Abstract
Zika has been associated with a variety of severe neurologic manifestations including meningitis and encephalitis. We hypothesized that it may also cause mild to subclinical neurocognitive alterations during acute infection or over the long term. In this observational cohort study, we explored whether Zika cause subclinical or mild neurocognitive alterations, estimate its frequency and duration, and compare it to other acute illnesses in a cohort of people with suspected Zika infection, in the region of Tapachula in Chiapas, Mexico during 2016–2018. We enrolled patients who were at least 12 years old with suspected Zika virus infection and followed them up for 6 months. During each visit participants underwent a complete clinical exam, including a screening test for neurocognitive dysfunction (Montreal Cognitive Assessment score). We enrolled 406 patients [37 with Zika, 73 with dengue and 296 with other acute illnesses of unidentified origin (AIUO)]. We observed a mild and transient impact over cognitive functions in patients with Zika, dengue and with other AIUO. The probability of having an abnormal MoCA score (<26 points) was significantly higher in patients with Zika and AIUO than in those with dengue. Patients with Zika and AIUO had lower memory scores than patients with dengue (Zika vs. Dengue: −0.378, 95% CI−0.678 to −0.078; p = 0.014: Zika vs. AIUO 0.264, 95% CI 0.059, 0.469; p = 0.012). The low memory performance in patients with Zika and AIUO accounts for most of the differences in the overall MoCA score when compared with patients with dengue. Our results show a decrease in cognitive function during acute illness and provides no evidence to support the hypothesis that Zika might cause neurocognitive alterations longer than the period of acute infection or different to other infectious diseases. While effects on memory or perhaps other cognitive functions over the long term are possible, larger studies using more refined tools for neurocognitive functioning assessment are needed to identify these.Trial Registration: NCT02831699.
Highlights
Zika virus (ZIKV) infection has been associated with severe neurological disease in adults [1]
We modeled the longitudinal behavior of education-adjusted Montreal Cognitive Assessment (MoCA) scores across study visits, and compared these results between disease groups (Zika, dengue, and acute illnesses of unidentified origin (AIUO)), using a regression model and generalized estimable equations (GEE) to account for intrasubject correlation using the geepack package [29] in R [30]
Patients with dengue virus infection and AIUO more frequently presented fever, arthralgia, headache, malaise, behavior alterations, and disability at baseline than patients with ZIKV; while rash was more frequent in ZIKV and dengue virus infection patients compared with those with AIUO
Summary
Zika virus (ZIKV) infection has been associated with severe neurological disease in adults [1]. Experimental models and human studies have shown that ZIKV has an exquisite affinity for human neural progenitor cells that might explain pre-natal neural damage [8], the mechanisms that induce neuronal damage and explains other neurological manifestations in adults are not clearly understood. Severe manifestations in adults and infants have received considerable attention given its conspicuousness and ramifications but it is reasonable to hypothesize that ZIKV infection may cause subclinical or mild disease, which might include neurocognitive impairment during acute infection or over the long term [9,10,11]. We aimed to explore whether ZIKV infection may cause subclinical or mild neurocognitive alterations, estimate its frequency and duration, and to compare it to other acute illnesses in a cohort of people with suspected Zika infection in Mexico
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