• Pediatric Infection and Vaccine
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• 제10권1호
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• pp.87-94
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• 2003

목 적 : 호흡기 바이러스는 인간에게 가장 전염성이 강한 병원체의 하나로 급성 호흡기 감염 특히 하기도 감염증은 소아에서의 유병률과 사망률의 주요 원인이 되고 있다. 저자들은 하기도 감염증에 이환된 환아들을 대상으로 influenza A, B virus, adenovirus, enterovirus의 감염 연령 분포와 계절적 유행 양상, 바이러스별 임상 양상을 알기 위하여 이 연구를 시작하였다. 방 법 : 2002년 1월부터 2002년 12월까지 부산 메리놀병원에 입원하거나 외래 방문한 하기도 감염증 소아들을 대상으로 인후 가검물, 콧물, 타액 분비물 등을 채취하여 바이러스를 동정하였고, 검사를 시행한 568명 중 바이러스가 동정된 54명을 대상으로 호발 연령, 유행 시기, 임상 증상을 후향적으로 조사하였다. 결 과 : 1) 대상 환아의 연령 분포는 2개월부터 14세 사이였고, 남녀비는 1.8 : 1이었다. 3~6세가 29.6%로 가장 많았고, 2~3세 사이가 14.8%, 12세 이상이 13% 순이었다. 2) 동정된 바이러스는 influenza A virus가 59.3%로 가장 많았고, enterovirus가 33.3%, adenovirus 5.6%, influenza B virus 1.9%였고, parainfluenza virus와 RSV는 동정되지 않았다. 3) 임상 양상은 폐렴이 51.9%로 가장 많았고, 기관지염이 31.5%, 크루프 9.3%, 모세기관지염 7.4%의 순이었다. 4) 호흡기 바이러스는 각각의 유행 시기가 있어, influenza A virus는 3~5월, 11월에 2차례의 유행이 있어 주로 겨울에 유행하는 양상을 보였으며, influenza B virus는 3월에, adenovirus는 3월과 7월에, enterovirus는 3~7월에 유행하여 주로 봄부터 여름까지 유행하는 양상을 보였다. 결 론 : 2002년 부산 지역 호흡기 바이러스 감염의 주된 원인은 influenza virus였다. 이러한 결과는 influenza virus의 유행을 보여주는 것으로 이에 대한 지속적인 감시와 예방, 조기 진단과 치료가 필요하다고 하겠다.

• Clinical and Experimental Pediatrics
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• 제56권4호
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• pp.165-175
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• 2013

Purpose: There was a global increase in the prevalence of oseltamivir-resistant influenza viruses during the 2007-2008 influenza season. This study was conducted to investigate the occurrence and characteristics of oseltamivir-resistant influenza viruses during the 2007-2008 and 2008-2009 influenza seasons among patients who were treated with oseltamivir (group A) and those that did not receive oseltamivir (group B). Methods: A prospective study was conducted on 321 pediatric patients who were hospitalized because of influenza during the 2007-2008 and 2008-2009 influenza seasons. Drug resistance tests were conducted on influenza viruses isolated from 91 patients. Results: There was no significant difference between the clinical characteristics of groups A and B during both seasons. Influenza A/H1N1, isolated from both groups A and B during the 2007-2008 and 2008-2009 periods, was not resistant to zanamivir. However, phenotypic analysis of the virus revealed a high oseltamivir $IC_{50}$ range and that H275Y substitution of the neuraminidase (NA) gene and partial variation of the hemagglutinin (HA) gene did not affect its antigenicity to the HA vaccine even though group A had a shorter hospitalization duration and fewer lower respiratory tract complications than group B. In addition, there was no significant difference in the clinical manifestations between oseltamivir-susceptible and oseltamivir-resistant strains of influenza A/H1N1. Conclusion: Establishment of guidelines to efficiently treat influenza with oseltamivir, a commonly used drug for treating influenza in Korean pediatric patients, and a treatment strategy with a new therapeutic agent is required.

