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Transmissibility of Influenza

Klick, Brendan; Nishiura, Hiroshi; Cowling, Benjamin J.

doi: 10.1097/EDE.0b013e3182590554
Letters
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School of Public Health The University of Hong Kong Pokfulam Hong Kong Special Administrative Region People's Republic of China (Klick)

School of Public Health The University of Hong Kong Pokfulam Hong Kong Special Administrative Region People's Republic of China PRESTO Japan Science and Technology Agency Saitama, Japan (Nishiura)

School of Public Health The University of Hong Kong Pokfulam Hong Kong Special Administrative Region People's Republic of China bcowling@hku.hk (Cowling)

Supported by the Harvard Center for Communicable Disease Dynamics from the National Institute of General Medical Sciences (grant no. U54 GM088558), the Research Fund for the Control of Infectious Disease, Food and Health Bureau, Government of the Hong Kong SAR (grant no. PHE-2), and the Area of Excellence Scheme of the Hong Kong University Grants Committee (grant no. AoE/M-12/06). B.K. is supported by a Hong Kong PhD Fellowship from the Research Grants Council, Hong Kong. H.N. is supported by the JST PRESTO program. B.J.C. has received study funding from MedImmune Inc., a manufacturer of influenza vaccines. The authors reported no other financial interests related to this research.

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The authors respond:

We thank Farrell and colleagues1 for further discussion on our recent article in Epidemiology.2 In a separate transmission study, we estimated similar secondary infection risks among household contacts of index cases with pandemic and seasonal influenza.3 One concern in that study was whether selecting index cases based on a positive rapid test could have led to bias. The study presently under discussion followed a cohort design, which should minimize such selection bias.2 An advantage of both studies is that pandemic and seasonal influenza viruses were cocirculating, allowing fair comparison between the strains under the same study design and procedures. It is challenging to compare secondary infection risks between different studies, given the substantial effects of study design and procedures.4

Our household study was designed before the 2009 pandemic, and we were able to take the opportunity to estimate the household secondary infection risks. For this reason, we agree with Farrell and colleagues1 that a weakness of our study is the small sample size.5 Rather than aiming to detect small differences in transmissibility, we used the existing data for statistical modeling to qualitatively validate our earlier findings.3

As Farrell and colleagues1 have noted, receipt of influenza vaccination could affect the results. Although valid estimation of secondary infection risks is based on the assumption of uniform susceptibility among household contacts,6 we currently lack good correlates of immunity. In a sensitivity analysis, we excluded everyone who received seasonal vaccine (eAppendix Table 3, http://links.lww.com/EDE/A519) and came to similar conclusions. Including or excluding those with antibody titers ≥1:160 did not change secondary infection risks for seasonal and pandemic strains. In summary, the results on relative transmissibility were not influenced by vaccination and thus we believe are generalizable.

We chose to use an age cutoff of 15 years based on early work assessing antibody responses in children and adults7 and because this cutoff was used in several studies addressing transmission of influenza within households.8,9 The immune system undergoes changes during puberty, which would support the use of a threshold at this age or even younger.10 Alternatively, expanding the threshold to include all school-age children would have had minimal effect, as only 16 people (4%) in our study were 15–17 years of age.

Finally, we completely agree that there is a critical need to elucidate genetic variation between host generations of influenza infection.11

Brendan Klick

School of Public Health

The University of Hong Kong

Pokfulam

Hong Kong Special Administrative Region

People's Republic of China

Hiroshi Nishiura

School of Public Health

The University of Hong Kong

Pokfulam

Hong Kong Special Administrative Region

People's Republic of China

PRESTO

Japan Science and Technology Agency

Saitama, Japan

Benjamin J. Cowling

School of Public Health

The University of Hong Kong

Pokfulam

Hong Kong Special Administrative Region

People's Republic of China

bcowling@hku.hk

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REFERENCES

1. Farrell E, Mohamed I, Robbe IJ. Transmissibility of Influenza (letter). Epidemiology. 2012;23:650.
2. Klick B, Nishiura H, Ng S, et al.. Transmissibility of seasonal and pandemic influenza in a cohort of households in Hong Kong in 2009. Epidemiology. 2011;22:793–796.
3. Cowling BJ, Chan KH, Fang VJ, et al.. Comparative epidemiology of pandemic and seasonal influenza A in households. N Engl J Med. 2010;362:2175–2184.
4. Lau LL, Nishiura H, Kelly H, Ip DK, Leung GM, Cowling BJ. Household transmission of 2009 pandemic influenza A(H1N1): a systematic review and meta-analysis. Epidemiology. 2012;23:531–542.
5. Cowling BJ, Ng S, Ma ES, et al.. Protective efficacy of seasonal influenza vaccination against seasonal and pandemic influenza virus infection during 2009 in Hong Kong. Clin Infect Dis. 2010;51:1370–1379.
6. Halloran ME. Secondary attack rate. In: Armitage P, Colton Teds. Encyclopedia of Biostatistics. 1st ed. New York: John Wiley and Sons, Inc., 1998; 4025–4029.
7. Fulk RV, Fedson DS, Huber MA, Fitzpatrick JR, Kasel JA. Antibody responses in serum and nasal secretions according to age of recipient and method of administration of A2-Hong Kong-68 inactivated influenza virus vaccine. J Immunol. 1970;104:8–13.
8. Cauchemez S, Carrat F, Viboud C, Valleron AJ, Boelle PY. A Bayesian MCMC approach to study transmission of influenza: application to household longitudinal data. Stat Med. 2004;23:3469–3487.
9. Viboud C, Boelle PY, Cauchemez S, et al.. Risk factors of influenza transmission in households. Br J Gen Pract. 2004;54:684–689.
10. Verthelyi D. Sex hormones as immunomodulators in health and disease. Int Immunopharmacol. 2001;1:983–993.
11. Poon LL, Chan KH, Chu DK, et al.. Viral genetic sequence variations in pandemic H1N1/2009 and seasonal H3N2 influenza viruses within an individual, a household and a community. J Clin Virol. 2011;52:146–150.

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