Single nucleotide polymorphism analysis of pvmdr-1 in Plasmodium vivax isolated from military personnel of Republic of Korea in 2016 and 2017.

BACKGROUND: Malaria chemoprophylaxis using chloroquine (CQ) and primaquine (PQ) has been administered to resident soldiers in the 3rd Army of Republic of Korea (ROK) to prevent malaria infection since the year 1997. Due to mass chemoprophylaxis against malaria, concern exists about the occurrence of chloroquine resistance (CQR). This study aimed to investigate the single nucleotide polymorphisms (SNPs) of the Plasmodium vivax multi-drug resistance protein-1 (pvmdr-1) gene to monitor the risk of CQR. METHODS: SNPs of the pvmdr-1 gene were analysed in 73 soldiers of the 3rd Army of ROK diagnosed with infection by P. vivax. RESULTS: Quintuple mutations (G698S, L845F, M908L, T958M, and F1076L) were detected in 73 soldiers. A newly identified non-synonymous mutation in the Y541C position had been introduced into P. vivax malaria-endemic areas in ROK, at a frequency of 1.3% (1/73). In addition, synonymous mutations were detected at positions K44 (38.4%, 28/73), L493 (26%, 19/73), T529 (61.6%, 45/73), and E1233 (52.1%, 38/73). Based on these SNPs, pvmdr-1 sequences of ROK were classified into 6 haplotypes. The phylogenetic analysis closed to the type of North Korean showed that P. vivax malaria of ROK could be a reason of influx from North Korea. CONCLUSIONS: This study showed that synonymous and non-synonymous mutations of pvmdr-1 were observed in the malaria chemoprophylaxis-executed regions of ROK from 2016 to 2017. Based on the rapid transition of pvmdr-1 SNPs, continuous surveillance for SNPs of pvmdr-1 related to CQR in the malaria-endemic regions of ROK is essential.

Whole-genome sequence analysis of Zika virus, amplified from urine of traveler from the Philippines.

Zika virus (ZIKV) (genus Flavivirus, family Flaviviridae) is an emerging pathogen associated with microcephaly and Guillain-Barré syndrome. The rapid spread of ZIKV disease in over 60 countries and the large numbers of travel-associated cases have caused worldwide concern. Thus, intensified surveillance of cases among immigrants and tourists from ZIKV-endemic areas is important for disease control and prevention. In this study, using Next Generation Sequencing, we reported the first whole-genome sequence of ZIKV strain AFMC-U, amplified from the urine of a traveler returning to Korea from the Philippines. Phylogenetic analysis showed geographic-specific clustering. Our results underscore the importance of examining urine in the diagnosis of ZIKV infection.

Comparison of the accuracy of noninvasive hemoglobin sensor (NBM-200) and portable hemoglobinometer (HemoCue) with an automated hematology analyzer (LH500) in blood donor screening.

BACKGROUND: The Hb levels of prospective blood donors are usually determined using a finger prick test. A new noninvasive Hb device has the advantage of not causing any sampling pain. The purpose of this study was to evaluate the accuracy of the noninvasive Hb sensor and to compare its measurements with those of a currently used portable hemoglobinometer. METHODS: Hb was measured using a noninvasive Hb sensor (NBM-200; OrSense, Israel), a portable hemoglobinometer (HemoCue; HemoCue AB, Sweden), and an automated hematology analyzer (LH500; Beckman Coulter, USA). The correlations between Hb measurements taken by the NBM-200 and HemoCue with those by an automated hematology analyzer were assessed using intraclass correlation coefficients (ICCs). Hb measurements were compared among 3 different Hb level groups. RESULTS: The mean Hb values of 506 blood donors were 14.1 g/dL by the NBM-200, 14.0 g/dL by the LH500, and 14.3 g/dL by the HemoCue. The correlation between the LH500 and the NBM-200 was substantial (ICC=0.69), while that between the LH500 and the HemoCue agreed almost perfectly (ICC=0.86). CONCLUSIONS: The possibility to judge to be eligible for donors who are ineligible to donate was substantial when using NBM-200. Even though the NBM-200 has the apparent advantage of noninvasiveness, its use in pre-screening should be given meticulous attention. Since pre-donation testing is crucial to protecting donors' health, complete evaluation of the instrument should be performed prior to use.

