Please use this identifier to cite or link to this item: https://doi.org/10.3390/v10050268
Title: Paradoxical effect of chloroquine treatment in enhancing chikungunya virus infection
Authors: Roques, P
Thiberville, S.-D
Dupuis-Maguiraga, L
Lum, F.-M
Labadie, K
Martinon, F
Gras, G
Lebon, P
Ng, L.F.P 
de Lamballerie, X
Le Grand, R
Keywords: chloroquine
immunoglobulin M
chloroquine
Article
chikungunya
controlled study
enzyme linked immunosorbent assay
enzyme linked immunospot assay
general practitioner
high performance liquid chromatography
human
human cell
lymphocytopenia
Macaca fascicularis
nonhuman
reverse transcription polymerase chain reaction
viremia
virus replication
animal
cell culture
chikungunya
Chikungunya virus
cohort analysis
comparative study
disease model
drug effect
epidemic
fibroblast
immunity
immunology
macrophage
male
Reunion
virology
virus load
Animals
Cells, Cultured
Chikungunya Fever
Chikungunya virus
Chloroquine
Cohort Studies
Disease Models, Animal
Disease Outbreaks
Fibroblasts
Humans
Immunity
Macaca fascicularis
Macrophages
Male
Reunion
Viral Load
Virus Replication
Issue Date: 2018
Publisher: MDPI AG
Citation: Roques, P, Thiberville, S.-D, Dupuis-Maguiraga, L, Lum, F.-M, Labadie, K, Martinon, F, Gras, G, Lebon, P, Ng, L.F.P, de Lamballerie, X, Le Grand, R (2018). Paradoxical effect of chloroquine treatment in enhancing chikungunya virus infection. Viruses 10 (5) : 268. ScholarBank@NUS Repository. https://doi.org/10.3390/v10050268
Rights: Attribution 4.0 International
Abstract: Since 2005, Chikungunya virus (CHIKV) re-emerged and caused numerous outbreaks in the world, and finally, was introduced into the Americas in 2013. The lack of CHIKV-specific therapies has led to the use of non-specific drugs. Chloroquine, which is commonly used to treat febrile illnesses in the tropics, has been shown to inhibit CHIKV replication in vitro. To assess the in vivo effect of chloroquine, two complementary studies were performed: (i) a prophylactic study in a non-human primate model (NHP); and (ii) a curative study “CuraChik”, which was performed during the Reunion Island outbreak in 2006 in a human cohort. Clinical, biological, and immunological data were compared between treated and placebo groups. Acute CHIKV infection was exacerbated in NHPs treated with prophylactic administration of chloroquine. These NHPs displayed a higher viremia and slower viral clearance (p < 0.003). Magnitude of viremia was correlated to the type I IFN response (Rho = 0.8, p < 0.001) and severe lymphopenia (Rho = 0.8, p < 0.0001), while treatment led to a delay in both CHIKV-specific cellular and IgM responses (p < 0.02 and p = 0.04, respectively). In humans, chloroquine treatment did not affect viremia or clinical parameters during the acute stage of the disease (D1 to D14), but affected the levels of C-reactive Protein (CRP), IFN?, IL-6, and MCP1 over time (D1 to D16). Importantly, no positive effect could be detected on prevalence of persistent arthralgia at Day 300. Although inhibitory in vitro, chloroquine as a prophylactic treatment in NHPs enhances CHIKV replication and delays cellular and humoral response. In patients, curative chloroquine treatment during the acute phase decreases the levels of key cytokines, and thus may delay adaptive immune responses, as observed in NHPs, without any suppressive effect on peripheral viral load. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.
Source Title: Viruses
URI: https://scholarbank.nus.edu.sg/handle/10635/178533
ISSN: 1999-4915
DOI: 10.3390/v10050268
Rights: Attribution 4.0 International
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