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      Arbo-Score: A Rapid Score for Early Identification of Patients with Imported Arbovirosis Caused by Dengue, Chikungunya and Zika Virus

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          Abstract

          Background: Chikungunya (CHIKV), Dengue (DENV), and Zika (ZIKV) viruses present significant clinical and epidemiological overlap, making an accurate and rapid diagnosis challenging. Timely activation of preventive vector control measures is crucial to avoid outbreaks in non-endemic settings. Diagnosis is based on combination of serological and molecular assays which could be time consuming and sometimes disappointing. Methods: We report the results of a retrospective case-control study carried out at a tertiary teaching hospital in Italy, including all febrile subjects returning from tropical countries during the period 2014–2019. Controls were travelers with other febrile illnesses who tested negative in laboratory analysis for CHIKV, DENV, ZIKV arbovirosis. A score weighted on the regression coefficients for the independent predictors was generated. Results: Ninety patients were identified: 34 cases (22 DENV, 4 CHIKV, and 8 ZIKV) and 56 controls. According to our results, myalgia, cutaneous rash, absence of respiratory symptoms, leukopenia, and hypertransaminasemia showed the strongest association with arbovirosis. Combining these variables, we generated a scoring model that showed an excellent performance (AUC 0.93). The best cut-off (>=2) presented a sensitivity of 82.35% and specificity of 96.43%. Conclusion: A handy and simple score, based on three clinical data (myalgia, cutaneous rash and absence of respiratory symptoms) and two laboratory results (leukopenia and hypertransaminasemia), provides a useful tool to help diagnose arboviral infections and appropriately activate vector control measures in order to avoid local transmission.

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          Most cited references48

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          Receiver-operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine.

          The clinical performance of a laboratory test can be described in terms of diagnostic accuracy, or the ability to correctly classify subjects into clinically relevant subgroups. Diagnostic accuracy refers to the quality of the information provided by the classification device and should be distinguished from the usefulness, or actual practical value, of the information. Receiver-operating characteristic (ROC) plots provide a pure index of accuracy by demonstrating the limits of a test's ability to discriminate between alternative states of health over the complete spectrum of operating conditions. Furthermore, ROC plots occupy a central or unifying position in the process of assessing and using diagnostic tools. Once the plot is generated, a user can readily go on to many other activities such as performing quantitative ROC analysis and comparisons of tests, using likelihood ratio to revise the probability of disease in individual subjects, selecting decision thresholds, using logistic-regression analysis, using discriminant-function analysis, or incorporating the tool into a clinical strategy by using decision analysis.
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            Zika virus outbreak on Yap Island, Federated States of Micronesia.

            In 2007, physicians on Yap Island reported an outbreak of illness characterized by rash, conjunctivitis, and arthralgia. Although serum from some patients had IgM antibody against dengue virus, the illness seemed clinically distinct from previously detected dengue. Subsequent testing with the use of consensus primers detected Zika virus RNA in the serum of the patients but no dengue virus or other arboviral RNA. No previous outbreaks and only 14 cases of Zika virus disease have been previously documented. We obtained serum samples from patients and interviewed patients for information on clinical signs and symptoms. Zika virus disease was confirmed by a finding of Zika virus RNA or a specific neutralizing antibody response to Zika virus in the serum. Patients with IgM antibody against Zika virus who had a potentially cross-reactive neutralizing-antibody response were classified as having probable Zika virus disease. We conducted a household survey to estimate the proportion of Yap residents with IgM antibody against Zika virus and to identify possible mosquito vectors of Zika virus. We identified 49 confirmed and 59 probable cases of Zika virus disease. The patients resided in 9 of the 10 municipalities on Yap. Rash, fever, arthralgia, and conjunctivitis were common symptoms. No hospitalizations, hemorrhagic manifestations, or deaths due to Zika virus were reported. We estimated that 73% (95% confidence interval, 68 to 77) of Yap residents 3 years of age or older had been recently infected with Zika virus. Aedes hensilli was the predominant mosquito species identified. This outbreak of Zika virus illness in Micronesia represents transmission of Zika virus outside Africa and Asia. Although most patients had mild illness, clinicians and public health officials should be aware of the risk of further expansion of Zika virus transmission. 2009 Massachusetts Medical Society
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              Human antibody responses after dengue virus infection are highly cross-reactive to Zika virus.

