Strategies to control the spread of seasonal influenza outbreaks work to help curb influenza A(H1N1) outbreaks as well, suggest two studies published in the June 10 issue of the New England Journal of Medicine.

In the first report, standard containment strategies along with “ring chemoprophylaxis” were effective at controlling transmission of H1N1 in Singapore early in the course of the 2009 pandemic, according to Dr. Vernon J. Lee of the Singapore Ministry of Defense’s Center for Health Services Research.

In a separate report on the early H1N1 experience in Hong Kong, researchers found that in community households, the virus showed traits that were broadly similar to those of seasonal influenza A in transmissibility, viral shedding, and clinical illness.

While these findings have implications for future outbreaks, they do not necessarily “inform the success of potential containment efforts implemented at the source of the next influenza pandemic or implemented to prevent the introduction of influenza into a community,” Dr. Timothy M. Uyeki of the U.S. Centers for Disease Control and Prevention, Atlanta, pointed out in an editorial accompanying the two reports (N. Engl. J. Med. 2010;362:2221-3).

In the first study, Dr. Lee and associates described early H1N1 outbreaks in four military camps, including one military hospital. This is one of the first studies to document the real-world effectiveness antiviral “ring chemoprophylaxis” in a pandemic, they said.

“Ring chemoprophylaxis” entails containing a viral outbreak within a targeted geographic area surrounding an index case by administering a drug – in this case, oseltamivir – to everyone in the area, not just to known, close contacts. In this study, all members of the affected military units, where opportunities for contact were substantial, were included in prophylaxis effort, even though they did not fulfill standard criteria as close contacts. Larger “rings” of prophylaxis were established if cases developed in multiple units.

All personnel suspected of being infected were isolated in the hospital if they tested positive. All asymptomatic personnel in the same unit were screened three times per week using nasopharyngeal swabs and polymerase chain reaction testing plus symptom questionnaires and monitoring of body temperature, until the outbreak subsided.

This setting had the potential for intense transmission of the virus, similar to environments such as hospital wards, schools, and long-term care facilities. However, the “ring” approach based on spatial proximity brought an early halt to transmission, they noted.

Among 1,175 personnel, a total of 82 confirmed cases of H1N1 virus were documented during the four outbreaks. Only 7 of these patients (0.6% of the study population) developed symptoms after the prophylaxis program had begun; the remaining 75 had been infected before the intervention was implemented. The overall infection rate was 5.9%.

By comparison, the rate of influenza infection was 57% in another study of Taiwanese military recruits, 42% aboard a U.S. Navy ship, 71% in a British boarding school, and 35% in a New York City school, Dr. Lee and his colleagues said (N. Engl. J. Med. 2010;362:2166-74).

“Our experience provides evidence that early case detection and the use of antiviral ring prophylaxis effectively truncate the spread of infection during an epidemic, giving empirical support to theoretical mathematical models,” they said.

“Aggressive prophylaxis may be justifiable ... to protect vulnerable populations such as frail or elderly residents of long-term care facilities or persons in closed or semiclosed environments such as schools, prisons, and military camps,” Dr. Lee and his associates added.

In the second study, Benjamin J. Cowling, Ph.D., of the University of Hong Kong, and his associates assessed both H1N1 and seasonal flu transmission among 99 index patients and their 284 contacts in 99 households throughout the city at the beginning of the pandemic.

Clinical illness was similar between H1N1 and the seasonal flu. The incubation period was estimated to be 3.2 days for H1N1, very similar to the 3.4-day incubation period for the seasonal flu. Also similar was the duration of viral shedding, which was 5-7 days for both infections.

The secondary attack rate – the rate at which household contacts acquired the virus from index cases – also was similar between H1N1 and seasonal flu. However, the initial attack rate, meaning the rate at which index cases became infected, was much higher with H1N1 than with seasonal flu, as was reported worldwide.

“This difference in attack rates could be associated with the lack of preexisting immunity against the pandemic influenza virus, rather than an inherent difference in transmissibility” between H1N1 and seasonal flu, Dr. Cowling and his colleagues pointed out (N. Engl. J. Med. 2010;362:2175-84).

Overall, their findings suggest that H1N1 flu and seasonal flu viruses “are associated with similar viral-load dynamics, severity of clinical illness, and transmissibility,” the investigators said.

Dr. Lee’s study was supported by the Singapore Ministry of Defense; the National University of Singapore; and the Singapore Agency for Science, Research, and Technology. Dr. Cowling’s study was supported by the National Institute of Allergy and Infectious Diseases (U.S.) and Hong Kong University. Dr. Lee’s associates reported ties to GlaxoSmithKline, Novartis, Adamas Pharmaceuticals, Baxter, MerLion Pharmaceuticals, Pfizer, and Wyeth.

