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CSU 34/2009: FIVE ON H1N1 INFLUENZA

Friday, 29th of May 2009 Print
CSU 34/2009:  FIVE ON H1N1 INFLUENZA
 
 As of this writing (Friday, 22 May), the world has reported 11168 lab
 confirmed cases (9664 from North America) and 86 deaths from H1N1.
 
 For updated case counts on lab confirmed H1N1 cases and deaths, go to the
 homepage of the World Health Organization,
 http://www.who.int/csr/don/2009_05_22/en/index.html
 
 The Lancet has set up an H1N1 resource center on its homepage. Here is the
 URL address for those wanting to look at 50 open source articles on the
 epidemiology of H1N1: http://www.thelancet.com/H1N1-flu/epidemiology
 The New England Journal of Medicine has a site on H1N1 at
 http://h1n1.nejm.org/
 
 In addition, here are three other items related to H1N1: a little
 publicized Cochrane review on effective public health measures against
 respiratory viruses and a pair of articles from Eurosurveillance on the
 reproduction rate from the Mexican outbreak.
 
 Good reading.
 
 Bob Davis
 
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 echege@unicef.org
 
 Interventions for the interruption or reduction of the spread of
 respiratory viruses
 
 
 This is a Cochrane review abstract and plain language summary, prepared and
 maintained by The Cochrane Collaboration, currently published in The
 Cochrane Database of Systematic Reviews 2009 Issue 2, Copyright © 2009 The
 Cochrane Collaboration. Published by John Wiley and Sons, Ltd.. The full
 text of the review is available in The Cochrane Library (ISSN 1464-780X).
 
 This record should be cited as: Jefferson T, Foxlee R, Del Mar C, Dooley L,
 Ferroni E, Hewak B, Prabhala A, Nair S, Rivetti A. Interventions for the
 interruption or reduction of the spread of respiratory viruses. Cochrane
 Database of Systematic Reviews 2007, Issue 4. Art. No.: CD006207. DOI:
 10.1002/14651858.CD006207.pub2.
 This version first published online: October 17. 2007
 
 Abstract
 Background
 Viral epidemics or pandemics such as of influenza or severe acute
 respiratory syndrome (SARS) pose a significant threat. Antiviral drugs
 and vaccination may not be adequate to prevent catastrophe in such an
 event.
 Objectives
 To systematically review the evidence of effectiveness of interventions
 to interrupt or reduce the spread of respiratory viruses (excluding
 vaccines and antiviral drugs, which have been previously reviewed).
 Search strategy
 We searched the Cochrane Central Register of Controlled Trials (CENTRAL)
 (The Cochrane Library 2006, issue 4); MEDLINE (1966 to November 2006);
 OLDMEDLINE (1950 to 1965); EMBASE (1990 to November 2006); and CINAHL
 (1982 to November 2006).
 Selection criteria
 We scanned 2300 titles, excluded 2162 and retrieved the full papers of
 138 trials, including 49 papers of 51 studies. The quality of three
 randomised controlled trials (RCTs) was poor; as were most cluster RCTs.
 The observational studies were of mixed quality. We were only able to
 meta-analyse case-control data. We searched for any interventions to
 prevent viral transmission of respiratory viruses (isolation, quarantine,
 social distancing, barriers, personal protection and hygiene). Study
 design included RCTs, cohort studies, case-control studies, cross-over
 studies, before-after, and time series studies.
 Data collection and analysis
 We scanned the titles, abstracts and full text articles using a
 standardised form to assess eligibility. RCTs were assessed according to
 randomisation method, allocation generation, concealment, blinding, and
 follow up. Non-RCTs were assessed for the presence of potential
 confounders and classified as low, medium, and high risk of bias.
 Main results
 The highest quality cluster RCTs suggest respiratory virus spread can be
 prevented by hygienic measures around younger children. Additional
 benefit from reduced transmission from children to other household
 members is broadly supported in results of other study designs, where the
 potential for confounding is greater. The six case-control studies
 suggested that implementing barriers to transmission, isolation, and
 hygienic measures are effective at containing respiratory virus
 epidemics. We found limited evidence that the more uncomfortable and
 expensive N95 masks were superior to simple surgical masks. The
 incremental effect of adding virucidals or antiseptics to normal
 handwashing to decrease respiratory disease remains uncertain. The lack
 of proper evaluation of global measures such as screening at entry ports
 and social distancing prevent firm conclusions about these measures.
 Authors' conclusions
 Many simple and probably low-cost interventions would be useful for
 reducing the transmission of epidemic respiratory viruses. Routine
 long-term implementation of some of the measures assessed might be
 difficult without the threat of a looming epidemic.
 
