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.

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...

Clinical Drug Trial Registry-India, www.ctri.nic.in, CTRI/2008/091/000063.

The multidisciplinary “New Millennium Indian Technology Leadership Initiative” Arthritis Project was undertaken to validate Ayurvedic medicines. Herbal formulations in popular use were selected by expert consensus and standardized using modern tools. Our clinical strategy evolved from simple exploratory evaluations to better powered statistically designed drug trials. The results of the first drug trial are presented here. Five oral formulations (coded A, B, C, D and E), with a common base of Zingiber officinale and Tinospora cordifolia with a maximum of four plant extracts, were evaluated; with placebo and glucosamine as controls. 245 patients suffering from symptomatic OA knees were randomized into seven arms (35 patients per arm) of a double blind, parallel efficacy, multicentric trial of sixteen weeks duration. The groups matched well at baseline. There were no differences for patient withdrawals (17.5%) or adverse events (AE) of mild nature. Intention-to-treat efficacy analysis, demonstrated no significant differences (P < .05) for pain (weight bearing) and WOMAC questionnaire (knee function); placebo response was high. Based on better pain relief, significant (P < .05) least analgesic consumption and improved knee status, “C” formulation was selected for further development. Controlled exploratory drug trials with multiple treatment arms may be used to economically evaluate several candidate standardized formulations.