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The frequency and clinical presentation of Zika virus coinfections: a systematic review

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Zika virus (ZIKV) is an Aedes mosquito-borne flavivirus that recently emerged in the Americas. First recognised in Brazil in early 2015, the ZIKV epidemic spread explosively, with autochthonous transmission reported in more than 86 countries and territories by 2018. Given the widespread circulation of this emerging infection of public health concern, it is critical that healthcare practitioners can readily recognise ZIKV disease across the full range of its clinical presentations.

Current evidence indicates that ZIKV infections typically present with no or mild clinical features. A 2018 meta-analysis of 23 studies by Haby and colleagues estimated a prevalence of asymptomatic ZIKV infections of 62% (95% CI 33% to 87%). For symptomatic ZIKV disease, the WHO describes a mild clinical presentation marked by fever, rash, conjunctivitis, myalgia, arthralgia, malaise and headache. Nevertheless, ZIKV is neurotropic and, in a subset of cases, infections have been associated with severe neurological complications, including the polyneuropathy Guillain-Barré syndrome (GBS) and congenital Zika syndrome (CZS), a constellation of congenital central nervous system malformations resulting from the vertical transmission of ZIKV during pregnancy. It has been estimated that GBS arises in approximately 2 per 10 000 ZIKV infections, and the absolute risk of adverse birth outcomes (ie, miscarriage, stillbirth, premature birth and CZS) has been reported to range between 7% and 46% in pregnancies with quantitative real-time PCR (qRT-PCR)-confirmed ZIKV infection.

Although the clinical presentation of ZIKV monoinfections has been well characterised, one factor that may influence the clinical spectrum of ZIKV disease is coinfection. Given the high incidence of infectious diseases in the subtropical and tropical areas where ZIKV is prevalent, a proportion of all ZIKV infections occur concurrently with infections by one or multiple pathogens. ZIKV disease in the context of coinfection remains inadequately investigated, and it is uncertain whether specific coinfections may influence the presentation and severity of ZIKV-related signs and symptoms. A 2019 literature review by Vogels and colleagues hypothesised that coinfecting agents have the potential to enhance, inhibit, compete with or have no effect on ZIKV replication and the resulting clinical disease. To advance understanding on this topic, this systematic review aims to quantify how frequently ZIKV coinfections occur among ZIKV-infected populations and to investigate whether the clinical course of ZIKV disease in humans is altered in the context of coinfection.