 
  THE REPRODUCTION RATE FROM THE MEXICAN H1N1 OUTBREAK
 
  Writing from the European Centre for Disease Prevention and Control,
 Coulumbier and Giesecke comment on the Mexican data, which show an
 estimated reproduction rate probably lower than 2.2-3.1.  The reproduction
 rate, R or R0, is the number of new persons infected by each case.  The
 higher the reproduction rate, other things being equal, the more difficult
 the outbreak to control.  Measles, for example, with an R0 of about 12, is
 notoriously contagious. 'If R 1 this means that each case infects more
 than one new person, and the outbreak is likely to continue. If R < 1 the
 outbreak will eventually die out.'
 
 R0 does not exist in isolation. Household size, population density, immune
 status, and the mobility of infecteds all serve to raise or lower the R0.
 
 Commenting on the estimated reproduction rate from Mexico, also
 published in Eurosurveillance,  at
 http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19205  the
 authors conclude that ‘[an] Ro just above 1 could mean that a containment
 strategy might be successful.’
 
 
 
 Eurosurveillance, Volume 14, Issue 19, 14 May 2009
 Editorials
 
 Why are Mexican data important?
 D Coulombier1, J Giesecke 1
 1.        European Centre for Disease Prevention and Control,
 Stockholm, Sweden
 
 Citation style for this article: Coulombier D, Giesecke J. Why are Mexican
 data important?. Euro Surveill. 2009;14(19):pii=19212.
 Full text, with figure, is at
 http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19212
 
 Date of submission: 14 May 2009
 
 This issue of Eurosurveillance contains an article by a French team on the
 transmission of the new influenza A(H1N1) in Mexico, which uses published
 figures from the outbreak to estimate important parameters for
 transmission, among them the reproduction rate, R [1]. Such studies may
 have important implications for public health action in Europe.
 What is R?
 
 The growth rate of an epidemic is determined by two factors: the number of
 new persons infected by each case and the time from start of infectiousness
 in one case to start of infectiousness in the secondary cases caused by
 him/her. The first factor is called ’reproduction rate’ and is usually
 denoted R. If the disease is spreading in a population that is totally
 susceptible the term ’basic reproduction rate’ (Ro) is used. R is the
 product of four terms: the risk of transmission in one single contact
 between an infectious and a susceptible person, the frequency of such
 contacts in the population, the duration of infectivity of a case, and the
 proportion of susceptibles in the population. If R 1 this means that each
 case infects more than one new person, and the outbreak is likely to
 continue. If R < 1 the outbreak will eventually die out, even if there may
 be a number of cases before that. The time from infectiousness in one case
 to infectiousness in his/her secondary cases is called ’generation
 time’ (Tg) and is basically a biological constant, even if its exact value
 depends on how it is estimated.
 
 Values for the factors that determine R can be calculated on the basis of
 scientific knowledge of the disease, its context of transmission, and the
 immunity status of the population. However, during an epidemic an R value
 usually has to be derived from the analysis of the epidemic curve or by the
 study of transmission chains.
 
 Several studies have now tried to estimate R (or Ro) and Tg for the new
 influenza A(H1N1) virus from Mexican data. In the one published in this
 issue of Eurosurveillance [1], the authors use one exponential fitting and
 one real-time estimation model to arrive at an estimate of R between 2.2
 and 3.1. This is higher than the value found in an article in Science [2],
 which estimated Ro to be 1.4-1.6 using three models: one exponential
 fitting, one genetic analysis, and two standard SIR models for a confined
 outbreak in La Gloria. Another analysis of the minor genetic changes in the
 virus over time arrived at a Ro estimate of 1.16 [3].
 Why is Ro important in public health?
 
