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1.
Rev Prat ; 70(3): 329-332, 2020 Mar.
Artigo em Francês | MEDLINE | ID: mdl-32877071

RESUMO

Zika virus infection: what advice in post-epidemic situation? Zika virus transmission is vector-borne, but it can also be sexual. The Zika disease contracted by an adult or child is most often mild but infection of the woman during pregnancy can lead to severe neurological congenital lesions. The Zika virus continues to circulate in many parts of the world. Risk of infection during travel is low but cannot be overlooked. An infected man can be infectious, during sexual intercourse, up to 3 months after contracting the disease. Information of pregnant women and couples with a child project is warranted if at least one of the two trips or has travelled in Zika virus transmission zone. Laboratory serologic tests can be used to determine if the partners have been infected and to verify, through the investigation of the virus in the semen, that there is no risk of sexual transmission.


Assuntos
Epidemias , Complicações Infecciosas na Gravidez , Infecção por Zika virus , Zika virus , Adulto , Criança , Feminino , Humanos , Masculino , Gravidez , Viagem , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/prevenção & controle , Infecção por Zika virus/transmissão
2.
Vaccine ; 38(44): 6922-6929, 2020 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-32893036

RESUMO

INTRODUCTION: Despite historical exclusion, there has been recent recognition of the need to address the health of pregnant women in research on vaccines against emerging pathogens. However, pregnant women's views and decision-making processes about vaccine research participation during infectious disease outbreaks remain underexplored. This study aims to examine women's decision-making processes around vaccine research participation during infectious disease outbreaks. METHODS: We conducted qualitative semi-structured in-depth interviews with pregnant and recently pregnant women (n = 13), eliciting their views on four hypothetical Zika Virus vaccine research scenarios and probing their decision-making processes around participation. After recorded interviews were transcribed, thematic analysis was conducted based on a priori and emergent themes. RESULTS: Most women interviewed were accepting of vaccine research scenarios. Three broad themes-evidence, risk, and trust-characterized women's decision-making processes. Women varied in how different types and levels of evidence impacted their considerations, which risks were most salient to their decision-making processes, and from whom they trusted recommendations about vaccine research participation. Exemplary quotes from each theme are presented, and lessons for vaccine development during the current COVID-19 pandemic and future outbreaks are discussed. CONCLUSION: Some pregnant women are accepting of participation in vaccine research during infectious disease outbreaks. Incorporating their priorities into trial design may facilitate their participation and generation of evidence for this important population.


Assuntos
Ensaios Clínicos como Assunto , Tomada de Decisões , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Gestantes/psicologia , Infecção por Zika virus/prevenção & controle , Adulto , Feminino , Humanos , Entrevistas como Assunto , Gravidez , Complicações Infecciosas na Gravidez/prevenção & controle , Medição de Risco , Vacinação , Vacinas , Vacinas Virais
3.
BMC Public Health ; 20(1): 1385, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32912177

RESUMO

BACKGROUND: In El Salvador, Aedes aegypti mosquitoes transmitting Zika and other arboviruses use water storage containers as important oviposition sites. Promotion of water storage container cleaning is a key element of prevention programs. We explored community perceptions surrounding cleaning practices among pregnant women, male partners of pregnant women, and women likely to become pregnant. METHODS: Researchers conducted 11 focus groups and 12 in-depth interviews which included individual elicitations of Zika prevention measures practiced in the community. Focus group participants rated 18 images depicting Zika-related behaviors according to effectiveness and feasibility in the community context, discussed influencing determinants, voted on community intentions to perform prevention behaviors, and performed washbasin cleaning simulations. In-depth interviews with male partners of pregnant women used projective techniques with images to explore their perceptions on a subset of Zika prevention behaviors. RESULTS: General cleaning of the home, to ensure a healthy environment, was a strong community norm. In this context, participants gave water storage container cleaning a high rating, for both its effectiveness and feasibility. Participants were convinced that they cleaned their water storage containers effectively against Zika, but their actual skills were inadequate to destroy Aedes aegypti eggs. A further constraint was the schedule of water availability. Even during pregnancy, male partners rarely cleaned water storage containers because water became available in homes when they were at work. Furthermore, prevailing gender norms did not foster male participation in domestic cleaning activities. Despite these factors, many men were willing to provide substantial support with cleaning when their partners were pregnant, in order to protect their family. CONCLUSIONS: Behavior change programs for the prevention of Zika and other arboviruses need to improve community members' mosquito egg destruction skills rather than perpetuate the promotion of non-specific cleaning in and around the home as effective. Egg elimination must be clearly identified as the objective of water storage container maintenance and programs should highlight the effective techniques to achieve this goal. In addition, programs must build the skills of family members who support pregnant women to maintain the frequency of effective egg destruction in all water storage containers of the home.


Assuntos
Aedes/virologia , Conhecimentos, Atitudes e Prática em Saúde , Controle de Mosquitos/métodos , Abastecimento de Água , Água , Infecção por Zika virus/prevenção & controle , Zika virus , Adolescente , Adulto , Animais , El Salvador , Feminino , Grupos Focais , Humanos , Masculino , Pessoa de Meia-Idade , Gravidez , Pesquisa Qualitativa , Características de Residência , Adulto Jovem , Zika virus/crescimento & desenvolvimento , Infecção por Zika virus/transmissão , Infecção por Zika virus/virologia
4.
PLoS Pathog ; 16(8): e1008754, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32776975

