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      Chikungunya virus infection in Aruba: Diagnosis, clinical features and predictors of post-chikungunya chronic polyarthralgia

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          Abstract

          Background

          Chikungunya virus (CHIKV) emerged in Aruba for the first time in 2014. We studied the clinical presentation of acute CHIKV infection and the contribution of serologic and molecular assays to its diagnosis. In a cohort of confirmed CHIKV cases, we analysed the frequency, duration and predictors of post-chikungunya chronic polyarthralgia (pCHIK-CPA), defined as joint pains lasting longer than 6 weeks or longer than 1 year.

          Methodology

          Patient sera obtained within 10 days of symptom onset were tested for CHIKV, using an indirect immunofluorescence test for the detection of CHIKV-specific Immunoglobulin M (IgM) and post-hoc, by reverse-transcription polymerase chain reaction (RT-PCR). CHIKV was isolated from selected samples and genotyped. For confirmed CHIKV cases, clinical data from chart review were complemented by a Telephone survey, conducted 18–24 months after diagnosis. When joint pain was reported, the duration, presence of inflammatory signs, type and number of joints affected, were recorded. Joint involvement was scored according to the 2010 ‘American College of Rheumatology/ European League Against Rheumatism’ criteria for seronegative rheumatoid arthritis (ACR-score). Risk factors for pCHIK-CPA were identified by logistic regression.

          Principal findings

          Acute CHIKV infection was diagnosed in 269 of 498 sera, by detection of IgM (n = 105), by RT-PCR (n = 59), or by both methods (n = 105). Asian genotype was confirmed in 7 samples. Clinical data were complete for 171 of 248 (69.0%) patients, aged 15 years or older (median 49.4 [35.0–59.6]). The female-to-male ratio was 2.2. The main acute symptoms were arthralgia (94%), fever (85%), myalgia (85%), headache (73%) and rash (63%). In patients with arthralgia (n = 160), pCHIK-CPA longer than 6 weeks was reported by 44% and longer than 1 year by 26% of cases. Inflammatory signs, stiffness, edema and redness were frequent (71%, 39% and 21%, respectively). Joints involved were knees (66%), ankles (50%), fingers (52%), feet (46%), shoulders (36%), elbows (34%), wrists (35%), hips (31%), toes (28.1%) and spine (28.1%). Independent predictors of pCHIK-CPA longer than 1 year were female gender (OR 5.9, 95%-CI [2.1–19.6]); high ACR-score (7.4, [2.7–23.3]), and detection of CHIKV-RNA in serum beyond 7 days of symptom onset (6.4, [1.4–34.1].

          Conclusions

          We identified 269 CHIKV patients after the first outbreak of Asian genotype CHIKV in Aruba in 2014–2015. RT-PCR yielded 59 (28%) additional CHIKV diagnoses compared to IgM antibody detection alone. Arthralgia, fever and skin rash were the dominant acute phase symptoms. pCHIK-CPA longer than 1 year affected 26% of cases and was predicted by female gender, high ACR-score and CHIKV-RNA detection beyond 7 days of symptom onset.

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          Most cited references60

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          Chikungunya: a re-emerging virus.

          In the past decade, chikungunya--a virus transmitted by Aedes spp mosquitoes--has re-emerged in Africa, southern and southeastern Asia, and the Indian Ocean Islands as the cause of large outbreaks of human disease. The disease is characterised by fever, headache, myalgia, rash, and both acute and persistent arthralgia. The disease can cause severe morbidity and, since 2005, fatality. The virus is endemic to tropical regions, but the spread of Aedes albopictus into Europe and the Americas coupled with high viraemia in infected travellers returning from endemic areas increases the risk that this virus could establish itself in new endemic regions. This Seminar focuses on the re-emergence of this disease, the clinical manifestations, pathogenesis of virus-induced arthralgia, diagnostic techniques, and various treatment modalities. Copyright © 2012 Elsevier Ltd. All rights reserved.
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            The Newala epidemic. III. The virus: isolation, pathogenic properties and relationship to the epidemic.

            R. W. Ross (1956)
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              Outbreak of chikungunya on Reunion Island: early clinical and laboratory features in 157 adult patients.

