Investigators have made rapid progress on a number of fronts in understanding the novel influenza A(H1N1) virus responsible for the current pandemic, according to a series of reports published online June 29 in the New England Journal of Medicine.

Investigators tracing the virus’s evolutionary history have learned that the novel swine-origin influenza A(H1N1) virus is a direct, fourth generation descendent of the virus that caused the disastrous 1918 flu pandemic. They’ve learned that the most common rapid influenza test is highly specific but not very sensitive for detecting the influenza A(H1N1) virus.

In addition, the virus’s worldwide spread closely matched historic patterns of airline travel from Mexico. Furthermore, the unusual age distribution of severe illness and death associated with the virus, affecting mostly children and young adults, may have resulted from relative protection among older individuals who had been exposed to H1N1 during childhood before the 1957 pandemic.

Some of the reports will be published in the July 16 print edition of the journal. All are available online at the journal’s H1N1 Influenza Center (http://h1n1.nejm.org).

A review article, by Dr. Shanta M. Zimmer and Dr. Donald S. Burke of the University of Pittsburgh, traced the emergence of the influenza A(H1N1) virus to an avian virus that simultaneously appeared in humans and swine in 1918. That virus killed 40-50 million people.

The influenza A(H1N1) virus consists of eight genes that have mutated steadily between 1918 in the present, but the virus has acquired no new gene segments from avian or other sources.

The virus disappeared entirely from humans in 1957 and was replaced by a new strain called H2N2. H1N1 was not detected again until 1976, when the virus was transmitted from a swine to humans, causing an outbreak of respiratory disease among soldiers at Fort Dix, New Jersey.

Beginning in 1977, the H1N1 virus, accompanied by H3N2, began to co-circulate seasonally in humans. Since then, new H1N1 strains have emerged in swine, with occasional cross-species transmission to humans. In 2008, two distinct H1 swine viruses combined to produce the virus causing the current pandemic.

In an editorial, Dr. David M. Morens, Dr. Jeffrey K. Taubenberger, and Dr. Anthony S. Fauci of the U.S. National Institute of Allergy and Infectious Diseases likened the interaction between the various descendants of the 1918 virus and the human community as an “elaborate dance.” They wrote that the “partners have remained linked and in step, even as each strives to take the lead,” and that there’s little evidence that this era is about to come to an end.

In a letter to the editor, Dr. Dennis J. Faix of the U.S. Naval Health Research Center in San Diego and his colleagues determined that the most commonly used rapid influenza test, called QuickVue Influenza A+B, widely available in doctors’ offices in the United States, has a 99% specificity for the novel influenza A(H1N1) virus, compared with definitive polymerase chain reaction–based tests. This means that if the test indicates that the patient’s virus is H1N1, it almost certainly is. On the other hand, the sensitivity of the test ranged from 31% to 63% in various populations, meaning that the test may well miss genuine cases of novel influenza A(H1N1).

In another letter to the editor, Dr. Kamran Khan, of St. Michael’s Hospital in Toronto, and colleagues found that the March-April 2009 worldwide spread of the virus closely matched patterns of global airline transportation originating from Mexico during the same period in 2008. Of 20 countries with the highest volumes of international passengers arriving from Mexico, 16 had confirmed importations of H1N1. (The exceptions were Japan, Chile, Venezuela, and Peru.) They calculated that countries receiving more than 1,400 passengers from Mexico were at significantly higher risk of importation, and that international air-traffic volume alone was 92% sensitive and more than 92% specific in predicting importation.

In an original research study, Dr. Rogelio Pérez-Padilla of the National Institute of Respiratory Diseases of Mexico in Mexico City and colleagues investigated 18 patients who were hospitalized with pneumonia between March 24 and April 24, 2009 and confirmed swine flu infection. More than half those patients were between ages 13 and 47 years, and only eight had pre-existing medical conditions. Twelve patients required mechanical ventilation, and 7 died. Within 7 days after contact with these initial case patients, 22 health care workers developed mild or moderate flu-like illness, but none required hospitalization.

In a much larger study involving 2,155 cases of severe pneumonia reported to the Mexican Ministry of Health, Gerardo Chowell, Ph.D., of the U.S. National Institutes of Health, Bethesda, Maryland, and colleagues found that 87% of the deaths and 71% of the cases of severe pneumonia involved patients between ages 5 and 59 years. This contrasts with 17% of deaths and 32% of cases of severe pneumonia in that age group during the peak of seasonal influenza periods from 2005 to 2008.

Morbidity and mortality among patients aged 60 years and older during the current pandemic has been significantly lower than among younger individuals. The investigators suggested that older individuals were more likely to have acquired some immunity by being exposed to H1N1 strains before those strains disappeared from the human population in 1957.

“If there is good news,” wrote Dr. Morens, Dr. Taubenberger, and Dr. Fauci, “it is that successive pandemics and pandemic-like events generally appear to be decreasing in severity over time. This diminution is surely due in part to advances in medicine and public health, but it may also reflect viral evolutionary ‘choices’ that favor optimal transmissibility with minimal pathogenicity – a virus that kills its hosts or sends them to bed is not optimally transmissible.”

One of the authors of the report on rapid influenza tests acknowledged receiving grant support from Sanofi Pasteur. All the other authors of that article and all the authors of the other articles stated that they had no relevant conflicts of interest.

