Advertisement
Editorial

Arrival of Chikungunya Virus in the New World: Prospects for Spread and Impact on Public Health

  • Scott C. Weaver mail

    sweaver@utmb.edu

    Affiliations: Institute for Human Infections and Immunity, Galveston, Texas, United States of America, Center for Tropical Diseases, Galveston, Texas, United States of America, Department of Pathology, University of Texas Medical Branch, Galveston, Texas, United States of America

    X
  • Published: June 26, 2014
  • DOI: 10.1371/journal.pntd.0002921

For the first time in modern scientific history, chikungunya virus has established its mosquito-human transmission cycle in the Americas. The history of dengue control, recent findings on chikungunya strain variation, and public health preparedness indicate the likelihood of the further spread of this outbreak.

The mosquito-borne chikungunya virus (CHIKV; Togaviridae: Alphavirus) causes a febrile illness (chikungunya fever, or CHIK) typically accompanied by rash and severe, debilitating arthralgia. Pain and swelling are usually focused in the hands, wrists, ankles, and feet and can persist for years to cause not only major public health effects but also economic damage due to lost human productivity [1]. Most cases are not life threatening, although slightly increased mortality is associated with CHIKV infection. The virus is believed to have originated in Africa, where it still circulates enzootically among nonhuman primates, and is transmitted by arboreal Aedes mosquitoes (Figure 1) [2], [3]. These cycles lead to regular outbreaks of spillover infection in Africa, but most human cases result from CHIKV emergence into a human–mosquito cycle in urban areas of Africa, followed sometimes by spread beyond Africa. Evidence from historic accounts suggest that this emergence began as early as the 18th century in Indonesia and possibly the Americas, presumably via sailing ships that carried the essential ingredients for on-board circulation: susceptible humans and the peridomestic mosquito vector, Aedes aegypti [4]. Two other viruses that circulate in the same cycle, dengue and yellow fever, are also known to have caused outbreaks in port cities where this tropical mosquito was introduced, either temporarily during the summer in temperate climates where it cannot survive cold winters or permanently throughout tropical and subtropical regions of Asia, Europe, Australia, and the Americas.

thumbnail

Figure 1. Map showing the distribution of chikungunya virus enzootic strains in Africa and the emergence and spread of the Asian lineage (red arrows and dots) and the Indian Ocean lineage (yellow arrows and dots) from Africa.

doi:10.1371/journal.pntd.0002921.g001

Following its discovery in 1952, the first documented CHIKV emergence spread to generate urban outbreaks in India and Southeast Asia (Figure 1). This introduction has been traced to an Eastern/Central/Southern African (ECSA) enzootic CHIKV lineage that evolved sometime during or before the early 1950s [2], [3]. The resultant “Asian” endemic/epidemic CHIKV lineage persisted in Southeast Asia, where it continues to circulate sporadically in the urban cycle, transmitted among humans by A. aegypti without conclusive evidence of an enzootic component (Table 1). The second documented CHIKV emergence began in coastal Kenya in 2004 [5] and spread independently into islands in the Indian Ocean and to India, presumably via infected air travelers, a documented source of introductions [6][8]. Later, autochthonous transmission occurred in Italy [9] and France [10], initiated by infected travelers from India (Table 1). Although many imported cases were also detected in the Americas [6], including in dengue-endemic locations with both A. aegypti and A. albopictus vectors, no local transmission was detected. As with the Asian lineage, the etiologic CHIKV strain, called the Indian Ocean lineage (IOL) was again identified as a descendent from an enzootic ECSA strain [11]. However, some IOL adapted to a new vector, A. albopictus, through adaptive mutations in the E1 [12], [13] and E2 [14], [15] envelope glycoprotein genes. These mutations allowed the new epidemic IOL strains to use both A. aegypti and A. albopictus as vectors, resulting in millions of human cases. Because A. albopictus can survive cold winters and is generally less adapted to urban habitats than A. aegypti, IOL CHIKV strains adapted to this vector circulated both in temperate climates such as Italy [9] and in more rural habitats where the former species is more common than the latter [16].

thumbnail

Table 1. Representative chikungunya fever outbreaks documented in the literature.

doi:10.1371/journal.pntd.0002921.t001

During the ongoing IOL CHIK epidemics, the nearly completely naïve human populations in the Americas and the presence of both epidemic vectors, combined with the arrival of infected travelers, raised major concerns that an epidemic in the Caribbean and/or Latin America was inevitable [17]. However, with the gradual subsidence of epidemic transmission in many parts of Asia, this risk was perceived to have declined, because fewer infected travelers were documented in recent years.