              Chikungunya is a reemerging disease. In 2005-2006, a severe outbreak occurred on Reunion Island in the southwestern part of the Indian Ocean. Other islands in this area were affected during the same period. Adult patients with acute chikungunya (defined as onset of fever and/or polyarthralgia in the 5 days preceding consultation) and laboratory-confirmed chikungunya who were referred to Groupe Hospitalier Sud Reunion during the period from March 2005 through April 2006 were included in this retrospective study. Their clinical and laboratory features are reported. Laboratory-confirmed acute chikungunya was documented in 157 patients. The mean age of patients was 57.9 years, and the ratio of male to female patients was 1.24 : 1. Sixty percent of patients had at least 1 comorbidity. Ninety-seven patients (61.8%) were hospitalized, and 60 (38.2%) were treated as outpatients. Five fatalities were reported. One hundred fifty-one patients (96.1%) experienced polyarthralgia, and 129 (89%) experienced fever. Gastrointestinal symptoms were reported by 74 patients (47.1%), and skin rash was reported by 63 (40.1%). Hemorrhagic signs were rare. Lymphopenia and hypocalcemia were the prominent laboratory findings. Severe thrombocytopenia was rarely observed. Chikungunya virus can be responsible for explosive outbreaks of disease. Polyarthralgia and fever are the 2 main clinical features. In this era of travel and globalization, chikungunya should be considered in the differential diagnosis of febrile polyarthralgia with an abrupt onset.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: Writing – review & editing
                Role: Data curationRole: Investigation
                Role: Data curationRole: Investigation
                Role: Formal analysis
                Role: Data curationRole: Investigation
                Role: Investigation
                Role: InvestigationRole: Resources
                Role: ConceptualizationRole: SupervisionRole: Writing – review & editing
                Role: Formal analysisRole: Funding acquisitionRole: InvestigationRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                30 April 2018
                2018
                : 13
                : 4
                : e0196630
                Affiliations
                [1 ] Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium
                [2 ] Department of Internal Medicine, Horacio Oduber Hospital, Oranjestad, Aruba
                [3 ] Landslaboratorium Aruba, Oranjestad, Aruba
                [4 ] Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium
                [5 ] Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium
                [6 ] Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium
                Emory University School of Medicine, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                [¤]

                Current address: Department of Public Health, Oranjestad, Aruba

                ‡ These authors also contributed equally to this work.

                Author information
                http://orcid.org/0000-0001-8803-9468
                http://orcid.org/0000-0001-7565-1359
                Article
                PONE-D-18-02588
                10.1371/journal.pone.0196630
                5927412
                29709007
                80c46e82-20b6-4915-a847-b73364e5b6b3
                © 2018 Huits et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 24 January 2018
                : 16 April 2018
                Page count
                Figures: 3, Tables: 3, Pages: 21
                Funding
                The authors received no external funding for this work. The National Reference Center of arboviruses (ITM) is partially supported by the Belgian Ministry of Social Affairs through a fund within the Health Insurance System. LC holds an innovation mandate (140779) from the Flanders Innovation & Entrepreneurship.
                Categories
                Research Article
                Biology and life sciences
                Organisms
                Viruses
                RNA viruses
                Togaviruses
                Alphaviruses
                Chikungunya Virus
                Biology and Life Sciences
                Microbiology
                Medical Microbiology
                Microbial Pathogens
                Viral Pathogens
                Togaviruses
                Alphaviruses
                Chikungunya Virus
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Pathogens
                Microbial Pathogens
                Viral Pathogens
                Togaviruses
                Alphaviruses
                Chikungunya Virus
                Biology and Life Sciences
                Organisms
                Viruses
                Viral Pathogens
                Togaviruses
                Alphaviruses
                Chikungunya Virus
                Medicine and Health Sciences
                Tropical Diseases
                Neglected Tropical Diseases
                Chikungunya Infection
                Medicine and Health Sciences
                Infectious Diseases
                Viral Diseases
                Chikungunya Infection
                Biology and Life Sciences
                Anatomy
                Musculoskeletal System
                Joints (Anatomy)
                Medicine and Health Sciences
                Anatomy
                Musculoskeletal System
                Joints (Anatomy)
                Medicine and Health Sciences
                Pain Management
                Arthralgia
                Biology and Life Sciences
                Molecular Biology
                Molecular Biology Techniques
                Artificial Gene Amplification and Extension
                Polymerase Chain Reaction
                Reverse Transcriptase-Polymerase Chain Reaction
                Research and Analysis Methods
                Molecular Biology Techniques
                Artificial Gene Amplification and Extension
                Polymerase Chain Reaction
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                Caribbean
                Aruba
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                Biology and Life Sciences
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                Anatomy
                Musculoskeletal System
                Joints (Anatomy)
                Knee Joints
                Medicine and Health Sciences
                Anatomy
                Musculoskeletal System
                Joints (Anatomy)
                Knee Joints
                Custom metadata
                The data supporting the findings of this study/publication are retained at the Institute of Tropical Medicine, Antwerp and will not be made openly accessible due to ethical and privacy concerns. Data can however be made available after approval of a motivated and written request to the Institute of Tropical Medicine at ITMresearchdataaccess@ 123456itg.be/ .

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