Current Status of Q Fever and the Challenge of Outbreak Preparedness in Korea: One Health Approach to Zoonoses

Human Q fever, a zoonosis caused by Coxiella burnetii, presents with diverse clinical manifestations ranging from mild self-limited febrile illnesses to life-threatening complications such as endocarditis or vascular infection. Although acute Q fever is a benign illness with a low mortality rate, a large-scale outbreak of Q fever in the Netherlands led to concerns about the possibility of blood transfusion-related transmission or obstetric complications in pregnant women. Furthermore, a small minority (< 5%) of patients with asymptomatic or symptomatic infection progress to chronic Q fever. Chronic Q fever is fatal in 5–50% of patients if left untreated. In South Korea, Q fever in humans was designated as a notifiable infectious disease in 2006, and the number of Q fever cases has increased sharply since 2015. Nonetheless, it is still considered a neglected and under-recognized infectious disease. In this review, recent trends of human and animal Q fever in South Korea, and public health concerns regarding Q fever outbreaks are reviewed, and we consider how a One Health approach could be applied as a preventive measure to prepare for zoonotic Q fever outbreaks.

Frequency of Red Blood Cell Antigens According to Parent Ethnicity in Korea Using Molecular Typing

Frequencies of red blood cell (RBC) blood group antigens differ by ethnicity. Since the number of immigrants is increasing in Korea, RBC antigens should be assessed in children/youths with parents of different ethnicities to ensure safe transfusions. We investigated the frequency of RBC antigens, except for ABO and RhD, in 382 children and youths with parents having Korean and non-Korean ethnicities. Subjects were divided into those with ethnically Korean parents (Korean group; N=252) and those with at least one parent of non-Korean ethnicity (non-Korean group; N=130). The 37 RBC antigens were genotyped using the ID CORE XT system (Progenika Biopharma-Grifols, Bizkaia, Spain). The frequencies of the Rh (E, C, e, hr(S), and hr(B)), Duffy (Fy(a)), MNS (Mi(a)), and Cartwright (Yt(b)) antigens differed significantly between the two groups. Eight and 11 subjects in the Korean and non-Korean groups, respectively, exhibited negative expression of high-frequency antigens, whereas 14 subjects in the non-Korean group showed positive expression of low-frequency antigens. The frequency of RBC antigens has altered alongside demographic changes in Korea and might lead to changes in distribution of RBC antibodies that cause acute or delayed hemolytic transfusion reaction.

Transfusion Strategy of RhD-negative/variant Patients in the Korean Population

The prevalence of RhD-negative individuals in the Korean population is approximately 0.15-0.30% and the supply of RhD-negative blood often faces potential shortage. Furthermore, 15-17% of serologically RhD-negative Korean individuals were revealed to be DEL variants and should be treated as RhD-positive when being considered as blood donors. This change is expected to result in a further shortage of RhD-negative blood supply, whereas surplus DEL variant blood stock is created. Therefore, it is now required to amend blood donation and supply policies, and transfusion strategies. In this review, a new transfusion strategy for patients with RhD-negative or variant blood in Korea is discussed, with particular interest in women of child-bearing age, patients with anti-D, and Asia type DEL (c.1227G>A) variants.

Report on External Proficiency Testing for the ABO and D Blood Group Typing Tests in Blood Centers (2015) / 대한수혈학회지

BACKGROUND: The Korean Blood Safety Commission has implemented external proficiency testing (PT) for blood grouping test (BGT) since 2011. We analyzed the results of 2015 PT for BGT including hemagglutination grade for ABO BGT to help in planning the future PT for BGT and improving the quality of blood centers (BC). METHODS: Two kinds of whole blood survey samples composed of three panels for ABO grouping and three panels for D typing were sent to 68 institutes. Evaluation criteria for BGT were as follows: 'Good' for the answers matched with intended results, 'Acceptable' for the consensus answers other than that of 'Good', 'Unacceptable' for the answers other than those of 'Good+acceptable' as correct answers. RESULTS: The answer rates of 'Unacceptable' for ABO BGT were 0% for A(A1) antigen (Ag), 1.5% for B Ag, and 1.5% for ABW (A2BW) Ag, 15% of blood centers were graded as 'Acceptable' for ABW (A2BW) Ag because they could not detect BW Ag. All answers for D typing were 'Good' except one institute reported wrong switched results as D positive and D negative. Hemagglutination grade for ABO BGT varied from 77.2%~100% depending on blood groups and laboratories. CONCLUSION: Because some hospital BC could not detect BW Ag and there was a clerical error, continuous education should be required, and comparison of hemagglutination grade for ABO BGT of each BC would be helpful in improving quality of BC.