Thus, the detection of active CHIKV circulation in Saint Martin beginning in October 2013 [18] was somewhat surprising. Furthermore, the characterization of the etiologic strain as belonging to the old Asian lineage rather than to the IOL was unexpected, considering that the former was viewed as displacing the latter in many parts of Asia [19]. However, because it apparently infects A. aegypti slightly more efficiently than CHIKV strains with the A. albopictus-adaptive E1 protein substitution [20], the Asian lineage may remain prevalent in urban areas of Asia, from which infected travelers are more likely to depart for global travel.

There is much bad news and only very limited good news in the 2013 CHIKV introduction into the Caribbean. The bad news includes: (1) CHIKV appears to be spreading nearly uncontrolled in the Caribbean, with over 4,300 confirmed cases as of May 23rd (Pan American Health Organization data). (2) Autochthonous transmission has resulted in at least 176 CHIK cases in French Guiana on the South American mainland. If transmission cannot be controlled quickly there, the historic inability to control dengue suggests that CHIKV will spread throughout Latin America. (3) Most of the Latin American population is presumably naïve, setting the stage for major epidemics and rapid spread. (4) Diagnostic capabilities for CHIKV in Latin America remain very limited, and it is possible that undetected circulation is already occurring in the region because of the difficulty in clinically distinguishing dengue from CHIK. And finally, (5) there could be the potential for CHIKV to establish an enzootic, monkey–human cycle in the Americas, as occurred for yellow fever virus hundreds of years ago after its importation from Africa [21].

If there is any good news related to this CHIK outbreak, it is that the etiologic strain, a member of the old Asian lineage, does not infect A. albopictus as efficiently as the adapted IOL strains, and is epistatically constrained in its ability to adapt to this vector via the E1-226 protein substitution [22]. This suggests that most CHIKV transmission in the Americas will occur via A. aegypti, which may limit geographic spread, particularly to temperate climates where this mosquito does not normally occur. However, A. aegypti reinfestation of most tropical and subtropical regions of Latin America since the 1970s [23], along with its persistence in the southern United States, leaves hundreds of millions of persons at risk for CHIKV infection. The presence of the closely related Mayaro alphavirus in South America could provide limited cross-protection [24], but this virus circulates enzootically, mainly in forested areas, where A. aegypti-borne CHIKV is expected to be less prevalent. Finally, the introduction of CHIKV during the beginning of the dry season in the Caribbean and northern hemisphere of Latin America may improve prospects for containing its spread, at least temporarily.

In summary, the prospects for controlling CHIKV circulation in Latin America since its arrival on the mainland of South America are not good, and many parts of the Americas are now at high risk for major epidemics. Because vaccines and specific antiviral therapies for CHIKV are not yet available [25], the only means for controlling its spread are reductions in A. aegypti populations and limiting human contact with this vector. It is therefore critical that public health officials implement robust surveillance based on existing dengue programs, establish local diagnostic capacity to test mosquitoes and patient sera from suspected cases, and develop outbreak response plans, including educational efforts to reduce contact with vectors. Health care workers should also be trained to include CHIK in their differential diagnoses for dengue-like illness and to optimally use available medications to alleviate the severe symptoms of CHIK.

