Chikungunya: Establishing a New Home in the Western Hemisphere
Authors: Davidson H. Hamer, Lin H. Chen
Journal: Annals of Internal Medicine (2014)

Ideas and Opinions2 December 2014Chikungunya: Establishing a New Home in the Western HemisphereFREEDavidson H. Hamer, MD and Lin H. Chen, MDDavidson H. Hamer, MDFrom the Center for Global Health and Development, Boston University, Boston, and Mount Auburn Hospital, Cambridge, Massachusetts.Search for more papers by this author and Lin H. Chen, MDFrom the Center for Global Health and Development, Boston University, Boston, and Mount Auburn Hospital, Cambridge, Massachusetts.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M14-1958 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Chikungunya, a mosquito-borne viral pathogen responsible for a febrile illness that is usually accompanied by a rash and severe, incapacitating arthralgias, emerged in the Caribbean in October 2013. Since its detection in Saint Martin, chikungunya virus has rapidly spread throughout the Caribbean and to Central and South America, where local transmission has now been documented in El Salvador, Costa Rica, Panama, Venezuela, Guyana, Suriname, French Guiana, Colombia, Brazil, and Paraguay. According to the Pan American Health Organization, as of 6 November 2014, there have been 874 103 suspected cases, 14 703 confirmed cases, and 153 deaths, with many afflicted patients in the Dominican Republic and El Salvador (1). In the continental United States, 1616 imported cases have been reported, with autochthonous transmission in southern Florida. Given the widespread presence of competent mosquito vectors (Aedes aegypti and A. albopictus), it may spread further within the United States.EpidemiologyChikungunya is an RNA virus in the Alphavirus genus of the Togaviridae family, initially described in an epidemic in Tanzania (formerly southern Tanganyika) among the Makonde tribe (2). The name originated from a Kimakonde word meaning “that which bends up” or “to be contorted.” Since the first description of chikungunya in the 1950s, outbreaks have occurred in West Africa, the Indian Ocean, India, and Southeast Asia. There are 3 major geographically defined viral lineages: West African; East, Central, and South African (ECSA); and Asian.In 2004, an epidemic began in East Africa, then spread in 2005 and 2006 to several islands in the Indian Ocean. La Réunion, Comoros, Mayotte, and the Seychelles were especially hard-hit, and the virus subsequently traveled to Asian countries bordering the Indian Ocean; Southeast Asia; and the Pacific Islands and, most recently, American Samoa. This major epidemic was notable for a high attack rate, with one third of the population in La Réunion infected (3).Travelers from India to Europe introduced chikungunya, resulting in local transmission in France and Italy. During this outbreak, the virus seems to have acquired mutations in glycoprotein E1, which is important for membrane fusion and virion assembly (4). This mutation resulted in the ECSA Indian Ocean lineage, which is adapted to and efficiently transmitted by A. albopictus.In October 2013, chikungunya virus was detected in Saint Martin and thereafter rapidly spread to Martinique and Guadeloupe. In the first half of 2014, this outbreak grew in magnitude, affecting nearly every island in the Caribbean. It also was introduced via travelers to several Central and South American countries, with resulting autochthonous transmission.The viral strain responsible for the growing epidemic in the Western hemisphere is the Asian rather than the ECSA Indian Ocean lineage, which is less efficiently transmitted by A. albopictus (5, 6); the preferred vector for the current outbreak seems to be A. aegypti. Nevertheless, the combination of 2 competent mosquito vectors (6), frequent travel between the Caribbean and Latin and North America (7), and an immunologically naive human population has set the stage for a continued epidemic with a high attack rate.Given the relatively widespread presence of