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1.  Hospital-based influenza morbidity and mortality surveillance system for influenza-like illnesses: a comparison with national influenza surveillance systems 
The Hospital-based Influenza Morbidity and Mortality (HIMM) surveillance system is an emergency room (ER)-based influenza surveillance system in Korea that was established in 2011. The system was established under the assumption that integrated clinical and virologic surveillance could be performed rapidly and easily at seven tertiary hospitals' ER. Here, we assessed the correlation between data generated from the HIMM surveillance system and the Korean national influenza surveillance systems during the 2011–2012 influenza season using cross-correlation analysis and found strong correlations. Rapid antigen-test-based HIMM surveillance would predict the start of influenza epidemic earlier than pre-existing influenza-like-illness-based surveillance.
PMCID: PMC4177793  PMID: 24020512
Influenza; influenza-like illness; Korea; surveillance
2.  Influenza Vaccines: Unmet Needs and Recent Developments 
Infection & Chemotherapy  2013;45(4):375-386.
Influenza is a worldwide public health concern. Since the introduction of trivalent influenza vaccine in 1978, vaccination has been the primary means of prevention and control of influenza. Current influenza vaccines have moderate efficacy, good safety, and acceptable tolerability; however, they have unsatisfactory efficacy in older adults, are dependent on egg supply for production, and are time-consuming to manufacture. This review outlines the unmet medical needs of current influenza vaccines. Recent developments in influenza vaccines are also described.
PMCID: PMC3902815  PMID: 24475351
Influenza, Human; Influenza Vaccines; Pandemics
3.  Depression Among HIV-infected Patients in Korea: Assessment of Clinical Significance and Risk Factors 
Infection & Chemotherapy  2013;45(2):211-216.
With prolonged life expectancies, mental illness has emerged as a disabling disorder among people with HIV.
Materials and Methods
This study was conducted to assess the prevalence of depression and its risk factors among Korean patients with HIV infections. Eighty-two HIV-infected patients completed structured questionnaires including the Beck Depression Inventory and the State-Trait Anxiety Inventory. Subjects with depression were compared to those without depression in terms of demographics, comorbidities, CD4 T-cell count, RNA copy numbers, highly active antiretroviral therapy (HAART) regimens, and adherence.
The estimated depression rate was 21% (17 of 82 subjects). Comorbidities (47% vs. 20%, P = 0.01) and unemployment (65% vs. 31%, P = 0.02) were risk factors for depression. Depressive patients were more likely to be anxious (71% vs. 29%, P < 0.01), to frequently miss clinical appointments each year (P = 0.04), and to have higher cumulative time lost to follow-up per month (P <0.01) compared to non-depressive patients. Only three depressive patients were referred to neuropsychologists.
More than 20% of the Korean HIV patients in this study suffered from depression associated with poor adherence. Considering the low level of recognition of depression by clinicians, risk factor-based active assessment is recommended to manage depression properly in HIV-infected patients.
PMCID: PMC3780946  PMID: 24265969
HIV; Acquired immunodeficiency syndrome; Depression; Anxiety
4.  Concurrent Tuberculosis and Influenza, South Korea 
Emerging Infectious Diseases  2013;19(1):165-167.
PMCID: PMC3557969  PMID: 23260033
Tuberculosis; influenza; pandemics; South Korea; respiratory infections; tuberculosis and other mycobacteria; viruses
5.  The Clinical Usefulness of the SD Bioline Influenza Antigen Test® for Detecting the 2009 Influenza A (H1N1) Virus 
Yonsei Medical Journal  2011;52(4):683-685.
Though the 2009 worldwide influenza A (H1N1) pandemic has been declared to have ended, the influenza virus is expected to continue to circulate from some years as a seasonal influenza. A rapid antigen test (RAT) can aid in rapid diagnosis and allow for early antiviral treatment. We evaluated the clinical usefulness of RAT using SD Bioline Influenza Antigen Test® kit to detect the influenza virus, considering various factors. From August 1, 2009 to October 10, 2009, a total of 938 patients who visited the outpatient clinic at Korea University Guro Hospital with influenza-like illnesses were enrolled in the study. Throat or nasopharyngeal swab specimens were obtained from each of the patients. Using these specimens, we evaluated the influenza detection rate by rapid antigen test based on the real-time reverse-transcriptase polymerase chain reaction (rRT-PCR) method. In comparison with rRT-PCR, the sensitivity and specificity of the RAT were 44.0% and 99.9%, respectively. The cyclic threshold values of RAT negative specimens were higher than RAT positive specimens (30.1±3.1 vs. 28.3±3.9, p=0.031). The sensitivity of the RAT kit was higher in patients who visited clinics within two days of symptom onset (60.4% vs. 11.1%, p=0.026). The results of this study show that the RAT cannot be recommended for general use in all patients with influenza-like illness because of its low sensitivity. The RAT may be used, only in the settings with limited diagnostic resources, for patients who visit a clinic within two days of symptom onset.