References

  1. 1. Caglioti C, Lalle E, Castilletti C, Carletti F, Capobianchi MR, et al. (2013) Chikungunya virus infection: an overview. New Microbiol 36: 211–227.
  2. 2. Powers AM, Brault AC, Tesh RB, Weaver SC (2000) Re-emergence of Chikungunya and O'nyong-nyong viruses: evidence for distinct geographical lineages and distant evolutionary relationships. J Gen Virol 81: 471–479.
  3. 3. Volk SM, Chen R, Tsetsarkin KA, Adams AP, Garcia TI, et al. (2010) Genome-scale phylogenetic analyses of chikungunya virus reveal independent emergences of recent epidemics and various evolutionary rates. J Virol 84: 6497–6504. doi: 10.1128/jvi.01603-09
  4. 4. Carey DE (1971) Chikungunya and dengue: a case of mistaken identity? J Hist Med Allied Sci 26: 243–262. doi: 10.1093/jhmas/xxvi.3.243
  5. 5. Chretien JP, Anyamba A, Bedno SA, Breiman RF, Sang R, et al. (2007) Drought-associated chikungunya emergence along coastal East Africa. Am J Trop Med Hyg 76: 405–407.
  6. 6. Lanciotti RS, Kosoy OL, Laven JJ, Panella AJ, Velez JO, et al. (2007) Chikungunya virus in US travelers returning from India, 2006. Emerg Infect Dis 13: 764–767. doi: 10.3201/eid1305.070015
  7. 7. Taubitz W, Cramer JP, Kapaun A, Pfeffer M, Drosten C, et al. (2007) Chikungunya fever in travelers: clinical presentation and course. Clin Infect Dis 45: e1–4. doi: 10.1086/518701
  8. 8. Hochedez P, Hausfater P, Jaureguiberry S, Gay F, Datry A, et al. (2007) Cases of chikungunya fever imported from the islands of the South West Indian Ocean to Paris, France. Euro Surveill 12 E-pub ahead of print.
  9. 9. Rezza G, Nicoletti L, Angelini R, Romi R, Finarelli AC, et al. (2007) Infection with chikungunya virus in Italy: an outbreak in a temperate region. Lancet 370: 1840–1846. doi: 10.1016/s0140-6736(07)61779-6
  10. 10. Grandadam M, Caro V, Plumet S, Thiberge JM, Souares Y, et al. (2011) Chikungunya virus, southeastern France. Emerg Infect Dis 17: 910–913. doi: 10.3201/eid1705.101873
  11. 11. Schuffenecker I, Iteman I, Michault A, Murri S, Frangeul L, et al. (2006) Genome microevolution of chikungunya viruses causing the Indian Ocean outbreak. PLoS Med 3: e263. doi: 10.1371/journal.pmed.0030263
  12. 12. Tsetsarkin KA, Vanlandingham DL, McGee CE, Higgs S (2007) A single mutation in chikungunya virus affects vector specificity and epidemic potential. PLoS Pathog 3: e201. doi: 10.1371/journal.ppat.0030201
  13. 13. Vazeille M, Moutailler S, Coudrier D, Rousseaux C, Khun H, et al. (2007) Two Chikungunya isolates from the outbreak of La Reunion (Indian Ocean) exhibit different patterns of infection in the mosquito, Aedes albopictus. PLoS ONE 2: e1168. doi: 10.1371/journal.pone.0001168
  14. 14. Tsetsarkin KA, Weaver SC (2011) Sequential adaptive mutations enhance efficient vector switching by chikungunya virus and its epidemic emergence. PLoS Pathog 7: e1002412. doi: 10.1371/journal.ppat.1002412
  15. 15. Tsetsarkin K, Chen C, Yun R, Rossi SL, Plante KS, et al. (2014) Multi-peaked adaptive landscape for chikungunya virus evolution predicts continued fitness optimization in Aedes albopictus mosquitoes. Nature Comm In press. doi: 10.1038/ncomms5084