The Change in Distribution of Red Blood Cell Antigens in Korean Youth: In an Era of Multicultural Society / 대한수혈학회지

BACKGROUND: It is important to check the blood group antigens to ensure the safety of blood transfusions. Recently, the number of multicultural families and foreigners has increased in Korea; therefore, a survey for red blood cell antigens for multicultural families is need. We performed a phenotyping of their red blood cell antigens and found the characteristics in providing basic data. METHODS: We recruited young people under the age of 26 years from multicultural family between September 2015 and March 2016. The participants were divided into two groups: the multicultural youth group (MCY) and the non-multicultural youth group (non-MCY). Subjects underwent phenotyping of ABO, Rh, Kell, Kidd, Duffy, MNS, and Diego blood group, and the results were compared and characterized between the two groups. RESULTS: A total of 226 subjects (89 MCY, 137 non-MCY) were recruited. The blood groups with differences between MCY and non-MCY were E, e in Rh and S in MNS. In MCY, the frequency of CDe expression in the Rh blood group was higher and the cDE expression was lower. There were 3.4% and 2.2% of MCY with no expression of Fy(a) and s, respectively, which were rare blood types in Koreans. CONCLUSION: The difference in frequency of red blood cell antigens between MCY and non-MCY have been identified. These results suggest that the national blood policy reflects an increasing number of multicultural families and Korea needs to be prepared for a population change.

Results of Proficiency Tests for HBsAg and Anti-HCV as the Blood Donor Screening Testing (2012~2015) / 대한수혈학회지

BACKGROUND: Donor screening test is one of the most important processes for blood safety management. Korea Center for Disease Control and Prevention (KCDC) has been conducting an annual proficiency test program that includes the distribution of specially manufactured panels for hepatitis B surface antigen (HBsAg) and antibody to hepatitis C virus (anti-HCV) to blood centers. Here, KCDC reports the results of these proficiency tests for HBsAg and anti-HCV blood donor screening for all licensed blood centers in Korea between 2012 and 2015. METHODS: Panels for the proficiency tests were manufactured and distributed to blood centers by Chung-Ang University Hospital, which has been participating in the Korea Blood Safety Commission. Well-proven reactive sera and healthy donor's sera acquired from the Human Serum Bank in Chung-Ang University were used to make the panels. To identify the S/CO ratio of the panel, three medical institutes triple-checked the results of each panel. RESULTS: Most blood centers reported correct answers for the proficiency test with six panels. The average percentages (year) of correct answers were as follows: 98.7% (2012), 98.5% (2013), 99.1% (2014) and 99.6% (2015) for the HBsAg proficiency tests; and 97.7% (2012), 99.5% (2013), 99.1% (2014), and 99.8% (2015) for the anti-HCV proficiency tests. CONCLUSION: To improve the blood center's ability for donor screening tests, KCDC will continue the proficiency test program by managing specialized panels for HBsAg and Anti-HCV tests. Furthermore, we will investigate the level of satisfaction to improve the quality of the program.

Serious Adverse Transfusion Reactions Reported in the National Recipient-Triggered Trace Back System in Korea (2006-2014)

BACKGROUND: Adverse transfusion reactions (ATRs) are clinically relevant to patients with significant morbidity and mortality. This study aimed to review the cases of ATR reported in the recipient-triggered trace back system for a recent nine-year period in Korea. METHODS: Nine-year data obtained from 2006 to 2014 by the trace back system at the Division of Human Blood Safety Surveillance of the Korean Centers for Disease Control (KCDC) were reviewed. The suspected cases were assessed according to six categories: (i) related to, (ii) probably related to, (iii) probably not related to, (iv) not related to transfusion, (v) unable to investigate, and (vi) under investigation. RESULTS: Since 2006, 199 suspected serious ATRs were reported in hospitals and medical institutions in Korea, and these ATRs were reassessed by the division of Human Blood Safety Surveillance of the KCDC. Among the reported 193 cases as transfusion related infections, hepatitis C virus (HCV) infection (135, 67.8%) was reported most frequently, followed by hepatitis B virus (HBV) infection (27, 13.6%), HIV infection (13, 6.5%), syphilis (9, 4.5%), malarial infection (4, 2.0%), other bacterial infections (3, 1.5%), HTLV infection (1, 0.5%), and scrub typhus infection (1, 0.5%), respectively. Of the 199 cases, 13 (6.5%) cases were confirmed as transfusion-related (3 HCV infections, 3 malarial infections, 1 HBV infection, 2 Staphylococcus aureus sepsis, 3 transfusion-related acute lung injuries, and 1 hemolytic transfusion reaction). CONCLUSIONS: This is the first nationwide data regarding serious ATRs in Korea and could contribute to the implementation of an effective hemovigilance system.