RESUMO

Arbovirus infection of Aedes aegypti salivary glands (SGs) determines transmission. However, there is a dearth of knowledge on SG immunity. Here, we characterized SG immune response to dengue, Zika and chikungunya viruses using high-throughput transcriptomics. We also describe a transcriptomic response associated to apoptosis, blood-feeding and lipid metabolism. The three viruses differentially regulate components of Toll, Immune deficiency (IMD) and c-Jun N- terminal Kinase (JNK) pathways. However, silencing of the Toll and IMD pathway components showed variable effects on SG infection by each virus. In contrast, regulation of the JNK pathway produced consistent responses in both SGs and midgut. Infection by the three viruses increased with depletion of the activator Kayak and decreased with depletion of the negative regulator Puckered. Virus-induced JNK pathway regulates the complement factor, Thioester containing protein-20 (TEP20), and the apoptosis activator, Dronc, in SGs. Individual and co-silencing of these genes demonstrate their antiviral effects and that both may function together. Co-silencing either TEP20 or Dronc with Puckered annihilates JNK pathway antiviral effect. Upon infection in SGs, TEP20 induces antimicrobial peptides (AMPs), while Dronc is required for apoptosis independently of TEP20. In conclusion, we revealed the broad antiviral function of JNK pathway in SGs and showed that it is mediated by a TEP20 complement and Dronc-induced apoptosis response. These results expand our understanding of the immune arsenal that blocks arbovirus transmission.


Assuntos
Aedes/imunologia , Apoptose , Febre de Chikungunya/imunologia , Proteínas do Sistema Complemento/imunologia , Dengue/imunologia , Sistema de Sinalização das MAP Quinases , Glândulas Salivares/imunologia , Infecção por Zika virus/imunologia , Aedes/virologia , Animais , Febre de Chikungunya/metabolismo , Febre de Chikungunya/prevenção & controle , Febre de Chikungunya/virologia , Vírus Chikungunya/imunologia , Proteínas do Sistema Complemento/metabolismo , Dengue/metabolismo , Dengue/prevenção & controle , Dengue/virologia , Vírus da Dengue/imunologia , Feminino , Interações Hospedeiro-Patógeno , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Insetos Vetores/imunologia , Insetos Vetores/virologia , Glândulas Salivares/virologia , Transcriptoma , Replicação Viral , Zika virus/imunologia , Infecção por Zika virus/metabolismo , Infecção por Zika virus/prevenção & controle , Infecção por Zika virus/virologia
5.
Trends Biotechnol ; 38(9): 943-947, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32600777

RESUMO

Vaccine solutions rarely reach the public until after an outbreak abates; an Ebola vaccine was approved 5 years after peak outbreak and SARS, MERS, and Zika vaccines are still in clinical development. Despite massive leaps forward in rapid science, other regulatory bottlenecks are hamstringing the global effort for pandemic vaccines.


Assuntos
Infecções por Coronavirus/prevenção & controle , Aprovação de Drogas/organização & administração , Doença pelo Vírus Ebola/prevenção & controle , Influenza Humana/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Virais/biossíntese , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Vacinas contra Ebola/administração & dosagem , Vacinas contra Ebola/biossíntese , Ebolavirus/efeitos dos fármacos , Ebolavirus/imunologia , Ebolavirus/patogenicidade , Europa (Continente)/epidemiologia , Saúde Global/tendências , Regulamentação Governamental , Doença pelo Vírus Ebola/epidemiologia , Doença pelo Vírus Ebola/imunologia , Doença pelo Vírus Ebola/virologia , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/imunologia , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/biossíntese , Influenza Humana/epidemiologia , Influenza Humana/imunologia , Influenza Humana/virologia , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Vírus da SARS/efeitos dos fármacos , Vírus da SARS/imunologia , Vírus da SARS/patogenicidade , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/prevenção & controle , Síndrome Respiratória Aguda Grave/virologia , Estados Unidos/epidemiologia , Vacinas Virais/administração & dosagem , Zika virus/efeitos dos fármacos , Zika virus/imunologia , Zika virus/patogenicidade , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/imunologia , Infecção por Zika virus/prevenção & controle , Infecção por Zika virus/virologia
6.
J Neuropathol Exp Neurol ; 79(8): 823-842, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32647884

RESUMO

Biological evolution of the microbiome continually drives the emergence of human viral pathogens, a subset of which attack the nervous system. The sheer number of pathogens that have appeared, along with their abundance in the environment, demand our attention. For the most part, our innate and adaptive immune systems have successfully protected us from infection; however, in the past 5 decades, through pathogen mutation and ecosystem disruption, a dozen viruses emerged to cause significant neurologic disease. Most of these pathogens have come from sylvatic reservoirs having made the energetically difficult, and fortuitously rare, jump into humans. But the human microbiome is also replete with agents already adapted to the host that need only minor mutations to create neurotropic/toxic agents. While each host/virus symbiosis is unique, this review examines virologic and immunologic principles that govern the pathogenesis of different viral CNS infections that were described in the past 50 years (Influenza, West Nile Virus, Zika, Rift Valley Fever Virus, Hendra/Nipah, Enterovirus-A71/-D68, Human parechovirus, HIV, and SARS-CoV). Knowledge of these pathogens provides us the opportunity to respond and mitigate infection while at the same time prepare for inevitable arrival of unknown agents.