PMCID: PMC3104440  PMID: 21623614
Influenza; diagnosis; sensitivity; specificity
6.  Immunogenicity and Safety of Trivalent Inactivated Influenza Vaccine: A Randomized, Double-Blind, Multi-Center, Phase 3 Clinical Trial in a Vaccine-Limited Country 
Journal of Korean Medical Science  2011;26(2):191-195.
Influenza vaccines are the primary method for controlling influenza and its complications. This study was conducted as a phase 3, randomized, double-blind, controlled, multi-center trial at seven university hospitals to evaluate the immunogenicity and safety of an inactivated, split, trivalent influenza vaccine (GC501, Green Cross Corporation, Yongin, Korea), which was newly manufactured in Korea in 2008. Between September 21 and 26, a total of 329 healthy subjects were recruited for the immunogenicity analysis, while 976 subjects were enrolled for the safety analysis. The GC501 vaccine met both FDA and EMEA criteria with ≥ 80% of subjects achieving post-vaccination titers ≥ 40 for all three subtypes, even in the elderly. The vaccine was well tolerated with only mild systemic and local adverse events. In summary, GC501 showed excellent immunogenicity and a good safety profile in both young adults and the elderly. The licensure of GC501 might be an important basis in preparation for the future influenza pandemic.
PMCID: PMC3031001  PMID: 21286008
Influenza Vaccines; Influenza, Human; Vaccines, Inactivated
7.  Characteristics of Non-typhoidal Salmonella Isolates from Human and Broiler-chickens in Southwestern Seoul, Korea 
Journal of Korean Medical Science  2007;22(5):773-778.
Non-typhoidal Salmonella (NTS) is an important commensal microorganism. The purpose of this study was to determine the epidemiological relation between NTS isolates from livestock and NTS isolates from human by analyzing antimicrobial susceptibilities and performing molecular typing. We determined the serotypes of 36 human clinical isolates and 64 livestock isolates, performed antimicrobial susceptibility testing against 8 antibiotics, and determined the molecular types of isolated NTS spp. by pulsed field gel electrophoresis (PFGE). In human isolates, S. enteritidis was the most common serotype (17 isolates; 47.2%) and S. typhimurium the second most (8 isolates; 22.2%). In livestock isolates, S. typhimurium was the most common serotype (15 isolates; 23.44%), and S. enteritidis was the second most (14 isolates; 21.88%). Ampicillin and tetracycline resistance were 50% (32/64 isolates) each among broiler-chicken NTS isolates. No human or livestock NTS isolates showed resistance to ciprofloxacin, TMP-SMX, or ceftriaxone. However, 19.4% (7/36) and 46.8% (30/64) of the human and livestock NTS isolates were resistant to nalidixic acid (MIC ≥16 mg/mL), respectively. The presence of the three identical PFGE molecular types from human and broiler-chicken NTS isolates suggests the possibility of transmission from livestock to humans.
PMCID: PMC2693839  PMID: 17982221
Salmonella Infections; Salmonella Enteritidis; Salmonella Typhimurium; Epidemiology
8.  Prevalence and Molecular Epidemiology of Vancomycin-Resistant Enterococci (VRE) Strains Isolated from Animals and Humans in Korea 
To assess the possibility of VRE transmission from animals to humans, we studied the prevalence of vancomycin-resistant enterococci (VRE) in farm animals, raw chicken meat, and healthy people. We then determined the molecular relatedness of VRE isolates between animals and humans in Korea.
We aimed to isolate VRE from 150 enterococci specimens of farm animals, 15 raw chicken meat samples, and stools from 200 healthy people. Species differentiation was done with conventional biochemical tests. Vancomycin resistance genotyping was done by polymerase chain reaction (PCR). Using the agar dilution method, antimicrobial susceptibility was tested for 8 antimicrobials and pulsed-field gel electrophoresis (PFGE) was done to evaluate the molecular relatedness of VRE isolates.
