Introduction

Q fever, a zoonosis caused by Coxiella burnetii (C. burnetti), has been reported in most parts of the world [1]. The primary animal reservoirs are cattle, sheep, and goats, but they are usually asymptomatic, except for reproductive disorders in females. Most human infection is through direct contact with infected livestock or inhalation of contaminated aerosols. The clinical manifestation is characterized by prolonged fever, headache, myalgia, pneumonia or hepatitis in an acute form, as well as endocarditis and vascular infection in its chronic form [2]. There has been no known outbreak of the disease in Korea, but there were a few reports of patients with Q fever. Seroepidemiological studies showed relatively high infection rates in animals and a concern for the risk of human Q fever [3, 4]. In 2006, Q fever was included in the National Notifiable Infectious Diseases, and management at a national level was initiated. The number of hospital consultations for confirmed diagnosis of Q fever increased during 2006–2011. We reviewed the general characteristics, clinical spectrums, and risk factors of patients with Q fever from nationally reported cases during this period.

Materials and Methods

2.1. Study subjects

We identified 72 patients with Q fever registered in Korea Centers for Disease Control (KCDC) National Notifiable Diseases Surveillance System from 2006 to 2011. We excluded seven patients without serological diagnosis, and thus reviewed the epidemiological data of 65 patients. Patients’ information, such as sex, age, job, region and disease onset date, was available from the surveillance records. Additional information such as risk factor exposures and clinical characteristics had been collected for 35 patients since 2008, when the regional public health departments began epidemiological investigations of all reported cases of Q fever, with the disease-specific case report form.

2.2. Serological methods

Serological diagnosis was performed by indirect immunofluorescence antibody assay (IFA) using C. burnetii Nine Mile strain. If immunoglobulin G (IgG) antibodies level against the C. burnetii phase II antigen from the convalescent phase, is >four times the amount from the initial acute phase, or the IgG titers are ≥1:256, or IgM titers to phase II antigen are ≥1:16, then the sample was considered positive for acute infection. Further, an IFA diagnosis kit (Commercial Slide, Focus Diagnostics, Cyprus, California, USA) was used to reconfirm the initial diagnosis, by determining the presence of phase I and phase II antibodies in the samples. If IgG titers to phase I antigen were >1:800 in the diagnosis kit, Q fever patients were classified as having chronic infection [5]. All testing was performed at Korea National Institute of Health.

Results

Acute and chronic Q fever infection was notified continuously since 2006 and we identified 65 serologically confirmed patients (Figure 1). Twelve patients (18.5%) were considered as chronic, based on the serological analysis results. The average annual notification rate of Q fever was 0.22 cases per million persons during the study period. The general characteristics of all patients are shown in Table 1. The mean (±SD) age of the patients was 49.1 years (±14.5), and they were all adults except for one adolescent patient. There were 57 men (87.7%) and eight women (12.3%). Fifteen patients (23.1%) had high-risk occupations for Q fever, e.g., livestock raiser, veterinarian, slaughterhouse worker, and farmer. The number of patients in urban areas (44; 67.1%) was more than twice that in rural areas (21; 32.3%). Among the 16 provinces and metropolitan cities of Korea, Gyeonggi, Daegu, Chungnam, and Gyeongnam accounted for 61.5% of all notified cases of Q fever. Acute Q fever cases occurred throughout the year, but based on the data from 47 patients for whom the disease onset time was verified, the highest incidence was observed in the spring season (Figure 2).

The risk factors and clinical symptoms of 35 patients, who were investigated by local health departments from 2008, are summarized in Tables 2 and 3. The most common risk factor was contact with animals (15; 42.9%), followed by visiting animal farms (7; 20%), and participating in animal birthing (6; 17.1%). The most frequently contact was with cattle. The other 19 patients (54.3%) had not been exposed to any such known risk factors. However, in three cases, ingestion of raw beef or deer blood was the only possible risk factor. The proportion of risk exposures by sex was 48.3% in men and 33.3% in women. Fever was present in 85.7% of all patients. Hepatitis and pneumonia were present in 21.4% and 10.7% of acute patients, respectively, and one patient had a rare complication of encephalitis. Among seven chronic patients, endocarditis was observed in two patients who previously had valvular heart disease. No mortality was identified.