Assuntos
Viroses do Sistema Nervoso Central/epidemiologia , Viroses do Sistema Nervoso Central/transmissão , Zoonoses/epidemiologia , Zoonoses/transmissão , Animais , Aves , Viroses do Sistema Nervoso Central/prevenção & controle , Ecossistema , Humanos , Influenza Aviária/epidemiologia , Influenza Aviária/prevenção & controle , Influenza Aviária/transmissão , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Influenza Humana/transmissão , Febre do Nilo Ocidental/epidemiologia , Febre do Nilo Ocidental/prevenção & controle , Febre do Nilo Ocidental/transmissão , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/prevenção & controle , Infecção por Zika virus/transmissão , Zoonoses/prevenção & controle
7.
Lancet Infect Dis ; 20(9): 1061-1070, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32618279

RESUMO

BACKGROUND: The development of an effective vaccine against Zika virus remains a public health priority. A Zika purified inactivated virus (ZPIV) vaccine candidate has been shown to protect animals against Zika virus challenge and to be well tolerated and immunogenic in humans up to 8 weeks of follow-up. We aimed to assess the safety and immunogenicity of ZPIV in humans up to 52 weeks of follow-up when given via standard or accelerated vaccination schedules. METHODS: We did a single-centre, double-blind, randomised controlled, phase 1 trial in healthy adults aged 18-50 years with no known history of flavivirus vaccination or infection at Beth Israel Deaconess Medical Center in Boston, MA, USA. Participants were sequentially enrolled into one of three groups: ZPIV given at weeks 0 and 4 (standard regimen), weeks 0 and 2 (accelerated regimen), or week 0 alone (single-dose regimen). Within each group, participants were randomly assigned using a computer-generated randomisation schedule to receive an intramuscular injection of 5 µg ZPIV or saline placebo, in a ratio of 5:1. The sponsor, clinical staff, investigators, participants, and laboratory personnel were masked to treatment assignment. The primary endpoint was safety up to day 364 after final dose administration, and secondary endpoints were proportion of participants with positive humoral immune responses (50% microneutralisation titre [MN50] ≥100) and geometric mean MN50 at observed peak response (ie, the highest neutralising antibody level observed for an individual participant across all timepoints) and week 28. All participants who received at least one dose of ZPIV or placebo were included in the safety population; the analysis of immunogenicity at observed peak included all participants who received at least one dose of ZPIV or placebo and had any adverse events or immunogenicity data after dosing. The week 28 immunogenicity analysis population consisted of all participants who received ZPIV or placebo and had immunogenicity data available at week 28. This trial is registered with ClinicalTrials.gov, NCT02937233. FINDINGS: Between Dec 8, 2016, and May 17, 2017, 12 participants were enrolled into each group and then randomly assigned to vaccine (n=10) or placebo (n=2). There were no serious or grade 3 treatment-related adverse events. The most common reactions among the 30 participants who received the vaccine were injection-site pain (24 [80%]), fatigue (16 [53%]), and headache (14 [46%]). A positive response at observed peak titre was detected in all participants who received ZPIV via the standard regimen, in eight (80%) of ten participants who received ZPIV via the accelerated regimen, and in none of the ten participants who received ZPIV via the single-dose regimen. The geometric mean of all individual participants' observed peak values was 1153·9 (95% CI 455·2-2925·2) in the standard regimen group, 517·7 (142·9-1875·6) in the accelerated regimen group, and 6·3 (3·7-10·8) in the single-dose regimen group. At week 28, a positive response was observed in one (13%) of eight participants who received ZPIV via the standard regimen and in no participant who received ZPIV via the accelerated (n=7) or single-dose (n=10) regimens. The geomteric mean titre (GMT) at this timepoint was 13·9 (95% CI 3·5-55·1) in the standard regimen group and 6·9 (4·0-11·9) in the accelerated regimen group; antibody titres were undetectable at 28 weeks in participants who received ZPIV via the single-dose regimen. For all vaccine schedules, GMTs peaked 2 weeks after the final vaccination and declined to less than 100 by study week 16. There was no difference in observed peak GMTs between the standard 4-week and the accelerated 2-week boosting regimens (p=0·4494). INTERPRETATION: ZPIV was safe and well tolerated in humans up to 52 weeks of follow-up. ZPIV immunogenicity required two doses and was not durable. Additional studies of ZPIV to optimise dosing schedules are ongoing. FUNDING: The Henry M Jackson Foundation for the Advancement of Military Medicine.


Assuntos
Imunogenicidade da Vacina , Vacinas de Produtos Inativados/imunologia , Vacinas Virais/imunologia , Infecção por Zika virus/prevenção & controle , Zika virus/imunologia , Adolescente , Adulto , Feminino , Humanos , Esquemas de Imunização , Masculino , Pessoa de Meia-Idade , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/efeitos adversos , Vacinas Virais/administração & dosagem , Vacinas Virais/efeitos adversos , Adulto Jovem
8.
PLoS Negl Trop Dis ; 14(6): e0007870, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32569323

RESUMO

Emerging mosquito-borne viruses like Zika, dengue, and chikungunya pose a major threat to public health, especially in low-income regions of Central and South America, southeast Asia, and the Caribbean. Outbreaks of these diseases are likely to have long-term social and economic consequences due to Zika-induced congenital microcephaly and other complications. Larval control of the container-inhabiting mosquitoes that transmit these infections is an important tool for mitigating outbreaks. However, metapopulation theory suggests that spatiotemporally uneven larvicide treatment can impede control effectiveness, as recolonization compensates for mortality within patches. Coordinating the timing of treatment among patches could therefore substantially improve epidemic control, but we must also consider economic constraints, since coordination may have costs that divert resources from treatment. To inform practical disease management strategies, we ask how coordination among neighbors in the timing of mosquito control efforts influences the size of a mosquito-borne infectious disease outbreak under the realistic assumption that coordination has costs. Using an SIR (Susceptible-Infectious-Recovered)/metapopulation model of mosquito and disease dynamics, we examine whether sharing surveillance information and coordinating larvicide treatment among neighboring patches reduces human infections when incorporating coordination costs. We examine how different types of coordination costs and different surveillance methods jointly influence the effectiveness of larval control. We find that the effect of coordination depends on both costs and the type of surveillance used to inform treatment. With epidemiological surveillance, coordination improves disease outcomes, even when costly. With demographic surveillance, coordination either improves or hampers disease control, depending on the type of costs and surveillance sensitivity. Our results suggest coordination among neighbors can improve management of mosquito-borne epidemics under many, but not all, assumptions about costs. Therefore, estimating coordination costs is an important step for most effectively applying metapopulation theory to strategies for managing outbreaks of mosquito-borne viral infections.


