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1.
BMC Infect Dis ; 20(1): 947, 2020 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-33308203

RESUMEN

BACKGROUND: Early detection of Zika virus (ZIKV) infection during the viremia and viruria facilitates proper patient management and mosquito control measurement to prevent disease spread. Therefore, a cost-effective nucleic acid detection method for the diagnosis of ZIKV infection, especially in resource-deficient settings, is highly required. METHODS: In the present study, a single-tube reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay was developed for the detection of both the Asian and African-lineage ZIKV. The detection limit, strain coverage and cross-reactivity of the ZIKV RT-LAMP assay was evaluated. The sensitivity and specificity of the RT-LAMP were also evaluated using a total of 24 simulated clinical samples. The ZIKV quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay was used as the reference assay. RESULTS: The detection limit of the RT-LAMP assay was 3.73 ZIKV RNA copies (probit analysis, P ≤ 0.05). The RT-LAMP assay detected the ZIKV genomes of both the Asian and African lineages without cross-reacting with other arthropod-borne viruses. The sensitivity and specificity of the RT-LAMP assay were 90% (95% CI = 59.6-98.2) and 100% (95% CI = 78.5-100.0), respectively. The RT-LAMP assay detected ZIKV genome in 9 of 24 (37.5%) of the simulated clinical samples compared to 10 of 24 (41.7%) by qRT-PCR assay with a high level of concordance (κ = 0.913, P < 0.001). CONCLUSION: The RT-LAMP assay is applicable for the broad coverage detection of both the Asian and African ZIKV strains in resource-deficient settings.


Asunto(s)
Técnicas de Diagnóstico Molecular/métodos , Técnicas de Amplificación de Ácido Nucleico/métodos , Infección por el Virus Zika/diagnóstico , Infección por el Virus Zika/epidemiología , Virus Zika/clasificación , Virus Zika/genética , África/epidemiología , Asia/epidemiología , Humanos , ARN Viral/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Sensibilidad y Especificidad , Infección por el Virus Zika/virología
2.
Artículo en Inglés | MEDLINE | ID: mdl-33027393

RESUMEN

The Northeast of Brazil has experienced a triple epidemic, with the simultaneous circulation of dengue virus (DENV), chikungunya virus (CHIKV) and Zika virus (ZIKV), which may have contributed to the observed increase across this region of atypical forms of disease and deaths. In view of this fact, non-congenital neurological disorders related to arboviruses were compared with other etiologies, mortality and survival rates of patients admitted to referral neurology hospitals in Pernambuco State, Northeast Brazil, from 2015 to 2018. Blood and cerebrospinal fluid samples were collected and tested using molecular and serological assays. The arbovirus-exposed groups were compared with respect to epidemiological, clinical and neurologic characteristics by using the Pearson's chi-square test. For the survival analysis, the Kaplan-Meier and Hazard Ratio (HR) tests were used, with a 95% confidence interval (CI). Encephalitis and encephalomyelitis were more frequent in arboviruses, while myelitis predominated in the neurological disorders of other etiologies. Guillain-Barré Syndrome (GBS) was similarly distributed amongst the groups. Exposure to one of the arboviruses caused a six-fold increase in the risk of death (HR: 6.37; CI: 2.91 - 13.9). Amongst the arbovirus-exposed groups, infection (DENV/CHIKV) increased nine times the risk of death (HR: 9.07; CI: 3.67 - 22.4). The survival curve indicates that have been exposed to some arbovirus decreased the likelihood of survival compared to those with other etiologies (Log-Rank: p<0.001). Within this scenario, neurologic manifestations of DENV, CHIKV and ZIKV have the potential to increase mortality and decrease survival, and concomitant infection (DENV/CHIKV) is an aggravating factor in reducing the likelihood of survival when compared to monoinfections.


Asunto(s)
Fiebre Chikungunya/diagnóstico , Virus del Dengue/aislamiento & purificación , Dengue/diagnóstico , Encefalitis Viral/epidemiología , Encefalomielitis/virología , Enfermedades del Sistema Nervioso/virología , Infección por el Virus Zika/diagnóstico , Virus Zika/aislamiento & purificación , Adulto , Brasil , Fiebre Chikungunya/complicaciones , Dengue/complicaciones , Encefalomielitis/epidemiología , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Enfermedades del Sistema Nervioso/diagnóstico , Análisis de Supervivencia , Infección por el Virus Zika/complicaciones
4.
PLoS Negl Trop Dis ; 14(9): e0008532, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32956416

