PLP MS protein revealed a homology of 5/6 consecutive amino acids (CSSVPV/CSAVPV) with 83% identity, deducing a molecular mimicry. Analysis of the 3D structures revealed a similar conformation with alpha helix presentation. Conclusions Molecular mimicry between NS5 Zika virus antigen and PLP MS autoantigens emerge as a possible mechanism for IDD spectrum in genetically susceptible individuals. Resumo Antecedentes Evidências indicam uma forte ligação entre o vírus Zika (ZikV) e complicações neurológicas. Mielite aguda, neurite óptica, polineuropatia e encefalomielite que mimetizam distúrbios inflamatórios de desmielinização idiopáticos (DDII) após infecção por ZikV têm sido relatadas no Brasil. Obejtivo O presente estudo tem como objetivo investigar a possível ocorrência de mimetismo molecular entre antígenos do ZikV e autoantígenos da Esclerose Múltipla (EM), a DDII mais frequente do sistema nervoso central (SNC). Métodos Foi realizado um estudo de coorte retrospectivo com 305 pacientes internados por suspeita de infecção por arbovirus no Rio de Janeiro, todos os indivíduos foram submetidos a exame neurológico e coleta de amostra biológica para diagnóstico sorológico e molecular. Ferramentas de bioinformática foram usadas para analisar os peptídeos compartilhados entre antígenos do ZikV e autoantígenos da EM. Resultados Dos 305 pacientes, vinte e seis foram positivos para ZikV e 4 apresentaram padrão IDD encontrado em casos de EM. As comparações de homologia de sequência por abordagem de bioinformática entre a proteína NS5 ZikV e PLP EM revelaram uma homologia de 5/6 aminoácidos consecutivos (CSSVPV/CSAVPV) com 83% de identidade, deduzindo um mimetismo molecular. A análise das estruturas 3D revelou uma conformação semelhante com apresentação em alfa-hélice. Conclusões O mimetismo molecular entre o antígeno NS5 do vírus Zika e o autoantígeno PLP da EM surge como um possível mecanismo para o espectro IDD em indivíduos geneticamente suscetíveis.

Malaria, Zika virus, West Nile virus, Dengue fever, and Lyme disease are common causes of morbidity and mortality around the world. While arthropod bites may cause local inflammation and discomfort, a greater concern is the potential to develop deadly systemic infection. The use of insect repellents (IR) to prevent systemic infections constitutes a fundamental public health effort. Cost-effectiveness, availability, and high-efficacy against arthropod vectors are key characteristics of an ideal IR. Currently, numerous IRs are available on the market, with DEET (N,N-diethyl-3-methylbenzamide) being the most widely used. DEET has an excellent safety profile and remarkable protection against mosquitoes and various other arthropods. Other EPA-registered IR ingredients (permethrin, picaridin, IR3535, oil of lemon eucalyptus, oil of citronella, catnip oil, and 2-undecanone) are alternative IRs of great interest due to some having efficacies comparable to that of DEET. These alternative IRs possess low toxicity and favorable customer experiences in utilization (e.g., cosmetically pleasant, naturally occurring). This review summarizes currently available EPA-registered IRs: the origins, mechanisms of action, side effect profiles, and available formulations will be discussed. This review will enable the clinician to select the best IR option to meet patients' needs and provide the greatest protection from arthropod bites and sequelae.

Epidemiologic studies have provided evidence that prenatal exposure to maternal infection is associated with an increased risk of developing schizophrenia in the offspring. Research over the past decade has added further to our understanding of the role of prenatal infection in schizophrenia risk. These investigations include several well-powered designs, and like some earlier studies, measured maternal antibodies to specific infectious agents in stored serum samples and large registers to identify clinically diagnosed infections during pregnancy. Convergent findings from antibody studies suggest that prenatal maternal infection with Toxoplasma gondii is associated with increased schizophrenia risk in the offspring, while associations with HSV-2 infection are likely attributable to confounding. Maternal influenza infection remains a viable candidate for schizophrenia, based on an early serological study, though there has been only one attempt to replicate this finding, with a differing methodology. A prior association between maternal serologically confirmed cytomegalovirus infections require further study. Clinically diagnosed maternal infection, particularly bacterial infection, also appears to be associated with increased risk of offspring schizophrenia, and heterogeneity in these findings is likely due to methodological differences between studies. Further clarification may be provided by future studies that address the timing, type, and clinical features of infections. Important insight may be gained by examining the long-term offspring outcomes in emerging epidemics such as Zika virus and COVID-19, and by investigating the interaction between exposure to prenatal infection and other risk or protective factors.

In the present study, we develop a fractional Zika virus model with mutation, which causes new birth problems in infected pregnant women and further spread in society. As a consequence, we apply this notion to the fractional dynamics of the Zika virus. We also use fractional derivatives to gain a better understanding of biological processes and their crossover behavior. The model simulation is based on realColombia data. Mathematical modeling of an infectious disease helps out us in predicting the future spread. Recently, many mathematical models describe the dynamics of infectious disease based on classical integer-order and non-integer order models. Therefore, we study the dynamics of the Zika virus based on non-integer order derivatives for better understanding seen and deeper insight into several biological models. We also describe the different properties of the model like the positivity of the model solution, equilibrium points, and invariant property of the proposed model. The reproduction number is computed with the next-generation technique. The parameters are estimated from confirmed infected cases in Colombia for the year 2016 seems that the model is appropriate for this data set. Moreover, the sensitivity of R 0 on the parameters calculated by the direct differentiation approach. The local and global stability analysis at disease-free and endemic states are investigated. The numerical approach generalized predictor–corrector is implemented for the validation of theoretical results and analyzing the effects of sensitive factors that might be helpful in reducing the infection. From graphical results, it is observed that the fractional model gives more insight and a better understanding of disease dynamics. These findings assist us in controlling the virus through contact precautions and recommended therapy, as well as projecting its future spread.

The aim of this study was to analyze the prevention and control practices against Zika virus (ZIKV) infection among pregnant women in Malaysia. A cross-sectional study was conducted among pregnant women who received antenatal care. Only 7.8% reported that they abstained from sex or used barrier methods during sexual intercourse to prevent ZIKV transmission. The odds of abstaining from sex or using barrier methods were significantly higher among the Chinese ethnic group than the Malay ethnic group (odds ratio [OR] = 4.569; 95% confidence interval [CI]: 2.696-7.743). A total ZIKV knowledge score of 12-24 was also significantly associated with higher odds of abstaining from sex or using barrier methods than a score of 0-11 (OR = 2.819; 95% CI: 1.682-4.725). In total, 38.6% of women had a higher mean total score for all the current mosquito control practices than they did before hearing of ZIKV. Participants living in bungalows or village houses (OR = 2.006; 95% CI: 1.023-3.936) and low-rise houses (OR = 1.566; 95% CI: 1.109-2.212) were more likely to have a higher mean total score of current mosquito control practices than the practices before hearing of ZIKV compared to those in high-rise houses. The lack of ZIKV knowledge and control practices provides insight for the pre-emptive and prompt development of health education systems for pregnant women during antenatal care visits.