Performance evaluation of the OraQuick hepatitis C virus rapid antibody test.

BACKGROUND: A reliable rapid assay for hepatitis C virus (HCV) may be helpful in various clinical settings. We evaluated the performance of the OraQuick HCV Rapid Antibody Test (OraSure Technologies Inc., Bethlehem, PA, USA). METHODS: Clinical sensitivity and specificity were evaluated with oral fluids and sera from 137 patients diagnosed with hepatitis C and 300 healthy blood donors in a multi-center collaborative study. The stored sera of 200 proven HCV-infected patients and 200 healthy subjects were also evaluated. Analytical sensitivity was estimated with 4 commercial seroconversion panels and 7 Korean reference panels. The performance of 4 laboratory-based tests (3 chemiluminescence assays and 1 enzyme immunoassay) and 4 rapid test kits was compared. We also assessed the interference due to bilirubin, hemoglobin, lipid, rheumatoid factor, multipara, and several viral infections. RESULTS: The clinical sensitivity and specificity of the OraQuick HCV test using oral fluid were 97.8% (95% confidence interval [CI], 93.2-99.4%) and 100% (95% CI, 98.4-100%), respectively. The clinical sensitivity using serum samples was 100%. Using the 4 seroconversion panels, the OraQuick HCV test showed results comparable to those of the laboratory-based assays; its analytical sensitivity was higher than that of the other rapid test kits. There was no cross-reactivity with common interfering factors. CONCLUSIONS: The clinical performance of the OraQuick HCV Test is comparable to that of laboratory-based tests with both serum and oral fluid. This supports the supplementary use of rapid HCV testing using oral fluid in various medical and non-medical settings.

Upper limit of normal serum alanine and aspartate aminotransferase levels in Korea.

BACKGROUND AND AIM: The widely accepted range of upper limits of normal (ULN) alanine aminotransferase (ALT) levels (ULN < 40 U/L) was recently challenged by several reports. Both ALT and aspartate aminotransferase (AST) are commonly used as surrogate markers of liver disease, but almost all studies of aminotransferase activity were conducted on ALT. We investigated not only ULN of ALT but also AST activity and to identify factors modulating them in healthy Korean. METHODS: A cross-sectional study of 411,240 registered blood donors in all nationwide blood banks belonging to the Korean Red Cross were conducted. ULN of ALT and AST was evaluated adjusting their age according to the national population census database. "Decision tree model" was used to identify the affecting factors of ALT and AST and optimal cut-off points of affecting factors. RESULTS: "ULN of ALT" was 34 U/L in men and 24 U/L in women and "ULN of AST" was 32 U/L in men and 26 U/L in women in the blood donor database. Decision tree analysis showed that ALT levels were mostly influenced by body mass index level and its critical two cut-off points were 23.5 kg/m2 and 25.8 kg/m2 , respectively. The most affecting factor of AST was gender. CONCLUSION: Upper limits of normal of ALT and AST in Koreans were lower than conventional accepted values (< 40 U/L) but higher than recently suggested values (male < 30 U/L and female < 19 U/L). Body mass index was the most determining factor for ALT and gender was the most influencing factor for AST activity.

Residual risk of transfusion-transmitted infection with human immunodeficiency virus, hepatitis C virus, and hepatitis B virus in Korea from 2000 through 2010.