RESUMEN

BACKGROUND: After Zika virus (ZIKV) emerged in the Americas, laboratory-based surveillance for arboviral diseases in Puerto Rico was adapted to include ZIKV disease. METHODS AND FINDINGS: Suspected cases of arboviral disease reported to Puerto Rico Department of Health were tested for evidence of infection with Zika, dengue, and chikungunya viruses by RT-PCR and IgM ELISA. To describe spatiotemporal trends among confirmed ZIKV disease cases, we analyzed the relationship between municipality-level socio-demographic, climatic, and spatial factors, and both time to detection of the first ZIKV disease case and the midpoint of the outbreak. During November 2015-December 2016, a total of 71,618 suspected arboviral disease cases were reported, of which 39,717 (55.5%; 1.1 cases per 100 residents) tested positive for ZIKV infection. The epidemic peaked in August 2016, when 71.5% of arboviral disease cases reported weekly tested positive for ZIKV infection. Incidence of ZIKV disease was highest among 20-29-year-olds (1.6 cases per 100 residents), and most (62.3%) cases were female. The most frequently reported symptoms were rash (83.0%), headache (64.6%), and myalgia (63.3%). Few patients were hospitalized (1.2%), and 13 (<0.1%) died. Early detection of ZIKV disease cases was associated with increased population size (log hazard ratio [HR]: -0.22 [95% confidence interval -0.29, -0.14]), eastern longitude (log HR: -1.04 [-1.17, -0.91]), and proximity to a city (spline estimated degrees of freedom [edf] = 2.0). Earlier midpoints of the outbreak were associated with northern latitude (log HR: -0.30 [-0.32, -0.29]), eastern longitude (spline edf = 6.5), and higher mean monthly temperature (log HR: -0.04 [-0.05, -0.03]). Higher incidence of ZIKV disease was associated with lower mean precipitation, but not socioeconomic factors. CONCLUSIONS: During the ZIKV epidemic in Puerto Rico, 1% of residents were reported to public health authorities and had laboratory evidence of ZIKV disease. Transmission was first detected in urban areas of eastern Puerto Rico, where transmission also peaked earlier. These trends suggest that ZIKV was first introduced to Puerto Rico in the east before disseminating throughout the island.


Asunto(s)
Epidemias/estadística & datos numéricos , Análisis Espacio-Temporal , Infección por el Virus Zika/epidemiología , Femenino , Humanos , Incidencia , Masculino , Puerto Rico/epidemiología , Estudios Retrospectivos , Virus Zika/aislamiento & purificación , Infección por el Virus Zika/diagnóstico
5.
Lancet Neurol ; 19(10): 826-839, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32949543

RESUMEN

BACKGROUND: Since 2015, the arthropod-borne viruses (arboviruses) Zika and chikungunya have spread across the Americas causing outbreaks, accompanied by increases in immune-mediated and infectious neurological disease. The spectrum of neurological manifestations linked to these viruses, and the importance of dual infection, are not known fully. We aimed to investigate whether neurological presentations differed according to the infecting arbovirus, and whether patients with dual infection had a different disease spectrum or severity. METHODS: We report a prospective observational study done during epidemics of Zika and chikungunya viruses in Recife, Pernambuco, a dengue-endemic area of Brazil. We recruited adults aged 18 years or older referred to Hospital da Restauração, a secondary-level and tertiary-level hospital, with suspected acute neurological disease and a history of suspected arboviral infection. We looked for evidence of Zika, chikungunya, or dengue infection by viral RNA or specific IgM antibodies in serum or CSF. We grouped patients according to their arbovirus laboratory diagnosis and then compared demographic and clinical characteristics. FINDINGS: Between Dec 4, 2014, and Dec 4, 2016, 1410 patients were admitted to the hospital neurology service; 201 (14%) had symptoms consistent with arbovirus infection and sufficient samples for diagnostic testing and were included in the study. The median age was 48 years (IQR 34-60), and 106 (53%) were women. 148 (74%) of 201 patients had laboratory evidence of arboviral infection. 98 (49%) of them had a single viral infection (41 [20%] had Zika, 55 [27%] had chikungunya, and two [1%] had dengue infection), whereas 50 (25%) had evidence of dual infection, mostly with Zika and chikungunya viruses (46 [23%] patients). Patients positive for arbovirus infection presented with a broad range of CNS and peripheral nervous system (PNS) disease. Chikungunya infection was more often associated with CNS disease (26 [47%] of 55 patients with chikungunya infection vs six [15%] of 41 with Zika infection; p=0·0008), especially myelitis (12 [22%] patients). Zika infection was more often associated with PNS disease (26 [63%] of 41 patients with Zika infection vs nine [16%] of 55 with chikungunya infection; p≤0·0001), particularly Guillain-Barré syndrome (25 [61%] patients). Patients with Guillain-Barré syndrome who had Zika and chikungunya dual infection had more aggressive disease, requiring intensive care support and longer hospital stays, than those with mono-infection (median 24 days [IQR 20-30] vs 17 days [10-20]; p=0·0028). Eight (17%) of 46 patients with Zika and chikungunya dual infection had a stroke or transient ischaemic attack, compared with five (6%) of 96 patients with Zika or chikungunya mono-infection (p=0·047). INTERPRETATION: There is a wide and overlapping spectrum of neurological manifestations caused by Zika or chikungunya mono-infection and by dual infections. The possible increased risk of acute cerebrovascular disease in patients with dual infection merits further investigation. FUNDING: Fundação do Amparo a Ciência e Tecnologia de Pernambuco (FACEPE), EU's Horizon 2020 research and innovation programme, National Institute for Health Research. TRANSLATIONS: For the Portuguese and Spanish translations of the abstract see Supplementary Materials section.