How does the news media respond to health emergencies abroad? Between 2015 and 2018, Zika virus spread rapidly throughout Latin America before arriving in the continental United States. Despite the risks to adults and newborns, it is unclear how media coverage developed and framed the threat for its audience. In this paper, we argue that while the frequency of coverage was responsive to infections, its content failed to promote proactive health behaviour. To assess these claims, we analyse each of 442 articles dealing with Zika virus published by The New York Times from 2015-18. We find that the amount of coverage reflected infections but did not change once the disease emerged in the US. Furthermore, content analysis using Linguistic Inquiry and Word Count software reveals that coverage emphasised differences between communities (those affected and those at home) and that present and past time orientations dominated coverage as opposed to future time orientations.كيف تستجيب وسائل الإعلام لحالات الطوارئ الصحية في الخارج ؟ من عام 2015 إلى عام 2018، انتشر مرض فيروس زيكا بسرعة في جميع أنحاء أمريكا اللاتينية قبل وصوله إلى الولايات المتحدة القارية. على الرغم من المخاطر التي يتعرض لها البالغون والأطفال حديثي الولادة، فمن غير الواضح كيف استجابت التغطية الإعلامية وصورت المخاطر لمتتبعيها. في هذا المقال، نناقش بأنه على الرغم من أن تكرار التغطية كان مستجيباً لانتشار العدوى إلا أن محتواها فشل في تعزيز السلوك الصحي الاستباقي. لتقييم هذه الادعاءات، سنقوم بتحليل كل مقال يتناول فيروس زيكا تم نشره بين 2015-2018 بواسطة صحيفة نيويورك تايمز. نجد أن مقدار التغطية ينعكس على مدى انتشار العدوى لكنها لم تتغير بمجرد وصول الفيروس إلى الولايات المتحدة. علاوة على ذلك، يكشف تحليل المحتوى باستخدام برنامج تحليل النصوص LIWC أن التغطية أكدت الاختلافات بين المجتمعات (المتأثرة وتلك الموجودة في المنزل) وأن التوجهات الزمنية الحالية والماضية سيطرت على التغطية بدلاً من التوجهات الزمنية المستقبلية. الكلمات المفتاحية: الوباء، التأطير، التغطية الإعلامية، الصحة العامة، فيروس زيكا.新闻媒体如何应对国外的卫生突发事件？从2015年到2018年，寨卡病毒疾病在抵达美国大陆之前迅速蔓延整个拉丁美洲。尽管成人和新生儿面临风险，但目前还不清楚媒体报道是如何为其受众回应和定调风险的。在这篇文章中，我们认为，虽然报道的频率对感染有响应，但其内容未能促进主动的健康行为。为了评估这些主张，我们分析了《纽约时报》在2015-2018年间发表的每一篇涉及寨卡病毒的文章（442篇）。我们发现，报道数量反映了感染情况，但在病毒到达美国后，报道数量并没有改变。此外，使用LIWC文本分析程序进行的内容分析显示，报道强调了群体之间的差异（受影响的人和居家的人），而且现在和过去的时间取向在报道中占主导地位，未来的时间取向并没有占主导。 关键词: 流行病，定调，媒体报道，公共卫生，寨卡病毒.

Zika virus (ZIKV), a flavivirus associated with neurological disorders, constitutes a global health threat. During pregnancy, ZIKV traverses the placenta and causes congenital disease such as microcephaly and Guillain-Barre syndrome in newborns. To develop a specific antiviral therapy against ZIKV-induced microcephaly that could cross placental and blood-brain barriers, we designed targeted small extracellular vesicles (sEVs) encapsulating antiviral siRNA (small interfering RNA) to inhibit ZIKV. The neuro-specific targeting was achieved by engineering EVs membrane protein lamp2b fused with a neuron-specific rabies virus glycoprotein derived peptide (RVG). Intravenous administration of the RVG-engineered sEVs loaded with siRNA (ZIKV-specific siRNA) protected pregnant AG6 mice against vertical transmission of ZIKV. Particularly, sEVsRVG-siRNA traversed placental and blood-brain barriers and suppressed ZIKV infection in fetal brains. Moreover, sEVsRVG-siRNA alleviated the neuroinflammation and neurological damage caused by ZIKV in the fetal mouse model. In general, we developed a sEVs-based targeted system of antiviral therapy for brain and fetal brain infections.

As ZIKV continues to spread, many “unknowns” remain and research is needed to advance the understanding of this important pathogen. Viral RNA dependent-RNA polymerases (RdRp) are validated targets for inhibitors of the replication of several viruses. Several studies have set up in vitro enzymatic assays of the RdRp of the Zika virus for testing of candidate inhibitors. While most of these studies use short synthetic polymers, we have shown in a previous work that the Zika polymerase domain is capable of a de novo synthesis of the viral genome using the natural viral RNA as template. Here we have studied the role of the sequences at the 3′end of the minus-strand RNA in the initiation of the RNA synthesis by the Zika isolated RdRp. Our results strongly suggest that the region containing the 105 first nucleotides from the 3′ end of the minus-strand RNA is important for initiation of the positive RNA synthesis. This indicates that this region displays all the primary and secondary structures to be efficiently recognized by the recombinant RdRp in vitro. Moreover, we show that the 46 nucleotides are sufficient to initiate RNA synthesis. In addition, the ZIKV polymerase domain poorly replicated the RNA of other RNA viruses and appeared highly selective for its own RNA.

Several Zika virus (ZIKV) seroprevalence studies have been conducted in Africa, Asia, Oceania, the Americas, and the Caribbean. However, studies on ZIKV seroprevalence are limited in Malaysia though several studies have shown that the disease is endemic in the Malaysian state of Sabah. To evaluate the seroprevalence of ZIKV infection, 818 serum samples were collected from febrile patients and healthy blood donors from the Kudat and Kota Kinabalu districts in Sabah from 2017 to 2018. They were screened for ZIKV infection by IgM and IgG ELISA, and positive ZIKV IgM samples were subjected to a 90% neutralization test for confirmation. Twenty-four (6% [95% CI 4 to 8]) confirmed and two (0.5% [95% CI 0.13 to 1.8]) probable ZIKV infections were detected among 400 febrile illness patients. Of 418 healthy blood donor samples, six (1.4% [95% CI 0.65 to 3]) were determined as confirmed ZIKV infections and six (1.4% [95% CI 0.65 to 3]) indicated probable ZIKV infection. This is the first study on the seroprevalence of ZIKV infections among patients and healthy blood donors in Sabah. Compared with previous studies in Malaysia, this study shows that the incidence of ZIKV infection has increased. It also suggests that a sero-surveillance system is essential to determine the circulation of ZIKV in Sabah, Malaysia.

Zika virus (ZIKV) can be sexually transmitted and can lead to severe neonatal and child health issues. The current study examines whether ZIKV-related ideational factors, including awareness of ZIKV and associated birth defects, are related to modern contraceptive use among women and men with sexual partners in four Latin American and Caribbean (LAC) countries. Data used are from cross-sectional household surveys conducted in 2018 in the Dominican Republic, El Salvador, Guatemala, and Honduras with representative samples of men and women aged 18–49 (N = 1,100). The association between self-reported use of modern contraception and measures of Zika knowledge, risk perceptions and social norms, and contraceptive self-efficacy was examined via sex disaggregated multivariate logistic regression models. Both men (OR 3.70, 95% CI 1.36–10.06, P P P

The article deals with the topical issue of today — the disease caused by Zika virus. The etiology and pathogenesis of the disease were described, attention is paid to the examination of a patient with suspected Zika virus. Laboratory tests available in the Synevo laboratory are listed. Recommendations for the treatment are given taking into account the fact that today the causal antiviral treatment is not developed.

