Review
Chikungunya, an epidemic arbovirosis

https://doi.org/10.1016/S1473-3099(07)70107-XGet rights and content

Summary

Chikungunya is an arboviral disease transmitted by aedes mosquitoes. The virus was first isolated in 1953 in Tanzania. Chikungunya virus is a member of the genus Alphavirus and the family Togaviridae. The disease typically consists of an acute illness characterised by fever, rash, and incapacitating arthralgia. The word chikungunya, used for both the virus and the disease, means “to walk bent over” in some east African languages, and refers to the effect of the joint pains that characterise this dengue-like infection. Chikungunya is a specifically tropical disease, but it is geographically restricted and outbreaks are relatively uncommon. It is only occasionally observed in travellers and military personnel. More than 266 000 people have been infected during the ongoing outbreak in Réunion, in which Aedes albopictus is the presumed vector. In the ongoing Indian outbreak, in which Aedes aegypti is the presumed vector, 1 400 000 cases of chikungunya were reported during 2006. The reasons for the re-emergence of chikungunya on the Indian subcontinent, and for its unprecedented incidence rate in the Indian Ocean region, are unclear. Plausible explanations include increased tourism, chikungunya virus introduction into a naive population, and viral mutation.

Introduction

Chikungunya is a viral disease transmitted by Aedes mosquitoes. The disease typically consists of an acute illness with fever, skin rash, and incapacitating arthralgia.1 The latter distinguishes chikungunya virus from dengue, which otherwise shares the same vectors, symptoms, and geographical distribution.2, 3 The word chikungunya, which is used for both the virus and the disease, means “to walk bent over” in the African dialect Swahili or Makonde, and refers to the effect of the incapacitating arthralgia.4

Chikungunya is a specifically tropical disease. It is relatively uncommon and poorly documented.3, 5 A chikungunya outbreak is currently ongoing in Réunion (Indian Ocean), where about 266 000 of the 775 000 inhabitants have reported symptoms of the disease. The probable vector is Aedes albopictus, a mosquito species endemic to Réunion and other islands in the Indian Ocean (figure 1A).4 In India, where the main vector is Aedes aegypti (figure 1B),6 1 400 000 cases were reported during 2006.7 The last outbreak of the infection in India occurred in 1973.

Section snippets

Chikungunya virus

Chikungunya virus, an arbovirus belonging to the genus Alphavirus (Togaviridae family), has a single-stranded RNA genome, a 60–70 nm diameter capsid and a phospholipid envelope. It is sensitive to desiccation and to temperatures above 58°C.8, 9 The Alphavirus group comprises 28 viruses, six of which can cause human joint disorders—namely chikungunya virus, o'nyong-nyong virus (central Africa), Ross River and Barmah Forest viruses (Australia and the Pacific), Sindbis virus (cosmopolitan), and

Recent outbreaks: India and Indian Ocean islands

The ongoing epidemic in the Indian Ocean region probably emerged first in Kenya (Lamu and Mombasa; July, 2004), before reaching the Comoros (January, 2005) and Seychelles (March, 2005), followed by Mauritius. Systematic studies showed a prevalence of 75% of the population in the Kenya (Lamu) outbreak, 63% in the Comoros, and 26% in Mayotte (2006).14, 31, 52, 67, 68

The virus reached Réunion (figure 2) in March–April, 2005, and around 266 000 cases had been diagnosed by Feb 19, 2007. For the

Chikungunya virus in travellers

The Indian Ocean islands, India, and Malaysia are popular tourist destinations. According to the World Tourism Organization, an estimated 1 474 218 people travelled from Madagascar, Mauritius, Mayotte, Réunion, and the Seychelles to European countries in 2004.13, 27 The outbreak in the Indian Ocean islands has substantially dented the region's tourist industry.23

Among travellers returning from the tropics, febrile arthralgia with exanthema may be caused by a variety of viral and bacterial

Common chikungunya virus infection

After infection with chikungunya virus, there is a silent incubation period lasting 2–4 days on average (range 1–12 days).19 Clinical onset is abrupt (see table), with high fever, headache, back pain, myalgia, and arthralgia; the latter can be intense, affecting mainly the extremities (ankles, wrists, phalanges) but also the large joints.1, 19, 51, 53, 68 Skin involvement is present in about 40–50% of cases, and consists of (1) a pruriginous maculopapular rash predominating on the thorax, (2)

Biological diagnosis of chikungunya virus infection

Virus isolation is based on inoculation of mosquito cell cultures, mosquitoes, mammalian cell cultures, or mice. Two main diagnostic methods are available, namely RT-PCR and serology (IgM or IgG) (figure 6).

