Research Article: Urbanization of Scrub Typhus Disease in South Korea

Date Published: May 22, 2015

Publisher: Public Library of Science

Author(s): Sang-Won Park, Na-Young Ha, Boyeong Ryu, Ji Hwan Bang, Hoyeon Song, Yuri Kim, Gwanghun Kim, Myoung-don Oh, Nam-Hyuk Cho, Jong-koo Lee, Darren J. Gray.

Abstract: BackgroundScrub typhus is an endemic disease in Asia. It has been a rural disease, but indigenous urban cases have been observed in Seoul, South Korea. Urban scrub typhus may have a significant impact because of the large population.MethodsIndigenous urban scrub typhus was epidemiologically identified in Seoul, the largest metropolitan city in South Korea, using national notifiable disease data from 2010 to 2013. For detailed analysis of clinical features, patients from one hospital that reported the majority of cases were selected and compared to a historic control group. Chigger mites were prospectively collected in the city using a direct chigger mite-collecting trap, and identified using both phenotypic and 18S rDNA sequencing analyses. Their infection with Orientia tsutsugamushi was confirmed by sequencing the 56-kDa antigen gene.ResultsEighty-eight cases of urban scrub typhus were determined in Seoul. The possible sites of infection were mountainous areas (56.8%), city parks (20.5%), the vicinity of one’s own residence (17.0%), and riversides (5.7%). Eighty-seven chigger mites were collected in Gwanak mountain, one of the suspected infection sites in southern Seoul, and seventy-six (87.4%) of them were identified as Helenicula miyagawai and eight (9.2%) as Leptotrombidium scutellare. Pooled DNA extracted from H. miyagawai mites yielded O. tsutsugamushi Boryong strain. Twenty-six patients from one hospital showed low APACHE II score (3.4 ± 2.7), low complication rate (3.8%), and no hypokalemia.ConclusionsWe identified the presence of indigenous urban scrub typhus in Seoul, and a subgroup of them had mild clinical features. The chigger mite H. miyagawai infected with O. tsutsugamushi within the city was found. In endemic area, urban scrub typhus needs to be considered as one of the differential febrile diseases and a target for prevention.

Partial Text: Scrub typhus, also known as tsutsugamushi disease, is a mite-borne infectious disease that is endemic in a triangular geographic region containing the Indian subcontinent, northern Australia and the Far East. In endemic areas, the risk of infection is mainly associated with farming and outdoor activities in rural areas, which have a high disease burden [1–4]. In non-endemic area, scrub typhus is one of the most important febrile diseases affecting returning travelers [5]. Clinical clues that lead to a diagnosis include maculopapular skin rash, regional lymphadenopathy, and eschar. The presence of characteristic eschar varies according to the geographical region [6–9]. Low eschar positivity makes proper diagnostic suspicion difficult. The endemicity of scrub typhus is closely associated with the habitation of vector mites carrying the causative agent, Orientia tsutsugamushi. The major vector mites (the Leptotrombidium species) can often be collected from the mountainous regions and rural farm lands within endemic regions. If a disease flows into a densely populated urban area and attains its endemicity, it will have a significant impact in terms of a disease burden and differential diagnosis in clinical practices. Recently, urban scrub typhus cases that were suspected to occur within Seoul, the largest city in South Korea, have been frequently noted in clinical practices. Seoul is the capital city of South Korea which is located in the northwestern region. It is a densely populated metropolitan city with a population of 10.369 million people (in 2014) living in a land area of 605.21 km2 (, which is comparable in density to Manhattan in the United States with a population of 1.585 million people (in 2010) in an area of 59.5 km2. In South Korea, scrub typhus was first reported in 1951 during the Korean War [10], and it has re-emerged since 1986 [11]. The incidence of scrub typhus has increased steadily [12], and it was the 3rd most frequent notifiable infectious disease in South Korea in 2012 (S1 Table) [13]. There have been studies about urban scrub typhus in the literature [14–16]. Our study was conducted to investigate the status of indigenous urban scrub typhus and its clinical characteristics in Seoul at more northern latitude. In addition, we prospectively determined the causative vector mites within the city.

Scrub typhus is caused by O. tsutsugamushi, which is transmitted by the trombiculid chigger mite during its human bite. O. tsutsugamushi is naturally maintained within the life cycle of mites [25]. It can be transovarially transmitted in mites. The incidence of scrub typhus is influenced by multiple factors. The behavior and population densities of Trombiculidae and wild rodents and the types of human activity may affect the infection. There have been surveys investigating the distribution of wild rodents and Trombiculidae in South Korea [23,26]. Apodemus agrarius is a dominant wild rodent harboring chigger mites with O. tsutsugamushi. Its typical habitats are forests, cornfields and other agricultural land, but urban areas are also well-adapted sites [27]. Trombiculidae have a nationwide distribution, and seven species (L. pallidum, L. scutellare, L. palpale, L. orientale, L. zetum, Eushoengastia koreaensis, and Neotrombicula japonica) can carry O. tsutsugamushi in South Korea [28]. The dominant species of Trombiculidae primarily responsible for O. tsutsugamushi infection in South Korea are L. pallidum in the colder central area and L. scutellare in the warmer southern area. Dry fields and the surrounding bush and grassy land have been identified as risk areas for the high frequency of O. tsutsugamushi infection [12,29]. These environments seem to be appropriate places for the survival of the vectors. As described in the results section in this study, rural areas in southern and southwestern fields of South Korea have a high incidence of scrub typhus, and recent trends indicate that the high incidence areas are expanding. The trend of expansion includes a higher density of pre-existing endemic areas and an upward expansion to the northern region. This trend was also shown recently by Jin et al using geographic information system (GIS)-based spatial analysis [30]. Global warming might have contributed to this expansion. An annual average temperate of 10°C was estimated to be a northern limit for the distribution of the warm temperature adapted L. scutellare, and an overall increase in temperature may promote the expansion of its habitat to the north [28]. The urban environment is different from rural areas. However, the eco-friendly trend of having more natural parks within the city and preserving the natural environment surrounding the city may create more suitable habitats for vectors and small rodents [31–33]. Seoul has such geographical characteristics as a river (Han River) passing through the city and relatively large peaks surrounding the city accompanied by dry fields at the peak’s base. Under the high infection pressure of surrounding suburbs, the inflow of the vectors into the city may only be a matter of time. Current presence of urban scrub typhus could be interpreted as an incursion of vectors into the urban setting or an incursion of an expanding human population into relatively less habitable natural areas. As described in the introduction section, Seoul is a densely populated area and there has been no room for further expansion into less inhabitable natural area within Seoul. The area around Mt. Gwanak is one of the populated residential area since long ago. The estimated sites of infection depicted in the Fig 1 showed their central locations within the city. There has been little change in the aspect of human contacts but the urban scrub typhus is a new phenomenon. Seroprevalence study in the urban area deserves consideration [34,35]. Although it can’t differentiate urban vs. non-urban infection under free moving society, the seroprevalence study combined with serial monitoring of reported patients will help estimate the size of urban exposure to scrub typhus. The comparison of intra-municipal locations may indicate risk area.