Zika virus and microcephaly: where do we go from here?

Costa, Federico; Ko, Albert I.

doi:10.1016/s1473-3099(17)30697-7

Cited by 13 publications

(11 citation statements)

References 13 publications

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“…From our results we cannot anticipate if the effect of previous DENV immunity or the time between DENV and ZIKV infection may have any implications during the pregnancy. More complex studies using a large number of NHPs and well controlled prospective studies in human populations are needed to elucidate such a relationship (79). Based on other results from our group, it is possible to argue that the sequence of ZIKV-DENV infections (41) induce a different immunological response—in terms of the neutralization magnitude, cytokines profile and functionality of the cellular immune response—compared to the DENV-ZIKV scenario shown here.…”

Section: Discussionmentioning

confidence: 99%

Significant control of Zika infection in macaques depends on the elapsing time after dengue exposure

Serrano-Collazo

Pantoja

et al. 2019

Preprint

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29Prior exposure to a single serotype of dengue virus (DENV) predisposes individuals to severe 30 disease upon secondary heterologous DENV infection. Here we show that the length of time 31 between DENV/Zika (ZIKV) infections has a qualitative impact on controlling ZIKV replication. 32We identified limited but significant differences in the magnitude of the early humoral immune 33 response associated with a period of twelve months but not three months of DENV 34 convalescence. However, their role limiting ZIKV replication is not conclusive. There was no 35 evidence of in vivo antibody-dependent amplification of ZIKV by DENV immunity in any group. 36We are also showing that the significant differences among groups may be linked to a pre-37 existing polyfunctional CD4+ T cells response (increased IFN-g and Cd107a before ZIKV 38 infection) and to an early and continuous expansion of the CD4+ effector memory cells early on 39 after ZIKV infection. Those significant differences were associated with a period of 12 months 40 after DENV infection that were not observed in a span of 3-months. These results suggest that 41 there is a window of optimal cross-protection between ZIKV and DENV with significant 42 consequences. These results have pivotal implications while interpreting ZIKV pathogenesis in 43 flavivirus-experimented populations, diagnostic results interpretation and vaccine designs 44 among others. 45 46 Author Summary 47impact on controlling the ZIKV infection. In this study, as in our prior work we did not observe 100 evidence of ZIKV disease enhancement associated with prior DENV exposure. We also 101 confirmed that the significant differences among groups are mediated by the pre-existence of a 102 robust effector memory T cell (TEM) and cytotoxic activity mainly mediated by CD4 + T cells 103 more than qualitative differences in the humoral immune response. However, by conducting a 104 detailed study of the ZIKV-neutralizing titers vs. ZIKV RNAemia at early time points after 105 infection, we were able to determine a possible contribution of the neutralizing antibodies 106 limiting the ZIKV replication at 7 days after infection in the animals with 12 months but not 3 107 months of DENV immunity or in the control group. Overall, we demonstrated that exposure to 108 ZIKV 12 months after DENV infection afford a high level of T cell-mediated cross protection than 109 it was observed at the 3-month span. Based on our previous study we believe this protection 110 wanes as macaques exposed to ZIKV 2.8 years after DENV were not afforded this protection. 111These results suggest that there is a window of optimal T cell cross-protection between ZIKV 112 and DENV. 113 114 Results 115

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Section: Discussionmentioning

confidence: 99%

Significant control of Zika infection in macaques depends on the elapsing time after dengue exposure

Serrano-Collazo

Pantoja

et al. 2019

Preprint

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“…A case-control study does not allow establishing the risk of ZIKV infection according to pregnancy trimester. This question has to be answered by followup studies, currently under way 74 .…”

