Yu Bin Seo

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

Background 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). Conclusions 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.

Etiology and Clinical Outcomes of Acute Respiratory Virus Infection in Hospitalized Adults

Background 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. Results 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). Conclusions The etiologic virus of an acute respiratory infection can be cautiously inferred based on a patients 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.

Comparison of the Immunogenicity and Safety of the Conventional Subunit, MF59-Adjuvanted, and Intradermal Influenza Vaccines in the Elderly

ABSTRACT 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.

Long-term and cross-reactive immunogenicity of inactivated trivalent influenza vaccine in the elderly: MF59-adjuvanted vaccine versus unadjuvanted vaccine

Elderly people are at great risk for influenza‐related serious complications. However, influenza vaccine‐induced antibodies are believed to decline more rapidly in the elderly. This study was designed to evaluate the long‐term and cross‐reactive immunogenicity among those aged ≥65 years for two seasonal trivalent influenza vaccines during the 2009–2010 influenza season. One vaccine had the MF59 adjuvant, while the other did not contain an adjuvant. Serum hemagglutinin inhibition (HI) titers were determined pre‐vaccination and at 1 and 6 months post‐vaccination. Of the 100 subjects, 95 (95%) were followed‐up for 1 month after vaccination, and 76 (76%) were followed‐up for 6 months after vaccination. Both vaccines met the European Medicines Agency (EMA) criteria 1 month after vaccination. However, seroprotection for influenza B was not satisfactory, with a rate of 55.3% for the MF59 adjuvant vaccine and 47.9% for the vaccine without adjuvant. At 6 months post‐vaccination, the MF59‐adjuvanted vaccine showed a higher seroprotection rate than the unadjuvanted vaccine. At this point, the MF59‐adjuvanated vaccine still met the criteria of EMA for A/H1N1 (62.5% vs. 55.5%, P = 0.64) and A/H3N2 (72.5% vs. 47.2%, P = 0.04). Both vaccines showed excellent cross‐reactive immunogenicity for influenza A/Solomon Island/3/2006 (H1N1) and A/Wisconsin/67/2005 (H3N2), without significant differences. In comparison, cross‐reactive immunogenicity was not remarkable for the A/California/7/2009 (H1N1) and A/New Caledonia/20/1999 (H1N1) strains, which have a greater antigenic distance. In conclusion, the MF59‐adjuvanted influenza vaccine showed superior long‐term immunogenicity in the elderly compared to the unadjuvanted vaccine. However, cross‐reactive immunogenicity was not remarkably enhanced with the MF59 adjuvant. J. Med. Virol. 85:1591–1597, 2013.

Effectiveness of the influenza vaccine at preventing hospitalization due to acute lower respiratory infection and exacerbation of chronic cardiopulmonary disease in Korea during 2010–2011

BACKGROUND Influenza epidemics are accompanied by a considerable increase in hospitalization due to acute lower respiratory infection and exacerbation of underlying medical conditions. We estimated the effectiveness of the influenza vaccine at preventing hospitalization due to acute lower respiratory infection and new onset or acute exacerbation of chronic cardiopulmonary disease. METHOD During the peak influenza period in 2010-2011, we performed a multicenter, case-control, retrospective cohort study of patients who were hospitalized due to newly developed pneumonia, bronchitis, and bronchiolitis, or new onset or acute exacerbation of asthma, COPD, ischemic heart disease, and CHF. Controls were selected from outpatients who visited study hospitals but who were not hospitalized during the same study period. Controls were matched 1:1 to cases based on age, gender, and date of hospital visit. Univariate and multivariate logistic regression analyses were used to determine the effectiveness of the influenza vaccine at decreasing hospitalization. RESULTS Between December 2010 and February 2011, 556 hospitalized subjects were identified. Age, gender, and body mass index (BMI) were similar between case and control groups. The influenza vaccination rate of the hospitalized and non-hospitalized patients was 42.4% and 52.2%, respectively (p<0.001). The overall vaccine effectiveness for preventing hospitalization was 32.5% (odds ratio 0.675, 95% confidence interval [CI] 0.486-0.937; p=0.019). Multivariate logistic analysis showed that influenza vaccination significantly reduced the risk of hospitalization, especially due to new onset or acute exacerbation of ischemic heart disease and CHF in patients aged 65 years and older (OR 0.274, 95% CI 0.114-0.658, p=0.004). The estimated vaccine effectiveness in these patients was 72.6%. CONCLUSION Influenza vaccination reduced the rate of hospitalization among patients with underlying chronic heart disease, particularly those patients 65 years old and greater.