Asunto(s)
Fiebre Chikungunya/diagnóstico , Fiebre Chikungunya/epidemiología , Enfermedades del Sistema Nervioso/diagnóstico , Enfermedades del Sistema Nervioso/epidemiología , Infección por el Virus Zika/diagnóstico , Infección por el Virus Zika/epidemiología , Adulto , Anciano , Brasil/epidemiología , Fiebre Chikungunya/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/sangre , Estudios Prospectivos , Infección por el Virus Zika/sangre
6.
Braz J Infect Dis ; 24(5): 405-411, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32941805

RESUMEN

Several major epidemics of Zika fever, caused by the ZIKA virus (ZIKV), have emerged in Brazil since early 2015, eventually spreading to other countries on the South American continent. The present study describes the clinical manifestations and laboratory findings of patients with confirmed acute ZIKV infection during the first epidemic that occurred in Salvador, Brazil. All included patients were seen at the emergency room of a private tertiary hospital located in Salvador, Brazil from 2015 through 2017. Patients were considered eligible if signs of systemic viral febrile disease were present. All individuals were tested for ZIKV and Chikungunya infection using PCR, while rapid test was used to detect Dengue virus antibodies or, alternatively, the NS1 antigen. A diagnosis of acute ZIKV infection was confirmed in 78/434 (18%) individuals with systemic viral febrile illness. Positivity was mainly observed in blood, followed by saliva and urine. Coinfection with Chikungunya and/or Dengue virus was detected in 5% of the ZIKV-infected patients. The most frequent clinical findings were myalgia, arthralgia and low-grade fever. Laboratory analysis demonstrated normal levels of hematocrit, platelets and liver enzymes. In summary, in acute settings where molecular testing remains unavailable, clinicians face difficulties to confirm the diagnosis of ZIKV infection, as they rely only on clinical examinations and conventional laboratory tests.


Asunto(s)
Fiebre Chikungunya , Virus Chikungunya , Virus del Dengue , Dengue , Epidemias , Infección por el Virus Zika , Virus Zika , Brasil/epidemiología , Fiebre Chikungunya/epidemiología , Dengue/epidemiología , Humanos , Infección por el Virus Zika/diagnóstico , Infección por el Virus Zika/epidemiología
7.
Sci Adv ; 6(39)2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32978154

RESUMEN

Detection of viruses is critical for controlling disease spread. Recent emerging viral threats, including Zika virus, Ebola virus, and SARS-CoV-2 responsible for coronavirus disease 2019 (COVID-19) highlight the cost and difficulty in responding rapidly. To address these challenges, we develop a platform for low-cost and rapid detection of viral RNA with DNA nanoswitches that mechanically reconfigure in response to specific viruses. Using Zika virus as a model system, we show nonenzymatic detection of viral RNA with selective and multiplexed detection between related viruses and viral strains. For clinical-level sensitivity in biological fluids, we paired the assay with sample preparation using either RNA extraction or isothermal preamplification. Our assay requires minimal laboratory infrastructure and is adaptable to other viruses, as demonstrated by quickly developing DNA nanoswitches to detect SARS-CoV-2 RNA in saliva. Further development and field implementation will improve our ability to detect emergent viral threats and ultimately limit their impact.


Asunto(s)
Betacoronavirus/genética , Infecciones por Coronavirus/diagnóstico , ADN de Cadena Simple/genética , Electroforesis en Gel de Agar/métodos , Neumonía Viral/diagnóstico , ARN Viral/genética , Análisis de Secuencia de ARN/métodos , Secuencia de Bases , Línea Celular Tumoral , Infecciones por Coronavirus/virología , Dengue/diagnóstico , Dengue/virología , Virus del Dengue/genética , Electroforesis en Gel de Agar/economía , Humanos , Límite de Detección , Pandemias , Neumonía Viral/virología , Saliva/virología , Análisis de Secuencia de ARN/economía , Virus Zika/genética , Infección por el Virus Zika/diagnóstico , Infección por el Virus Zika/virología
8.
Rev. cuba. pediatr ; 92(3): e996, jul.-set. 2020. tab
Artículo en Español | LILACS, CUMED | ID: biblio-1126768