Zika virus disease — an infectious disease caused by a virus of the same name from the Flaviviridae family. The main route of transmission of the virus is the infection through the blood during a bite by tropical mosquitoes of Aedes genus and sexual contact with a patient. Only in Brazil in 2015 Zika fever affected a half million people. There is a serious risk of further spread of the infection, for this reason, the disease has been given a status of pandemic. The incubation period is 3 to 12 days. In 75 % of cases, Zika fever is asymptomatic. Symptomatic form is usually occurs in a mild, rarely — in moderate-to-severe form. The symptoms — weakness, often low-grade fever, chills, heada­che, retro-orbital pain, myalgia and arthralgia, maculopapular rash on the face and body. Conjunctivitis, intolerance of bright light develop. Nausea, abdominal pain, diarrhea, cough, sore throat, lymphadenopathy occur less often. Cases of death in people with fever Zika are extremely rare. In areas, where Zika fever outbreak is detected, an increased number of children born with microcephaly is recorded. The disease is diagnosed by polymerase chain reaction. Drugs for the treatment and vaccines for the prevention of the disease do not exist. Conventional antiviral drugs are ineffective. The only way of medical exposure is symptomatic treatment. After recovery, lifelong immunity is formed. Protection against disease is only avoiding mosquito bites in areas where there is Zika fever., Болезнь, вызванная вирусом Зика, — инфекционное заболевание, вызываемое одноименным вирусом, относящимся к семейству Flaviviridae. Основным путем передачи вируса является заражение через кровь во время укуса тропическими комарами рода Aedes и при половом контакте с заболевшим. Только в Бразилии в 2015 году лихорадкой Зика переболели полтора миллиона человек. Присутствует серьезная угроза дальнейшего распространения инфекции, по этой причине заболеванию присвоен статус пандемии. Инкубационный период от 3 до 12 дней. В 75 % случаев лихорадка Зика протекает бессимптомно. Манифестная форма протекает, как правило, в легкой, реже — в среднетяжелой форме. Симптомы — слабость, чаще незначительное повышение температуры, озноб, головная боль, ретроорбитальные боли, миалгия и артралгия, макулопапулезная сыпь на лице и туловище. Развивается конъюнктивит, непереносимость яркого света. Реже беспокоит тошнота, боли в животе, диарея, кашель, боль в горле, лимфаденопатия. Случаи смерти людей с лихорадкой Зика крайне редки. В регионах, где замечена вспышка лихорадки Зика, регистрируют увеличенное число случаев рождения детей с микроцефалией. Диагностируется заболевание методом полимеразной цепной реакции. Препарата для лечения и вакцины для профилактики заболевания не существует. Обычные противовирусные лекарства неэффективны. Единственным способом медикаментозного воздействия является симптоматическое лечение. После выздоровления формируется стойкий пожизненный иммунитет. Защититься от болезни можно, только избегая укусов комаров в районах, где есть лихорадка Зика., Хвороба, викликана вірусом Зіка, — інфекційне захворювання, що викликається однойменним вірусом сімейства Flaviviridae. Основним шляхом передачі вірусу є зараження через кров під час укусу тропічними комарами роду Aedes і при статевому контакті зі хворим. Тільки в Бразилії в 2015 році на лихоманку Зіка перехворіли півтора мільйона людей. Присутня серйозна загроза подальшого розповсюдження інфекції, з цієї причини захворюванню наданий статус пандемії. Інкубаційний період від 3 до 12 днів. У 75 % випадків лихоманка Зіка перебігає безсимптомно. Маніфестна форма перебігає, як правило, у легкій, рідше — в середньотяжкій формі. Симптоми — слабкість, частіше незначне підвищення температури, озноб, головний біль, ретроорбітальний біль, біль у м’язах та суглобах, макулопапульозний висип на обличчі та тулубі. Розвивається кон’юнктивіт, непереносимість яскравого світла. Рідше турбує нудота, болі в животі, діарея, кашель, біль у горлі, лімфаденопатія. Випадки смерті людей із лихоманкою Зіка вкрай рідкісні. У регіонах, де відмічений спалах лихоманки Зіка, реєструють збільшене число випадків народження дітей із мікроцефалією. Діагностується захворювання методом полімеразної ланцюгової реакції. Препарату для лікування і вакцини для профілактики захворювання не існує. Звичайні противірусні ліки неефективні. Єдиним способом медикаментозного впливу є симптоматичне лікування. Після одужання формується стійкий довічний імунітет. Захиститися від хвороби можна, тільки уникаючи укусів комарів у районах, де є лихоманка Зіка.

Dengue virus (DENV), chikungunya virus (CHIKV), and Zika virus (ZIKV) are arboviruses that can affect maternal and fetal outcome if acquired during pregnancy. This study was done to estimate the positivity of DENV, CHIKV, and ZIKV in febrile pregnant women attending a tertiary care hospital in north India. Symptomatic pregnant women were tested for these viruses by IgM ELISA and/or by Trioplex real-time polymerase chain reaction. Their symptoms and laboratory parameters were recorded and were followed up till delivery to know their immediate delivery outcome. Of 104 women tested, 50 (48.1%) were positive for viral markers. Of these, evidence of infection by DENV, CHIKV, and both was found in 34 (32.7%), 10 (9.6%), and 6 (5.8%), respectively. ZIKV was not detected in any woman. Maximum DENV positivity occurred in the third trimester of pregnancy and in women residing in urban than rural areas. Chills and rigors, arthralgia, retro-orbital pain, anemia, and vaginal bleeding were more commonly associated with DENV positivity. Backache, arthralgia, jaundice, and vaginal bleeding were more common in CHIKV positives but the difference between positives and nonpositives regarding these symptoms was not statistically significant. Dengue infections were associated with more frequent hospitalizations (OR = 8.38, 95% confidence intervals [CI] = 3.29–21.30) and mortality (OR = 19.0, 95% CI = 1.01–357.10). Hence, to conclude, in India wherever possible, all symptomatic pregnant women should be screened for DENV, CHIKV, and ZIKV as part of sentinel surveillance for ZIKV.

Fourteen asymptomatic normocephalic newborns with confirmed congenital Zika infection were investigated. All newborns presented Zika virus (ZIKV) positivity on reverse transcriptase polymerase chain reaction. Following ZIKV-specific NS5 gene fragment sequencing in one child, phylogenetic analysis revealed that this isolate belonged to the Asian genotype, and clustered closely with other sequences previously isolated in north-east and northern regions of Brazil.

Zika virus (ZIKV) is an arthropod-borne flavivirus that reemerged in 2007 and, since then, has caused several outbreaks and spread to over 80 countries worldwide. Along with this, ZIKV infections have been associated with severe clinical outcomes, including neurological manifestations, especially in newborns, posing a major threat to human health. However, there are no licensed vaccines or specific antiviral agents available yet; thereby, there is an urgent need for the discovery of novel therapeutic strategies to fight this infection. In this context, seaweeds are proven sources of biologically relevant products, including antiviral ones, that remain poorly explored. Herein, we evaluated the antiviral potential of the dichloromethane extract of the red seaweed Bryotamnion triquetrum against ZIKV. MTT assay was carried out to evaluate the extract's toxicity in Vero cells, while standard plaque assays were performed for viral titer quantification in the antiviral assays. The B. triquetrum extract possessed great inhibitory activity on the ZIKV replication in Vero cells, with an EC50 of 1.38 µg/ml and a higher selectivity index than ribavirin (289.85 and 75.20, respectively), a licensed antiviral drug. The investigation of its mechanism of action revealed a moderate virucidal effect while it strongly impaired virus replication at both early and late steps of the virus replication cycle with moderate inhibition at the attachment stage. Finally, the B. triquetrum extract presented a remarkable synergistic effect with ribavirin at suboptimal concentrations, which also highlights the promising antiviral potential of this product as a drug candidate to combat ZIKV infection. Keywords: Rhodophyta; Algae; arbovirus; antiviral; Zika.