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

6月10日发表于《新英格兰医学杂志》(New England Journal of Medicine)上的两项研究表明，控制季节性流感疫情蔓延的策略也有助于遏制甲型流感(H1N1)暴发。

 

第一项研究的研究者——新加坡国防部卫生服务研究中心的Vernon J. Lee博士指出，在2009年H1N1流感大流行的早期阶段，标准控制策略与“环形区域化学预防”的联合实施有效地控制了H1N1在新加坡的传播。

 

另一项在香港进行的有关早期H1N1控制经验的研究显示，在社区家庭中，H1N1流感病毒在传播性、病毒脱落和临床症状方面的特征与季节性甲型流感病毒具有广泛相似性。

 

亚特兰大美国疾病预防控制中心(CDC)的Timothy M. Uyeki博士在随刊编者按中对这两项研究评论道，尽管这些结果对控制未来流感暴发有所启示，但它们并不一定 “意味着在下一波流感大流行的源头实施潜在控制措施就一定能取得成功，或所实施的潜在控制措施就一定能成功防止流感进入社区。”(N. Engl. J. Med. 2010;362:2221-3)

 

在第一项研究中，Lee博士及其同事对4个军营(包括1家军队医院)的早期H1N1暴发情况进行了调查。 他们表示，这是记录抗病毒“环形区域化学预防”在流感大流行中真实有效性的首批研究之一。

 

 “环形区域化学预防”意即在出现指示病例的周围目标地区内，通过对该地区所有人(不只是已知的亲密接触者)给予某种药物来控制病毒暴发。在该研究中，研究者使用奥司他韦对受累军事单位的所有人员进行了预防，因为在这样的场所中，人与人之间尽管不是标准意义上的亲密接触，但接触较多。如果多个单位出现病例，则进一步扩大预防的“环形区域”。

 

所有疑似感染者如检测结果为阳性，则应被隔离在医院中。每周通过鼻咽拭子和聚合酶链反应检测，加上症状问卷调查和体温监测，对同一单位的所有无症状人员筛查3次，直至疫情消除。

 

与诸如医院病房、学校和长期护理机构等环境相似，军营环境也存在出现明显病毒传播的可能性。 但他们指出，基于空间邻近性的“环形区域”预防方法可及早遏制传播。

 

在4次暴发期间，1,175人中的82人被确诊为H1N1感染病例。其中，在预防干预措施实施后仅7例(占研究人群的0.6%)出现症状；其他75例在预防干预措施实施前就已感染。总感染率为5.9%。

 

Lee博士及其同事表示，相比之下，流感感染率在另一项台湾新兵研究中为57%，在一艘美国海军舰艇上为42%，在一所英国寄宿学校中为71%，在一家纽约市学校中为35%(N. Engl. J. Med. 2010;362:2166-74)。

 

他们说：“我们的经验证明，在流感大流行期间，通过早期病例检测并实施抗病毒环形区域预防措施可有效控制感染传播，这为数学理论模型提供了经验性支持依据。”

 

Lee博士及其同事补充说：“采取积极的预防措施来保护易感人群(如长期护理机构中的体弱或老年居住者，或学校、监狱和军营等封闭或半封闭环境中的人员)是合理的。”

 

在第二项研究中，香港大学的Benjamin J. Cowling博士及其同事在流感大流行开始时，在来自市区99个家庭的99例索引患者及其284位接触者中对H1N1和季节性流感传播情况进行了评价。

 

H1N1流感与季节性流感的临床症状相似。H1N1流感与季节性流感的潜伏期非常相似，分别约为3.2天和3.4天。病毒脱落期也相似，均为5~7天。

 

此外，H1N1流感与季节性流感的续发率(家庭成员因接触指示病例所致感染率)也相似。但据报道，在全球范围内，H1N1初发率(即指示病例感染率)比季节性流感要高得多。

 

Cowling博士及其同事指出：“这种发病率差异可能与对大流行性流感病毒缺乏既有免疫力相关，而与H1N1和季节性流感病毒的内在传播性差异无关。”(N. Engl. J. Med. 2010;362:2175-84)

 

研究者表示，总体而言，他们的结果表明，H1N1流感病毒与季节性流感病毒在病毒载量动力学、临床症状严重程度和传播性方面相似。

 

Lee博士的研究获得新加坡国防部、新加坡国立大学和新加坡科技研究局的支持。Cowling博士的研究获得国家过敏和传染性疾病研究所及香港大学的支持。Lee博士的同事声明与以下公司存在联系：葛兰素史克、诺华、Adamas Pharmaceuticals、百特、MerLion Pharmaceuticals、辉瑞和惠氏。

 

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