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11_ms_ravichandranBrief Original Article
Ribavirin therapy for Chikungunya arthritis
Rajan Ravichandran, Manju Manian.
Madras Institute of Nephrology, Vijaya Heath Centre, N.S.K Salai, Chennai-600026, India.
Background: Chikungunya is an acute viral infection presenting with a febrile episode and severe arthralgia, swelling of soft
tissues, especially around the ankles. Many patients recover with nonspecific treatment of analgesics. Some patients continue to
have subacute crippling arthritis in the legs affecting their mobility. This study was undertaken to see the effect of the antiviral
drug Ribavirin in the clinical outcome of these patients.
Methodology: Ten patients who continued to have crippling lower limb pains and arthritis for at least two weeks after a febrile
episode were taken up for the drug study. Ten similar patients during the same period were included as controls. In the study
group Ribavirin was given at 200 mg twice a day for seven days. Both groups were followed up for four weeks
Results: All patients in the drug group reported improvement in the joint pains with six of them capable of walking freely. The soft
tissue swelling also reduced in eight. In three patients the pain returned after mobilization. Seven patients continued not to
receive analgesics after four weeks.
Conclusions: Ribavirin may have a direct antiviral property against Chikungunya leading to faster resolution of joint and soft
Key Words: Chikungunya, lower limb arthritis, Ribavirin, observational study.
J Infect Developing Countries 2008; 2(2):140-142.
Received 16 August 2007 - Accepted 14 February 2008.
Copyright 2007 Ravichandran et al. This is an open access article distributed under the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
the effects on the patient’s mobility. The crippling Chikungunya is a viral fever transmitted to pain can last several months .There has been humans by the bite of the Aedes Aegypti mosquito. no specific treatment described for Chikungunya. The virus belongs to the Genus Alpha virus, family Antipyretics and analgesics form the mainstay of Togaviridae. The disease was first described in treatment. In those patients who continue to have 1955 by Marion Robinson and W H R Lumsden in chronic joint pains, Chloroquine has been tried the African subcontinent. The outbreak was in the with some success . This observational study year 1952 [1,2]. Since then, several cases have was undertaken to determine the effect of the also been reported from the Asian subcontinent antiviral drug Ribavirin in the outcome of joint . Recently there have been large outbreaks of manifestations of Chikungunya. A randomized Chikungunya in several districts of India in the last placebo controlled trial could not be undertaken few months . According to the World Health since the disease disappeared from the country. Organization (WHO), more than 1.25 million suspected cases have been reported from India up Materials and Methods
to October 2006 .The clinical picture of the Ten patients who had severe arthralgia, lower disease is high fever after a short incubation limb swelling, pain and difficulty in walking after a period with constitutional symptoms including headache, photophobia, etc .Migratory arthralgia administration of Ribavirin. Ten similar patients of the small joints of the hand, wrist, feet and ankle during the same period were included as controls. are common. Rash may also appear. The fever Those patients who recovered spontaneously disappears in two to three days. However several within two weeks after the febrile episode were patients may have pain, stiffness, and swelling of excluded from the study. All critical patients and the joints, especially in the lower limb around the those with systemic disease were excluded from ankles. This leads to considerable morbidity due to the study. Routine hematological and biochemical Ravichandran & Manian – Ribavirin theraphy for Chikungunya arthritis J Infect Developing Countries 2008; 2(2): 140-142 investigations were conducted in the beginning even lasting for years. Brighton reported the use of and end of the study. CRP and IgM antibodies to Chloroquine phosphate for twenty weeks with Chikungunya were estimated in all the patients. significant improvement in Chikungunya arthritis. Only patients with positive antibodies were included in the study. All the patients were Table 1. Clinical Features and Outcomes in the
