Direct effectiveness of pneumococcal polysaccharide vaccine against invasive pneumococcal disease and non-bacteremic pneumococcal pneumonia in elderly population in the era of pneumococcal conjugate vaccine: A case-control study.

BACKGROUND: While herd effects and serotype replacement by childhood pneumococcal protein conjugated vaccines (PCVs) continues to accumulate worldwide, direct effectiveness of 23-valent pneumococcal polysaccharide vaccine (PPV23) against pneumococcal diseases in the elderly has been challenged. We estimated the direct effectiveness of PPV23 in the elderly population. METHODS: For a hospital-based case-control study, cases of invasive pneumococcal disease (IPD) and non-bacteremic pneumococcal pneumonia (NBPP) (adults ≥ 65 years) were identified in 14 hospitals participated in the pneumococcal surveillance program from March 2013 to October 2015, following implementation of PPV23 national immunization program (NIP) for the elderly in the Republic of Korea. Controls matched by age, sex, and hospital were selected at ratios of 1:2 (IPD) or 1:1 (NBPP). Clinical data and vaccination records were collected. Vaccine effectiveness was calculated as (1-adjusted odds ratio) × 100. RESULTS: We enrolled 148 IPD and 557 NBPP cases, and 295 IPD and 557 NBPP controls for analyses. Overall effectiveness of PPV23 against IPD was 28.5% [95% confidence interval (CI) -5.8%-51.6%] and against NBPP was 10.2% (-15.1-30.6) in all patients ≥ 65 years. However, in subgroup analysis of patients aged 65-74 years, PPV23 was protective against IPD [effectiveness 57.4% (19.4-77.5)] and against NBPP [effectiveness 35.0% (2.3-56.7)]. Furthermore, serotype-specific effectiveness of PPV23 against IPD was 90.6% (27.6-98.8) for PPV23-unique serotypes and 81.3% (38.6-94.3) for PPV23 serotypes excluding serotype 3. CONCLUSIONS: This study indicates that PPV23 with broad serotype coverage might be beneficial in preventing IPD and NBPP due to non-PCV13 serotypes in the young-elderly, with potentially increasing effectiveness in the setting of childhood PCV NIP.

Adult invasive pneumococcal disease in the Republic of Korea: Risk medical conditions and mortality stratified by age group.

OBJECTIVES: This study aimed to characterize the risk factors for mortality in adult patients with invasive pneumococcal disease (IPD) stratified by age groups, after implementation of the national immunization program of 23-valent polysaccharide vaccine (PPSV23) for those aged ≥65 years in the Republic of Korea (ROK). METHODS: Clinical data and pneumococcal isolates from adult patients with IPD (≥18 years of age) were collected prospectively from 20 hospitals through the nationwide surveillance program from March 2013 to October 2015. RESULTS: A total of 319 patients with IPD were enrolled. Median age was 69 years. Overall in-hospital mortality was 34.2%: 17.1% in those aged 18-49 years, 23.7% in those aged 50-64 years, 33.0% in those aged 65-74 years, and 51.0% in those aged ≥75 years (p<0.001). In particular, early death within 7days of hospitalization accounted for 60.6% (66/109). While old age (≥65 years), higher Pitt bacteremia score (≥4), and bacteremic pneumonia were independently associated with IPD mortality in all age groups, an additional mortality risk factor of immunocompromised status was identified for patients aged 50-64 years. PPSV23 serotypes accounted for 64.4% (122/189) of the pneumococcal isolates serotyped. CONCLUSIONS: This study suggests that vaccine-type IPD continues to place a substantial burden on older adults in the ROK, necessitating an effective vaccination strategy for those at higher risk.

Hospital-based Influenza Morbidity and Mortality (HIMM) Surveillance for A/H7N9 Influenza Virus Infection in Returning Travelers.

Since 2013, the Hospital-based Influenza Morbidity and Mortality (HIMM) surveillance system began a H7N9 influenza surveillance scheme for returning travelers in addition to pre-existing emergency room (ER)-based influenza-like illness (ILI) surveillance and severe acute respiratory infection (SARI) surveillance. Although limited to eastern China, avian A/H7N9 influenza virus is considered to have the highest pandemic potential among currently circulating influenza viruses. During the study period between October 1st, 2013 and April 30th, 2016, 11 cases presented with ILI within seven days of travel return. These patients visited China, Hong Kong, or neighboring Southeast Asian countries, but none of them visited a livestock market. Seasonal influenza virus (54.5%, 6 among 11) was the most common cause of ILI among returning travelers, and avian A/H7N9 influenza virus was not detected during the study period.