RESUMEN

Introducción: El zika es considerado una virosis emergente, nunca antes presente en Cuba. Objetivo: Caracterizar desde el punto de vista clínico epidemiológico a pacientes pediátricos con zika confirmado. Métodos: Estudio descriptivo transversal realizado en el Hospital Pediátrico Leonor Pérez entre 2016- 2017, en el transcurso de la epidemia. Se analizaron 140 historias clínicas de pacientes con zika confirmado por reacción en cadena de la polimerasa en suero y orina. Se midieron variables clínicas, de laboratorio y se calculó la tasa asistida. Resultados: La tasa asistida fue 44,35 × 100 casos sospechosos. De las historias clínicas analizadas, 72,1 por ciento correspondió al sexo masculino y el grupo de edad de 10 a 15 años. La reacción en cadena de la polimerasa fue positiva en mayor porcentaje en orina que en suero: 52,1 y 40,7 por ciento respectivamente y en correspondencia con el día de toma de la muestra de orina. El exantema estuvo presente en 84,3 por ciento de pacientes y la fiebre en 70 por ciento. El prurito, ojos rojos, cefalea, malestar general, dolor retroocular, odinofagia, artralgia, anorexia y edemas, se observó en menos de 35 por ciento de los casos. Los promedios de los componentes del hemograma con diferencial y la eritrosedimentación fueron normales. Conclusiones: El exantema y la fiebre son los síntomas de mayor presencia y el estudio en orina por reacción en cadena de la polimerasa informa mayor número de pacientes positivos que en suero, según el momento del ingreso. Los complementarios de rutina son poco sugerentes de zika en los casos sospechosos(AU)


Introduction: Zika virus is considerd as an emergent virus with no previous presence in the Cuban population. Objective: To characterize clinically patients with confirmed Zika virus. Methods: Descriptive cross-sectional study conducted in Leonor Pérez Pediatric Hospital between 2016 and 2017 during the epidemics. There were analyzed 140 clinical records of patients with zika confirmed by chain reaction of polymerase in serum and urine. There were measured clinical and laboratory variables and it was calculated the assisted rate. Results: The assisted rate was 44.35 × 100 suspected cases. From the analyzed clinical records, 72.1 percent corresponded to the male sex and the average age was 10.9 ± 5.5 years. The chain reaction of polimerase was positive in a higher percentage of patients in urine than in serum: 52.1 percent and 40.7 percent, respectively and corresponding with the day when the urine sample was taken. Rash was present in 84.3 percent of the patients and fever in 70.0 percent. Pruritus, red eyes, cephalalgia, general discomfort, pain behind the eyes, odynophagia, arthralgia, anorexia and edemas were observed in less than 35.0 percent of the cases. The averages of the components of blood count with differential and the erythrocyte sedimentation were normal. Conclusions: Rash and fever are the most frequent symptoms and the study of urine by chain reaction of polimerase informs of a higher number of positive patients than in the study of serum, according to the time of admittion. The routine complementary tests are not suggestive of zika in suspected cases(AU)


Asunto(s)
Humanos , Masculino , Femenino , Lactante , Preescolar , Niño , Adolescente , Infecciones por Coronavirus/transmisión , Infección por el Virus Zika/diagnóstico , Infección por el Virus Zika/epidemiología , Epidemiología Descriptiva , Estudios Transversales
9.
Artículo en Inglés | MEDLINE | ID: mdl-32844907

RESUMEN

This study analyzed possible associations between the trimester of maternal Zika virus infection (ZIKV) in pregnancy, severity of brain computed tomography (CT) findings and the presence of microcephaly at birth in children with Congenital Zika Syndrome (CZS). It was an analytical study in a cohort of children with CZS. Symptoms of maternal infection were dichotomized into the 1st trimester of pregnancy and other trimesters. Head circumference (HC) at birth was used to calculate the z-score. Mild microcephaly was defined as HC between 2 and ≥3 standard deviations (SD) below the mean for each gestational age and sex, and severe microcephaly when HC <3 SD below average. Brain CT images were evaluated by two radiologists and classified, according to the severity, into mild, moderate and severe. Fisher's exact, Mann-Whitney and Kruskal-Wallis tests were used to verify the associations between variables. In 108 children, maternal infection in the 1st trimester of pregnancy was associated with more severe brain CT abnormalities (p=0.038), greater severity of microcephaly at birth (p=0.013) and lower HC z-scores at birth (p=0.021). The severity of brain CT lesions was also associated with lower HC z-scores at birth (p<0.001). Maternal ZIKV infection during the first trimester of pregnancy proved to be an important risk factor for a more severe spectrum of CZS, as it is associated with more severe brain CT abnormalities and, consequently, with lower HC z-scores at birth.