The prevalence of VRE was 14.7% (22/150) in farm animal specimens, 1% (2/200) in healthy people, and 60% (9/15) in raw chicken meat. Of 22 animal VRE isolates, 1 vanA E. faecium, 15 vanC1 E. gallinarum, and 6 vanC2 E. casseliflavus were identified. All of the 9 VRE from raw chicken meat and all of the 20 clinical VRE strains were vanA E. faecium. However, in healthy people, only 2 vanC2 E. casseliflavus were isolated. These showed low-level resistance to vancomycin and susceptibility to teicoplanin. However, 9 VRE strains from raw chicken meat had high-level resistance to vancomycin (MIC50,90: >128 µg/mL), teicoplanin (MIC50,90: >128 µg/mL), ampicillin (MIC50,90: >128 µg/mL), erythromycin (MIC50,90: >128 µg/mL), and tetracycline (MIC50,90: 128/>128 µg/mL).
This study demonstrated little evidence of VRE colonization in healthy people despite high recovery of VRE among raw chicken meat. It is suggested that there is little evidence of VRE transmission from animals to healthy people. However, we assumed that there exists the possibility of VRE contamination during the processing of chicken meat.
PMCID: PMC3891413  PMID: 15906954
Vancomycin-resistant enterococcus; Domestic animals; Healthy person; PCR; PFGE (electrophoresis, gel, pulsed-field)
9.  Effect of the Influenza Virus Rapid Antigen Test on a Physician's Decision to Prescribe Antibiotics and on Patient Length of Stay in the Emergency Department 
PLoS ONE  2014;9(11):e110978.
Influenza virus infection is a common reason for visits to the emergency department (ED) during the influenza season. A rapid and accurate diagnosis of influenza virus infection is important to reduce unnecessary antibiotic prescription and to improve patient care. The aim of this study was to examine whether using the Influenza Virus Rapid Antigen Test (IVRAT) in the ED affects the decision to prescribe antibiotics or the length of hospital stay (LOS).
Data from patients suffering from an influenza-like illness (ILI) and who were discharged after visiting the ED at Chungbuk National University Hospital were reviewed over two influenza seasons: 2010–2011, when IVRAT was not used in the ED, and 2011–2012, when it was. The numbers of antibiotic prescriptions issued and the ED LOS during these two seasons were then compared.
The number of antibiotic prescriptions was significantly lower in 2011–2012 (54/216, 25.0%) than in 2010–2011 (97/221, 43.9%; P<0.01). However, the median ED LOS for patients in 2011–2012 was much longer than that of patients in 2010–2011 (213 minutes vs. 257 minutes; P<0.01). During the 2011–2012 influenza season, 73 ILI patients showed a positive IVRAT result whereas 123 showed a negative result. Upon discharge, antibiotics were given to 42/123 (34.1%) ILI patients with a negative IVRAT result, but to only 7/73 (9.6%) patients with a positive IVRAT result (P<0.01).
Performing IVRAT in the ED reduced the prescription of antibiotics to ILI patients discharged after ED care. However, the ED LOS for patients who underwent IVRAT was longer than that for patients who did not. Thus, performing IVRAT in the ED reduces the unnecessary prescription of antibiotics to ILI patients during the influenza season.
PMCID: PMC4222913  PMID: 25375835
10.  Clinical and Molecular Epidemiological Features of Hemorrhagic Fever with Renal Syndrome in Korea over a 10-year Period 
Laboratory diagnosis of hemorrhagic fever with renal syndrome (HFRS), an infectious disease caused by rodent-borne hantaviruses in Asia and Europe, depends primarily on serological methods. Since the advent of such serodiagnostic tests, few reports are available about the clinical and molecular epidemiological features of HFRS.
To investigate the epidemioclinical features of HFRS treated at a tertiary-care teaching hospital in Seoul over a 10-year period.
Study design
Medical records of HFRS patients, visited to a tertiary-care teaching hospital during February 2002 to February 2012, were reviewed. Sera from patients were tested for Hantaan virus (HTNV) and Seoul virus (SEOV) RNA using RT-PCR.
Among 35 HFRS patients (mean age was 44.2 ± 14.7 years), 29 were male (82.9%). Acute renal failure developed in 27 patients (77.1%), and 12 patients (34.3%) were admitted to the intensive care unit (ICU). Conjunctival injection (OR 10.32, 95% CI 1.09–97.77, P = .04) and initial serum albumin less than 3 g/dL (OR 22.83, 95% CI 1.45–359.93, P = .03) were risk factors for ICU admission. Of 35 acute-phase sera, 11 (31.4%) were positive for HTNV RNA. None were positive for SEOV RNA.