• Journal of Microbiology and Biotechnology
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• 제33권12호
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• pp.1576-1586
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• 2023

Vaccination is the most effective method for preventing the spread of the influenza virus. Cell-based influenza vaccines have been developed to overcome the disadvantages of egg-based vaccines and their production efficiency has been previously discussed. In this study, we investigated whether treatment with forskolin (FSK), an adenylyl cyclase activator, affected the output of a cell-based influenza vaccine. We found that FSK increased the propagation of three influenza virus subtypes (A/H1N1/California/4/09, A/H3N2/Mississippi/1/85, and B/Shandong/7/97) in Madin-Darby canine kidney (MDCK) cells. Interestingly, FSK suppressed the growth of MDCK cells. This effect could be a result of protein kinase A (PKA)-Src axis activation, which downregulates extracellular signal-regulated kinase (ERK)1/2 activity and delays cell cycle progression from G1 to S. This delay in cell growth might benefit the binding and entry of the influenza virus in the early stages of viral replication. In contrast, FSK dramatically upregulated ERK1/2 activity via the cAMP-PKA-Raf-1 axis at a late stage of viral replication. Thus, increased ERK1/2 activity might contribute to increased viral ribonucleoprotein export and influenza virus propagation. The increase in viral titer induced by FSK could be explained by the action of cAMP in assisting the entry and binding of the influenza virus. Therefore, FSK addition to cell culture systems could help increase the production efficiency of cell-based vaccines against the influenza virus.

• IMMUNE NETWORK
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• 제21권4호
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• pp.28.1-28.14
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• 2021

Lung-resident memory T cells (T_RM) play an essential role in protecting against pulmonary virus infection. Parenteral administration of DNA vaccine is generally not sufficient to induce lung CD8 T_RM cells. This study investigates whether intramuscularly administered DNA vaccine expressing the nucleoprotein (NP) induces lung T_RM cells and protects against the influenza B virus. The results show that DNA vaccination poorly generates lung T_RM cells and massive secondary effector CD8 T cells entering the lungs after challenge infection do not offer sufficient protection. Nonetheless, intranasal administration of non-replicating adenovirus vector expressing no Ag following priming DNA vaccination deploys NP-specific CD8 T_RM cells in the lungs, which subsequently offers complete protection. This novel 'prime and deploy' strategy could be a promising regimen for a universal influenza vaccine targeting the conserved NP Ag.

• Tuberculosis and Respiratory Diseases
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• 제79권2호
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• pp.70-73
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• 2016

In late March of 2009, an outbreak of influenza in Mexico, was eventually identified as H1N1 influenza A. In June 2009, the World Health Organization raised a pandemic alert to the highest level. More than 214 countries have reported confirmed cases of pandemic H1N1 influenza A. In Korea, the first case of pandemic influenza A/H1N1 infection was reported on May 2, 2009. Between May 2009 and August 2010, 750,000 cases of pandemic influenza A/H1N1 were confirmed by laboratory test. The H1N1-related death toll was estimated to reach 252 individuals. Almost one billion cases of influenza occurs globally every year, resulting in 300,000 to 500,000 deaths. Influenza vaccination induces virus-neutralizing antibodies, mainly against hemagglutinin, which provide protection from invading virus. New quadrivalent inactivated influenza vaccine generates similar immune responses against the three influenza strains contained in two types of trivalent vaccines and superior responses against the additional B strain.