Copyright (c) 2009 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

根据 6月29日《新英格兰医学杂志》在线发表的一系列报道，研究者在了解造成当前大流行的新型A型流感(H1N1)病毒的许多方面已取得了快速进步。

跟踪病毒演变史的研究人员已了解到，新型A型猪流感 (H1N1)病毒是造成1918年灾难性流感大流行病毒的直系、第四代衍生病毒。他们了解到，最常见的快速流感检测方法具有高度特异性，但对检测A型流感 (H1N1)病毒不是很敏感。

此外，该病毒的全球蔓延趋势几乎与墨西哥出港航班的历史记录一致。而且，严重疾病和病毒相关死亡不同寻常的年龄分布——主要影响儿童和青少年——可能是因为在1957年大流行前于儿童时期接触过H1N1，使得老年人产生了相对保护力 。

一些报道将在该杂志7月16日的印刷版上刊登。可从该杂志网上H1N1流感中心的获得所有报道 (http://h1n1.nejm.org)。

由匹兹堡大学的Shanta M. Zimmer博士和Donald S. Burke博士合著的一篇综述文章追踪了A型流感 (H1N1)病毒的起源，他们认为A型流感病毒源自一种禽流感病毒，该病毒在1918年同时出现在人类和猪中。该病毒导致4,000万~5,000万人死亡。

A型流感(H1N1)病毒包括8个基因，1918年至今，这些基因突变呈稳定状态，且没有来自禽类或其他来源的新的基因片段。

该病毒于1957年从人类中完全消失，被一种称为H2N2的新病毒株所取代。直到1976年才发现了H1N1，当时该病毒是由猪传染给人类，导致在新泽西州Fort Dix的士兵中爆发呼吸系统疾病。

1977年，H1N1病毒，同时伴随有H3N2病毒，开始在人群中呈季节性传播。自那时以来，新型H1N1病毒株已在猪中出现，偶而跨物种传染给人类。在2008年，2种不同的H1猪病毒结合起来产生了H1N1病毒，从而造成当前的大流行。

在一篇编者按中，美国国立过敏和传染病研究所的David M. Morens博士、Jeffrey K. Taubenberger博士以及Anthony S. Fauci博士，把1918年病毒的各种不同衍生病毒与人类社会之间的相互作用比作是一场“精心制作的舞蹈”。 他们写道， “即便任何一方努力先前行一步，后者仍紧跟步调，保持相伴相随，”几乎没有证据表明，这个时代即将结束。

在致编辑的信中，圣地亚哥海军卫生研究中心的Dennis J. Faix博士及其同事确定了最常用的快速流感检测方法，即QuickVue Influenza A+B，该方法在美国门诊中广泛应用。与确定的以聚合酶链反应(PCR)为基础的检测方法相比，QuickVue Influenza A+B对新型A型流感(H1N1)病毒的特异性为99%。这意味着，如果该检测方法证明患者的病毒是H1N1，那就几乎肯定是。另一方面，该检测方法的灵敏度在不同人群中介于31%~63%，这意味着，该检测方法很可能遗漏真正的新型A型流感(H1N1)病例 。

在另一封致编辑的信中，多伦多St. Michael医院的Kamran Khan博士及其同事发现，2009年3月~4月间，该病毒的全球蔓延趋势几乎与2008年该时间段墨西哥出港的全球航班运输模式一致。在20个接收墨西哥国际旅客数量最高的国家中，16个国家已证实有H1N1的输入(日本、智利、委内瑞拉和秘鲁除外)。他们估算，接收1,400名以上来自墨西哥乘客的国家输入风险明显较高；国际航运量在预测输入方面的灵敏度为92%，特异性为92%以上。

在一项原始研究中，墨西哥城的墨西哥国家呼吸疾病研究所的Rogelio Pérez-Padilla博士及其同事研究了在2009年3月24日~4月24日期间18例因肺炎住院、被确诊为猪流感感染的患者。一半以上的患者年龄介于13~47岁，只有8例患者先前患有内科疾病。12例患者需要机械通气，7例死亡。在接触这些初步诊断病例后的7天内，22例卫生工作者出现轻度或中度流感样疾病，但无一例需要住院治疗。

在一项纳入2,155例、已向墨西哥卫生部报告的重症肺炎患者的更大规模研究中，马里兰州Bethesda的美国国立卫生研究院的Gerardo Chowell博士及其同事发现，参与研究的5~59岁患者中87%死亡，71%为重症肺炎病例。而与之相比，在2005~2008年季节性流感高峰期，同一年龄组患者的死亡率仅为17%，重症肺炎发病率仅为32%。

在当前大流行期间，60岁及以上患者的发病率和死亡率明显较年轻者低。研究表明，年龄较大者更可能是通过在1957年病毒株从人类中消失之前接触了H1N1病毒株，从而获得了某种程度的免疫力。

“如果有好消息，”Morens博士、Taubenberger博士以及Fauci博士写到，“那么就是随着时间的推移，连续大流行和大流行样事件在严重程度方面似乎正在下降。当然，这一下降应部分归因于医学和公共卫生的进步，但是它也可能反映了病毒进化的‘选择’，这证实了病毒尽管具有最小致病性但是具有最佳传播性——杀死其宿主或将宿主推上病床的病毒其传染性往往不是最强的。”

报道快速流感检测法的作者之一承认接受来自赛诺菲巴斯德的资金支持。该文章的其他所有作者以及其他文章的所有作者声明，他们没有相关利益冲突。

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