  16. 16. Kumar NP, Joseph R, Kamaraj T, Jambulingam P (2008) A226V mutation in virus during the 2007 chikungunya outbreak in Kerala, India. J Gen Virol 89: 1945–1948. doi: 10.1099/vir.0.83628-0
  17. 17. Weaver SC, Reisen WK (2009) Present and future arboviral threats. Antiviral Res 85: 328–345. doi: 10.1016/j.antiviral.2009.10.008
  18. 18. Leparc-Goffart I, Nougairede A, Cassadou S, Prat C, de Lamballerie X (2014) Chikungunya in the Americas. Lancet 383: 514. doi: 10.1016/s0140-6736(14)60185-9
  19. 19. Coffey LL, Forrester N, Tsetsarkin K, Vasilakis N, Weaver SC (2013) Factors shaping the adaptive landscape for arboviruses: implications for the emergence of disease. Future Microbiol 8: 155–176. doi: 10.2217/fmb.12.139
  20. 20. Arias-Goeta C, Mousson L, Rougeon F, Failloux AB (2013) Dissemination and transmission of the E1-226V variant of chikungunya virus in Aedes albopictus are controlled at the midgut barrier level. PLoS ONE 8: e57548. doi: 10.1371/journal.pone.0057548
  21. 21. Bryant JE, Holmes EC, Barrett AD (2007) Out of Africa: a molecular perspective on the introduction of yellow fever virus into the Americas. PLoS Pathog 3: e75. doi: 10.1371/journal.ppat.0030075
  22. 22. Tsetsarkin KA, Chen R, Leal G, Forrester N, Higgs S, et al. (2011) Chikungunya virus emergence is constrained in Asia by lineage-specific adaptive landscapes. Proc Natl Acad Sci U S A 108: 7872–7877. doi: 10.1073/pnas.1018344108
  23. 23. Gubler DJ (2011) Dengue, Urbanization and Globalization: The Unholy Trinity of the 21(st) Century. Trop Med Health 39: 3–11. doi: 10.2149/tmh.2011-s05
  24. 24. Weaver SC, Reisen WK (2010) Present and future arboviral threats. Antiviral Res 85: 328–345. doi: 10.1016/j.antiviral.2009.10.008
  25. 25. Weaver SC, Osorio JE, Livengood JA, Chen R, Stinchcomb DT (2012) Chikungunya virus and prospects for a vaccine. Expert Rev Vaccines 11: 1087–1101. doi: 10.1586/erv.12.84
  26. 26. Ross RW (1956) The Newala epidemic. III. The virus: isolation, pathogenic properties and relationship to the epidemic. J Hyg (Lond) 54: 177–191. doi: 10.1017/s0022172400044442
  27. 27. Lumsden WH (1955) An epidemic of virus disease in Southern Province, Tanganyika Territory, in 1952–53. II. General description and epidemiology. Trans R Soc Trop Med Hyg 49: 33–57. doi: 10.1016/0035-9203(55)90081-x
  28. 28. Chastel C (1963) [Human Infections in Cambodia by the Chikungunya Virus or an Apparently Closely Related Agent. Ii. Experimental Pathological Anatomy.]. Bull Soc Pathol Exot Filiales 56: 915–924.
  29. 29. Jupp PG, Kemp A (1996) What is the potential for future outbreaks of chikungunya, dengue and yellow fever in southern Africa? S Afr Med J 86: 35–37.
  30. 30. Rodger LM (1961) An outbreak of suspected Chikungunya fever in Northern Rhodesia. S Afr Med J 35: 126–128.
  31. 31. McIntosh BM, Harwin RM, Paterson HE, Westwater ML (1963) An Epidemic of Chikungunya in South-Eastern Southern Rhodesia. Cent Afr J Med 43: 351–359.
  32. 32. Rudnick A, Hammon WM (1962) Entomological aspects of Thai hemorrhagic fever epidemics in Bangkok, the Phillipines and Singapore, 1956–1961. SEATO Med Res Monograph 2: 24–29.
