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1.
Nat Commun ; 15(1): 1696, 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38402207

RESUMO

The yellow fever 17D vaccine (YF17D) is highly effective but is frequently administered to individuals with pre-existing cross-reactive immunity, potentially impacting their immune responses. Here, we investigate the impact of pre-existing flavivirus immunity induced by the tick-borne encephalitis virus (TBEV) vaccine on the response to YF17D vaccination in 250 individuals up to 28 days post-vaccination (pv) and 22 individuals sampled one-year pv. Our findings indicate that previous TBEV vaccination does not affect the early IgM-driven neutralizing response to YF17D. However, pre-vaccination sera enhance YF17D virus infection in vitro via antibody-dependent enhancement (ADE). Following YF17D vaccination, TBEV-pre-vaccinated individuals develop high amounts of cross-reactive IgG antibodies with poor neutralizing capacity. In contrast, TBEV-unvaccinated individuals elicit a non-cross-reacting neutralizing response. Using YF17D envelope protein mutants displaying different epitopes, we identify quaternary dimeric epitopes as the primary target of neutralizing antibodies. Additionally, TBEV-pre-vaccination skews the IgG response towards the pan-flavivirus fusion loop epitope (FLE), capable of mediating ADE of dengue and Zika virus infections in vitro. Together, we propose that YF17D vaccination conceals the FLE in individuals without prior flavivirus exposure but favors a cross-reactive IgG response in TBEV-pre-vaccinated recipients directed to the FLE with potential to enhance dengue virus infection.


Assuntos
Dengue , Vírus da Encefalite Transmitidos por Carrapatos , Vacina contra Febre Amarela , Infecção por Zika virus , Zika virus , Humanos , Anticorpos Antivirais , Anticorpos Neutralizantes , Infecção por Zika virus/prevenção & controle , Epitopos , Imunoglobulina G , Dengue/prevenção & controle
2.
Lancet Infect Dis ; 23(10): 1175-1185, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37390836

RESUMO

BACKGROUND: Zika virus infection is a threat to at-risk populations, causing major birth defects and serious neurological complications. Development of a safe and efficacious Zika virus vaccine is, therefore, a global health priority. Assessment of heterologous flavivirus vaccination is important given co-circulation of Japanese encephalitis virus and yellow fever virus with Zika virus. We investigated the effect of priming flavivirus naive participants with a licensed flavivirus vaccine on the safety and immunogenicity of a purified inactivated Zika vaccine (ZPIV). METHODS: This phase 1, placebo-controlled, double-blind trial was done at the Walter Reed Army Institute of Research Clinical Trials Center in Silver Spring, MD, USA. Eligible participants were healthy adults aged 18-49 years, with no detectable evidence of previous flavivirus exposure (by infection or vaccination), as measured by a microneutralisation assay. Individuals with serological evidence of HIV, hepatitis B, or hepatitis C infection were excluded, as were pregnant or breastfeeding women. Participants were recruited sequentially into one of three groups (1:1:1) to receive no primer, two doses of intramuscular Japanese encephalitis virus vaccine (IXIARO), or a single dose of subcutaneous yellow fever virus vaccine (YF-VAX). Within each group, participants were randomly assigned (4:1) to receive intramuscular ZPIV or placebo. Priming vaccinations were given 72-96 days before ZPIV. ZPIV was administered either two or three times, at days 0, 28, and 196-234. The primary outcome was occurrence of solicited systemic and local adverse events along with serious adverse events and adverse events of special interest. These data were analysed in all participants receiving at least one dose of ZPIV or placebo. Secondary outcomes included measurement of neutralizing antibody responses following ZPIV vaccination in all volunteers with available post-vaccination data. This trial is registered at ClinicalTrials.gov, NCT02963909. FINDINGS: Between Nov 7, 2016, and Oct 30, 2018, 134 participants were assessed for eligibility. 21 did not meet inclusion criteria, 29 met exclusion criteria, and ten declined to participate. 75 participants were recruited and randomly assigned. 35 (47%) of 75 participants were male and 40 (53%) were female. 25 (33%) of 75 participants identified as Black or African American and 42 (56%) identified as White. These proportions and other baseline characteristics were similar between groups. There were no statistically significant differences in age, gender, race, or BMI between those who did and did not opt into the third dose. All participants received the planned priming IXIARO and YF-VAX vaccinations, but one participant who received YF-VAX dropped out before receipt of the first dose of ZPIV. 50 participants received a third dose of ZPIV or placebo, including 14 flavivirus-naive people, 17 people primed with Japanese encephalitis virus vaccine, and 19 participants primed with yellow fever vaccine. Vaccinations were well tolerated across groups. Pain at the injection site was the only adverse event reported more frequently in participants who received ZPIV than in those who received placebo (39 [65%] of 60 participants, 95% CI 51·6-76·9 who received ZPIV vs three [21·4%] of 14 who received placebo; 4·7-50·8; p=0·006). No patients had an adverse event of special interest or serious adverse event related to study treatment. At day 57, the flavivirus-naive volunteers had an 88% (63·6-98·5, 15 of 17) seroconversion rate (neutralising antibody titre ≥1:10) and geometric mean neutralising antibody titre (GMT) against Zika virus of 100·8 (39·7-255·7). In the Japanese encephalitis vaccine-primed group, the day 57 seroconversion rate was 31·6% (95% CI 12·6-56·6, six of 19) and GMT was 11·8 (6·1-22·8). Participants primed with YF-VAX had a seroconversion rate of 25% (95% CI 8·7-49·1, five of 20) and GMT of 6·6 (5·2-8·4). Humoral immune responses rose substantially following a third dose of ZPIV, with seroconversion rates of 100% (69·2-100; ten of ten), 92·9% (66·1-99·8; 13 of 14), and 60% (32·2-83·7, nine of 15) and GMTs of 511·5 (177·6-1473·6), 174·2 (51·6-587·6), and 79 (19·0-326·8) in the flavivirus naive, Japanese encephalitis vaccine-primed, and yellow fever vaccine-primed groups, respectively. INTERPRETATION: We found ZPIV to be well tolerated in flavivirus naive and primed adults but that immunogenicity varied significantly according to antecedent flavivirus vaccination status. Immune bias towards the flavivirus antigen of initial exposure and the timing of vaccination may have impacted responses. A third ZPIV dose overcame much, but not all, of the discrepancy in immunogenicity. The results of this phase 1 clinical trial have implications for further evaluation of ZPIV's immunisation schedule and use of concomitant vaccinations. FUNDING: Department of Defense, Defense Health Agency; National Institute of Allergy and Infectious Diseases; and Division of Microbiology and Infectious Disease.