HFRS was characterized by the clinical triad of fever, renal insufficiency and gastrointestinal symptoms. Conjunctival injection and serum albumin level were related to severity. Large scaled multi-center study is needed to enhance an insight to epidemioclinical characteristics of HFRS in Korea.
PMCID: PMC4153883  PMID: 23871164
Hantaan virus; Hantavirus; Hemorrhagic fever with renal syndrome; Korea
11.  Physician Attitudes toward the Herpes Zoster Vaccination in South Korea 
Infection & Chemotherapy  2014;46(3):194-198.
This survey investigated Korean physician attitudes toward the herpes zoster (HZ) vaccine. A total of 400 physicians answered a self-reported questionnaire. Most physicians knew that HZ poses a significant socioeconomic burden and had good knowledge about HZ and its vaccine. Physicians who did not recommend HZ vaccine were concerned about costs (90.7%, 78/86) and doubted the effectiveness of the vaccine (58.1%, 50/86). Patient demand had a profound effect on physicians decisions; 84.9% (73/86) of them who said not recommending HZ vaccine reported that they would provide the vaccine upon patient request. In conclusion, educational initiatives should be targeted toward both physicians and patients.
PMCID: PMC4189135  PMID: 25298909
Herpes zoster; Physician; Vaccination; Awareness; Health surveys
12.  Pulmonary Toxocariasis Mimicking Invasive Aspergillosis in a Patient with Ulcerative Colitis 
A 45-year-old-male who had underlying ulcerative colitis and presented with fever and dry cough. Initially, the patient was considered to have invasive aspergillosis due to a positive galactomannan assay. He was treated with amphotericin B followed by voriconazole. Nevertheless, the patient deteriorated clinically and radiographically. The lung biopsy revealed eosinophilic pneumonia, and ELISA for Toxocara antigen was positive, leading to a diagnosis of pulmonary toxocariasis. After a 10-day treatment course with albendazole and adjunctive steroids, the patient recovered completely without any sequelae. Pulmonary toxocariasis may be considered in patients with subacute or chronic pneumonia unresponsive to antibiotic agents, particularly in cases with eosinophilia.
PMCID: PMC4170039  PMID: 25246722
Toxocara canis; toxocariasis; eosinophilia; respiratory disorder; aspergillosis; ulcerative colitis
13.  Comparison of the Immunogenicity and Safety of the Conventional Subunit, MF59-Adjuvanted, and Intradermal Influenza Vaccines in the Elderly 
The influenza vaccination is known as the most effective method for preventing influenza infection and its complications in the elderly. Conventional subunit (Agrippal S1; Novartis), MF59-adjuvanted (Fluad; Novartis), and intradermal (IDflu15; Sanofi Pasteur) influenza vaccines are widely used throughout South Korea. However, few comparative studies evaluating the safety and immunogenicity of these vaccines are available. Prior to the beginning of the 2011-2012 influenza season, 335 healthy elderly volunteers randomly received one of three seasonal trivalent influenza vaccines, the conventional subunit, MF59-adjuvanted, or intradermal influenza vaccine. Serum hemagglutination-inhibiting antibody levels were measured at the time of vaccination and at 1 and 6 months after vaccination. Adverse events were recorded prospectively. A total of 113 conventional subunit, 111 MF59-adjuvanted, and 111 intradermal influenza vaccine volunteers were followed up during a 6-month postvaccination period. One month after vaccination, all three vaccines satisfied Committee for Medical Products for Human Use (CHMP) immunogenicity criteria for the A/H1N1 and A/H3N2 strains but not for the B strain. Compared with the subunit vaccine, the intradermal vaccine exhibited noninferiority, while the MF59-adjuvanted vaccine exhibited superiority. Furthermore, the MF59-adjuvanted vaccine was more immunogenic against the A/H3N2 strain than was the subunit vaccine up to 6 months postvaccination. The most common local and systemic reactions to the conventional subunit, MF59-adjuvanted, and intradermal influenza vaccines were pain at the injection site (7.1%, 10.8%, and 6.3%, respectively) and generalized myalgia (0.9%, 8.1%, and 5.4%, respectively). Local and systemic reactions were similar among the three vaccine groups. MF59-adjuvanted vaccine exhibited superior immunogenicity compared with a conventional subunit vaccine and had a comparable safety profile. For older adults, the MF59-adjuvanted vaccine is preferable for providing superior immunogenicity.