Assuntos
Custos e Análise de Custo , Transmissão de Doença Infecciosa/prevenção & controle , Controle de Mosquitos/métodos , Controle de Mosquitos/organização & administração , Doenças Transmitidas por Vetores/prevenção & controle , Infecção por Zika virus/prevenção & controle , Humanos , Modelos Teóricos , Controle de Mosquitos/economia , Doenças Transmitidas por Vetores/transmissão , Infecção por Zika virus/transmissão
9.
PLoS Negl Trop Dis ; 14(5): e0008285, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32463814

RESUMO

Little is known about the contribution of virus-specific and cross-reacting antibodies (Abs) or the cellular immune response generated by a primary dengue (DENV) infection on the course of a secondary zika (ZIKV) infection in vivo. Here we show that the length of time between DENV/ZIKV infections has a qualitative impact on controlling early ZIKV replication. Depletion of DENV2-specific Abs in sera confirmed that those type-specific Abs do not contribute to ZIKV control. We show that the magnitude and durability of the neutralizing antibodies (nAbs) induced by a secondary ZIKV infection is modest compared to the response induced after a secondary heterologous DENV infection. Our in vivo results are showing a complex interplay between the cellular and innate immune responses characterized by a high frequency of plasmacytoid dendritic cells (pDC) correlating with an increase in the frequency of DENV antigen specific T cells and a significant control of ZIKV replication which is time dependent. Taken together, our results suggest that early after ZIKV infection other mechanisms such as the innate and cellular immune responses may play a predominant role in controlling ZIKV replication. Regardless of the time elapsed between infections there was no evidence of in vivo antibody-dependent enhancement (ADE) of ZIKV by DENV immunity. These findings have pivotal implications while interpreting ZIKV pathogenesis in flavivirus-experimented populations, diagnostic results interpretation and vaccine designs and schedules among others.


Assuntos
Dengue/imunologia , Imunidade Celular , Imunidade Humoral , Imunidade Inata , Infecção por Zika virus/imunologia , Infecção por Zika virus/prevenção & controle , Zika virus/imunologia , Animais , Células Dendríticas/imunologia , Fatores Imunológicos , Macaca mulatta , Masculino , Linfócitos T/imunologia , Fatores de Tempo
10.
Womens Health Issues ; 30(4): 268-276, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32376188

RESUMO

BACKGROUND: The Zika Contraception Access Network (Z-CAN) was designed to provide women in Puerto Rico who chose to delay or avoid pregnancy during the 2016-2017 Zika virus outbreak access to high-quality client-centered contraceptive counseling and the full range of reversible contractive methods on the same day and at no cost through a network of trained providers. We evaluated the implementation of Z-CAN from the patient perspective. METHODS: An online survey, administered to a subset of women served by the Z-CAN program approximately 2 weeks after their initial Z-CAN visit, assessed patient satisfaction and receipt of services consistent with select program strategies: receipt of high-quality client-centered contraceptive counseling, same-day access to the contraceptive method they were most interested in after counseling, and no-cost contraception. RESULTS: Of 3,503 respondents, 85.2% reported receiving high-quality client-centered contraceptive counseling. Among women interested in a contraceptive method after counseling (n = 3,470), most reported same-day access to that method (86.8%) and most reported receiving some method of contraception at no cost (87.4%). Women who reported receiving services according to Z-CAN program strategies were more likely than those who did not to be very satisfied with services. Women who received high-quality client-centered contraceptive counseling and same-day access to the method they were most interested in after counseling were also more likely to be very satisfied with the contraceptive method received. CONCLUSIONS: A contraception access program can be rapidly implemented with high fidelity to program strategies in a fast-moving and complex public health emergency setting.


Assuntos
Anticoncepcionais/provisão & distribução , Aconselhamento/métodos , Acesso aos Serviços de Saúde/organização & administração , Satisfação do Paciente , Assistência Centrada no Paciente , Infecção por Zika virus/prevenção & controle , Zika virus , Adulto , Anticoncepção/métodos , Comportamento Contraceptivo , Surtos de Doenças/prevenção & controle , Serviços de Planejamento Familiar/organização & administração , Feminino , Acesso aos Serviços de Saúde/estatística & dados numéricos , Humanos , Gravidez , Porto Rico/epidemiologia , Infecção por Zika virus/epidemiologia
11.
PLoS Pathog ; 16(5): e1008521, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32392268

RESUMO

Zika virus (ZIKV) infection may lead to congenital microcephaly and pregnancy loss in pregnant women. In the context of pregnancy, folic acid (FA) supplementation may reduce the risk of abnormal pregnancy outcomes. Intriguingly, FA may have a beneficial effect on the adverse pregnancy outcomes associated with ZIKV infection. Here, we show that FA inhibits ZIKV replication in human umbilical vein endothelial cells (HUVECs) and a cell culture model of blood-placental barrier (BPB). The inhibitory effect of FA against ZIKV infection is associated with FRα-AMPK signaling. Furthermore, treatment with FA reduces pathological features in the placenta, number of fetal resorptions, and stillbirths in two mouse models of in utero ZIKV transmission. Mice with FA treatment showed lower viral burden and better prognostic profiles in the placenta including reduced inflammatory response, and enhanced integrity of BPB. Overall, our findings suggest the preventive role of FA supplementation in ZIKV-associated abnormal pregnancy and warrant nutritional surveillance to evaluate maternal FA status in areas with active ZIKV transmission.