RT-PCR is useful during the initial viraemic phase (day 0 to day 7),39, 84, 85 but classic serological methods are simpler (haemagglutination inhibition, complement binding, immunofluorescence, and ELISA).86, 87 IgM is detectable after an average of 2 days by ELISA immunofluorescent assay

Specific immunity and vaccination

Chikungunya virus infection seems to elicit long-lasting protective immunity. Experiments in animal models have shown cross-protection among chikungunya virus and other alphaviruses.92, 93

There is currently no commercial vaccine for chikungunya virus, although some candidate vaccines have been tested in human beings.92, 94 In the latest trials, conducted by the US Army Medical Research Institute, very satisfactory seroconversion rates (98% on day 28) and neutralising antibody titres were

Prevention

Pending vaccine development, the only effective preventive measures consist of individual protection against mosquito bites and vector control. Control of both adult and larval mosquito populations uses the same model as for dengue and has been relatively effective in many countries and settings. Mosquito control is the best available method for preventing chikungunya. Breeding sites must be removed, destroyed, frequently emptied, and cleaned or treated with insecticides.65 Large-scale

Treatment

There is currently no effective antiviral treatment for chikungunya. Treatment is therefore purely symptomatic and is based on non-salicylate analgesics and non-steroidal anti-inflammatory drugs. Synergistic efficacy was reported between interferon-α and ribavirin on chikungunya virus in vitro.97 A trial in southern Africa failed to confirm the efficacy of chloroquine on arthralgia.98

Conclusion

Several lessons can be drawn from the ongoing outbreaks of chikungunya in India and the Indian Ocean islands. First, clinical manifestations are highly variable and may be more severe than previously reported. Second, economic development does not protect countries from vector-borne diseases (eg, West Nile virus in the USA, and dengue fever in Rio or Singapore); on the contrary, modern lifestyles may amplify an epidemic through travel, population ageing, and production of solid waste that can

Search strategy and selection criteria

Data for this Review were collected by searching the English and French literature from 1955–2007 through PubMed, Current Contents, and the reference lists of relevant articles. The key words were “arboviruses”, “alphavirus”, “chikungunya”, “Aedes albopictus”, “India outbreak”, “Aedes aegypti”, and “Reunion Island outbreak”. We also searched comprehensive and authoritative websites such as http://www.chikungunya.re, http://www.medecinetropicale.com, http://www.invs.sante.fr, //www.who.int

References (98)

  • C van den Bosch et al.

    Chikungunya fever as a risk factor for endemic Burkitt's lymphoma in Malawi

    Trans R Soc Trop Med Hyg

    (2000)
  • JM Guilherme et al.

    Seroprevalence of five arboviruses in Zebu cattle in the Central African Republic

    Trans R Soc Trop Med Hyg

    (1996)
  • K Pavri

    Disappearance of chikungunya virus from India and south east Asia

    Trans R Soc Trop Med Hyg

    (1986)
  • C Chastel

    Chikungunya virus: its recent spread to the southern Indian Ocean and Reunion Island (2005–2006)

    Bull Acad Natl Med

    (2005)
  • PE McGill

    Viral infections: alpha-viral arthropathy

    Baillieres Clin Rheumatol

    (1995)
  • PY Robillard et al.

    Vertical maternal fetal transmission of the chikungunya virus. Ten cases among 84 pregnant women

    Presse Med

    (2006)
  • Y Lenglet et al.

    Chikungunya infection in pregnancy: Evidence for intrauterine infection in pregnant women and vertical transmission in the parturient. Survey of the Reunion Island outbreak

    J Gynecol Obstet Biol Reprod (Paris)

    (2006)
  • B Pastorino et al.

    Development of a TaqMan RT-PCR assay without RNA extraction step for the detection and quantification of African chikungunya viruses

    J Virol Methods

    (2005)
  • S Thein et al.

    Development of a simple indirect enzyme-linked immunosorbent assay for the detection of immunoglobulin M antibody in serum from patients following an outbreak of chikungunya virus infection in Yangon, Myanmar

    Trans R Soc Trop Med Hyg

    (1992)
  • NK Blackburn et al.