For many centuries human populations have been suffering and trying to fight with disease-bearing mosquitoes. Emerging and reemerging diseases such as Dengue, Zika, and Chikungunya affect billions of people around the world and recently has been appealing to control with chemical pesticides. Malathion (MT) is one of the main pesticides used against mosquitoes, the vectors of these diseases. This study aimed to assess cytotoxicity and mutagenicity of the malathion for the bioindicator Allium cepa L. using a multivariate and integrative approach. Moreover, an appendix table was compiled with all available literature of insecticides assessed by the Allium cepa system to support our discussion. Exposures during 48h to 0.5 mg mL-1 and 1.0 mg mL-1 MT were compared to the negative control (distilled water) and positive control (MMS solution at 10 mg L-1). The presence of chromosomal aberrations, micronuclei frequency, and mitotic index abnormalities was evaluated. Anaphase bridges were the alterations with higher incidence and presented a significantly elevated rate in the concentration of 0.5 mg mL-1, including when compared to the positive control. The integrative discriminant analysis summarizes that MT in assessed concentrations presented effects like the positive control, corroborating its potential of toxicity to DNA. Therefore, it is concluded that MT in its pure composition and in realistic concentrations used, has genotoxic potential in the biological assessment of A. cepa cells. The multivariate integrative analysis was fundamental to show a whole response of all data, providing a global view of the effect of MT on DNA. Resumo Por muitos séculos, as populações humanas sofrem e tentam combater os mosquitos transmissores de doenças. Doenças emergentes e reemergentes como Dengue, Zika e Chikungunya afetam bilhões de pessoas em todo o mundo e, recentemente, vem apelando ao controle com pesticidas químicos. O Malation (MT) é um dos principais pesticidas usados contra mosquitos, vetores dessas doenças. O objetivo deste estudo foi avaliar a citotoxicidade e a mutagenicidade do MT para o bioindicador Allium cepa L. usando uma abordagem multivariada e integrativa. Além disso, uma tabela suplementar foi compilada com toda a literatura disponível de inseticidas avaliada pelo sistema Allium cepa para apoiar nossa discussão. Exposições ao MT durante 48h a 0,5 mg mL-1 e 1,0 mg mL-1 foram comparadas a um controle negativo (água destilada) e um controle positivo (10 mg L-1 de MMS). Foram avaliadas a presença de aberrações cromossômicas, frequência de micronúcleos e anormalidades no índice mitótico. As pontes anafásicas foram as alterações com maior incidência e apresentaram uma taxa significativamente elevada na concentração de 0,5 mg mL-1, inclusive quando comparadas ao controle positivo. A análise discriminante integrativa resume que o MT nas concentrações avaliadas apresentou efeitos semelhantes ao controle positivo, corroborando seu potencial de toxicidade para o DNA. Portanto, conclui-se que o MT, em sua composição pura e nas concentrações realistas utilizadas, possui potencial genotóxico na avaliação biológica de células de A. cepa. A análise integrativa multivariada foi fundamental para mostrar uma resposta completa de todos os dados, fornecendo uma visão global do efeito da MT no DNA.

The Interferon (IFN) response is crucial to restrain pathogenic infections. Investigations into flavivirus-host interactions reported that the high virulence is linked to innate immune evasion. Zika Virus (ZIKV) has developed diversified strategies to evade the innate immune system. We report that the viral protein NS2A counteracts the IFN response by strongly suppressing the IFN signaling. NS2A targets transcription factors STAT1 and STAT2, to impede their nuclear localization, thereby suppressing the transcription of ISRE promoter and IFN-stimulated genes. We found that NS2A promotes degradation of STAT1 and STAT2. Treatment of NS2A transfected cells with MG132 restores the levels of both transcription factors, suggesting the involvement of the proteasome system. Given the impact that the IFN antagonism has on flavivirus virulence, the knowledge gained by characterizing the mechanism through which ZIKV evades the IFN response paves the ground for new strategies to attenuate the pathogenesis and to develop countermeasures against effective pharmacological targets.

Half of the world's population is at risk of arthropod-borne virus (arbovirus) infections. Several arbovirus infections have been associated with Guillain-Barré syndrome (GBS). We investigated whether arboviruses are driving GBS beyond epidemic phases of transmission and studied the antibody response to glycolipids. The protocol of the International Guillain-Barré syndrome Outcome Study (IGOS), an observational prospective cohort study, was adapted to a case-control design. Serum samples were tested for a recent infection with Zika virus (ZIKV), dengue virus (DENV), chikungunya (CHIKV) virus, hepatitis E virus, Epstein-Barr virus (EBV), cytomegalovirus (CMV), Campylobacter jejuni, and Mycoplasma pneumoniae, and for antibodies to glycolipids. Forty-nine patients were included from Brazil (63%), Argentina (14%), and Malaysia (22%). Evidence of a recent infection was found in 27/49 (55%) patients: C jejuni (n = 15, 31%), M pneumoniae (n = 5, 10%), CHIKV (n = 2, 4%), EBV (n = 1, 2%), C jejuni and M pneumoniae (n = 2, 4%), CMV and DENV (n = 1, 2%), and C jejuni and DENV (n = 1, 2%). In 22 patients, 35 paired controls were collected. Odds ratio for recent infections did not significantly differ between cases and controls. No typical anti-ganglioside antibody binding was associated with recent arbovirus infection. We conclude that arbovirus infections occur in GBS patients outside of epidemic viral transmission, although not significantly more than in controls. Broad infection and anti-ganglioside antibody serology are important to establish the most likely pathogenic trigger in GBS patients. Larger studies are necessary to determine the association between arboviruses and GBS.

Recent reports have shown that Zika virus (ZIKV) has oncolytic potential against human glioblastoma (GBM); however, the mechanisms underlying its tropism and cell entry are not completely understood. The receptor tyrosine kinase AXL has been identified as an entry receptor for ZIKV in a cell-type-specific manner. Interestingly, AXL is frequently overexpressed in GBM patients. Using commercially available GBM cell lines, we first show that cells expressing AXL are permissive for ZIKV infection, while cells that do not express AXL are not. Furthermore, inhibition of AXL kinase using R428 and antibody blockade of AXL receptor strongly attenuated virus entry in GBM cell lines. Additionally, CRISPR knockout of the AXL gene in GBM cell lines completely abolished ZIKV infection, significantly inhibited viral replication, and significantly reduced apoptosis compared with parental lines. Lastly, introduction of AXL receptor into non-expressing cell lines renders the cells susceptible to ZIKV infection. Together, these findings demonstrate that ZIKV entry into GBM cells in vitro is mediated by the AXL receptor and that following cell entry, productive infection is cytotoxic. Thus, ZIKV is a potential oncolytic virus for GBM., Graphical abstract, Zika virus (ZIKV) can infect glioblastoma (GBM) cells. We show that ZIKV entry and infection is mediated by the tyrosine kinase receptor AXL. AXL antibody blockade, CRISPR knockout, and kinase inhibition all mitigate ZIKV entry and infection. This receptor-mediated tropism suggests ZIKV as a candidate oncolytic virus for GBM.

Zika virus (ZIKV) is a positive-single strand RNA virus that belongs to the Flaviviridae family. ZIKV infection causes congenital ZIKV syndrome (CZS) in children and Guillain Barre Syndrome (GBS) in adults. ZIKV infected cells secrete non-structural protein 1 (sNS1), which plays an important role in viral replication and immune evasion. The microglial cells are the brain resident macrophages that mediate the immune responses in CNS. The miRNAs are small non-coding RNAs that regulate the expression of their target genes by binding to the 3'UTR region. The present study highlights the bystander effect of ZIKV-NS1 via miR-146a. The Real-Time PCR, Immunoblotting, overexpression, knockdown studies, and reactive oxygen species measurement have been done to study the immunomodulatory effects of ZIKV-NS1 in human microglial cells. ZIKV-NS1 induced the expression of miR-146a and suppressed the ROS activity in human microglial cells. The up-regulated miR-146a led to the decreased expression of TRAF6 and STAT-1. The reduced expression of TRAF6 in turn led to the suppression of pNF-κBp65 and TNF-α downstream. The miR-146a suppressed the pro-inflammatory and cellular antiviral responses in microglial cells. Our findings demonstrate the bystander role of ZIKV-NS1 in suppressing the pro-inflammatory and cellular antiviral responses through miR-146a in human microglial cells.

Zika virus (ZIKV) emerged as a global public health concern due to its relationship with severe neurological disorders. Non-structural (NS) proteins of ZIKV are essential for viral replication, regulatory function, and subversion of host responses. NS2B is a membrane protein responsible for the regulation of viral protease activity. This protein has transmembrane domains critical for the localization of viral protease to the endoplasmic reticulum membrane and a hydrophilic domain essential for folding, recruitment, and protease activity. Therefore, NS2B is considered a cofactor of viral protease which processes viral polyprotein and is essential for virus replication, making it an attractive antiviral drug target. Here, we report the backbone 1H, 15N, 13C resonance assignments of the full-length NS2B by high-resolution NMR. The backbone assignment will be necessary for determining the three-dimensional structure and backbone dynamics of NS2B, interaction mapping and screening potential of antiviral drugs against ZIKV and related pathogenic flaviviruses.