Assuntos
Vírus da Encefalite Japonesa (Espécie) , Vacinas contra Encefalite Japonesa , Vacinas Virais , Vacina contra Febre Amarela , Infecção por Zika virus , Zika virus , Adulto , Feminino , Humanos , Masculino , Anticorpos Neutralizantes , Anticorpos Antivirais , Método Duplo-Cego , Imunogenicidade da Vacina , Vacinas contra Encefalite Japonesa/efeitos adversos , Vacinas de Produtos Inativados , Vacina contra Febre Amarela/efeitos adversos , Vírus da Febre Amarela , Infecção por Zika virus/prevenção & controle , Febre Amarela/prevenção & controle
3.
Public Health Rep ; 138(2): 208-217, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36752215

RESUMO

OBJECTIVE: Public Health Reports (PHR) is the oldest public health journal in the United States and has reported on viral epidemics since the 19th century. We describe the creation and analysis of a collection of historic PHR articles on emerging viral epidemics in the United States to inform public health response to COVID-19 and future epidemics. METHODS: We searched databases from 1878 through 2021 using custom search strings and conducted a manual search for articles published under previously used names for PHR. We evaluated all articles based on inclusion/exclusion criteria and coded the final list for virus/disease, article type, public health emergency preparedness and response capabilities from the Centers for Disease Control and Prevention (CDC), and PubMed citation count. RESULTS: We identified 349 relevant articles including 130 commentaries/reviews/editorials, 79 epidemiologic reports, 75 research articles, and 65 case study/practice articles. The collection focused on influenza (n = 244), COVID-19 (n = 75), dengue (n = 14), and other emerging viruses, such as Zika and Ebola (n = 25). The collection included 48 articles on health disparities/health of various disadvantaged populations, highlighting such disparities as race and ethnicity (n = 22), socioeconomic status (n = 17), and age (n = 15). When we categorized articles by CDC public health emergency preparedness and response capabilities, we found that 207 addressed surveillance and epidemiologic investigation, 36 addressed community preparedness, and 28 addressed medical countermeasure dispensing and administration. The articles addressing surveillance and epidemiologic investigation, nonpharmaceutical interventions, and community preparedness had the most PubMed citations (799, 334, and 308, respectively). CONCLUSIONS: PHR's historic articles on US emerging viral epidemics covered a range of virus/disease types, emergency preparedness and response capabilities, and contribution types and were widely cited in the scholarly literature. This publicly available and continuously updated collection is a valuable resource for pandemic planning and response.


Assuntos
COVID-19 , Equidade em Saúde , Viroses , Infecção por Zika virus , Zika virus , Humanos , Estados Unidos/epidemiologia , Saúde Pública , COVID-19/epidemiologia , Pandemias/prevenção & controle
4.
Lancet Infect Dis ; 23(5): 621-633, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36682364

RESUMO

BACKGROUND: Developing a safe and immunogenic vaccine against Zika virus remains an unmet medical need. We did two phase 1 studies that evaluated the safety and immunogenicity of two mRNA-based Zika virus vaccines (mRNA-1325 and mRNA-1893) in adults. METHODS: Two randomised, placebo-controlled, dose-ranging, multicentre, phase 1 trials, one of mRNA-1325 (mRNA-1325 trial) and one of mRNA-1893 (mRNA-1893 trial), were done. For both studies, eligible participants were healthy adults (aged 18-49 years) who were flavivirus seronegative or flavivirus seropositive at baseline. Participants in the mRNA-1325 trial, which was done at three centres in the USA, were randomly assigned centrally (1:4), using a randomisation table, to the placebo group or one of three mRNA-1325 dose groups (10, 25, or 100 µg). All participants received two doses. The mRNA-1325 vaccine encoded the premembrane and envelope E structural proteins (prME) from a Micronesia 2007 Zika virus isolate. Participants in the mRNA-1893 trial, which was done at three centres in the USA and one centre in Puerto Rico, were randomly assigned (1:4) to the placebo group or one of four mRNA-1893 dose groups (10, 30, 100, or 250 µg) using centralised interactive response technology. All participants in the mRNA-1893 trial received dose one on day 1 and then dose two on day 29. The mRNA-1893 vaccine encoded the prME from the RIO-U1 Zika virus isolate. Safety was the primary outcome of each study, which was evaluated in the respective safety populations (mRNA-1325 trial: participants who received at least one dose and provided safety data; mRNA-1893 trial: participants who received at least one dose) and the solicited safety population (mRNA-1893 trial only: received at least 1 dose and contributed solicited adverse reaction data). Endpoints in both trials included solicited adverse reactions within 7 days after vaccination and unsolicited adverse events within 28 days after vaccination. The secondary outcome of both trials was immunogenicity assessed by Zika virus-specific neutralising antibodies (nAbs) in the per-protocol populations in either trial (participants with no major protocol deviations received full dose[s] of assigned dose level within the acceptable time window, had samples drawn within acceptable time window, and had prevaccination and corresponding post-vaccination serum samples for testing). These were descriptive studies, with no formal hypothesis testing in either trial. Both trials are registered with ClinicalTrials.gov, NCT03014089 (mRNA-1325 trial) and NCT04064905 (mRNA-1893 trial). FINDINGS: The mRNA-1325 trial was done from Dec 14, 2016, to Aug 16, 2018. 90 participants were enrolled: 53 (59%) participants were women and 37 (41%) were men; 84 (93%) were White; and 74 (82%) were not Hispanic or Latino. All three dose levels of mRNA-1325 (10, 25, and 100 µg) were generally well tolerated, but the vaccine elicited poor Zika virus-specific nAb responses. At 28 days after dose two, geometric mean titres (GMTs) were highest for mRNA-1325 10 µg (10·3 [95% CI 5·9-18·2]). The mRNA-1893 trial was done from July 23, 2019, to March 22, 2021. 120 participants (70 [58%] women and 50 [42%] men) were enrolled, most participants were White (89 [74%]), and not Hispanic or Latino (91 [76%]). In the mRNA-1893 trial, solicited adverse reactions in participants who received a vaccine were mostly grade 1 or 2 and occurred more frequently at higher dose levels and after dose two. No participants withdrew due to an unsolicited treatment-emergent adverse event and most of these events were not treatment related. On day 57, all evaluated mRNA-1893 dose levels induced robust Zika virus-specific nAb responses, independent of flavivirus serostatus, that persisted until month 13. At day 57 in participants who were flavivirus seronegative, plaque reduction neutralisation titre test nAb GMTs were highest for mRNA-1893 100 µg (454·2 [330·0-619·6]); in participants who were flavivirus seropositive, GMTs were highest for mRNA-1893 10 µg (224·1 [43·5-1153·5]) and mRNA-1893 100 µg (190·5 [19·2-1887·2]). INTERPRETATION: These findings support the continued development of mRNA-1893 against Zika virus, which was well tolerated at all evaluated dose levels and induced strong Zika virus-specific serum nAb responses after two doses, regardless of baseline flavivirus serostatus. FUNDING: Biomedical Advanced Research and Development Authority and Moderna.