 The reproduction rate reflects effectiveness of transmission, and therefore
 has important implications for the efforts that public health authorities
 would have to make in implementing health measures aiming at containing or
 mitigating the outbreak.
 For example, with a Ro of 1.16, preventing 14% of cases will result in
 eventually interrupting transmission, while with a Ro of 3.1, preventing
 68% cases would be needed – assuming a total random mixing of contacts in
 the population.
 Why are Ro estimates so different for influenza?
 
 A few studies have tried to measure Ro for seasonal influenza [4], and
 found it to be in the order of 1.2 to 1.4. However, for most of the
 seasonal strains, there is already some immunity in the population from
 past seasons, which lowers the reproduction rate (and it should thus really
 not be called Ro in this situation). For any epidemic of a disease that
 leads to immunity after infection the initial Ro will also be higher than
 the actual R at any later stage, since the proportion still susceptible in
 the population will decrease. It should also be realised that delayed
 reporting of cases will affect an estimate of R; a problem that adheres to
 the study in this issue and the others cited above.
 What influences Ro?
 
 The risk of transmission in a contact when an infective meets a susceptible
 is basically a biological constant (even if it varies over the time course
 of the infection), as is the duration of infectiveness. However, frequency
 of contacts varies considerably between populations and population groups.
 For example, among children in schools or day care, the contact frequency
 is higher than among adults [5], and it also varies by culture, by family
 size in a society, by types of social interaction, etc.
 Why is the Ro from Mexico important?
 
 One could question why there is so much interest around studies of R and Ro
 based on Mexican data. Would they apply to Europe? One could guess that
 contact density might be higher in a Mexican setting, but on the other
 hand, since the epidemic has already run its course for some time there,
 the proportion of non-susceptibles would be higher in Mexico and the
 European situation would more approach a ‘true’ (higher) Ro, with a totally
 susceptible population.
 
 In the graph, we have just compared the daily reported cumulative number of
 cases in Mexico, Canada, United States, and European Union and European
 Free Trade Association (EU/EFTA) countries. On a semi-logarithmic scale it
 is evident that the slope for Europe is very much the same as for Mexico.
 It is difficult to estimate the time lag for Europe, but it seems that we
 are some 1-2 months behind. If the generation times are the same for both
 epidemics – which seems highly plausible – then an estimate of Ro for
 Mexico would apply also to Europe. A Ro just above 1 could mean that a
 containment strategy might be successful.
 Figure. Daily reported cumulative number of cases in Mexico, Canada, US and
 EU/EFTA countries, outbreak of new influenza A(H1N1), April-May 2009
 
 
 The European Centre for Disease Prevention and Control (ECDC) is
 continuously monitoring the situation and with more data being available
 every day in Europe we will obviously be able to have a better picture here
 soon as well. Nevertheless, the similarities of the shapes of the epidemics
 indicate that lessons from Mexico could apply also to Europe.
 
 References
 
 1. Boëlle PY, Bernillon P, Desenclos JC. A preliminary estimation of the
 reproduction ratio for new influenza A(H1N1) from the outbreak in Mexico,
 March-April 2009. Euro Surveill. 2009;14(19):pii=19205. Available from:
 http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19205
 2. Fraser C, Donnelly CA, Cauchelmes S, Hanage WP, Van Kerkhove MD,
 Hollingsworth TD, et al. Pandemic potential of a strain of influenza A
 (H1N1): early findings. Published 11 May 2009 on Science Express. DOI:
 10.1126/science.1176062. Available from:
 http://www.sciencemag.org/cgi/content/abstract/1176062
 3. Rambaut A. Human/Swine A/H1N1 flu outbreak - BEAST analysis. Available
 from:
 http://tree.bio.ed.ac.uk/groups/influenza/wiki/178c5/BEAST_Analysis_29_Apr_2008_-_Andrew_Rambaut.html
 
 4. Chowell G, Miller MA, Viboud C. Seasonal influenza in the United States,
 France, and Australia: transmission and prospects for control. Epidemiol
 Infect. 2008;136(6):852-64.
 5. Keeling MJ, Eames KT. Networks and epidemic models. J R Soc Interface.
 2005;2(4):295-307.

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