              Zika virus (ZIKV) is an emerging mosquito-borne flavivirus of significant public health concern. ZIKV shares a high degree of sequence and structural homology compared with other flaviviruses, including dengue virus (DENV), resulting in immunological cross-reactivity. Improving our current understanding of the extent and characteristics of this immunological cross-reactivity is important, as ZIKV is presently circulating in areas that are highly endemic for dengue. To assess the magnitude and functional quality of cross-reactive immune responses between these closely related viruses, we tested acute and convalescent sera from nine Thai patients with PCR-confirmed DENV infection against ZIKV. All of the sera tested were cross-reactive with ZIKV, both in binding and in neutralization. To deconstruct the observed serum cross-reactivity in depth, we also characterized a panel of DENV-specific plasmablast-derived monoclonal antibodies (mAbs) for activity against ZIKV. Nearly half of the 47 DENV-reactive mAbs studied bound to both whole ZIKV virion and ZIKV lysate, of which a subset also neutralized ZIKV. In addition, both sera and mAbs from the dengue-infected patients enhanced ZIKV infection of Fc gamma receptor (FcγR)-bearing cells in vitro. Taken together, these findings suggest that preexisting immunity to DENV may impact protective immune responses against ZIKV. In addition, the extensive cross-reactivity may have implications for ZIKV virulence and disease severity in DENV-experienced populations.
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                Author and article information

                Journal
                Microorganisms
                Microorganisms
                microorganisms
                Microorganisms
                MDPI
                2076-2607
                04 November 2020
                November 2020
                : 8
                : 11
                : 1731
                Affiliations
                [1 ]Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy; iacopo.vellere@ 123456unifi.it (I.V.); filippo.lagi@ 123456unifi.it (F.L.); michele.spinicci@ 123456unifi.it (M.S.); antonia.mantella@ 123456unifi.it (A.M.); giampaolo.corti@ 123456unifi.it (G.C.); gianmaria.rossolini@ 123456unifi.it (G.M.R.); alessandro.bartoloni@ 123456unifi.it (A.B.)
                [2 ]Infectious and Tropical Diseases Unit, Careggi University Hospital, 50134 Florence, Italy; mantengolie@ 123456aou-careggi.toscana.it
                [3 ]Referral Centre for Tropical Diseases of Tuscany, Infectious and Tropical Diseases Unit, Careggi University Hospital, 50134 Florence, Italy
                [4 ]Clinical Microbiology and Virology Unit, Careggi University Hospital, 50134 Florence, Italy; colaog@ 123456aou-careggi.toscana.it
                [5 ]Department of Infectious/Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, 37024 Negrar, Verona, Italy; federico.gobbi@ 123456sacrocuore.it
                Author notes
                [* ]Correspondence: lorenzo.zammarchi@ 123456unifi.it ; Tel.: +39-0557949431
                Author information
                https://orcid.org/0000-0003-3883-0766
                https://orcid.org/0000-0002-7321-454X
                https://orcid.org/0000-0001-9758-1523
                https://orcid.org/0000-0003-0892-8404
                Article
                microorganisms-08-01731
                10.3390/microorganisms8111731
                7716211
                33158274
                f80bbae8-0a48-4e05-a8c2-be527a94ab30
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 08 October 2020
                : 02 November 2020
                Categories
                Article

                dengue,zika,chikungunya,imported,timing,diagnosis,travelers,score
                dengue, zika, chikungunya, imported, timing, diagnosis, travelers, score

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