Rapid Increase of Scrub Typhus, South Korea, 2001–2006

To the Editor: Scrub typhus, or tsutsugamushi disease, is a febrile illness caused by the rickettsial bacteria Orientia tsutsugamushi. Scrub typhus is endemic to a geographically distinct region, the so-called tsutsugamushi triangle, which includes Japan, Taiwan, China, and South Korea (1,2). Scrub typhus is a public health issue in Asia, where 1 billion persons may be at risk for the disease (3). In South Korea, scrub typhus is the most common rickettsial disease, and public health authorities are concerned about its increased incidence. 
 
Scrub typhus has been a reportable disease in South Korea since 1994. Physicians who diagnose suspected or confirmed cases must report these cases to their local health bureau and the Korea Centers for Disease Control and Prevention (KCDC) through the National Notifiable Disease Surveillance System (NNDSS). For a patient’s illness to meet the case definition for scrub typhus, the clinical signs (acute febrile illness and skin eschar) must be present or there must be laboratory confirmation (4-fold rise in antibody titer, antigen detected in blood, or genetic material detected by PCR). 
 
We analyzed NNDSS data confirmed by KCDC and classified all reported cases into 2 groups according to residential area. Cases with rural administrative address codes “eup” or “myun” were defined as rural cases, whereas cases with a city administrative address code of “dong” were defined as urban cases. All case-patients were classified by occupation as farmer or nonfarmer; all agricultural, fishery, and forest workers from rural areas were defined as farmers. 
 
In total, 23,929 cases, including 16,199 (67.7%) serologically confirmed cases, were reported between 2001 and 2006, of which 35.5% were male patients and 64.5% female patients. The greatest number of cases was in the age group 50–69 years, in both male (47.2%) and female (51.7%) patients; however, there were 167 boys (2.0%) and 119 girls (0.8%) <10 years of age. The number of cases peaked in 2005, with 2,331 and 4,449 cases in male and female patients, respectively. In 2006, a total of 6,480 cases (2,364 and 4,116 in males and females patients), which is 2.5× the number reported in 2001, were reported. The autumn epidemic period was from October through November; 96.2% of all cases were reported during this period (Figure). The proportion of cases identified in farmers decreased from 2001 (44.4%) to 2006 (36.4%); the number of cases in nonfarmers reached 4,121 (63.6%) in 2006. The number and proportion of patients living in urban areas increased from 1,059 (40.2%) in 2001 to 3,230 (49.9%) in 2006. This trend was observed in both farmers and nonfarmers. The number of cases among farmers living in urban areas increased from 150 (12.8%) to 443 (18.8%), while the corresponding number of cases in nonfarmers went from 909 (62.0%) to 2,787 (67.6%). In addition, we identified different features of scrub typhus epidemicity, compared with those reported in previous studies (4–7). Many of the values reported in this study (64.5% of cases in female patients, 59.5% in nonfarmers, and 96.2% occurring in autumn) are higher than the values reported previously in Japan (4), Taiwan (5), and China (6). The higher incidence in female workers may be associated with conventional South Korean working behavior. Female workers typically work in a squatting position, with bare hands, and usually in dry fields, whereas male workers tend to work in a standing position, with tools, and in rice fields. Therefore, female workers are more likely to be exposed to infected mites. 
 
 
 
Figure 
 
Monthly occurrence of scrub typhus cases in South Korea, 2001–2006. 
 
 
 
Previously, farmers were considered a high-risk group, but our results imply that the same or even more attention should be given to nonfarmers. Leptotrombidium pallidum, a common mite in Korea, first appears in September. Its population then peaks in October and November and to a lesser degree in April and May (7). In autumn, especially around Chusok (Korean Thanksgiving), nonfarmers and urban residents also take part in agricultural activities, such as the chestnut harvest, mowing around graves, and assisting their farmer relatives. A sharp peak in the number of cases occurred during October–November, which is inconsistent with a previous report on vector density showing a secondary peak during April–May (7). This finding suggests that many cases are misreported, especially in spring. Unfortunately, there are still no reports on the comprehensiveness of the scrub typhus surveillance system in South Korea. We cannot exclude other modes of exposure such as golf, climbing, and other outdoor leisure activities. A 5-day work week was introduced in 2004, and, as a result, more leisure time has been available to urban residents. In addition, improved surveillance and diagnostic methods as well as changes in atmospheric temperature (8) may have contributed to the increase. 
 
We report the rapid increase of scrub typhus and the proportion of infected persons living in urban areas in South Korea. This information will be used to establish strategies for prevention, surveillance, and management in South Korea and in other countries where scrub typhus is endemic.

