Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Primer
  • Published:

Chikungunya fever

Nature Reviews Disease Primers volume 9, Article number: 17 (2023) Cite this article

Subjects

An Author Correction to this article was published on 19 May 2023

This article has been updated

Abstract

Chikungunya virus is widespread throughout the tropics, where it causes recurrent outbreaks of chikungunya fever. In recent years, outbreaks have afflicted populations in East and Central Africa, South America and Southeast Asia. The virus is transmitted by Aedes aegypti and Aedes albopictus mosquitoes. Chikungunya fever is characterized by severe arthralgia and myalgia that can persist for years and have considerable detrimental effects on health, quality of life and economic productivity. The effects of climate change as well as increased globalization of commerce and travel have led to growth of the habitat of Aedes mosquitoes. As a result, increasing numbers of people will be at risk of chikungunya fever in the coming years. In the absence of specific antiviral treatments and with vaccines still in development, surveillance and vector control are essential to suppress re-emergence and epidemics.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Phylogenetic tree of alphaviruses and spread of CHIKV lineages.
Fig. 2: CHIKV replication.
Fig. 3: CHIKV infection and symptoms.
Fig. 4: CHIKV-associated immunopathology.
Fig. 5: Management of chikungunya fever.

Similar content being viewed by others

Change history

References

  1. Kramer, I. M. et al. The ecophysiological plasticity of Aedes aegypti and Aedes albopictus concerning overwintering in cooler ecoregions is driven by local climate and acclimation capacity. Sci. Total. Environ. 778, 146128 (2021).

    Article  CAS  PubMed  Google Scholar 

  2. Laporta, G. Z. et al. Global distribution of Aedes aegypti and Aedes albopictus in a climate change scenario of regional rivalry. Insects 14, 49 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  3. Mercier, A. et al. Impact of temperature on dengue and chikungunyatransmission by the mosquito Aedes albopictus. Sci. Rep. 12, 6973 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Zaid, A. et al. Arthritogenic alphaviruses: epidemiological and clinical perspective on emerging arboviruses. Lancet Infect. Dis. 21, e123–e133 (2021). This review focuses on CHIKV and other arthritogenic alphaviruses that have been identified globally, and provides a comprehensive appraisal of present and future research directions.

    Article  CAS  PubMed  Google Scholar 

  5. Weaver, S. C., Chen, R. & Diallo, M. Chikungunya virus: role of vectors in emergence from enzootic cycles. Annu. Rev. Entomol. 65, 313–332 (2020).

    Article  CAS  PubMed  Google Scholar 

  6. Azar, S. R., Campos, R. K., Bergren, N. A., Camargos, V. N. & Rossi, S. L. Epidemic alphaviruses: ecology, emergence and outbreaks. Microorganisms 8, 1167 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. CEPI. Priority diseases. CEPI https://cepi.net/research_dev/priority-diseases/ (2017).

  8. Mehand, M. S., Al-Shorbaji, F., Millett, P. & Murgue, B. The WHO R&D Blueprint: 2018 review of emerging infectious diseases requiring urgent research and development efforts. Antivir. Res. 159, 63–67 (2018).

    Article  CAS  PubMed  Google Scholar 

  9. Kril, V., Aïqui-Reboul-Paviet, O., Briant, L. & Amara, A. New insights into chikungunya virus infection and pathogenesis. Annu. Rev. Virol. 8, 327–347 (2021).

    Article  PubMed  Google Scholar 

  10. Longbottom, J. et al. Aedes albopictus invasion across Africa: the time is now for cross-country collaboration and control. Lancet Glob. Health https://doi.org/10.1016/S2214-109X(23)00046-3 (2023).

    Article  PubMed  Google Scholar 

  11. Kolimenakis, A. et al. The role of urbanisation in the spread of Aedes mosquitoes and the diseases they transmit — a systematic review. PLoS Negl. Trop. Dis. 15, e0009631 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  12. Sharif, N. et al. Molecular epidemiology, evolution and reemergence of chikungunya virus in South Asia. Front. Microbiol. 12, 689979 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  13. Gloria-Soria, A. et al. Vector competence of Aedes albopictus populations from the northeasters United States for Chikungunya, Dengue, and Zika Viruses. Am. J. Trop. Med. Hyg. 104, 1123–1130 (2020).

    PubMed  PubMed Central  Google Scholar 

  14. de Lima Cavalcanti, T. Y. V., Pereira, M. R., de Paula, S. O. & Franca, R. F. O. A review on chikungunya virus epidemiology, pathogenesis and current vaccine development. Viruses 14, 969 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  15. Powers, A. M., Brault, A. C., Tesh, R. B. & Weaver, S. C. Re-emergence of Chikungunya and O’nyong-nyong viruses: evidence for distinct geographical lineages and distant evolutionary relationships. J. Gen. Virol. 81, 471–479 (2000).

    CAS  PubMed  Google Scholar 

  16. Schuffenecker, I. et al. Genome microevolution of chikungunya viruses causing the Indian Ocean outbreak. PLoS Med. 3, e263 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  17. Volk, S. M. et al. Genome-scale phylogenetic analyses of chikungunya virus reveal independent emergences of recent epidemics and various evolutionary rates. J. Virol. 84, 6497–6504 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Selhorst, P. et al. Molecular characterization of chikungunya virus during the 2019 outbreak in the Democratic Republic of the Congo. Emerg. Microbes Infect. 9, 1912–1918 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Kariuki Njenga, M. et al. Tracking epidemic Chikungunya virus into the Indian Ocean from East Africa. J. Gen. Virol. 89, 2754–2760 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Sergon, K. et al. Seroprevalence of Chikungunya virus (CHIKV) infection on Lamu Island, Kenya, October 2004. Am. J. Trop. Med. Hyg. 78, 333–337 (2008).

    Article  PubMed  Google Scholar 

  21. Chretien, J. P. et al. Drought-associated chikungunya emergence along coastal East Africa. Am. J. Trop. Med. Hyg. 76, 405–407 (2007).

    Article  PubMed  Google Scholar 

  22. Gérardin, P. et al. Estimating Chikungunya prevalence in La Réunion Island outbreak by serosurveys: two methods for two critical times of the epidemic. BMC Infect. Dis. 8, 99 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  23. Josseran, L. et al. Chikungunya disease outbreak, Reunion Island. Emerg. Infect. Dis. 12, 1994–1995 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  24. Powers, A. M. & Logue, C. H. Changing patterns of chikungunya virus: re-emergence of a zoonotic arbovirus. J. Gen. Virol. 88, 2363–2377 (2007).

    Article  CAS  PubMed  Google Scholar 

  25. Arankalle, V. A. et al. Genetic divergence of Chikungunya viruses in India (1963–2006) with special reference to the 2005–2006 explosive epidemic. J. Gen. Virol. 88, 1967–1976 (2007).

    Article  CAS  PubMed  Google Scholar 

  26. Angelini, P. et al. Chikungunya epidemic outbreak in Emilia-Romagna (Italy) during summer 2007. Parassitologia 50, 97–98 (2008).

    CAS  PubMed  Google Scholar 

  27. Delisle, E. et al. Chikungunya outbreak in Montpellier, France, September to October 2014. Eurosurveillance 20, 21108 (2015).

    Article  PubMed  Google Scholar 

  28. Cassadou, S. et al. Emergence of chikungunya fever on the French side of Saint Martin island, October to December 2013. Eurosurveillance 19, 20752 (2014).

    Article  PubMed  Google Scholar 

  29. Van Bortel, W. et al. Chikungunya outbreak in the Caribbean region, December 2013 to March 2014, and the significance for Europe. Eurosurveillance 19, 20759 (2014).

    PubMed  Google Scholar 

  30. de Oliveira, E. C. et al. Short report: Introduction of chikungunya virus ECSA genotype into the Brazilian Midwest and its dispersion through the Americas. PLoS Negl. Trop. Dis. 15, e0009290 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  31. Tsetsarkin, K. A., Vanlandingham, D. L., McGee, C. E. & Higgs, S. A single mutation in chikungunya virus affects vector specificity and epidemic potential. PLoS Pathog. 3, e201 (2007). This paper demonstrated that the E1-A226V mutation was directly responsible for a significant increase in CHIKV infectivity for Ae. albopictus and led to more efficient viral dissemination into mosquito secondary organs and transmission to suckling mice.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Tsetsarkin, K. A., Chen, R. & Weaver, S. C. Interspecies transmission and chikungunya virus emergence. Curr. Opin. Virol. 16, 143–150 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  33. Tsetsarkin, K. A. et al. Chikungunya virus emergence is constrained in Asia by lineage-specific adaptive landscapes. Proc. Natl Acad. Sci. USA 108, 7872–7877 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Tsetsarkin, K. A. & Weaver, S. C. Sequential adaptive mutations enhance efficient vector switching by Chikungunya virus and its epidemic emergence. PLoS Pathog. 7, e1002412 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Tsetsarkin, K. A. et al. Epistatic roles of E2 glycoprotein mutations in adaption of chikungunya virus to Aedes albopictus and Ae. aegypti mosquitoes. PLoS ONE 4, e6835 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  36. Weaver, S. C., Forrester, N. L., Liu, J. & Vasilakis, N. Population bottlenecks and founder effects: implications for mosquito-borne arboviral emergence. Nat. Rev. Microbiol. 19, 184–195 (2021). This review discusses the role of genetic drift following population bottlenecks and founder effects in arboviral evolution and spread, and the emergence of human disease.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Nsoesie, E. O. et al. Global distribution and environmental suitability for chikungunya virus 1952 to 2015. Eurosurveillance 21, https://doi.org/10.2807/1560-7917.ES.2016.21.20.30234 (2016).

