Epidemiological Characterization of Opportunistic Mycoses between the Years 2006 and 2010 in Korea
Epidemiological Characterization of Opportunistic Mycoses between the Years 2006 and 2010 in Korea
Journal of Microbiology and Biotechnology. 2016. Jan, 26(1): 145-150
Copyright © 2016, The Korean Society For Microbiology And Biotechnology
  • Received : August 21, 2015
  • Accepted : September 23, 2015
  • Published : January 28, 2016
Export by style
Cited by
About the Authors
Je-Seop, Park
Department of Biomedical Laboratory Science, College of Medical Science, Konyang University, Daejeon 35365, Republic of Korea
Seung-Hak, Cho
Division of Enteric Diseases, Center for Infectious Diseases, Korea National Institute of Health, Cheongju 28159, Republic of Korea
Seung-Ki, Youn
Division of Quarantine Support, Korea Centers for Disease Control and Prevention, Cheongju 28159, Republic of Korea
Young-Seok, Bak
Department of Emergency Medical Service, College of Medical Science, Konyang University, Daejeon 35365, Republic of Korea
Young-Bin, Yu
Department of Biomedical Laboratory Science, College of Medical Science, Konyang University, Daejeon 35365, Republic of Korea
Young Kwon, Kim
Department of Biomedical Laboratory Science, College of Medical Science, Konyang University, Daejeon 35365, Republic of Korea

In order to perform an epidemiological characterization of opportunistic mycosis infections, we collected health insurance data between the years 2006 and 2010 from the Health Insurance Corporation and analyzed the data to determine the prevalence of opportunistic mycoses and treatment management of opportunistic mycoses. The prevalence within the study increased consecutively by 0.02% to 0.12% every year. The annual prevalence of opportunistic mycoses increased from 2.437% in 2006 to 2.709% in 2010. The average annual prevalence was 2.605%. Candidiasis occurred the most frequently, followed by aspergillosis, zygomycosis, and cryptococcosis. The regions with the highest incidences were the capital areas, Gyeonggi and Seoul. By sex, the prevalence in females (4.851%) was 14 times higher than that in males (0.352%). Interestingly, the adults from the 20- to 49-year-old age group showed higher prevalence than children and the elderly. The average duration of hospitalized treatment was 17.31 days and of outpatient treatment was 2.21 days; 3,577 hundred million won was used in total for medical expenses. This study provides useful data to study trends of opportunistic mycoses.
Opportunistic fungal infections are emerging as an important public health concern and cost burden [11] . The frequency of infections has increased significantly over the past 3 decades [25 , 35] . This increase in the frequency of infections is due to the increasing number of critically ill patients [11 , 23 , 25 , 31] .
The incidence of fungal infections in South Korea is increasing consistently; however, epidemiological national survey data and other related information for mycoses are lacking.
Opportunistic mycosis is a disease caused by pathogenic fungi when changes in the total number of normal flora occur in people with an abnormal immune system, such as loss of health due to a fungi with limited toxicity, use of immunosuppressive agents due to organ transplant, invasive central venous catheter, invasive surgery to place a medical device, or long-term administration of broad-spectrum antibiotics [11 , 12 , 24] .
The most well-known opportunistic fungal pathogens are Candida species. Although >100 species of Candida have been described, only 10% of them have been implicated in opportunistic mycosis [25] . Candidiasis is a serious disease with a mortality rate of 10% to 49% for bloodstream infections [8 , 18 , 25 , 26 , 32 , 34] . The majority of cases (50% to 70%) are caused by Candida albicans , followed by C. tropicalis , C. glabrata , and C. parapsilosis for newborns [3 , 5 , 7 , 9 , 19 , 20 , 25 , 31] .