To the Editor: Scrub typhus, or tsutsugamushi disease, is a febrile illness caused by the rickettsial bacteria Orientia tsutsugamushi. Scrub typhus is endemic to a geographically distinct region, the so-called tsutsugamushi triangle, which includes Japan, Taiwan, China, and South Korea (1,2). Scrub typhus is a public health issue in Asia, where 1 billion persons may be at risk for the disease (3). In South Korea, scrub typhus is the most common rickettsial disease, and public health authorities are concerned about its increased incidence.
Scrub typhus has been a reportable disease in South Korea since 1994. Physicians who diagnose suspected or confirmed cases must report these cases to their local health bureau and the Korea Centers for Disease Control and Prevention (KCDC) through the National Notifiable Disease Surveillance System (NNDSS). For a patient's illness to meet the case definition for scrub typhus, the clinical signs (acute febrile illness and skin eschar) must be present or there must be laboratory confirmation (4-fold rise in antibody titer, antigen detected in blood, or genetic material detected by PCR).
We analyzed NNDSS data confirmed by KCDC and classified all reported cases into 2 groups according to residential area. Cases with rural administrative address codes "eup" or "myun" were defined as rural cases, whereas cases with a city administrative address code of "dong" were defined as urban cases. All case-patients were classified by occupation as farmer or nonfarmer; all agricultural, fishery, and forest workers from rural areas were defined as farmers.
In total, 23,929 cases, including 16,199 (67.7%) serologically con- In addition, we identified different features of scrub typhus epidemicity, compared with those reported in previous studies (4)(5)(6)(7). Many of the values reported in this study (64.5% of cases in female patients, 59.5% in nonfarmers, and 96.2% occurring in autumn) are higher than the values reported previously in Japan (4), Taiwan (5), and China (6). The higher incidence in female workers may be associated with conventional South Korean working behavior. Female workers typically work in a squatting position, with bare hands, and usually in dry fields, whereas male workers tend to work in a standing position, with tools, and in rice fields. Therefore, female workers are more likely to be exposed to infected mites.
Previously, farmers were considered a high-risk group, but our results imply that the same or even more attention should be given to nonfarmers. Leptotrombidium pallidum, a common mite in Korea, first appears in September. Its population then peaks in October and November and to a lesser degree in April and May (7). In autumn, especially around Chusok (Korean Thanksgiving), nonfarmers and urban residents also take part in agricultural activities, such as the chestnut harvest, mowing around graves, and assisting their farmer relatives. A sharp peak in the number of cases occurred during October-November, which is inconsistent with a previous report on vector density showing a secondary peak during April-May (7). This finding suggests that many cases are misreported, especially in spring. Unfortunately, there are still no reports on the comprehensiveness of the scrub typhus surveillance system in South Korea. We cannot exclude other modes of exposure such as golf, climbing, and other outdoor leisure activities. A 5-day work week was introduced in 2004, and, as a result, more leisure time has been available to urban residents. In addition, improved surveillance and diagnostic methods as well as changes in atmospheric temperature (8) may have contributed to the increase.
We report the rapid increase of scrub typhus and the proportion of infected persons living in urban areas in South Korea. This information will be used to establish strategies for prevention, surveillance, and management in South Korea and in other countries where scrub typhus is endemic.

Fatal Algaemia in Patient with Chronic Lymphocytic Leukemia
To the Editor: Prototheca species are achlorophyllic lower algae, ubiquitous in nature, which can cause human infections, particularly in immunocompromised patients (1). Human protothecosis is mostly caused by P. wickerhamii and P. zopfii. Although such infections are infrequent, they can manifest themselves clinically as cutaneous lesions, olecranon bursitis, and, even more rarely, as disseminated or systemic infections (1). These infections occur in severely immunocompromised patients, such as persons with AIDS, or patients undergoing extensive treatment, such as cancer treatment or organ transplantation (1-4). We describe a fatal case of P. wickerhamii algaemia in a patient with chronic lymphocytic leukemia.
In July 2007, a 79-year-old man, who had been monitored since 1993 for stage C chronic lymphocytic leukemia (5), was hospitalized July 13-20 for a depressive syndrome with fever, asthenia, and weight loss (3 kg over 2 months). Blood and urinary cultures on admission were sterile. The patient was hospitalized again on July 30 for fever (39°C), anorexia, and diarrhea, with ≈7 stools per day. He had lost 10 kg in 2 weeks. Blood cultures for bacteria (in BD Bactec Plus Aerobic/F and BD Bactec Lytic Anaerobic/F vials; Becton Dickinson, Le Pont de Claix, France) and fungi (BD Bactec Mycosis IC/F; Becton Dickinson) and stool cultures for bacteria were negative. Blood cultures were incubated in a Bactec 9240 instrument (Becton Dickinson). Aspergillus fumigatus was found in a bronchoalveolar lavage specimen, but no Aspergillus galactomannan antigen was detected in blood.
The patient was treated with piperacillin-tazobactam, ciprofloxacin, acyclovir, voriconazole, and lop-eramide. Voriconazole (400 mg/day) was used from day 17 to day 27. On day 21, Cryptosporidium parvum was detected on parasitologic stool examination. Symptoms persisted on day 26, with strong asthenia and deterioration of general state. At that time, the leukocyte count was 178 × 10 9 /L with 3.56 × 10 9 /L polymorphonuclear neutrophils and 172 × 10 9 /L lymphocytes. Three peripheral blood samples were cultured for detection of bacteria and fungi. On day 27, septic shock developed in the patient. A blood culture showed an Escherichia coli strain susceptible to piperacillin-tazobactam, aminoglycosides, and quinolones. Amikacin was added to the treatment regimen. Nonetheless, the patient died on day 28.
Two blood cultures for bacteria in aerobic vials grew the day of the patient's death, but tests of blood cultures for fungus remained negative. After Gram staining, gram-positive spherical unicellular organisms were observed (Figure). After 48 hours of incubation, creamy, yeast-like colonies grew on chocolate agar (bio-Mérieux, Marcy l'Etoile, France), but not on Sabouraud agar containing gentamicin and chloramphenicol (Becton Dickinson). Microscopy and the API 20C AUX system (bioMérieux) identified P. wickerhamii.
Sequencing the 18S rDNA with the primers Pw18SF 5′-TCAAAAA GTCCCGGCTAATCTCGTGC-3′ and Pw18SR 5′-CGCTTTCGTGCCT CAATGTCAGTGTT-3′ confirmed the identification. The sequence of the amplified product was compared with sequences published in the database of the National Center for Biotechnology Information (Bethesda, MD, USA). The most likely identification, according to BLAST analysis (www. ncbi.nlm.nih.gov/blast/Blast.cgi), was P. wickerhamii.
In vitro susceptibility tests were performed by the Etest method (AB Biodisk, Solna, Sweden), on RPMI agar. P. wickerhamii was found to be

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