followed up for a period of four weeks. An arthritis score was used to assess the joint involved, joint pain, joint tenderness and swelling in a scale of Similarly, an evaluation by the patient on a five-point scale was also undertaken. The patients were evaluated on a weekly basis for 4 weeks and called again after 8 weeks. In the study group all analgesics were stopped and Ribavirin in the dose of 200mg twice a day was given for seven days. The female patients were screened for pregnancy before administering the drug. The control group continued to receive analgesics as and when required. Although the drug is well established for other viral infections, approval of the ethics committee of the hospital was obtained since it is a Ribavirin is a synthetic nucleoside analogue that inhibits a wide range of RNA and DNA viruses. The mechanism of action of Ribavirin is not completely defined and may be different for In the study group out of the ten patients, five different groups of viruses. It has been used were males and five were females. Ages ranged successfully in chronic Hepatitis C in association from 27 to 74 years. Interval from the febrile with interferon, respiratory syncytial virus, Lassa episode was two weeks to two months. Three fever virus, and Hantaan virus [8,9,10]. This study patients had leucopenia. In six patients the CRP was undertaken to determine whether antiviral was positive. In the control group, five were males treatment would make any difference in those and five were females. Ages ranged from 25 to 70. patients who continue to have arthritis even after CRP was positive in five patients. In the study two weeks after the febrile episode. Ribavirin was group all patients reported improvement in pain. chosen in view of its broad spectrum. Our Seven patients were able walk better. In eight patients there was reduction in joint and soft tissue improvement in these patients. Since we had swelling. In three patients the pain relapsed. At the chosen patients in the subacute phase, some end of four weeks, analgesics were discontinued in improvement could be attributed to the natural seven patients. Two patients complained of history. Briolant et al. have shown in vitro a nausea and weakness. No other side effects were combination of interferon alfa 2B and Ribavirin has seen. Three patients were restarted on analgesics. a synergestic antiviral effect against Chikungunya The results of both groups are shown in the Our study has several limitations: a) it involves only a small number of patients; b) it was not a Discussion
planned study where the patients could be Although Chikungunya is a self-limiting viral distributed randomly and compared with a group disease with hardly any mortality, a considerable receiving placebo. This was not possible since the number of patients continue to have crippling joint disease rapidly disappeared from the country. pain in the lower limbs which affects their mobility. However, our observations may assist other These patients continue to take analgesics for long centers in the world undertaking clinical trials of periods of time with possible complications. The joint manifestations could also become chronic, Ravichandran & Manian – Ribavirin theraphy for Chikungunya arthritis J Infect Developing Countries 2008; 2(2): 140-142 References
chronic hepatitis C; New Eng J Med,339 (21),1485- 1. Robinson M (1952-53) An epidemic of virus disease in Southern Province, Tanganyika Territory, in Clinical 9. Hall CB et al. (1983) Aerolised ribavarin treatment of features.Trans Royal Society Trop Med Hyg.1955;49:28- infants with respiratory syncytial viral infection: A randomized double blind study. N Eng J Med 308, 1443- 2. Lumsden WHR. (1952-53) An epidemic of virus disease in Southern Province, Tanganyika Territory, General 10. McCormick JB, King IJ, Webb PA, Scribregner CL, Description And Epidemology Trans Royal Society Trop Craver RB, Johnson KM, Elliot LH, Belmont-Williams (1986) Lassa fever: Effective therapy with ribavirin. N.Eng 3. Campos LE San Juan A, Cenabre LC, Almagro EF (1969) Isolation of Chikungunya virus in the Philippines. 11. Briolant S, Gavin D, Scaramozzino N, Jouan A, Crance JM (2004) In vitro inhibition of Chikungunya and Semiliki 4. Sandhya K, Das AK, Falgun SP (2006) Chikungunya forest viruses replication by antiviral compounds: Synergistic Effect of Interferon Alfa and Ribavirin 5. Epidemic and Pandemic Alert and Response (EPR) combination Antiviral Res 61(2) 111-117. Corresponding Author: Rajan Ravichandran, Director,
6. Kennedy AC, Fleming J,Solomon L;Chikungunya viral Madras Institute of Nephrology, Tel: 91 44 24833340, arthropathy:a clinical description J Rheumotol 1980;(2): Fax: 91 44 23723244, Email: [email protected] 7. Brighton SW (1984) Chloroquine phosphate treatment of Conflict of interest: No conflict of interest is declared.
chronic Chikungunya arthritis. An open pilot study. S Afr 8. McHutchison JG et al. (1998) Interferon alfa 2-b alone or in combination with ribavirin as initial treatment for
Pharmaceutical analysis and Quality control Ph-343 Submitted to: Submitted by: Date of submission: 20 – 02 - 07 APPLICATIONS OF HPLC 1.The wide verity of packing materials allows the separation ofmost chemical species. Chemical Separations can be accomplished using HPLC by utilizing the fact that certain compounds have differentmigration rates given a particular co