Assuntos
Ácido Fólico/farmacologia , Placenta , Complicações Infecciosas na Gravidez , Infecção por Zika virus/prevenção & controle , Zika virus/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Camundongos , Microcefalia/metabolismo , Microcefalia/patologia , Microcefalia/prevenção & controle , Microcefalia/virologia , Placenta/metabolismo , Placenta/patologia , Placenta/virologia , Gravidez , Complicações Infecciosas na Gravidez/metabolismo , Complicações Infecciosas na Gravidez/patologia , Complicações Infecciosas na Gravidez/prevenção & controle , Infecção por Zika virus/metabolismo , Infecção por Zika virus/patologia
12.
PLoS Comput Biol ; 16(4): e1007743, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32310958

RESUMO

Recent years have seen rising incidence of dengue and large outbreaks of Zika and chikungunya, which are all caused by viruses transmitted by Aedes aegypti mosquitoes. In most settings, the primary intervention against Aedes-transmitted viruses is vector control, such as indoor, ultra-low volume (ULV) spraying. Targeted indoor residual spraying (TIRS) has the potential to more effectively impact Aedes-borne diseases, but its implementation requires careful planning and evaluation. The optimal time to deploy these interventions and their relative epidemiological effects are, however, not well understood. We used an agent-based model of dengue virus transmission calibrated to data from Iquitos, Peru to assess the epidemiological effects of these interventions under differing strategies for deploying them. Specifically, we compared strategies where spray application was initiated when incidence rose above a threshold based on incidence in recent years to strategies where spraying occurred at the same time(s) each year. In the absence of spraying, the model predicted 361,000 infections [inter-quartile range (IQR): 347,000-383,000] in the period 2000-2010. The ULV strategy with the fewest median infections was spraying twice yearly, in March and October, which led to a median of 172,000 infections [IQR: 158,000-183,000], a 52% reduction from baseline. Compared to spraying once yearly in September, the best threshold-based strategy utilizing ULV had fewer median infections (254,000 vs. 261,000), but required more spraying (351 vs. 274 days). For TIRS, the best strategy was threshold-based, which led to the fewest infections of all strategies tested (9,900; [IQR: 8,720-11,400], a 94% reduction), and required fewer days spraying than the equivalent ULV strategy (280). Although spraying twice each year is likely to avert the most infections, our results indicate that a threshold-based strategy can become an alternative to better balance the translation of spraying effort into impact, particularly if used with a residual insecticide.


Assuntos
Biologia Computacional/métodos , Dengue/prevenção & controle , Controle de Mosquitos/métodos , Aedes/fisiologia , Animais , Simulação por Computador , Dengue/epidemiologia , Dengue/transmissão , Surtos de Doenças , Humanos , Incidência , Inseticidas , Modelos Teóricos , Mosquitos Vetores , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/prevenção & controle , Infecção por Zika virus/transmissão
13.
Obstet Gynecol ; 135(5): 1095-1103, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32282596

RESUMO

OBJECTIVE: To describe characteristics of the full population of women who participated in the Zika Contraception Access Network program in Puerto Rico during the virus outbreak and to examine factors associated with removal of a long-acting reversible contraception (LARC) method by a Zika Contraception Access Network provider during the program's duration (May 2016-September 2017). METHODS: We conducted an observational cohort study. The Zika Contraception Access Network program was designed to increase access to contraception services in Puerto Rico for women who chose to prevent pregnancy during the Zika virus outbreak as a primary strategy to reduce adverse Zika virus-related pregnancy and birth outcomes. Among program participants, an observational cohort of women served by the Zika Contraception Access Network Program, we describe their demographic and program-specific characteristics, including contraceptive method mix before and after the program. We also report on LARC removals by Zika Contraception Access Network providers during the program. We examined factors associated with LARC removal using multivariable logistic regression. RESULTS: A total of 29,221 women received an initial Zika Contraception Access Network visit during the program. Ninety-six percent (27,985) of women received same-day provision of a contraceptive method and 70% (20,381) chose a LARC method. While the program was active, 719 (4%) women who chose a LARC at the initial visit had it removed. Women with a college degree or higher were more likely to have their LARC removed (adjusted prevalence ratio [aPR] 1.24); breastfeeding women (aPR 0.67) and those using a LARC method before Zika Contraception Access Network (aPR 0.55) were less likely to have their LARC removed. CONCLUSION: The Zika Contraception Access Network program was designed as a short-term response for rapid implementation of contraceptive services in a complex emergency setting in Puerto Rico and served more than 29,000 women. The Zika Contraception Access Network program had high LARC uptake and a low proportion of removals by a Zika Contraception Access Network provider during the program. A removal-inclusive design, with access to removals well beyond the program period, maximizes women's reproductive autonomy to access LARC removal when desired. This model could be replicated in other settings where the goal is to increase contraception access.