Phase IV: randomized controlled trial to evaluate lot consistency of trivalent split influenza vaccines in healthy adults.

Influenza vaccines are the primary method for preventing influenza and its complications. Considering the increasing demand for influenza vaccines, vaccine manufacturers are required to establish large-scale production systems. This phase IV randomized trial was conducted to evaluate the lot consistency of trivalent split influenza vaccines regarding immunogenicity and safety. A total of 1,023 healthy adults aged 18-64 y were enrolled in the study. Subjects were randomly assigned in a 1:1 ratio to receive the GC FLU® Prefilled Syringe or the GC FLU® Injection, and they were further randomized to one of 3 lots of each vaccine in a 1:1:1 ratio. In both GC FLU® Injection and GC FLU® Prefilled Syringe groups, immune responses were equivalent between lots for each of the 3 vaccine strains on day 21. The 2-sided 95% CI of GMT ratios between pairs of lots were between 0.67 and 1.5, meeting the equivalence criteria. After vaccination, all 3 criteria of the European Medicines Agency were met in both GC FLU® Injection and GC FLU® Prefilled Syringe groups. The vaccines showed tolerable safety profiles without serious adverse events. The demonstration of lot consistency, robust immunogenic responses and favorable safety profiles support the reliability of mass-manufacturing systems for the GC FLU® Injection and GC FLU® Prefilled Syringe.

Severe influenza treatment guideline

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.

Leukemia cutis in a patient with acute monocytic leukemia diagnosed simultaneously with hepatocellular carcinoma: A case study.

Acute myeloid leukemia presenting as leukemia cutis (LC) with hepatocellular carcinoma is extremely rare. The current study presents a case of a 53-year-old male with generalized cutaneous nodules on the face and anterior chest wall. Laboratory tests, including bone marrow biopsy revealed acute myelomonocytic leukemia (AML-M4) with skin and tonsilar involvement. Liver magnetic resonance imaging (MRI) revealed a 6-cm mass in hepatic segments 4 and 8, and a liver biopsy demonstrated that hepatocellular carcinoma cells and immature blast cells coexisted. Although LC has been reported in Korea, a case of LC associated with acute myelomonocytic leukemia was diagnosed simultaneously with hepatocellular carcinoma and tonsillar involvement. The present study describes this case with a review of the literature.

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.

Healthcare-associated risk factors of vancomycin-resistant Enterococci colonization among outpatients undergoing hemodialysis.

Stool specimens and data were obtained from 399 outpatients undergoing hemodialysis (HD) in order to estimate the colonization rate of vancomycin-resistant enterococci (VRE) and to determine risk factors for VRE acquisition. The prevalence of VRE colonization in outpatients ranged from 0%-22.2%. Risk factors associated with VRE colonization were high hierarchy of hospital, short duration of HD, recent hospitalization, prior use of antimicrobial products, high platelet count, and low hemoglobin/albumin/blood urea nitrogen/creatinine levels, showing that VRE colonization was more common in patients with prior infections and poor nutritional status. Although pulsed-field gel electrophoresis (PFGE) analysis showed that most VRE isolates had diverse patterns, 2 paired cases from separate hospitals presented identical PFGE types.

The clinical usefulness of the SD Bioline Influenza Antigen Test® for detecting the 2009 influenza A (H1N1) virus.

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 onse.

Effectiveness of the pandemic influenza A/H1N1 2009 monovalent vaccine in Korea.

The 2009 influenza pandemic was caused by a novel triple-reassortant influenza A/H1N1 virus that was further recombined with a Eurasian pig flu virus. Vaccination is a key countermeasure for disease; however, little data assessing vaccine effectiveness (VE) against the pandemic H1N1 virus are available. We conducted a matched case-control study to assess effectiveness of the 2009 influenza A/H1N1 monovalent vaccine against laboratory-confirmed, medically attended influenza patients. Subjects included in the study were ≥ 10 years of age and were treated at five university hospitals in the Republic of Korea (ROK) from December 2009 through March 2010. For subjects visiting outpatient clinics with influenza-like illness (ILI), real time reverse transcription polymerase chain reaction (rRT-PCR) was used to diagnose 2009 H1N1 influenza virus infection. Subjects with positive rRT-PCR were classified as cases, while those testing negative were controls. A valid vaccination corresponded to ≥ 14 days between receiving a dose of vaccine and symptom onset. Overall, 416 ILI subjects were analyzed, and 60 (14.4%) were vaccinated with the 2009 influenza A/H1N1 monovalent vaccine. The overall VE against pandemic 2009 A/H1N1 virus illness after adjustment for age group and presence of chronic medical conditions was 73.4% (95% confidence interval [CI]=49.1-86.1%). Both vaccine formulations (unadjuvanted and MF-59 adjuvanted) showed a statistically significant VE. In conclusion, the 2009 influenza A/H1N1 monovalent vaccine was substantially protective against pandemic influenza in the ROK during the 2009-2010 season.