both species of Aedes in the United States, risk for further spread in the Southeast is substantial, particularly for autochthonous transmission. However, in contrast to West Nile virus, a zoonotic pathogen that spreads in a bird–mosquito cycle, transmission of chikungunya is limited to human–Aedes species interactions.Clinical Manifestations and DiagnosisAfter an incubation period averaging 3 to 7 days (range, 2 to 12 days) (8), infected persons have abrupt onset of high fever, headache, back pain, myalgia, and polyarthralgia. The joint pain is typically symmetrical; can be severe; and usually affects the phalanges, ankles, and wrists, although large joints may also be involved. Rash occurs in approximately one half of patients and usually consists of a pruritic, erythematous, maculopapular eruption on the trunk. Although most symptoms resolve within 7 to 10 days, severe relapsing and debilitating arthralgia can persist for months and, in some patients, several years.Severe disease is relatively uncommon, and complications, including meningoencephalitis and death, have been rarely reported. During the large outbreak in La Réunion between 2005 and 2006, mother–child transmission was documented in pregnant women infected close to delivery. Vertical transmission occurred predominantly in nearly full-term pregnancies and was associated with symptomatic neonatal infections a median of 4 days after parturition (9).Symptoms among patients infected with chikungunya and dengue viruses substantially overlap, and co-infection can occur. The severity and persistence of joint pain are clues to distinguish between these 2 viral infections. During the acute phase of infection (days 1 to 8 of symptoms), real-time polymerase chain reaction and IgM testing should be done, although IgM may not appear for 5 to 7 days after symptom onset (8). Acute and convalescent sera can be tested for IgG to confirm the diagnosis, with the acute sample obtained in the first 8 days of symptomatic infection and the convalescent sample obtained at least 2 to 3 weeks after symptom onset. Because of geographic and clinical overlap, serum testing for dengue should also be done.Treatment, Prevention, and ControlNo antiviral agents are licensed to treat chikungunya, so therapy is supportive with anti-inflammatory agents, such as acetaminophen and nonsteroidal anti-inflammatory drugs. Antivector measures, including use of diethyltoluamide- or picaridin-containing insect repellents during the daytime, help to reduce the risk for exposure from the daytime-biting Aedes species. Prevention campaigns include drainage of breeding sites, application of insecticides, and insecticide-treated bed nets for such populations as hospitalized patients who are immobilized during the day. No licensed vaccine is currently available, but efforts to develop live, attenuated, inactivated DNA and recombinant subunit vaccines are ongoing (10).Clinician AdvisoryThe effect of chikungunya virus in travelers since its recent arrival in the Western hemisphere underscores the interconnectedness of the continental United States, the Caribbean, and Central and South America. Clinicians should advise patients to use antivector measures when traveling to regions with chikungunya transmission. Clinicians should consider chikungunya in the differential diagnosis of febrile travelers with arthralgia and rash after visiting regions with chikungunya transmission, including the Caribbean and Central and South America.References1. Pan American Health Organization; World Health Organization. Chikungunya. 