Comparative Effects of Bivalent, Quadrivalent, and Nonavalent Human Papillomavirus Vaccines in The Prevention of Genotype-Specific Infection: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Human papillomavirus (HPV) infection is a major global disease burden and the main cause of cervical cancer. Certain HPV genotypes, with are the most common etiologic pathogens and cause a significant disease burden, are being targeted for vaccine development. However, few studies have focused on the comparative effectiveness of the bivalent HPV (2v-HPV), quadrivalent HPV (4v-HPV), and nonavalent HPV (9v-HPV) vaccines against HPV strain-specific infection. This study investigated the comparative effects of these vaccines against genotype-specific infection. MATERIALS AND METHODS: We conducted a pairwise and network meta-analysis of published randomized clinical trials of HPV vaccines according to sex and HPV infection status for nine HPV genotypes (HPV 6/11/16/18/31/33/45/52/58). RESULTS: Overall, 10 randomized controlled trials (12 articles) were included in this study. In the network meta-analysis, no statistically significant differences were observed in the prevention of carcinogenic HPV strains (16/18/31/33/45/52/58) between the 2v-HPV and 4v-HPV vaccines in female HPV infection-naïve populations. However, the 9v-HPV vaccine showed a significantly superior effect compared with 2v-HPV and 4v-HPV vaccines in preventing HPV 31/33/45/52/58 infections. Although 2v-HPV and 4v-HPV vaccines provided some cross-protection against HPV 31/33/45/52/58 infections, the effect was significant only on HPV 31 infection. For HPV 16 and 18, neither statistically significant nor small differences were found in the prevention of HPV infection among the 2v-HPV, 4v-HPV, and 9v-HPV vaccines. CONCLUSION: Our study complements previous understanding of how the effect of HPV vaccines differs according to the HPV genotype. This is important because HPV genotype prevalence varies among countries. We advocate for continued efforts in vaccinating against HPV, while public health agencies should consider the difference in the vaccine effect and HPV genotype prevalence when implementing HPV vaccination in public vaccination programs.

Pediatric Deaths Associated With Coronavirus Disease 2019 (COVID-19) in Korea.

As of September 3, 2022, 5,388,338 coronavirus disease 2019 (COVID-19) cases and 46 deaths (3 in 2021 and 43 in 2022) were reported in children ≤ 18 years in Korea. Cumulative confirmed cases accounted for 67.3% of the population aged ≤ 18 years and case fatality rate was 0.85/100,000. Among 46 fatal cases, 58.7% were male and median age was 7 years. Underlying diseases were present in 47.8%; neurologic diseases (63.6%) and malignancy (13.6%) most common. Only four had history of COVID-19 immunization. COVID-19 associated deaths occurred at median 2 days from diagnosis (range: -1 to 21). Among COVID-19 deaths, 41.3% occurred before admission; 2 before hospital arrival and 17 in the emergency department. Among children whose cause was documented, myocarditis, respiratory and multiorgan failure were most common. COVID-19 associated death was seen early after diagnosis in children and public health policies to provide access to medical care for children with COVID-19 are essential during the pandemic.

A global epidemiological analysis of COVID-19 vaccine types and clinical outcomes.

OBJECTIVES: To compare messenger RNA (mRNA)-based and adenovirus-vectored vaccines (ADVVs) with inactivated virus vaccines (IVVs) using real-world aggregate data. METHODS: We performed longitudinal analyses of publicly accessible epidemiological, clinical, virological, vaccine-related, and other public health data from 41 eligible countries during the first half of 2021. The relationships between vaccination coverage and clinical outcomes were analyzed using repeated measures correlation analyses and mixed-effects modeling to adjust for potential mediating and confounding factors. RESULTS: Countries that used mRNA and/or ADVV (n = 31) vs IVV, among other vaccine types (n = 10), had different distributions of age (42.4 vs 33.9 years, respectively; P-value = 0.0006), gross domestic product per capita ($ 38,606 vs $ 20,422, respectively; P <0.0001), and population sizes (8,655,541 vs 5,139,162, respectively; P-value = 0.36). After adjustment for country differences, the stringency of nonpharmaceutical interventions, and dominant SARS-CoV-2 variant types, populations that received mRNA and/or ADVV had significantly lower rates of cases and deaths over time (P <0.001 for each analysis). Populations vaccinated with IVV, among others, had significantly higher rates of cases and deaths over time (P <0.05 for each analysis). CONCLUSION: The real-world effectiveness of IVV may be inferior to mRNA and/or ADVV, and prospective comparative studies are needed to critically evaluate the role of IVV in the context of contemporary SARS-CoV-2 variants.