Assuntos
Flavivirus , Infecção por Zika virus , Zika virus , Masculino , Adulto , Humanos , Feminino , Zika virus/genética , Método Duplo-Cego , Vacinação , Porto Rico , Imunogenicidade da Vacina , Infecção por Zika virus/prevenção & controle , Anticorpos Antivirais
5.
BMC Med ; 20(1): 291, 2022 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-36100910

RESUMO

BACKGROUND: Zika virus (ZIKV), first discovered in Uganda in 1947, re-emerged globally in 2013 and was later associated with microcephaly and other birth defects. We determined the incidence of ZIKV infection and its association with adverse pregnancy and fetal outcomes in a pregnancy cohort in Kenya. METHODS: From October 2017 to July 2019, we recruited and followed up women aged ≥ 15 years and ≤ 28 weeks pregnant in three hospitals in coastal Mombasa. Monthly follow-up included risk factor questions and a blood sample collected for ZIKV serology. We collected anthropometric measures (including head circumference), cord blood, venous blood from newborns, and any evidence of birth defects. Microcephaly was defined as a head circumference (HC) < 2 standard deviations (SD) for sex and gestational age. Severe microcephaly was defined as HC < 3 SD for sex and age. We tested sera for anti-ZIKV IgM antibodies using capture enzyme-linked immunosorbent assay (ELISA) and confirmed positives using the plaque reduction neutralization test (PRNT90) for ZIKV and for dengue (DENV) on the samples that were ZIKV neutralizing antibody positive. We collected blood and urine from participants reporting fever or rash for ZIKV testing. RESULTS: Of 2889 pregnant women screened for eligibility, 2312 (80%) were enrolled. Of 1916 recorded deliveries, 1816 (94.6%) were live births and 100 (5.2%) were either stillbirths or spontaneous abortions (< 22 weeks of gestation). Among 1236 newborns with complete anthropometric measures, 11 (0.9%) had microcephaly and 3 (0.2%) had severe microcephaly. A total of 166 (7.2%) participants were positive for anti-ZIKV IgM, 136 of whom became seropositive during follow-up. Among the 166 anti-ZIKV IgM positive, 3 and 18 participants were further seropositive for ZIKV and DENV neutralizing antibodies, respectively. Of these 3 and 18 pregnant women, one and 13 (72.2%) seroconverted with antibodies to ZIKV and DENV, respectively. All 308 samples (serum and urine samples collected during sick visits and samples that were anti-ZIKV IgM positive) tested by RT-PCR were negative for ZIKV. No adverse pregnancy or neonatal outcomes were reported among the three participants with confirmed ZIKV exposure. Among newborns from pregnant women with DENV exposure, four (22.2%) were small for gestational age and one (5.6%) had microcephaly. CONCLUSIONS: The prevalence of severe microcephaly among newborns in coastal Kenya was high relative to published estimates from facility-based studies in Europe and Latin America, but little evidence of ZIKV transmission. There is a need for improved surveillance for microcephaly and other congenital malformations in Kenya.


Assuntos
Microcefalia , Infecção por Zika virus , Zika virus , Anticorpos Antivirais , Feminino , Humanos , Imunoglobulina M , Recém-Nascido , Quênia/epidemiologia , Microcefalia/epidemiologia , Gravidez , Prevalência , Infecção por Zika virus/complicações , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/epidemiologia
6.
Mol Psychiatry ; 27(1): 19-33, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34580416

RESUMO

Infectious diseases, including COVID-19, are crucial public health issues and may lead to considerable fear among the general public and stigmatization of, and discrimination against, specific populations. This meta-analysis aimed to estimate the pooled prevalence of stigma in infectious disease epidemics. We systematically searched PubMed, PsycINFO, Embase, MEDLINE, Web of Science, and Cochrane databases since inception to June 08, 2021, and reported the prevalence of stigma towards people with infectious diseases including SARS, H1N1, MERS, Zika, Ebola, and COVID-19. A total of 50 eligible articles were included that contributed 51 estimates of prevalence in 92722 participants. The overall pooled prevalence of stigma across all populations was 34% [95% CI: 28-40%], including enacted stigma (36% [95% CI: 28-44%]) and perceived stigma (31% [95% CI: 22-40%]). The prevalence of stigma in patients, community population, and health care workers, was 38% [95% CI: 12- 65%], 36% [95% CI: 28-45%], and 30% [95% CI: 20-40%], respectively. The prevalence of stigma in participants from low- and middle-income countries was 37% [95% CI: 29-45%], which is higher than that from high-income countries (27% [95% CI: 18-36%]) though this difference was not statistically significant. A similar trend of prevalence of stigma was also observed in individuals with lower education (47% [95% CI: 23-71%]) compared to higher education level (33% [95% CI: 23-4%]). These findings indicate that stigma is a significant public health concern, and effective and comprehensive interventions are needed to counteract the damaging effects of the infodemics during infectious disease epidemics, including COVID-19, and reduce infectious disease-related stigma.