Aspergillus species that induce aspergillosis have many spores in the air and account for most of the fungi that infect people through the air. A. fumigatus is the most frequent cause of aspergillosis, responsible for about 90% of all cases [30] . The mortality rate with invasive aspergillosis is high, ranging from 50% to 100% in almost all groups of immunocompromised patients [4 , 21] . Other important aspergillus species are A. niger , A. flavus , A. nidulans , and A. terreus [6 , 22 , 24] .
Cryptococcosis represents a major life-threatening fungal infection in patients with defective cell-mediated immunity and may also complicate organ transplantation. The mass outbreak of serotype B Cryptococcus neoformans , which generally occurs in the subtropics, infected and killed healthy people with normal immune systems in Vancouver, Canada, and in the Northwest region of the USA; this proved that fungal infections do not occur only in people with compromised immune systems [10] .
The class zygomycetes contains the genera Rhizopus , Mucor , Rhizomucor , and Lichtheimia (formerly Absidia ); fungal infections are most commonly linked to Rhizopus species [27] . Zygomycosis is a rare emerging opportunistic infection frequently associated with immunosuppressed patients, including hematopoietic stem-cell transplantation recipients, those with poorly controlled diabetes mellitus, and patients with hematologic malignancies (especially with neutropenia) [1 , 13 - 15] . The prevalence and overall mortality of zygomycosis were 36% and 44%, respectively [28] .
In Korea, however, the epidemiology of opportunistic fungal infections is not well described and data regarding incidence are scant. Therefore, the purpose of this study was to build a basic database for effective fungal infection control by performing the epidemiological characterization of these infections from 2006 to 2010, using the database of Health Insurance Corporation.
Materials and Methods
- Study Design
Health insurance data between the years 2006 and 2010 were collected from the Health Insurance Corporation and analyzed. The diseases of opportunistic fungal infections were divided into four groups, including candidiasis (KoICD, Korea International Classification of Diseases : B37), aspergillosis (B44), cryptococcosis (B45), and zygomycosis (B46).
The number of incidence was analyzed by considering medical records for one case if the case was duplicated within 2 months for candidiasis and 6 months in the case of aspergillosis, cryptococcosis, and zygomycosis ( Fig. 1 ).
PPT Slide
Lager Image
Analysis algorithm chart of the National Health Insurance database.
- Epidemiological Analysis
In order to determine the significance of opportunistic mycosis that causes diseases, we performed an epidemiological analysis of annual and regional prevalence and age- and sex-specific patterns of the prevalence for each opportunistic mycosis. The annual prevalence of opportunistic infections was calculated, where patients with the disease who had been treated multiple times were counted as one case per year in the data analysis. The regional prevalence was calculated according to the locations of the medical institutions where the treatments had been provided.
- Duration of Hospitalization and Cost Analysis of Therapy
The number of convalescence days of inpatients and outpatients for opportunistic mycosis was calculated for the last 5 years, and medical care cost was calculated and classified as personal charges and insurance charges from insurance items from the Health Insurance Corporation database. No insurance charge item was excluded from the medical care cost.
Gyeonggi (1,560,554 cases) and Seoul (1,393,553 cases) had the highest rates of occurrence of infection, and Jeju (64,231 cases) had the lowest rate of occurrence ( Table 1 ). The prevalence in females (93.17%) was 14 times higher than that in males. The highest rates of infection occurred in patients in their 20s to 40s ( Table 2 ). The average duration of hospitalized treatment was 17.31 days and of outpatient treatment was 2.21 days. Total medical expenses cost 3,577 hundred million won. Among the total expenses, hospitalizations cost 1,461 hundred million won and outpatient treatments cost 2,116 hundred million won ( Table 3 ).
Prevalence rate of opportunistic mycoses by year and regions.
PPT Slide
Lager Image
Prevalence rate of opportunistic mycoses by year and regions.
Prevalence rate of opportunistic mycoses by age and sex.
PPT Slide
Lager Image
Prevalence rate of opportunistic mycoses by age and sex.
Convalescence days and medical costs for opportunistic mycoses.
