N Engl J Med. Safety and Effectiveness of a 2009 H1N1 Vaccine in Beijing

[Giuseppe]

Safety and Effectiveness of a 2009 H1N1 Vaccine in Beijing (NEJM, abstract, edited)


[Source: New England Journal of Medicine, full text: <cite cite="http://www.nejm.org/doi/full/10.1056/NEJMoa1006736?query=TOC">Safety and Effectiveness of a 2009 H1N1 Vaccine in Beijing ? NEJM</cite>. Abstract, edited.]

Safety and Effectiveness of a 2009 H1N1 Vaccine in Beijing

Jiang Wu, M.D., Fujie Xu, Ph.D., Li Lu, M.Sc., Min Lu, Ph.D., Liang Miao, M.Sc., Ting Gao, M.D., Wenyan Ji, Ph.D., Luodan Suo, M.Sc., Donglei Liu, M.S., Rui Ma, M.Sc., Rui Yu, B.A., Jiazi Zhangzhu, B.A., Weixiang Liu, B.A., Yang Zeng, M.Sc., Xiaomei Li, M.Sc., Xuechun Zhang, B.A., Xinghuo Pang, M.D., and Ying Deng, M.D.

N Engl J Med 2010; 363:2416-2423
December 16, 2010


Abstract

Background
After the first monovalent 2009 pandemic influenza A (H1N1) vaccine became available in September 2009, Chinese officials conducted a mass vaccination program in Beijing. We evaluated the safety and effectiveness of the vaccine.

Methods
During a 5-day period in September 2009, a total of 95,244 children and adults received the PANFLU.1 vaccine (Sinovac Biotech), a monovalent split-virion vaccine of 15 μg of hemagglutinin antigen without adjuvant. We assessed adverse events after immunization through an enhanced passive-surveillance system and through active surveillance, using diary cards and telephone interviews. Active surveillance for neurologic diseases was implemented in hospitals citywide. To assess vaccine effectiveness, we compared the rates of reported laboratory-confirmed cases of 2009 H1N1 virus infection in students who received the vaccine with the rates in those who did not receive the vaccine, starting 2 weeks after the mass vaccination.

Results
As of December 31, 2009, adverse events were reported by 193 vaccine recipients. Through hospital-based active surveillance, 362 cases of incident neurologic diseases were identified within 10 weeks after the mass vaccination, including 27 cases of the Guillain?Barr? syndrome. None of the neurologic conditions occurred among vaccine recipients. From 245 schools, 25,037 students participated in the mass vaccination and 244,091 did not. During the period from October 9 through November 15, 2009, the incidence of confirmed cases of 2009 H1N1 virus infection per 100,000 students was 35.9 (9 of 25,037) among vaccinated students and 281.4 (687 of 244,091) among unvaccinated students. Thus, the estimated vaccine effectiveness was 87.3% (95% confidence interval, 75.4 to 93.4).

Conclusions
Among 95,244 children and adults in Beijing, the PANFLU.1 vaccine had a safety profile similar to those of seasonal influenza vaccines and appeared to be effective against confirmed H1N1 virus infection in school-age children.

(Funded by the Beijing Municipal Health Bureau.)

From the Beijing Centers for Disease Control and Prevention, Beijing (J.W., L.L., M.L., L.M., T.G., W.J., L.S., D.L., R.M., R.Y., J.Z., W.L., Y.Z., X.L., X.Z., X.P., Y.D.); and the Division of STD Prevention, Centers for Disease Control and Prevention, Atlanta (F.X.).

Address reprint requests to Dr. Xu at the Centers for Disease Control and Prevention, 1600 Clifton Rd., Mailstop E-02, Atlanta, GA 30333, or at fax1@cdc.gov.

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[tetano]

Re: N Engl J Med. Safety and Effectiveness of a 2009 H1N1 Vaccine in Beijing

Coirrepondence

Safety and Effectiveness of a 2009 H1N1 Vaccine in Beijing

N Engl J Med 2011; 364:1181-1182March 24, 2011

Article
To the Editor:

The study by Wu et al. (Dec. 16 issue)1 has serious methodologic issues that limit the interpretation of their estimate of the effectiveness of a 2009 pandemic influenza A (H1N1) vaccine. First, the cumulative incidence of influenza was 2.5 times as high in the unvaccinated cohort as in the vaccinated cohort even before a protective effect from the vaccine could have been achieved (Fig. 2 of the article). Because of bias or confounding, these two cohorts did not have the same risk of influenza. In addition, many students may have been infected with the pandemic virus before the study began. Vaccine trials in China that preceded this study reported that 18 to 25% of children who were 12 to 18 years of age were positive for the pandemic H1N1 antibody.2 At one Chinese school, 32% of the students were infected.3 A subsequent serologic survey conducted in Beijing showed that 19.4% of children and young people between 6 and 17 years of age were seropositive for the pandemic virus.4 Yet in the study by Wu et al., less than 0.30% of the unvaccinated cohort and 0.01% of the vaccinated cohort were infected. Numerous cases must have been missed in both cohorts before the study began and while it was being conducted.

Nicholas S. Kelley, M.S.P.H.
Michael T. Osterholm, Ph.D., M.P.H.
University of Minnesota, Minneapolis, MN
mto@umn.edu

Edward A. Belongia, M.D.
Marshfield Clinic Research Foundation, Marshfield, WI

No potential conflict of interest relevant to this letter was reported.
4 References

1.

