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.
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.
Vaccines; Influenza vaccines; Immunogenicity; Intradermal injections; Adult
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.
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.
Cost of illness; Pneumococcal infection; Pneumococcal vaccines; Streptococcus pneumoniae
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.
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.
Despite the ready availability of pneumococcal vaccine, vaccination rates are quite low in South Korea. This study was designed to assess perceptions and awareness about pneumococcal vaccines among subjects at risk and find strategies to increases vaccine coverage rates.
Materials and Methods
A cross sectional, community-based survey was conducted to assess perceptions about the pneumococcal vaccine at a local public health center. In a tertiary hospital, an outpatient-based pneumococcal vaccine campaign was carried out for the elderly and individuals with chronic co-morbidities from May to July of 2007.
Based on the survey, only 7.6% were ever informed about pneumococcal vaccination. The coverage rates of the pneumococcal vaccine before and after the hospital campaign showed an increased annual rate from 3.39% to 5.91%. The most common reason for vaccination was "doctor's advice" (53.3%). As for the reasons for not receiving vaccination, about 75% of high risk patients were not aware of the pneumococcal vaccine, which was the most important barrier to vaccination. Negative clinician's attitude was the second most common cause of non-vaccination.
Annual outpatient-based campaigns early in the influenza season may improve pneumococcal vaccine coverage rates. Doctor's advice was the most important encouraging factor for vaccination.
Pneumococcal infections; pneumococcal vaccination; health education
Streptococcus pneumoniae can asymptomatically colonize the nasopharynx and cause a diverse range of illnesses. This clinical spectrum from colonization to invasive pneumococcal disease (IPD) appears to depend on the pneumococcal capsular serotype rather than the genetic background. According to a literature review, serotypes 1, 4, 5, 7F, 8, 12F, 14, 18C, and 19A are more likely to cause IPD. Although serotypes 1 and 19A are the predominant causes of invasive pneumococcal pneumonia, serotype 14 remains one of the most common etiologic agents of non-bacteremic pneumonia in adults, even after 7-valent pneumococcal conjugate vaccine (PCV7) introduction. Serotypes 1, 3, and 19A pneumococci are likely to cause empyema and hemolytic uremic syndrome. Serotype 1 pneumococcal meningitis is prevalent in the African meningitis belt, with a high fatality rate. In contrast to the capsule type, genotype is more closely associated with antibiotic resistance. CC320/271 strains expressing serotype 19A are multidrug-resistant (MDR) and prevalent worldwide in the era of PCV7. Several clones of MDR serotype 6C pneumococci emerged, and a MDR 6D clone (ST282) has been identified in Korea. Since the pneumococcal epidemiology of capsule types varies geographically and temporally, a nationwide serosurveillance system is vital to establishing appropriate vaccination strategies for each country.
Streptococcus pneumoniae; Polysaccharides, Bacterial; Bacterial Capsules; Serotyping; Pneumococcal Infections
Tuberculosis; influenza; pandemics; South Korea; respiratory infections; tuberculosis and other mycobacteria; viruses
Since the first reports of the A/H1N1 virus in April 2009, the pandemic influenza virus spread globally and circulated for a long time. The primary method for the control of influenza is vaccination, but levels of influenza vaccine-induced antibody are known to decline rapidly during a 6-month period. In adults aged 18 to 64 years, we compared the long-term immunogenicity of two of the influenza A/H1N1 2009 monovalent vaccines, 3.75-μg MF59-adjuvanted vaccine and 15-μg unadjuvanted vaccine. The serum hemagglutinin inhibition (HI) titers were determined prevaccination and at 1, 6, and 10 months after vaccination. One hundred six (88.3%) of the 120 subjects were monitored for the entire 10-month period after receiving the influenza A/H1N1 2009 monovalent vaccine. There were 60 patients who received the unadjuvanted vaccine and 46 patients who received the MF59-adjuvanted vaccine. The seroprotection rates, seroconversion rates, and the geometric mean titer (GMT) folds fulfilled the criteria of the European Medicines Agency (EMA) for influenza A/California/7/2009 (H1N1) at 1 month after vaccination irrespective of the vaccine composition. Although the GMTs at 1 month postvaccination were somewhat higher in the unadjuvanted vaccine recipients than in the MF59-adjuvanted vaccine recipients, the difference was not significant (P = 0.29). The seroprotection rates at 6 and 10 months postvaccination were preserved above 70% but only in the MF59-adjuvanted vaccine recipients. In conclusion, low-dose MF59-adjuvanted influenza vaccine, even with 3.75 μg hemagglutinin antigen, might induce excellent long-term immunity that is comparable to the conventional dose of unadjuvanted vaccine among healthy adults aged 18 to 64 years.