PPT Slide
Lager Image
Convalescence days and medical costs for opportunistic mycoses.
- Prevalence of Opportunistic Mycosis Infections Between the Year 2006 and 2010 in Korea
A total of 6,255,789 infections by opportunistic mycosis were analyzed during the 5-year study period. Approximately 1.25 million cases occurred each year ( Table 1 ). The prevalence rate according to resident population increased consecutively. The annual prevalence of opportunistic mycoses increased from 2.437% in 2006 to 2.709% in 2010. The average annual prevalence was 2.605%. The rate of infection according to region ranged from 3.199% in Ulsan to 1.908% in Gyeongbuk.
As shown in Table 2 , age-specific patterns were observed in the opportunistic mycoses. By age group, there was a high rate of prevalence in people aged 30 to 39 years (4.35%), whereas the prevalence rate was low in people aged 10 to 19 years (0.430%) and aged 80 years and over (0.570% to 0.772%).
- Prevalence of Different Opportunistic Mycoses
As shown in Table 1 , candidiasis (6,238,869 cases, 99.73%) occurred most frequently, followed by aspergillosis (10,878 cases, 0.17%), zygomycosis (3,951 cases, 0.06%) and cryptococcosis (2,091 cases, 0.03%).
Candidiasis. Candidiasis was the most frequently observed opportunistic mycosis, and the annual prevalence of candidiasis increased from 2.430% in 2006 to 2.702% in 2010. The average annual prevalence of candidiasis was highest at 2.597% among all of the types of opportunistic mycoses. The regional prevalence was highest in Ulsan (3.190%) and lowest in Gyeongbuk (1.908%) ( Table 1 ). As shown Table 2 , age-specific patterns of candidiasis prevalence showed that the prevalence in patients in their 30s (4.352%) was highest, especially in fertile women. The prevalence among females (4.845%) was 14 times higher than that among males (0.344%).
Aspergillosis. The prevalence of aspergillosis decreased slightly from 0.0050% in 2006 to 0.0042% in 2010. The regional prevalence was highest in Jeonbuk (0.0091%) and lowest in Jeju (0.0026%) ( Table 1 ). The age-specific prevalence rate was highest in patients in their 60s (0.0138%) to 70s (0.0136%), and the gender-specific rates were similar between females (0.0039%) and males (0.0051%) ( Table 2 ).
Cryptococcosis. The prevalence rate of cryptococcosis was highest in 2009 (0.0010%), but decreased in 2010 (0.0005%). The prevalence was highest in Jeonbuk (0.0021%) ( Table 1 ). The age-specific prevalence rate was highest in patients in their 70s (0.0036%) to 80s (0.0035%), and the genderspecific rates were similar between females (0.0010%) and males (0.0008%) ( Table 2 ).
Zygomycosis. The prevalence of zygomycosis gradually rose from 0.0014% in 2006 to 0.0019% in 2008, but decreased thereafter ( Table 1 ). By region, the prevalence was highest in Gwangju (0.0031%). The age-specific prevalence was highest in patients in their 70s (0.0042%) and genderspecific rates were similar between females (0.0017%) and males (0.0016%) ( Table 2 ).
- Convalescence Days and Medical Care Charges According to Different Opportunistic Mycoses
The number of convalescence days for inpatients was 15.13 days for candidiasis, 34.11 days for aspergillosis, 25.56 days for cryptococcosis, and 22.93 days for zygomycosis ( Table 3 ). The number of convalescence days for outpatients was 2.2 days for candidiasis, 8.20 days for aspergillosis, 8.78 days for cryptococcosis, and 3.86 days for zygomycosis.
The treatment cost for opportunistic mycosis from 2006 to 2010 was 3,577 hundred million won, with personal charges of 796 hundred million won and insurance charges of 2,781 hundred million won. Among the total cost, about 83% (2,959 hundred million won of the cost) was used for the treatment of candidiasis.
