Elsevier

Travel Medicine and Infectious Disease

Volume 15, January–February 2017, Pages 8-22
Travel Medicine and Infectious Disease

Review
Long-term sequelae of chikungunya virus disease: A systematic review

https://doi.org/10.1016/j.tmaid.2017.01.004Get rights and content

Abstract

Background

The acute phase of chikungunya is well documented; less so are its long-term effects. This systematic literature review provides an overview of the currently available data.

Methods

We performed an electronic search in PubMed/Medline and checked reference lists. We included studies in English on long-term sequelae of chikungunya in adults and on long-term sequelae of congenital infection from 2000 to 2016. Case reports, reviews and studies with a follow-up shorter than 6 weeks were excluded.

Results

In total, 37 studies were included; with follow-up periods ranging from 1.5 to 72 months. Most studies were questionnaire-based studies only, in which clinical diagnoses such as arthritis, alopecia and depression were mostly recorded without professional verification.

Persisting arthralgia/arthritis (arthralgia/joint stiffness plus joint swelling) was the most frequent problem encountered. Further frequently mentioned sequelae were alopecia and depression. Quality of life was reduced in many for months to years after the acute phase of chikungunya. Female gender, older age, some co-morbidities and the severity of the acute phase were associated with persistent arthralgia. Congenital infection was associated with neurocognitive dysfunctioning in early childhood.

Conclusion

Chikungunya leads to (self-perceived) long-term sequelae in a considerable proportion of patients, impacting significantly on quality of life. Long-term chikungunya sequelae must be taken into account when dealing with this disease because of its important effect on public and individual health. Prospective large-scale, long-term studies with objective assessment of signs and symptoms attributed to the disease are needed to optimally quantify and qualify these problems.

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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