Assuntos
COVID-19 , Doenças Transmissíveis , Vírus da Influenza A Subtipo H1N1 , Infecção por Zika virus , Zika virus , Humanos , Prevalência
7.
Artigo em Inglês | MEDLINE | ID: mdl-34502007

RESUMO

Dengue is a continuous health burden in Laos and Thailand. We assessed and mapped dengue vulnerability in selected provinces of Laos and Thailand using multi-criteria decision approaches. An ecohealth framework was used to develop dengue vulnerability indices (DVIs) that explain links between population, social and physical environments, and health to identify exposure, susceptibility, and adaptive capacity indicators. Three DVIs were constructed using two objective approaches, Shannon's Entropy (SE) and the Water-Associated Disease Index (WADI), and one subjective approach, the Best-Worst Method (BWM). Each DVI was validated by correlating the index score with dengue incidence for each spatial unit (district and subdistrict) over time. A Pearson's correlation coefficient (r) larger than 0.5 and a p-value less than 0.05 implied a good spatial and temporal performance. Spatially, DVIWADI was significantly correlated on average in 19% (4-40%) of districts in Laos (mean r = 0.5) and 27% (15-53%) of subdistricts in Thailand (mean r = 0.85). The DVISE was validated in 22% (12-40%) of districts in Laos and in 13% (3-38%) of subdistricts in Thailand. The DVIBWM was only developed for Laos because of lack of data in Thailand and was significantly associated with dengue incidence on average in 14% (0-28%) of Lao districts. The DVIWADI indicated high vulnerability in urban centers and in areas with plantations and forests. In 2019, high DVIWADI values were observed in sparsely populated areas due to elevated exposure, possibly from changes in climate and land cover, including urbanization, plantations, and dam construction. Of the three indices, DVIWADI was the most suitable vulnerability index for the study area. The DVIWADI can also be applied to other water-associated diseases, such as Zika and chikungunya, to highlight priority areas for further investigation and as a tool for prevention and interventions.


Assuntos
Dengue , Infecção por Zika virus , Zika virus , Técnicas de Apoio para a Decisão , Dengue/epidemiologia , Sistemas de Informação Geográfica , Humanos , Laos/epidemiologia , Tailândia/epidemiologia
8.
Epidemics ; 37: 100491, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34454353

RESUMO

INTRODUCTION: Zika virus (ZIKV) is primarily transmitted byAedes aegypti and Aedes albopictus mosquitoes between humans and non-human primates. Climate change may enhance virus reproduction in Aedes spp. mosquito populations, resulting in intensified ZIKV outbreaks. The study objective was to explore how an outbreak similar to the 2016 ZIKV outbreak in Brazil might unfold with projected climate change. METHODS: A compartmental infectious disease model that included compartments for humans and mosquitoes was developed to fit the 2016 ZIKV outbreak data from Brazil using least squares optimization. To explore the impact of climate change, published polynomial relationships between temperature and temperature-sensitive mosquito population and virus transmission parameters (mosquito mortality, development rate, and ZIKV extrinsic incubation period) were used. Projections for future outbreaks were obtained by simulating transmission with effects of projected average monthly temperatures on temperature-sensitive model parameters at each of three future time periods: 2011-2040, 2041-2070, and 2071-2100. The projected future climate was obtained from an ensemble of regional climate models (RCMs) obtained from the Co-Ordinated Regional Downscaling Experiment (CORDEX) that used Representative Concentration Pathways (RCP) with two radiative forcing values, RCP4.5 and RCP8.5. A sensitivity analysis was performed to explore the impact of temperature-dependent parameters on the model outcomes. RESULTS: Climate change scenarios impacted the model outcomes, including the peak clinical case incidence, cumulative clinical case incidence, time to peak incidence, and the duration of the ZIKV outbreak. Comparing 2070-2100 to 2016, using RCP4.5, the peak incidence was 22,030 compared to 10,473; the time to epidemic peak was 12 compared to 9 weeks, and the outbreak duration was 52 compared to 41 weeks. Comparing 2070-2100 to 2016, using RCP8.5, the peak incidence was 21,786 compared to 10,473; the time to epidemic peak was 11 compared to 9 weeks, and the outbreak duration was 50 compared to 41weeks. The increases are due to optimal climate conditions for mosquitoes, with the mean temperature reaching 28 °C in the warmest months. Under a high emission scenario (RCP8.5), mean temperatures extend above optimal for mosquito survival in the warmest months. CONCLUSION: Outbreaks of ZIKV in locations similar to Brazil are expected to be more intense with a warming climate. As climate change impacts are becoming increasingly apparent on human health, it is important to quantify the effect and use this knowledge to inform decisions on prevention and control strategies.


Assuntos
Aedes , Infecção por Zika virus , Zika virus , Animais , Brasil/epidemiologia , Surtos de Doenças , Mosquitos Vetores , Infecção por Zika virus/epidemiologia
9.
PLoS One ; 16(1): e0244981, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33400705

RESUMO

Zika virus (ZIKV) has been detected in blood, urine, semen, cerebral spinal fluid, saliva, amniotic fluid, and breast milk. In most ZIKV infected individuals, the virus is detected in the blood to one week after the onset of symptoms and has been found to persist longer in urine and semen. To better understand virus dynamics, a prospective cohort study was conducted in Brazil to assess the presence and duration of ZIKV and related markers (viral RNA, antibodies, T cell response, and innate immunity) in blood, semen, saliva, urine, vaginal secretions/menstrual blood, rectal swab and sweat. The objective of the current manuscript is to describe the cohort, including an overview of the collected data and a description of the baseline characteristics of the participants. Men and women ≥ 18 years with acute illness and their symptomatic and asymptomatic household contacts with positive reverse transcriptase-polymerase chain reaction test for ZIKV in blood and/or urine were included. All participants were followed up for 12 months. From July 2017 to June 2019, a total of 786 participants (284 men, 502 women) were screened. Of these, 260 (33.1%) were enrolled in the study; index cases: 64 men (24.6%), 162 (62.3%) women; household contacts: 12 men (4.6%), 22 (8.5%) women. There was a statistically significant difference in age and sex between enrolled and not enrolled participants (p<0.005). Baseline sociodemographic and medical data were collected at enrollment from all participants. The median and interquartile range (IQR) age was 35 (IQR; 25.3, 43) for men and 36.5 years (IQR; 28, 47) for women. Following rash, which was one of the inclusion criteria for index cases, the most reported symptoms in the enrollment visit since the onset of the disease were fever, itching, arthralgia with or without edema, non-purulent conjunctivitis, headache, and myalgia. Ten hospitalizations were reported by eight patients (two patients were hospitalized twice) during follow up, after a median of 108 days following symptom onset (range 7 to 266 days) and with a median of 1.5 days (range 1 to 20 days) of hospital stay. A total of 4,137 visits were performed, 223 (85.8%) participants have attended all visits and 37 (14.2%) patients were discontinued.