Characteristics of non-typhoidal Salmonella isolates from human and broiler-chickens in southwestern Seoul, Korea.

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 > or = 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.

Disease spectrum of cervical lymphadenitis: analysis based on ultrasound-guided core-needle gun biopsy.

OBJECTIVES: Despite the high frequency of cervical lymphadenopathy in the outpatient clinics, there was no published data on the disease spectrum of cervical lymphadenopathy among adult outpatients. We are evaluating the disease spectrum of cervical lymphadenitis in the outpatient setting. METHODS: As for the patients with cervical lymphadenitis, ultrasound-guided core-needle gun biopsy has been performed in Korea University Hospital. We reviewed medical records of adult outpatients with cervical lymphadenitis between January 2004 and April 2006, and compared the clinical, laboratory and radiological differences among them. RESULTS: The study included 147 patients with the mean age of 33.7 years. Histopathological diagnoses were obtained from 137 (93.2%) cases: Kikuchi's disease (34.7%), tuberculous lymphadenitis (22.4%), non-specific lymphadenitis (22.4%), lymphoma (6.1%), metastatic carcinoma (3.4%), etc. Overall, clinical manifestations were indistinguishable among tuberculous lymphadenitis, Kikuchi's disease and non-specific lymphadenitis. Leucopenia was characteristic of Kikuchi's disease, while anemia, thrombocytosis and pulmonary tuberculosis (irrespective of activity) were more common in the tuberculous lymphadenitis. CONCLUSION: Kikuchi's disease and tuberculosis were the most common and clinically important causes of cervical lymphadenitis. Complete blood count, chest X-ray and ultrasound-guided core-needle gun biopsy would be helpful in the differential diagnosis of cervical lymphadenitis, especially between Kikuchi's disease and tuberculous lymphadenitis.

Influenza vaccine coverage rates and perceptions on vaccination in South Korea.

OBJECTIVE: This survey was performed to assess the level of influenza vaccine coverage, to understand the driving forces and barriers to vaccination and determine vaccination interventions for the following year in Korean population. METHODS: A national sample of 1720 community dwelling adults of age 18 and older were surveyed by individual visits during April 2005. Demographics, state of influenza vaccination, reasons for vaccination or non-vaccination and perceptions on vaccinations were asked by questionnaire. RESULTS: Influenza vaccination coverage in general population and high risk group was 34.3% and 61.3%, respectively. Predictors for vaccination were > or =65 of age, performance of regular exercise, vaccination in the previous season, experience of influenza-like illness, belief that vaccine can prevent common cold and opinion that vaccine must be taken annually. The most common reason for vaccination for both whole population and high risk groups was to prevent both influenza and common cold, while the most common reason for non-vaccination was the thought that he/she was healthy enough not to be in need for vaccination. Having more information on influenza and vaccination as well as doctor's recommendation for vaccination appeared to be the most important modus operandi to encourage influenza vaccination among non-vaccinees. CONCLUSIONS: Doctor's recommendation was the most important factor in encouraging people to be vaccinated against influenza. Doctors should be geared up with precise information and actively encourage high risk population in order to increase vaccination coverage.

Clinical impact of influenza immunization in patients with liver cirrhosis.

BACKGROUND: Influenza vaccine is considered to reduce influenza-related morbidity and mortality in patients with underlying chronic medical conditions. Yet in liver cirrhosis, influenza vaccines have received little attention in determining the potential benefits. OBJECTIVES: We intended to evaluate the clinical benefits of influenza vaccination and clinical outcomes of influenza in patients with liver cirrhosis. METHODS: We performed a controlled, prospective clinical trial of 311 cirrhotic patients, who were enrolled in October 2004. Among them, 198 patients were vaccinated with a trivalent influenza vaccine and the rest were not vaccinated. Both groups were followed with respect to the occurrence of influenza-like illness (ILI) until May 2005. RESULTS: Overall incidences of ILI (p=0.064) and culture positivity of influenza (p=0.009) were remarkably higher in unvaccinated group compared to the vaccinated group. Most of the cirrhotic patients with influenza had fever (91.6%) and complained of myalgia (83.3%) without respiratory symptoms, which were not typical clinical presentations of influenza. Influenza vaccination also decreased influenza-related complication rates in patients with liver cirrhosis. CONCLUSION: Influenza vaccination should be recommended to all cirrhotic patients. High suspicion is required for early diagnosis and antiviral treatment, allowing for the frequent hepatic decompensation among cirrhotic patients.