  33. 33. Myers RM, Carey DE, Reuben R, Jesudass ES, De Ranitz C, et al. (1965) The 1964 epidemic of dengue-like fever in South India: isolation of chikungunya virus from human sera and from mosquitoes. Indian J Med Res 53: 694–701.
  34. 34. Shah KV, Gibbs CJ Jr, Banerjee G (1964) Virological Investigation of the Epidemic of Haemorrhagic Fever in Calcutta: Isolation of Three Strains of Chikungunya Virus. Indian J Med Res 52: 676–683.
  35. 35. Dandawate CN, Thiruvengadam KV, Kalyanasundaram V, Rajagopal J, Rao TR (1965) Serological survey in Madras city with special reference to chikungunya. Indian J Med Res 53: 707–714.
  36. 36. Rao TR (1966) Recent epidemics caused by chikungunya virus in India, 1963–1965. Scientific Culture 32: 215.
  37. 37. Halstead SB, Scanlon JE, Umpaivit P, Udomsakdi S (1969) Dengue and chikungunya virus infection in man in Thailand, 1962–1964. IV. Epidemiologic studies in the Bangkok metropolitan area. Am J Trop Med Hyg 18: 997–1021.
  38. 38. Deller JJ Jr, Russell PK (1967) An analysis of fevers of unknown origin in American soldiers in Vietnam. Ann Intern Med 66: 1129–1143. doi: 10.7326/0003-4819-66-6-1129
  39. 39. Moore DL, Reddy S, Akinkugbe FM, Lee VH, David-West TS, et al. (1974) An epidemic of chikungunya fever at Ibadan, Nigeria, 1969. Ann Trop Med Parasitol 68: 59–68.
  40. 40. Lam SK, Chua KB, Hooi PS, Rahimah MA, Kumari S, et al. (2001) Chikungunya infection–an emerging disease in Malaysia. Southeast Asian J Trop Med Public Health 32: 447–451.
  41. 41. Muyembe-Tamfum JJ, Peyrefitte CN, Yogolelo R, Mathina Basisya E, Koyange D, et al. (2003) [Epidemic of Chikungunya virus in 1999 and 200 in the Democratic Republic of the Congo]. Med Trop (Mars) 63: 637–638.
  42. 42. Sang RC, Ahmed O, Faye O, Kelly CL, Yahaya AA, et al. (2008) Entomologic investigations of a chikungunya virus epidemic in the Union of the Comoros, 2005. Am J Trop Med Hyg 78: 77–82.
  43. 43. Kariuki Njenga M, Nderitu L, Ledermann JP, Ndirangu A, Logue CH, et al. (2008) Tracking epidemic Chikungunya virus into the Indian Ocean from East Africa. J Gen Virol 89: 2754–2760. doi: 10.1099/vir.0.2008/005413-0
  44. 44. Charrel RN, de Lamballerie X, Raoult D (2007) Chikungunya outbreaks–the globalization of vectorborne diseases. N Engl J Med 356: 769–771. doi: 10.1056/nejmp078013
  45. 45. Gerardin P, Guernier V, Perrau J, Fianu A, Le Roux K, et al. (2008) Estimating Chikungunya prevalence in La Reunion Island outbreak by serosurveys: two methods for two critical times of the epidemic. BMC Infect Dis 8: 99. doi: 10.1186/1471-2334-8-99
  46. 46. Organization WH (2007) Outbreak and spread of Chikungunya. Wkly Epidemiol Rec 82: 409–415.
  47. 47. Mavalankar D, Shastri P, Raman P (2007) Chikungunya epidemic in India: a major public-health disaster. Lancet Infect Dis 7: 306–307. doi: 10.1016/s1473-3099(07)70091-9
  48. 48. AbuBakar S, Sam IC, Wong PF, MatRahim N, Hooi PS, et al. (2007) Reemergence of endemic Chikungunya, Malaysia. Emerg Infect Dis 13: 147–149. doi: 10.3201/eid1301.060617
  49. 49. Peyrefitte CN, Rousset D, Pastorino BA, Pouillot R, Bessaud M, et al. (2007) Chikungunya virus, Cameroon, 2006. Emerg Infect Dis 13: 768–771. doi: 10.3201/eid1305.061500