Transfusion Strategy and Laboratory Update on the DEL Variant / 대한수혈학회지

Red cells that express extremely low levels of D antigen that cannot be detected by routine serologic tests are designated as DEL. Most DEL blood donors are typed as D-negative. However, DEL red blood cells can be recognized by serological adsorption and elution test or molecular RHD genotyping. Anti-D production in patients with D-negative who received transfusion containing DEL blood has reported, therefore distinction between DEL variant and true D- negative is clinically important. This review highlights a transfusion strategy and laboratory update on the DEL variant in the Korean population.

Report on External Proficiency Testing for the ABO and D Blood Group Typing Tests in Blood Centers (2014) / 대한수혈학회지

BACKGROUND: Korean Blood Safety Commission has implemented external proficiency testing (PT) for blood grouping test (BGT) to help improve the quality of blood centers since 2011. We analyzed the results of 2014 PT for BGT to help in planning the future PT for BGT and to improve the quality of blood centers. METHODS: Whole blood survey samples including three panels for ABO grouping and three panels for D typing were sent to 69 institutes. Evaluation criteria for BGT were as follows: 'Good' for answers matched with intended results, 'Acceptable' for correct answers other than that of 'Good', 'Unacceptable' for answers other than those of 'Good+acceptable' as correct answers; and 'Not graded' for answers in case of different answers in the two standard laboratories. RESULTS: All of the answer rates of 'Good' for D typing were 100%. However, the answer rates of 'Good' for cell typing, serum typing and interpretation for 14-ABO-2 samples with discrepant result between cell typing and serum typing were 39.1%, 29%, and 47.8%, respectively. Those of 'Unacceptable' for cell typing and interpretation for 14-ABO-2 samples were 2.8% and 1.4%. CONCLUSION: Because the answer rates of ABO grouping for samples with discrepant result between cell typing and serum typing were not high, education for this case is needed. Diversity of materials for PT would be necessary for more accurate evaluation of the performance of BGT in blood centers.

Report on External Proficiency Testing for the ABO and D Blood Typing in Blood Centers in 2012 and 2013 / 대한수혈학회지

BACKGROUND: It was reported that a continuous education program and external proficiency testing (PT) for blood grouping test (BGT) might be necessary because some blood centers of medical institutions could not correctly examine ABO subtype and D variant, according to the results of the first year project in 2011. Therefore, the results of PT for BGT in blood centers in 2012 and 2013 were compared to those in 2011 in order to assess the impact of projects during a period of three years and to help in planning the future PT for BGT. METHODS: Whole blood survey samples composed of three panels for ABO grouping and three panels for D typing were sent to 74 and 71 institutes in 2012 and 2013, respectively. Evaluation criteria for BGT were as follows: 'Good' for the answers matched with intended results, 'Acceptable' for the correct answers other than that of 'Good', and 'Unacceptable' for the answers other than those of 'Good+acceptable' as correct answers. RESULTS: The answer rates of 'Unacceptable' for ABO subtype were 1.4% in 2012 and 4.2% in 2013. However, the answer rate of 'Good' increased from 44.6% in 2012 to 83.1% in 2013. The answer rate of 'Unacceptable' for D variants showed a marked decrease, from 16.2% in 2012 to 1.4% in 2013. CONCLUSION: Projects for PT for BGT during a period of three years have improved laboratory quality in blood centers. However, the acquisition and change of the materials for PT would be necessary in order to continuously and practically provide help to blood centers.