Assuntos
Leite Humano/virologia , RNA Viral/sangue , Saliva/virologia , Infecção por Zika virus/virologia , Zika virus/isolamento & purificação , Adulto , Brasil , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Carga Viral , Eliminação de Partículas Virais , Adulto Jovem
10.
J Child Neurol ; 36(7): 537-544, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33406966

RESUMO

BACKGROUND: We aim to describe the long term follow-up of a cohort of children exposed in utero to the Zika virus. METHODS: Descriptive study of a cohort of microcephalic children due to Zika virus. Logistic regression was used to evaluate variables associated with worse prognosis epilepsy. RESULTS: We followed 28 children (15 females), with a median follow-up of 24 months (IQR = 12-28). During the follow-up, 1 infant died. The median head circumference at birth was 29 cm (IQR = 27-31). All presented a global developmental delay. The most frequent central nervous system abnormalities were on cortical development in 22 participants; dysgenesis of corpus callosum in 13; ventriculomegaly in 25; and calcifications in 24. A total of 9 presented ocular abnormalities, 4 auditory impairment. During follow-up, 12 presented with sleep disorders, 10 with irritability, and 23 with epilepsy (2 with generalized tonic-clonic, 3 with generalized tonic-clonic and spasms, 12 with spasms, 3 tonic and spasms, and 3 motor focal and spasms). The median age at the begin of the epilepsy was 4 months (IQR = 2-10), the median number of drugs used to control the epilepsy was 2 (IQR = 2-3). Maternal illicit drug use during pregnancy was associated with worse prognosis epilepsy (Lennox-Gastaut syndrome, West syndrome, or status epilepticus). A total of 19 presented with dysphagia, 10 children required gastrostomy. CONCLUSION: Children with microcephaly due to Zika virus presented with several complications during follow-up, as epilepsy, spastic diplegia, and global developmental delay.


Assuntos
Epilepsia/epidemiologia , Microcefalia/complicações , Microcefalia/virologia , Infecção por Zika virus/complicações , Paralisia Cerebral/epidemiologia , Pré-Escolar , Deficiências do Desenvolvimento/epidemiologia , Epilepsia/diagnóstico , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Microcefalia/psicologia , Prognóstico , Fatores de Tempo
11.
Artigo em Inglês | MEDLINE | ID: mdl-33229424

RESUMO

Emerging flaviviruses are causative agents of severe and life-threatening diseases, against which no approved therapies are available. Among the nucleoside analogues, which represent a promising group of potentially therapeutic compounds, fluorine-substituted nucleosides are characterized by unique structural and functional properties. Despite having first been synthesized almost 5 decades ago, they still offer new therapeutic opportunities as inhibitors of essential viral or cellular enzymes active in nucleic acid replication/transcription or nucleoside/nucleotide metabolism. Here, we report evaluation of the antiflaviviral activity of 28 nucleoside analogues, each modified with a fluoro substituent at different positions of the ribose ring and/or heterocyclic nucleobase. Our antiviral screening revealed that 3'-deoxy-3'-fluoroadenosine exerted a low-micromolar antiviral effect against tick-borne encephalitis virus (TBEV), Zika virus, and West Nile virus (WNV) (EC50 values from 1.1 ± 0.1 µM to 4.7 ± 1.5 µM), which was manifested in host cell lines of neural and extraneural origin. The compound did not display any measurable cytotoxicity up to concentrations of 25 µM but had an observable cytostatic effect, resulting in suppression of cell proliferation at concentrations of >12.5 µM. Novel approaches based on quantitative phase imaging using holographic microscopy were developed for advanced characterization of antiviral and cytotoxic profiles of 3'-deoxy-3'-fluoroadenosine in vitro In addition to its antiviral activity in cell cultures, 3'-deoxy-3'-fluoroadenosine was active in vivo in mouse models of TBEV and WNV infection. Our results demonstrate that fluoro-modified nucleosides represent a group of bioactive molecules with excellent potential to serve as prospective broad-spectrum antivirals in antiviral research and drug development.


Assuntos
Vírus da Encefalite Transmitidos por Carrapatos , Infecção por Zika virus , Zika virus , Animais , Antivirais/farmacologia , Desoxiadenosinas/farmacologia , Camundongos , Estudos Prospectivos , Replicação Viral
12.
PLoS Negl Trop Dis ; 14(9): e0008527, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32898136

RESUMO

BACKGROUND: Zika virus (ZIKV) emerged in the Pacific Ocean and subsequently caused a dramatic Pan-American epidemic after its first appearance in the Northeast region of Brazil in 2015. The virus is transmitted by Aedes mosquitoes. We evaluated the role of temperature and infectious doses of ZIKV in vector competence of Brazilian populations of Ae. aegypti and Ae. albopictus. METHODOLOGY/PRINCIPAL FINDINGS: Two Ae. aegypti (Rio de Janeiro and Natal) and two Ae. albopictus (Rio de Janeiro and Manaus) populations were orally challenged with five viral doses (102 to 106 PFU / ml) of a ZIKV strain (Asian genotype) isolated in Northeastern Brazil, and incubated for 14 and 21 days in temperatures mimicking the spring-summer (28°C) and winter-autumn (22°C) mean values in Brazil. Detection of viral particles in the body, head and saliva samples was done by plaque assays in cell culture for determining the infection, dissemination and transmission rates, respectively. Compared with 28°C, at 22°C, transmission rates were significantly lower for both Ae. aegypti populations, and Ae. albopictus were not able to transmit the virus. Ae. albopictus showed low transmission rates even when challenged with the highest viral dose, while both Ae. aegypti populations presented higher of infection, dissemination and transmission rates than Ae. albopictus. Ae. aegypti showed higher transmission efficiency when taking virus doses of 105 and 106 PFU/mL following incubation at 28°C; both Ae. aegypti and Ae. albopictus were unable to transmit ZIKV with virus doses of 102 and 103 PFU/mL, regardless the incubation temperature. CONCLUSIONS/SIGNIFICANCE: The ingested viral dose and incubation temperature were significant predictors of the proportion of mosquito's biting becoming infectious. Ae. aegypti and Ae. albopictus have the ability to transmit ZIKV when incubated at 28°C. However Brazilian populations of Ae. aegypti exhibit a much higher transmission potential for ZIKV than Ae. albopictus regardless the combination of infection dose and incubation temperature.


