Chikungunya Disease: Infection-Associated Markers from the Acute to the Chronic Phase of Arbovirus-Induced Arthralgia

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Abstract

At the end of 2005, an outbreak of fever associated with joint pain occurred in La Réunion. The causal agent, chikungunya virus (CHIKV), has been known for 50 years and could thus be readily identified. This arbovirus is present worldwide, particularly in India, but also in Europe, with new variants returning to Africa. In humans, it causes a disease characterized by a typical acute infection, sometimes followed by persistent arthralgia and myalgia lasting months or years. Investigations in the La Réunion cohort and studies in a macaque model of chikungunya implicated monocytes-macrophages in viral persistence. In this Review, we consider the relationship between CHIKV and the immune response and discuss predictive factors for chronic arthralgia and myalgia by providing an overview of current knowledge on chikungunya pathogenesis. Comparisons of data from animal models of the acute and chronic phases of infection, and data from clinical series, provide information about the mechanisms of CHIKV infection–associated inflammation, viral persistence in monocytes-macrophages, and their link to chronic signs.

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Macrophage activation switching: an asset for the resolution of inflammation.

F Porcheray, S Viaud, A-C Rimaniol … (2005)

Macrophages play a central role in inflammation and host defence against microorganisms, but they also participate actively in the resolution of inflammation after alternative activation. However, it is not known whether the resolution of inflammation requires alternative activation of new resting monocytes/macrophages or if proinflammatory activated macrophages have the capacity to switch their activation towards anti-inflammation. In order to answer this question, we first characterized differential human macrophage activation phenotypes. We found that CD163 and CD206 exhibited mutually exclusive induction patterns after stimulation by a panel of anti-inflammatory molecules, whereas CCL18 showed a third, overlapping, pattern. Hence, alternative activation is not a single process, but provides a variety of different cell populations. The capacity of macrophages to switch from one activation state to another was then assessed by determining the reversibility of CD163 and CD206 expression and of CCL18 and CCL3 production. We found that every activation state was rapidly and fully reversible, suggesting that a given cell may participate sequentially in both the induction and the resolution of inflammation. These findings may provide new insight into the inflammatory process as well as new fields of investigation for immunotherapy in the fields of chronic inflammatory diseases and cancer.

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Outbreak of chikungunya on Reunion Island: early clinical and laboratory features in 157 adult patients.

Gianandrea Borgherini, Patrice Poubeau, Frederik Staikowsky … (2007)

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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Persistent Arthralgia Induced by Chikungunya Virus Infection is Associated with Interleukin-6 and Granulocyte Macrophage Colony-Stimulating Factor

Angela Chow, Zhisheng Her, Edward Ong … (2011)

Background. Chikungunya virus (CHIKV) infection induces arthralgia. The involvement of inflammatory cytokines and chemokines has been suggested, but very little is known about their secretion profile in CHIKV-infected patients. Methods. A case-control longitudinal study was performed that involved 30 adult patients with laboratory-confirmed Chikungunya fever. Their profiles of clinical disease, viral load, and immune mediators were investigated. Results. When patients were segregated into high viral load and low viral load groups during the acute phase, those with high viremia had lymphopenia, lower levels of monocytes, neutrophilia, and signs of inflammation. The high viral load group was also characterized by a higher production of pro-inflammatory cytokines, such as interferon-α and interleukin (IL)–6, during the acute phase. As the disease progressed to the chronic phase, IL-17 became detectable. However, persistent arthralgia was associated with higher levels of IL-6 and granulocyte macrophage colony-stimulating factor, whereas patients who recovered fully had high levels of Eotaxin and hepatocyte growth factor. Conclusions. The level of CHIKV viremia during the acute phase determined specific patterns of pro-inflammatory cytokines, which were associated with disease severity. At the chronic phase, levels of IL-6, and granulocyte macrophage colony-stimulating factor found to be associated with persistent arthralgia provide a possible explanation for the etiology of arthralgia that plagues numerous CHIKV-infected patients.

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: Role: Editor

Journal

Journal ID (nlm-ta): PLoS Negl Trop Dis

Journal ID (iso-abbrev): PLoS Negl Trop Dis

Journal ID (publisher-id): plos

Journal ID (pmc): plosntds

Title: PLoS Neglected Tropical Diseases

Publisher: Public Library of Science (San Francisco, USA )

ISSN (Print): 1935-2727

ISSN (Electronic): 1935-2735

Publication date Collection: March 2012

Publication date (Electronic): 27 March 2012

Volume: 6

Issue: 3

Electronic Location Identifier: e1446

Affiliations

[1 ]CEA, Division of Immuno-Virologie, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses, France

[2 ]UMR E1, University Paris Sud 11, Orsay, France

Centre for Cellular and Molecular Biology (CCMB), India

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* E-mail: Pierre.roques@ 123456cea.fr

Article

Publisher ID: PNTD-D-11-00592

DOI: 10.1371/journal.pntd.0001446

PMC ID: 3313943

PubMed ID: 22479654

SO-VID: 3be0d855-01c9-4a22-8a67-81369e86438d

Copyright © Dupuis-Maguiraga 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.

Chikungunya Disease: Infection-Associated Markers from the Acute to the Chronic Phase of Arbovirus-Induced Arthralgia

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Most cited references 58

Macrophage activation switching: an asset for the resolution of inflammation.

Outbreak of chikungunya on Reunion Island: early clinical and laboratory features in 157 adult patients.

Persistent Arthralgia Induced by Chikungunya Virus Infection is Associated with Interleukin-6 and Granulocyte Macrophage Colony-Stimulating Factor

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