The Status of Use of Leukoreduced Blood Products in Korean Hospitals

BACKGROUND: Leukoreduced blood components are recommended for prevention of non-hemolytic febrile transfusion reactions, HLA alloimmunization, platelet transfusion refractoriness, and transfusion-transmissible diseases. In addition, prestorage leukoreduction may be advantageous to poststorage leukoreduction. The authors investigated the current status of usage of leukoreduced blood components in Korea. METHODS: We surveyed 2,373 medical facilities, where blood components were supplied from Korean Red Cross blood centers and/or Hanmaeum blood center during one year period between January and December 2009. The survey was conducted about the current situation of usage of leukoreduction by web-based program (http://bms.cdc.go.kr), and 743 facilities answered and were analyzed. RESULTS: The leukoreduced RBC components comprised 10.3% (prestorage leukoreduction, 91,066 units, 5.7%; poststorage leukoreduction 73,192 units, 4.6%) of the total 1,593,098 units of RBC components used in 743 medical facilities. The leukoreduced platelet concentrates comprised 33.1% (458,552 units) of the total 1,386,184 units of platelet concentrates used in 397 medical facilities. If 1 single donor platelet is counted as 6 platelet concentrates, 48.9% of the total platelet components used were leukoreduced. CONCLUSIONS: The proportion of leukoreduced blood components to the total blood components used in Korea was much lower than that in Unites States of America, especially lower in the use of prestorage leukoreduction of RBC components. Further studies are required for cost-effectiveness and demand-supply amounts of leukoreduced blood components, and appropriate prestorage leukoreduction has to be performed in Korea based on these studies.

The Current Status of Informed Consent for Transfusion in Korea and Development of a Standard Informed Consent for Transfusion / 대한수혈학회지

BACKGROUND: This study was conducted to standardize the written informed consent form for transfusion to establish the recipient's self-determination and safe blood transfusion procedures of hospitals. This survey focused on doctors' acknowledgment on informed consent before conducting a transfusion and its current situation. METHODS: Data collection was conducted in 11 tertiary hospitals from February 2010 to March 2010 with random sampling among the 30 hospitals that have a blood transfusion committee. The survey was carried out in the division of medical services that supports blood transfusion or in the blood transfusion committee of each hospital. The questionnaires focused on the necessity of written consent and its contents before transfusion. Also, informed consent forms were collected when a hospital already had an informed content form. RESULTS: The majority of hospitals (94.9%) agreed about the necessity of informed consent. However, only 6.7% of hospitals were obtaining informed consent before transfusion. The contents of the written form were the necessity of blood transfusion (94.9%), the adverse effects of transfusion (84.1%) and beneficiary of the transfusion (64.6%). Twenty-eight point two percent of the medical institutions were obtaining informed written consent forms and keeping them in the medical records. The problems for obtaining informed consent before a transfusion was insufficient standardized forms (40.4%) and a lack of time (33.9%). CONCLUSION: Though doctors agreed to the provision of information through consent forms, there were no standardized procedures and forms. Therefore, this study introduced the written form to medical institutions and academies. Also, it was applied to hospitals as an evaluation index in 2010. The written informed consent form can contribute to the safety of blood transfusions in the medical area.

An Analysis of Blood Usage and Blood Wastage in Korea Hospitals in 2008 / 대한수혈학회지

BACKGROUND: Investigating the blood usage and blood wastage in Korea hospitals national wide, and including all types of medical institutes, has not been sufficient with the only study having been carried out by the KCDC thorough an Academic Research Contract in 2007. Yet that study was limited due to lack of participation from hospitals. Our study tried to establish a fundamental database for blood transfusion management by investigating the current status of blood products usage, under the KCDC's supervision, to improve participation from medical institutes. METHODS: From January to December in 2008, the Blood Bank, Red Cross of the Republic of Korea looked into the blood product supply of all the medical institutes and we conducted a national survey using questionnaires distributed via the local public health centers on the blood use, blood waste, the reasons for waste and the inventory of the remaining blood. The supply, as compared to the actual use of blood products in the same period, was analyzed by the Korean Red Cross. RESULTS: The total amount of blood products distributed by the Korean Red Cross to medical institutes in 2008 increased by 13.8% for platelets, 11.5% for RBC products, 8.4% for apheresis products and 2% for FFPs, as compared with that of 2006. A total of 2,500 institutions participated in the questionnaire and 60.7% (1,517 out of 2,500 institutes) of the institutes sent feed-back. The total amount of blood use was 3,483,636 units and 52% of the consumption was focused in metropolitan areas like Seoul, Geong-Ki and Busan. The total wastage rate for blood was 1.2% and it was 4.8% for institutes with admitting capacities of 100 beds or less, with expiration of the storage date being the main reason for wastage, while the wastage rate was 1.1% for general hospitals with admitting capacities of 500 beds or more, with an improving patient status or death being the main reason. CONCLUSION: The results of this study were similar to those of 2007, but the participation rate from medical institutes was much increased. Establishment of an investigational system for the use of blood products in medical institutes on a national level is needed to secure data for dealing with the increased projected demand of blood/blood products in the future.