Treatment patterns of anti-tumour necrosis factor-alpha and prognosis of paediatric and adult-onset inflammatory bowel disease in Korea: a nationwide population-based study.

BACKGROUND: The global prevalence of inflammatory bowel disease (IBD) is increasing. However, population-level data are scarce for Asian populations. AIMS: To outline and compare paediatric and adult IBD incidence and prevalence data in Korea, describe prescription patterns, and analyse outcomes of anti-tumour necrosis factor (anti-TNF) use in a nationally representative cohort METHODS: IBD was identified based on the presence of Rare and Intractable Disease diagnosis codes for Crohn's disease (CD) and ulcerative colitis (UC). We calculated age-based prevalence and incidence, and examined prescription patterns. We used a Cox proportional hazard model to calculate the hazard ratio (HR) for undergoing surgery. RESULTS: The prevalence of CD increased between 2006 and 2015, particularly among those aged 10-19 years (12.7-35.5 patients per 100,000 people). The use of anti-TNF agents increased from 3.2% to 22.9% in paediatric CD patients. Early use of an anti-TNF agent increased 25-fold in CD patients. Further, CD patients aged 0-14 years were most likely to undergo fistulectomy (HR, 2.63; 95% confidence interval [CI], 1.73-3.97). Children with UC had a higher risk of undergoing surgery (HR, 3.01; 95% CI, 1.33-6.83) than adults. Early use of an anti-TNF agent in CD patients was associated with lower odds of surgery than late-stage use. CONCLUSION: The prevalence of IBD has increased over time, especially among paediatric patients. Given the magnitude of paediatric IBD disease burden, a multi-faceted approach is needed for early detection and vigilant monitoring to aim for better prognosis.

Ambient Air Pollution and Kawasaki Disease in Korean Children: A Study of the National Health Insurance Claim Data.

Background Kawasaki disease (KD) is a systemic vasculitis of unknown etiology that primarily affects children under 5 years of age. Some researchers suggested a potential triggering effect of air pollution on KD, but the findings are inconsistent and limited by small sample size. We investigated the association between ambient air pollution and KD among the population of South Korea younger than 5 years using the National Health Insurance claim data between 2007 and 2019. Methods and Results We obtained the data regarding particulate matter ≤10 or 2.5 µm in diameter, nitrogen dioxide, sulfur dioxide, carbon monoxide, and ozone from 235 regulatory monitoring stations. Using a time-stratified case-crossover design, we performed conditional logistic regression to estimate odds ratios (OR) of KD according to interquartile range increases in each air pollutant concentration on the day of fever onset after adjusting for temperature and relative humidity. We identified 51 486 children treated for KD during the study period. An interquartile range increase (14.67 µg/m3) of particulate matter ≤2.5 µm was positively associated with KD at lag 1 (OR, 1.016; 95% CI, 1.004-1.029). An interquartile range increase (2.79 ppb) of sulfur dioxide concentration was associated with KD at all lag days (OR, 1.018; 95% CI, 1.002-1.034 at lag 0; OR, 1.022; 95% CI, 1.005-1.038 at lag 1; OR, 1.017; 95% CI, 1.001-1.033 at lag 2). Results were qualitatively similar in the second scenario of different fever onset, 2-pollutant model and sensitivity analyses. Conclusions In a KD-focused national cohort of children, exposure to particulate matter ≤2.5 µm and sulfur dioxide was positively associated with the risk of KD. This finding supports the triggering role of ambient air pollution in the development of KD.