Discussion

To our knowledge, this is the first official report on the characteristics of Q fever patients in Korea. The annual incidence of Q fever in Korea is much lower than that in France, Australia and Taiwan (0.02 vs. 2.5, 0.1, and 0.38 per 100,000 population, respectively) [5–7]. As the disease has a broad spectrum of clinical manifestations, from nonspecific febrile illness to neurological disorder, and there are no known outbreaks in Korea, it is difficult for physicians to diagnose Q fever without an increased awareness. Serological diagnostic testing is limited, because it is available at only one national laboratory. Therefore, Q fever is likely to be under-diagnosed and under-reported in Korea.

Similar to other studies, the majority of Q fever cases were men and adults [8–10]. In this study, men were more involved in the ‘at risk’ exposures than women, but the gender difference could be explained by the protective role of female hormones [11]. There were no cases of children <15 years old, and it seems to be related with low clinical expression after infection at a young age [12]. A clustering of cases in spring is associated with the animal birth season, as C. burnetti is highly concentrated in the amniotic fluids or placental tissues of infected animals [13]. Occupational contribution was not high in comparison with other countries [10,14]. It needs to be interpreted with regards to the workforce structure of Korea. More than half of the patients were not exposed to any risk factors. This suggests that Q fever might occur in urban areas, even without direct contact with primary reservoirs, as the bacteria can spread through contaminated dust by wind from the remote areas and infect humans at very low doses of inhalation [15].

Hepatitis or pneumonia are known to accompany symptomatic acute Q fever, but our results indicated that mild illness was dominant [9,16,17]. More detailed clinical reviews of patients are necessary in future studies. Q fever endocarditis, most frequent presentation of chronic infection, was also observed in an acute patient without previous cardiac abnormalities. Q fever testing is recommended for discovering the cause of endocarditis in patients with valvulopathies. In addition, clinical and serological follow-up after acute Q fever should be considered for early detection of cardiac involvement [18]. Raw milk consumption is unusual in Korea, but ingestion of raw beef or deer blood is preferred by some people. Although a recent study showed a low seroprevalence of C. burnetti in meat cattle and farm-raised deer in Korea, the risk of transmission to humans by the oral route should be assessed [2,19].

According to national surveys of C. burnetti seroprevalence in the Korean population, the seropositivity rate of high-risk occupation groups, such as dairy farmers, slaughterhouse workers, and veterinarians, was 3.7–10.2% (data not shown). Q fever is not currently considered as a significant threat to public health in Korea. Only sporadic cases have been reported to date, but there is a possibility of an epidemic. Therefore, increased awareness among physicians for better detection and treatment of Q fever, expansion of the diagnostic system, and further investigations for undiscovered risk factors, are persistently required.