2014. Accessed at www.paho.org/hq/index.php?option=com_topics&view=article&id=343&Itemid=40931&lang=en on 6 November 2014. Google Scholar2. Robinson MC. An epidemic of virus disease in Southern Province, Tanganyika Territory, in 1952-53. I. Clinical features. Trans R Soc Trop Med Hyg. 1955;49:28-32. [PMID: 14373834] CrossrefMedlineGoogle Scholar3. Josseran L, Paquet C, Zehgnoun A, Caillere N, LeTertre A, Solet JL, et al. Chikungunya disease outbreak, Reunion Island [Letter]. Emerg Infect Dis. 2006;12:1994-5. [PMID: 17354339] CrossrefMedlineGoogle Scholar4. Schuffenecker I, Iteman I, Michault A, Murri S, Frangeul L, Vaney MC, et al. Genome microevolution of chikungunya viruses causing the Indian Ocean outbreak. PLoS Med. 2006;3:e263. [PMID: 16700631] CrossrefMedlineGoogle Scholar5. Lanciotti RS, Valadere AM. Transcontinental movement of Asian genotype chikungunya virus [Letter]. Emerg Infect Dis. 2014;20:1400-2. [PMID: 25076384] doi:10.3201/eid2008.140268 CrossrefMedlineGoogle Scholar6. Vega-Rúa A, Zouache K, Girod R, Failloux AB, Lourenço-de-Oliveira R. High level of vector competence of Aedes aegypti and Aedes albopictus from ten American countries as a crucial factor in the spread of chikungunya virus. J Virol. 2014;88:6294-306. [PMID: 24672026] doi:10.1128/JVI.00370-14 CrossrefMedlineGoogle Scholar7. Khan K, Bogoch I, Brownstein JS, Miniota J, Nicolucci A, Hu W, et al. Assessing the origin of and potential for international spread of chikungunya virus from the Caribbean. PLoS Curr. 2014;6. [PMID: 24944846] doi:10.1371/currents.outbreaks.2134a0a7bf37fd8d388181539fea2da5 CrossrefMedlineGoogle Scholar8. Staples JE, Breiman RF, Powers AM. Chikungunya fever: an epidemiological review of a re-emerging infectious disease. Clin Infect Dis. 2009;49:942-8. [PMID: 19663604] doi:10.1086/605496 CrossrefMedlineGoogle Scholar9. Gérardin P, Barau G, Michault A, Bintner M, Randrianaivo H, Choker G, et al. Multidisciplinary prospective study of mother-to-child chikungunya virus infections on the island of La Réunion. PLoS Med. 2008;5:e60. [PMID: 18351797] doi:10.1371/journal.pmed.0050060 CrossrefMedlineGoogle Scholar10. Weaver SC, Osorio JE, Livengood JA, Chen R, Stinchcomb DT. Chikungunya virus and prospects for a vaccine. Expert Rev Vaccines. 2012;11:1087-101. [PMID: 23151166] doi:10.1586/erv.12.84 CrossrefMedlineGoogle Scholar Comments 0 Comments Sign In to Submit A Comment Davidson H. Hamer, MD, Lin H. Chen, MDBoston University School of Public Health29 January 2015 Author's Response We agree with Dr. Rodriguez-Cintron regarding the importance of chikungunya virus infections in Puerto Rico. Due to the large numbers of islands and countries affected by this widespread outbreak, our commentary on chikungunya in the Americas was unable to include a comprehensive list of all those with autochthonous transmission (1); however, the Pan American Health Organization (PAHO) regularly provides updated case numbers and incidence rates for each island and country (2). As of January 23, 2015, Puerto Rico has reported 21,518 suspected and 4,278 confirmed cases, with an incidence rate of 700 cases/100,000 population. According to PAHO, the chikungunya outbreaks in Dominican Republic and Saint Martin (French part) are even more dramatic, with over 500,000 suspected cases in the former, and an incidence rate of 18,246 cases/100,000 population in the latter (2). Because of the high volume of travel between the United States and all infected areas, it is imperative that we raise awareness of clinicians practicing in the contiguous United States regarding chikungunya in the Americas – all Caribbean islands, and most countries in Central and South America. We appreciate the comment from Drs. Al-Araimi and Mittoo regarding the similarity in presentation of chikungunya arthritis and rheumatoid arthritis, and that work-up is warranted for connective tissue disease in patients diagnosed with chikungunya who experience persistent or recurrent arthritis. Following the chikungunya epidemic in La Reunion in 2005, a cohort study of 147 chikungunya-infected patients found that 57% reported rheumatic symptoms at 15 months (nearly 2/3 with persistent symptoms and 1/3 were recurrent/relapsing) (3). These findings are similar to the patient described by Drs. Al-Arami and Mittoo. As noted by Drs. Al-Araimi and Mittoo, it is not yet known whether chikungunya virus triggers an autoimmune process, although some immunologic findings suggest inflammatory mechanisms (4). In chikungunya-infected