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

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. 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 dengueendemic 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]. During the ongoing IOL CHIK epidemics, the nearly completely naive 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