    Antigenic relationship between chikungunya virus strains and o'nyong nyong virus using monoclonal antibodies

    Res Virol

    (1995)
  • NH Levitt et al.

    Development of an attenuated strain of chikungunya virus for use in vaccine production

    Vaccine

    (1986)
  • S Briolant et al.

    In vitro inhibition of chikungunya and Semliki Forest viruses replication by antiviral compounds: synergistic effect of interferon-alpha and ribavirin combination

    Antiviral Res

    (2004)
  • A Savarino et al.

    New insights into the antiviral effects of chloroquine

    Lancet Infect Dis

    (2006)
  • DE Carey

    Chikungunya and dengue: a case of mistaken identity?

    J Hist Med Allied Sci

    (1971)
  • JJ Deller et al.

    Chikungunya disease

    Am J Trop Med Hyg

    (1968)
  • M Enserink

    Infectious diseases. Massive outbreak draws fresh attention to little-known virus

    Science

    (2006)
  • AM Powers et al.

    Re-emergence of chikungunya and o'nyong-nyong viruses: evidence for distinct geographical lineages and distant evolutionary relationships

    J Gen Virol

    (2000)
  • P Yergolkar et al.

    Chikungunya outbreaks caused by African genotype, India

    Emerg Infect Dis

    (2006)
  • AH Khan et al.

    Complete nucleotide sequence of chikungunya virus and evidence for an internal polyadenylation site

    J Gen Virol

    (2002)
  • JH Strauss et al.

    The alphaviruses: gene expression, replication, and evolution

    Microbiol Rev

    (1994)
  • P Yadav et al.

    Genotyping of chikungunya virus isolates from India during 1996–2000 by reverse transcription-polymerase chain reaction

    Acta Virol

    (2003)
  • I Schuffenecker et al.

    Genome microevolution of chikungunya viruses causing the Indian Ocean outbreak

    PLoS Med

    (2006)
  • P Parola et al.

    Novel chikungunya virus variant in travelers returning from Indian Ocean Islands

    Emerg Infect Dis

    (2006)
  • Chikungunya fever among US Peace Corps volunteers—Republic of the Philippines

    MMWR Morb Mortal Wkly Rep

    (1986)
  • P Jeandel et al.

    Exotic viral arthritis: role of alphavirus

    Med Trop

    (2004)
  • HG Zeller

    Dengue, arbovirus and migrations in the Indian Ocean

    Bull Soc Pathol Exot

    (1998)
  • SK Lam et al.

    Chikungunya infection—an emerging disease in Malaysia

    Southeast Asian J Trop Med Public Health

    (2001)
  • PG Jupp et al.

    Aedes furcifer and other mosquitoes as vectors of chikungunya virus at Mica, northeastern Transvaal, South Africa

    J Am Mosq Control Assoc

    (1990)
  • AB Knudsen

    Global distribution and continuing spread of Aedes albopictus

    Parassitologia

    (1995)
  • S Higgs

    The 2005–2006 chikungunya epidemic in the Indian Ocean

    Vector Borne Zoonotic Dis

    (2006)
  • F Pages et al.

    Aedes albopictus: chronical of a spreading vector

    Med Trop

    (2006)
  • A Rohani et al.

    Rapid detection of chikungunya virus in laboratory infected Aedes aegypti by reverse-transcriptase-polymerase chain reaction (RT-PCR)

    Trop Biomed

    (2005)
  • E Depoortere et al.

    Chikungunya risk assessment for Europe: recommendations for action

    Euro Surveill

    (2006)
  • S Inoue et al.

    Distribution of three arbovirus antibodies among monkeys (Macaca fascicularis) in the Philippines

    J Med Primatol

    (2003)
  • ND Wolfe et al.

    Sylvatic transmission of arboviruses among Bornean orangutans

    Am J Trop Med Hyg

    (2001)
  • JS Mackenzie et al.

    Emerging viral diseases of southeast Asia and the western Pacific

    Emerg Infect Dis

    (2001)
  • F Macasaet

    Further observation on chikungunya fever

    J Philipp Med Assoc

    (1970)
  • NG Gratz

    Critical review of the vector status of Aedes albopictus

    Med Vet Entomol

    (2004)
  • KR Porter et al.

    A serological study of chikungunya virus transmission in Yogyakarta, Indonesia: evidence for the first outbreak since 1982

    Southeast Asian J Trop Med Public Health

    (2004)
  • Cited by (0)

    View full text