  50. 50. Demanou M, Antonio-Nkondjio C, Ngapana E, Rousset D, Paupy C, et al. (2010) Chikungunya outbreak in a rural area of Western Cameroon in 2006: A retrospective serological and entomological survey. BMC Res Notes 3: 128. doi: 10.1186/1756-0500-3-128
  51. 51. Peyrefitte CN, Bessaud M, Pastorino BA, Gravier P, Plumet S, et al. (2008) Circulation of Chikungunya virus in Gabon, 2006–2007. J Med Virol 80: 430–433. doi: 10.1002/jmv.21090
  52. 52. Leroy EM, Nkoghe D, Ollomo B, Nze-Nkogue C, Becquart P, et al. (2009) Concurrent chikungunya and dengue virus infections during simultaneous outbreaks, Gabon, 2007. Emerg Infect Dis 15: 591–593. doi: 10.3201/eid1504.080664
  53. 53. Paupy C, Ollomo B, Kamgang B, Moutailler S, Rousset D, et al. (2010) Comparative role of Aedes albopictus and Aedes aegypti in the emergence of Dengue and Chikungunya in central Africa. Vector Borne Zoonotic Dis 10: 259–266. doi: 10.1089/vbz.2009.0005
  54. 54. Hertz JT, Munishi OM, Ooi EE, Howe S, Lim WY, et al. (2012) Chikungunya and dengue fever among hospitalized febrile patients in northern Tanzania. Am J Trop Med Hyg 86: 171–177. doi: 10.4269/ajtmh.2012.11-0393
  55. 55. Rianthavorn P, Prianantathavorn K, Wuttirattanakowit N, Theamboonlers A, Poovorawan Y (2010) An outbreak of chikungunya in southern Thailand from 2008 to 2009 caused by African strains with A226V mutation. Int J Infect Dis 14 Suppl 3: e161–165. doi: 10.1016/j.ijid.2010.01.001
  56. 56. Pulmanausahakul R, Roytrakul S, Auewarakul P, Smith DR (2011) Chikungunya in Southeast Asia: understanding the emergence and finding solutions. Int J Infect Dis 15: e671–676. doi: 10.1016/j.ijid.2011.06.002
  57. 57. Sam IC, Chan YF, Chan SY, Loong SK, Chin HK, et al. (2009) Chikungunya virus of Asian and Central/East African genotypes in Malaysia. J Clin Virol 46: 180–183. doi: 10.1016/j.jcv.2009.07.016
  58. 58. Leo YS, Chow AL, Tan LK, Lye DC, Lin L, et al. (2009) Chikungunya outbreak, Singapore, 2008. Emerg Infect Dis 15: 836–837. doi: 10.3201/eid1505.081390
  59. 59. Ng LC, Tan LK, Tan CH, Tan SS, Hapuarachchi HC, et al. (2009) Entomologic and virologic investigation of Chikungunya, Singapore. Emerg Infect Dis 15: 1243–1249. doi: 10.3201/eid1508.081486
  60. 60. Gould EA, Gallian P, De Lamballerie X, Charrel RN (2010) First cases of autochthonous dengue fever and chikungunya fever in France: from bad dream to reality!. Clin Microbiol Infect 16: 1702–1704. doi: 10.1111/j.1469-0691.2010.03386.x
  61. 61. Paupy C, Kassa Kassa F, Caron M, Nkoghe D, Leroy EM (2012) A chikungunya outbreak associated with the vector Aedes albopictus in remote villages of Gabon. Vector Borne Zoonotic Dis 12: 167–169. doi: 10.1089/vbz.2011.0736
  62. 62. Wu D, Wu J, Zhang Q, Zhong H, Ke C, et al. (2012) Chikungunya outbreak in Guangdong Province, China, 2010. Emerg Infect Dis 18: 493–495. doi: 10.3201/eid1803.110034
  63. 63. Duong V, Andries AC, Ngan C, Sok T, Richner B, et al. (2012) Reemergence of Chikungunya virus in Cambodia. Emerg Infect Dis 18: 2066–2069. doi: 10.3201/eid1812.120471
  64. 64. Wangchuk S, Chinnawirotpisan P, Dorji T, Tobgay T, Dorji T, et al. (2013) Chikungunya fever outbreak, Bhutan, 2012. Emerg Infect Dis 19: 1681–1684. doi: 10.3201/eid1910.130453