  38. Leta, S. et al. Global risk mapping for major diseases transmitted by Aedes aegypti and Aedes albopictus. Int. J. Infect. Dis. 67, 25–35 (2018).

    Article  PubMed  Google Scholar 

  39. Mora, C. et al. Over half of known human pathogenic diseases can be aggravated by climate change. Nat. Clim. Change 12, 869–875 (2022).

    Article  Google Scholar 

  40. Tjaden, N. B. et al. Modelling the effects of global climate change on Chikungunya transmission in the 21st century. Sci. Rep. 7, 3813 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  41. Dorléans, F. et al. Outbreak of Chikungunya in the French Caribbean islands of Martinique and Guadeloupe: findings from a hospital-based surveillance system (2013-2015). Am. J. Trop. Med. Hyg. 98, 1819–1825 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  42. Sharp, T. M. et al. Centers for disease control and prevention (CDC). Chikungunya cases identified through passive surveillance and household investigation — Puerto Rico, May 5-August 12, 2014. MMWR Morb. Mortal. Wkly Rep. 63, 1121–1128 (2014).

    PubMed  PubMed Central  Google Scholar 

  43. Silva Junior, G. B. D., Pinto, J. R., Mota, R. M. S., Pires Neto, R. D. J. & Daher, E. F. Impact of chronic kidney disease on chikungunya virus infection clinical manifestations and outcome: highlights during an outbreak in northeastern Brazil. Am. J. Trop. Med. Hyg. 99, 1327–1330 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  44. Soumahoro, M. K. et al. The Chikungunya epidemic on La Réunion Island in 2005-2006: a cost-of-illness study. PLoS Negl. Trop. Dis. 5, e1197 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  45. Freitas, A. R. R., Alarcón-Elbal, P. M., Paulino-Ramírez, R. & Donalisio, M. R. Excess mortality profile during the Asian genotype chikungunya epidemic in the Dominican Republic, 2014. Trans. R. Soc. Trop. Med. Hyg. 112, 443–449 (2018).

    Article  PubMed  Google Scholar 

  46. Jaffar-Bandjee, M. C. et al. Emergence and clinical insights into the pathology of Chikungunya virus infection. Expert Rev. Anti. Infect. Ther. 8, 987–996 (2010).

    Article  PubMed  Google Scholar 

  47. Brito, C. A. A. Alert: severe cases and deaths associated with Chikungunya in Brazil. Rev. Soc. Bras. Med. Trop. 50, 585–589 (2017).

    Article  PubMed  Google Scholar 

  48. Fred, A. et al. SEROCHIK group. Individual and contextual risk factors for chikungunya virus infection: the SEROCHIK cross-sectional population-based study. Epidemiol. Infect. 146, 1056–1064 (2018).

    Article  CAS  PubMed  Google Scholar 

  49. Paixão, E. S. et al. Chikungunya chronic disease: a systematic review and meta-analysis. Trans. R. Soc. Trop. Med. Hyg. 112, 301–316 (2018).

    Article  PubMed  Google Scholar 

  50. Westaway, E. G. et al. Togaviridae. Intervirology 24, 125–139 (1985).

    Article  CAS  PubMed  Google Scholar 

  51. Voss, J. E. et al. Glycoprotein organization of Chikungunya virus particles revealed by X-ray crystallography. Nature 468, 709–712 (2010).

    Article  CAS  PubMed  Google Scholar 

  52. Akahata, W. et al. A virus-like particle vaccine for epidemic Chikungunya virus protects nonhuman primates against infection. Nat. Med. 16, 334–338 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Mukhopadhyay, S. et al. Mapping the structure and function of the E1 and E2 glycoproteins in alphaviruses. Structure 14, 63–73 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Khan, A. H. et al. Complete nucleotide sequence of chikungunya virus and evidence for an internal polyadenylation site. J. Gen. Virol. 83, 3075–3084 (2002).

    Article  CAS  PubMed  Google Scholar 

  55. Hyde, J. L. et al. The 5′ and 3′ ends of alphavirus RNA — non-coding is not non-functional. Virus Res. 206, 99–107 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Frolov, I. & Frolova, E. I. Molecular virology of Chikungunya virus. Curr. Top. Microbiol. Immunol. 435, 1–31 (2022). This review summarizes the current understanding of molecular mechanisms of alphavirus RNA replication and interaction with host cells. Emphasis was placed on demonstrating the distinct features of CHIKV in utilizing host factors to build replication complexes and modify the intracellular environment for efficient viral replication and inhibition of the innate immune response.

    CAS  PubMed  Google Scholar 

  57. Ahola, T., McInerney, G. & Merits, A. Alphavirus RNA replication in vertebrate cells. Adv. Virus Res. 111, 111–156 (2021).

    Article  CAS  PubMed  Google Scholar 

  58. Hardy, W. R. & Strauss, J. H. Processing the nonstructural polyproteins of sindbis virus: nonstructural proteinase is in the C-terminal half of nsP2 and functions both in cis and in trans. J. Virol. 63, 4653–4664 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Tomar, S., Hardy, R. W., Smith, J. L. & Kuhn, R. J. Catalytic core of alphavirus nonstructural protein nsP4 possesses terminal adenylyltransferase activity. J. Virol. 80, 9962–9969 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Vasiljeva, L., Merits, A., Auvinen, P. & Kaariainen, L. Identification of a novel function of the alphavirus capping apparatus. RNA 5′ -triphosphatase activity of Nsp2. J. Biol. Chem. 275, 17281–17287 (2000).

    Article  CAS  PubMed  Google Scholar 

  61. Ahola, T. & Kaariainen, L. Reaction in alphavirus mRNA capping: formation of a covalent complex of nonstructural protein nsP1 with 7-methyl-GMP. Proc. Natl Acad. Sci. USA 92, 507–511 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Zhang, K. et al. Molecular basis of specific viral RNA recognition and 5′-end capping by the Chikungunya virus nsP1. Cell Rep. 40, 111133 (2022).

    Article  CAS  PubMed  Google Scholar 

  63. Jones, R., Bragagnolo, G., Arranz, R. & Reguera, J. Capping pores of alphavirus nsP1 gate membranous viral replication factories. Nature 589, 615–619 (2021).

    Article  CAS  PubMed  Google Scholar 

  64. Laakkonen, P., Auvinen, P., Kujala, P. & Kaariainen, L. Alphavirus replicase protein NSP1 induces filopodia and rearrangement of actin filaments. J. Virol. 72, 10265–10269 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Laurent, T. et al. Architecture of the chikungunya virus replication organelle. eLife 11, e83042 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  66. Strauss, J. H. & Strauss, E. G. The alphaviruses: gene expression, replication, and evolution. Microbiol. Rev. 58, 491–562 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Lemm, J. A., Rumenapf, T., Strauss, E. G., Strauss, J. H. & Rice, C. M. Polypeptide requirements for assembly of functional Sindbis virus replication complexes: a model for the temporal regulation of minus- and plus-strand RNA synthesis. EMBO J. 13, 2925–2934 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Lemm, J. A. & Rice, C. M. Roles of nonstructural polyproteins and cleavage products in regulating Sindbis virus RNA replication and transcription. J. Virol. 67, 1916–1926 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Liu, Y., Yuan, Y. & Zhang, L. Innate immune evasion by alphaviruses. Front. Immunol. 13, 1005586 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Jones, P. H. et al. BST-2/tetherin-mediated restriction of chikungunya (CHIKV) VLP budding is counteracted by CHIKV non-structural protein 1 (nsP1). Virology 438, 37–49 (2013).

    Article  CAS  PubMed  Google Scholar 

  71. Göertz, G. P. et al. The methyltransferase-like domain of chikungunya virus nsP2 inhibits the interferon response by promoting the nuclear export of STAT1. J. Virol. 92, e01008–e01018 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  72. Fros, J. J., van der Maten, E., Vlak, J. M. & Pijlman, G. P. The C-terminal domain of chikungunya virus nsP2 independently governs viral RNA replication, cytopathicity, and inhibition of interferon signaling. J. Virol. 87, 10394–10400 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Fros, J. J. et al. Chikungunya virus nsP3 blocks stress granule assembly by recruitment of G3BP into cytoplasmic foci. J. Virol. 86, 10873–10879 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Bae, S., Lee, J. Y. & Myoung, J. Chikungunya virus nsP2 impairs MDA5/RIG-I-mediated induction of NF-κB promoter activation: a potential target for virus-specific therapeutics. J. Microbiol. Biotechnol. 30, 1801–1809 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Nair, S. R., Abraham, R., Sundaram, S. & Sreekumar, E. Interferon regulated gene (IRG) expression-signature in a mouse model of chikungunya virus neurovirulence. J. Neurovirol. 23, 886–902 (2017).

    Article  CAS  PubMed  Google Scholar 

  76. Sanchez David, R. Y. et al. Comparative analysis of viral RNA signatures on different RIG-I-like receptors. eLife 5, e11275 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  77. Priya, R., Patro, I. K. & Parida, M. M. TLR3 mediated innate immune response in mice brain following infection with Chikungunya virus. Virus Res. 189, 194–205 (2014).