Assuntos
Aedes/virologia , Saliva/virologia , Infecção por Zika virus/transmissão , Animais , Brasil , Mordeduras e Picadas de Insetos/virologia , Mosquitos Vetores/virologia , Estações do Ano , Temperatura , Distribuição Tecidual , Carga Viral , Zika virus
13.
JAMA Netw Open ; 3(7): e209303, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32633763

RESUMO

Importance: Zika virus (ZIKV) is a mosquito-borne flavivirus recognized as teratogenic since the 2015 to 2016 epidemic. Antenatal ZIKV exposure causes brain anomalies, yet the full spectrum has not been delineated. Objective: To characterize the clinical features of ZIKV infection at a pediatric referral center in Rio de Janeiro, Brazil, among children with antenatal ZIKV exposure. Design, Setting, and Participants: Retrospective cohort study conducted from May to July 2019 of a prospective cohort of 296 infants with antenatal ZIKV exposure followed up since December 2015 at a tertiary maternity-pediatric hospital. Exposures: Zika virus infection during pregnancy. Main Outcomes and Measures: Characterization of clinical features with anthropometric, neurologic, cardiologic, ophthalmologic, audiometric, and neuroimaging evaluations in infancy and neurodevelopmental assessments (Bayley Scales of Infant and Toddler Development, Third Edition) from 6 to 42 months of age, stratified by head circumference at birth (head circumference within the reference range, or normocephaly [NC] vs microcephaly [MC]). Results: Antenatal exposure to ZIKV was confirmed for 219 of 296 children (74.0%) referred to Instituto Fernandes Figueira with suspected ZIKV infection through positive maternal or neonatal polymerase chain reaction analysis or IgM serology results. Of these children, 110 (50.2%) were boys, ages ranged from 0 to 4 years, and 53 (24.2%) had congenital microcephaly. The anomalies observed in ZIKV-exposed children with MC or NC were failure to thrive (MC: 38 of 53 [71.7%]; NC: 73 of 143 [51.0%]), cardiac malformations (MC: 19 of 46 [41.3%]; NC: 20 of 100 [20.0%]), excess nuchal skin (MC: 16 of 22 [72.7%]; NC: 35 of 93 [37.6%]), auditory abnormalities (MC: 13 of 50 [26.0%]; NC: 14 of 141 [9.9%]), and eye abnormalities (MC: 42 of 53 [79.2%]; NC: 28 of 158 [17.7%]). Although they experienced fewer neurologic abnormalities than children born with MC, those with NC also had frequent neurologic abnormalities (109 of 160 [68.1%]), including hyperreflexia (36 of 136 [26.5%]), abnormal tone (53 of 137 [38.7%]), congenital neuromotor signs (39 of 93 [41.9%]), feeding difficulties (15 of 143 [10.5%]), and abnormal brain imaging results (44 of 150 [29.3%]). Among 112 children with NC with Bayley-III evaluations, 72 (64.3%) had average or above-average scores; 30 (26.8%) scored 1 SD below average in at least 1 domain; and 10 (8.9%) scored 2 SD below average in at least 1 domain. Among 112 children with NC, a smaller head circumference at birth was significantly associated with subsequent below-average cognitive scores (U = 499.5; z = -2.833; P = .004) and language scores (U = 235.5; z = -2.491; P = .01). Conclusions and Relevance: Children without MC who were exposed to ZIKV in utero had a high frequency of anatomical and neurodevelopmental abnormalities. The head circumference at birth for children with NC was associated with neurocognitive development. Recognition of the wide spectrum of clinical phenotypes is critical to ensure early referral to rehabilitative interventions.


Assuntos
Microcefalia , Transtornos do Neurodesenvolvimento , Complicações Infecciosas na Gravidez , Efeitos Tardios da Exposição Pré-Natal , Infecção por Zika virus , Encéfalo/diagnóstico por imagem , Brasil/epidemiologia , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Masculino , Microcefalia/diagnóstico , Microcefalia/epidemiologia , Microcefalia/etiologia , Transtornos do Neurodesenvolvimento/diagnóstico , Transtornos do Neurodesenvolvimento/epidemiologia , Transtornos do Neurodesenvolvimento/etiologia , Neuroimagem/métodos , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/virologia , Estudos Retrospectivos , Infecção por Zika virus/complicações , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/epidemiologia
14.
J Infect Public Health ; 13(5): 724-729, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32224108

RESUMO

BACKGROUND: The co-circulation of Chikungunya (CHIKV), Dengue (DENV) and Zika (ZIKV) viruses increased the risk of outbreaks and coinfections among them. Here, we report cases of coinfection in clinical samples from state of Tocantins, Brazil. METHODS: In 2017, the Central Public Health Laboratory (LACEN) received samples of patients who consulted health units with symptoms compatible with arboviral infections. A total of 102 samples were sent to the Retrovirology Laboratory at the Federal University of São Paulo, where they were tested by RT-qPCR to confirm DENV, ZIKV and CHIKV infections and to detect coinfected patients. RESULTS: We identified with CHIKV monoinfection (52), DENV serotypes 1 (28) and serotypes 2 (22). We did not detect ZIKV. Five patients were characterized with coinfection involving CHIKV and DENV serotype 2. CONCLUSIONS: The presence of co-circulating arboviruses increases the chance of coinfection and demonstrates the importance of differential diagnosis and vector control.


Assuntos
Febre de Chikungunya/epidemiologia , Coinfecção/epidemiologia , Dengue/epidemiologia , Infecção por Zika virus/epidemiologia , Adolescente , Adulto , Brasil/epidemiologia , Febre de Chikungunya/sangue , Febre de Chikungunya/diagnóstico , Febre de Chikungunya/genética , Vírus Chikungunya/isolamento & purificação , Criança , Coinfecção/diagnóstico , Estudos Transversais , Dengue/sangue , Dengue/diagnóstico , Dengue/genética , Vírus da Dengue/isolamento & purificação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sorogrupo , Adulto Jovem , Zika virus/isolamento & purificação , Infecção por Zika virus/sangue
15.
J Virol ; 94(5)2020 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-31801867

RESUMO

By the end of the 2016 Zika virus (ZIKV) outbreak, it is estimated that there were up to 100 million infections in the Americas. In approximately one in seven infants born to mothers infected during pregnancy, ZIKV has been linked to microcephaly, developmental delays, or other congenital disorders collectively known as congenital Zika syndrome, as well as Guillain-Barré syndrome, in ZIKV-infected adults. It is a global health priority to develop a vaccine against ZIKV that elicits long-lasting immunity; however, the durability of immunity to ZIKV is unknown. Previous studies in mice and nonhuman primates have been crucial in vaccine development but have not defined the duration of immunity generated by ZIKV infection. In this study, we rechallenged five rhesus macaques with ZIKV 22 to 28 months after a primary ZIKV infection. We show that primary ZIKV infection generates high titers of neutralizing antibodies that protect from detectable plasma viremia following rechallenge and persist for at least 22 to 28 months. While additional longitudinal studies are necessary with longer time frames, this study establishes a new experimentally defined minimal length of protective ZIKV immunity.IMPORTANCE ZIKV emerged as a vector-borne pathogen capable of causing illness in infected adults and congenital birth defects in infants born to mothers infected during pregnancy. Despite the decrease in ZIKV cases since the 2015-2016 epidemic, questions concerning the prevalence and longevity of protective immunity have left vulnerable communities fearful that they may become the center of next ZIKV outbreak. Although preexisting herd immunity in regions of past outbreaks may dampen the potential for future outbreaks to occur, we currently do not know the longevity of protective immunity to ZIKV after a person becomes infected. Here, we establish a new experimentally defined minimal length of protective ZIKV immunity. We show that five rhesus macaques initially infected with ZIKV 22 to 28 months prior to rechallenge elicit a durable immune response that protected from detectable plasma viremia. This study establishes a new minimal length of protective immunity.