Acknowledgments

References

• 1. Maurin M, Raoult D. Q fever. Clin Microbiol Rev 1999;10;12(4): 518−53. PMID: 10515901.ArticlePubMedPMC
• 2. Angelakis E, Raoult D. Q fever. Vet Microbiol 2010;1;140(3–4): 297−309. PMID: 19875249.ArticlePubMed
• 3. Kim WJ, Hahn TW, Kim DY, et al. Seroprevalence of Coxiella burnetii infection in dairy cattle and non-symptomatic people for routine health screening in Korea. J Korean Med Sci 2006;10;21(5): 823−6. PMID: 17043413.ArticlePubMedPMC
• 4. Komiya T, Sadamasu K, Kang MI, et al. Seroprevalence of Coxiella burnetii infections among cats in different living environments. J Vet Med Sci 2003;9;65(9): 1047−8. PMID: 14532705.ArticlePubMed
• 5. Frankel D, Richet H, Renvoisé A, Raoult D. Q fever in France, 1985–2009. Emerg Infect Dis 2011;3;17(3): 350−6. PMID: 21392423.ArticlePubMedPMC
• 6. NNDSS Annual Report Writing Group. Australia’s notifiable disease status, 2010: annual report of the National Notifiable Diseases Surveillance System. Commun Dis Intell 2012;3;36(1): 1−69.
• 7. Centers for Disease Control, Department of Health, R.O.C. (Taiwan). Statistics of communicable diseases and surveillance report, Republic of China 2010. Taipei, Centers for Disease Control, Department of Health, R.O.C. (Taiwan). 2011.
• 8. Lai CH, Huang CK, Chin C, et al. Acute Q fever: an emerging and endemic disease in southern Taiwan. Scand J Infect Dis 2008;40(2): 105−10. PMID: 17852909.ArticlePubMed
• 9. Raoult D, Tissot-Dupont H, Foucault C, et al. Q fever 1985–1998. Clinical and epidemiologic features of 1,383 infections. Medicine (Baltimore) 2000;3;79(2): 109−23. PMID: 10771709.ArticlePubMed
• 10. Lowbridge CP, Tobin S, Seale H, Ferson MJ. EpiReview: notifications of Q fever in NSW, 2001–2010. N S W Public Health Bull 2012;Jan-Feb;23(1–2): 31−5. PMID: 22487331.ArticlePubMed
• 11. Leone M, Honstettre A, Lepidi H, et al. Effect of sex on Coxiella burnetii infection: protective role of 17beta-estradiol. J Infect Dis 2004;1;189(2): 339−45. PMID: 14722900.ArticlePubMed
• 12. Maltezou HC, Raoult D. Q fever in children. Lancet Infect Dis 2002;11;2(11): 686−91. PMID: 12409049.ArticlePubMed
• 13. Porter SR, Czaplicki G, Mainil J, et al. Q Fever: current state of knowledge and perspectives of research of a neglected zoonosis. Int J Microbiol 2011;2011:248418PMID: 22194752.ArticlePubMedPMC
• 14. Bacci S, Villumsen S, Valentiner-Branth P, et al. Epidemiology and clinical features of human infection with Coxiella burnetii in Denmark during 2006–07. Zoonoses Public Health 2012;2;59(1): 61−8. PMID: 21824371.ArticlePubMed
• 15. Tigertt WD, Benenson AS, Gochenour WS. Airborne Q fever. Bacteriol Rev 1961;9;25:285−93. PMID: 13921201.ArticlePubMedPMC
• 16. Domingo P, Muñoz C, Franquet T, et al. Acute Q fever in adult patients: report on 63 sporadic cases in an urban area. Clin Infect Dis 1999;10;29(4): 874−9. PMID: 10589906.ArticlePubMed
• 17. Luksić B, Punda-Polić V, Ivić I, et al. Clinical and epidemiological features of hospitalized acute Q fever cases from Split-Dalmatia County (Croatia), 1985–2002. Med Sci Monit 2006;3;12(3): CR126−31. PMID: 16501424.PubMed
• 18. Landais C, Fenollar F, Thuny F, Raoult D. From acute Q fever to endocarditis: serological follow-up strategy. Clin Infect Dis 2007;5;44(10): 1337−40. PMID: 17443471.ArticlePubMed
• 19. Jang Y, Kim H, Heo I, et al. Seroprevalence of Coxiella burnetii in cattle and farm-raised deer in Korea. Afr J Microbiol Res 2011;10;5(24): 4234−6.

Figure 1

Notified cases of human Q fever in Korea, 2006–2011. Gray bars indicate chronic cases and white bars indicate acute cases.

Figure 2

Monthly distribution of 47 cases of acute Q fever in Korea, 2006–2011.

Table 1

General characteristics of Q fever patients in Korea, 2006–2011

		All cases (n = 65)
		n	%
Sex	Male	57	87.7
	Female	8	12.3
Age (y)	<20	1	1.5
	20–29	6	9.2
	30–39	11	16.9
	40–49	11	16.9
	50–59	20	30.8
	≥60	16	24.6
Occupation	Livestock raiser	5	7.7
	Veterinarian	2	3.1
	Slaughterhouse worker	2	3.1
	Agricultural farmer	6	9.2
	Others	50	76.9
Inhabitant area	Urban	44	67.7
	Rural	21	32.3
Region	Seoul	6	9.2
	Busan	0	0
	Daegu	10	15.4
	Incheon	3	4.6
	Gwangju	1	1.5
	Daejeon	1	1.5
	Ulsan	0	0
	Gyeonggi	16	24.6
	Gangwon	3	4.6
	Chungbuk	4	6.2
	Chungnam	7	10.8
	Jeonbuk	2	3.1
	Jeonnam	0	0
	Gyeongbuk	4	6.2
	Gyeongnam	7	10.8
	Jeju	1	1.5