• Journal of Preventive Medicine and Public Health
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• 제52권5호
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• pp.308-315
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• 2019

Objectives: Estimating influenza-associated mortality is important since seasonal influenza affects persons of all ages, causing severe illness or death. This study aimed to estimate influenza-associated mortality, considering both periodic changes and age-specific mortality by influenza subtypes. Methods: Using the Microdata Integrated Service from Statistics Korea, we collected weekly mortality data including cause of death. Laboratory surveillance data of respiratory viruses from 2009 to 2016 were obtained from the Korea Centers for Disease Control and Prevention. After adjusting for the annual age-specific population size, we used a negative binomial regression model by age group and influenza subtype. Results: Overall, 1 859 890 deaths were observed and the average rate of influenza virus positivity was 14.7% (standard deviation [SD], 5.8), with the following subtype distribution: A(H1N1), 5.0% (SD, 5.8); A(H3N2), 4.4% (SD, 3.4); and B, 5.3% (SD, 3.7). As a result, among individuals under 65 years old, 6774 (0.51%) all-cause deaths, 2521 (3.05%) respiratory or circulatory deaths, and 1048 (18.23%) influenza or pneumonia deaths were estimated. Among those 65 years of age or older, 30 414 (2.27%) all-cause deaths, 16 411 (3.42%) respiratory or circulatory deaths, and 4906 (6.87%) influenza or pneumonia deaths were estimated. Influenza A(H3N2) virus was the major contributor to influenza-associated all-cause and respiratory or circulatory deaths in both age groups. However, influenza A(H1N1) virus-associated influenza or pneumonia deaths were more common in those under 65 years old. Conclusions: Influenza-associated mortality was substantial during this period, especially in the elderly. By subtype, influenza A(H3N2) virus made the largest contribution to influenza-associated mortality.

• Childhood Kidney Diseases
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• 제21권2호
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• pp.89-93
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• 2017

Purpose: Virus-associated rhabdomyolysis is very rare. We report 15 patients with rhabdomyolysis caused by various viruses. Methods: Fifteen patients who were diagnosed with rhabdomyolysis and a viral infection were included in this study. Clinical, laboratory, and radiologic findings were evaluated through retrospective chart reviews. Results: Chief complaints were severe bilateral lower leg pain and leg weakness. The median age was 5.7 years. The male:female ratio was 2:5. The viral infections were caused by influenza virus B, parainfluenza virus, and rhinovirus. One patient with influenza virus B had coinfection with coronavirus. Median initial laboratory values and ranges were as follows: serum creatinine, 0.4 (0.1-0.5) mg/dL; serum aspartate transaminase, 124 (48-1,098) IU/L; serum alanine transaminase, 30 (16- 1,455) IU/L; serum creatine kinase, 2,965 (672-16,594) IU; serum lactate dehydrogenase, 400 (269-7,394) IU/L; serum myoglobin, 644 (314-3,867) ng/mL; urine myoglobin, 3 (3-10,431) ng/mL. All patients recovered without complications. Conclusion: This is the first report of the simultaneous occurrence of rhabdomyolysis caused by various viruses. This is also the first report of rhinovirus-associated rhabdomyolysis.

• IMMUNE NETWORK
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• 제20권4호
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• pp.32.1-32.15
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• 2020

Influenza virus is the major cause of seasonal and pandemic flu. Currently, oseltamivir, a potent and selective inhibitor of neuraminidase of influenza A and B viruses, is the drug of choice for treating patients with influenza virus infection. However, recent emergence of oseltamivir-resistant influenza viruses has limited its efficacy. Morin hydrate (3,5,7,2',4'-pentahydroxyflavone) is a flavonoid isolated from Morus alba L. It has antioxidant, anti-inflammatory, neuroprotective, and anticancer effects partly by the inhibition of the NF-κB signaling pathway. However, its effects on influenza virus have not been studied. We evaluated the antiviral activity of morin hydrate against influenza A/Puerto Rico/8/1934 (A/PR/8; H1N1) and oseltamivir-resistant A/PR/8 influenza viruses in vitro. To determine its mode of action, we carried out time course experiments, and time of addition, hemolysis inhibition, and hemagglutination assays. The effects of the co-administration of morin hydrate and oseltamivir were assessed using the murine model of A/PR/8 infection. We found that morin hydrate reduced hemagglutination by A/PR/8 in vitro. It alleviated the symptoms of A/PR/8-infection, and reduced the levels of pro-inflammatory cytokines and chemokines, such as TNF-α and CCL2, in infected mice. Co-administration of morin hydrate and oseltamivir phosphate reduced the virus titers and attenuated pulmonary inflammation. Our results suggest that morin hydrate exhibits antiviral activity by inhibiting the entry of the virus.

