Persistent serotype 3 and 19A invasive pneumococcal diseases in adults in vaccine era: Serotype-dependent difference in ceftriaxone susceptibility.

BACKGROUND: Invasive pneumococcal disease (IPD) is associated with substantial morbidity and mortality in children and elderly populations. Serotype distribution and antibiotic susceptibility of IPD isolates are changing with the implementation of pneumococcal vaccination and increasing antibiotic use worldwide. We aimed to determine serotype distribution, antibiogram, and molecular epidemiology of pneumococci in the late stage of PCV13 era. METHODS: Prospective multicenter IPD surveillance study was conducted for adults aged ≥ 19 years from July 2019 to June 2021. Clinical and epidemiologic data were collected. In addition, antibiotic susceptibility test, serotype identification and multi-locus sequence typing (MLST) was taken for pneumococcal isolates. RESULTS: A total of 160 IPD cases were collected with mean age of 65.1 years (male, 72.5%). Serotyping was taken for 116 available pneumococcal isolates. PCV13 and PPSV23 serotypes were 32.8% (n = 38) and 56.0% (n = 65), respectively. Serotype 3 (13.8%) and 19A (9.5%) were the most common causative agents of IPD, followed by serogroup 11 (6.9%), 23A (6.9%), 10A (4.3%), and 15B (4.3%). Notably, 32.5% of invasive pneumococcal isolates were non-susceptible to ceftriaxone. Serotypes 11A, 11E and 19A pneumococci showed high ceftriaxone non-susceptible rate (80%, 100% and 81.8% respectively), and they were related to sequence type (ST) 166 and ST320. In comparison, most serotype 3 isolates were ceftriaxone susceptible and related to ST180. CONCLUSIONS: PCV serotypes, especially 3 and 19A, are still prevalent in adult IPDs, suggesting that individual PCV13 immunization would be necessary for the elderly people and chronically ill patients. Ceftriaxone non-susceptible rate was remarkably high in invasive pneumococcal isolates.

Immunogenicity and safety of a tetanus-diphtheria vaccine and a 13-valent pneumococcal conjugate vaccine after concomitant vaccination in ≥ 50-year-old adults.

BACKGROUND: When two or more vaccines are administered concurrently, there is concern about safety and immunogenicity from vaccine interaction. METHODS: Subjects aged ≥50 years were randomized 1:1:1 to receive tetanus-diphtheria (Td) + 13-valent pneumococcal conjugate vaccine (PCV13; Group 1), PCV13 alone (Group 2), or Td alone (Group 3). After single or concomitant vaccination, enzyme-linked immunosorbent assay and opsonophagocytic assay (OPA) were performed to compare immunogenicity for Td and PCV13, respectively. RESULTS: A total of 448 subjects were available for the assessment. After concomitant administration, the non-inferiority criteria of geometric mean titer (GMT) ratios were met for tetanus, diphtheria, and all four pneumococcal serotypes (1, 5, 18C, and 19A). However, subjects in Group 3 (Td alone) were more likely to have a high IgG anti-tetanus antibody titer (≥ 0.5 U/mL) than those in Group 1 (Td + PCV13) (p <  0.01). As for the pneumococcal serotype 1, the OPA GMT was significantly higher in Group 1 (PCV13 + Td) compared to Group 2 (PCV13 alone) (p = 0.02). No serious adverse event occurred. CONCLUSIONS: Concomitant Td and PCV13 administration induced sufficient immunity without significant interference and showed good safety profiles. TRIALS REGISTRATION: NCT03552445 registered at http://www.clinicaltrials.gov on June 11, 2018 (retrospectively registered).

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.

Analysis of Risk Factors for Severe Acute Respiratory Infection and Pneumonia and among Adult Patients with Acute Respiratory Illness during 2011-2014 Influenza Seasons in Korea.