Aims To describe oral manifestations in children born with microcephaly attributed to congenital Zika virus syndrome (CZS). Methods Data was collected in semiannual intervals from 2017 to 2019, by oral exams of the children and interview with caregivers at a Public Dental Center in Rio de Janeiro, Brazil. A single calibrated examiner performed clinical examinations. Results Of 38 eligible children, 34 were followed-up from 12 to 30 months of age, 20 boys and 14 girls. The mean age of emergence of their first primary tooth was 12.4 months (SD = 2.9). By 30 months of age only 14.7% (n = 5) had complete primary dentition. Alteration in the sequence of tooth emergence was observed in 41.1% (n = 14). Radiographic examination demonstrated dental agenesis (14.7% n = 5). Dental developmental alterations (38.2%, n = 13), enamel defects (14.7%, n = 5), eruption cysts/hematoma (23.5%, n = 8), gingival bleeding (55.8%, n = 19), narrow palate, and bruxism (64.7%, n = 22) were also observed. No child had dental caries. Conclusion Children with microcephaly attributed to CZS presented oral manifestations early in life.

Background IR3535 is among the most widely used synthetic insect repellents, particularly for the mitigation of mosquito-borne diseases such as malaria, yellow fever, dengue, and Zika, as well as to control flies, ticks, fleas, lice, and mites. These insects are well-known vectors of deadly diseases that affect humans, livestock, and crops. Moreover, global warming could increase the populations of these vectors. Results Here, we performed IR3535 dose-response analyses on Drosophila melanogaster, a well-known insect model organism, using electrophysiology and binary food choice assays. Our findings indicated that bitter-sensing gustatory receptor neurons (GRNs) are indispensable to detect IR3535. Further, potential candidate gustatory receptors were screened, among which GR47a was identified as a key molecular sensor. 0.1%-0.4% ranges of IR3535 affected larval development and mortality. Additionally, DEET (i.e., another commonly used insecticide) was found to exert synergistic effects when co-administered with IR3535. Conclusion Our findings confirmed that IR3535 directly activates bitter-sensing GRNs, which are mediated by GR47a. This relatively safe and highly potent insecticide can be largely used in combination with DEET to increase its efficiency to protect livestock and crops. Collectively, our findings suggest that the molecular sensors elucidated herein could be used as targets for the development of alternative insecticides. This article is protected by copyright. All rights reserved.

In contrast to the extensive research about viral protein–host protein interactions that has revealed major insights about how RNA viruses engage with host cells during infection, few studies have examined interactions between host factors and viral RNAs (vRNAs). Here, we profiled vRNA–host protein interactomes for three RNA virus pathogens (SARS-CoV-2, Zika, and Ebola viruses) using ChIRP-MS. Comparative interactome analyses discovered both common and virus-specific host responses and vRNA-associated proteins that variously promote or restrict viral infection. In particular, SARS-CoV-2 binds and hijacks the host factor IGF2BP1 to stabilize vRNA and augment viral translation. Our interactome-informed drug repurposing efforts identified several FDA-approved drugs (e.g., Cepharanthine) as broad-spectrum antivirals in cells and hACE2 transgenic mice. A co-treatment comprising Cepharanthine and Trifluoperazine was highly potent against the newly emerged SARS-CoV-2 B.1.351 variant. Thus, our study illustrates the scientific and medical discovery utility of adopting a comparative vRNA–host protein interactome perspective.

Species differences are among the main reasons for the high failure rate of preclinical studies. A better awareness and understanding of these differences might help to improve the outcome of preclinical research. In reproduction, the placenta is the central organ regulating fetal exposure to a substance circulating in the maternal organism. Exact information about placental transfer can help to better estimate the toxic potential of a substance. From an evolutionary point of view, the chorioallantoic placenta is the organ with the highest anatomical diversity among species. Moreover, frequently used animal models in reproduction belong to rodents and lagomorphs, two groups that are characterized by the generation of an additional type of placenta, which is crucial for fetal development, but absent from humans: the inverted yolk sac placenta. Taken together, the translatability of placental transfer studies from laboratory animals to humans is challenging, which is supported by the fact that numerous species-dependent toxic effects are described in literature. Thus, reliable human-relevant data are frequently lacking and the toxic potential of chemicals and pharmaceuticals for humans can hardly be estimated, often resulting in recommendations that medical treatments or exposure to chemicals should be avoided for safety reasons. Although species differences of placental anatomy have been described frequently and the need for human-relevant research models has been emphasized, analyses of substances with species-dependent placental transfer have been performed only sporadically. Here, we present examples for species-specific placental transfer, including that of nanoparticles and pharmaceuticals, and discuss potential underlying mechanisms. With respect to the COVID 19-pandemic it might be of interest that some antiviral drugs are reported to feature species-specific placental transfer. Further, differences in placental structure and antibody transfer may affect placental transfer of ZIKA virus.

Objective To investigate whether the presented rheotaxis-based microfluidic device could be used to separate spermatozoa from viruses (i.e., Zika) in the infected semen sample during the selection and washing process. Design Quantitative and experimental study of the sperm washing/selection process through the microfluidic platform exploiting the positive rheotaxis of sperm. Setting None. Patient(s) None. Intervention(s) None. Main Outcome Measure(s) Human sperm were purchased from a sperm bank. The raw semen sample was mixed with viruses and loaded into a microfluidic device. Experiments were performed with 2 different flow rates (0 and 25 μL/minute) to investigate the washing efficiency of the device in the sperm selection process. The sperm sample was collected after 45 minutes and analyzed to check whether the collected sample is free of any infections (viruses) after isolation. Result(s) Fluorescent microscopy and quantitative polymerase chain reaction-based analysis showed that the sperm selected with the presented rheotaxis-based microfluidic device at the optimal flow rate (25 μL/minute) was free of any viruses. Conclusion(s) We have developed a simple, cost-effective microfluidic device that mimics the conditions of the female genital tract while washing out the raw semen efficiently during the selection process for assisted reproductive technology.

Epidemic vector-borne viral infections pose a serious threat to public health worldwide. There is currently no specific preventive treatment for most of them. One of the promising solutions for combating viral fevers is development of vector vaccines, including MVA-based vaccines, which have virtually no adverse side effects. The safety of the MVA strain and absent reactogenicity of recombinant MVA vaccines have been supported by many clinical trials.The article focuses on test results for similar preventive products against viral fevers: Crimean-Congo hemorrhagic fever, Rift Valley fever, yellow fever, Chikungunya and Zika fevers.Their immunogenicity was evaluated on immunocompetent and immunocompromised white mice; their protective efficacy was assessed on immunocompromised white mice deficient in IFN-α/β receptors, that are used for experimental modeling of the infection. Nearly all the new recombinant vaccines expressing immunodominant antigens demonstrated 100% protective efficacy. It has been found that although the vaccine expressing Zika virus structural proteins induced antibodies against specific viral glycoproteins, it can be associated with high risks when used for prevention of Zika fever in individuals who had dengue fever in the past, due to the phenomenon known as antibody-dependent enhancement of infection, which can occur in diseases caused by antigenically related flaviruses. For this reason, the vaccine expressing non-structural protein 1 (NS1) was developed for vaccination against Zika fever.The yellow fever vaccine developed on the MVA platform had immunogenicity similar to that of the commercial 17D vaccine, outperforming the latter in safety.

