Influenza A (H1N1) 2009 reinfection in Thailand

In 2009, a novel influenza A (H1N1) virus emerged and rapidly spread around the world, leading to a pandemic. In contrast to the high rate of primary infection, reinfection with influenza A (H1N1) 2009 is rather rare. In this report, we describe a case of influenza A (H1N1) 2009 reinfection that occurred within an interval of 5 months in Thailand.     

Influenza A (H1N1) 2009: Impact on Frankfurt in due consideration of health care and public health

Background  

In April 2009 a novel influenza A H1N1/2009 virus was identified in Mexico and in the United States which quickly spread around the world. Most of the countries established infection surveillance systems in order to track the number of (laboratory-confirmed) H1N1 cases, hospitalizations and deaths.     

安徽省早期甲型H1N1流感病毒的血凝素基因序列分析

目的检测、分析安徽省甲型H1N1流感早期病例的病毒血凝素（HA）基因的序列特征。方法RT-PCR方法扩增我省早期流感样病例的病毒核酸并对其HA基因序列进行分析比对。结果我省早期甲型H1N1流感病例的病毒HA基因与2009年全球流行的甲型H1N1流感病毒高度同源,与古典型猪流感亲缘性较近,与欧洲和亚洲分离的A/H1N1猪流感和A/H1N1禽流感亲缘关系较远。结论我省早期流行的甲型H1N1流感毒株HA基因可能由古典型猪流感进化而来,与WHO选定的甲型H1N1疫苗候选株同源性较高,对于人季节性流感A/H1N1疫苗可能并不敏感。     

Surveillance of illness associated with pandemic (H1N1) 2009 virus infection among adults using a global clinical site network approach: the INSIGHT FLU 002 and FLU 003 studies

The novel pandemic influenza A (H1H1) 2009 virus spread rapidly around the world in 2009. The paucity of prospective international epidemiologic data on predictors of clinical outcomes with pandemic (H1N1) 2009 virus infection stimulated the INSIGHT network, an international network of community and hospital-based investigators, to commence two worldwide clinical observational studies to describe pandemic (H1N1) 2009 virus activity. The purpose of these two studies was to estimate the percent of adult patients with illness due to laboratory-confirmed pandemic (H1N1) 2009 virus infection that experience clinically significant outcomes and to study factors related to these outcomes. Enrollment commenced in October 2009 and will continue until August 2011: as of the end of 2010, 62 sites in 14 countries in Australasia (12 sites), Europe (37) and North America (13) have enrolled 1365 adult patients, with 1049 enrollments into the FLU 002 outpatient study and 316 into the FLU 003 hospitalization study. These 'in progress' INSIGHT influenza observational studies may act as a model for obtaining epidemiological, clinical and laboratory information in future international disease outbreaks.     

Molecular characterization and epidemiology of the highly pathogenic avian influenza H5N1 in Nigeria

Avian influenza caused infection and spread throughout Nigeria in 2006. Carcass samples (lung, liver, spleen, heart, trachea and intestine) from the different regions of Nigeria were processed for virus isolation. Infective allantoic fluids were tested for avian influenza viruses (AIV) and Newcastle disease virus using monospecific antisera. Thirty-five isolates were generated and characterized molecularly using the haemagglutinin gene. The molecular analysis indicated that different sublineages of the highly pathogenic avian influenza (HPAI) H5N1 viruses spread throughout Nigeria. We compared the Nigerian isolates with others from Africa and results indicated close similarities between isolates from West Africa and Sudan. Some of the analysed viruses showed genetic drift, and the implications of these for future epidemiology and ecology of avian influenza in Africa require further evaluation. The spread of primary outbreaks was strongly linked to trade (legal and illegal), live bird markets, inappropriate disposal, and poorly implemented control measures. No strong correlation existed between wild birds and HPAI H5N1 in Nigeria.     

Avian influenza (H5N1) susceptibility and receptors in dogs

Inoculation of influenza (H5N1) into beagles resulted in virus excretion and rapid seroconversion with no disease. Binding studies that used labeled influenza (H5N1) showed virus attachment to higher and lower respiratory tract tissues. Thus, dogs that are subclinically infected with influenza (H5N1) may contribute to virus spread.     