• Journal of Microbiology and Biotechnology
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• 제28권10호
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• pp.1683-1690
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• 2018

Accurate and rapid diagnosis of influenza infection is essential to enable early antiviral treatment and reduce the mortality associated with seasonal and epidemic infections. Immunochromatography is one of the most common methods used for the diagnosis of seasonal human influenza; however, it is less effective in diagnosing pandemic influenza virus. Currently, rapid diagnostic kits for pandemic influenza virus rely on the detection of nucleoprotein (NP) or hemagglutinin (HA). NP detection shows higher specificity and is more sensitive than HA detection. In this study, we time-dependently screened expression conditions, and herein report optimal conditions for the expression of recombinant nucleoprotein (rNP), which was 48 h after infection. In addition, we report the use of the expressed rNP in a rapid influenza diagnostic test (SGT i-flex Influenza A&B Test). We constructed expression vectors that synthesized rNP (antigen) of influenza A and B in insect cells (Sf9 cells), employed the purified rNP to the immunoassay test kit, and clearly distinguished NPs of influenza A and influenza B using this rapid influenza diagnostic kit. This approach may improve the development of rapid test kits for influenza using NP.

• Pediatric Infection and Vaccine
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• 제21권3호
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• pp.207-213
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• 2014

목적: 본 연구는 소아에서 호흡기바이러스 감염과 폐렴구균의 상기도 보균율 간의 연관성을 분석하고자 하였다. 방법: 2009년 5월부터 2010년 6월까지 서울대학교 어린이병원에 호흡기 증상을 주소로 내원한 18세 미만 소아로부터 채취한 비인두 흡인물을 대상으로 폐렴구균을 배양하고 RT-PCR을 통해 호흡기 바이러스(influenza virus A와 B, parainfluenza virus 1, 2와 3, respiratory syncytial virus A와 B, adenovirus, rhinovirus A/B, human metapneumovirus, human coronavirus 229E/NL63, OC43/HKU1)를 검출하여 호흡기바이러스 검출과 폐렴구균 보균 사이의 연관성을 분석하였다. 결과: 대상 환자의 중앙 연령은 27개월이었다. 총 1,367건의 비인두 흡인물 중 폐렴구균이 배양된 검체는 228개(16.7%)이었고, 호흡기바이러스가 검출된 검체는 731개(53.5%)이었다. 흔히 분리된 바이러스는, rhinovirus(18.4%), respiratory syncytial virus (RSV) A (10.6%), adenovirus (6.9%), influenza virus A (6.8%) 순으로 나타났다. 폐렴구균 보균율은 호흡기바이러스 양성인 경우가 21.3% (156/731)로 음성인 경우 11.3% (72/636)보다 높았다(P<0.001). 검출된 호흡기바이러스의 종류에 따라서는 influenza virus A [24.7% (23/93) vs 16.1% (205/1274), P=0.001], RSV A [28.3% (41/145) vs 15.3% (187/1222), P=0.001], RSV B [31.3% (10/32) vs 16.3% (218/1335), P=0.042], rhino-virus A/B [22.6% (57/252) vs 15.3% (171/1115), P=0.010]가 양성인 소아는 음성인 소아에 비하여 폐렴구균 보균율이 높게 나타났다. 결론: 본 연구 결과, 호흡기 증상이 있는 소아에서 호흡기바이러스가 검출된 경우 폐렴구균 보균율이 높았다. 향후 호흡기바이러스와 폐렴구균의 보균에 의한 호흡기 감염병의 임상발현 기전을 밝히는 데 도움이 될 것으로 생각된다.