Comparison of the Long-Term Immunogenicity of Two Pandemic Influenza A/H1N1 2009 Vaccines, the MF59-Adjuvanted and Unadjuvanted Vaccines, in Adults

ABSTRACT 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.

Epidemiology and clinical features of toxigenic culture-confirmed hospital–onset Clostridium difficile infection: A multicentre prospective study in tertiary hospitals of South Korea

Hypervirulent Clostridium difficile strains, most notably BI/NAP1/027, have been increasingly emerging in Western countries as local epidemics. We performed a prospective multicentre observational study from December 2011 to May 2012 to identify recent incidences of toxigenic culture-confirmed hospital-onset C. difficile infections (CDI) and their associated clinical characteristics in South Korea. Patients suspected of having been suffering from CDI more than 48 h after admission and aged ≥20 years were prospectively enrolled and provided loose stool specimens. Toxigenic C. difficile culture (anaerobic culture+toxin A/B/binary gene PCR) and PCR ribotyping were performed in one central laboratory. We enrolled 98 toxigenic culture-confirmed CDI-infected patients and 250 toxigenic culture-negative participants from three hospitals. The incidence of toxigenic culture-confirmed hospital-onset CDI cases was 2.7 per 10,000 patient-days. The percentage of severe CDI cases was relatively low at only 3.1%. UK ribotype 018 was the predominant type (48.1%). There were no hypervirulent BI/NAP1/027 isolates identified. The independent risk factors for toxigenic culture-confirmed hospital-onset CDI were invasive procedure (odds ratio (OR) 7.3, P=0.003) and past CDI history within 3 months (OR 28.5, P=0.003). In conclusion, the incidence and severity of CDI in our study were not higher than reported in Western countries.

Prospective Cohort Study on the Effectiveness of Influenza and Pneumococcal Vaccines in Preventing Pneumonia Development and Hospitalization

ABSTRACT Pneumonia and acute exacerbation of chronic illness are leading causes of influenza-related hospitalization. Therefore, influenza and pneumococcal vaccinations are strongly recommended for adults with comorbidities. Using a hospital-based influenza surveillance system, we performed a multicenter, prospective cohort study of patients visiting emergency rooms with influenza-like illness (ILI) during the influenza epidemic period in 2013 to 2014. Patients aged ≥19 years were enrolled, and clinical data were collected. Multivariate analyses were performed to estimate the effectiveness of influenza and pneumococcal vaccination in preventing pneumonia development and hospitalization. During study periods, 2,262 patients with ILI were registered. Among 2,217 patients with available vaccination records, 31.9% (707 patients) and 9.7% (216 patients) had received influenza and pneumococcal vaccines, respectively. Among patients who had been administered a pneumococcal vaccine, 94.4% had received the 23-valent polysaccharide vaccine (PPV23). The adjusted rates of effectiveness of the influenza vaccine for preventing pneumonia development and hospitalization were 64.0% (95% confidence interval [CI] = 29% to 81%) and 35.0% (95% CI = 12% to 52%), respectively. Pneumococcal vaccination did not reduce pneumonia development or hospitalization. In conclusion, influenza rather than PPV23 vaccination may reduce pneumonia development and hospitalization in patients with preceding ILI.

Severe influenza treatment guideline

Background and purpose Severe influenza is defined as influenza with a severe symptom or syndrome such as respiratory distress or deceased consciousness or accompanying a severe complication such as encephalopathy or renal failure. In contrast to mild influenza, for which patients recover mostly by ambulatory care, severe influenza requires hospital admission in most cases or intensive treatment in the intensive care unit in some cases. In particular, the elderly, infants, and chronic patients are known to be at high risk for severe influenza because they may have accompanying complications such as exacerbation of an underlying disease, development of pneumonia, and another organ dysfunction or they may die. Therefore, there is an increasing need for an effective treatment method applicable to severe influenza. Severe influenza treatment methods, which have been recently discussed, include high-dose, long-term antiviral therapy, combination antiviral therapy, administration of antibiotics, application of extracorporeal membrane oxygenation (ECMO), administration of a corticosteroid, administration of intravenous immunoglobulin (IVIG), application of plasmapheresis, and administration of a statin. However, no comprehensive, specific expert guideline for these methods is available yet. The Transgovernmental Enterprise for Pandemic Influenza in Korea published in 2012 a guideline for the use of an antiviral agent for seasonal influenza. But the guideline deals with only the use of an antiviral agent, not the various treatment methods which can be applied to severe influenza [1]. Therefore, this guideline was developed by analyzing and evaluating domestic and international literature and guidelines with respect to the various treatment methods so that severe influenza could be effectively treated.

Depression Among HIV-infected Patients in Korea: Assessment of Clinical Significance and Risk Factors

Background 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. Results 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. Conclusions 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.