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.
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.
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
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
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.
HIV; Acquired immunodeficiency syndrome; Depression; Anxiety
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.
Pertussis; Vaccination; Tdap; Childbearing age; Perception
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.
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
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.
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.
Antiviral medications with activity against influenza viruses are important in controlling influenza. We compared intravenous peramivir, a potent neuraminidase inhibitor, with oseltamivir in patients with seasonal influenza virus infection. In a multinational, multicenter, double-blind, double-dummy randomized controlled study, patients aged ≥20 years with influenza A or B virus infection were randomly assigned to receive either a single intravenous infusion of peramivir (300 or 600 mg) or oral administration of oseltamivir (75 mg twice a day [b.i.d.] for 5 days). To demonstrate the noninferiority of peramivir in reducing the time to alleviation of influenza symptoms with hazard model analysis and a noninferiority margin of 0.170, we planned to recruit 1,050 patients in South Korea, Japan, and Taiwan. A total of 1,091 patients (364 receiving 300 mg and 362 receiving 600 mg of peramivir; 365 receiving oseltamivir) were included in the intent-to-treat infected population. The median durations of influenza symptoms were 78.0, 81.0, and 81.8 h in the groups treated with 300 mg of peramivir, 600 mg of peramivir, and oseltamivir, respectively. The hazard ratios of the 300- and 600-mg-peramivir groups compared to the oseltamivir group were 0.946 (97.5% confidence interval [CI], 0.793, 1.129) and 0.970 (97.5% CI, 0.814, 1.157), respectively. Both peramivir groups were noninferior to the oseltamivir group (97.5% CI, <1.170). The overall incidence of adverse drug reactions was significantly lower in the 300-mg-peramivir group, but the incidence of severe reactions in either peramivir group was not different from that in the oseltamivir group. Thus, a single intravenous dose of peramivir may be an alternative to a 5-day oral dose of oseltamivir for patients with seasonal influenza virus infection.
We report results of a randomized, double-blinded, active-controlled, phase III study conducted to evaluate the immunogenicity and safety of a new trivalent inactivated split-virus influenza vaccine (GC501) manufactured by the Green Cross Corporation in Korea. A total of 283 healthy children aged 6 months to < 18 yr were randomized to receive either GC501 or control. Of the GC501 recipients, seroconversion occurred in 48.5% for A/H1N1, 67.7% for A/H3N2 and 52% for influenza B. The proportion of subjects who had post-vaccination hemagglutination-inhibition titers of 1:40 or greater was 90.7% for A/H1N1, 86.8% for A/H3N2 and 82.4% for influenza B in the GC501 recipients. No serious adverse events related to vaccination, or withdrawals because of adverse events were reported. The majority of solicited adverse events were mild in intensity. GC501 vaccine has good tolerability and favorable immunogenicity in children aged 6 months to < 18 yr. The addition of one more brand of influenza vaccine may allow for better global accessibility of vaccine for epidemics or future pandemics.
Influenza Vaccines; Child; Immunogenicity; Safety
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