Assuntos
Remoção de Dispositivo/estatística & dados numéricos , Serviços de Planejamento Familiar/estatística & dados numéricos , Contracepção Reversível de Longo Prazo/estatística & dados numéricos , Complicações Infecciosas na Gravidez/prevenção & controle , Infecção por Zika virus/prevenção & controle , Adolescente , Adulto , Surtos de Doenças , Serviços de Planejamento Familiar/métodos , Feminino , Humanos , Contracepção Reversível de Longo Prazo/métodos , Gravidez , Complicações Infecciosas na Gravidez/virologia , Avaliação de Programas e Projetos de Saúde , Porto Rico/epidemiologia , Adulto Jovem , Zika virus , Infecção por Zika virus/epidemiologia
14.
Public Health Rep ; 135(3): 343-353, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32243762

RESUMO

OBJECTIVES: The spread of Zika virus throughout Latin America and parts of the United States in 2016 and 2017 presented a challenge to public health communicators. The objective of our study was to describe emergency risk communication practices during the 2016-2017 Zika outbreak to inform future infectious disease communication efforts. METHODS: We conducted semi-structured telephone interviews with 13 public health policy makers and practitioners, 10 public information officers, and 5 vector-control officials from May through August 2017. RESULTS: Within the public health macro-environment, extended outbreak timeframe, government trust, US residence status, and economic insecurity set the backdrop for Zika communication efforts. Limited resources, staffing, and partnerships negatively affected public health structural capacity for communication efforts. Public health communicators and practitioners used a range of processes and practices to engage in education and outreach, including fieldwork, community meetings, and contact with health care providers. Overall, public health agencies' primary goals were to prevent Zika infection, reduce transmission, and prevent adverse birth outcomes. CONCLUSIONS: Lessons learned from this disease response included understanding the macro-environment, developing partnerships across agencies and the community, and valuing diverse message platforms. These lessons can be used to improve communication approaches for health officials at the local, state, and federal levels during future infectious disease outbreaks.


Assuntos
Surtos de Doenças/prevenção & controle , Comunicação em Saúde/métodos , Administração em Saúde Pública/métodos , Infecção por Zika virus/epidemiologia , Controle de Doenças Transmissíveis/métodos , Comportamento Cooperativo , Planejamento em Desastres/organização & administração , Humanos , Fatores Socioeconômicos , Infecção por Zika virus/prevenção & controle
15.
PLoS Negl Trop Dis ; 14(4): e0008149, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32251455

RESUMO

BACKGROUND: Individual behavior, particularly choices about prevention, plays a key role in infection transmission of vector-borne diseases (VBDs). Since the actual risk of infection is often uncertain, individual behavior is influenced by the perceived risk. A low risk perception is likely to diminish the use of preventive measures (behavior). If risk perception is a good indicator of the actual risk, then it has important implications in a context of disease elimination. However, more research is needed to improve our understanding of the role of human behavior in disease transmission. The objective of this study is to explore whether preventive behavior is responsive to risk perception, taking into account the links with disease knowledge and controlling for individuals' socioeconomic and demographic characteristics. More specifically, the study focuses on malaria, dengue fever, Zika and cutaneous leishmaniasis (CL), using primary data collected in Guyana-a key country for the control and/or elimination of VBDs, given its geographic location. METHODS AND FINDINGS: The data were collected between August and December 2017 in four regions of the country. Questions on disease knowledge, risk perception and self-reported use of preventive measures were asked to each participant for the four diseases. A structural equation model was estimated. It focused on data collected from private households only in order to control for individuals' socioeconomic and demographic characteristics, which led to a sample size of 497 participants. The findings showed evidence of a bidirectional association between risk perception and behavior. A one-unit increase in risk perception translated into a 0.53 unit increase in self-reported preventive behavior for all diseases, while a one-unit increase in self-reported preventive behavior (i.e. the use of an additional measure) led to a 0.46 unit decrease in risk perception for all diseases (except CL). This study also showed that higher education significantly improves knowledge and that better knowledge increases the take up of preventive measures for malaria and dengue, without affecting risk perception. CONCLUSIONS: In trying to reach elimination, it appears crucial to promote awareness of the risks and facilitate access to preventive measures, so that lower risk perception does not translate into lower preventive behavior.


Assuntos
Comportamento , Conhecimentos, Atitudes e Prática em Saúde , Doenças Transmitidas por Vetores/prevenção & controle , Doenças Transmitidas por Vetores/transmissão , Demografia , Dengue/prevenção & controle , Dengue/transmissão , Características da Família , Feminino , Guiana , Humanos , Leishmaniose Cutânea/prevenção & controle , Leishmaniose Cutânea/transmissão , Malária/prevenção & controle , Malária/transmissão , Masculino , Fatores de Risco , Autorrelato , Fatores Socioeconômicos , Inquéritos e Questionários , Infecção por Zika virus/prevenção & controle , Infecção por Zika virus/transmissão
16.
PLoS Negl Trop Dis ; 14(4): e0008219, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32298261

RESUMO

Aedes aegypti is the primary vector of dengue, chikungunya, Zika, and urban yellow fever. Insecticides are often the most effective tools to rapidly decrease the density of vector populations, especially during arbovirus disease outbreaks. However, the intense use of insecticides, particularly pyrethroids, has selected for resistant mosquito populations worldwide. Mutations in the voltage gated sodium channel (NaV) are among the principal mechanisms of resistance to pyrethroids and DDT, also known as "knockdown resistance," kdr. Here we report studies on the origin and dispersion of kdr haplotypes in samples of Ae. aegypti from its worldwide distribution. We amplified the IIS6 and IIIS6 NaV segments from pools of Ae. aegypti populations from 15 countries, in South and North America, Africa, Asia, Pacific, and Australia. The amplicons were barcoded and sequenced using NGS Ion Torrent. Output data were filtered and analyzed using the bioinformatic pipeline Seekdeep to determine frequencies of the IIS6 and IIIS6 haplotypes per population. Phylogenetic relationships among the haplotypes were used to infer whether the kdr mutations have a single or multiple origin. We found 26 and 18 haplotypes, respectively for the IIS6 and IIIS6 segments, among which were the known kdr mutations 989P, 1011M, 1016I and 1016G (IIS6), 1520I, and 1534C (IIIS6). The highest diversity of haplotypes was found in African samples. Kdr mutations 1011M and 1016I were found only in American and African populations, 989P + 1016G and 1520I + 1534C in Asia, while 1534C was present in samples from all continents, except Australia. Based primarily on the intron sequence, IIS6 haplotypes were subdivided into two well-defined clades (A and B). Subsequent phasing of the IIS6 + IIIS6 haplotypes indicates two distinct origins for the 1534C kdr mutation. These results provide evidence of kdr mutations arising de novo at specific locations within the Ae. aegypti geographic distribution. In addition, our results suggest that the 1534C kdr mutation had at least two independent origins. We can thus conclude that insecticide selection pressure with DDT and more recently with pyrethroids is selecting for independent convergent mutations in NaV.