Table 2

Distribution of exposures for Q fever infection among the investigated patients, 2008–2011

Risk factors	All cases (n = 35)
	N	%
Animal contact	15	42.9
Cattle	7	20.0
Deer	4	11.4
Goat	3	8.6
Horse	1	2.9
Pig	1	2.9
Unspecified	2	5.7
Unpasteurized milk	0	0
Visiting animal farm	7	20.0
Birthing animals	6	17.1
None	19	54.3

Table 3

Distribution of symptoms and signs among the investigated patients with Q fever, 2008–2011

	All cases, n (%)
	Acute infection n = 28	Chronic infection n = 7
Fever	25 (89.3)	5 (71.4)
Myalgia	19 (67.9)	0 (0.0)
Asthenia	15 (53.6)	2 (28.6)
Skin rash	1 (3.6)	1 (14.3)
Cough	4 (14.3)	0 (0.0)
Headache	7 (25.0)	1 (14.3)
Dizziness	5 (17.9)	0 (0.0)
Nausea	6 (21.4)	0 (0.0)
Vomiting	2 (7.1)	0 (0.0)
Diarrhea	2 (7.1)	0 (0.0)
Chill	14 (50.0)	4 (57.1)
Sweating	5 (17.9)	1 (14.3)
Splenomegaly	3 (10.7)	0 (0.0)
Hepatomegaly	1 (3.6)	0 (0.0)
Pneumonia	3 (10.7)	0 (0.0)
Hepatitis	6 (21.4)	1 (14.3)
Endocarditis	1 (3.6)	2 (28.6)