In vitro activities of carbapenem/sulbactam combination, colistin, colistin/rifampicin combination and tigecycline against carbapenem-resistant Acinetobacter baumannii.

OBJECTIVES: To determine the in vitro activities and interactions of imipenem, colistin and tigecycline with old antibacterial agents against carbapenem-resistant Acinetobacter baumannii. METHODS: Forty-three carbapenem-resistant A. baumannii isolates from the intensive care unit of a university hospital were collected and their MICs of imipenem, colistin and tigecycline were determined. With eight randomly selected carbapenem-resistant isolates, an in vitro time-kill study was performed for the evaluation of antibacterial activity of colistin, tigecycline, imipenem/sulbactam and colistin/rifampicin. RESULTS: The time-kill study of colistin demonstrated bactericidal activity against A. baumannii at concentrations of 4xMIC and 8xMIC, whereas tigecycline showed bacteriostatic activity at all concentrations. The combination regimens of imipenem/sulbactam and colistin/rifampicin were synergistic and bactericidal at 1xMIC. CONCLUSIONS: Imipenem/sulbactam combination, colistin and tigecycline showed good in vitro activities against carbapenem-resistant A. baumannii isolates. Even though colistin is bactericidal against carbapenem-resistant A. baumannii, the colistin/rifampicin combination is more warranted in order to be certain.

Debate on annual influenza vaccination in healthcare workers for the same subtype under the vaccine shortage.

BACKGROUND: Influenza vaccination is the primary method for preventing influenza and its severe complications. Healthcare workers (HCWs) are one of the priority groups for the influenza vaccination. OBJECTIVES: To determine whether healthy HCWs, who were vaccinated with the same subtype for the two previous years, could be given less priority for influenza immunization under the vaccine shortage. STUDY DESIGN: We measured hemagglutination-inhibition antibody titers from sequential serum samples in 50 pre-immune subjects and 50 age-matched vaccine-naive subjects: immediately prior to the administration of the vaccine, 4-6 weeks, and 6 months after the vaccination. RESULTS: Prevaccination titers were maintained above protective level and high protection rates were observed for all three strains in pre-immune subjects: A/H1N1, A/H3N2, and B strains. As for the sequential changes, the protection rates for all three strains still remained above 70% until 6 months following the vaccination. CONCLUSION: Skipping influenza vaccination for a year could be considered in healthy pre-immune HCWs under the epidemic of the same subtype as two previous years.

Disseminated Mycobacterium avium complex infection in an immunocompetent pregnant woman.

BACKGROUND: Disseminated mycobacterium avium complex (MAC) occurs mainly in immunocompromised hosts, which is associated with abnormal cellular immunity. CASE PRESENTATION: 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. CONCLUSION: 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.

Active influenza immunization in hemodialysis patients: comparison between single-dose and booster vaccination.

BACKGROUND/AIMS: Hemodialysis (HD) patients are recommended to be immunized against influenza annually, but the immune response after vaccination is known to be weakened in these patients. We intended to compare the efficacy of influenza vaccines in HD patients with that in healthy people, and we also evaluated the additive effect of a booster vaccination in HD patients. METHODS: During the 2003-2004 influenza season, 100 patients on HD and 50 age-matched healthy controls were recruited from the Korea University Guro Hospital. The HD patients were divided into two groups: single-dose group (50 patients) and booster group (50 patients). Eight weeks following the influenza vaccination, the serum antibody responses were compared. RESULTS: Although the antibody response of the HD patients was impaired in comparison with that of healthy controls, more than 90% of the HD patients showed protective antibody levels. Booster vaccination did not significantly increase the immune response in HD patients. CONCLUSIONS: Influenza vaccination in HD patients should be encouraged, but the immune response was comparatively impaired in subpopulations, including patients with a long-term HD history (>2.5 years), with a higher urea reduction rate, or with underlying diabetes. There was no effect of a booster vaccine dose on the antibody titers.