Zika virus (ZIKV) induces neurological and autoimmune complications such as microcephaly and Guillain-Barre syndrome. Effective vaccines are necessary to prevent the ZIKV infection. E protein of ZIKV is responsible for virus attachment, entry, and fusion. The domain III of E protein (EDIII) contains the neutralizing epitopes and is ideal to act as an antigen for ZIKV vaccine. However, EDIII is poorly immunogenic. CRM197 is a carrier protein and can activate T helper cells for EDIII. Mannan is a ligand of TLR-4 or TLR-2. Eight-arm PEG can link multiple EDIII molecules in one entity. In the present study, EDIII was covalently conjugated with CRM197, 8-arm PEG and mannan to improve the immunogenicity of EDIII. The conjugate (CRM-EDIII-PM) elicited high EDIII-specific antibody titers in the BALB/c mice. Th1-type cytokines (IFN-γ and IL-2) and Th2-type cytokines (IL-5 and IL-10) were secreted at a marked level. Thus, CRM-EDIII-PM could stimulate potent humoral and cellular immune response to EDIII. The serum exposure of CRM-EDIII-PM to the immune system was prolonged. Moreover, CRM-EDIII-PM did not lead to apparent toxicity to the organs. Therefore, CRM-EDIII-PM was expected as a promising vaccine candidate for its ability to induce strong immune responses.

Zika Virus (ZIKV) belongs to the family of flaviviruses, and is neurotrophic. It has been known to cause severe congenital disabilities including microcephaly in neonates. The virus has a specific preference towards neural stem cells (NSCs). ZIKV impairs proliferation and differentiation of NSCs during in-utero brain development of the fetus. However, molecular pathways involved in ZIKV induced alteration in NSCs are yet to be explored. In our previous study, we have described that ZIKV E protein dysregulates microRNA circuitry in NSCs and also impairs their proliferative and differentiation abilities. WNT signalling was found to be the target of differentially expressed miRNAs as suggested by PANTHER PATHWAY analysis of differentially expressed miRNA targets. In our current follow-up study, we investigate that WNT2 is downregulated in response to ZIKV E protein in human fetal NSCs and WNT2 is the molecular target of microRNA miR-204-5p. We provide pieces of evidences that miR-204-5p/WNT2 axis is involved in ZIKV induced impairment in the proliferation and immature differentiation of neural stem cells.

The mosquito continues to be the most lethal animal to humans due to the devastating diseases that it carries and transmits. Controlling mosquito-borne diseases relies heavily on vector management using neurotoxic insecticides with limited modes of action. This has led to the emergence of resistance to pyrethroids and other neurotoxic insecticides in mosquitoes, which has reduced the efficacy of chemical control agents. Moreover, many neurotoxic insecticides are not selective for mosquitoes and negatively impact beneficial insects such as honeybees. Developing new mosquitocides with novel mechanisms of action is a clear unmet medical need; this review covers the efforts made toward this end by targeting the renal inward rectifier potassium channel (Kir) of the mosquito.

The genus flavivirus of the Flaviridae family includes several human pathogens, like dengue, Zika, Japanese encephalitis, and yellow fever virus. These viruses continue to be a significant threat to human health. Vaccination remains the most useful approach to reduce the impact of flavivirus fever. However, currently available vaccines can induce severe side effects or have low effectiveness. An alternative is the use of recombinant vaccines, of which virus-like particles (VLP) and single-round infectious particles (SRIP) are of especial interest. VLP consist of the virus structural proteins produced in a heterologous system that self-assemble in a structure almost identical to the native virus. They are highly immunogenic and have been effective vaccines for other viruses for over 30 years. SRIP are promising vaccine candidates, as they induce both cellular and humoral responses, as viral proteins are expressed. Here, the state of the art to produce both types of particles and their use as vaccines against flaviviruses are discussed. We summarize the different approaches used for the design and production of flavivirus VLP and SRIP, the evidence for their safety and efficacy, and the main challenges for their use as commercial vaccines.

Zika virus (ZIKV) is one of the arboviruses implicated in febrile illness, microcephaly and other neurological disorders in babies whose mothers were infected during pregnancy. Information on ZIKV in Nigeria is limited. Hence, this study was aimed at investigating the seroprevalence of Zika virus among pregnant women in Lagos State. In a cross-sectional study, blood samples collected from 352 randomly selected pregnant women in four hospitals in Lagos State were separated and plasma analyzed using Zika virus IgG and IgM capture Enzyme-linked immunosorbent assay (Demeditec Diagnostics, Germany). The optical densities were read using Precision Microplate reader (Molecular devices) and cut-off calculated according to manufacturer’s guide. Parameters and symptoms such as history of fever, rashes on the body, exposure to mosquito were extracted from the questionnaire and analyzed. IgM seropositive samples were screened for ZIKV RNA on RT-qPCR. Out of 352 samples screened, 7(2.0%) and 5(1.4%) of the pregnant women tested positive for IgG and IgM respectively. None tested positive for both IgG and IgM markers. Statistical analysis showed that there is no significant relationship between the symptoms analyzed in this study at 95% Confidence interval except conjunctivitis. None of the ZIKV IgM seropositive samples tested positive for ZIKV RNA on RT-qPCR. The results show that there is evidence of exposure to Zika virus among the population studied in Lagos, Nigeria. Also, the low level seroprevalence of the virus in the population studied indicates that there is lack of herd immunity of Zika virus infection in Lagos, Nigeria.

Objective We investigate how beliefs about scientists and presidents affect views about two pandemics, Zika virus (2016) and COVID‐19 (2020). Methods Three New Hampshire surveys in 2016 and 2020 provide data to test how beliefs about scientists’ practices and presidential approval relate to pandemic views. Results Support for presidents consistently predicts perceptions of scientists’ integrity and trust in science agencies for information, but the directionality changes from 2016 to 2020—increased trust among Obama‐supporters; decreased trust among Trump‐supporters. Respondents who believe scientists lack objectivity are also less likely to trust science agencies during both Zika and COVID‐19 and are less apt to be confident in the government's response in 2016. Assessments of pandemic responses become increasingly political during 2020; most notably, support for President Trump strongly predicts confidence in the government's efforts. Conclusion Results highlight how beliefs about scientists’ practices and presidents are central to the science–politics nexus during pandemics.

Objective To evaluate the protective effect of house-screening (HS) on indoor Ae. aegypti infestation, abundance and arboviral infection in Merida, Mexico. Methods In 2019, we performed a cluster randomized controlled trial (6 control and 6 intervention areas: 100 households/area). Intervention clusters received permanently fixed fiberglass HS on all windows and doors. The study included two cross-sectional entomologic surveys, one baseline (dry season in May 2019) and one post-intervention (PI, rainy season between September-October 2019). The presence and number of indoor Aedes females and blood-fed females (indoor mosquito infestation) as well as arboviral infections with dengue (DENV) and Zika (ZIKV) viruses were evaluated in a subsample of 30 houses within each cluster. Results HS houses had significatively lower risk for having Aedes aegypti female mosquitoes (odds ratio [OR]=0.56, 95% C. I. 0.33-0.97, P=0.04) and blood-fed females (OR=0.53, 95% C. I. 0.28-0.97, P=0.04) than unscreened households from the control arm. Compared to control houses, HS houses had significantly lower indoor Ae. aegypti abundance (rate ratio [RR]=0.50, 95% C. I. 0.30-0.83, P=0.01), blood-fed Ae. aegypti females (RR=0.48, 95% C. I. 0.27-0.85, P=0.01) and female Ae. aegypti positive for arboviruses (OR=0.29, 95% CI 0.10-0.86, P=0.02). The estimated intervention efficacy in reducing Ae. aegypti arbovirus infection was 71%. Conclusions These results provide evidence supporting the use of HS as an effective pesticide-free method to control house infestations with Aedes aegypti and reduce the transmission of Aedes-transmitted viruses such as DENV, chikungunya (CHIKV), and ZIKV.