A prospective multicenter observational study was performed to investigate the epidemiology and outcomes of community-acquired severe sepsis and septic shock. Subjects included 1,192 adult patients admitted to the 22 participating intensive care units (ICUs) of 12 university hospitals in the Korean Sepsis Registry System from April, 2005 through February, 2009. Male accounted for 656 (55%) patients. Mean age was 65.0 ± 14.2 yr. Septic shock developed in 740 (62.1%) patients. Bacteremia was present in 422 (35.4%) patients. The 28-day and in-hospital mortality rates were 23.0% and 28.0%, respectively. Men were more likely to have comorbid illnesses and acute organ dysfunctions, and had higher mortality and clinical severity compared to women. While respiratory sources of sepsis were common in men, urinary sources were predominant in women. In the multivariate logistic regression analysis, cancer (odds ratio 1.89; 95% confidence interval 1.13-3.17), urinary tract infection (0.25; 0.13-0.46), APACHE II score (1.05; 1.02-1.09), SOFA score on day 1 (1.13; 1.06-1.21) and metabolic dysfunction (2.24, 1.45-3.45) were independent clinical factors for gender-related in-hospital mortality. This study provided epidemiological and clinical characteristics of community-acquired severe sepsis and septic shock in ICUs in Korea, and demonstrated the impact of clinical factors on gender difference in mortality.
Epidemiology; Severe Sepsis; Septic Shock; Mortality; Risk Factor; Gender
Women who are pregnant, planning to become pregnant in the influenza season or caring for infant 6-59 months of age are identified as priority groups for influenza vaccination. Vaccination rate is presumed to be low in those women. The purpose of this study was to investigate perceptions of childbearing age women about influenza vaccination.
Materials and Methods
Childbearing age women visiting the department of Obstetrics and Gynecology in 3 University hospitals in Seoul and Gyeonggi-do province were surveyed. Individual interviews were performed to them with questionnaire for 2 months from April to May 2012. Demographic data, Immunization history, general understanding and factors associated with vaccination were asked.
Three hundred fifty-five (71.0%) of total 500 reproductive age women had the experience of influenza vaccination. Among 343 women who has been pregnant at least once, 48 women (16.4%) had vaccination during pregnancy, and 46 of them got vaccination since 2009. One hundred ninety women of total 500 women responded that they would get vaccination if pregnant in the next influenza season (38.0%). In multivariate analysis, statistically significant factors associated with plans of influenza vaccination in pregnancy were as follows: experience of childbirth (odds ratio [OR], 1.97; 95% CI, 1.32 to 2.93), high level of education (OR, 1.96; 95% CI, 1.22 to 3.15), previous influenza vaccination (OR, 1.88; 95% CI, 1.17 to 3.01).
Influenza vaccine coverage on childbearing age women including pregnant women is low because of misperception of vaccination during pregnancy. It is necessary for healthcare provider to correct misunderstanding and to recommend vaccination actively.
Influenza; Vaccination; Pregnancy; Childbearing age; Perception
Since initial reports in April 2009, the pandemic influenza A (H1N1) virus has spread globally. Influenza vaccines are the primary method for the control of influenza and its complications. We conducted a multicenter clinical trial to evaluate the immunogenicity and safety of H1N1 vaccine (Green Cross Co.) in young adults (18 to 64 years) and the elderly (≥65 years) using a two-dose regimen, with the doses administered 21 days apart. Three different regimens of hemagglutinin antigen were comparatively analyzed: 3.75 μg (MF59 adjuvanted) versus 7.5 μg (MF59 adjuvanted) versus 15 μg (nonadjuvanted) in young adults and 3.75 μg (MF59 adjuvanted) versus 7.5 μg (MF59 adjuvanted) in the elderly. In young adults, all three vaccine regimens met the European Agency for the Evaluation of Medicinal Products (EMA) criteria after the first dose. In the elderly, on day 21 after the first dose, the rates of seroprotection and seroconversion were significantly higher for the 7.5-μg dose of MF59 adjuvanted vaccine than for the 3.75-μg dose (58.0% versus 44.3% [P = 0.03] and 53.7% versus 37.2% [P < 0.01], respectively). After the second dose, the geometric mean titer (GMT) increment was blunted with a 15-μg dose of nonadjuvanted vaccine, whereas the GMT increased about 2-fold with MF59 adjuvanted vaccines. In conclusion, a single 7.5-μg dose of MF59 adjuvanted vaccine would have a practical advantage over a two-dose, 3.75-μg, MF59 adjuvanted vaccine priming schedule. Following a two-dose priming schedule, the increase in hemagglutinin inhibition titers was higher with MF59 adjuvanted vaccine than with nonadjuvanted vaccine.
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.
Influenza; diagnosis; sensitivity; specificity
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.