Assuntos
Imunidade/imunologia , Macaca mulatta/imunologia , Infecção por Zika virus/imunologia , Infecção por Zika virus/prevenção & controle , Zika virus/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Surtos de Doenças/prevenção & controle , Viremia , Infecção por Zika virus/epidemiologia
16.
Travel Med Infect Dis ; 33: 101543, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31805400

RESUMO

BACKGROUND: From the first Zika virus (ZIKV) description, it has progressively widespread worldwide. We analyzed demographic, clinical, microbiologic and travel-related characteristic from returned patients from a ZIKV endemic country in a referral Tropical Medicine Unit. METHOD: A prospective cohort study performed in a Spanish referral center with the aim of determining the significant factors associated with confirmed Zika virus (ZIKV) infection. RESULTS: 817 patients, (56% women, median age 36 [IQR, Interquartile Range: 32-42]) were enrolled. Most had returned from Latin America (n = 486; 59.4%), travelled for tourism (n = 404; 49.4%) and stayed a median of 18 days (IQR: 10-30). 602 (73.6%) presented symptoms, but only 25 (4%) were finally diagnosed with confirmed ZIKV infection (including two pregnant women, without adverse fetal outcomes), 88% (n:22) presented with fever and 92% (n:23) with rash. 56% (n:14) arthralgia and/or myalgia and 28% (n:7) conjunctivitis. The presence of conjunctivitis, fever and rash were associated with an 8.9 (95% CI: 2.2-34.9), 6.4 (95% CI: 1.2-33.3) and 72.3 (95% CI: 9.2-563.5) times greater probability of confirmed ZIKV infection, respectively. CONCLUSION: Travel characteristics and clinical presentation may help clinicians to optimize requests for microbiological testing. Diagnosis of arboviriasis in travellers arriving form endemic areas remains a challenge for clinicians, but must be detected for the possible transmission outside endemic areas, where the vector is present.


Assuntos
Doença Relacionada a Viagens , Infecção por Zika virus/diagnóstico , Adulto , Ásia , Feminino , Humanos , América Latina , Masculino , Pessoa de Meia-Idade , Gravidez , Estudos Prospectivos , Encaminhamento e Consulta , Espanha/epidemiologia , Espanha/etnologia , Viagem , Adulto Jovem , Zika virus/isolamento & purificação , Infecção por Zika virus/epidemiologia
17.
J Intern Med ; 285(2): 215-222, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30222212

RESUMO

BACKGROUND: Vertical transmission of Zika virus (ZIKV) is associated with congenital malformations but the mechanism of pathogenesis remains unclear. Although host genetics appear to play a role, no genetic association study has yet been performed to evaluate this question. In order to investigate if maternal genetic variation is associated with Congenital Zika Syndrome (CZS), we conducted a case-control study in a cohort of Brazilian women infected with ZIKV during pregnancy. METHODS: A total of 100 women who reported symptoms of zika during pregnancy were enrolled and tested for ZIKV. Among 52 women positive for ZIKV infection, 28 were classified as cases and 24 as controls based on the presence or absence of CZS in their infants. Variations in the coding region of 205 candidate genes involved in cAMP signaling or immune response were assessed by high throughput sequencing and tested for association with development of CZS. RESULTS: From the 817 single nucleotide variations (SNVs) included in association analyses, 22 SNVs in 17 genes were associated with CZS under an additive model (alpha = 0.05). Variations c.319T>C (rs11676272) and c.1297G>A, located at ADCY3 and ADCY7 genes showed the most prominent effect. The association of ADCY3 and ADCY7 genes was confirmed using a Sequence Kernel Association Test to assess the joint effect of common and rare variations, and results were statistically significant after adjustment for multiple comparisons (P < 0.002). CONCLUSION: These results suggest that maternal ADCY genes contribute to ZIKV pathogenicity and influence the outcome of CZS, being promising candidates for further replication studies and functional analysis.


Assuntos
Adenilil Ciclases/genética , Mutação , Complicações Infecciosas na Gravidez , Infecção por Zika virus/genética , Adenilil Ciclases/metabolismo , Brasil/epidemiologia , Análise Mutacional de DNA , DNA Viral/análise , Feminino , Seguimentos , Humanos , Incidência , Gravidez , Estudos Retrospectivos , Zika virus/genética , Zika virus/patogenicidade , Infecção por Zika virus/enzimologia , Infecção por Zika virus/epidemiologia
18.
Obstet Gynecol ; 132(2): 487-495, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29995729

RESUMO

OBJECTIVE: To describe and compare differences in the epidemiologic, clinical, and laboratory characteristics of pregnant women with confirmed or probable Zika virus infection and to compare the risk of having a neonate with laboratory evidence of Zika virus infection with that of having a neonate without evidence of Zika virus infection by maternal characteristics. METHODS: We conducted a retrospective cohort study of women with Zika virus infection who completed pregnancy in New York City from January 1, 2016 to June 30, 2017. Confirmed Zika virus infection was defined as 1) nucleic acid amplification test-detected Zika virus, or 2) a nonnegative enzyme-linked immunosorbent assay test result and a plaque-reduction neutralization test result positive for Zika virus but negative for dengue virus, or 3) delivery of a neonate with laboratory evidence of Zika virus infection. Probable infection was defined as a nonnegative enzyme-linked immunosorbent assay test result and a positive plaque-reduction neutralization test result for Zika virus and dengue virus. RESULTS: We identified 390 women with confirmed (28%) or probable (72%) Zika virus infection. Fever, rash, arthralgia, or conjunctivitis was reported by 31% of women and were more common among women with confirmed than with probable infection (43% vs 26%, P=.001). Of 366 neonates born to these women, 295 (81%) were tested for Zika virus and 22 (7%) had laboratory-diagnosed congenital Zika virus infection. The relative risk (RR) for having a neonate with laboratory evidence of Zika virus infection was greater among women with fever (RR 4.8, 95% CI 2.1-10.7), tingling (RR 4.8, CI 1.7-13.7), or numbness (RR 6.9, CI 2.6-18.2) during pregnancy or the periconception period. However, the RR did not differ whether the mother had confirmed or probable Zika virus infection (RR 1.6, CI 0.7-4.1). CONCLUSION: In New York City, a greater proportion of women had probable Zika virus infection than confirmed infection. Women with some symptoms during pregnancy or periconceptionally were more likely to have a neonate with laboratory evidence of Zika virus infection. Neonates born to women with confirmed or probable Zika virus infection should be tested for Zika virus infection.