PMCID: PMC4097439  PMID: 24828092
14.  Etiology and Clinical Outcomes of Acute Respiratory Virus Infection in Hospitalized Adults 
Infection & Chemotherapy  2014;46(2):67-76.
Etiologies and clinical profiles of acute respiratory viral infections need to be clarified to improve preventive and therapeutic strategies.
Materials and Methods
A retrospective observational study at a single, university-affiliated center was performed to evaluate the respiratory viral infection etiologies in children compared to that in adults and to document the clinical features of common viral infections for adults from July 2009 to April 2012.
The common viruses detected from children (2,800 total patients) were human rhinovirus (hRV) (31.8%), adenovirus (AdV) (19.2%), respiratory syncytial virus (RSV) A (17.4%), RSV B (11.7%), and human metapneumovirus (hMPV) (9.8%). In comparison, influenza virus A (IFA) had the highest isolation rate (28.5%), followed by hRV (15.5%), influenza virus B (IFB) (15.0%), and hMPV (14.0%), in adults (763 total patients). Multiple viruses were detected in single specimens from 22.4% of children and 2.0% of adults. IFA/IFB, RSV A/B, and hMPV exhibited strong seasonal detection and similar circulating patterns in children and adults. Adult patients showed different clinical manifestations according to causative viruses; nasal congestion and rhinorrhea were more common in hRV and human coronavirus (hCoV) infection. Patients with RSV B, hRV, or AdV tended to be younger, and those infected with RSV A and hMPV were likely to be older. Those with RSV A infection tended to stay longer in hospital, enter the intensive care unit more frequently, and have a fatal outcome more often. The bacterial co-detection rate was 26.5%, and those cases were more likely to have lower respiratory tract involvement (P = 0.001), longer hospital stay (P = 0.001), and higher mortality (P = 0.001).
The etiologic virus of an acute respiratory infection can be cautiously inferred based on a patient's age and clinical features and concurrent epidemic data. Large-scale prospective surveillance studies are required to provide more accurate information about respiratory viral infection etiology, which could favorably influence clinical outcomes.
PMCID: PMC4091371  PMID: 25024868
Adult; Children; Etiology; Respiratory virus
15.  Impact of Preceding Flu-Like Illness on the Serotype Distribution of Pneumococcal Pneumonia 
PLoS ONE  2014;9(4):e93477.
Even though the pathogenicity and invasiveness of pneumococcus largely depend on capsular types, the impact of serotypes on post-viral pneumococcal pneumonia is unknown.
Methods and Findings
This study was performed to evaluate the impact of capsular serotypes on the development of pneumococcal pneumonia after preceding respiratory viral infections. Patients with a diagnosis of pneumococcal pneumonia were identified. Pneumonia patients were divided into two groups (post-viral pneumococcal pneumonia versus primary pneumococcal pneumonia), and then their pneumococcal serotypes were compared. Nine hundred and nineteen patients with pneumococcal pneumonia were identified during the study period, including 327 (35.6%) cases with post-viral pneumococcal pneumonia and 592 (64.4%) cases with primary pneumococcal pneumonia. Overall, serotypes 3 and 19A were the most prevalent, followed by serotypes 19F, 6A, and 11A/11E. Although relatively uncommon (33 cases, 3.6%), infrequently colonizing invasive serotypes (4, 5, 7F/7A, 8, 9V/9A, 12F, and 18C) were significantly associated with preceding respiratory viral infections (69.7%, P<0.01). Multivariate analysis revealed several statistically significant risk factors for post-viral pneumococcal pneumonia: immunodeficiency (OR 1.66; 95% CI, 1.10–2.53), chronic lung diseases (OR 1.43; 95% CI, 1.09–1.93) and ICI serotypes (OR 4.66; 95% CI, 2.07–10.47).
Infrequently colonizing invasive serotypes would be more likely to cause pneumococcal pneumonia after preceding respiratory viral illness, particularly in patients with immunodeficiency or chronic lung diseases.
PMCID: PMC3972234  PMID: 24691515
17.  Age- and Influenza Activity-Stratified Case Definitions of Influenza-Like Illness: Experience from Hospital-Based Influenza Surveillance in South Korea 
PLoS ONE  2014;9(1):e84873.
This study aims to identify clinical case definitions of influenza with higher accuracy in patients stratified by age group and influenza activity using hospital-based surveillance system.