    Article  CAS  PubMed  Google Scholar 

  78. Fros, J. J. et al. Chikungunya virus non-structural protein 2-mediated host shut-off disables the unfolded protein response. J. Gen. Virol. 96, 580–589 (2015).

    Article  CAS  PubMed  Google Scholar 

  79. Ekchariyawat, P. et al. Inflammasome signaling pathways exert antiviral effect against Chikungunya virus in human dermal fibroblasts. Infect. Genet. Evol. 32, 401–408 (2015).

    Article  CAS  PubMed  Google Scholar 

  80. Chen, W. et al. Specific inhibition of NLRP3 in chikungunya disease reveals a role for inflammasomes in alphavirus-induced inflammation. Nat. Microbiol. 2, 1435–1445 (2017). This paper showed that peripheral blood mononuclear cells isolated from patients with CHIKV infection had elevated NLRP3, caspase 1 and IL-18 mRNA expression and, using a mouse model of CHIKV infection, found that high NLRP3 expression was associated with peak inflammatory symptoms and that subsequent inhibition of NLRP3 activation using a small-molecule inhibitor resulted in reduced CHIKV-induced inflammation and abrogated osteoclastogenic bone loss and myositis.

    Article  CAS  PubMed  Google Scholar 

  81. Ozden, S. et al. Inhibition of Chikungunya virus infection in cultured human muscle cells by furin inhibitors: impairment of the maturation of the E2 surface glycoprotein. J. Biol. Chem. 283, 21899–21908 (2008).

    Article  CAS  PubMed  Google Scholar 

  82. Yap, M. L. et al. Structural studies of Chikungunya virus maturation. Proc. Natl Acad. Sci. USA 114, 13703–13707 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Basore, K. et al. Cryo-EM structure of Chikungunya virus in complex with the Mxra8 receptor. Cell 177, 1725–1737.e16 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Holmes, A. C., Basore, K., Fremont, D. H. & Diamond, M. S. A molecular understanding of alphavirus entry. PLoS Pathog. 16, e1008876 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. De Caluwe, L., Arien, K. K. & Bartholomeeusen, K. Host factors and pathways involved in the entry of mosquito-borne alphaviruses. Trends Microbiol. 29, 634–647 (2021). This review summarizes the most important virus–host interactions during the early events of the alphavirus replication cycle.

    Article  PubMed  Google Scholar 

  86. Jose, J., Snyder, J. E. & Kuhn, R. J. A structural and functional perspective of alphavirus replication and assembly. Future Microbiol. 4, 837–856 (2009).

    Article  CAS  PubMed  Google Scholar 

  87. Brown, R. S., Anastasakis, D. G., Hafner, M. & Kielian, M. Multiple capsid protein binding sites mediate selective packaging of the alphavirus genomic RNA. Nat. Commun. 11, 4693 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Kielian, M., Chanel-Vos, C. & Liao, M. Alphavirus entry and membrane fusion. Viruses 2, 796–825 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Ramsey, J. & Mukhopadhyay, S. Disentangling the frames, the state of research on the alphavirus 6K and TF proteins. Viruses 9, 228 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  90. van Duijl-Richter, M. K. S., Blijleven, J. S., van Oijen, A. M. & Smit, J. M. Chikungunya virus fusion properties elucidated by single-particle and bulk approaches. J. Gen. Virol. 96, 2122–2132 (2015).

    Article  PubMed  Google Scholar 

  91. Hoornweg, T. E. et al. Dynamics of chikungunya virus cell entry unraveled by single-virus tracking in living cells. J. Virol. 90, 4745–4756 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Zhang, R. et al. Mxra8 is a receptor for multiple arthritogenic alphaviruses. Nature 557, 570–574 (2018). This paper reports on the identification of the cell adhesion molecule MXRA8 as an entry mediator for multiple emerging arthritogenic alphaviruses, including CHIKV, Ross River virus, Mayaro virus and ONNV, using a genome-wide CRISPR–Cas9-based screen.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Zhang, R. et al. Expression of the Mxra8 receptor promotes alphavirus infection and pathogenesis in mice and Drosophila. Cell Rep. 28, 2647–2658.e5 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Wintachai, P. et al. Identification of prohibitin as a Chikungunya virus receptor protein. J. Med. Virol. 84, 1757–1770 (2012).

    Article  CAS  PubMed  Google Scholar 

  95. De Caluwe, L. et al. The CD147 protein complex is involved in entry of Chikungunya virus and related alphaviruses in human cells. Front. Microbiol. 12, 615165 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  96. McAllister, N. et al. Chikungunya virus strains from each genetic clade bind sulfated glycosaminoglycans as attachment factors. J. Virol. 94, e01500-20 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  97. Clark, L. E. et al. Abraham J. VLDLR and ApoER2 are receptors for multiple alphaviruses. Nature 602, 475–480 (2022).

    Article  CAS  PubMed  Google Scholar 

  98. Ma, H. et al. LDLRAD3 is a receptor for Venezuelan equine encephalitis virus. Nature 588, 308–314 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Fongsaran, C. et al. Involvement of ATP synthase β subunit in chikungunya virus entry into insect cells. Arch. Virol. 159, 3353–3364 (2014).

    Article  CAS  PubMed  Google Scholar 

  100. Ghosh, A., Desai, A., Ravi, V., Narayanappa, G. & Tyagi, B. K. Chikungunya virus interacts with heat shock cognate 70 protein to facilitate its entry into mosquito cell line. Intervirology 60, 247–262 (2017).

    Article  CAS  PubMed  Google Scholar 

  101. MacDonald, G. H. & Johnston, R. E. Role of dendritic cell targeting in Venezuelan equine encephalitis virus pathogenesis. J. Virol. 74, 914–922 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Rudolph, K. E., Lessler, J., Moloney, R. M., Kmush, B. & Cummings, D. A. Incubation periods of mosquito-borne viral infections: a systematic review. Am. J. Trop. Med. Hyg. 90, 882–891 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  103. Waggoner, J. J. et al. Viremia and clinical presentation in nicaraguan patients infected with Zika virus, Chikungunya virus, and Dengue virus. Clin. Infect. Dis. 63, 1584–1590 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  104. Matusali, G. et al. Tropism of the Chikungunya virus. Viruses 11, 175 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Pingen, M. et al. Host inflammatory response to mosquito bites enhances the severity of Arbovirus infection. Immunity 44, 1455–1469 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Thangamani, S. et al. Host immune response to mosquito-transmitted chikungunya virus differs from that elicited by needle inoculated virus. PLoS ONE 5, e12137 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  107. Broeckel, R., Haese, N., Messaoudi, I. & Streblow, D. N. Nonhuman primate models of Chikungunya virus infection and disease (CHIKV NHP model). Pathogens 4, 662–681 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Labadie, K. et al. Chikungunya disease in nonhuman primates involves long-term viral persistence in macrophages. J. Clin. Invest. 120, 894–906 (2010). This paper describes a macaque infection model that recapitulates the viral, clinical and pathological features observed in human CHIKV disease. The study identified macrophages as the main cellular reservoirs during the late stages of CHIKV infection in vivo.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Lentscher, A. J. et al. Chikungunya virus replication in skeletal muscle cells is required for disease development. J. Clin. Invest. 130, 1466–1478 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Haese, N. N. et al. Animal models of Chikungunya virus infection and disease. J. Infect. Dis. 214, S482–S487 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Ruiz Silva, M., van der Ende-Metselaar, H., Mulder, H. L., Smit, J. M. & Rodenhuis-Zybert, I. A. Mechanism and role of MCP-1 upregulation upon chikungunya virus infection in human peripheral blood mononuclear cells. Sci. Rep. 6, 32288 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Her, Z. et al. Active infection of human blood monocytes by Chikungunya virus triggers an innate immune response. J. Immunol. 184, 5903–5913 (2010).

    Article  CAS  PubMed  Google Scholar 

  113. Ozden, S. et al. Human muscle satellite cells as targets of Chikungunya virus infection. PLoS ONE 2, e527 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  114. Lohachanakul, J. et al. Differences in response of primary human myoblasts to infection with recent epidemic strains of Chikungunya virus isolated from patients with and without myalgia. J. Med. Virol. 87, 733–739 (2015).

    Article  CAS  PubMed  Google Scholar 

  115. Rohatgi, A. et al. Infection of myofibers contributes to increased pathogenicity during infection with an epidemic strain of chikungunya virus. J. Virol. 88, 2414–2425 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  116. Hoarau, J. J. et al. Persistent chronic inflammation and infection by Chikungunya arthritogenic alphavirus in spite of a robust host immune response. J. Immunol. 184, 5914–5927 (2010).

    Article  CAS  PubMed  Google Scholar 

  117. Young, A. R. et al. Dermal and muscle fibroblasts and skeletal myofibers survive chikungunya virus infection and harbor persistent RNA. PLoS Pathog. 15, e1007993 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Suhrbier, A. Rheumatic manifestations of chikungunya: emerging concepts and interventions. Nat. Rev. Rheumatol. 15, 597–611 (2019). This review paper discusses the most current concepts of CHIKV-related rheumatic manifestations.

    Article  CAS  PubMed  Google Scholar 

  119. Roy, E., Shi, W., Duan, B. & Reid, S. P. Chikungunya virus infection impairs the function of osteogenic cells. mSphere 5, e00347-20 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  120. Chen, W. et al. Arthritogenic alphaviral infection perturbs osteoblast function and triggers pathologic bone loss. Proc. Natl Acad. Sci. USA 111, 6040–6045 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Amaral, J. K., Bilsborrow, J. B. & Schoen, R. T. Chronic Chikungunya arthritis and rheumatoid arthritis: what they have in common. Am. J. Med. 133, e91–e97 (2020).