Asunto(s)
Encéfalo/diagnóstico por imagen , Microcefalia/virología , Primer Trimestre del Embarazo , Tomografía Computarizada por Rayos X/métodos , Infección por el Virus Zika/diagnóstico , Virus Zika , Adulto , Femenino , Humanos , Recién Nacido , Embarazo , Complicaciones Infecciosas del Embarazo/epidemiología , Trimestres del Embarazo , Índice de Severidad de la Enfermedad , Infección por el Virus Zika/congénito , Infección por el Virus Zika/epidemiología
11.
Arq Neuropsiquiatr ; 78(7): 403-411, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32627805

RESUMEN

BACKGROUND: The congenital Zika syndrome involves structural brain changes, including ventriculomegaly, thin cerebral cortices, abnormal gyral pattern, cortical malformations, hypoplasia of the corpus callosum, myelination delay, subcortical diffuse calcifications, brainstem hypoplasia, and microcephaly in newborns. OBJECTIVE: This study aimed to describe the clinical characteristics of children with congenital Zika syndrome; to compare the outcomes of infants infected in the first (1T, n=20) and second trimesters of pregnancy (2T, n=11); to investigate correlations between birth weight, birth and follow-up head circumference, birth gestational age, and gross motor scores. METHODS: Participants were evaluated with Alberta Infant Motor Scale (AIMS) and part A of the Gross Motor Function Measure (GMFM-A). ANOVA compared head circumference, birth gestational age, birth weight, and gross motor performance of 1T and 2T. RESULTS: The correlations were investigated by Pearson correlation coefficients. ANOVA showed differences in birth and follow-up head circumferences. Head circumference was smaller in 1T, compared to 2T. Motor performance was classified as below the fifth percentile in AIMS in all children and 1T showed lower scores in prone, sitting, and total AIMS score, compared to 2T. Children ranged from 8 to 78% on GMFM-A and there was a poorer motor performance of 1T. Nineteen children showed hypertonia, six showed normal tone and six showed hypotonia. Birth head circumference was correlated with AIMS prone postural control. Follow-up head circumference was correlated to prone, supine and total AIMS scores. Smaller head circumference at birth and follow-up denoted poorer postural control. DISCUSSION: Children with congenital Zika syndrome showed microcephaly at birth and follow-up. Smaller head circumferences and poorer motor outcomes were observed in 1T. Infants showed poor visual and motor outcomes. Moderate positive correlations between birth and follow-up head circumference and gross motor function were found.


Asunto(s)
Microcefalia/virología , Infección por el Virus Zika/diagnóstico , Virus Zika/aislamiento & purificación , Encéfalo , Cefalometría , Niño , Femenino , Humanos , Lactante , Recién Nacido , Imagen por Resonancia Magnética , Microcefalia/diagnóstico , Destreza Motora , Embarazo , Complicaciones Infecciosas del Embarazo , Infección por el Virus Zika/complicaciones , Infección por el Virus Zika/congénito
12.
Proc Natl Acad Sci U S A ; 117(18): 9865-9875, 2020 05 05.
Artículo en Inglés | MEDLINE | ID: mdl-32321830

RESUMEN

Recent epidemics demonstrate the global threat of Zika virus (ZIKV), a flavivirus transmitted by mosquitoes. Although infection is usually asymptomatic or mild, newborns of infected mothers can display severe symptoms, including neurodevelopmental abnormalities and microcephaly. Given the large-scale spread, symptom severity, and lack of treatment or prophylaxis, a safe and effective ZIKV vaccine is urgently needed. However, vaccine design is complicated by concern that elicited antibodies (Abs) may cross-react with other flaviviruses that share a similar envelope protein, such as dengue virus, West Nile virus, and yellow fever virus. This cross-reactivity may worsen symptoms of a subsequent infection through Ab-dependent enhancement. To better understand the neutralizing Ab response and risk of Ab-dependent enhancement, further information on germline Ab binding to ZIKV and the maturation process that gives rise to potently neutralizing Abs is needed. Here we use binding and structural studies to compare mature and inferred-germline Ab binding to envelope protein domain III of ZIKV and other flaviviruses. We show that affinity maturation of the light-chain variable domain is important for strong binding of the recurrent VH3-23/VK1-5 neutralizing Abs to ZIKV envelope protein domain III, and identify interacting residues that contribute to weak, cross-reactive binding to West Nile virus. These findings provide insight into the affinity maturation process and potential cross-reactivity of VH3-23/VK1-5 neutralizing Abs, informing precautions for protein-based vaccines designed to elicit germline versions of neutralizing Abs.