Opportunistic mycoses are fungal infections of the human body that occur in immunocompromised patient and the virulence of these fungi are naturally low. Several surveys indicate a rising incidence of fungal infections. National autopsy data from Japan between 1969 and 1994 showed increased prevalence of visceral mycoses [33] , and national hospital admission data in Australia between 1995 and 1999 showed increasing hospitalizations for candidiasis and aspergillosis [29] . According to US death certificate data from 1980 to 1997, the number of deaths due to fungal infections increased 3.4 times [16] . Single-center data from India also show an increase in mucormycosis over time [17] . The impact of human immunodeficiency virus infection and the improvement of medical technology in the region have resulted in an increased population of immunocompromised patients and, consequently, more hospitals are reporting invasive fungal infections [2] . The incidence of fungal infections increased as the number of diabetes mellitus, organ transplant, AIDS, and chemotherapy for malignant neoplasm also increased.
Rapid industrialization and urbanization have concentrated the population and instigated global warming. Economic development has changed cultural life and the westernized diet has changed ecosystems. Owing to all these factors, new and various pathogens such as opportunistic infectioncausing fungi have increased.
Opportunistic mycoses mainly occurred in individuals of under 9 years and elders over the age of 60 with weak immune systems. Aspergillosis had a high prevalence among those in their 60s to 70s, cryptococcosis had a high prevalence among those in their 70s to 80s, and zygomycosis had a high prevalence among those in their 70s. Interestingly, candidiasis had a higher prevalence rate for childbearing women in their 20s to 40s.
Since the disease threatens healthy life and is predicted to increase health care cost, effective management and epidemiological studies are needed to reduce the high medical costs, facilitate healthy lifestyles, and establish a variety of preventive measures such as dietary improvement for the recovery of the immune system and environmental improvements for preventing the spread of infection from unclean surroundings. Patients with opportunistic mycoses experience a reduced quality of life and increased medical costs. If we adequately analyze and observe the progress of opportunistic mycoses with effective management and systematic study, these patients will be able to lead a better life.
This study attempted to determine the roadmap for diagnosis and treatment as well as steps to curb the rising prevalence of opportunistic fungal infections by using the data obtained from the National Health Insurance Corporation database. If the trends of prevalence according to year, region, gender, and age can be continuously analyzed and observed, these data can be a useful resource for determining the changes in the trend of opportunistic fungal pathogens.
This work was supported by the Research Program funded by the Korea Centers for Disease Control and Prevention (fund code No. 2012-E2400200).
Ambrosioni J , Bouchuiguir-Wafa K , Garbino J 2010 Emerging invasive zygomycosis in a tertiary care center: epidemiology and associated risk factors. Int. J. Infect. Dis. 14 e100 - e103    DOI : 10.1016/j.ijid.2009.11.024
Auberger J , Lass-Flörl C , Ulmer H , Nogler-Semenitz E , Clausen J , Gunsilius E 2008 Significant alterations in the epidemiology and treatment outcome of invasive fungal infections in patients with hematological malignancies. Int. J. Hematol. 88 508 - 515    DOI : 10.1007/s12185-008-0184-2