    Article  CAS  PubMed  Google Scholar 

  122. Chang, A. Y. et al. Chikungunya arthritis mechanisms in the Americas: a cross-sectional analysis of chikungunya arthritis patients twenty-two months after infection demonstrating no detectable viral persistence in synovial fluid. Arthritis Rheumatol. 70, 585–593 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Raghavendhar, B. S. et al. Virus load and clinical features during the acute phase of Chikungunya infection in children. PLoS ONE 14, e0211036 (2019).

    Article  Google Scholar 

  124. Dutta, S. K., Pal, T., Saha, B., Mandal, S. & Tripathi, A. Copy number variation of Chikungunya ECSA virus with disease symptoms among Indian patients. J. Med. Virol. 86, 1386–1392 (2014).

    Article  CAS  PubMed  Google Scholar 

  125. Paul, B. J. & Sadanand, S. Chikungunya infection: a re-emerging epidemic. Rheumatol. Ther. 5, 317–326 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  126. Chhabra, M., Mittal, V., Bhattacharya, D., Rana, U. & Lal, S. Chikungunya fever: a re-emerging viral infection. Indian J. Med. Microbiol. 26, 5–12 (2008).

    Article  CAS  PubMed  Google Scholar 

  127. Couderc, T. et al. A mouse model for chikungunya: young age and inefficient type-I interferon signaling are risk factors for severe disease. PLoS Pathog. 4, e29 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  128. Win, M. K., Chow, A., Dimatatac, F., Go, C. J. & Leo, Y. S. Chikungunya fever in Singapore: acute clinical and laboratory features, and factors associated with persistent arthralgia. J. Clin. Virol. 49, 111–114 (2010).

    Article  CAS  PubMed  Google Scholar 

  129. Appassakij, H., Khuntikij, P., Kemapunmanus, M., Wutthanarungsan, R. & Silpapojakul, K. Viremic profiles in asymptomatic and symptomatic chikungunya fever: a blood transfusion threat? Transfusion 53, 2567–2574 (2013).

    Article  PubMed  Google Scholar 

  130. Lanciotti, R. S. et al. Chikungunya virus in US travelers returning from India, 2006. Emerg. Infect. Dis. 13, 764–767 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Laurent, P. et al. Development of a sensitive real-time reverse transcriptase PCR assay with an internal control to detect and quantify chikungunya virus. Clin. Chem. 53, 1408–1414 (2007).

    Article  CAS  PubMed  Google Scholar 

  132. Parola, P. et al. Novel Chikungunya virus variant in travelers returning from Indian Ocean islands. Emerg. Infect. Dis. 12, 1493–1499 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Gardner, J. et al. Chikungunya virus arthritis in adult wild-type mice. J. Virol. 84, 8021–8032 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Chow, A. et al. Persistent arthralgia induced by Chikungunya virus infection is associated with interleukin-6 and granulocyte macrophage colony-stimulating factor. J. Infect. Dis. 203, 149–157 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Noret, M. et al. Interleukin 6, RANKL, and osteoprotegerin expression by Chikungunya virus-infected human osteoblasts. J. Infect. Dis. 206, 455–457 (2012).

    Article  CAS  PubMed  Google Scholar 

  136. Sharp, T. M. et al. Clinical characteristics, histopathology, and tissue immunolocalization of Chikungunya virus antigen in fatal cases. Clin. Infect. Dis. 73, e345–e354 (2021).

    Article  CAS  PubMed  Google Scholar 

  137. Economopoulou, A. et al. Atypical Chikungunya virus infections: clinical manifestations, mortality and risk factors for severe disease during the 2005–2006 outbreak on Réunion. Epidemiol. Infect. 137, 534–541 (2009).

    Article  CAS  PubMed  Google Scholar 

  138. Tandale, B. V. et al. Systemic involvements and fatalities during Chikungunya epidemic in India, 2006. J. Clin. Virol. 46, 145–149 (2009).

    Article  PubMed  Google Scholar 

  139. Das, S., Sarkar, N., Majumder, J., Chatterjee, K. & Aich, B. Acute disseminated encephalomyelitis in a child with chikungunya virus infection. J. Pediatr. Infect. Dis. 9, 37–41 (2014).

    Google Scholar 

  140. Mehta, R. et al. The neurological complications of chikungunya virus: a systematic review. Rev. Med. Virol. 28, e1978 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  141. Maity, P., Roy, P., Basu, A., Das, B. & Ghosh, U. S. A case of ADEM following Chikungunya fever. J. Assoc. Physicians India 62, 441–442 (2014).

    PubMed  Google Scholar 

  142. Ganesan, K. et al. Chikungunya encephalomyeloradiculitis: report of 2 cases with neuroimaging and 1 case with autopsy findings. Am. J. Neuroradiol. 29, 1636–1637 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Gérardin, P. et al. Chikungunya virus-associated encephalitis: a cohort study on La Réunion Island, 2005-2009. Neurology 86, 94–102 (2016).

    Article  PubMed  Google Scholar 

  144. Inglis, F. M. et al. Neuropathogenesis of Chikungunya infection: astrogliosis and innate immune activation. J. Neurovirol. 22, 140–148 (2016).

    Article  CAS  PubMed  Google Scholar 

  145. Kashyap, R. S. et al. Determination of Toll-like receptor-induced cytokine profiles in the blood and cerebrospinal fluid of Chikungunya patients. Neuroimmunomodulation 21, 338–346 (2014).

    Article  CAS  PubMed  Google Scholar 

  146. da Silva, L. C. M. et al. Ocular manifestations of chikungunya infection: a systematic review. Pathogens 11, 412 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  147. Salceanu, S. O. & Raman, V. Recurrent chikungunya retinitis. BMJ Case Rep. 2018, bcr2017222864 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  148. Scripsema, N. K., Sharifi, E., Samson, C. M., Kedhar, S. & Rosen, R. B. Chikungunya-associated uveitis and exudative retinal detachment: a case report. Retinal Cases Brief. Rep. 9, 352–356 (2015).

    Article  Google Scholar 

  149. Babu, K., Kini, R., Philips, M. & Subbakrishna, D. K. Clinical profile of isolated viral anterior uveitis in a South Indian patient population. Ocul. Immunol. Inflamm. 22, 356–359 (2014).

    Article  PubMed  Google Scholar 

  150. Borgherini, G. et al. Outbreak of chikungunya on Reunion Island: early clinical and laboratory features in 157 adult patients. Clin. Infect. Dis. 44, 1401–1407 (2007).

    Article  PubMed  Google Scholar 

  151. Lee, V. J. et al. Simple clinical and laboratory predictors of Chikungunya versus dengue infections in adults. PLoS Negl. Trop. Dis. 6, e1786 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  152. Silva, J. V. J. et al. A scoping review of Chikungunya virus infection: epidemiology, clinical characteristics, viral co-circulation complications, and control. Acta Tropica 188, 213–224 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  153. Simon, F. et al. French guidelines for the management of chikungunya (acute and persistent presentations). November 2014. Méd. Mal. Infect. 45, 243–263 (2015). Comprehensive guidelines for the clinical management of CHIKV infection.

    Article  CAS  PubMed  Google Scholar 

  154. Chopra, A., Anuradha, V., Ghorpade, R. & Saluja, M. Acute Chikungunya and persistent musculoskeletal pain following the 2006 Indian epidemic: a 2-year prospective rural community study. Epidemiol. Infect. 140, 842–850 (2012).

    Article  CAS  PubMed  Google Scholar 

  155. Heath, C. J. et al. The identification of risk factors for chronic Chikungunya Arthralgia in Grenada, West Indies: a cross-sectional cohort study. Open Forum Infect. Dis. 5, ofx234 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  156. Sissoko, D. et al. Post-epidemic Chikungunya disease on Reunion Island: course of rheumatic manifestations and associated factors over a 15-month period. PLoS Negl. Trop. Dis. 3, e389 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  157. Manimunda, S. P. et al. Clinical progression of chikungunya fever during acute and chronic arthritic stages and the changes in joint morphology as revealed by imaging. Trans. R. Soc. Trop. Med. Hyg. 104, 392–399 (2010).

    Article  PubMed  Google Scholar 

  158. Rodríguez-Morales, A. J., Cardona-Ospina, J. A., Fernanda Urbano-Garzón, S. & Sebastian Hurtado-Zapata, J. Prevalence of post-chikungunya infection chronic inflammatory arthritis: a systematic review and meta-analysis. Arthritis Care Res. 68, 1849–1858 (2016).

    Article  Google Scholar 

  159. Ganu, M. A. & Ganu, A. S. Post-chikungunya chronic arthriti–our experience with DMARDs over two year follow up. J. Assoc. Physicians India 59, 83–86 (2011).

    PubMed  Google Scholar 

  160. Contopoulos-Ioannidis, D., Newman-Lindsay, S., Chow, C. & LaBeaud, A. D. Mother-to-child transmission of Chikungunya virus: a systematic review and meta-analysis. PLoS Negl. Trop. Dis. 12, e0006510 (2018). This systematic review provides a comprehensive overview of the risk for mother-to-child transmission, antepartum fetal deaths, symptomatic neonatal disease and neonatal deaths from maternal CHIKV infections during gestation.