Shifting Patterns of Respiratory Virus Activity Following Social Distancing Measures for Coronavirus Disease 2019 in South Korea.

BACKGROUND: We hypothesized that nationwide social distancing and other preventive measures for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were associated with reduced detection of other respiratory viruses in South Korea. METHODS: We analyzed national surveillance data to compare incidence of respiratory viruses during 2016-2019 vs 2020. Results of multiplex reverse-transcription polymerase chain reaction assays for 8 respiratory viruses were included: adenovirus (ADV), parainfluenza virus (PIV), respiratory syncytial virus (RSV), influenza virus (IFV), human coronavirus (HCoV; non-SARS-CoV-2), human rhinovirus (HRV), human bocavirus (HBoV), and human metapneumovirus (HMPV). RESULTS: During 2016-2019, rates of detection of respiratory viruses were relatively stable: ADV, 3.7%-9.2%; PIV, 1.4%-17.0%; RSV, 0.3%-15.3%; IFV, 0.4%-35.6%; HCoV, 1.5%-8.4%; HRV, 7.0%-25.1%; HBoV, 0.6%-6.3%; and HMPV, 0.7%-14.5%. Following implementation of social distancing in February 2020, rates of detection of enveloped viruses (HCoV, HMPV, IFV, PIV, and RSV) were significantly reduced by up to 100%. However, nonenveloped viruses (ADV, HRV, and HBoV) persisted throughout 2020, and HRV rates in hospitalized patients significantly increased. CONCLUSIONS: After implementation of social distancing for SARS-CoV-2 in South Korea, rates of detection of enveloped respiratory viruses decreased significantly, whereas nonenveloped viruses persisted, suggesting that enhanced infection prevention strategies are required to mitigate spread of these viruses.

Co-seasonality and co-detection of respiratory viruses and bacteraemia in children: a retrospective analysis.

OBJECTIVES: The aim of this study was to assess the co-seasonality and co-detection of respiratory viral infections and bacteraemia in children since the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13). METHODS: Children <18 years old were eligible for inclusion if they had a respiratory infection and a positive PCR-based assay for respiratory viruses as well as a positive blood culture between 2010 and 2018 at a single referral centre in the United States, regardless of their underlying medical condition or antibiotic treatment history. Monthly incidence rates of respiratory viruses and bacteraemia were analysed with a seasonal-trend decomposition procedure based on loess (STL) and cross-correlation functions using time series regression modelling. RESULTS: We identified 7415 unique positive respiratory virus tests, including 2278 respiratory syncytial virus (RSV) (31%), 1825 influenza viruses (24%), 1036 parainfluenza viruses (14%), 1017 human metapneumovirus (hMPV) (14%), 677 seasonal coronaviruses (9%), and 582 adenoviruses (8%), together with a total of 11 827 episodes of bacteraemia. Significant co-seasonality was found between all-cause bacteraemia and RSV (OR = 1.76, 95%CI 1.50-2.06, p < 0.001), influenza viruses (OR = 1.38, 95%CI 1.13-1.68, p 0.002), and seasonal coronaviruses (OR = 1.18, 95%CI 1.09-1.28, p < 0.001), respectively. Analysis of linked viral-bacterial infections in individual children indicated that the rate ratio (RR) of bacteraemia associated with hMPV (RR = 2.73, 95%CI 1.12-6.85, p 0.019) and influenza (RR = 2.61, 95%CI 1.21-6.11, p 0.013) were more than double that of RSV. Staphylococcus aureus and Streptococcus pneumoniae were the most commonly identified pathogens causing bacteraemia. CONCLUSIONS: There is a significant association between hMPV and influenza viruses and bacteraemia of all causes in hospitalized children at a single paediatric centre in the United States. Large multicentre studies are needed to confirm these findings and to elucidate the mechanisms by which hMPV potentiates the virulence and invasive capacity of diverse bacteria.