Influenza Vaccines; Influenza, Human; Vaccines, Inactivated
Lactococcus lactis cremoris infections are very rare in humans. We experienced liver abscess and empyema due to L. lactis cremoris in an immunocompetent adult. A 42-yr-old man was admitted with fever and abdominal pain. Abdominal computed tomography (CT) revealed a liver abscess and chest CT showed loculated pleural effusion consistent with empyema. L. lactis cremoris was isolated from culture of the abscess material and blood. The patient was treated with pus drainage from liver abscess, video-assisted thoracoscopic decortications for empyema, and antibiotics including cefotaxime and levofloxacin. The patient was completely recovered with the treatment. To our knowledge, this is the first report of a L. lactis cremoris infection in Korea.
Lactococcus lactis; Liver Abscess; Empyema
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.
Salmonella Infections; Salmonella Enteritidis; Salmonella Typhimurium; Epidemiology
Disseminated mycobacterium avium complex (MAC) occurs mainly in immunocompromised hosts, which is associated with abnormal cellular immunity.
A 26-year-old pregnant woman presented with fever and general weakness. Miliary lung nodules were noted on chest X-ray. Under the impression of miliary tuberculosis, anti-tuberculosis medication was administered. However, the patient was not improved. Further work-up demonstrated MAC in the sputum and placenta. The patient was treated successfully with clarithromycin-based combination regimen.
This appears to be the first case of disseminated MAC in an otherwise healthy pregnant woman. Clinicians should be alert for the diagnosis of MAC infection in diverse clinical conditions.
Spontaneous bacterial peritonitis (SBP) is an ascitic fluid infection as a complication of end stage liver disease. The outcome is related to the severity of hepatorenal function, gastrointestinal bleeding, and many others; however it is not well known whether the infection acquisition sites have an effect on the prognosis of SBP. In order to identify the prognostic significance of the acquisition sites, we studied 106 patients who were diagnosed as culture positive SBP between October 1998 and August 2003. Thirty-two episodes were nosocomial and 74 were community acquired. Gram-negative bacilli such as Escherichia coli were dominant in both of the nosocomial and community-acquired SBPs. Despite significantly higher resistance to cefotaxime in nosocomial isolates compared to community-acquired isolates (77.8% vs. 13.6%, p=0.001), no difference was found regarding short or long term prognosis. Infection acquisition sites were not related to short or long term prognosis either. Shock, gastrointestinal bleeding and renal dysfunction were related to short term prognosis. Only Child-Pugh class C was identified as an independent prognostic factor of long-term survival.
Liver Cirrhosis; Peritonitis; Cross Infection; Community-Acquired Infections
We conducted an epidemiologic study to understand temporal and spatial patterns of hemorrhagic fever with renal syndrome (HFRS) in the Republic of Korea (ROK). We estimated the incidence among civilians in endemic areas through the active surveillance system during the major epidemic periods, from September to December, between 1996 and 1998. We also estimated the prevalence among Korean military personnel from 1995 to 1998. In addition, we assessed seroprevalence, subclinical infection rate, and vaccination rates in both civilians and military personnel. The incidence in civilians ranged from 2.1 to 6.6 per 100,000 person-months. The annual prevalence in the military personnel was 40-64 per 100,000 military populations, and remained generally constant throughout the study period with seasonal variation. This is the prospective epidemiologic data set on HFRS in the ROK since the inactivated Hantaan virus vaccine was licensed for use in the late 1990s. These results will be invaluable in establishing a national immunization program against HFRS.
Hemorrhagic Fever with Renal Syndrome; Hantaan virus; Epidemiology; Incidence; Prevalence; Korea
Despite the increasing popularity of acupuncture, the importance of infection control is not adequately emphasized in Oriental medicine. In December 2001, an Oriental medical doctor in Seoul, South Korea, encountered several patients with persistent, culture-negative skin lesions on the trunk and extremities at the sites of prior acupuncture treatment. We identified and investigated an outbreak of Mycobacterium abscessus cutaneous infection among the patients who attended this Oriental medicine clinic.
Patients were defined as clinic patients with persistent cutaneous infections at the acupuncture sites. Medical records for the previous 7 months were reviewed. Clinical specimens were obtained from the patients and an environmental investigation was performed. M. abscessus isolates, cultured from patients, were compared by pulsed-field gel electrophoresis (PFGE).
Forty patients who attended the Oriental medicine clinic and experienced persistent cutaneous wound infections were identified. Cultures from five of these patients proved positive, and all other diagnoses were based on clinical and histopathologic examinations. All environmental objects tested were negative for M. abscessus, however, most were contaminated by various nosocomial pathogens. Molecular analysis using PFGE found all wound isolates to be identical.
We have identified a large outbreak of rapidly growing mycobacterial infection among patients who received acupuncture at a single Oriental medicine clinic. Physicians should suspect mycobacterial infections in patients with persistent cutaneous infections following acupuncture, and infection control education including hygienic practice, should be emphasized for Oriental medical doctors practicing acupuncture.