Asunto(s)
Anticuerpos Neutralizantes/aislamiento & purificación , Anticuerpos Antivirales/inmunología , Proteínas del Envoltorio Viral/inmunología , Infección por el Virus Zika/inmunología , Virus Zika/inmunología , Animales , Anticuerpos Monoclonales/inmunología , Anticuerpos Neutralizantes/inmunología , Virus del Dengue/inmunología , Virus del Dengue/patogenicidad , Epítopos/inmunología , Células Germinativas/inmunología , Humanos , Recién Nacido , Dominios Proteicos/inmunología , Vacunas Virales/inmunología , Virus del Nilo Occidental/inmunología , Virus del Nilo Occidental/patogenicidad , Virus de la Fiebre Amarilla/inmunología , Virus de la Fiebre Amarilla/patogenicidad , Virus Zika/aislamiento & purificación , Infección por el Virus Zika/diagnóstico , Infección por el Virus Zika/virología
13.
Obstet Gynecol ; 135(5): 1185-1197, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32282593

RESUMEN

OBJECTIVE: To examine the relationship between prenatal diagnostics (ultrasound examination and amniotic fluid Zika virus testing) and postnatal congenital Zika syndrome abnormalities. DATA SOURCES: Systematic searches were performed in 27 databases, including ClinicalTrials.gov, from inception to July 1, 2019, for articles with the keywords "Zika," "prenatal," "ultrasound," and "amniocentesis." METHODS OF STUDY SELECTION: A total of 3,049 unique records were identified. Two reviewers independently assessed titles, abstracts, and full texts for relevance; 84 articles met the inclusion criteria. These articles describe 402 mother-fetus or mother-neonate dyads; 385 were included in the review of prenatal ultrasound examination, and 56 in the review of amniocentesis (39 in both). TABULATION, INTEGRATION, AND RESULTS: Among 195 fetuses with congenital Zika syndrome findings on prenatal ultrasound examination, postnatal congenital Zika syndrome abnormalities were reported for 153 (78%; 95% CI 7-84%). High proportions of microcephaly (76%; 95% CI 69-82%) and brain abnormalities (78%; 95% CI 69-86%) were confirmed postnatally. Among 190 fetuses without congenital Zika syndrome findings on prenatal ultrasound examination, 17% (95% CI 12-24%) had congenital Zika syndrome abnormalities identified postnatally. Structural congenital Zika syndrome abnormalities were identified postnatally in approximately equal proportions among dyads with and without Zika virus RNA detected in an amniotic fluid specimen (68% and 67%; 95% CI 52-82% and 95% CI 38-88%). In six pregnancies, Zika virus RNA was detected in amniotic fluid but not in a subsequent amniocentesis specimen. CONCLUSION: Prenatal ultrasound examination frequently detects structural findings associated with Zika virus infection; however, not all abnormalities are detected, and some may represent transient findings. As with other congenital infections, prenatal detection may vary with timing of infection, timing of ultrasound examination, technical expertise, and severity of abnormalities. The detection of Zika virus RNA in amniotic fluid in the included studies did not predict the risk for congenital Zika syndrome abnormalities in these cases, and clearance of Zika virus RNA from amniotic fluid appears possible after maternal infection. Diagnostic testing for Zika virus infection remains a shared decision between patients and clinicians, and more data are needed to define clinical predictors that will inform these decisions. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42018080959.


Asunto(s)
Amniocentesis/métodos , Enfermedades Fetales/diagnóstico , Ultrasonografía Prenatal/métodos , Infección por el Virus Zika/diagnóstico , Virus Zika , Adulto , Femenino , Enfermedades Fetales/virología , Humanos , Embarazo , Adulto Joven , Infección por el Virus Zika/embriología , Infección por el Virus Zika/virología
14.
Am J Trop Med Hyg ; 102(5): 985-987, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32228787

RESUMEN

We tested 700 serum samples collected throughout Panama from 2015 to 2016 for detecting antibodies and RNA of arboviruses. In convalescent specimens, microsphere immunoassay detected an antibody prevalence of 59.3% for dengue virus (DENV) and 30.3% for Zika virus (ZIKV), which included samples that were collected before the Panamanian surveillance system reported the first case of Zika in the country. For acute sera, the most common arbovirus was DENV with 18 positive samples (6%), followed by four (1.3%) of ZIKV and one (0.6%) of chikungunya virus (CHIKV). Our results indicate a change in the chronology of when ZIKV was first detected in Panama and stress the importance of integrating various approaches to enable improved surveillance of both endemic and emerging arboviruses.


Asunto(s)
Arbovirus , Vigilancia de la Población/métodos , Infección por el Virus Zika/diagnóstico , Virus Zika , Anticuerpos Antivirales/sangre , Virus Chikungunya , Virus del Dengue , Técnica del Anticuerpo Fluorescente , Humanos , Panamá/epidemiología , Prevalencia , Reacción en Cadena en Tiempo Real de la Polimerasa , Infección por el Virus Zika/epidemiología
15.
Infez Med ; 28(1): 11-16, 2020 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-32172256

RESUMEN

There is a massive burden of acute febrile diseases during the post-monsoon season in tropical countries. Despite this, there is a lack of clarity amongst the primary care physicians and travel medicine experts on how to approach such patients in a syndromic fashion. In this review, the authors summarize a case-based approach in the management of acute febrile diseases.


