Clinical Features and Neurodevelopmental Outcomes for Infants with Perinatal Vertical Transmission of Zika Virus, Colombia (original) (raw)
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The challenge of the laboratory diagnosis in a confirmed congenital Zika virus syndrome in utero
Medicine, 2019
Introduction: Zika virus (ZIKV) has caused one of the most challenging global infectious epidemics in recent years because of its causal association with severe microcephaly and other congenital malformations. The diagnosis of viral infections usually relies on the detection of virus proteins or genetic material in clinical samples as well as on the infected host immune responses. Serial serologic testing is required for the diagnosis of congenital infection when diagnostic molecular biology is not possible. Patient concerns: A 2-year-old girl, born to a mother with confirmed ZIKV infection during pregnancy, with a confirmed ZIKV infection in utero, showed at birth a severe microcephaly and clinical characteristics of fetal brain disruption sequence compatible with a congenital ZIKV syndrome (CZS). Diagnosis: ZIKV-RNA and ZIKV-IgM serological response performed at birth and during the follow-up time tested always negative. Serial serologic ZIKV-IgG tests were performed to assess the laboratory ZIKV diagnosis, ZIKV-IgG seroreversion was observed at 21 months of age. ZIKV diagnosis of this baby had to be relied on her clinical and radiological characteristics that were compatible with a CZS. Interventions: The patient was followed-up as per protocol at approximately 1, 4, 9, 12, 18-21, and 24 months of age. Neurological, radiological, audiological, and ophthalmological assessment were performed during this period of time. Prompt rehabilitation was initiated to prevent potential adverse long-term neurological outcomes. Outcomes: The growth of this girl showed a great restriction at 24 months of age with a weight of 8.5 kg (À2.5 z-score) and a head circumference of 40.5 cm (À4.8 z-score). She also had a great neurodevelopmental delay at the time of this report. Conclusion: We presume that as a consequence of prenatal ZIKV infection, the fetal brain and other organs are damaged before birth through direct injury. Following this, active infection ends during intrauterine life, and as a consequence the immune system of the infant is unable to build up a consistent immune response thereafter. Further understanding of the mechanisms taking part in the pathogenesis of ZIKV congenital infection is needed. This finding might change our paradigm regarding serological response in the ZIKV congenital infection. Abbreviations: AF = amniotic fluid, CSF = cerebrospinal fluid, CZS = Congenital ZIKV syndrome, DENV = dengue virus, HIV = Human immunodeficiency virus, IgG = immunoglobulin G antibodies, IgM = immunoglobulin M antibodies, MRI = magnetic resonance imaging, PRNT = plaque reduction neutralization test, RNA = ribonucleic acid, RT-PCR = reverse-transcriptase-polymerase-chainreaction, TORCH = Toxoplasma gondii, rubella virus, cytomegalovirus, herpes virus I and II, and HIV, ZIKV = Zika virus.
Zika virus from a neonatologist’s perspective
Journal of Pediatric and Neonatal Individualized Medicine, 2017
Zika virus has been known for more than half a century. Its clinical significance was just recently discovered, after the epidemic of Zika virus emerged in South and Central America. A task force established in 2015 by the Brazil Ministry of Health investigated the possible association between congenital Zika infection and microcephaly in fetuses and newborns. Since then more and more evidence emerged, supporting this hypothesis. The objective of this article is to review and summarize the currently available literature regarding Zika virus from a neonatologist’s standpoint and provide some guidance to medical providers who may have to care for potentially exposed pregnant patients and their newborns.
