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A True Case Definition of Zika Virus Infection Should Still Be Pursued in Arbovirus Co-Transmission Areas

Until the French Polynesia outbreak, the Zika virus (ZIKV) was a self-limited disease with few human cases documented and restricted distribution on the Africa and Asia continents. In 2015, ZIKV began spreading rapidly in the Americas, and those countries saw increasing numbers of infections associated with complications such as Guillain-Barré syndrome, and non-previously predicted severe presentation such as congenital Zika virus syndrome. This changed the history of the arbovirus infection.

In 2015 through 2016, the fast globalization of ZIKV urged the creation of an interim case definition for the virus. It was hoped that this would optimize the detection of suspected cases to help public health organizations improve surveillance and management of the cases to gain control of the epidemic. However, we now know that slight differences in the clinical presentations of ZIKV infection which are occurring in different parts of the world might be an obstacle to setting a case definition that is good for use in all areas, particularly those with active co-transmission of other arboviruses. In this article, I discuss the points that need to be considered when developing a case definition for ZIKV infection.

Much like other arboviruses, such as Dengue (DENV) and Chikungunya (CHIKV) virus, those individuals infected with ZIKV may not have any symptoms or they may present with clinical manifestations that vary from mild to severe. In addition, because most arboviruses do not produce a singular and/or characteristic symptom, similar clinical features can be induced by distinct viruses.

In terms of coinfections of ZIKV and another arbovirus, the problem is not only that clinical manifestations do not distinguish a single arbovirus infection from another, but also that ZIKV co-infections cannot be “suspected” based on clinical presentation. Furthermore, most ZIKV cases are presumably asymptomatic, and make up those “suspected cases” that may be invisible to the surveillance system. As a result, the accuracy of case definitions can change, depending on the clinical features depicted to define the suspected cases in areas of arbovirus co-transmission.

What we do know is that suspected cases are considered probable when anti-ZIKV IgM reactivity is present. However, validated tests for the detection of anti-ZIKV IgM by serological methods are lacking, and those that are available have variable performance depending on the population tested. In areas of flavivirus co-transmission, such as areas with ZIKV and DENV, serum cross-reactivity occurs in moderate to high rates of flavivirus secondary infections. Therefore, ZIKV and DENV co-infection cannot be reliably diagnosed based on the serological reactivity.

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