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.

Association between CYP2D6 phenotype and recurrence of Plasmodium vivax infection in south Korean patients.

BACKGROUND: Primaquine is activated by CYP2D6 in the hepatocytes. In Korea, primaquine is the only hypnozoitocidal agent used for patients with vivax malaria. Thus, patients with poor CYP2D6 activity could have an increased risk of primaquine failure and subsequent relapse. The study sought to identify the association between CYP2D6 phenotype and recurrence of malaria in Korean patients. METHODS: A total of 102 patients with vivax malaria were prospectively enrolled from eight institutions in Korea. An additional 38 blood samples from patients with recurred vivax malaria were provided by the Korea Disease Control and Prevention Agency. Malaria recurrence was defined as more than one episode of vivax malaria in the same or consecutive years. CYP2D6 star alleles, phenotypes, and activity scores were examined. RESULTS: Genotyping for CYP2D6 was successful in 101 of the prospectively enrolled patients and 38 samples from the Korea Disease Control and Prevention Agency, of which 91 were included in the no-recurrence group and 48 were included in the recurrence group. Reduced CYP2D6 activity (intermediate metabolizer) phenotype was more common in the recurrence group than in the no-recurrence group (OR, 2.33 (95% CI, 1.14-4.77); p = 0.02). Patients with lower CYP2D6 activity had a higher probability of recurrence (p = 0.029). CONCLUSION: This study suggests that CYP2D6 polymorphism may affect primaquine efficacy and thus Plasmodium vivax recurrence in Korea.

Increased Prevalence of Thalassemia in Young People in Korea: Impact of Increasing Immigration.

BACKGROUND: Thalassemia is highly prevalent in Southeast Asia but is rare in Korea; however, Southeast Asian immigrant population is recently rising in Korea. We investigated the prevalence of thalassemia in Korea in the context of increasing immigration. METHODS: This prospective, observational, multicenter study was conducted between September 2015 and August 2017. A total of 669 subjects <30 years living in Korea were grouped into the multiethnic (N=314) and Korean (N=355) groups. Hb electrophoresis and complete blood count (CBC) were performed. If low mean corpuscular volume with high red blood cell distribution width coefficient of variation or a high fetal Hb (HbF) or Hb alpha 2 (HbA2) level was observed, genetic testing of the α- and ß-globin genes was performed. In addition, the number of potential thalassemia carriers in Korea was estimated by multiplying the prevalence of thalassemia in a specific ethnicity by the number of immigrants of that ethnicity. RESULTS: Twenty-six multiethnic and 10 Korean subjects showed abnormal results for Hb electrophoresis and CBC. Eighteen multiethnic subjects and four Korean subjects were tested for α-globin and ß-globin gene mutations. Within the multiethnic group, five subjects (1.5%) were α-thalassemia carriers, and six (1.9%) were ß-thalassemia minor. The SEA deletion in HBA1 and HBA2, and c. 126_129delCTTT (p.Phe42Leufs*19) mutation of HBB were the dominant inherited mutations. CONCLUSIONS: The prevalence of thalassemia in young people in Korea is increasing due to the increasing number of Southeast Asian immigrants.

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.

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.

Genotyping of 22 blood group antigen polymorphisms and establishing a national recipient registry in the Korean population.

It is often difficult for standard blood banks in Korea to supply adequate amounts of blood for patients with rare phenotype. Moreover, the definition of a blood in need is ambiguous, and much remains to be learned. In this study, we determined the prevalence of various red blood cell (RBC) antigens from a donor viewpoint and estimated the demand for specific antigen-negative blood from a patient viewpoint. Our data will aid the establishment of a Rare Blood Program in Korea (KRBP). RBC genotyping of 419 blood donors was performed using a Lifecodes RBC/RBC-R typing kit (Immucor, Norcross, GA). A national recipient registry website has been established. Each hospital-based blood bank voluntarily enters data on antibodies detected and identified and the outcomes of specific antigen testing. We calculated the availabilities of specific antigen-negative blood components based on these registry data and predicted the prevalence of RBC antigens via RBC genotyping. The prevalences of various RBC antigens in the D-negative population were determined for the first time, and the Cartwright, Scianna, Dombrock, Colton, Landsteiner-Wiener, Cromer, and Knops blood group systems were identified. The availabilities of specific antigen-negative units differed when calculations were based on serotyping or genotyping, especially in the D-negative group. Data on the prevalences of various blood antigens are essential for estimating the availabilities of blood components that are appropriate for use by patients expressing relevant antibodies. Then, blood banks would be able to efficiently supply safe blood products.