Assuntos
Aedes/efeitos dos fármacos , Aedes/genética , Genes de Insetos , Resistência a Inseticidas/genética , Mutação , Aedes/virologia , África , Alelos , Animais , Ásia , Austrália , Febre de Chikungunya/prevenção & controle , Febre de Chikungunya/transmissão , DNA/genética , Dengue/prevenção & controle , Dengue/transmissão , Frequência do Gene , Genótipo , Inseticidas , Mosquitos Vetores/genética , Mosquitos Vetores/virologia , América do Norte , Piretrinas , Febre Amarela/prevenção & controle , Febre Amarela/transmissão , Infecção por Zika virus/prevenção & controle , Infecção por Zika virus/transmissão
17.
J Virol ; 94(10)2020 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-32132233

RESUMO

Members of the flavivirus genus share a high level of sequence similarity and often circulate in the same geographical regions. However, whether T cells induced by one viral species cross-react with other related flaviviruses has not been globally addressed. In this study, we tested pools of epitopes derived from dengue (DENV), Zika (ZIKV), Japanese encephalitis (JEV), West Nile (WNV), and yellow fever (YFV) viruses by intracellular cytokine staining (ICS) using peripheral blood mononuclear cells (PBMCs) of individuals naturally exposed to DENV or immunized with DENV (TV005) or YF17D vaccine. CD8 T cell responses recognized epitopes from multiple flaviviruses; however, the magnitude of cross-reactive responses was consistently severalfold lower than those to the autologous epitope pools and was associated with lower expression of activation markers such as CD40L, CD69, and CD137. Next, we characterized the antigen sensitivity of short-term T cell lines (TCL) representing 29 different individual epitope/donor combinations. TCL derived from DENV monovalent vaccinees induced CD8 and CD4 T cells that cross-reacted within the DENV serocomplex but were consistently associated with >100-fold-lower antigen sensitivity for most other flaviviruses, with no cross-recognition of YFV-derived peptides. CD8 and CD4 TCL from YF17D vaccinees were associated with very limited cross-reactivity with any other flaviviruses and in five out of eight cases >1,000-fold-lower antigen sensitivity. Overall, our data suggest limited cross-reactivity for both CD4 and CD8 T cell responses between flaviviruses and have implications for understanding immunity elicited by natural infection and strategies to develop live attenuated vaccines against flaviviral species.IMPORTANCE The envelope (E) protein is the dominant target of neutralizing antibodies for dengue virus (DENV) and yellow fever virus (YFV). Accordingly, several DENV vaccine constructs use the E protein in a live attenuated vaccine format, utilizing a backbone derived from a heterologous flavivirus (such as YF) as a delivery vector. This backbone comprises the nonstructural (NS) and capsid (C) antigens, which are dominant targets of T cell responses. Here, we demonstrate that cross-reactivity at the level of T cell responses among different flaviviruses is very limited, despite high levels of sequence homology. Thus, the use of heterologous flavivirus species as a live attenuated vaccine vector is not likely to generate optimal T cell responses and might thus impair vaccine performance.


Assuntos
Reações Cruzadas/imunologia , Infecções por Flavivirus/imunologia , Flavivirus/imunologia , Vacinação , Vacinas Atenuadas/imunologia , Vacinas Virais/imunologia , Adolescente , Adulto , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos/imunologia , Dengue/imunologia , Dengue/prevenção & controle , Vacinas contra Dengue/imunologia , Vírus da Dengue/imunologia , Encefalite Japonesa/imunologia , Encefalite Japonesa/prevenção & controle , Epitopos de Linfócito T/genética , Feminino , Infecções por Flavivirus/prevenção & controle , Humanos , Leucócitos Mononucleares/imunologia , Masculino , Pessoa de Meia-Idade , Homologia de Sequência , Febre do Nilo Ocidental/imunologia , Febre do Nilo Ocidental/prevenção & controle , Febre Amarela/imunologia , Febre Amarela/prevenção & controle , Vacina contra Febre Amarela , Vírus da Febre Amarela/imunologia , Adulto Jovem , Zika virus/imunologia , Infecção por Zika virus/imunologia , Infecção por Zika virus/prevenção & controle
18.
Proc Natl Acad Sci U S A ; 117(14): 7981-7989, 2020 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-32209664