In seven tertiary hospitals across South Korea during 2011–2012 influenza season, respiratory specimens were obtained from patients presenting an influenza-like illness (ILI), defined as having fever plus at least one of following symptoms: cough, sore throat or rhinorrhea. Influenza was confirmed by reverse transcriptase-polymerase chain reaction. We performed multivariate logistic regression analyses to identify clinical variables with better relation with laboratory-confirmed influenza, and compared the accuracy of combinations.
Over the study period, we enrolled 1417 patients, of which 647 had laboratory-confirmed influenza. Patients with cough, rhinorrhea, sore throat or headache were more likely to have influenza (p<0.05). The most accurate criterion across the study population was the combination of cough, rhinorrhea, sore throat and headache (sensitivity 71.3%, specificity 60.1% and AUROC 0.66). The combination of rhinorrhea, sore throat and sputum during the peak influenza activity period in the young age group showed higher accuracy than that using the whole population (sensitivity 89.3%, specificity 72.1%, and AUROC 0.81).
The accuracy of clinical case definitions of influenza differed across age groups and influenza activity periods. Categorizing the entire population into subgroups would improve the detection of influenza patients in the hospital-based surveillance system.
PMCID: PMC3901651  PMID: 24475034
19.  Case-Control Study of the Effectiveness of the 2010-2011 Seasonal Influenza Vaccine for Prevention of Laboratory-Confirmed Influenza Virus Infection in the Korean Adult Population 
We evaluated the effectiveness of the 2010-2011 seasonal influenza vaccine for preventing laboratory-confirmed influenza in a South Korean population. A retrospective case-control study was conducted among patients who visited selected hospitals from September 2010 to May 2011. A total of 483 laboratory-confirmed influenza patients were included in the analysis as case subjects. For each case patient, two types of control patients were chosen at a ratio of 1:1:1, and 966 control subjects were selected. Vaccine effectiveness (VE) was defined as 100 × (1 − odds ratio for influenza in vaccinated versus nonvaccinated persons). The VE of the 2010-2011 seasonal influenza vaccine was 49.5% to 45.8% for both influenza A and B viruses and 50.8% to 47.2% for influenza A virus, according to the control type. The age-specific adjusted VE was 50.8% to 46.5% among subjects aged 19 to 49 years and 58.7% to 63.3% among those aged 50 to 64 years, according to the control type. Statistically significant VE was not found among those aged ≥65 years or against influenza B virus. The 2010-2011 seasonal influenza vaccine was effective for preventing laboratory-confirmed influenza, especially for influenza A virus, in a South Korean population. Evidence of the effectiveness of the influenza vaccine in older adults or against influenza B virus was not found.
PMCID: PMC3675970  PMID: 23576674
20.  Long-Term Immunogenicity of the Pandemic Influenza A/H1N1 2009 Vaccine among Health Care Workers: Influence of Prior Seasonal Influenza Vaccination 
Health care workers (HCWs) are at great risk of influenza infection and transmission. Vaccination for seasonal influenza is routinely recommended, but this strategy should be reconsidered in a pandemic situation. Between October 2009 and September 2010, a multicenter study was conducted to assess the long-term immunogenicity of the A/H1N1 2009 monovalent influenza vaccine among HCWs compared to non-health care workers (NHCWs). The influence of prior seasonal influenza vaccination was also assessed with respect to the immunogenicity of pandemic H1N1 influenza vaccine. Serum hemagglutinin inhibition titers were determined prevaccination and then at 1, 6, and 10 months after vaccination. Of the 360 enrolled HCW subjects, 289 participated in the study up to 10 months after H1N1 monovalent influenza vaccination, while 60 of 65 NHCW subjects were followed up. Seroprotection rates, seroconversion rates, and geometric mean titer (GMT) ratios fulfilled the European Union's licensure criteria for influenza A/California/7/2009 (H1N1) at 1 month after vaccination in both the HCWs and NHCWs, without any significant difference. At 6 months after vaccination, the seroprotection rate was more significantly lowered among the NHCWs than among the HCWs (P < 0.01). Overall, postvaccination (1, 6, and 10 months after vaccination) GMTs for A/California/7/2009 (H1N1) were significantly lower among the seasonal influenza vaccine recipients than among the nonrecipients (P < 0.05). In conclusion, HCWs should be encouraged to receive an annual influenza vaccination, considering the risk of repeated exposure. However, prior reception of seasonal influenza vaccine showed a negative influence on immunogenicity for the pandemic A/H1N1 2009 influenza vaccine.