BACKGROUND: The World Health Organization recommends the surveillance of influenza-like illness (ILI) and severe acute respiratory infection (SARI) to respond effectively to both seasonal influenza epidemics and pandemics. In Korea, the "Hospital-based Influenza Morbidity and Mortality (HIMM)" surveillance system has been operated to monitor ILI and SARI occurrences. MATERIALS AND METHODS: A multi-center prospective observational study was conducted. Adult patients with acute respiratory infection (ARI) were enrolled during the 2011-12, 2012-2013, and 2013-2014 influenza seasons at the 10 university hospitals using the HIMM surveillance system. With respect to SARI and pneumonia development, risk profiles were analyzed in patients with ARI in Korea. RESULTS: A total of 5,459 cases were eligible for this analysis. Among 5,459 cases with ARI, 2,887 cases (52.9%) were identified that they had influenza infection. Among enrolled cases, 750 cases belonged to the SARI group, while 4,709 cases belonged to the non-SARI group. With respect to pneumonia development, 317 cases were accompanied by pneumonia, and 5,142 cases were not. Multivariate analyses revealed that the following factors were associated with an increased risk of SARI: Old age (≥65 years) (odds ratio [OR] 2.69, 95% confidence interval [CI] 2.2-3.32), chronic heart disease (CHD) (OR 2.24, 95% CI 1.68-2.98), cerebrovascular disease (CVD) (OR 1.49, 95% CI 1.05-2.10), chronic obstructive pulmonary disease (COPD) (OR 2.34, 95% CI 1.48-3.69), asthma (OR 2.33, 95% CI 1.62-3.36), chronic kidney disease (CKD) (OR 2.62, 95% CI 1.73-3.99), chronic liver disease (OR 1.71, 95% CI 1.04-2.81), and autoimmune diseases (OR 2.53, 1.57-4.08). Multivariate analyses revealed that the following factors were independent risk factors for pneumonia development: Old age (≥65 years) (OR 5.71, 95% CI 4.10-7.94), CHD (OR 1.54, 95% CI 1.07-2.22), COPD (OR 2.34, 95% CI 1.48-3.69), asthma (OR 2.33, 95% CI 1.62-3.36), CKD (OR 2.62, 95% CI 1.73-3.99), immunocompromised conditions (OR 3.12, 95% CI 1.47-6.62), and autoimmune diseases (OR 3.35, 95% CI 1.79-6.27). The risk of SARI and pneumonia was increased by the number of concurrent chronic medical conditions. CONCLUSION: The risk of SARI and pneumonia development among adult patient with ARI was significantly increased by the presence or number of concurrent chronic medical conditions in Korea.

Viral shedding from diverse body fluids in a patient with severe fever with thrombocytopenia syndrome.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne disease characterized by high fever, thrombocytopenia, leukopenia, and multiple organ failure and is caused by a novel bunyavirus. Human-to-human transmission has been reported previously, but the mode of transmission has not been clarified thoroughly. STUDY DESIGN: We identified a case of a 73-year-old woman with SFTS and performed a semi-quantitative real-time reverse transcription PCR (real-time RT-PCR) assay on her blood, tracheal aspirate, gastric aspirate and urine to detect SFTS virus (SFTSV). RESULTS: During 7-day hospitalization, all the serum samples showed positive Ct values lower than 35 in both the S and M segments, suggesting the presence of the SFTSV RNA. After initiation of plasma exchange, serum SFTSV load markedly decreased, but still remained positive. The SFTS viral RNA was also detected in other body fluids, including tracheal aspirate and gastric aspirate. CONCLUSION: These results suggest that droplet transmission can occur through close contact with infected patients.

Perceptions of influenza vaccination during pregnancy in Korean women of childbearing age.