Zika virus (ZIKV) infections are associated with severe neurological complications and are a global public health concern. There are no approved vaccines or antiviral drugs to inhibit ZIKV replication. NS2B-NS3 protease (NS2B-NS3 pro), which is essential for viral replication, is a promising molecular target for anti-ZIKV drugs. We conducted a systematic review to identify compounds with promising effects against ZIKV; we discussed their pharmacodynamic and pharmacophoric characteristics. The online search, performed using the PubMed/MEDLINE and SCOPUS databases, yielded 56 articles; 7 relevant studies that reported nine promising compounds with inhibitory activity against ZIKV NS2B-NS3 pro were selected. Of these, five (niclosamide, nitazoxanide, bromocriptine, temoporfin, and novobiocin) are currently available on the market and have been tested for off-label use against ZIKV. The 50% inhibitory concentration values ​​of these compounds for the inhibition of NS2B-NS3 pro ranged at 0.38-21.6 µM; most compounds exhibited non-competitive inhibition (66%). All compounds that could inhibit the NS2B-NS3 pro complex showed potent in vitro anti-ZIKV activity with a 50% effective concentration ranging 0.024-50 µM. The 50% cytotoxic concentration of the compounds assayed using A549, Vero, and WRL-69 cell lines ranged at 0.6-1,388.02 µM and the selectivity index was 3.07-1,698. This review summarizes the most promising antiviral agents against ZIKV that have inhibitory activity against viral proteases. This article is protected by copyright. All rights reserved.

The twenty-first century has witnessed a wave of severe infectious disease outbreaks, not least the COVID-19 pandemic, which has had a devastating impact on lives and livelihoods around the globe. The 2003 severe acute respiratory syndrome coronavirus outbreak, the 2009 swine flu pandemic, the 2012 Middle East respiratory syndrome coronavirus outbreak, the 2013–2016 Ebola virus disease epidemic in West Africa and the 2015 Zika virus disease epidemic all resulted in substantial morbidity and mortality while spreading across borders to infect people in multiple countries. At the same time, the past few decades have ushered in an unprecedented era of technological, demographic and climatic change: airline flights have doubled since 2000, since 2007 more people live in urban areas than rural areas, population numbers continue to climb and climate change presents an escalating threat to society. In this Review, we consider the extent to which these recent global changes have increased the risk of infectious disease outbreaks, even as improved sanitation and access to health care have resulted in considerable progress worldwide., Global change, including climate change, urbanization and global travel and trade, has affected the emergence and spread of infectious diseases. In the Review, Baker, Metcalf and colleagues examine how global change affects infectious diseases, highlighting examples ranging from COVID-19 to Zika virus disease.

Here, we describe the development of the in-house anti-Zika virus (ZIKV) IgM antibody capture ELISA (in-house ZIKV IgM ELISA) for the detection and diagnosis of acute ZIKV infections. We compared the in-house ZIKV IgM ELISA assay performance against two commercial kits, Euroimmun ZIKV IgM and InBios 2.0 ZIKV IgM ELISA. We tested the assays’ ability to detect anti-ZIKV IgM using a well-defined serum sample panel. This panel included 80 ZIKV negative samples (20 negative, 20 found to be primary dengue virus [DENV][ infections, 20 secondary DENV infections, and 20 Japanese encephalitis virus [JEV] infections) and 67 ZIKV reverse transcriptase–polymerase chain reaction–positive acute serum samples. The OD values were calculated to enzyme immunoassay (EIA) unts by comparing them to weak positive controls. The results demonstrated the high sensitivity (88.06%) and specificity (90.00%) of our in-house ZIKV IgM ELISA and its 89.12% overall percentage agreement. The kappa values were deemed to be within excellent range and comparable to the InBios ZIKV IgM ELISA. Some cross-reactivity was observed among secondary DENV and JEV samples, and to a much lower extent, among primary DENV samples. These data indicate that our in-house ZIKV IgM ELISA is a reliable assay for the detection of anti-ZIKV IgM antibodies in serum.

The American Zika virus (ZIKV) epidemic has highlighted the need to gain a better understanding of this emerging virus. The goal of this study was to describe the clinical symptoms, laboratory findings, and risk factors for symptomatic ZIKV infection in an area with ongoing transmission of other arboviral infections. We recruited patients at least 2 years of age seeking care at public health centers in León, Nicaragua, between January 2016 and August 2017, for fever, maculopapular rash, and/or nonsuppurative conjunctivitis with a duration of less than 1 week. A laboratory diagnosis of ZIKV was established using a combination of molecular and serological tests. Clinical and laboratory findings and potential risk factors were compared between participants with and without acute ZIKV infection. Fifty-eight (26%) of the 225 participants included in the analysis were found to have acute ZIKV infection. Pregnancy and reports of previous arboviral infection were associated with a higher risk of ZIKV infection. Rash, conjunctivitis, sore throat, and lower absolute neutrophil counts were associated with acute ZIKV infection. The clinical characteristics and risk factors identified were consistent with those identified by previous studies; however, we found sore throat to be a feature of ZIKV infection. We also found that neutrophil counts were lower in ZIKV-infected subjects. These clinical symptoms and laboratory data may help clinicians suspect ZIKV infection during future outbreaks.

Infections with Flaviviridae constitute a major public health concern, especially considering the limited availability of prophylactic and therapeutic treatments. Most notably, the recent emergence of Zika virus in the Americas was associated with the dramatic increase of severe symptoms such as congenital microcephaly, while hepatitis C virus causes the death of approximately 300,000 individuals annually. Flaviviridae have evolved to hijack cellular organelles and to favor their replication, often via divergent molecular mechanisms. In addition to the remodeling of the endoplasmic reticulum, which is required for the replication of the viral genome and the assembly of the neosynthesized virions, Flaviviridae induce drastic morphological alterations of the mitochondria. This is associated with the viral co-opting of several key mitochondrial functions in apoptosis, innate immunity and metabolism. This review recapitulates the current knowledge about the morphological and functional relationship between Flaviviridae and mitochondria and explains how this contributes to the establishment of a cytoplasmic environment which is favorable to viral replication.

Zika virus (ZIKV) has the ability to cross placental and brain barriers, causing congenital malformations in neonates and neurological disorders in adults. However, the pathogenic mechanisms of ZIKV-induced neurological complications in adults and congenital malformations are still not fully understood. Gas6 is a soluble TAM receptor ligand able to promote flavivirus internalization and downregulation of immune responses. Here we demonstrate that there is a correlation between ZIKV neurological complications with higher Gas6 levels and the downregulation of genes associated with anti-viral response, as type I IFN due to Socs1 upregulation. Also, Gas6 gamma-carboxylation is essential for ZIKV invasion and replication in monocytes, the main source of this protein, which was inhibited by warfarin. Conversely, Gas6 facilitates ZIKV replication in adult immunocompetent mice and enabled susceptibility to transplacental infection. Our data indicate that ZIKV promotes the upregulation of its ligand Gas6, which contributes to viral infectivity and drives the development of severe adverse outcomes during ZIKV infection.