Colombo AL , Nucci M , Park BJ , Nouér SA , Arthington-Skaggs B , da Matta DA 2006 Epidemiology of candidemia in Brazil: a nationwide sentinel surveillance of candidemia in eleven medical centers. J. Clin. Microbiol. 44 2816 - 2823    DOI : 10.1128/JCM.00773-06
Denning DW 1996 Therapeutic outcome in invasive aspergillosis. Clin. Infect. Dis. 23 608 - 615    DOI : 10.1093/clinids/23.3.608
Eggimann P , Garbino J , Pittet D 2003 Epidemiology ofCandidaspecies infection in critically ill non-immunosuppressed patients. Lancet Infect. Dis. 3 685 - 702    DOI : 10.1016/S1473-3099(03)00801-6
Garnacho-Montero J , Amaya-Villar R , Ortiz-Leyba C , León C , Alvarez-Lerma F , Nolla-Salas J 2005 Isolation ofAspergillusspp. from the respiratory tract in critically ill patients: risk factors, clinical presentation and outcome. Crit. Care 9 R191 - R199    DOI : 10.1186/cc3488
Gonzalez GM , Elizondo M , Ayala J 2008 Trends in species distribution and susceptibility of bloodstream isolates ofCandidacollected in Monterrey, Mexico, to seven antifungal agents: results of a 3-year (2004 to 2007) surveillance study. J. Clin. Microbiol. 46 2902 - 2905    DOI : 10.1128/JCM.00937-08
Gudlaugsson O , Gillespie S , Lee K , Vande Berg J , Hu J , Messer S 2003 Attributable mortality of nosocomial candidemia, revised. Clin. Infect. Dis. 37 1172 - 1177    DOI : 10.1086/378745
Hajjeh RA , Sofair AN , Harrison LH , Lyon GM , Arthington-Skaggs BA , Mirza SA 2004 Incidence of bloodstream infections due toCandidaspecies and in vitro susceptibilities of isolates collected from 1998 to 2000 in a population-based active surveillance program. J. Clin. Microbiol. 42 1519 - 1527    DOI : 10.1128/JCM.42.4.1519-1527.2004
Hoang LM , Maquire JA , Doyle P , Fyfe M , Roscoe DL 2004 Cryptococcus neoformansinfections at Vancouver Hospital and Health Sciences Centre (1997–2002): epidemiology, microbiology and histopathology. J. Med. Microbiol. 53 935 - 940    DOI : 10.1099/jmm.0.05427-0
Jain A , Jain S , Rawar S 2010 Emerging fungal infections among children: a review on its clinical manifestations, diagnosis, and prevention. J. Pharm. Bioallied Sci. 2 314 - 320    DOI : 10.4103/0975-7406.72131
Javis WR 1995 Epidemiology of nosocomial fungal infections, with emphasis onCandidaspecies. Clin. Infect. Dis. 20 1526 - 1530    DOI : 10.1093/clinids/20.6.1526
Kauffman CA 2004 Zygomycosis: reemergence of an old pathogen. Clin. Infect. Dis. 39 588 - 590    DOI : 10.1086/422729
Kontoyiannis DP , Marr KA , Park BJ , Alexander BD , Anaissie EJ , Walsh TJ 2010 Prospective surveillance for invasive fungal infections in hematopoietic stem cell transplant recipients, 2001-2006: overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) Database. Clin. Infect. Dis. 50 1091 - 1100    DOI : 10.1086/651263
Marr KA , Carter RA , Crippa F , Wald A , Corey L 2002 Epidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients. Clin. Infect. Dis. 34 909 - 917    DOI : 10.1086/339202
McNeil MM , Nash SL , Hajjeh RA , Phelan MA , Conn LA , Plikaytis BD , Warnock DW 2001 Trends in mortality due to invasive mycotic diseases in the United States, 1908-1997. Clin. Infect. Dis. 33 641 - 647    DOI : 10.1086/322606
Meis JF , Chakrabarti A 2009 Changing epidemiology of an emerging infection: zygomycosis. Clin. Microbiol. Infect. 15 10 - 14    DOI : 10.1111/j.1469-0691.2009.02973.x