The rate of maternal influenza vaccination in Korea is much lower than the general population. We evaluated the influenza vaccination rate during pregnancy and assessed women's perceptions of the influenza vaccine. One thousand women of childbearing age were surveyed from April through May 2014, using a questionnaire about vaccination history, general understanding of influenza vaccination and that examined factors that influence decisions about influenza vaccination. We also conducted an intervention to evaluate potential improvement in vaccination behavior. The influenza vaccination rate during pregnancy was 37.3%. The common reasons listed in support of vaccination included the perception of the risk of influenza infection, recommendations from health care providers, and belief in the effectiveness of the influenza vaccine. The most common reasons for not vaccinating included concern about harmful effects and the lack of recommendation from health care providers. Based on the results of the questionnaire and intervention, it is important to provide accurate information and for health care providers to recommend the influenza vaccine to pregnant women. It is also necessary for the government to encourage women to receive the influenza vaccination as a healthcare policy.

Clinical features of lung adenocarcinomas with epidermal growth factor receptor mutations and miliary disseminated carcinomatosis.

BACKGROUND: We have occasionally encountered advanced lung cancer patients with disseminated carcinomatosis throughout the body and/or within the lung. This study investigated the clinical characteristics and outcomes of advanced lung adenocarcinoma patients with miliary disseminated carcinomatosis. METHODS: Patients with adenocarcinomas harboring epidermal growth factor receptor (EGFR) mutations who presented with miliary disseminated carcinomatosis (either intrapulmonary or distant site) were enrolled in the study. Clinical characteristics, treatment responses, and survival outcomes were collected from medical records. RESULTS: The most frequent EGFR mutation was an in-frame deletion in exon 19 (n = 44, 68.8%). Arginine substitution of leucine 858 in exon 21 and alanine substitution of glycine 719 in exon 18 were detected in 19 patients (29.7%) and one patient (1.6%), respectively. Patients with miliary disseminated carcinomatosis tended to be female and non-smokers. They expressed the E19 deletion more frequently than patients without miliary dissemination and had shorter progression-free survival times in response to EGFR tyrosine kinase inhibitors (9.7 vs. 12.8 months, P = 0.003) and poorer overall survival (15.9 vs. 29.0 months, P = 0.077). Multivariate analyses revealed that metabolic tumor volume correlated with shorter overall survival time. CONCLUSIONS: Our data indicate that lung adenocarcinoma patients with miliary dissemination have relatively shorter survival times than those without miliary dissemination. The poor prognosis of patients with miliary dissemination may reflect a high tumor burden, as represented by metabolic tumor volume.

Clinical usefulness of pneumococcal urinary antigen test, stratified by disease severity and serotypes.

Early diagnosis of pneumococcal pneumonia facilitates appropriate antibiotic therapy. The urinary antigen test (UAT) is known to be useful for the diagnosis of pneumococcal pneumonia. This study aimed to evaluate the usefulness of UAT in the 13-valent pneumococcal conjugated vaccine (PCV13) era. Community-acquired pneumonia (CAP) cases aged ≥19 years were reviewed retrospectively. This study evaluated the utility of Streptococcus pneumoniae UAT (BinaxNOW(®) assay) for diagnosis of pneumococcal CAP, and the relation of the UAT positive rate to age, comorbidities, pneumonia severity, and pneumococcal serotypes. Among 752 microbiologically identified CAP cases, S. pneumoniae (36.7%) was the most common isolate, and of those cases, 56.4% were positive for UAT. UAT positivity varied by pneumococcal serotype (serotype 3, 50%; 9V/9A, 85%; 11A/11E, 54%; 14, 36.4%; 19A, 50%; and 23F, 37.5%), and was significantly increased since 2012, two years after introduction of PCV13. The positive rate of UAT was significantly related to CRP level (P = 0.007) and lobar pneumonia (P = 0.006), but not to age, co-morbidities or prior antibiotic therapy. In conclusion, urinary antigen detection varied depending on the S. pneumoniae serotype. In the PCV13 era, the serotype distribution of pneumococcal pneumonia may be changing, and the clinical usefulness of UAT needs to be monitored. The positive rate of UAT may be influenced by a localized bacterial burden and host reactions.