甲型H1N1流感病毒基因组序列分析及其特性研究

目的 分析甲型H1N1流感病毒的基因组序列特征,阐明该毒株的遗传变异及分子特性.方法 GenBank中获取流感病毒全序列,对各段基因与已知序列进行分析比较,绘制进化树,并分析和预测甲型毒株的致病性、药物敏感性和现有疫苗的预防保护作用.结果 甲型H1N1病毒的HA、PB2、PB1、PA、NP、NS基因与美国本土的猪流感病毒序列具有高度同源性,NA和M基因具有典型的欧亚株系猪流感病毒特征.该病毒具有人传人的分子基础,HA上HA1和HA2裂解位点序列为PSIQSR↓+GLFGAI,尚不具备高致病性流感病毒的特征.病毒对金刚烷胺类药物耐药,而对达菲和扎那米韦敏感.HA片段5个抗原决定区氨基酸序列与人用流感疫苗具有较大差异,推测现有疫苗对预防本次疫情基本无效.结论 甲型H1N1是一种北美和欧亚两种猪流感病毒的混合体,开发针对本病毒的流感疫苗有助于进一步控制疫情蔓延.     

Vaccination with a soluble recombinant hemagglutinin trimer protects pigs against a challenge with pandemic (H1N1) 2009 influenza virus

In 2009 a new influenza A/H1N1 virus strain (“pandemic (H1N1) 2009”, H1N1v) emerged that rapidly spread around the world. The virus is suspected to have originated in swine through reassortment and to have subsequently crossed the species-barrier towards humans. Several cases of reintroduction into pigs have since been reported, which could possibly create a reservoir for human exposure or ultimately become endemic in the pig population with similar clinical disease problems as current swine influenza strains. A soluble trimer of hemagglutinin (HA), derived from the H1N1v, was used as a vaccine in pigs to investigate the extent to which this vaccine would be able to protect pigs against infection with the H1N1v influenza strain, especially with respect to reducing virus replication and excretion. In a group of unvaccinated control pigs, no clinical symptoms were observed, but (histo)pathological changes consistent with an influenza infection were found on days 1 and 3 after inoculation. Live virus was isolated from the upper and lower respiratory tract, with titres up to 10⁶ TCID₅₀ per gram of tissue. Furthermore, live virus was detected in brain samples. Control pigs were shedding live virus for up to 6 days after infection, with titres of up to 10⁵ TCID₅₀ per nasal or oropharyngeal swab. The soluble H1N1v HA trimer diminished virus replication and excretion after a double vaccination and subsequent challenge. Live virus could not be detected in any of the samples taken from the vaccinated pigs. Vaccines based on soluble HA trimers provide an attractive alternative to the current inactivated vaccines.     

Time-series model to predict impact of H1N1 influenza on a children's hospital

The spring of 2009 witnessed the emergence of a novel influenza A(H1N1) virus resulting in the first influenza pandemic since 1968. In autumn of 2010, the 2009 novel H1N1 influenza strain re-emerged. We performed a retrospective time-series analysis of all patients with laboratory-confirmed H1N1 influenza who presented to our institution during 2009. Cases of influenza were assembled into 3-day aggregates and forecasting models of H1N1 influenza incidence were created. Forecasting estimates of H1N1 incidence for the 2010-2011 season were compared to actual values for our institution to assess model performance. Ninety-five percent confidence intervals calculated around our model's forecasts were accurate to ±3·6 cases per 3-day period for our institution. Our results suggest that time-series models may be useful tools in forecasting the incidence of H1N1 influenza, helping institutions to optimize distribution of resources based on the changing burden of illness.     