Asunto(s)
Tormentas Ciclónicas , Países en Desarrollo , Fiebre/etiología , Enfermedad Aguda , Adulto , Fiebre Chikungunya/complicaciones , Fiebre Chikungunya/diagnóstico , Dengue/complicaciones , Dengue/diagnóstico , Humanos , Leptospirosis/complicaciones , Leptospirosis/diagnóstico , Malaria Falciparum/complicaciones , Malaria Falciparum/diagnóstico , Masculino , Tifus por Ácaros/complicaciones , Tifus por Ácaros/diagnóstico , Evaluación de Síntomas/métodos , Fiebre Tifoidea/complicaciones , Fiebre Tifoidea/diagnóstico , Infección por el Virus Zika/complicaciones , Infección por el Virus Zika/diagnóstico
16.
Acta Trop ; 206: 105438, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32165128

RESUMEN

INTRODUCTION: Typical symptoms of primary Zika virus infection are not specific and share similarities with other arbovirus infections such as dengue fever and chikungunya. As acute infection can be asymptomatic in up to 73% of cases, infants with microcephaly represent a diagnostic challenge for pediatricians. We describe the frequency of congenital Zika syndrome (CZS) in Brazilian children born to asymptomatic pregnant mothers and its differential diagnosis. METHODS: This longitudinal, observational study was conducted on children with suspected CZS whose mothers did not report rash during pregnancy, referred to the reference hospital in a metropolitan area of ​ Rio de Janeiro, Brazil. The diagnosis of suspected CZS was based on Brazilian Ministry of Health protocol. RESULTS: Forty-three (17%) of 246 referred children were born to mothers without rash history during pregnancy. Thirteen (30%) of 43 children met the Brazilian Ministry of Health criteria for CZS, all with microcephaly (two post-natal). The other children included 11 cases with post-natal microcephaly due to hypoxic-ischemic encephalopathy (6), non-progressive encephalopathy of unknown etiology (2), microcephaly under investigation (2) and congenital toxoplasmosis (1); 17 children were misdiagnosed with microcephaly and progressed with normal head circumference during the follow-up period; one child was included because of epidemiological link and one was loss to follow-up. All children who underwent laboratory investigation for ZIKV infection during neonatal period had negative RT-qPCR tests. CONCLUSION: We emphasize the increasing importance of CZS in differential diagnosis of microcephaly at birth or post-natal period. Detailed clinical investigation assisted by neuroimaging tests may clarify the diagnosis of CZS when laboratory tests are not available during the acute phase of the disease.


Asunto(s)
Microcefalia/diagnóstico , Complicaciones Infecciosas del Embarazo , Infección por el Virus Zika/congénito , Infección por el Virus Zika/diagnóstico , Adulto , Infecciones Asintomáticas , Diagnóstico Diferencial , Femenino , Humanos , Lactante , Estudios Longitudinales , Embarazo
17.
Am J Trop Med Hyg ; 102(6): 1244-1248, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32157991

RESUMEN

Recent expansions of vector-borne diseases highlight the need for improved surveillance, especially in resource-poor settings. Dengue virus (DENV), chikungunya virus (CHIKV), and Zika virus (ZIKV) share the same vectors as well as similar clinical presentations, suggesting that combined surveillance would be useful. We hypothesized that blood spotted on dengue rapid diagnostic tests (RDTs) could be harnessed for sample collection in remote areas for subsequent detection of DENV, CHIKV, and ZIKV by reverse transcription real-time polymerase chain reaction (RT-qPCR). CHIKV and ZIKV dilutions were spotted on dengue RDTs (SD BIOLINE Dengue DUO, Standard Diagnostics, Gyeonggi-do, Republic of Korea), dried, and extracted. As reference, aliquots of each viral dilution were directly extracted. Using specific RT-qPCR tests, both viruses were successfully detected from RDT extracts. However, the limit of detection was slightly lower in comparison to direct extracts, two logfold for CHIKV and one logfold for ZIKV. For analysis of temperature stability, DENV dilutions were spotted on RDTs and stored for up to 2 months at -80°C, 4°C, or 35°C before testing. Storage of RDTs for 2 months at 35°C did not compromise detection of RNA by RT-qPCR; only minimal degradation was observed. This proof-of-principle study demonstrates the potential of using dengue RDTs for DENV/CHIKV/ZIKV combined surveillance in areas without access to laboratory facilities. Further investigations are needed for evaluation of tri-viral surveillance under field conditions using patient samples. Large-scale implementation of surveillance for these viruses is of crucial public health importance for the early detection of epidemics. This method also has important implications for improving understanding of the molecular epidemiology of the three viruses.


