Are Chikungunya and Other Zoonotic Diseases Unbeatable?

A recent review article published in Curr Opin Virol on the emergence and transmission history of the chikungunya virus (CHIKV) may provide infectious disease specialists with an enhanced understanding of how to predict the outcome of current and future CHIKV outbreaks.

CHIKV is a mosquito-borne alphavirus that causes CHIK fever, a sudden onset illness typically accompanied by severe joint pain (arthralgia), as well as sequelae including post-CHIK chronic inflammatory rheumatism. It is known to circulate in forested regions of sub-Saharan Africa in ancestral sylvatic, enzootic transmission cycles involving nonhuman primate (NHP) hosts and arboreal mosquito vectors.^1,2 The virus can also enter an urban transmission cycle through transmission from animals to humans. The spread of CHIKV and its associated clinical manifestations amongst humans has been heavily amplified by the rapid transit between distant regions in our increasingly small world.

Aside from its clinical burden, CHIKV outbreaks can also have large-scale economic ramifications. For example, the results of a cost burden analysis of the 2014 CHIKV disease outbreak in Columbia estimated the associated costs to be at least $73.6 million.³ At present, there are no specific therapeutic measures for treating or preventing CHIKV infection, no known risk factors for severe or chronic forms of the disease, and a lack of studies describing how to manage disease sequelae.⁴

First author Konstantin A. Tsetsarkin, PhD, a research scientist working in the National Institute of Allergy and Infectious Diseases at the National Institutes of Health in Bethesda, Maryland, describes the emergence history of CHIKV, the phylogenetic reconstruction of CHIKV evolution, its enzootic and urban transmission, and how its host range and distribution are expanding.

The historical perspective includes a description of the initially reported outbreak amongst humans in present-day Tanzania in the early 1950s, as well as subsequent human epidemics in Africa, Asia, Europe, the South Pacific, and the Americas This discussion is intertwined with information on the multiple CHIKV lineages (West African, East/Central/South African, Asian, and Indian Ocean) and their movements throughout the world over time.

The reviewed data pertaining to the phylogenetic reconstruction of CHIKV evolution explain the relationships among enzootic and endemic/epidemic CHIKV lineages. Additionally, these data highlight changes in CHIKV biology that enhance transmission by a new vector, Aedes albopictus.

Regarding enzootic transmission cycles, Tsetsarkin and colleagues suggest that, ... "CHIKV appears to use several different NHPs and Aedes spp. vectors for enzootic circulation in Africa." The reviewed data pertaining to the role of various NHPs in enzootic CHIKV amplification suggest that while NHPs are important amplification hosts, a role for other vertebrates in enzootic maintenance cannot be ruled out at present.

In the review of data on vector and primate host range changes associated with urban CHIKV emergence, Tsetsarkin et al state that, "... presumably a person infected from enzootic CHIKV spillover occasionally reaches a location where populations of these mosquitoes and their contact with people are sufficient to initiate interhuman transmission." There is also an in-depth discussion of how CHIKV mutations have allowed for increased CHIKV fitness for human infection.

The review concludes with the speculation that, "Its historic evidence of repeated reemergence combined with the lack of evidence for adaptive barriers to initiation of the urban transmission cycle by enzootic progenitors strongly suggests that CHIKV will continue to emerge periodically and indefinitely from Africa to initiate epidemics." Additionally, Tsetsarkin and colleagues assert that, "Experimental infections of New World primates and sylvatic, primatophilic mosquitoes as well as incorporation of sylvatic regions into CHIKV surveillance will be important for determining the potential for enzootic establishment, which could stabilize CHIKV endemicity in the Americas and ensure continuous risk."

The information presented in the review and its conclusions highlight a long list of unanswered questions regarding the future of CHIKV transmission, strains, vectors, hosts, and affected regions, but strongly suggest that the ever-mutating CHIKV strains will continue to be a source of both enzootic and urban transmission worthy of careful and continuous surveillance.

William Perlman, PhD, CMPP is a former research scientist currently working as a medical/scientific content development specialist. He earned his BA in Psychology from Johns Hopkins University, his PhD in Neuroscience at UCLA, and completed three years of postdoctoral fellowship in the Neuropathology Section of the Clinical Brain Disorders Branch of the National Institute of Mental Health.

References

1. Volk SM, Chen R, Tsetsarkin KA, et al. Genome-scale phylogenetic analyses of chikungunya virus reveal independent emergences of recent epidemics and various evolutionary rates. J Virol 2010;84:6497—504.
2. Powers AM, Brault AC, Tesh RB, Weaver SC. Re-emergence of Chikungunya and O’nyong-nyong viruses: evidence for distinct geographical lineages and distant evolutionary relationships. J Gen Virol 2000;81:471—9.
3. Cardona-Ospina JA, Villamil-Gómez WE, Jimenez-Canizales CE, Castañeda-Hernández DM, Rodríguez-Morales AJ. Estimating the burden of disease and the economic cost attributable to chikungunya, Colombia, 2014. Trans R Soc Trop Med Hyg 2015;109:793—802.
4. Cardona-Ospina JA, Vera-Polania F, Rodriguez-Morales AJ. Chikungunya or not, differential diagnosis and the importance of laboratory confirmation for clinical and epidemiological research: comment on the article by Rosario et al. Clin Rheumatol 2016;35:829—30.