Influenza A (H5N1) in Hong Kong: an overview

Worldwide pandemics of human influenza virus caused extensive morbidity and mortality around the world had been documented in the 20th century. However, the mechanisms involved in the emergence of novel influenza virus and the epidemiological factors leading to pandemics are unpredictable. Southern China is postulated as the epicentre of influenza epidemics due to its agricultural-based communities and high population density. Pandemic influenza viruses are through to arise from avian viruses through genetic reassortment among influenza viruses. An influenza virus (H5N1) known to infect only birds previously was found to infect human causing disease and death in Hong Knog in 1997 and the outbreak involved 18 patients with six deaths. Prior to the human outbreak, the H5N1 virus was found to cause extensive death in chickens in three farms in Hong Kong. The significance of this outbreak raised worldwide concern on the possibilities that such an influenza virus may become the next influenza pandemic strain. Investigations were initiated to find the source of the virus. In addition the extend of spread in individuals in contact with the index case and infected poultry was studied by H5-specific serology. Results demonstrated that individuals in close contact with the index case or with exposure to poultry were at risk of being infected. Out of the 18 cases of human infection, eleven had severe infection with symptoms of pneumonia and multi-organ failure. All severe cases presented with lower respiratory infection and lymphopenia and six eventually died. Case-fatality ratio was high among patients over 12 years of age (five out of nine). Control measures aimed at reducing exposure of human to potential H5-positive poultry were instituted which included culling of all poultry in Hong Kong, the segregation of water fowls and chicken, and the introduction of import control measures for chickens. Such measures had successfully controlled the outbreak and continuous surveillance of the poultry in Hong Kong of H5N1 infection is maintained to minimize future human exposure.     

人感染禽流感家庭聚集性病例研究进展

1997年以来,全球多个国家相继出现人感染H5N1禽流感家庭聚集性病例,随后中国局部地区也陆续报告了人感染H7N9禽流感相关病例。目前存在的人传人的现象是有限非持续的,具体的人际间传播途径与方式并不清楚且尚无证据证实上述2种病毒可以在人间持续传播。家庭聚集性病例多发生在与禽类接近或接触的人群中,可能存在的遗传易感性以及个体间受体表达的差异增加了家庭成员感染禽流感病毒的风险。随着人感染H5N1与H7N9禽流感病毒的持续流行以及病毒自身变异的发生,不排除其获得对人类的适应性突变可能性。人感染H7N9病例中未检测出的症状轻微感染者可能会引起更难以控制的人际间流行。本文将从人感染H5N1、H7N9病毒家庭聚集性病例的流行病学特征、传播模式以及传播能力等方面进行系统阐述,为今后禽流感疫情的防控提供一定的科学依据。     

Influenza in China in 1977: recurrence of influenzavirus A subtype H1N1.

Preliminary results from epidemiological and laboratory studies on the new H1N1 influenza virus show that the 7-20 years age group suffered the highest morbidity; some adults over 20 years of age were also affected. The influenza epidemic caused by the H1N1 virus was characterized by slow spread, unevenness of attack rates, and the occurrence of many mild cases and inapparent infections. At least up to the end of 1977 there was concurrent persistence and spread of both H1N1 and H3N2 viruses. The H and N antigens of the new H1N1 virus, as well as its behaviour toward nonspecific inhibitors, were found to be closely similar to the old H1N1 virus prevalent during the first half of the 1950s. Most of the new H1N1 isolates in eggs were found to be temperature sensitive.     

龙岩市1999～2002年流感监测结果分析

目的 :探索流感流行的规律 ,掌握流感流行信息 ,及时对疫点进行疫情调查 ,为制定防制方案提供科学依据。方法 :对门诊就诊的上感病例进行流行病学观察。用常规鸡胚双腔法分离流感病毒。以微量血凝抑制试验 (HI)法测定正常人群免疫水平。结果 :1999年及 2 0 0 0年未检出流感病毒 ,2 0 0 1年分离到 A1(H1N1)亚型流感病毒 12株 ,2 0 0 2年分离得B型 Victoria系流感病毒 2 8株与 A3(H3N2 )亚型流感病毒 2株。正常人群免疫水平 ,1999年阳性率以 A3(H3N2 )亚型阳性率最高 ,达 79.2 5 % (GMT 79.2 3) ;2 0 0 0年以 A1(H1N1)亚型最高 ,达 88.6 8% (GMT 6 4 .32 ) ;2 0 0 1年以 A1(H1N1)亚型最高 ,达 76 .4 0 % (GMT2 8.2 8) ;2 0 0 2年以 A1(H1N1)亚型阳性率最高 ,达 78.2 6 % (GMT15 .2 9)。两系B型流感中该市只有 Yam agata系在人群中有抗体 ,而 Victoria系抗体在低年龄组人群中未检出。结论 :该市 2 0 0 3年应重点加强防范 B型 Victoria系流感病毒株向乡镇流行以及 A3亚型流感病毒株可能引起的爆发或流行     