Asunto(s)
Fiebre Chikungunya/epidemiología , Dengue/epidemiología , Vigilancia de la Población/métodos , Infección por el Virus Zika/epidemiología , Virus Chikungunya/genética , Virus Chikungunya/aislamiento & purificación , Dengue/diagnóstico , Virus del Dengue/genética , Virus del Dengue/aislamiento & purificación , Humanos , Laos/epidemiología , ARN Viral/genética , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Virus Zika/genética , Virus Zika/aislamiento & purificación , Infección por el Virus Zika/diagnóstico
18.
Parasit Vectors ; 13(1): 128, 2020 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-32171303

RESUMEN

BACKGROUND: Zika virus (ZIKV) is transmitted to humans during the bite of an infected mosquito. In a scenario of globalization and climate change, the frequency of outbreaks has and will increase in areas with competent vectors, revealing a need for continuous improvement of ZIKV detection tools in vector populations. A simple, rapid and sensitive assay for viral detection is quantitative reverse transcription polymerase chain reaction (qRT-PCR), yet oligos optimized for ZIKV detection in mammalian cells and samples have repeatedly shown high background when used on mosquito ribonucleic acid (RNA). In this paper, we present a one-step qRT-PCR protocol that allows for the detection of ZIKV in mosquitoes and for the evaluation of gene expression from the same mosquito sample and RNA. This assay is a less expensive qRT-PCR approach than that most frequently used in the literature and has a much lower background, allowing confident detection. METHODS: Our new oligo design to detect ZIKV RNA included in silico analysis of both viral and mosquito (Ae. aegypti and Ae. albopictus) genomes, targeting sequences conserved between Asian and African ZIKV lineages, but not matching Aedes genomes. This assay will allow researchers to avoid nonspecific amplification in insect samples due to viral integration into the mosquito genome, a phenomenon known to happen in wild and colonized populations of mosquitoes. Standard curves constructed with in vitro transcribed ZIKV RNA were used to optimize the sensitivity, efficiency and reproducibility of the assay. RESULTS: Finally, the assay was used with success to detect both ZIKV RNA in infected mosquitoes and to detect expression of the Defensin A gene, an antimicrobial peptide (AMP) involved in Aedes aegypti immune response to virus infection. CONCLUSIONS: The experimental approach to detect ZIKV RNA in Aedes aegypti presented here has demonstrated to be specific, sensitive and reliable, and additionally it allows for the analysis of mosquito gene expression during ZIKV infection.


Asunto(s)
Aedes/virología , Regulación Viral de la Expresión Génica , Mosquitos Vectores/virología , ARN Viral/aislamiento & purificación , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Infección por el Virus Zika/diagnóstico , Virus Zika/genética , Virus Zika/aislamiento & purificación , Aedes/genética , Animales , Chlorocebus aethiops , Culicidae/virología , ARN Viral/genética , Reproducibilidad de los Resultados , Alineación de Secuencia , Células Vero , Proteínas no Estructurales Virales/genética , Infección por el Virus Zika/virología
19.
Am J Trop Med Hyg ; 102(4): 880-883, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32043455

RESUMEN

Zika virus (ZIKV) caused a public health threat in the United States in 2016, leading to rapid development and implementation of blood screening assays for ZIKV RNA. Several ZIKV sequences from clinical cases have been reported, but none from asymptomatic/pre-symptomatic infections. We isolated and sequenced ZIKV from asymptomatic/pre-symptomatic blood donor (ABD-ZIKV) samples and compared with reported clinical sequences. Twelve ABD-ZIKV isolates were produced from 67 cultivated samples, and isolates were genetically similar among themselves. Most isolates shared mutations with the clinical isolate PRVABC59 2015, whereas two ABD-ZIKV isolates shared specific mutations with U.S. clinical isolates from 2016. The ABD-ZIKV strains clustered into two distinct subclades: one comprised mostly ABD-ZIKV from Puerto Rico, and another one comprised ABD-ZIKV from Florida and QTX-02 isolate (Puerto Rico). In this study, we showed the circulation of two slightly distinct virus strains among Puerto Rico blood donors, one of which was also reported in Florida.


Asunto(s)
Donantes de Sangre , Filogenia , Infección por el Virus Zika/sangre , Virus Zika/genética , Virus Zika/aislamiento & purificación , Adulto , Enfermedades Transmisibles Emergentes/sangre , Enfermedades Transmisibles Emergentes/epidemiología , Florida/epidemiología , Genómica , Humanos , Puerto Rico/epidemiología , Infección por el Virus Zika/diagnóstico , Infección por el Virus Zika/epidemiología
20.
Virology ; 543: 34-42, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32056845

RESUMEN

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


Asunto(s)
Antivirales/uso terapéutico , Mosquitos Vectores/virología , Vacunas Virales , Infección por el Virus Zika/epidemiología , Infección por el Virus Zika/transmisión , Virus Zika/genética , Brasil/epidemiología , Cabo Verde/epidemiología , Brotes de Enfermedades , Femenino , Genoma Viral , Humanos , Masculino , Islas del Pacífico/epidemiología , Vacunas Virales/inmunología , Virus Zika/inmunología , Virus Zika/patogenicidad , Infección por el Virus Zika/diagnóstico , Infección por el Virus Zika/tratamiento farmacológico
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