Early maternal Zika infection predicts severe neonatal neurological damage: results from the prospective Natural History of Zika Virus Infection in Gestation cohort study

Coutinho, Conrado Milani; Negrini, SFBM; Araújo, Daniel Cardoso de Almeida e; Teixeira, Sara Reis; Amaral, FR; Moro, M. Martin; Fernandes, J. N.; Motta, M; Negrini, Bento Vidal de Moura; Caldas, C. Feito; Anastásio, Adriana Ribeiro Tavares; Furtado, João M.; Bárbaro, AAT; Yamamoto, Aparecida Yulie; Duarte, Geraldo; Mussi-Pinhata, Marisa Márcia

doi:10.1111/1471-0528.16490

Cited by 22 publications

(34 citation statements)

References 38 publications

(92 reference statements)

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“…This study was embedded in the Natural History of Zika Virus Infection in Gestation (NATZIG) project, which is a prospective population-based cohort study undertaken in the Ribeirão Preto region, Northeastern São Paulo State, Brazil [2]. This region experienced an outbreak of ZIKV infection that peaked during the last trimester of 2015 and the first trimester of 2016.…”

Section: Study Populationmentioning

confidence: 99%

“…The most well-known consequences of the intrauterine transmission of Zika virus (ZIKV) infection from mother to fetus are microcephaly and related severe brain abnormalities with neurological effects, defined as Congenital Zika Syndrome (CZS) [1]. However, as with other congenital infections, the ZIKV might also have a broad clinical spectrum [2][3][4]. Overall, considering estimates of a 20-30% vertical transmission rate [4] and the reported estimates of pregnancy losses (4-7%) and congenital disabilities characterized by CZS (5-14%) [5], one could suppose that up to 10% of infants born to ZIKV-infected mothers would be infected but clinically inapparent, limiting the identification of the virus [2].…”

Section: Introductionmentioning

confidence: 99%

“…However, as with other congenital infections, the ZIKV might also have a broad clinical spectrum [2][3][4]. Overall, considering estimates of a 20-30% vertical transmission rate [4] and the reported estimates of pregnancy losses (4-7%) and congenital disabilities characterized by CZS (5-14%) [5], one could suppose that up to 10% of infants born to ZIKV-infected mothers would be infected but clinically inapparent, limiting the identification of the virus [2]. Since the primary targets of ZIKV infection are mainly the central nervous system and eyes, infected infants without severe end-organ disease are most likely to benefit from long-term follow-up and the prevention of developmental delays by stimulation and rehabilitation.…”

Section: Introductionmentioning

confidence: 99%

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Persistence of Anti-ZIKV-IgG over Time Is Not a Useful Congenital Infection Marker in Infants Born to ZIKV-Infected Mothers: The NATZIG Cohort

Coutinho

Fernandes

Yamamoto

et al. 2021

Viruses

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Confirming ZIKV congenital infection is challenging because viral RNA is infrequently detected. We compared the presence of anti-ZIKV-IgM and the persistence of anti-ZIKV-IgG antibodies over 18 months in two cohorts of infants born to ZIKV-infected mothers: Cohort one: 30 infants with typical microcephaly or major brain abnormalities (Congenital Zika Syndrome-CZS); Cohort two: 123 asymptomatic infants. Serum samples obtained within 6 months of age were tested for anti-ZIKV-IgM. Anti-ZIKV-IgG was quantified in sequential samples collected at birth, 3–6 weeks, 3, 6, 12, and 18 months. ZIKV-RNA was never detected postnatally. Anti-ZIKV-IgM antibodies were detected at least once in 15/25 (60.0%; 95%CI: 38.7–78.9) infants with CZS and in 2/115 (1.7%; 95%CI: 0.2–6.1) asymptomatic infants. Although anti-ZIKV-IgG was always positive within 3–6 weeks of age, IgG levels decreased similarly over time in both cohorts. IgG levels decreased similarly in ZIKV-IgM-positive and ZIKV-IgM-negative CZS infants. Differently from other congenital infections, IgM would fail to diagnose 40% of severely symptomatic infants, and the persistence of IgG is not a useful marker for discriminating congenital infection among infants exposed to maternal ZIKV infection.

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Section: Study Populationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Persistence of Anti-ZIKV-IgG over Time Is Not a Useful Congenital Infection Marker in Infants Born to ZIKV-Infected Mothers: The NATZIG Cohort

Coutinho

Fernandes

Yamamoto

et al. 2021

Viruses

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“…WSLV was detected throughout the foetal brains in neuronal progenitor cells and differentiated cells: neurons, oligodendrocytes, microglia and astrocytes. WSLV infection early in gestation could lead to more severe neurological complications in a manner similar to what is reported for ZIKV [307][308][309] . ZIKV causes congenital disease by infection of the neural progenitor cells associated with persistent inflammatory responses 310,311 .…”

Section: Question 3 How Does Gestational Age Affect the Outcome Of Asupporting

confidence: 60%

“…Gestational age is an important determinant of the outcome of infection by vertically transmitting arboviruses. Several cohort studies have demonstrated a strong relationship between maternal infection with ZIKV early in pregnancy with more severe brain abnormalities compared to maternal infection late in pregnancy 307,308 . Additionally, a recent cohort of children with a normal baseline neurologic examination whose mothers were infected with ZIKV during pregnancy were found to be more likely to experience developmental delays if infection had occurred during the third trimester compared to those exposed during the first or second trimester 309 .…”