Assuntos
Complicações Infecciosas na Gravidez/epidemiologia , Doença Relacionada a Viagens , Infecção por Zika virus/epidemiologia , Adulto , Feminino , Humanos , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Cidade de Nova Iorque/epidemiologia , Gravidez , Complicações Infecciosas na Gravidez/etiologia , Complicações Infecciosas na Gravidez/virologia , Estudos Retrospectivos , Fatores de Risco , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/etiologia , Infecção por Zika virus/transmissão
19.
Am J Trop Med Hyg ; 98(3): 845-848, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29405105

RESUMO

Recent large-scale chikungunya virus (CHIKV) and Zika virus epidemics in the Americas pose a growing public health threat. Given that mosquito bite prevention and vector control are the main prevention methods available to reduce transmission of these viruses, we assessed adherence to these methods in the United States Virgin Islands (USVI). We interviewed 334 USVI residents between December 2014 and February 2015 to measure differences in mosquito prevention practices by gender, income, presence of CHIKV symptoms, and age. Only 27% (91/334) of participants reported having an air conditioner, and of the 91 with air-conditioners, 18 (20%) reported never using it. Annual household income > $50,000 was associated with owning and using an air conditioner (41%; 95% confidence interval [CI]: 28-53% compared with annual household income ≤ $50,000: 17%; 95% CI: 12-22%). The majority of participants reported the presence of vegetation in their yard or near their home (79%; 265) and a cistern on their property (78%; 259). Only 52 (16%) participants reported wearing mosquito repellent more than once per week. Although the majority (80%; 268) of participants reported having screens on all of their windows and doors, most (82%; 273) of those interviewed still reported seeing mosquitoes in their homes. Given the uniformly low adherence to individual- and household-level mosquito bite prevention measures in the USVI, these findings emphasize the need for improved public health messaging and investment in therapeutic and vaccine research to mitigate vector-borne disease outbreaks.


Assuntos
Aedes/virologia , Febre de Chikungunya/epidemiologia , Febre de Chikungunya/prevenção & controle , Vírus Chikungunya/patogenicidade , Surtos de Doenças , Controle de Insetos/métodos , Mosquitos Vetores/virologia , Adulto , Animais , Febre de Chikungunya/transmissão , Características da Família , Feminino , Humanos , Renda/estatística & dados numéricos , Repelentes de Insetos/economia , Repelentes de Insetos/provisão & distribuição , Masculino , Pessoa de Meia-Idade , Roupa de Proteção/economia , Roupa de Proteção/provisão & distribuição , Ilhas Virgens Americanas/epidemiologia
20.
Lancet ; 391(10120): 552-562, 2018 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-29217376

RESUMO

BACKGROUND: The Zika virus epidemic and associated congenital infections have prompted rapid vaccine development. We assessed two new DNA vaccines expressing premembrane and envelope Zika virus structural proteins. METHODS: We did two phase 1, randomised, open-label trials involving healthy adult volunteers. The VRC 319 trial, done in three centres, assessed plasmid VRC5288 (Zika virus and Japanese encephalitis virus chimera), and the VRC 320, done in one centre, assessed plasmid VRC5283 (wild-type Zika virus). Eligible participants were aged 18-35 years in VRC19 and 18-50 years in VRC 320. Participants were randomly assigned 1:1 by a computer-generated randomisation schedule prepared by the study statistician. All participants received intramuscular injection of 4 mg vaccine. In VRC 319 participants were assigned to receive vaccinations via needle and syringe at 0 and 8 weeks, 0 and 12 weeks, 0, 4, and 8 weeks, or 0, 4, and 20 weeks. In VRC 320 participants were assigned to receive vaccinations at 0, 4, and 8 weeks via single-dose needle and syringe injection in one deltoid or split-dose needle and syringe or needle-free injection with the Stratis device (Pharmajet, Golden, CO, USA) in each deltoid. Both trials followed up volunteers for 24 months for the primary endpoint of safety, assessed as local and systemic reactogenicity in the 7 days after each vaccination and all adverse events in the 28 days after each vaccination. The secondary endpoint in both trials was immunogenicity 4 weeks after last vaccination. These trials are registered with ClinicalTrials.gov, numbers NCT02840487 and NCT02996461. FINDINGS: VRC 319 enrolled 80 participants (20 in each group), and VRC 320 enrolled 45 participants (15 in each group). One participant in VRC 319 and two in VRC 320 withdrew after one dose of vaccine, but were included in the safety analyses. Both vaccines were safe and well tolerated. All local and systemic symptoms were mild to moderate. In both studies, pain and tenderness at the injection site was the most frequent local symptoms (37 [46%] of 80 participants in VRC 319 and 36 [80%] of 45 in VRC 320) and malaise and headache were the most frequent systemic symptoms (22 [27%] and 18 [22%], respectively, in VRC 319 and 17 [38%] and 15 [33%], respectively, in VRC 320). For VRC5283, 14 of 14 (100%) participants who received split-dose vaccinations by needle-free injection had detectable positive antibody responses, and the geometric mean titre of 304 was the highest across all groups in both trials. INTERPRETATION: VRC5283 was well tolerated and has advanced to phase 2 efficacy testing. FUNDING: Intramural Research Program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health.


Assuntos
Anticorpos Neutralizantes/biossíntese , Anticorpos Antivirais/biossíntese , Vacinas de DNA/administração & dosagem , Vacinas de DNA/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/imunologia , Zika virus/imunologia , Adulto , Citocinas/biossíntese , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Linfócitos T/imunologia , Vacinas de DNA/efeitos adversos , Vacinas Virais/efeitos adversos , Adulto Jovem , Infecção por Zika virus/prevenção & controle
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