Risk Factors for Mortality in Children with Acinetobacter baumannii Bacteremia in South Korea: The Role of Carbapenem Resistance.

Aims: Acinetobacter baumannii has become an important nosocomial pathogen that causes invasive infections. We conducted a retrospective study to evaluate the risk factors for mortality due to A. baumannii bacteremia in children. Materials and Methods: We reviewed data from Seoul National University Children's Hospital from 2002 to 2013 for children with A. baumannii bacteremia, including age, gender, underlying disease, associated site of infection, duration of hospitalization, presence of neutropenia, and antibiotic susceptibility data. The outcome measures were the 7- and 30-day mortality rates. Results: Among 74 A. baumannii bacteremia cases, 35.1% were carbapenem nonsusceptible. Common comorbidities were malignancy or hematologic diseases (28.4%), followed by gastrointestinal/hepatobiliary diseases (21.6%). A total of 47.3% of patients had isolated bacteremia, and in 33.8% of patients, pneumonia accompanied bacteremia. The mortality rates were 18.9% at 7 days and 35.1% at 30 days. The significant associated factors for 30-day mortality were carbapenem nonsusceptibility (adjusted hazard ratio [aHR]: 1.28, 95% confidence interval [CI]: 1.10-11.82, p = 0.034), neutropenia (aHR: 1.68, 95% CI: 1.60-18.03, p = 0.007), and prior intensive care unit (ICU) admission (aHR: 1.15, 95% CI: 1.03-9.73, p = 0.045). The mortality rate among neutropenic patients with inappropriate empirical antibiotics was higher than that among patients with appropriate empirical antibiotics (90.1% vs. 33.3%, p = 0.031). Conclusions: We identified carbapenem nonsusceptibility, neutropenia, and prolonged ICU stay as independent risk factors for mortality due to A. baumannii bacteremia in children. An early administration of appropriate antibiotics should be enacted, especially in patients with neutropenia.

Risk Factors and Clinical Features of Cytomegalovirus Disease in Children Receiving Anticancer Chemotherapy.

This study was conducted to identify risk factors for cytomegalovirus (CMV) infection and demonstrate the spectrum of CMV disease in children receiving anticancer chemotherapy without hematopoietic stem cell transplantation (HSCT). A total of 289 children who received chemotherapy and were tested for CMV infection were included in the study. CMV antigenemia and DNAemia were determined by identifying the pp65 antigen in leukocytes and performing real-time PCR. CMV disease was diagnosed by tissue biopsy, culture, or ophthalmic examination. Of the 289 children, CMV infection was demonstrated in 46 patients (15.9%). Young age at cancer diagnosis was the risk factor for CMV infection by multivariate analysis (7 mo vs. 7 y, P<0.001). Among 46 children with CMV infection, 10 (21.7%) were diagnosed with CMV disease; hepatitis (n=4), retinitis (n=3), hepatitis and pneumonia (n=2), and hepatitis and retinitis (n=1). The age of the patients with CMV disease was significantly younger than those without (3 vs. 16 mo, P=0.023). Retinoblastoma and neuroblastoma were the 2 most common underlying malignancies. There were 2 fatal cases associated with CMV disease, including 1 who died of CMV pneumonia. The findings of this study demonstrated significant morbidity of CMV infection and disease in young children during the course of chemotherapy without HSCT.

Antiviral treatment of influenza in South Korea.

Antiviral therapy has an important role in the treatment and chemoprophylaxis of influenza. At present, two classes of antiviral agents, adamantanes and neuraminidase inhibitors, are available for the treatment and chemoprophylaxis of influenza in Korea. Because of the widespread resistance against adamantanes, neuraminidase inhibitors are mainly used. Because each country has a unique epidemiology of influenza, the proper use of antiviral agents should be determined based on local data. Decisions on the clinical practice in the treatment of influenza in South Korea are guided by the local surveillance data, practice guidelines, health insurance system and the resistance patterns of the circulating influenza viruses. This review highlights the role of antiviral agents in the treatment and outcome of influenza in Korea by providing comprehensive information of their clinical usage in Korea.