Section: Question 3 How Does Gestational Age Affect the Outcome Of Amentioning

confidence: 99%

Crossing barriers : How neglected arboviruses journey through the placenta

Oymans¹

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The medical importance of arboviruses Over 500 species of viruses that are spread by arthropod vectors such as mosquitoes, midges, ticks, and sandflies are known. These viruses, belonging to 14 different virus families, are called arthropod-borne viruses, or arboviruses 1. Most arboviruses are not pathogenic to humans or animals, however more than 100 species have been described to cause human or animal disease 1,2. Virtually all viruses that are pathogenic to humans or animals belong to the families Flaviviridae, Togaviridae, Reoviridae and multiple families within the order Bunyavirales. Although these viruses differ greatly genetically and phenotypically, there are striking similarities in their lifecycles. Chapter 1 12 viral RNPs (vRNPs) into the cytosol 41-43. At the cytoplasm the vRNPs direct synthesis of mRNA and of complementary viral RNA (cRNA) 44. Progeny vRNPs, traffic by yet unknown mechanisms to the Trans-golgi-Network where newly produced glycoproteins assemble into virions and the RNPs are packaged 43,45. Rift Valley fever virus RVFV, a phlebovirus from the family Phenuiviridae, was first isolated during an outbreak among sheep on the shores of lake Naivasha in the Rift Valley of Kenya 46. The virus caused heavy mortality among the newborn lambs on the farm. Moreover, a high mortality rate of adult animals was observed as well as an increased rate of abortions 47. RVFV proved to be a zoonotic virus as laboratory workers became ill after exposure 48. Since the discovery of RVFV it has become apparent that RVFV is widespread in Africa, with occasionally major epidemics such as in 1951 in several states in South Africa 49. Many farmers lost a large proportion of their sheep and nearly all of their lambs, while the losses of cattle were less significant 50,51. Since then RVFV has remained endemic to South Africa, occasionally causing major epidemics with severe losses of sheep and cattle as a result, but also affecting humans 52,53. RVFV was reported in Egypt for the first time in 1977 after completion of the Aswan dam, which created a new breeding ground for mosquitoes 54. This outbreak was unique due to the large number of humans that were infected, which was estimated at 200,000 with 598 reported deaths 55-57. In 1987, RVFV outbreaks were reported for the first time in East Africa in Mauritania and Senegal 58,59. In the year 2000, the first incursion of RVFV outside of the African continent was reported, when two simultaneous outbreaks occurred on the Arabian Peninsula, one in northern Yemen and the other in Gazan 60. Nowadays, RVFV is endemic throughout the whole African continent and the Arabian Peninsula, occasionally causing major epidemics and epizootics 57. The history of these RVFV outbreaks, together with genomic analysis of RVFV strains from different regions suggest that RVFV is able to spread over long distances and is able to cause epizootics and epidemics after a single introduction 61. General introduction 13 often accompanied by jaundice and oedema. Haemorrhages can occur in the heart...

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Targeting first trimester trophoblast cell metabolism modulates its susceptibility to Zika virus infection

Kafer

Márquez

Merech

et al. 2023

Journal Cellular Physiology

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In the last 15 years Zika virus (ZIKV) caused several outbreaks of increasing scale in Micronesia, South Pacific islands, and more recently in the Caribbean and South America. The severity of the clinical presentation in neonates from pregnant women infected with ZIKV during the last outbreak supports the relevance of unraveling the mechanism of infection and viral persistence in the placenta with local viral isolates. Here, we investigated the relevance of trophoblast metabolic rewiring for viral multiplication and the role of the vasoactive intestinal peptide (VIP) as an endogenous factor associated with placental restriction to ZIKV infection at early pregnancy. Our in vitro model demonstrated that ZIKV triggers metabolic rewiring in first trimester cytotrophoblast‐derived cells by increasing glucose utilization as fuel to sustain its replication, decreasing long‐chain polyunsaturated fatty acid uptake, and promoting lipid droplets accumulation to favor its multiplication. Of note, variations in nutrient availability modulated viral spread in trophoblast cultures. The presence of VIP during trophoblast infection impaired ZIKV infective particle production and viral replication, restoring cell migration and metabolism. Moreover, the blockade of endogenous VIP signaling increased viral particle production and the viral entry receptor AXL expression. These results highlight the potential role of VIP as an endogenous antiviral factor related to trophoblast cell permissiveness to ZIKV infection at early pregnancy.

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Early maternal Zika infection predicts severe neonatal neurological damage: results from the prospective Natural History of Zika Virus Infection in Gestation cohort study

Cited by 22 publications

References 38 publications

Persistence of Anti-ZIKV-IgG over Time Is Not a Useful Congenital Infection Marker in Infants Born to ZIKV-Infected Mothers: The NATZIG Cohort

Persistence of Anti-ZIKV-IgG over Time Is Not a Useful Congenital Infection Marker in Infants Born to ZIKV-Infected Mothers: The NATZIG Cohort

Crossing barriers : How neglected arboviruses journey through the placenta

Targeting first trimester trophoblast cell metabolism modulates its susceptibility to Zika virus infection

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