Chikungunya virus (CHIKV) data from population studies are sparse. During the 2006 epidemic, 509 clinical cases (43% attack rate) were identified in a village survey (West India); laboratory investigations demonstrated normal blood cell counts, elevated acute-phase reactants [erythrocyte sedimentation rate, C-reactive protein and interleukin-6 (IL-6)] and excluded malaria and dengue. Acute CHIKV was characterized by high fever, severe peripheral polyarthralgias, axial myalgias and intense fatigue in over 90% of cases; skin rash (34%) and headache (19%) were uncommon. There were 49% and 62% of survey cases seropositive for IgM (rapid assay) and IgG (immunofluorescence) anti-CHIKV antibodies, respectively. Sixty-five percent of cases recovered within 4 weeks. None of the cases died. Of the population, 4·1% and 1·6% suffered from persistent rheumatic pains, predominantly non-specific, at 1 and 2 years, respectively. Chronic inflammatory arthritis was uncommon (0·3% at 1 year) although serum IL-6 often remained elevated in chronic cases. A larger population study is required to describe post-CHIKV rheumatism and its prognosis.
Firestein GS. Regulation of synoviocyte cytokine expression by acetylcholine and the ␣7 nicotinic receptor. Arthritis Rheum. In press.
A wide-spectrum phenotype of JIA is demonstrated by an Indian cohort. Although useful, RF and HLA-B27 in this population proved problematic to the ILAR classification.
Objective. To evaluate whether chloroquine (CQ) is more effective than meloxicam for treating early musculoskeletal pain and arthritis following acute chikungunya (CHIK) virus infection.Methods. During the 2006 CHIK epidemic, 509 rural community cases of acute CHIK virus infection were identified in the district of Sholapur in India. Seventy consenting adult patients (seropositive for IgM/ IgG anti-CHIK antibody) with early persistent musculoskeletal pain and arthritis were randomized into a 24-week, 2-arm, parallel efficacy trial of CQ (250 mg/ day) and meloxicam (7.5 mg/day). Assessors completed a rheumatology evaluation in a blinded manner and collected blood samples in the patients' homes, as per protocol. Laboratory parameters included serum cytokine assay (interleukin-6 [IL-6], interferon-␥ [IFN␥], tumor necrosis factor ␣, CXCL10/IFN␥-inducible protein 10, and IL-13). Twenty-two patients who failed to meet the eligibility criteria (low pain cohort) were also followed up with similar evaluations. An intent-to-treat analysis was completed. At baseline, the 2 groups (38 patients randomized to receive CQ and 32 patients randomized to receive meloxicam) were well matched.Results. There were no significant efficacy differences between the meloxicam group and the CQ group (mean changes in the visual analog scale score for pain ؊3.9 and ؊4.2, respectively). Patients improved significantly. Cytokine levels remained several-fold increased, were disproportionate to the clinical response, and were not different from those in the low pain cohort. Seven patients withdrew. Adverse events were mild and infrequent. Conclusion. This exploratory community intervention trial failed to identify an advantage of CQ over meloxicam to treat early musculoskeletal pain and arthritis following acute CHIK virus infection, but therapeutic efficacy of CQ was not ruled out. The inflammatory cytokine response was intense and was not consistent with clinical status.The 2006 chikungunya (CHIK) virus epidemic originated in East Africa and rapidly spread to the Indian subcontinent (1-3). Unlike previous epidemics, thousands of new cases and patients with persistent musculoskeletal pain and arthritis continue to be reported. We previously observed a wide spectrum of post-CHIK virus musculoskeletal pain and arthritis, but the etiology remains unknown (4). Oral chloroquine (CQ) has been used extensively to treat acute and chronic musculoskeletal pain and arthritis following CHIK virus infection; however, clinical data remain sparse (3).Acute CHIK virus infection is a self-limiting, excruciatingly painful arboviral illness of short duration. In our experience, acute symptoms subsided within 10 days, and approximately two-thirds of patients recovered within 3 weeks (4). Against this background, we carried out a controlled evaluation of CQ to treat patients with early persistent musculoskeletal pain and arthritis following CHIK virus infection. Selected cytokine assays were carried out to study the inflammatory nature of musculoskeletal pain and ar...
IntroductionAcute chikungunya (CHIKV) is predominantly an acute onset of excruciatingly painful, self-limiting musculoskeletal (MSK) arbovirus illness and this was further reported by us during the 2006 Indian epidemic [Chopra et al. Epidemiol Infect 2012]. Selected serum cytokines profile in subjects within one month of onset of illness is being presented.MethodsOut of 509 clinical CHIKV cases (43% population) identified during a rural population survey, 225 subjects consented blood investigations. 132 examined within 30 days of febrile onset are the study cohort. Anti-CHIKV IgM and IgG antibodies tested by immunochromatography and indirect immunofluorescence respectively. Interferons (IFN)-α, -β and -γ, Interferon Gamma-Induced Protein-10 (CXCL-10/IP-10), Tumor Necrosis Factor-α (TNF-α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6), Interleukin-13 (IL-13), Monocyte Chemoattractant Protein-1 (MCP-1), Interleukin–4 (IL-4) and Interleukin–10 (IL-10) performed by ELISA. Samples collected from neighboring community a year prior to the epidemic used as healthy controls.ResultsSeropositivity for anti-CHIKV IgM and IgG was 65% and 52% respectively. IFN-α, IFN-β, IFN-γ, CXCL10/IP-10 and IL-1β showed intense response in early acute phase. Cytokines (particularly TNF-α, MCP-1, IL-4, IL-6 and IL-10) was maximum in extended symptomatic phase and remained elevated in recovered subjects. Higher (p<0.05) IFN and IL-4 seen in patients seropositive for anti-CHIKV IgG. Elderly cases (≥65 years) showed elevated cytokines (except IFN) and anti-CHIKV antibodies near similar to younger subjects. Significant correlations (p<0.05) found between cytokines and clinical features (fatigue, low back ache, myalgia) and anti-CHIKV antibodies.ConclusionAn intense cytokine milieu was evident in the early and immediate persistent symptomatic phase and in recovered subjects. Early persistent IgM and lower IgG to anti-CHKV and intense Th2 cytokine phenotype seem to be associated with delay in resolution of MSK symptoms. Intriguingly, maximum TNF-α, IL-6 and IL-13 with low anti-CHIKV IgM response found in subjects recovered from CHIKV within one month of illness.
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