Imported pigs may have introduced the first classical swine influenza viruses into Mainland China

ObjectivesThe first classical swine influenza A H1N1 viruses were isolated in Mainland China in 1991. To aid surveillance of swine influenza viruses as part of pandemic preparedness, we sought to identify their origin.MethodsWe sequenced and phylogenically analyzed 19 swine influenza viruses isolated in 1991 and 1992 in China and compared them with viruses isolated from other regions during the same period.ResultsAll 19 swine influenza viruses analyzed in our study shared the highest similarity with the classical swine influenza virus A/Swine/Maryland/23239/1991 (H1N1). Phylogenetic trees of eight segmented genes exhibited similar topology, with all segments in the cluster of classical swine influenza viruses. In addition, antigenic analysis also indicated that the tested isolated were related to classical swine influenza isolates.ConclusionsClassical swine H1N1 influenza viruses were predominant in Beijing pig herds during this period. Since both antibody and virus detections did not indicate the presence of CS H1N1 before 1991 in Mainland China, we combined with the data on pigs imported to and exported from China and concluded that these viruses might spread to China via pigs imported from North America and that they could affect the genetic evolution and transmission dynamics of swine influenza viruses in Hong Kong.     

Cell culture (Vero) derived whole virus (H5N1) vaccine based on wild-type virus strain induces cross-protective immune responses

The rapid spread and the transmission to humans of avian influenza virus (H5N1) have induced world-wide fears of a new pandemic and raised concerns over the ability of standard influenza vaccine production methods to rapidly supply sufficient amounts of an effective vaccine. We report here on a robust and flexible strategy which uses wild-type virus grown in a continuous cell culture (Vero) system to produce an inactivated whole virus vaccine. Candidate vaccines based on clade 1 and clade 2 influenza H5N1 strains were developed and demonstrated to be highly immunogenic in animal models. The vaccines induce cross-neutralising antibodies, highly cross-reactive T-cell responses and are protective in a mouse challenge model not only against the homologous virus but also against other H5N1 strains, including those from another clade. These data indicate that cell culture-grown whole virus vaccines, based on the wild-type virus, allow the rapid high yield production of a candidate pandemic vaccine.     

A new concept of the epidemic process of influenza A virus

Influenza A virus was discovered in 1933, and since then four major variants have caused all the epidemics of human influenza A. Each had an era of solo world prevalence until 1977 as follows: H0N1 (old style) strains until 1946, H1N1 (old style) strains until 1957, H2N2 strains until 1968, then H3N2 strains, which were joined in 1977 by a renewed prevalence of H1N1 (old style) strains. Serological studies show that H2N2 strains probably had had a previous era of world prevalence during the last quarter of the nineteenth century, and had then been replaced by H3N2 strains from about 1900 to 1918. From about 1907 the H3N2 strains had been joined, as now, by H1N1 (old style) strains until both had been replaced in 1918 by a fifth major variant closely related to swine influenza virus A/Hswine1N1 (old style), which had then had an era of solo world prevalence in mankind until about 1929, when it had been replaced by the H0N1 strains that were first isolated in 1933. Eras of prevalence of a major variant have usually been initiated by a severe pandemic followed at intervals of a year or two by successive epidemics in each of which the nature of the virus is usually a little changed (antigenic drift), but not enough to permit frequent recurrent infections during the same era. Changes of major variant (antigenic shift) are large enough to permit reinfection. At both major and minor changes the strains of the previous variant tend to disappear and to be replaced within a single season, worldwide in the case of a major variant, or in the area of prevalence of a previous minor variant. Pandemics, epidemics and antigenic variations all occur seasonally, and influenza and its viruses virtually disappear from the population of any locality between epidemics, an interval of many consecutive months. A global view, however, shows influenza continually present in the world population, progressing each year south and then north, thus crossing the equator twice yearly around the equinoxes, the tropical monsoon periods. Influenza arrives in the temperate latitudes in the colder months, about 6 months separating its arrival in the two hemispheres. None of this behaviour is explained by the current concept that the virus is surviving like measles virus by direct spread from the sick providing endless chains of human influenza A.(ABSTRACT TRUNCATED AT 400 WORDS)     