patients who later are diagnosed with rheumatoid arthritis, the utility of therapy with disease-modifying anti-rheumatic drugs such as methotrexate, tumor necrosis factor blockers, hydroxychloroquine, and corticosteroids, has not yet been established (5). Finally, since persistent or relapsing arthralgia/arthritis may present to rheumatologists as well as primary care providers for evaluation, specialists should remain vigilant about assessing for chikungunya virus infection. Longitudinal natural history studies and randomized controlled trials of interventions for chikungunya patients with persistent arthritis are critically needed. Davidson H. Hamer, MD Center for Global Health and Development, Boston University School of Public Health, Boston, MA, USA Lin H. Chen, MD Mt. Auburn Hospital, Cambridge, MA, USA 1. Hamer DH, Chen LH. Chikungunya: Establishing a new home in the Western Hemisphere. Ann Intern Med. 2014;161:827-828. 2. Pan American Health Organization; World Health Organization. Chikungunya. Available at www.paho.org. Last accessed January 21, 2015. 3. Sissoko D, Malvy D, Ezzedine K, Renault P, Moscetti F, Ledrans M, Pierre V. Post-epidemic chikungunya disease on Reunion Island: course of rheumatic manifestations and associated factors over a 15-month period. PLoS Negl Trop Dis. 2009;3:e389. doi: 10.1371/journal.pntd.0000389. 4. Roques P, Gras G. Chikungunya fever: focus on peripheral markers of pathogenesis. J Infect Dis. 2011;203:141-3. 5. Simon F, Javelle E, Oliver M, Leparc-Goffart I, Marimoutou C. Chikungunya virus infection. Curr Infect Dis Rep. 2011;13:218-28. William Rodriguez-Cintron, MDPulm/CCM VA Caribbean Healthcare System16 December 2014 Chikugunya in the Caribbean Read with great interest the manuscript by Hamer and Chen (1) regarding Chikungunya. The manuscript however failed to mention and address the incidence of the disease in the Caribbean located US Commonwealth of Puerto Rico (PR). Though, this is eloquently addressed by the US Center for Diseases Control (CDC) in the latest Morbidity and Mortality Weekly Report (2). The first locally acquired, laboratory-confirmed chikungunya case was detected in PR in early May 2014 and 10,201 suspected cases (282 per 100,00 residents) had been reported by August 12, 2014. Certainly, there have been and there will be implications locally in terms of public health. However, because of the known shunt with the mainland USA, physicians within the mainland USA should become more aware of chikungunya when advising someone who is to travel to PR and/or treating an ill patient that is coming from PR. William Rodriguez-Cintron, MD, MACP Chief, Pulmonary/CCM VACHS 10 Casia St, SJ, PR 00921 1. Hamer D, Chen L : Chikungunya: Establishing a new Home in the western hemisphere; Ann Int Med 2014;161:827-828 2. Tyler S, et al, Chikungunya cases identified through passive surveillance and household investigations-Puerto Rico-, May 5-August 12, 2014; Centers for Disease Control and Prevention, Morbidity and Mortality Weekly Report; Vol 63, No 48: December 5, 2014 Tariq Al-Araimi, MD, Shikha Mittoo, MD, MHS, FRCPCDepartment of Internal Medicine, University of Toronto, Mount Sinai Hospital, University of Toronto20 October 2014 Chikungunya and Autoantibody positive arthritis: what is the connection? We read with great interest the article on Chikungunya by Hamer & Chen (1). However, chronic Chikungunya arthritis can persist for months post infection (2)(3). Among 47 travelers returning from the Indian Ocean island followed for a 14-month period, late arthropathy (after the 10th day), defined as having at least one of the following: symmetric oligo/polyarthritis accompanied by morning stiffness, non specific edema / tenosynovitis, worsening of mechanical pain in a pre-existing injured joint or bone was identified in 38 persons (2). In another series of 21 cases of newly diagnosed Chikungunya with a mean follow-up of 2 years, all of the 21 patients fulfilled the rheumatoid arthritis American College of Rheumatology (ACR) criteria