Chikungunya (CHIK) is a mosquito-borne febrile disease caused by the chikungunya virus (CHIKV), which belongs to the genus Alphavirus of the Togaviridae family [1]. The CHIKV has a single-stranded, positive-sense RNA genome, which consists of 5′-nsP1-nsP2-nsP3-nsP4-junction region-C-E3-E2-6K-E1-poly (A)-3′ [2]. The virus was first isolated from a febrile patient in Tanzania in 1953 and spread into Africa, Pacific, and South East Asian regions [3,4,5]. The virus has now been transmitted to more than 20 countries and is one of the most potential risks among the travel-associated diseases for travelers to tropical regions [6,7,8]. Since its re-emergence in the Indian Ocean Island in 2005, the virus was recognized as a global public health threat [9]. Three genotypes of CHIKV have been characterized based on their partial E1 sequences, which include Asian, East Central South African, and West African genotypes [10].

The CHIKV is transmitted to humans mainly by Aedes aegypti and Aedes albopictus mosquitoes. Clinical symptoms also resemble dengue, which include chills, fever, headache, myalgia, nausea, vomiting, and rashes [11]. In addition, overlap of disease-occurrence areas make it difficult to identify the exact pathogens involved, if the differential diagnostic methods are unavailable. In South Korea, dengue diagnosis began in 2001 at the Korea National Institute of Health (KNIH) and since then imported cases have been continuously reported [12,13]. Because no vaccines or therapeutic agents are available, early detection of the virus is important for timely vector control and prevention of viral dissemination into nonendemic regions. To cope with an abrupt re-emergence of CHIK in South East Asian regions, the Korean government designated CHIK as a communicable disease group IV in late 2010. However, before enacting this law, it was necessary to estimate the occurrence of CHIK cases introduced by patients with dengue-like diseases who had returned from dengue-endemic regions. In the present study, we first documented the travel-associated introduction of CHIKV into South Korea during 2009–2010, which stresses the importance of making modifications to the travel health policies.

In the present study, we investigated the extent of CHIKV infections in dengue-suspected patients who returned from travel. A total of 22 serum samples showed evidence of travel-related CHIK during 2009 and 2010. It was revealed that 4.5 % (17/379) of dengue-negative samples was CHIK-positive. Interestingly, results of ELISA showed that 4.7% (5/107) of dengue-positive cases were positive for CHIKV IgM in 2010. Generally, ELISA is just a screening test and a confirmatory testing such as plaque reduction neutralization test (PRNT) should be performed for differentiating CHIK and dengue. However, our laboratory had not set up the method at that time and it remains to be resolved later. We attempted to isolate the virus in the two RT-PCR-positive cases and one was recovered successfully from the serum collected within 2 days after onset of illness. A CHIKV infection has been categorized as a communicable disease group IV since late 2010 in South Korea. This functioned as a passive patient surveillance system based on compulsory case reporting by physicians. Since enacting the law, however, the number of requests for CHIK diagnosis from hospitals was only 25 cases by March 2013. It may be due to the low-level recognition of the disease in the medical community. From this viewpoint, the number of real CHIK might have been underestimated in South Korea. It is hard to differentiate dengue from CHIK with clinical symptoms alone. Therefore, we recommend serological and molecular testing of CHIKV as well as dengue to diagnose febrile patients who returned from tropical regions. It was revealed that mutant viruses with amino-acid substitution (alanine to valine at position 226) at the E1 gene have superior infectivity in Ae. albopictus than Ae. aegypti mosquitoes and are responsible for recent outbreaks in India, Malaysia, and Singapore [15,17,18]. An isolate, KNIH/2009/77, recovered in this study was also a mutant-type CHIKV that may have the potential to infect Ae. albopictus mosquitoes distributed in Korea. The possibility of importation and spread of CHIKV by acute febrile traveler was reported in 2007 in Italy [19]. Considering that Ae. albopictus mosquitoes are already distributed in Korea, we could not exclude an abrupt introduction of CHIKV as well as DENV.

In conclusion, we presented first evidence of travel-associated CHIKV infections in South Korea. This finding highlights the need to conduct laboratory and vector surveillance program for CHIKV as well as an urgent need to modify evidence-based travel health policies and recommendations.