Prioritization of the introduction of new vaccines to the national immunization program in the Republic of Korea.

BACKGROUND: This study was performed to determine the priority of vaccine introduction for five vaccine-preventable diseases (VPDs) caused by Haemophilus influenzae type b (Hib), pneumococcus (Spn), hepatitis A virus (HepA), rotavirus (RV), and human papillomavirus (HPV) to the future Korean National Immunization Program (NIP) and to suggest framework programs to assist decision makers on implementation of the NIP. METHODS: Following analysis of the disease burden and economics of the five VPDs by the core team and Korean Advisory Committee on Immunization Practices sub-committee members, a Delphi survey was administered to 94 Korean experts using structured questionnaires that provided the reference data. The two evaluation frameworks for NIP prioritization were (1) a disease-related framework and (2) a vaccine-related framework. After analyzing the responses, a meeting of experts was held to build a consensus for determining how to prioritize NIP implementation. RESULTS: The average scores for relative importance were 63.29 for the disease-related framework and 36.71 for the vaccine-related framework. Within the disease-related framework, the mortality and case fatality rate was the highest scored factor (8.97), whereas within the vaccine-related framework, efficacy of the vaccine was considered the most important factor (9.56). On average, Spn, Hib, and HepA had the highest priority scores. CONCLUSION: The Korean experts suggested that the main factors influencing the decision to adopt new vaccines in the Korean NIP should be disease mortality, case fatality, and the efficacy and effectiveness of the vaccine. Among the five selected VPDs, Spn, Hib, and HepA were considered to be of higher priority than RV and HPV.

Sudden death in the first 2 years of life following immunization in the Republic of Korea.

BACKGROUND: Because the peak age for incidence of sudden deaths in infancy temporally coincides with the age of infant primary immunization, some have raised the question as to whether immunization is a risk factor for sudden death in infancy. Recent occurrence of two sudden deaths in infants in Korea has renewed concerns about the causal association between immunization and sudden deaths in infants. METHODS: We carried out a retrospective review of data from the Korea Centers for Disease Control and Prevention Adverse Events Following Immunization Surveillance System and Vaccine Compensation programs. RESULTS: From 1994 to 2011, a total of 45 cases of sudden deaths in the first 2 years of life following immunization were reported in Korea. The causes of death were classified as follows: infectious diseases (n= 13); accidental injuries (n= 7); congenital abnormalities (n= 2); and malignancy (n= 1). Of 20 sudden deaths in infancy, nine deaths met Brighton Collaboration case definition level I and II, and therefore were classified as possible sudden infant death syndrome cases. Hepatitis B vaccine (n= 13) was the most frequent vaccine with temporal association with sudden deaths in the first 2 years of life. CONCLUSION: Few sudden deaths in the first 2 years of life following immunization have been reported, despite the use of universal immunization in Korea. The majority of deaths in infancy did not meet case definition for sudden infant death syndrome. Encouraging investigators to perform thorough investigation, including postmortem autopsy and death scene examination, may promote data comparability and provide guidance on decision-making in the vaccine-safety monitoring and response system in Korea.

Novel CFTR mutations in a Korean infant with cystic fibrosis and pancreatic insufficiency.

Cystic fibrosis (CF) is an autosomal recessive disease that is very rare in Asians: only a few cases have been reported in Korea. We treated a female infant with CF who had steatorrhea and failure to thrive. Her sweat chloride concentration was 102.0 mM/L. Genetic analysis identified two novel mutations including a splice site mutation (c.1766+2T >C) and a frameshift mutation (c.3908dupA; Asn1303LysfsX6). Pancreatic enzyme replacement and fat-soluble vitamin supplementation enabled the patient to get a catch-up growth. This is the first report of a Korean patient with CF demonstrating pancreatic insufficiency. CF should therefore be considered in the differential diagnosis of infants with steatorrhea and failure to thrive.