with symptoms starting from the onset of viral infection to rheumatoid arthritis diagnosis (3). In our department, we recently had a confirmed case of Chikungunya who returned to Canada after travelling to the Dominican Republic & Jamaica after presenting with an inflammatory polyarthritis. The patient still complained of joint pain, one of the initial symptoms, after 3 months of presentation. We still pursued work up for a connective tissue disease (initial ANA was speckled pattern, titre of (1:80) persisting to (1:160) a month later, initial Anti-DsDNA was (38.7 IU/mL) while repeat was normal by Farr, RF and anti-CCP were negative). It remains unknown whether the virus can trigger an autoimmune event. The main stay treatment in the acute phase is the use of analgesics or non-steroidal anti-inflammatory drugs as described by Hamer & Chen and allowing some time before considering starting immunosuppressive therapy. However, there is limited reports with regards resolution of symptoms by treating the chronic arthritic phase with hydroxichloriquine, methotrexate or steroids (3)(4).Research still ongoing on the mechanism of alpha viruses related arthritis, some data suggest presence of Chikungunya in synovial macrophages triggers release of pro-inflammatory mediators ( IL10 , IFN-alpha ) leading to activation of matrix metalloprotease (MMP), induction of apoptosis and fibroblast hyperplasia. This obviously suggests some similarity between the mechanism of Chikungunya arthritis and rheumatoid arthritis(5). In conclusion, consider work up for a connective tissue disease and follow-up among patients with prolonged arthralgias and/or arthritis. 1. Hamer DH, Chen LH. Chikungunya: Establishing a New Home in the Western Hemisphere. Ann Intern Med. [Epub ahead of print 23 September 2014] doi:10.7326/M14-1958. 2. Simon F, Parola P, Grandadam M, Fourcade S, Oliver M, Brouqui P, et al. Chikungunya infection: an emerging rheumatism among travelers returned from Indian Ocean islands. Report of 47 cases. Medicine. 2007;86(3):123-37. 3. Bouquillard E, Combe B. A report of 21 cases of rheumatoid arthritis following Chikungunya fever. A mean follow-up of two years. Joint, bone, spine. 2009;76(6):654-7. 4. Chopra A, Anuradha V, Lagoo-Joshi V, Kunjir V, Salvi S, Saluja M. Chikungunya virus aches and pains: an emerging challenge. Arthritis Rheum. 2008;58(9):2921-2. 5. Jaffar-Bandjee MC, Das T, Hoarau JJ, Krejbich Trotot P, Denizot M, Ribera A, et al. Chikungunya virus takes centre stage in virally induced arthritis: possible cellular and molecular mechanisms to pathogenesis. Microbes Infect. 2009;11(14-15):1206-18. Author, Article, and Disclosure InformationAuthors: Davidson H. Hamer, MD; Lin H. Chen, MDAffiliations: From the Center for Global Health and Development, Boston University, Boston, and Mount Auburn Hospital, Cambridge, Massachusetts.Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M14-1958.Corresponding Author: Davidson H. Hamer, MD, Center for Global Health and Development, 801 Massachusetts Avenue, Crosstown Third Floor, Boston, MA 02118; e-mail, dhamer@bu.edu.Current Author Addresses: Dr. Hamer: Center for Global Health and Development, 801 Massachusetts Avenue, Crosstown Third Floor, Boston, MA 02118.Dr. Chen: Division of Infectious Diseases, Mount Auburn Hospital, 330 Mount Auburn Street, South 2, Cambridge, MA 02138.Author Contributions:Conception and design: D.H. Hamer.Analysis and interpretation of the data: D.H. Hamer, L.H. Chen.Drafting of the article: D.H. Hamer, L.H. Chen.Critical revision of the article for important intellectual content:D.H. Hamer, L.H. Chen.Final approval of the article: D.H. Hamer, L.H. Chen.Collection and assembly of data: D.H. Hamer, L.H. Chen.This article was published online first at www.annals.org on 23 September 2014. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoChikungunya William Rodriguez-Cintron Chikungunya Tariq Al-Araimi and Shikha Mittoo Chikungunya Davidson H. Hamer and Lin H. 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