    Article  PubMed  PubMed Central  Google Scholar 

  161. Gérardin, P. et al. Multidisciplinary prospective study of mother-to-child chikungunya virus infections on the island of La Réunion. PLoS Med. 5, e60 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  162. Fritel, X. et al. Chikungunya virus infection during pregnancy, Reunion, France, 2006. Emerg. Infect. Dis. 16, 418–425 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  163. Foeller, M. E. et al. Chikungunya infection in pregnancy–reassuring maternal and perinatal outcomes: a retrospective observational study. BJOG 128, 1077–1086 (2021).

    Article  CAS  PubMed  Google Scholar 

  164. Touret, Y. et al. Early maternal-fetal transmission of the Chikungunya virus [French]. Presse Med. 35, 1656–1658 (2006).

    Article  PubMed  Google Scholar 

  165. Gérardin, P. et al. Neurocognitive outcome of children exposed to perinatal mother-to-child Chikungunya virus infection: the CHIMERE cohort study on Reunion Island. PLoS Negl. Trop. Dis. 8, e2996 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  166. PAHO. Guidelines for the Clinical Diagnosis and Treatment of Dengue, Chikungunya, and Zika (Pan American Health Organization, 2022).

  167. WHO. Chikungunya fact sheet. WHO http://www.who.int/mediacentre/factsheets/fs327/en/ (2016).

  168. CDC. Chikungunya virus. CDC http://www.cdc.gov/chikungunya/geo/index.html (2022).

  169. Johnson, B. W., Russell, B. J. & Goodman, C. H. Laboratory diagnosis of Chikungunya virus infections and commercial sources for diagnostic assays. J. Infect. Dis. 214, S471–S474 (2016).

    Article  CAS  PubMed  Google Scholar 

  170. Natrajan, M. S., Rojas, A. & Waggoner, J. J. Beyond fever and pain: diagnostic methods for chikungunya virus. J. Clin. Microbiol. 57, e00350-19 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  171. The International Diagnostics Center. Chikungunya virus infection diagnostics landscape 2017. The International Diagnostics Center https://idc-dx.net/resource/chikungunya-virus-infection-diagnostics-landscape-2017 (2019).

  172. Patel, P. et al. A field-deployable reverse transcription recombinase polymerase amplification assay for rapid detection of the Chikungunya virus. PLoS Negl. Trop. Dis. 10, e0004953 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  173. Karlikow, M. et al. Field validation of the performance of paper-based tests for the detection of the Zika and chikungunya viruses in serum samples. Nat. Biomed. Eng. 6, 246–256 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Moreira, J., Brasil, P., Dittrich, S. & Siqueira, A. M. Mapping the global landscape of chikungunya rapid diagnostic tests: a scoping review. PLoS Negl. Trop. Dis. 16, e0010067 (2022). This paper maps the global availability of CHIKV RDTs and evaluates their accuracy for the diagnosis of CHIKV.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Boeras, D. et al. Evaluation of Zika rapid tests as aids for clinical diagnosis and epidemic preparedness. EClinicalMedicine 49, 101478 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  176. Prat, C. M. et al. Evaluation of commercially available serologic diagnostic tests for chikungunya virus. Emerg. Infect. Dis. 20, 2129–2132 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Fischer, C. et al. Robustness of serologic investigations for Chikungunya and Mayaro viruses following Coemergence. mSphere 5, e00915-19 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  178. Lima, M. D. R. Q., de Lima, R. C., de Azeredo, E. L. & Dos Santos, F. B. Analysis of a routinely used commercial anti-Chikungunya IgM ELISA reveals cross-reactivities with Dengue in Brazil: a new challenge for differential diagnosis? Diagnostics 11, 819 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  179. Harrison, V. R., Binn, L. N. & Randall, R. Comparative immunogenicities of chikungunya vaccines prepared in avian and mammalian tissues. Am. J. Trop. Med. Hyg. 16, 786–791 (1967).

    Article  CAS  PubMed  Google Scholar 

  180. Harrison, V. R., Eckels, K. H., Bartelloni, P. J. & Hampton, C. Production and evaluation of a formalin-killed Chikungunya vaccine. J. Immunol. 107, 643–647 (1971).

    Article  CAS  PubMed  Google Scholar 

  181. Reyes-Sandoval, A. 51 years in of Chikungunya clinical vaccine development: a historical perspective. Hum. Vaccin. Immunother. 15, 2351–2358 (2019). This review provides a very complete overview of the development of CHIKV vaccines that have reached the stage of clinical trials since the late 1960s up until 2018.

    Article  PubMed  PubMed Central  Google Scholar 

  182. Valneva. Valneva initiates rolling submission of FDA biologics license application for its single-shot Chikungunya vaccine candidate. Valneva https://valneva.com/press-release/valneva-initiates-rolling-submission-of-fda-biologics-license-application-for-its-single-shot-chikungunya-vaccine-candidate/ (2022).

  183. International Vaccine Institute. Chikungunya: advancing the world’s first Chikungunya vaccine. International Vaccine Institute https://www.ivi.int/what-we-do/disease-areas/chikungunya/ (2021).

  184. Chen, R. et al. Comprehensive genome scale phylogenetic study provides new insights on the global expansion of chikungunya virus. J. Virol. 90, 10600–10611 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  185. Katzelnick, L. C. et al. Antigenic evolution of dengue viruses over 20 years. Science 374, 999–1004 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  186. Milligan, G. N., Schnierle, B. S., McAuley, A. J. & Beasley, D. W. C. Defining a correlate of protection for chikungunya virus vaccines. Vaccine 37, 7427–7436 (2019). This report reviews the current status of non-clinical and clinical testing and potential challenges for defining a suitable surrogate or correlate of protection for CHIKV.

    Article  PubMed  Google Scholar 

  187. Thompson, D., Metz, S. W., Abad, C., Beaty, S. & Warfield, K. Immunological implications of diverse production approaches for Chikungunya virus-like particle vaccines. Vaccine 40, 3009–3017 (2022).

    Article  CAS  PubMed  Google Scholar 

  188. Kam, Y. W. et al. Longitudinal analysis of the human antibody response to Chikungunya virus infection: implications for serodiagnosis and vaccine development. J. Virol. 86, 13005–13015 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  189. Verma, P. et al. Analysis of antibody response (IgM, IgG, IgG3) to Chikungunya virus using panel of peptides derived from envelope protein for serodiagnosis. Clin. Chem. Lab. Med. 52, 297–307 (2014).

    Article  CAS  PubMed  Google Scholar 

  190. Kam, Y. W. et al. Early neutralizing IgG response to Chikungunya virus in infected patients targets a dominant linear epitope on the E2 glycoprotein. EMBO Mol. Med. 4, 330–343 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  191. Henss, L. et al. Analysis of humoral immune responses in chikungunya virus (CHIKV)-infected patients and individuals vaccinated with a candidate CHIKV vaccine. J. Infect. Dis. 221, 1713–1723 (2020).

    Article  CAS  PubMed  Google Scholar 

  192. Kam, Y. W. et al. Early appearance of neutralizing immunoglobulin G3 antibodies is associated with chikungunya virus clearance and long-term clinical protection. J. Infect. Dis. 205, 1147–1154 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  193. Galatas, B. et al. Long-lasting immune protection and other epidemiological findings after Chikungunya emergence in a Cambodian Rural Community, April 2012. PLoS Negl. Trop. Dis. 10, e0004281 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  194. Nitatpattana, N. et al. Long-term persistence of Chikungunya virus neutralizing antibodies in human populations of North Eastern Thailand. Virol. J. 11, 183 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  195. Valneva. Valneva reports positive end-of-phase 2 Chikungunya meeting with the U.S. FDA; sets stage for phase 3 study. Valneva https://valneva.com/press-release/valneva-reports-positive-end-of-phase-2-chikungunya-meeting-with-the-u-s-fda-sets-stage-for-phase-3-study/ (2020).

  196. Valneva. Valneva completes BLA submission to U.S. FDA for its single-shot chikungunya vaccine candidate. Valneva https://valneva.com/press-release/valneva-completes-bla-submission-to-u-s-fda-for-its-single-shot-chikungunya-vaccine-candidate/ (2022).

  197. Levitt, N. H. et al. Development of an attenuated strain of chikungunya virus for use in vaccine production. Vaccine 4, 157–162 (1986).

    Article  CAS  PubMed  Google Scholar 

  198. McClain, D. J. et al. Immunologic interference from sequential administration of live attenuated alphavirus vaccines. J. Infect. Dis. 177, 634–641 (1998).

    Article  CAS  PubMed  Google Scholar 

  199. Edelman, R. et al. Phase II safety and immunogenicity study of live chikungunya virus vaccine TSI-GSD-218. Am. J. Trop. Med. Hyg. 62, 681–685 (2000).

    Article  CAS  PubMed  Google Scholar 

  200. Roques, P. et al. Attenuated and vectored vaccines protect nonhuman primates against Chikungunya virus. JCI Insight 2, e83527 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  201. Wressnigg, N. et al. Single-shot live-attenuated chikungunya vaccine in healthy adults: a phase 1, randomised controlled trial. Lancet Infect. Dis. 20, 1193–1203 (2020).