BACKGROUND: Despite screening blood donations with advanced technologies and improved donor screening, the risk of transfusion-transmitted infections persists. This risk is mainly due to blood donations collected during the window period. A precise estimate of the transfusion risk of viral infection will help to determine the effect of new and current safety measures and to prioritize and allocate limited resources. Therefore, we estimated the risk of transfusion-transmitted viral infection in blood donations collected in Korea from 2000 to 2010. METHODS: Blood donations collected at 16 blood centers were tested for HIV, HCV, and HBV to estimate the residual risk of transfusion-transmitted viral infection. The residual risk was calculated in two-year periods using the incidence/window model. The incidence rates for HIV/HCV and the confirmed positive rate for HIV/HCV in first-time and repeat donors were compared. RESULTS: The residual risks for HIV in 2004/2005 and 2009/2010 were 1 in 1,080,244 and 1 in 1,356,547, respectively. The risks for HCV in 2000/2001 and 2009/2010 were 1 in 81,431 and 1 in 2,984,415, and the risks for HBV in 2000/2001 and 2009/2010 were 1 in 45,891 and 1 in 43,666. These estimates indicate that the residual risks for HCV in Korea have declined 36.6-fold, and those for HIV and HBV have not improved significantly, compared to previous estimates. The odds ratios for HCV and HBV positivity in first-time donors compared to repeat donors were 11.8 and 19.6, respectively. CONCLUSIONS: The residual risk of HCV declined over the last decade due to improved screening reagents, implementation of the nucleic acid amplification test, and tight application of strict donor selection procedures. Current residual risk estimates for HIV and HCV in Korea are extremely low, but the risk for HBV is still high; therefore, urgent measures should focus on decreasing the residual risk of HBV. Despite the introduction of more sensitive assays in blood screening, several other factors may influence the actual residual risk of transfusion-transmitted infection. A continuous monitoring of residual risk of transfusion-transmitted infection is crucial in managing blood safety.

Prevalence of antibodies to hepatitis B core antigen and occult hepatitis B virus infections in Korean blood donors.

BACKGROUND: This study was performed to determine the prevalence of antibodies to hepatitis B core antigen (anti-HBc) among Korean blood donors and frequencies of hepatitis B virus (HBV) DNA and antibodies to hepatitis B surface antigen (anti-HBs) in anti-HBc-positive donors. STUDY DESIGN AND METHODS: A total of 12,461 consenting blood donors were consecutively enrolled from Korean Red Cross Blood Services from April to October 2008. All of the donors were screened for anti-HBc with an electrochemiluminescence immunoassay. Repeat-reactive anti-HBc-positive donors were assayed for anti-HBs and for HBV DNA using a multiplex test (Cobas TaqScreen, Roche Molecular Systems) on individual donation. RESULTS: Of the 12,461 donors, 1682 (13.5%) were reactive for anti-HBc. Among different age groups, there was a steady increase in the anti-HBc-positive rate, ranging from 2.0% in the age group of less than 20 years to 80.0% in the age group of 60 years and older (p<0.0001). Of the anti-HBc-positive donors, 1523 (90.5%) were anti-HBs positive. HBV DNA was detected in two donors who were anti-HBc positive and hepatitis B surface antigen negative. The prevalence of occult HBV infection was 0.016%, and the HBV nucleic acid test (NAT) yield was 1 in 838 (0.12%). CONCLUSION: This study helps to determine the current status of hepatitis B infection and the prevalence of occult HBV infection in the blood donor population in Korea. We estimate that in Korea, up to 161 units per million donated units from blood donors may contain HBV DNA. Although the potential infectivity of these units has been debated upon, the HBV NAT assay could prevent certain transfusion-transmitted HBV infections.

Lymphocyte subsets and mood states in panic disorder patients.

This study was conducted to examine lymphocyte subset counts and mood states in panic disorder patients. Twenty patients with panic disorder and 20 age- and gender-matched normal healthy subjects were recruited for the study. We used the Spielberger State (STAIS) & Trait (STAIT) Anxiety Inventory, Hamilton Depression Rating scale (HAMD) and Hamilton Anxiety Rating scale (HAMA) to measure mood states in all subjects. Lymphocyte subsets counts were made by flow cytometry. Panic patients showed significantly higher scores for anxiety and depression than normal subjects. Panic patients showed no differences in terms of the numbers of immune cells, as compared with normal healthy subjects, other than a lower proportion of T suppressor cells and a higher T helper cell/T suppressor cell ratio. HAMA and STAIS scores were common factors that could predict T cell numbers and proportions, T helper cell numbers, and natural killer cell proportions in panic disorder patients. We suggest that anxiety levels are related to the T-cell population in panic disorder patients and that quantitative immune differences may reflect altered immunity in this disorder.

Changes in lymphocyte subsets after short-term pharmacotherapy in patients with panic disorder.