RESUMO

Human infection by Zika virus (ZIKV) during pregnancy can lead to vertical transmission and fetal aberrations, including microcephaly. Prophylactic administration of antibodies can diminish or prevent ZIKV infection in animal models, but whether passive immunization can protect nonhuman primates and their fetuses during pregnancy has not been determined. Z004 and Z021 are neutralizing monoclonal antibodies to domain III of the envelope (EDIII) of ZIKV. Together the two antibodies protect nonpregnant macaques against infection even after Fc modifications to prevent antibody-dependent enhancement (ADE) in vitro and extend their half-lives. Here we report on prophylactic coadministration of the Fc-modified antibodies to pregnant rhesus macaques challenged three times with ZIKV during first and second trimester. The two antibodies did not entirely eliminate maternal viremia but limited vertical transmission, protecting the fetus from neurologic damage. Thus, maternal passive immunization with two antibodies to EDIII can shield primate fetuses from the harmful effects of ZIKV.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Complicações Infecciosas na Gravidez/prevenção & controle , Infecção por Zika virus/prevenção & controle , Zika virus/imunologia , Animais , Animais Recém-Nascidos , Anticorpos Monoclonais/genética , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/administração & dosagem , Anticorpos Neutralizantes/genética , Anticorpos Neutralizantes/imunologia , Modelos Animais de Doenças , Quimioterapia Combinada , Feminino , Feto/imunologia , Feto/virologia , Células HEK293 , Humanos , Fragmentos Fc das Imunoglobulinas/administração & dosagem , Fragmentos Fc das Imunoglobulinas/genética , Fragmentos Fc das Imunoglobulinas/imunologia , Imunoglobulina G/administração & dosagem , Imunoglobulina G/genética , Imunoglobulina G/imunologia , Gravidez , Complicações Infecciosas na Gravidez/imunologia , Complicações Infecciosas na Gravidez/virologia , Engenharia de Proteínas , RNA Viral/isolamento & purificação , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Zika virus/genética , Zika virus/patogenicidade , Infecção por Zika virus/imunologia , Infecção por Zika virus/transmissão , Infecção por Zika virus/virologia
19.
Insect Biochem Mol Biol ; 120: 103338, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32126277

RESUMO

Aedes aegypti is the main urban vector of dengue virus, chikungunya virus and Zika virus due to its great dispersal capacity and virus susceptibility. A. aegypti feed on plant-derived sugars but females need a blood meal for egg maturation. Haematophagous arthropods need to overcome host haemostasis and local immune reactions in order to take a blood meal. In this context, molecules present in the saliva and/or intestinal contents of these arthropods must contain inhibitors of the complement system (CS). CS salivary and/or intestinal inhibitors are crucial to protect gut cells of haematophagous arthropods against complement attack. The present work aimed to investigate the anti-complement activity of A. aegypti intestinal contents on the alternative, classical and lectin pathways of the human complement system. Here we show that A. aegypti gut contents inhibited the human classical and the lectin pathways but not the alternative pathway. The A. aegypti gut content has a serine protease able to specifically cleave and inactivate human C4, which is a novel mechanism for human complement inactivation in haematophagous arthropods. The gut of female A. aegypti was capable of capturing human serum factor H (a negative complement modulator), unlike males. C3 molecules in recently blood-fed female A. aegypti remain in their original state, being inactivated to iC3b soon after a blood feed. A transmission-blocking vaccine using these complement inhibitory proteins as antigens has the potential to interfere with the insect's survival, reproductive fitness and block their infection by the arboviruses they transmit to humans.


Assuntos
Aedes/fisiologia , Febre de Chikungunya/prevenção & controle , Proteínas Inativadoras do Complemento/metabolismo , Dengue/prevenção & controle , Microbioma Gastrointestinal/fisiologia , Infecção por Zika virus/prevenção & controle , Aedes/microbiologia , América , Animais , Vírus Chikungunya/fisiologia , Vírus da Dengue/fisiologia , Feminino , Masculino , Mosquitos Vetores/microbiologia , Mosquitos Vetores/fisiologia , Zika virus/fisiologia
20.
PLoS Negl Trop Dis ; 14(3): e0007994, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32142512

RESUMO

BACKGROUND: Zika remains an epidemiological threat in Latin America, including the Dominican Republic. Although transmitted by the same mosquito as Dengue and Chikungunya, Zika is unique in the potentially harmful consequences for babies born to women infected during pregnancy. Experts highlight the feminization of Zika, in terms of burden of disease and women's caregiving responsibilities. Understanding gender's role in Zika prevention, therefore, is key to strengthening current and future programs. METHODOLOGY/PRINCIPAL FINDINGS: This qualitative study, comprised of 12 focus group discussions and eight in-depth interviews, explored gender's role in Zika among pregnant and non-pregnant women as well as male partners of pregnant women in the Dominican Republic. Topics included perceptions about Zika and perceived feasibility and effectiveness of prevention behaviors (e.g. cleaning water storage containers, using condoms during pregnancy). Researchers applied grounded theory through a process of deductive coding-classifying data around predetermined categories-followed by inductive coding-identifying themes that emerged from coded data. Study findings uncovered three ways in which gender may influence Zika prevention. First, women are largely responsible for household chores-including cleaning water storage containers-with men as assistants. Second, men described their role in the family as the protector. Finally, men and women believed that partners would perceive suggesting condom use or abstinence during pregnancy as a sign of infidelity. CONCLUSIONS: Current/future Zika programs should address knowledge gaps, especially around water storage cleaning techniques and sexual transmission. Programs should also integrate gender into programming in culturally-relevant ways that avoid reinforcing stereotypes. Furthermore, programs should tailor activities for men, women, as well as the couple. In the end, integrating gender in a way that is mindful of the local context while not exploiting existing gender roles is critical for preventing Zika and similar mosquito-borne diseases, both in the Dominican Republic and throughout the region.


Assuntos
Comportamento , Transmissão de Doença Infecciosa/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Fatores Sexuais , Infecção por Zika virus/prevenção & controle , Adolescente , Adulto , Animais , República Dominicana , Feminino , Grupos Focais , Humanos , Masculino , Gravidez , Adulto Jovem
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