Figure & Data

References

Citations

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  A.-Tai Truong, Mi-Sun Yoo, Subin Min, Ji-Yeon Lim, Hyun-Ji Seo, Heung-Chul Kim, Sung-Tae Chong, Terry A. Klein, Chang-uk Park, Sook-Young Cho, Chang-Yong Choi, Young-Soo Kwon, Miran Kim, Soon-Seek Yoon, Yun Sang Cho
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  Se Ju Lee, Jung Ho Kim, Hi Jae Lee, Ki Hyun Lee, Eun Hwa Lee, Yae Jee Baek, Jin Nam Kim, Jin Young Ahn, Su Jin Jeong, Nam Su Ku, Seung Hyun Lee, Jun Yong Choi, Joon Sup Yeom, Young Goo Song
  Antibiotics.2021; 10(12): 1476.     CrossRef
• Q fever in Greece: Findings of a 13 years surveillance study
  Iosif Vranakis, Sofia Kokkini, Emmanouil Yachnakis, Yannis Tselentis, Dimosthenis Chochlakis, Anna Psaroulaki
  Comparative Immunology, Microbiology and Infectiou.2020; 69: 101340.     CrossRef
• Isolation of Coxiella burnetii in patients with nonspecific febrile illness in South Korea
  Seung Hun Lee, Jae Hoon Lee, Sungdo Park, Hae Kyung Lee, Seon Do Hwang, Hye Won Jeong, Jung Yeon Heo, Yeong Seon Lee
  BMC Infectious Diseases.2020;[Epub]     CrossRef
• Current Status of Tick-Borne Diseases in South Korea
  Jae Hyoung Im, JiHyeon Baek, Areum Durey, Hea Yoon Kwon, Moon-Hyun Chung, Jin-Soo Lee
  Vector-Borne and Zoonotic Diseases.2019; 19(4): 225.     CrossRef
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  Moonsuk Bae, Choong Eun Jin, Joung Ha Park, Min Jae Kim, Yong Pil Chong, Sang-Oh Lee, Sang-Ho Choi, Yang Soo Kim, Jun Hee Woo, Yong Shin, Sung-Han Kim
  Medicine.2019; 98(23): e15724.     CrossRef
• Clinical characteristics of acute Q fever patients in South Korea and time from symptom onset to serologic diagnosis
  Jung Yeon Heo, Young Wha Choi, Eun Jin Kim, Seung Hun Lee, Seung Kwan Lim, Seon Do Hwang, Ju Young Lee, Hye Won Jeong
  BMC Infectious Diseases.2019;[Epub]     CrossRef
• Serologic Survey and Risk Factors forCoxiella burnetiiInfection among Dairy Cattle Farmers in Korea
  Ji-Hyuk Park, Hyuk Chu, Seok-Ju Yoo, Kyu-Jam Hwang, Hyun-Sul Lim
  Journal of Korean Medical Science.2018;[Epub]     CrossRef
• Molecular detection of Coxiella burnetii in heart valve tissue from patients with culture-negative infective endocarditis
  Young-Rock Jang, Joon Seon Song, Choong Eun Jin, Byung-Han Ryu, Se Yoon Park, Sang-Oh Lee, Sang-Ho Choi, Yang Soo Kim, Jun Hee Woo, Jae-Kwan Song, Yong Shin, Sung-Han Kim
  Medicine.2018; 97(34): e11881.     CrossRef
• The Epidemiology and Characteristics of Q fever and Co-infections with Scrub Typhus, Murine Typhus or Leptospirosis in Taiwan: A Nationwide Database Study
  C.-H. Lai, W. Sun, C.-H. Lee, J.-N. Lin, M.-H. Liao, S.-S. Liu, T.-Y. Chang, K.-F. Tsai, Y.-C. Chang, H.-H. Lin, Y.-H. Chen
  Zoonoses and Public Health.2017; 64(7): 517.     CrossRef
• Acute Q fever in febrile patients in northwestern of Iran
  Saber Esmaeili, Farhad Golzar, Erfan Ayubi, Behrooz Naghili, Ehsan Mostafavi, Joseph M. Vinetz
  PLOS Neglected Tropical Diseases.2017; 11(4): e0005535.     CrossRef
• Clinical and Genetic Features ofCoxiella burnetiiin a Patient with an Acute Febrile Illness in Korea
  Seung Hun Lee, Jung Yeon Heo, Hae Kyung Lee, Yeong Seon Lee, Hye Won Jeong, Seon Do Hwang
  Journal of Korean Medical Science.2017; 32(6): 1038.     CrossRef
• Seroreactivity to Q Fever Among Slaughterhouse Workers in South Korea
  Hyuk Chu, Seok-Ju Yoo, Kyu-Jam Hwang, Hyun-Sul Lim, Kwan Lee, Mi-Yeoun Park
  Journal of Preventive Medicine and Public Health.2017; 50(3): 195.     CrossRef
• Prevalence of bovine tuberculosis, brucellosis and Q fever in Korean black goats
  Hyobi Kim, Seongjoon Kim, Kina Kim, Byeol Kim, Byungjoon Chang, Nong-Hoon Choe
  Korean Journal of Veterinary Research.2016; 56(4): 249.     CrossRef
• Chloroform-Methanol Residue of Coxiella burnetii Markedly Potentiated the Specific Immunoprotection Elicited by a Recombinant Protein Fragment rOmpB-4 Derived from Outer Membrane Protein B of Rickettsia rickettsii in C3H/HeN Mice
  Wenping Gong, Pengcheng Wang, Xiaolu Xiong, Jun Jiao, Xiaomei Yang, Bohai Wen, James E Samuel
  PLOS ONE.2015; 10(4): e0124664.     CrossRef
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  Stephanie Burniston, Anna L Okello, Boualam Khamlome, Phouth Inthavong, Jeffrey Gilbert, Stuart D Blacksell, John Allen, Susan C Welburn
  Infectious Diseases of Poverty.2015;[Epub]     CrossRef
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  Chung-Hsu Lai, Lin-Li Chang, Jiun-Nong Lin, Wei-Fang Chen, Yu-Feng Wei, Chien-Tung Chiu, Jiun-Ting Wu, Chi-Kuei Hsu, Jung-Yueh Chen, Ho-Sheng Lee, Hsi-Hsun Lin, Yen-Hsu Chen, Daniel E. Voth
  PLoS ONE.2014; 9(7): e102808.     CrossRef
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  Ji-Yeon Kim, So-Ra Sung, Ji-In Pyun, Moon Her, Sung-Il Kang, Hyang-Keun Lee, Suk Chan Jung
  Korean Journal of Veterinary Research.2014; 54(3): 147.     CrossRef
• Serological characterization of surface-exposed proteins of Coxiella burnetii
  Jun Jiao, Xiaolu Xiong, Yong Qi, Wenping Gong, Changsong Duan, Xiaomei Yang, Bohai Wen
  Microbiology .2014; 160(12): 2718.     CrossRef