Panic disorder is associated with a high frequency of comorbid immunological diseases, such as allergies and asthma, although the psychoneuroimmunology of panic disorder is relatively unexplored. The objective of this study was to determine whether panic patients have different immunological findings compared with normal healthy subjects and whether changes in immune function are associated with short-term pharmacotherapy. We also examined whether immunological variables were associated with clinical severity and serum catecholamine levels. Patients with panic disorder (n=26) and healthy control subjects (n=26) were recruited for this study. All patients were treated with paroxetine for 3 months. We measured the lymphocyte subsets, psychopathological characteristics and serum catecholamine (norepinephrine and epinephrine) levels. Panic patients did not differ initially from control subjects in peripheral lymphocyte phenotypic markers. After drug therapy, however, percentages of circulating CD3+, CD4+ and CD8+ T lymphocytes were significantly increased, while the percentage of CD19+ B lymphocytes was significantly decreased in the patients. The difference in the percentage of CD8+ T lymphocytes before and after treatment was negatively correlated with pretreatment Global Clinical Impression scores. The lymphocyte subsets were not significantly associated with serum catecholamine levels in panic patients. In conclusion, panic patients showed increased CD3+, CD4+ and CD8+ T lymphocyte proportions and a decreased B lymphocyte proportion after 3 months of drug therapy. This finding suggests that pharmacological treatment may affect immune function in panic patients.

MLL/SEPTIN6 chimeric transcript from inv ins(X;11)(q24;q23q13) in acute monocytic leukemia: report of a case and review of the literature.

Rearrangements of the MLL gene on chromosome 11, band q23, are one of the most common genetic changes in acute leukemia. Reciprocal translocation is the most common form of MLL rearrangement, and the partner genes in MLL translocation are notably diverse. Involvement of the SEPTIN6 gene on Xq24 in MLL rearrangements occurs very rarely, with only six cases having been documented in the literature. Of note, the MLL/SEPTIN6 rearrangements in these cases were cryptic or complex, and it was shown that the 5'-MLL/SEPTIN6-3' transcript resides on the derivative X chromosome rather than on the derivative chromosome 11 as in the majority of cases of MLL translocations. These observations suggested that MLL and SEPTIN6 reside on their respective chromosome loci in reverse orientation, that is, centromere-to-telomere and telomere-to-centromere, respectively. We here report a case of acute monocytic leukemia with inv ins(X;11)(q24;q23q13) in a 29-month-old child. Fluorescence in situ hybridization study revealed the break-apart 5'-MLL segment to be translocated to the derivative X chromosome, and reverse transcriptase-polymerase chain reaction followed by sequencing analysis confirmed the 5'-MLL/SEPTIN6-3' chimeric transcript. This case is the first to provide direct cytogenetic evidence for the salient nature of the MLL/SEPTIN6 rearrangement. We reviewed clinical and cytogenetic features of all cases of 11q23 and Xq22-24 rearrangements reported up to now, including six cases where the involvement of the SEPTIN6 gene was confirmed by molecular techniques.

Comparison of microvessel density before and after peripheral blood stem cell transplantation in multiple myeloma patients and its clinical implications: multicenter trial.

Bone marrow angiogenesis has been reported to increase in several hematologic malignant diseases, including multiple myeloma. Because high-dose chemotherapy combined with autologous stem cell transplantation (SCT) improves the response rate, event-free survival, and overall survival in patients with multiple myeloma (MM), we studied the changes in bone marrow microvessel density (MVD) in 21 patients who underwent high-dose chemotherapy combined with autologous SCT to determine whether there was persistently increased angiogenesis at the time of response. Bone marrow biopsy specimens were obtained before and after SCT for each patient and immunostained with anti-CD34 antibodies for the identification of microvascular endothelial cells. The mean value of MVD in 21 MM patients at initial diagnosis was 46.0 +/- 24.0 and in healthy controls was 26.8 +/- 8.54 (P = .046). The mean MVD at initial diagnosis was 46.0 +/- 24.0 compared with 29.0 +/- 12.5 after achievement of response with SCT, and there was a statistically significant difference (P = .004). Sixteen of 21 patients (76.2%) had decreased MVD after SCT, and 5 patients were found to have a greater than 50% decrease in MVD after SCT. However, there was no difference in overall survival between the patient group with decreased MVD after SCT and that without decreased MVD (P = .9370). These results suggest that angiogenesis plays an important role in MM. In addition, the persistence of MVD at the time of response indicates continuous stimulus of microvessels by minimal residual disease even after SCT.