    Article  PubMed  Google Scholar 

  202. Roques, P. et al. Effectiveness of CHIKV vaccine VLA1553 demonstrated by passive transfer of human sera. JCI Insight 7, e160173 (2022). This study evaluated the effectiveness of the live-attenuated CHIKV vaccine VLA1553 against wild-type CHIKV infection by using passive transfer of sera from vaccinated volunteers to non-human primates subsequently exposed to wild-type CHIKV and established a serological surrogate of protection. The study demonstrated that human VLA1553 sera transferred to non-human primates conferred complete protection from CHIKV viraemia and fever after challenge with homologous wild-type CHIKV and that serum transfer protected animals from other CHIKV-associated clinical symptoms and from CHIKV persistence in tissue.

    Article  PubMed  PubMed Central  Google Scholar 

  203. Mohsen, M. O. & Bachmann, M. F. Virus-like particle vaccinology, from bench to bedside. Cell Mol. Immunol. 19, 993–1011 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  204. Chang, L. J. et al. Safety and tolerability of chikungunya virus-like particle vaccine in healthy adults: a phase 1 dose-escalation trial. Lancet 384, 2046–2052 (2014).

    Article  CAS  PubMed  Google Scholar 

  205. Goo, L. et al. A virus-like particle vaccine elicits broad neutralizing antibody responses in humans to all Chikungunya virus genotypes. J. Infect. Dis. 214, 1487–1491 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  206. Bennett, S. R. et al. Safety and immunogenicity of PXVX0317, an aluminium hydroxide-adjuvanted chikungunya virus-like particle vaccine: a randomised, double-blind, parallel-group, phase 2 trial. Lancet Infect. Dis. 22, 1343–1355 (2022). This paper reports on a randomized, double-blind, parallel-group, phase II trial evaluating the safety and immunogenicity of PXVX0317, an aluminium hydroxide-adjuvanted formulation of a CHIKV VLP vaccine.

    Article  CAS  PubMed  Google Scholar 

  207. US National Library of Medicine. ClinicalTrials.gov http://www.clinicaltrials.gov/ct2/show/NCT05072080 (2022).

  208. PRNewswire. FDA grants PaxVax fast track designation for its Chikungunya vaccine. PRNewswire https://www.prnewswire.com/news-releases/fda-grants-paxvax-fast-track-designation-for-its-chikungunya-vaccine-300642602.html (2018).

  209. Reisinger, E. C. et al. Immunogenicity, safety, and tolerability of the measles-vectored chikungunya virus vaccine MV-CHIK: a double-blind, randomised, placebo-controlled and active-controlled phase 2 trial. Lancet 392, 2718–2727 (2019).

    Article  PubMed  Google Scholar 

  210. Ramsauer, K. et al. Immunogenicity, safety, and tolerability of a recombinant measles-virus-based chikungunya vaccine: a randomised, double-blind, placebo-controlled, active-comparator, first-in-man trial. Lancet Infect. Dis. 15, 519–527 (2015).

    Article  CAS  PubMed  Google Scholar 

  211. Brandler, S. et al. A recombinant measles vaccine expressing chikungunya virus-like particles is strongly immunogenic and protects mice from lethal challenge with chikungunya virus. Vaccine 31, 3718–3725 (2013).

    Article  CAS  PubMed  Google Scholar 

  212. Rossi, S. L. et al. Immunogenicity and efficacy of a measles virus-vectored Chikungunya vaccine in nonhuman primates. J. Infect. Dis. 220, 735–742 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  213. Themis Bioscience GmbH. Vaccines and related biological products advisory committee meeting: 08 November 2019: Themis company briefing document. Themis Bioscience GmbH https://fda.report/media/132288/VRBPAC-11.08.19-Meeting-Briefing-Document-Sponsor.pdf (2019).

  214. businesswire. Themis Bioscience receives FDA fast track designation for Chikungunya vaccine candidate. businesswire https://www.businesswire.com/news/home/20190225005236/en/Themis-Bioscience-Receives-FDA-Fast-Track-Designation-for-Chikungunya-Vaccine-Candidate (2019).

  215. European Medicines Agency. List of medicines currently in PRIME scheme. EMA https://www.ema.europa.eu/documents/report/list-products-granted-eligibility-prime_en-0.xlsx (2023).

  216. CEPI. CEPI awards up to US$21 million to Themis Bioscience for phase 3 Chikungunya vaccine development. CEPI https://cepi.net/news_cepi/cepi-awards-up-to-us21-million-to-themis-bioscience-for-phase-3-chikungunya-vaccine-development/ (2019).

  217. US National Library of Medicine. ClinicalTrials.gov http://www.clinicaltrials.gov/ct2/show/NCT03807843 (2022).

  218. US National Library of Medicine. ClinicalTrials.gov http://www.clinicaltrials.gov/ct2/show/NCT03101111 (2021).

  219. Tiwari, M. et al. Assessment of immunogenic potential of Vero adapted formalin inactivated vaccine derived from novel ECSA genotype of Chikungunya virus. Vaccine 27, 2513–2522 (2009).

    Article  CAS  PubMed  Google Scholar 

  220. CEPI. CEPI awards up to US$14.1 million to consortium of IVI and Bharat Biotech to advance development of Chikungunya vaccine in collaboration with Ind-CEPI. CEPI https://cepi.net/news_cepi/cepi-awards-up-to-us-14-1-million-to-consortium-of-ivi-and-bharat-biotech-to-advance-development-of-chikungunya-vaccine-in-collaboration-with-ind-cepi/ (2020).

  221. Shaw, C. et al. Safety and immunogenicity of a mRNA-based chikungunya vaccine in a phase 1 dose-ranging trial. Int. J. Infect. Dis. 79, 17 (2019).

    Article  Google Scholar 

  222. United States Securities and Exchange Commission. Moderna Inc. United States Securities and Exchange Commission https://www.sec.gov/Archives/edgar/data/1682852/000168285219000009/moderna10-k12312018.htm (2018).

  223. Folegatti, P. M. et al. A single dose of ChAdOx1 Chik vaccine induces neutralizing antibodies against four chikungunya virus lineages in a phase 1 clinical trial. Nat. Commun. 12, 4636 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  224. Wang, E., Kim, D. Y., Weaver, S. C. & Frolov, I. Chimeric Chikungunya viruses are nonpathogenic in highly sensitive mouse models but efficiently induce a protective immune response. J. Virol. 85, 9249–9252 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  225. Erasmus, J. H. et al. Utilization of an Eilat virus-based chimera for serological detection of Chikungunya infection. PLoS Negl. Trop. Dis. 9, e0004119 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  226. Chattopadhyay, A., Wang, E., Seymour, R., Weaver, S. C. & Rose, J. K. A chimeric vesiculo/alphavirus is an effective alphavirus vaccine. J. Virol. 87, 395–402 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  227. van den Doel, P. et al. Recombinant modified vaccinia virus Ankara expressing glycoprotein E2 of Chikungunya virus protects AG129 mice against lethal challenge. PLoS Negl. Trop. Dis. 8, e3101 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  228. García-Arriaza, J. et al. A novel poxvirus-based vaccine, MVA-CHIKV, is highly immunogenic and protects mice against chikungunya infection. J. Virol. 88, 3527–3547 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  229. Kose, N. et al. A lipid-encapsulated mRNA encoding a potently neutralizing human monoclonal antibody protects against chikungunya infection. Sci. Immunol. 4, eaaw6647 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  230. August, A. et al. A phase 1 trial of lipid-encapsulated mRNA encoding a monoclonal antibody with neutralizing activity against Chikungunya virus. Nat. Med. 27, 2224–2233 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  231. Wahid, B., Ali, A., Rafique, S. & Idrees, M. Global expansion of chikungunya virus: mapping the 64-year history. Int. J. Infect. Dis. 58, 69–76 (2017).

    Article  PubMed  Google Scholar 

  232. Perich, M. J., Davila, G., Turner, A., Garcia, A. & Nelson, M. Behavior of resting Aedes aegypti (Culicidae: Diptera) and its relation to ultra-low volume adulticide efficacy in Panama City, Panama. J. Med. Entomol. 37, 541–546 (2000).

    Article  CAS  PubMed  Google Scholar 

  233. Barrera, R. New tools for Aedes control: mass trapping. Curr. Opin. Insect Sci. 52, 100942 (2022).

    Article  PubMed  Google Scholar 

  234. Juarez, J. G. et al. Variable coverage in an autocidal gravid ovitrap intervention impacts efficacy of Aedes aegypti control. J. Appl. Ecol. 58, 2075–2086 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  235. Sippy, R. et al. Ingested insecticide to control Aedes aegypti: developing a novel dried attractive toxic sugar bait device for intra-domiciliary control. Parasit. Vectors 13, 78 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  236. Tambwe, M. M. et al. Semi-field evaluation of the exposure-free mosquito electrocuting trap and BG-Sentinel trap as an alternative to the human landing catch for measuring the efficacy of transfluthrin emanators against Aedes aegypti. Parasit. Vectors 14, 265 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  237. Hapairai, L. K. et al. Evaluation of large volume yeast interfering RNA lure-and-kill ovitraps for attraction and control of Aedes mosquitoes. Med. Vet. Entomol. 35, 361–370 (2021).

    Article  CAS  PubMed  Google Scholar 

  238. Leandro, A. S. et al. Citywide integrated Aedes aegypti mosquito surveillance as early warning system for arbovirus transmission, Brazil. Emerg. Infect. Dis. 28, 701–706 (2022).

