ReviewLong-term sequelae of chikungunya virus disease: A systematic review
Introduction
Chikungunya virus (CHIKV) is an arthropod-borne virus, or arbovirus, transmitted by Aedes albopictus and Aedes aegypti mosquitoes [1]. Since 1999, chikungunya has (re-)emerged epidemically across tropical and subtropical areas around the globe and most recently ripped through the Americas, causing an estimated 1.675.000 cases. From early 2014 onwards, there alone, cases of acute disease had long-term health impact in a considerable proportion of those afflicted [1].
The term ‘chikungunya’ (meaning ‘that which bends up’) refers to the severe arthralgia associated with the acute phase of the infection, making an upright gait fairly impossible in many individuals afflicted [1]. The arthralgia is often bilateral, symmetric and affects multiple, mostly distal, joints [2]. Other characteristic symptoms are high fever, myalgia and headache. In addition, a skin rash, gastrointestinal symptoms, fatigue, asthenia, peripheral edema and conjunctivitis occur in relative frequency [3], [4], [5], [6], [7], [8].
Long-term sequelae of arboviral infections in terms of persisting signs and symptoms have been known since long [42], [43], [44], [45], [46]. With regard to chikungunya, late manifestations remained poorly investigated until the epidemic spread of the disease stepped up its pace recently, beginning with the Indian Ocean islands outbreak only a decade ago [9].
The primary objective of this systematic literature review was to provide an overview of the published literature on long-term sequelae of CHIKV infections. Secondary objectives were:
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to investigate the prevalence of long-term sequelae;
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to identify study characteristics associated with a higher prevalence of long-term sequelae;
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to investigate their impact on quality of life (QoL);
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to assess the consequences of congenital CHIKV infection for the new-born; and
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to identify factors associated with an increased risk of long-term sequelae of CHIKV infection.
Section snippets
In- and exclusion criteria
This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and meta-analysis (PRISMA) guidelines [10].
In- and exclusion criteria were addressed to identify all relevant studies on long-term sequelae of CHIKV infection. We included studies from 2000 to 2016 for data collection and accepted only studies on humans, written in English. Case reports and reviews were excluded. Articles without information on manifestations and without structured results on
Results
The search flow is summarized in Fig. 1. The initial search strategy on Pubmed/Medline yielded 213 articles. Another 5 articles were identified through the search of reference lists, resulting in a total of 218 articles. After title and abstract screening, 48 articles were selected for full-text evaluations. Application of the exclusion criteria led to 37 included studies.
All studies were quantitative studies; 18 were retrospective [4], [8], [11], [14], [15], [17], [18], [19], [20], [21], [22],
Summary of main results
This systematic review of the long-term sequelae of CHIKV infection in 37 studies shows that a significant proportion of patients with a CHIKV infection suffers from chronic disease manifestations. Persistent arthralgia, arthritis, alopecia and depression were most frequently mentioned, impacting on the QoL. Female gender and older age were associated with long-term sequelae. Concerning congenital CHIKV infection, mother-to-child transmission was only described during the 2 days peri-partum; in
Conclusion
Long-term sequelae such as arthralgia, arthritis, depression and alopecia after CHIKV infection negatively impact on Quality of Life. Congenital infection can severely affect neurocognitive functioning in early childhood. A range of studies mainly from the Indian Ocean region, have examined long-term sequelae of chikungunya. However, heterogeneity in the methodology applied; variances in study design were multiple; the duration of follow-up was frequently limited and comparability between study
Conflicts of interest
None of the authors has any conflict of interest to declare.
Funding
None.
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Both authors contributed equally.