Section: Testing the Hypothesismentioning

confidence: 99%

Epidemia de microcefalia e vírus Zika: a construção do conhecimento em epidemiologia

et al. 2018

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Em agosto de 2015, neuropediatras de hospitais públicos do Recife, Pernambuco, Brasil, observaram um aumento do número de casos de microcefalia desproporcional associado a anomalias cerebrais. Esse fato gerou comoção social, mobilização da comunidade acadêmica e levou o Ministério da Saúde a decretar emergência de saúde pública nacional, seguida pela declaração de emergência de saúde pública de interesse internacional da Organização Mundial da Saúde. A hipótese formulada para o fenômeno foi a infecção congênita pelo vírus Zika (ZIKV), com base na correlação espaço-temporal e nas características clínico-epidemiológicas das duas epidemias. Evidências se acumularam e no âmbito do raciocínio epidemiológico preencheram critérios que deram sustentação à hipótese. Sua plausibilidade está ancorada no neurotropismo do ZIKV demonstrado em animais, atingindo neurônios progenitores do cérebro em desenvolvimento, e em seres humanos devido às complicações neurológicas observadas em adultos após a infecção. O isolamento do RNA e antígenos virais no líquido amniótico de mães infectadas e em cérebros de neonatos e fetos com microcefalia contribuíram para demonstrar a consistência da hipótese. O critério de temporalidade foi contemplado ao se identificar desfechos desfavoráveis em uma coorte de gestantes com exantema e positivas para o ZIKV. Finalmente, o primeiro estudo caso-controle conduzido demonstrou existir uma forte associação entre microcefalia e infecção congênita pelo ZIKV. O conhecimento construído no âmbito do paradigma epidemiológico recebeu a chancela da comunidade científica, construindo o consenso de uma relação causal entre o ZIKV e a epidemia de microcefalia.

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“…In a previous study the incidence of Zika by municipality in Brazil was estimated from the microcephaly cases rate [7]. However, whether the number of microcephaly cases depends only on the Zika incidence is debatable, and other factors -not considered in the aforementioned study -may be acting to modify the risk of this congenital malformation [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

“…One possible explanation is that, in these locations, dengue and/or chikungunya were more prevalent than Zika. However, it has been under discussion whether higher Zika incidence always translates into higher microcephaly incidence [9][10][11]. Microcephaly rates as high as those observed in Northeast Brazil were unprecedented and not observed anywhere else in the world where Zika has knowingly caused large epidemics.…”

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confidence: 99%

Identifying hidden Zika hotspots in Pernambuco, Brazil: A spatial analysis

Freitas

Lowe

et al. 2021

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Northeast Brazil has the world's highest rate of Zika-related microcephaly. Yet, in this hard-hit region, traditional case counts of Zika cannot accurately describe Zika risk. Reporting of Zika cases only became mandatory after its association with microcephaly in neonates, when the Zika epidemic was already declining in the region. To advance the study of the Brazilian Zika epidemic and its impacts, we identified hotspots of Zika in Pernambuco state, Northeast Brazil, using Aedes-borne diseases (dengue, chikungunya and Zika) and microcephaly data. We used the Kulldorff's Poisson purely spatial scan statistic to detect low- and high-risk clusters and combined the results to identify the municipalities most affected by the Zika epidemic. Municipalities were classified as hotspots if they were part of any high-risk cluster, and classified according to a gradient of Zika burden during the epidemic, considering the strength of the evidence. In Pernambuco, officials confirmed 123,934 dengue cases, 167 Zika cases, and 32,983 chikungunya cases between 2014-2017, and 800 microcephaly cases between 2015-2017. We identified 26 Aedes-borne diseases clusters (11 high-risk), and 5 microcephaly cases clusters (3 high-risk). Combining the results, sixty-three out of 184 municipalities were identified as hotspots for Zika. The northeast of Pernambuco and the Sertão region were hit hardest by the Zika epidemic. The first is the most populous area, while the second has one of the highest rates of social and economic inequality in Brazil. The identification of Sertão as a Zika hotspot was only possible because the clusters results were combined. The under-reporting of acute infectious diseases is expected to be higher in poor areas. Therefore, using only Aedes-borne data does not correctly identify the high-risk areas. We successfully identified hidden Zika hotspots using a simple methodology combining Aedes-borne diseases and microcephaly information.

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Zika virus and microcephaly: where do we go from here?

Abstract: The complex challenge of measurement to inform policy and the public.

Cited by 13 publications

References 13 publications

Significant control of Zika infection in macaques depends on the elapsing time after dengue exposure

Significant control of Zika infection in macaques depends on the elapsing time after dengue exposure

Epidemia de microcefalia e vírus Zika: a construção do conhecimento em epidemiologia

Identifying hidden Zika hotspots in Pernambuco, Brazil: A spatial analysis

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