    Article  PubMed  Google Scholar 

  239. Wang, G. H. et al. Combating mosquito-borne diseases using genetic control technologies. Nat. Commun. 12, 4388 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  240. Antunes de Brito, C. A. et al. Pharmacologic management of pain in patients with Chikungunya: a guideline. Rev. Soc. Bras. Med. Trop. 49, 668–679 (2016). Comprehensive guidelines for the clinical management of CHIKV infection.

    Article  Google Scholar 

  241. Webb, E. et al. An evaluation of global Chikungunya clinical management guidelines: a systematic review. eClinicalMedicine 54, 101672 (2022). The most recent comprehensive guidelines for the clinical management of CHIKV infection.

    Article  PubMed  PubMed Central  Google Scholar 

  242. Scott, S. S. et al. Immunoglobulin-responsive chikungunya encephalitis: two case reports. J. Neurovirol. 23, 625–631 (2017).

    Article  CAS  PubMed  Google Scholar 

  243. Fernandes, A. I. V., Souza, J. R., Silva, A. R., Cruz, S. B. S. C. & Castellano, L. R. C. Immunoglobulin therapy in a patient with severe chikungunya fever and vesiculobullous lesions. Front. Immunol. 10, 1498 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  244. Marques, C. D. L. et al. Recommendations of the Brazilian Society of Rheumatology for the diagnosis and treatment of chikungunya fever. Part 2 — treatment. Rev. Bras. Reumatol. 57 (Suppl. 2), 438–451 (2017).

    Article  Google Scholar 

  245. Zaid, A. et al. Chikungunya arthritis: implications of acute and chronic inflammation mechanisms on disease management. Arthritis Rheumatol. 70, 484–495 (2018).

    Article  PubMed  Google Scholar 

  246. Bouhassira, D. et al. Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4). Pain 114, 29–36 (2005).

    Article  PubMed  Google Scholar 

  247. de Andrade, D. C., Jean, S., Clavelou, P., Dallel, R. & Bouhassira, D. Chronic pain associated with the Chikungunya fever: long lasting burden of an acute illness. BMC Infect. Dis. 10, 31 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  248. Graham, B. S., Repik, P. M. & Yactayo, S. Chikungunya in the Americas: recommendations and conclusions. J. Infect. Dis. 214, S510–S513 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  249. Burt, F. J., Rolph, M. S., Rulli, N. E., Mahalingam, S. & Heise, M. T. Chikungunya: a re-emerging virus. Lancet 379, 662–671 (2012).

    Article  PubMed  Google Scholar 

  250. WHO. Guidelines on clinical management of Chikungunya fever. WHO https://www.who.int/westernpacific/publications-detail/guidelines-on-clinical-management-of-chikungunya-fever (2019).

  251. De Lamballerie, X. et al. On chikungunya acute infection and chloroquine treatment. Vector Borne Zoonotic Dis. 8, 837–839 (2008).

    Article  PubMed  Google Scholar 

  252. Kumar, R., Ahmed, S., Parray, H. A. & Das, S. Chikungunya and arthritis: an overview. Travel Med. Infect. Dis. 44, 102168 (2021).

    Article  PubMed  Google Scholar 

  253. Pitt Gameiro Sales, G. M. et al. Treatment of chikungunya chronic arthritis: a systematic review. Rev. Assoc. Med. Bras. 64, 63–70 (2018).

    Article  Google Scholar 

  254. Vairo, F. et al. Chikungunya: epidemiology, pathogenesis, clinical features, management, and prevention. Infect. Dis. Clin. North Am. 33, 1003–1025 (2019).

    Article  PubMed  Google Scholar 

  255. Pathak, H., Mohan, M. C. & Ravindran, V. Chikungunya arthritis. Clin. Med. 19, 381–385 (2019).

    Article  Google Scholar 

  256. Bank, A. M., Batra, A., Colorado, R. A. & Lyons, J. L. Myeloradiculopathy associated with chikungunya virus infection. J. Neurovirol. 22, 125–128 (2016).

    Article  CAS  PubMed  Google Scholar 

  257. Simon, F., Javelle, E. & Gasque, P. Chikungunya virus infections. N. Engl. J. Med. 373, 93–94 (2015).

    Article  CAS  PubMed  Google Scholar 

  258. Radu, A.-F. & Bungau, S. G. Management of rheumatoid arthritis: an overview. Cells 10, 2857 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  259. Kennedy Amaral Pereira, J. & Schoen, R. T. Management of chikungunya arthritis. Clin. Rheumatol. 36, 2179–2186 (2017).

    Article  CAS  PubMed  Google Scholar 

  260. McHugh, J. Long-term effects of chikungunya. Nat. Rev. Rheumatol. 14, 62–62 (2018).

    Article  PubMed  Google Scholar 

  261. Javelle, E. et al. Specific management of post-chikungunya rheumatic disorders: a retrospective study of 159 cases in Reunion Island from 2006-2012. PLoS Negl. Trop. Dis. 9, e0003603 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  262. Pandya, S. Methotrexate and hydroxychloroquine combination therapy in chronic chikungunya arthritis: a 16 week study. Indian J. Rheumatol. 3, 93–97 (2008).

    Article  Google Scholar 

  263. Faraone, I., Labanca, F., Ponticelli, M., De Tommasi, N. & Milella, L. Recent clinical and preclinical studies of hydroxychloroquine on RNA viruses and chronic diseases: a systematic review. Molecules 25, 5318 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  264. Ravindran, V. & Alias, G. Efficacy of combination DMARD therapy vs. hydroxychloroquine monotherapy in chronic persistent chikungunya arthritis: a 24-week randomized controlled open label study. Clin. Rheumatol. 36, 1335–1340 (2017).

    Article  PubMed  Google Scholar 

  265. Neumann, I. L. et al. Resistance exercises improve physical function in chronic Chikungunya fever patients: a randomized controlled trial. Eur. J. Phys. Rehabil. Med. 57, 620–629 (2021).

    Article  PubMed  Google Scholar 

  266. Silva-Filho, E. et al. Neuromodulation treats Chikungunya arthralgia: a randomized controlled trial. Sci. Rep. 8, 16010 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  267. Nascimento, A. S. D. et al. Ten sessions of transcranial direct current stimulation for chronic chikungunya arthralgia: study protocol for a randomised clinical trial. BMJ Open 12, e065387 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  268. Queyriaux, B. et al. Clinical burden of chikungunya virus infection. Lancet Infect. Dis. 8, 2–3 (2008).

    Article  PubMed  Google Scholar 

  269. Crosby, L. et al. Severe manifestations of chikungunya virus in critically ill patients during the 2013-2014 Caribbean outbreak. Int. J. Infect. Dis. 48, 78–80 (2016).

    Article  PubMed  Google Scholar 

  270. Mercado, M. et al. Clinical and histopathological features of fatal cases with dengue and chikungunya virus co-infection in Colombia, 2014 to 2015. Eurosurveillance 21, 30244 (2016).

    Article  Google Scholar 

  271. Ramachandran, V. et al. Impact of Chikungunya on health related quality of life Chennai, South India. PLoS ONE 7, e51519 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  272. Wei Chiam, C., Fun Chan, Y., Chai Ong, K., Thong Wong, K. & Sam, I. C. Neurovirulence comparison of chikungunya virus isolates of the Asian and East/Central/South African genotypes from Malaysia. J. Gen. Virol. 96, 3243–3254 (2015).

    Article  PubMed  Google Scholar 

  273. Doran, C. et al. The clinical manifestation and the influence of age and comorbidities on long-term chikungunya disease and health-related quality of life: a 60-month prospective cohort study in Curaçao. BMC Infect. Dis. 22, 948 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  274. Lopes Marques, C. D. et al. Recommendations of the Brazilian Society of Rheumatology for diagnosis and treatment of Chikungunya fever. Part 1 — diagnosis and special situations. Rev. Bras. Reumatol. Engl. Ed. 57, 421–437 (2017).

    Google Scholar 

  275. Martõâ-Carvajal, A. et al. Interventions for treating patients with chikungunya virus infection-related rheumatic and musculoskeletal disorders: a systematic review. PLoS ONE 12, e0179028 (2017).

    Article  Google Scholar 

  276. Watson, H. et al. Stiffness, pain, and joint counts in chronic chikungunya disease: relevance to disability and quality of life. Clin. Rheumatol. 39, 1679–1686 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  277. Doran, C. et al. Long-term Chikungunya sequelae and quality of life 2.5 years post-acute disease in a prospective cohort in Curaçao. PLoS Negl. Trop. Dis. 16, e0010142 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  278. Marimoutou, C., Ferraro, J., Javelle, E., Deparis, X. & Simon, F. Chikungunya infection: self-reported rheumatic morbidity and impaired quality of life persist 6 years later. Clin. Microbiol. Infect. 21, 688–693 (2015).

    Article  CAS  PubMed  Google Scholar 

  279. Venter, M. Assessing the zoonotic potential of arboviruses of African origin. Curr. Opin. Virol. 28, 74–84 (2018).

    Article  PubMed  Google Scholar 

  280. Rezza, G., Chen, R. & Weaver, S. C. O’nyong-nyong fever: a neglected mosquito-borne viral disease. Pathog. Glob. Health 111, 271–275 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  281. Weaver, S. C., Charlier, C., Vasilakis, N. & Lecuit, M. Zika, Chikungunya, and other emerging vector-borne viral diseases. Annu. Rev. Med. 69, 395–408 (2018).