PMCID: PMC3623406  PMID: 23365206
21.  Long-term immunogenicity of the influenza vaccine at reduced intradermal and full intramuscular doses among healthy young adults 
To prepare for vaccine shortages under an influenza pandemic, several antigen-sparing strategies have been investigated. This study was aimed to evaluate the immunogenicity of influenza vaccine at reduced intradermal and full intramuscular dose.
Materials and Methods
We compared the effect of one-fifth and one-half intradermal doses to the full intramuscular dose on immunogenicity in healthy young adults, using a commercial influenza vaccine. A hemagglutination inhibition assay was used to compare the immunogenicity of the vaccination methods.
The one-fifth intradermal dose (3 µg hemagglutinin antigen, HA) was given to 30 participants, the one-half intradermal dose (7.5 µg HA) was given to 30, and the full intramuscular dose (15 µg HA) was given to 32. No significant differences among injection routes and dosages were seen for seroprotection rate, seroconversion rate, or geometric mean titer (GMT) fold-increase for A/H1N1, A/H3N2, and B at around 4 weeks from vaccination. Although GMT for influenza B was significantly lower at six months for the one-fifth intradermal vaccination compared to the full-dose intramuscular vaccination (32.8 vs. 63.2, p=0.048), all three groups met the Evaluation of Medicinal Products (EMA) immunogenicity criteria through 1 to 6 months.
Intradermal administration of a one-fifth dose of influenza vaccine elicited antibody responses comparable to the intradermal one-half dose and a conventional intramuscular vaccination at 1 month post-vaccination. The immunogenicity of the one-fifth intradermal dose was sufficient to meet the requirement for the EMA criteria at six months after influenza vaccination.
PMCID: PMC3710919  PMID: 23858402
Vaccines; Influenza vaccines; Immunogenicity; Intradermal injections; Adult
22.  Perceptions of Tetanus-diphteria-acellular pertussis (Tdap) Vaccination among Korean Women of Childbearing Age 
Infection & Chemotherapy  2013;45(2):217-224.
The number of cases of pertussis reported has increased gradually in the last decade. Pertussis vaccination is the most effective strategy for the prevention of infection. Despite the fact that young infants are at the highest risk for pertussis, the rate of tetanus-diphtheria-acellular pertussis (Tdap) vaccination is presumed to be very low among women of childbearing age in Korea. The purpose of this study was to investigate the perceptions of women of childbearing age regarding Tdap vaccination in Korea.
Materials and Methods
Women of childbearing age, who visited the Department of Obstetrics and Gynecology at 3 University hospitals in the Seoul and Gyeonggi-do provinces of Korea, were surveyed. Individual questionnaires were administered from April to May 2012. Demographic data, Tdap vaccination history, general knowledge about pertussis, and information on factors associated with decision on vaccination were collected.
Of the 500 reproductive-age women enrolled, only 4 (0.8%) had received the Tdap. The most common reason for non-vaccination was the lack of awareness of pertussis and information about the Tdap. Totally, 171 (34.2%) responded that they would receive a Tdap vaccination in the future. By multivariate analysis, general confidence in the effectiveness of the vaccine (odds ratio [OR] = 1.88, 95% confidence interval [CI] 1.17 to 3.01) was indicated as an important factor for deciding whether to receive the Tdap vaccine (P < 0.01).
The coverage of Tdap vaccination of women of childbearing age, including pregnant women, is very low because of the lack of awareness of pertussis and the Tdap. Education of women of childbearing age about pertussis is very important to increase Tdap vaccination rates among these women, particularly during the perinatal period.
PMCID: PMC3780958  PMID: 24265970
Pertussis; Vaccination; Tdap; Childbearing age; Perception
23.  Laboratory Surveillance of Influenza-Like Illness in Seven Teaching Hospitals, South Korea: 2011–2012 Season 
PLoS ONE  2013;8(5):e64295.
A well-constructed and properly operating influenza surveillance scheme is essential for public health. This study was conducted to evaluate the distribution of respiratory viruses in patients with influenza-like illness (ILI) through the first teaching hospital-based surveillance scheme for ILI in South Korea.
Respiratory specimens were obtained from adult patients (≥18 years) who visited the emergency department (ED) with ILI from week 40, 2011 to week 22, 2012. Multiplex PCR was performed to detect respiratory viruses: influenza virus, adenovirus, coronavirus, respiratory syncytial virus, rhinovirus, human metapneumovirus, parainfluenza virus, bocavirus, and enterovirus.