Morgan J , Meltzer MI , Plikaytis BD , Sofair AN , Huie-White S , Wilcox S 2005 Excess mortality, hospital stay, and cost due to candidemia: a case-control study using data from population-based candidemia surveillance. Infect. Control Hosp. Epidemiol. 26 540 - 547    DOI : 10.1086/502581
Nucci M , Queiroz-Telles F , Tobón AM , Restrepo A , Colombo AL 2010 Epidemiology of opportunistic fungal infections in Latin America. Clin. Infect. Dis. 51 561 - 570    DOI : 10.1086/655683
Pappas PG , Rex JH , Lee J , Hamill RJ , Larsen RA , Powderly W 2003 A prospective observational study of candidemia: epidemiology, therapy, and influences on mortality in hospitalized adult and pediatric patients. Clin. Infect. Dis. 37 634 - 643    DOI : 10.1086/376906
Patterson TF , Kirkpatrick WR , White M , Hiemenz JW , Wingard JR , Dupont B 2000 Invasive aspergillosis. Disease spectrum, treatment practices, and outcomes. I3AspergillusStudy Group. Medicine 79 250 - 260    DOI : 10.1097/00005792-200007000-00006
Perfect JR , Cox GM , Lee JY , Kauffman CA , de Repentigny L , Chapman SW 2001 The impact of culture isolation ofAspergillusspecies: a hospital-based survey of aspergillosis. Clin. Infect. Dis. 33 1824 - 1833    DOI : 10.1086/323900
Perusquía-Ortiz AM , Vázquez-González D , Bonifaz A 2012 Opportunistic filamentous mycoses: aspergillosis, mucormycosis, phaeohyphomycosis and hyalohyphomycosis. J. Dtsch. Dermatol. Ges. 10 611 - 621
Pfaller MA 2004 An epidemiologic update on invasive fungal infections. Adv. Stud. Med. 4 S269 - S275
Pfaller MA , Pappas PG , Wingard JR 2006 Invasive fungal pathogens: current epidemiological trends. Clin. Infect. Dis. 43 S3 - S14    DOI : 10.1086/504490
Puzniak L , Teutsch S , Powderly W , Polish L. 2004 Has the epidemiology of nosocomial candidemia changed?. Infect. Control Hosp. Epidemiol. 25 628 - 633    DOI : 10.1086/502452
Ribes JA , Vanover-Sams CL , Baker DJ 2000 Zygomycetes in human disease. Clin. Microbiol. Rev. 13 236 - 301    DOI : 10.1128/CMR.13.2.236-301.2000
Roden MM , Zaoutis TE , Buchanan WL , Knudsen TA , Sarkisova TA , Schaufele RL 2005 Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin. Infect. Dis. 41 634 - 653    DOI : 10.1086/432579
Slavin M , Fastenau J , Sukarom I , Marvos P , Crowley S , Gerth WC 2004 Burden of hospitalization of patients withCandidaandAspergillusinfections in Australia. Int. J. Infect. Dis. 8 111 - 120    DOI : 10.1016/j.ijid.2003.05.001
Warnock DW , Hajjeh RA , Lasker BA 2001 Epidemiology and prevention of invasive aspergillosis. Curr. Infect. Dis. Rep. 3 507 - 516    DOI : 10.1007/s11908-001-0087-3
Warnock DW 2007 Trends in the epidemiology of invasive fungal infections. Jpn. J. Med. Mycol. 48 1 - 12    DOI : 10.3314/jjmm.48.1
Wenzel RP , Gennings C 2005 Bloodstream infections due toCandidaspecies in the intensive care unit: identifying especially high-risk patients to determine prevention strategies. Clin. Infect. Dis. 41 S389 - S393    DOI : 10.1086/430923
Yamazaki T , Kume H , Murase S , Yamashita E , Arisawa M 1999 Epidemiology of visceral mycoses: analysis of data in annual of the pathological autopsy cases in Japan. J. Clin. Microbiol. 37 1732 - 1738
Zaoutis TE , Argon J , Chu J , Berlin JA , Walsh TJ , Feudtner C 2005 The epidemiology and attributable outcomes of candidemia in adults and children hospitalized in the United States: a propensity analysis. Clin. Infect. Dis. 41 1232 - 1239    DOI : 10.1086/496922
Zilberberg MD , Shorr AF , Kollef MH 2008 Secular trends in candidemia-related hospitalization in the United States, 2000–2005. Infect. Control Hosp. Epidemiol. 29 978 - 980    DOI : 10.1086/591033