Zika Virus Infection in Pregnant Women in Rio de Janeiro
New England Journal of Medicine, 2016
BACKGROUND Zika virus (ZIKV) has been linked to central nervous system malformations in fetuses. To characterize the spectrum of ZIKV disease in pregnant women and infants, we followed patients in Rio de Janeiro to describe clinical manifestations in mothers and repercussions of acute ZIKV infection in infants. METHODS We enrolled pregnant women in whom a rash had developed within the previous 5 days and tested blood and urine specimens for ZIKV by reverse-transcriptase-polymerasechain-reaction assays. We followed women prospectively to obtain data on pregnancy and infant outcomes. RESULTS A total of 345 women were enrolled from September 2015 through May 2016; of these, 182 women (53%) tested positive for ZIKV in blood, urine, or both. The timing of acute ZIKV infection ranged from 6 to 39 weeks of gestation. Predominant maternal clinical features included a pruritic descending macular or maculopapular rash, arthralgias, conjunctival injection, and headache; 27% had fever (short-term and low-grade). By July 2016, a total of 134 ZIKV-affected pregnancies and 73 ZIKV-unaffected pregnancies had reached completion, with outcomes known for 125 ZIKV-affected and 61 ZIKV-unaffected pregnancies. Infection with chikungunya virus was identified in 42% of women without ZIKV infection versus 3% of women with ZIKV infection (P<0.001). Rates of fetal death were 7% in both groups; overall adverse outcomes were 46% among offspring of ZIKV-positive women versus 11.5% among offspring of ZIKV-negative women (P<0.001). Among 117 live infants born to 116 ZIKV-positive women, 42% were found to have grossly abnormal clinical or brain imaging findings or both, including 4 infants with microcephaly. Adverse outcomes were noted regardless of the trimester during which the women were infected with ZIKV (55% of pregnancies had adverse outcomes after maternal infection in the first trimester, 52% after infection in the second trimester, and 29% after infection in the third trimester). CONCLUSIONS Despite mild clinical symptoms in the mother, ZIKV infection during pregnancy is deleterious to the fetus and is associated with fetal death, fetal growth restriction, and a spectrum of central nervous system abnormalities. (Funded by Ministério da Saúde do Brasil and others.
Zika Virus Infection in Pregnant Women in Rio de Janeiro — Preliminary Report
New England Journal of Medicine, 2016
BACKGROUND Zika virus (ZIKV) has been linked to neonatal microcephaly. To characterize the spectrum of ZIKV disease in pregnancy, we followed patients in Rio de Janeiro to describe clinical manifestations in mothers and repercussions of acute ZIKV infection in fetuses. METHODS We enrolled pregnant women in whom a rash had developed within the previous 5 days and tested blood and urine specimens for ZIKV by reverse-transcriptase-polymerasechain-reaction assays. We followed the women prospectively and collected clinical and ultrasonographic data. RESULTS A total of 88 women were enrolled from September 2015 through February 2016; of these 88 women, 72 (82%) tested positive for ZIKV in blood, urine, or both. The timing of acute ZIKV infection ranged from 5 to 38 weeks of gestation. Predominant clinical features included pruritic descending macular or maculopapular rash, arthralgias, conjunctival injection, and headache; 28% had fever (short-term and low-grade). Women who were positive for ZIKV were more likely than those who were negative for the virus to have maculopapular rash (44% vs. 12%, P = 0.02), conjunctival involvement (58% vs. 13%, P = 0.002), and lymphadenopathy (40% vs. 7%, P = 0.02). Fetal ultrasonography was performed in 42 ZIKV-positive women (58%) and in all ZIKV-negative women. Fetal abnormalities were detected by Doppler ultrasonography in 12 of the 42 ZIKV-positive women (29%) and in none of the 16 ZIKV-negative women. Adverse findings included fetal deaths at 36 and 38 weeks of gestation (2 fetuses), in utero growth restriction with or without microcephaly (5 fetuses), ventricular calcifications or other central nervous system (CNS) lesions (7 fetuses), and abnormal amniotic fluid volume or cerebral or umbilical artery flow (7 fetuses). To date, 8 of the 42 women in whom fetal ultrasonography was performed have delivered their babies, and the ultrasonographic findings have been confirmed. CONCLUSIONS Despite mild clinical symptoms, ZIKV infection during pregnancy appears to be associated with grave outcomes, including fetal death, placental insufficiency, fetal growth restriction, and CNS injury.