Among 1,983 patients who visited the ED with ILI, 811 (40.9%) were male. The median age of patients was 43 years. Influenza vaccination rate was 21.7% (430/1,983) during the 2011–2012 season. At least one comorbidity was found in 18% of patients. The positive rate of respiratory viruses was 52.1% (1,033/1,983) and the total number of detected viruses was 1,100. Influenza A virus was the dominant agent (677, 61.5%) in all age groups. The prevalence of human metapneumovirus was higher in patients more than 50 years old, while adenovirus was detected only in younger adults. In 58 (5.6%) cases, two or more respiratory viruses were detected. The co-incidence case was identified more frequently in patients with hematologic malignancy or organ transplantation recipients, however it was not related to clinical outcomes.
This study is valuable as the first extensive laboratory surveillance of the epidemiology of respiratory viruses in ILI patients through a teaching hospital-based influenza surveillance system in South Korea.
PMCID: PMC3661466  PMID: 23717587
24.  Clinical and economic burden of invasive pneumococcal disease in adults: a multicenter hospital-based study 
BMC Infectious Diseases  2013;13:202.
Streptococcus pneumoniae causes a broad spectrum of illnesses ranging from mild upper respiratory tract infections to invasive pneumococcal disease (IPD). Quantitative data on the burden of pneumococcal disease, important for the establishment of appropriate vaccination strategies, is currently lacking in adults.
This multicenter, retrospective cohort study was designed to estimate the clinical and economic burden of IPD in adults over the last decade. Data were collected from patients with IPD at 10 university hospitals in South Korea. We estimated the proportion of IPD among all hospitalized patients, the case fatality rate, and the direct medical costs of IPD. Data were further analyzed according to age and risk groups.
During the study period, 970 patients with IPD were identified. The mean age for all patients was 60.9 years; patients aged 50–64 years (33.0%) were most numerous, followed by those aged 65–74 years (27.4%). Overall, the proportion of IPD was 0.36 cases/1000 hospitalized patients and the case fatality rate was 30.9%, which increased significantly with age (p < 0.01). The mean direct medical costs were estimated to be US $7,452 without a difference between age and risk groups. On multivariate analysis, old age, advanced ECOG performance status, bacteremic pneumonia, and nosocomial infection were independent risk factors of 30-day case fatality.
The clinical disease burden of IPD increased significantly with age and direct medical costs from IPD were substantial, regardless of age and co-morbid conditions. The current age-based vaccination strategy appears to be appropriate.
PMCID: PMC3660270  PMID: 23641904
Cost of illness; Pneumococcal infection; Pneumococcal vaccines; Streptococcus pneumoniae
25.  A Comparison of the Clinical and Epidemiological Characteristics of Adult Patients with Laboratory-Confirmed Influenza A or B during the 2011–2012 Influenza Season in Korea: A Multi-Center Study 
PLoS ONE  2013;8(5):e62685.
During the 2011/2012 winter influenza season in the Republic of Korea, influenza A (H3N2) was the predominant virus in the first peak period of influenza activity during the second half of January 2012. On the other hand, influenza B was the predominant virus in the second peak period of influenza activity during the second half of March 2012. The objectives of this study were to compare the clinical and epidemiological characteristics of patients with laboratory-confirmed influenza A or influenza B.
Methodology/Principal Findings
We analyzed data from 2,129 adult patients with influenza-like illnesses who visited the emergency rooms of seven university hospitals in Korea from October 2011 to May 2012. Of 850 patients with laboratory-confirmed influenza, 656 (77.2%) had influenza A (H3N2), and 194 (22.8%) influenza B. Age, and the frequencies of cardiovascular disorders, diabetes, hypertension were significantly higher in patients with influenza A (H3N2) (P<0.05). The frequencies of leukopenia or thrombocytopenia in patients with influenza B at initial presentation were statistically higher than those in patients with influenza A (H3N2) (P<0.05). The rate of hospitalization, and length of hospital stay were statistically higher in patients with influenza A (H3N2) (P<0.05), and of the 79 hospitalized patients, the frequency of diabetes, hypertension, cases having at least one of the comorbid conditions, and the proportion of elderly were significantly higher in patients with influenza A (H3N2) (P<0.05).
The proportion of males to females and elderly population were significantly higher for influenza A (H3N2) patients group compared with influenza B group. Hypertension, diabetes, chronic lung diseases, cardiovascular disorders, and neuromuscular diseases were independently associated with hospitalization due to influenza. Physicians should assess and treat the underlying comorbid conditions as well as influenza viral infections for the appropriate management of patients with influenza.
PMCID: PMC3643978  PMID: 23671624

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