Immunogenicity and safety of a monovalent vaccine for the 2009 pandemic influenza virus A (H1N1) in children and adolescents

The 2009 pandemic influenza A (H1N1) has caused significant morbidity and mortality around the world. Safety and immunogenicity studies of 2009 pandemic influenza A (H1N1) virus in children and adolescents are limited. In this prospective, open-label study, 2 doses of a monovalent, unadjuvanted, inactivated, split-virus 2009 pandemic influenza virus A (H1N1) vaccine (AdimFlu-S) were administered to 183 healthy children and adolescents aged 1–17 years. Adverse reactions were assessed, and hemagglutination inhibition antibody titers were determined. Three weeks after the first dose, 36.2% of children aged 1–2 years, 52.5% of children aged 3–5 years, 56.7% of children aged 6–9 years, and 90.3% of adolescents aged 10–17 years generated protective antibodies. A second vaccination given 3 weeks later induced protective antibodies in 89.4% of all age groups. No severe adverse effects were found 6 weeks after vaccination.     

Transmission dynamics, border entry screening, and school holidays during the 2009 influenza A (H1N1) pandemic, China

Pandemic influenza A (H1N1) 2009 virus spread rapidly around the world in 2009. We used multiple data sources from surveillance systems and specific investigations to characterize the transmission patterns of this virus in China during May-November 2009 and analyze the effectiveness of border entry screening and holiday-related school closures on transmission. In China, age distribution and transmission dynamic characteristics were similar to those in Northern Hemisphere temperate countries. The epidemic was focused in children, with an effective reproduction number of ≈1.2-1.3. The 8 days of national holidays in October reduced the effective reproduction number by 37% (95% credible interval 28%-45%) and increased underreporting by ≈20%-30%. Border entry screening detected at most 37% of international travel-related cases, with most (89%) persons identified as having fever at time of entry. These findings suggest that border entry screening was unlikely to have delayed spread in China by >4 days.     

甲型H1N1流感的现状及口岸预防

甲型H1N1流感的爆发流行给世界经济和人民身体健康带来沉重负担和危害。为了有效预防和控制甲型H1N1流感病毒在口岸的爆发和传播,本文对甲型H1N1流感病毒的现状、甲型H1N1流感病毒的检测技术和口岸预防工作进行了综述。     

Efficacy of seasonal live attenuated influenza vaccine against virus replication and transmission of a pandemic 2009 H1N1 virus in ferrets

In March 2009, a swine origin influenza A (2009 H1N1) virus was introduced into the human population and quickly spread from North America to multiple continents. Human serologic studies suggest that seasonal influenza virus vaccination or infection would provide little cross-reactive serologic immunity to the pandemic 2009 H1N1 virus. However, the efficacy of seasonal influenza infection or vaccination against 2009 H1N1 virus replication and transmission has not been adequately evaluated in vivo. Here, ferrets received one or two doses of the US licensed 2008-2009 live attenuated influenza vaccine (LAIV) intranasally. An additional group of ferrets were inoculated with the A/Brisbane/59/07 (H1N1) virus to model immunity induced by seasonal influenza virus infection. All vaccinated and infected animals possessed high titer homologous hemagglutination-inhibition (HI) and neutralizing antibodies, with no demonstrable cross-reactive antibodies against 2009 H1N1 virus. However, in comparison to non-immune controls, immunized ferrets challenged with pandemic A/Mexico/4482/09 virus displayed a significant reduction in body temperature and virus shedding. The impact of single-dose LAIV inoculation on 2009 H1N1 disease and virus transmission was also measured in vaccinated ferrets that were challenged with pandemic A/Netherlands/1132/09 virus. Although a single dose of LAIV reduced virus shedding and the frequency of transmission following homologous seasonal virus challenge, it failed to reduce respiratory droplet transmission of 2009 H1N1 virus. The results demonstrate that prior immunization with seasonal LAIV or H1N1 virus infection provides some cross-protection against the 2009 H1N1 virus, but had no significant effect on the transmission efficiency of the 2009 H1N1 virus.