Zika Virus Infection during Pregnancy and Congenital Abnormalities
Frontiers in microbiology, 2017
The presence of the Zika virus (ZIKV) infection has gone ahead to be a threat to people based on its adverse impacts. More specifically, the pregnant women have been discouraged from traveling to the areas affected by the ZIKV because of the likelihood of the virus causing congenital abnormalities especially the microcephaly. The pregnant women probably attracted the virus during their first trimester while visiting ZIKV affected territories. Although the ZIKV infected cases have reduced in some parts of countries, the global risk assessment has not been changed. The virus continues to spread geographically to areas where competent vectors are present. At present, there is still no treatment of ZIKV related illness, especially microcephaly.
Three-Year Clinical Follow-Up of Children Intrauterine Exposed to Zika Virus
Viruses
Congenital Zika virus (ZIKV) infection may present with a broad spectrum of clinical manifestations. Some sequelae, particularly neurodevelopmental problems, may have a later onset. We conducted a prospective cohort study of 799 high-risk pregnant women who were followed up until delivery. Eighty-three women and/or newborns were considered ZIKV exposed and/or infected. Laboratory diagnosis was made by polymerase chain reaction in the pregnant mothers and their respective newborns, as well as Dengue virus, Chikungunya virus, and ZIKV serology. Serology for toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus, and syphilis infections were also performed in microcephalic newborns. The newborns included in the study were followed up until their third birthday. Developmental delay was observed in nine patients (13.2%): mild cognitive delay in three patients, speech delay in three patients, autism spectrum disorder in two patients, and severe neurological abnormalities in one mic...
Lancet (London, England), 2016
In November, 2015, an epidemic of microcephaly was reported in Brazil, which was later attributed to congenital Zika virus infection. 7830 suspected cases had been reported to the Brazilian Ministry of Health by June 4, 2016, but little is known about their characteristics. We aimed to describe these newborn babies in terms of clinical findings, anthropometry, and survival. We reviewed all 1501 liveborn infants for whom investigation by medical teams at State level had been completed as of Feb 27, 2016, and classified suspected cases into five categories based on neuroimaging and laboratory results for Zika virus and other relevant infections. Definite cases had laboratory evidence of Zika virus infection; highly probable cases presented specific neuroimaging findings, and negative laboratory results for other congenital infections; moderately probable cases had specific imaging findings but other infections could not be ruled out; somewhat probable cases had imaging findings, but t...
Journal of Clinical Medicine, 2018
Introduction: The recent Zika virus(ZIKV) epidemic in Brazil was characterized by a range of different clinical presentations, particularly microcephaly, Guillain-Barré syndrome, and death. In this context, we determined the causal relationship between fatal microcephaly cases and ZIKV infection. Methods: Twelve fatal cases of neonates, whose mothers were infected with ZIKV during pregnancy, were examined; cases included nine neonatal deaths due to microcephaly, one miscarriage, and two stillbirths. Tissue samples were obtained from all cases at necropsy and were submitted for virological investigation (RT-qPCR and virus isolation) and/or histopathology (hematoxylin and eosin staining) and immunohistochemical assay for the detection of ZIKV antigens. Results: ZIKV antigens and/or ZIKV RNA were detected in tissue samples of all 12 cases examined. ZIKV was recovered in one case. Results of the virological and immunohistochemical analyses, as well as the anatomic abnormalities and hist...
Zika Virus Disease [Working Title]
Dengue, Chikungunya and Zika are arboviruses transmitted by Ae. aegypti with significant public health impact. In the first trimester of 2015, autochthonous Zika transmission was reported in Mexico. The state of Yucatan is an endemic region where pregnant women with acute infection and related congenital abnormalities in fetus and newborns were observed. We describe results from a cohort of pregnant women and their babies followed up in Yucatan during the first Zika transmission outbreak (2016-2018). Clinical manifestations of acute ZIKV infection, persistence of viral RNA in pregnant women, as well as congenital abnormalities were observed. In addition, we describe the phenotype of newborns from confirmed or suspected ZIKV prenatal infection.
Severe Neurologic Disorders in 2 Fetuses with Zika Virus Infection, Colombia
Emerging infectious diseases, 2017
We report the results of pathologic examinations of 2 fetuses from women in Colombia with Zika virus infection during pregnancy that revealed severe central nervous system defects and potential associated abnormalities of the eye, spleen, and placenta. Amniotic fluid and tissues from multiple fetal organs tested positive for Zika virus.