1

Wu J, Xu F, Lu L, et al. Safety and effectiveness of a 2009 H1N1 vaccine in Beijing. N Engl J Med 2010;363:2416-2423
Full Text | Web of Science | Medline
2.

2

Liang XF, Wang HQ, Wang JZ, et al. Safety and immunogenicity of 2009 pandemic influenza A H1N1 vaccines in China: a multicentre, double-blind, randomised, placebo-controlled trial. Lancet 2010;375:56-66[Erratum, Lancet 2010;375:1694.]
CrossRef | Web of Science | Medline
3.

3

Li T, Liu Y, Di B, et al. Epidemiological investigation of an outbreak of pandemic influenza A (H1N1) 2009 in a boarding school: serological analysis of 1570 cases. J Clin Virol 2011;50:235-239
CrossRef | Web of Science | Medline
4.

4

Yang P, Huang F, Shi W, et al. A survey on serological epidemiology of influenza A (H1N1) 3009 in Beijing. Zhonghua Liu Xing Bing Xue Za Zhi 2010;31:485-488
Medline

To the Editor:

Wu et al. evaluate the effectiveness of a 2009 H1N1 vaccine. In this study, the vaccinated students had all been participants in China's 60th National Day Celebration, whereas most of the unvaccinated students had not been participants. Generally, the students in the celebration were healthier and better educated about the prevention of infection, and most were living in urban districts ? all of which might lead to an overestimation of the effectiveness of the vaccine. Although aware of these differences between the two groups, the authors took no measures to eliminate them. In fact, a total of about 80,000 primary-school or middle-school students participated in the celebration, including 25,037 vaccinated students and 55,000 unvaccinated students. I wonder why these 55,000 unvaccinated students were not selected as the control group, which might have eliminated the interference of the above-mentioned factors.

Xiang-Dong Mu, M.D.
Peking University First Hospital, Beijing, China
muxiangdong@medmail.com.cn

No potential conflict of interest relevant to this letter was reported.
Author/Editor Response

In our study, both the unvaccinated cohort and the vaccinated cohort came from 245 schools. The vaccinated cohort consisted of students who participated in the 60th National Day Celebration and were vaccinated during a 5-day period in September 2009. The unvaccinated cohort included students who did and those who did not participate in the celebration. The students in the vaccinated cohort attended the same schools at the same times and had backgrounds similar to those in the unvaccinated cohort. Hence, both cohorts should have had similar exposure to influenza viruses.

The incidence data for our study were collected from October 9 through November 15, 2009. Yang et al. performed their study from November 27 through December 23, 2009, and their subjects were patients from outpatient sections of six hospitals (two children's hospitals and four general hospitals) in Beijing. Since Yang et al. used convenience sampling and the study subjects did not represent the entire student population, there is no conflict in this regard between our report and theirs. In addition, there is some debate about the cross-reactive antibody response between H1N1 and pandemic H1N1. The data from Chi et al. indicate that natural infection with the 2006 and 2008 seasonal H1N1 viruses in Taiwan may have induced a cross-reactive antibody response to the 2009 pandemic H1N1 virus.1 We detected a similar phenomenon. We tested 301 serum samples from volunteers after H5N1 vaccination in Beijing in 2007 and observed a cross-reaction in 2.9% of the group between 3 and 11 years of age and in 11.3% of the group between 12 and 17 years of age.2 There was also a report from the United States of a possible cross-reactive antibody response to the H1N1 and pandemic H1N1 viruses.3 Our experience with seasonal flu vaccine and pandemic H1N1 flu vaccine also indicated the existence of this phenomenon. Thus, measurement of serum antibodies probably did not fully reflect the actual infection status of the population.4

We agree that some cases may have been missed in our study, such as silent infection and mild cases. However, this phenomenon should have affected both the vaccinated and unvaccinated subjects.

Jiang Wu, M.D.
Min Lu, Ph.D.
Ying Deng, M.D.
Beijing Centers for Disease Control and Prevention, Beijing, China
yingdeng53@yahoo.com.cn

Since publication of their article, the authors report no further potential conflict of interest.

http://www.nejm.org/doi/full/10.1056/NEJMc1100442

[tetano]

Re: N Engl J Med. Safety and Effectiveness of a 2009 H1N1 Vaccine in Beijing

Correction
Safety of Influenza A (H1N1) Vaccine in Postmarketing Surveillance in China

N Engl J Med 2011; 364:1481April 14, 2011

Article

Safety of Influenza A (H1N1) Vaccine in Postmarketing Surveillance in China (Original Article, N Engl J Med 2011 ; 364 : 638 - 647) . In the No. of Doses Administered column of Table 1 (page 641), the number listed for age 10?19 yr should have been 38,144,994, rather than 38,144,944. In the Types of Events subsection of Results (page 643), the third sentence of the first paragraph should have begun, ?A total of 1050 of the vaccinees with more serious reactions (13.0% of vaccinees with adverse events; rate per 1 million doses, 11.7) had allergic reactions, including 838 with urticaria . . . ,? rather than, ?. . . had allergic reactions, including 838 with anaphylactic rash. . . .? Finally, in the stub column of Table 3 (page 644), under ?Rare, more serious vaccine reaction,? ?Peripheral neuropathy? should have been ?Polyneuritis.? We regret the errors. The article is correct at NEJM.org.

http://www.nejm.org/doi/full/10.1056/NEJMx110029