Background More than 5 years after the Zika virus (ZIKV) epidemic, Zika infection remains a major concern in regions with high Aedes infestation. The objectives of this study were (i) to identify clusters of ZIKV infection and microcephaly, and/or central nervous system (CNS) alterations associated with congenital infection during the epidemic peak in 2016 and subsequently, in 2017 and 2018; (ii) to measure the non-spatial correlation between ZIKV infection and microcephaly and/or CNS alterations associated with congenital infection; and (iii) to analyse the sociodemographic/economic, health, and environmental determinants associated with the incidence of ZIKV in a region of high infestation by Aedes aegypti in the Central-West Region of Brazil. Methods This ecological study analysed 246 municipalities in the state of Goiás (6.9 million inhabitants). The data were obtained from the Information System for Notifiable Diseases (ZIKV cases) and the Public Health Event Registry (microcephaly and/or CNS alterations associated with congenital infection). Incidence rates and prevalence of ZIKA infection were smoothed by an empirical Bayesian estimator (LEbayes), producing the local empirical Bayesian rate (LEBR). In the spatial analysis, ZIKV infection and microcephaly cases were georeferenced by the municipality of residence for 2016 and grouped for 2017 and 2018. Global Moran's I and the Hot Spot Analysis tool (Getis-Ord Gi* statistics) were used to analyse the spatial autocorrelation and clusters of ZIKV infection and microcephaly, respectively. A generalised linear model from the Poisson family was used to assess the association between ecological determinants and the smoothing incidence rate of ZIKV infection. Results A total of 9892 cases of acute ZIKV infection and 121 cases of microcephaly were confirmed. The mean LEBR of the ZIKV infection in the 246 municipalities was 22.3 cases/100,000 inhabitants in 2016, and 10.3 cases/100,000 inhabitants in 2017 and 2018. The LEBR of the prevalence rate of microcephaly and/or CNS alterations associated with congenital infection was 7 cases/10,000 live births in 2016 and 2 cases/10,000 live births during 2017–2018. Hotspots of ZIKV infection and microcephaly cases were identified in the capital and neighbouring municipalities in 2016, with new clusters in the following years. In a multiple regression Poisson analysis, ZIKV infection was associated with higher population density, the incidence of dengue, Aedes larvae infestation index, and average rainfall. The important determinant of ZIKV infection incidence reduction was the increase in households attended by endemic disease control agents. Conclusions Our analyses were able to capture, in a more granular way, aspects that make it possible to inform public managers of the sentinel areas identified in the post-epidemic hotspots.

Introduction Flaviviruses are a genus of enveloped single-stranded RNA viruses that include dengue virus (DENV), yellow fever virus, West Nile virus (WNV), Japanese encephalitis virus, and Zika virus. Nowadays, diverse serological assays are available to diagnose flaviviruses. However, infection with flaviviruses induces cross-reactive antibodies, which are a challenge for serological diagnosis. Objective This systematic review aimed to assess the magnitude of medically important mosquito-borne flavivirus-induced antibody cross-reactivity and its influence on serological test outcomes. Methods This study was designed based on the PRISMA guidelines. It includes original research articles published between 1994 and 2019 that reported serological cross-reactions between medically important mosquito-borne flaviviruses. Articles were searched on PubMed using controlled vocabulary. Eligibility was assessed by title, abstract, and finally by reading the full paper. The articles included are compared, evaluated, and summarized narratively. Results A total of 2,911 articles were identified, and finally 14 were included. About 15.4%-84% of antibodies produced against non-DENV flaviviruses were cross-reactive with DENV on different assays. Up to 30% IgM and up to 60% IgG antibodies produced against non-WNV flaviviruses were cross-reactive with WNV on EIA assays. The magnitude of antibodies produced against flaviviruses that are cross-reactive with chikungunya virus (Alphavirus) was minimal (only about 7%). The highest antibody cross-reactivity of flaviviruses was reported in IgG-based assays compared to IgM-based assays and assays based on E-specific immunoglobulin compared to NS1-specific immunoglobulin. It was found that preexisting immunity due to vaccination or prior flavivirus exposure to antigenetically related species enhanced the cross-reactive antibody titer. Conclusion This review found the highest cross-reaction between DENV and non-DENV flaviviruses, especially yellow fever virus, and the least between chikungunya virus and DENV. Moreover, cross-reaction was higher on IgG assays than IgM ones and assays based on Eprotein compared to NS1protein. This implies that the reliability of serological test results in areas where more than one flavivirus exists is questionable. Therefore, interpretation of the existing serological assays should be undertaken with a great caution. Furthermore, research on novel diagnostic signatures for differential diagnosis of flaviviruses is needed.

To date, there are no broad-spectrum antivirals available to treat infections with flaviviruses such as dengue (DENV) and Zika virus (ZIKV). In this study, we determine the broad antiviral activity of the lantibiotic Labyrinthopeptin A1. We show that Laby A1 inhibits all DENV serotypes and various ZIKV strains with IC50 around 1 μM. The structurally related Laby A2 also displayed a consistent, but about tenfold lower, antiviral activity. Furthermore, Laby A1 inhibits many viruses from divergent families such as HIV, YFV, RSV and Punta Torovirus. Of interest, Laby A1 does not show activity against non-enveloped viruses. Its antiviral activity is independent of the cell line or the used evaluation method, and can also be observed in MDDC, a physiologically relevant primary cell type. Furthermore, Laby A1 demonstrates low cellular toxicity and has a more favorable SI compared to duramycin, a well-described lantibiotic with broad-spectrum antiviral activity. Time-of-drug addition experiments demonstrate that Laby A1 inhibits infection and entry processes of ZIKV and DENV. We reveal that Laby A1 performs its broad antiviral activity by interacting with a viral factor rather than a cellular factor, and that it has virucidal properties. Finally, using SPR interaction studies we demonstrate that Laby A1 interacts with several phospholipids (i.e. PE and PS) present in the viral envelope. Together with other recent Labyrinthopeptin antiviral publications, this work validates the activity of Laby A1 as broad antiviral entry inhibitor with a unique mechanism of action and demonstrates its potential value as antiviral agent against emerging flaviviruses. ispartof: VIROLOGY vol:562 pages:74-86 ispartof: location:United States status: published

First laboratory confirmed Zika case in Kerala was reported in Thiruvananthapuram, on 8th July 2021. Since then, 68 ZIKV positive cases have been reported from Kerala, with majority of cases from Thiruvananthapuram Corporation area. Based on the preliminary investigation, micro containment zones were identified and detailed investigation was carried out in these areas. Entomological surveillance indicated that all the three species of Aedes mosquitoes - Ae. aegypti, Ae. albopictus and Ae. vittatus were present in the survey areas. The Aedes larval indices were found above the critical level. The most preferred habitats of Aedes mosquitoes were water stagnated areas in cemented floor of the newly constructing buildings followed by cement tanks/ cement pits and discarded tires. ZIKV could be detected from all the three Aedes mosquitoes collected from the micro containment zones. Trasovarial transmission of ZIKV could be noted in this outbreak. Vector control was intensified with the active participation of local bodies and local health institutions. The epidemiological study showed most of the Zika positive cases has fever, rash and conjunctivitis and in majority of cases, the duration of the illness lasts only for 2-3 days. The females were more affected. The most affected age group was 21-30 followed by 31-40. Among the 68 ZIKV positive cases, 7 (10.29%) were pregnant women. No major anomaly was detected in ZIKV positive cases; however there is a need to scale up surveillance and vector control activities to prevent further outbreaks in Kerala and elsewhere. How to cite this article:Sasi MS, Rajendran R, Meenakshy V, Dilip Kumar T, Vardhanan S, Suresh T, Regu K, Sharma SN. Zika Virus: An Emerging Mosquito-Borne Disease Threat in Kerala. J Commun Dis. 2021;53(3):201-212. DOI: https://doi.org/10.24321/0019.5138.202158

Objetivo: Descrever um caso de microcefalia congenita causada pela infeccao do Zika virus em uma gestacao gemelar monozigotica. Metodos: A ultrassonografia transfontanelar e a tomografia computadorizada de crânio revelaram diferentes padroes de lesao para ambos gemeos com microcefalia congenita causada pela infeccao do Zika virus. As avaliacoes do desenvolvimento motor foram realizadas por meio da Escala Motora Infantil de Alberta (EMIA) e da Medida de Funcao Motora Grossa antes, durante e apos o tratamento fisioterapeutico. Resultados: As avaliacoes mostraram diferencas na aquisicao motora entre os gemeos. Os valores nas avaliacoes do primeiro caso forambem menores do que os do segundo caso, que apresentou maior atraso motor. Conclusao: O presente estudo mostrou que apesar dos gemeos serem monozigoticos, os efeitos das lesoes neurologicas reveladas por exames de neuroimagem foram piores no primeiro caso, e mesmo com duas sessoes semanais de reabilitacao, o desenvolvimento motor ao longo do tempo foi consideravelmente pior no gemeo do caso 1 quando comparado ao caso 2.