    Article  CAS  PubMed  Google Scholar 

  282. Guzman, M. G., Gubler, D. J., Izquierdo, A., Martinez, E. & Halstead, S. B. Dengue infection. Nat. Rev. Dis. Primers 2, 16055 (2016).

    Article  PubMed  Google Scholar 

  283. Katzelnick, L. C. et al. Zika virus infection enhances future risk of severe dengue disease. Science 369, 1123–1128 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  284. Katzelnick, L. C. et al. Antibody-dependent enhancement of severe dengue disease in humans. Science 358, 929–932 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  285. Kam, Y. W. et al. Sero-prevalence and cross-reactivity of chikungunya virus specific anti-E2EP3 antibodies in arbovirus-infected patients. PLoS Negl. Trop. Dis. 9, e3445 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  286. Torres-Ruesta, A., Chee, R. S. & Ng, L. F. P. Insights into antibody-mediated alphavirus immunity and vaccine development landscape. Microorganisms 9, 899 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  287. Babaeimarzangou, S. S. et al. Vaccine development for zoonotic viral diseases caused by positive-sense single-stranded RNA viruses belonging to the Coronaviridae and Togaviridae families (Review). Exp. Ther. Med. 25, 42 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  288. WHO. WHO consultation on Chikungunya vaccine evaluation. WHO https://www.who.int/docs/default-source/blue-print/chikungunya-vaccines-workshop-29-november-2018.pdf?sfvrsn=7c40e201_2 (2018).

  289. Malonis, R. J. et al. Near-germline human monoclonal antibodies neutralize and protect against multiple arthritogenic alphaviruses. Proc. Natl Acad. Sci. USA 118, e2100104118 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  290. Zhou, Q. F. et al. Structural basis of Chikungunya virus inhibition by monoclonal antibodies. Proc. Natl Acad. Sci. USA 117, 27637–27645 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  291. Kim, A. S. & Diamond, M. S. A molecular understanding of alphavirus entry and antibody protection. Nat. Rev. Microbiol. https://doi.org/10.1038/s41579-022-00825-7 (2022). This review highlights recent advances in our understanding of the host factors required for alphavirus entry, the mechanisms of action by which protective antibodies inhibit different steps in the alphavirus infection cycle and candidate alphavirus vaccines currently under clinical evaluation that focus on humoral immunity.

    Article  PubMed  PubMed Central  Google Scholar 

  292. Jin, J. & Simmons, G. Antiviral functions of monoclonal antibodies against Chikungunya virus. Viruses 11, 305 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  293. Fox, J. M. et al. Broadly neutralizing alphavirus antibodies bind an epitope on E2 and inhibit entry and egress. Cell 163, 1095–1107 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  294. Abdelnabi, R. & Delang, L. Antiviral strategies against arthritogenic alphaviruses. Microorganisms 8, 1365 (2020). This article provides a complete overview of the reported antiviral strategies against arthritogenic alphaviruses and highlights future perspectives for the development and proper use of such antivirals.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  295. Skidmore, A. M. & Bradfute, S. B. The life cycle of the alphaviruses: from an antiviral perspective. Antivir. Res. 209, 105476 (2023).

    Article  CAS  PubMed  Google Scholar 

  296. Battisti, V., Urban, E. & Langer, T. Antivirals against the Chikungunya virus. Viruses 13, 1307 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  297. Tripathi, P. K. et al. Evaluation of novobiocin and telmisartan for anti-CHIKV activity. Virology 548, 250–260 (2020).

    Article  CAS  PubMed  Google Scholar 

  298. Delang, L., Abdelnabi, R. & Neyts, J. Favipiravir as a potential countermeasure against neglected and emerging RNA viruses. Antivir. Res. 153, 85–94 (2018).

    Article  CAS  PubMed  Google Scholar 

  299. Ferreira, A. C. et al. Beyond members of the flaviviridae family, sofosbuvir also inhibits Chikungunya virus replication. Antimicrob. Agents Chemother. 63, e01389-18 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  300. Fox, J. M. et al. Optimal therapeutic activity of monoclonal antibodies against chikungunya virus requires Fc-FcgammaR interaction on monocytes. Sci. Immunol. 4, eaav5062 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  301. WHO. Prioritizing diseases for research and development in emergency contexts. WHO https://www.who.int/activities/prioritizing-diseases-for-research-and-development-in-emergency-contexts (2015).

  302. Africa CDC. Risk ranking and prioritization of epidemic-prone diseases. Africa CDC https://africacdc.org/download/risk-ranking-and-prioritization-of-epidemic-prone-diseases/ (2023).

  303. Kamal, M., Kenawy, M. A., Rady, M. H., Khaled, A. S. & Samy, A. M. Mapping the global potential distributions of two arboviral vectors Aedes aegypti and Ae. albopictus under changing climate. PLoS ONE 13, e0210122 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  304. Kraemer, M. U. G. et al. Past and future spread of the arbovirus vectors Aedes aegypti and Aedes albopictus. Nat. Microbiol. 4, 854–863 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  305. Swan, T. et al. A literature review of dispersal pathways of Aedes albopictus across different spatial scales: implications for vector surveillance. Parasit. Vectors 15, 303 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  306. Oliveira, S., Rocha, J., Sousa, C. A. & Capinha, C. Wide and increasing suitability for Aedes albopictus in Europe is congruent across distribution models. Sci. Rep. 11, 9916 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  307. ECDC. Mosquito maps. ECDC https://ecdc.europa.eu/en/disease-vectors/surveillance-and-disease-data/mosquito-maps (2023).

  308. Strauss, E. G., Rice, C. M. & Strauss, J. H. Sequence coding for the alphavirus nonstructural proteins is interrupted by an opal termination codon. Proc. Natl Acad. Sci. USA 80, 5271–5275 (1983).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  309. Chen, K. C. et al. Comparative analysis of the genome sequences and replication profiles of chikungunya virus isolates within the East, Central and South African (ECSA) lineage. Virol. J. 10, 169 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  310. Tanabe, I. S. B. et al. Cellular and molecular immune response to Chikungunya virus infection. Front. Cell Infect. Microbiol. 8, 345 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  311. Ng, L. F. P. Immunopathology of Chikungunya virus infection: lessons learned from patients and animal models. Annu. Rev. Virol. 4, 413–427 (2017).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank C. Maeckelbergh, M. A. Kiener and P. Selhorst for their assistance during the revisions.

Author information

Authors and Affiliations

  1. Virology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine Antwerp, Antwerp, Belgium

    Koen Bartholomeeusen & Kevin K. Ariën

  2. Unité de Recherche en Pharmaco-Immunologie (UR-EPI), Université et CHU de La Réunion, Saint-Denis, France

    Matthieu Daniel & Philippe Gasque

  3. Service de Médecine d’Urgences-SAMU-SMUR, CHU de La Réunion, Saint-Denis, France

    Matthieu Daniel

  4. Department of Pediatrics, Division of Infectious Disease, Stanford University School of Medicine, Stanford, CA, USA

    Desiree A. LaBeaud

  5. Laboratoire d’Immunologie Clinique et Expérimentale Océan Indien LICE-OI, Université de La Réunion, Saint-Denis, France

    Philippe Gasque

  6. Clinical Research Department, London School of Hygiene and Tropical Medicine, London, UK

    Rosanna W. Peeling

  7. Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    Kathryn E. Stephenson

  8. Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA

    Kathryn E. Stephenson

  9. A*STAR Infectious Diseases Labs, Agency for Science, Technology and Research, Singapore, Singapore

    Lisa F. P. Ng

  10. National Institute of Health Research, Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, UK

    Lisa F. P. Ng

  11. Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK

    Lisa F. P. Ng

  12. Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium

    Kevin K. Ariën

Authors
  1. Koen Bartholomeeusen
    View author publications

    Search author on:PubMed Google Scholar

  2. Matthieu Daniel
    View author publications

    Search author on:PubMed Google Scholar

  3. Desiree A. LaBeaud
    View author publications

    Search author on:PubMed Google Scholar

  4. Philippe Gasque
    View author publications

    Search author on:PubMed Google Scholar

  5. Rosanna W. Peeling
    View author publications

    Search author on:PubMed Google Scholar

  6. Kathryn E. Stephenson
    View author publications

    Search author on:PubMed Google Scholar

  7. Lisa F. P. Ng
    View author publications

    Search author on:PubMed Google Scholar

  8. Kevin K. Ariën
    View author publications

    Search author on:PubMed Google Scholar

Contributions

Introduction (K.K.A. and K.B.); Epidemiology (K.K.A. and K.B.); Mechanisms/pathophysiology (K.K.A., K.B., D.A.L. and L.F.P.N.); Diagnosis, screening and prevention (K.K.A., K.B., R.W.P. and K.E.S.); Management (K.K.A., M.D. and P.G.); Quality of life (K.K.A., M.D. and P.G.); Outlook (K.K.A., K.B., D.A.L., R.W.P., K.E.S. and L.F.P.N.); Overview of the Primer (K.K.A. and K.B.).

Corresponding author

Correspondence to Kevin K. Ariën.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Reviews Disease Primers thanks S. C. Weaver, S. Mahalingam and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bartholomeeusen, K., Daniel, M., LaBeaud, D.A. et al. Chikungunya fever. Nat Rev Dis Primers 9, 17 (2023). https://doi.org/10.1038/s41572-023-00429-2

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41572-023-00429-2

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing