European Epidemiology
 
Weekly Influenza Surveillance Overview (WISO) April 23 Week 15 (12 April - 18 April 2010)

• All reporting countries experienced low intensity of influenza activity for the seventh consecutive week and reported sporadic activity at most. 
• Few sentinel specimens (15 of 160, 9.4%) tested positive for influenza virus. Influenza B viruses predominated, accounting for 32 of 49 (65%) influenza viruses detected in sentinel and non-sentinel specimens. 
• To date, very few (2.5%) tested 2009 pandemic viruses have shown resistance to oseltamivir and none were resistant to zanamivir. All 2009 pandemic viruses tested were resistant against M2 inhibitors. 
• The weekly reported number of severe acute respiratory infections (SARI) due to pandemic influenza has reached a very low level. 
• Even though, globally, the world remains in pandemic Phase 6, influenza activity caused by the 2009 pandemic influenza A(H1N1) virus is well past its winter peak in EU/EEA countries. However, sporadic cases continue to occur whilst most cases of influenza-like illness in EU/EEA countries are not due to influenza virus infection.

Deaths announced By Member States

In the week ending April 23rd, EU/EFTA Member States announced 20 deaths on their national web-sites meaning that as of April 23rd there were 2896 deaths due to the pandemic announced by these states.

ECDC has published a map showing population based rates of announced deaths by Member States.

Global Epidemiology – outside Europe

Outside of Europe WHO reports on 23 April that the most active areas of pandemic influenza virus transmission are in parts of the tropical zones of the Americas, West Africa, Eastern Africa and South East Asia. Although pandemic 2009 influenza A(H1N1) remains the predominant circulating influenza virus worldwide, seasonal influenza type B virus circulation continues to predominate in East Asia and Europe, and is being detected across other parts of Asia at low levels. Sporadic detections of seasonal influenza A(H3N2) viruses have been reported in Asia, Eastern Europe and Eastern Africa most notably in recent weeks in Indonesia and Tanzania. Few seasonal A(H1N1) viruses were reported in the Russian Federation and Northern China in the last week.  There is a link at the US Centers for Disease Control and Prevention (CDC) to a useful map showing relative virus distribution in the Northern Hemisphere.

CDC on April 23 also announced in its weekly Flu View update that in the week April 11– 17 no states reported widespread or regional influenza activity. This is the first week since mid-December 13, 2008 that no states were reporting widespread or regional flu activity. Local activity remained still higher than usual for this time of year in the South East United States.

News and Developments

MMWR Weekly; April 16, 2010 / 59(14); 423-430

The Centers for Disease Control and Prevention (CDC) in Atlanta has updated its regular report on influenza activity in the US with data from August 30, 2009 (officially classed as the start of the 2009-10 influenza season  in the US) up to March 27, 2010. In addition, reports on the 2010-11 Northern Hemisphere influenza vaccine strain selection for use in the US next season are also included in this update.
 
2. Paediatrics

CDC Emergency and Response section publishes a Workbook to guide on the handling of paediatric cases in the event of an influenza pandemic 

This workbook is to assist hospitals with coordinating medical care for paediatric influenza-like illness (ILI) across their community. Although many of the suggestions were based on experiences with the 2009 A(H1N1) pandemic, this tool can be adapted for use during pandemic spread of a novel influenza virus. This tool is presented in two sections, identified by type of hospital focus: Children's Hospital Focus and General Hospital Focus.

3. UK Lessons Learnt Publications

The UK’s Faculty of Public Health magazine first edition devoted to the lessons learnt of the 2009 influenza A(H1N1) pandemic in the UK

The magazine of the UK’s Faculty of Public Health (www.fph.org.uk) devotes its first edition in March 2010, to the experience with the 2009 influenza A(H1N1) pandemic in the UK. In addition, it contains extensive information of front line public health activities. A couple or articles in this first issue are related to influenza, these are titled “Flu brought us under pressure ‘we had never seen before’” (page 10) and ‘Twitter and blogs helped put Coventry ahead on flu’ (page 14).  

4.Global consultation on public health research agenda for influenza

The Global Influenza Programme (GIP) of WHO has developed a public health research agenda for influenza. The objective of the agenda is to identify knowledge gaps and information essential for the development of evidence-based public health guidance and actions for the control of influenza. After extensive review, the final version of the background document, "WHO Public Health Research Agenda for Influenza Version 1 2009", has been finalised. It is available on the research agenda web site.

5. European Pharmacovigilance Report – Sixteenth Edition.

This issue includes summary of Expert Meeting on Guillain-Barre Syndrome. The European Medicines Agency last week published the 16th in the now fortnightly series reviewing the centrally authorised products: three pandemic vaccines available in Europe; Celvapan, Focetria and Pandemrix and the antiviral oseltamivir. It included data to April 11th. The report remained reassuring. The former report, based on data from a minimum of 37.3 million patients immunised in Europe concluded again that  i) the vast majority of the adverse reactions that had been reported were considered to be non-serious and ii)  the benefit-risk balance of the centrally-authorised pandemic vaccines for the current A(H1N1) influenza pandemic continues to be positive. The same was true for oseltamivir where it is estimated 22.5 million doses have been given.

The report also contained a summary of a specific meeting on Guillain-Barré syndrome (GBS)  (March 29th).   Based on the analysis of spontaneous reports, the experts concluded that the data are currently reassuring and there was no sign of a risk of a similar magnitude as that found in relation to a vaccine in the USA in 1976. A possible association between the pandemic A/H1N1 vaccines and GBS cannot be totally ruled out at this stage but if there is such an association it would translate in a very small increase in risk. The expert group also considered the ongoing epidemiological studies carried-out in several European countries and concluded that the results of these studies should be awaited to obtain a valid estimate of the possible risk of GBS associated with the pandemic vaccines.

6.  Precautionary stop on the use of new triple seasonal influenza vaccine in Australia for children under age 5

In a statement on April 23 the Australian Department of Health and Aging announced that due to an increase in the numbers of young children in Western Australia experiencing fever and convulsions following seasonal flu vaccinations the government has advising all those giving immunisation to stop giving the vaccine to children five years and under until a cause is established.  The vaccine used is for the coming Southern Hemisphere Winter and includes the new pandemic 2009 A(H1N1) component as advised by WHO. The particular vaccine is made in Australia and is not known to be used in Europe.

Selected Scientific Publications

EPIDEMIOLOGY and VIROLOGY

Pregnant women, the 2009 pandemic and protection from early use of oseltmivir:

Pandemic 2009 Influenza A(H1N1) Virus Illness Among Pregnant Women in the United States
Siston AM, Rasmussen SA,  Honein MA, et al. JAMA 2010; 303(15): 1517-1525

The objective of this study was to describe the severity of the 2009 pandemic influenza A(H1N1) illness and the association with early antiviral treatment among pregnant women in the United States. The main outcome measures were severity of illness (hospitalizations, intensive care unit [ICU] admissions, and deaths) due to 2009 pandemic influenza A(H1N1) stratified by timing of antiviral treatment and pregnancy trimester at symptom onset. Among 788 women who had symptom onset from April through August 2009, 30 died (5% of all reported 2009 influenza A(H1N1) influenza deaths in this period). Among 509 hospitalized women, 115 (22.6%) were admitted to an ICU. Pregnant women with treatment more than 4 days after symptom onset were more likely to be admitted to an ICU than those treated within 2 days after symptom onset (56.9% versus 9.4%). Only 1 death occurred in a patient who received treatment within 2 days of symptom onset. The data were updated with CDC's continued surveillance of ICU admissions and deaths among pregnant women identifying an additional 165 women giving a total of 280 women admitted to ICUs, 56 of whom died. Among the deaths, 4 occurred in the first trimester (7.1%), 15 in the second (26.8%), and 36 in the third (64.3%). In conclusion, this study adds to the literature indicating that pregnant women had a disproportionately high risk of mortality in the 2009 pandemic. In addition, it suggests that early antiviral treatment was associated with fewer admissions to an ICU and fewer deaths.

Two studies from Singapore about serology aspects on the 2009 influenza A(H1N1) pandemic:
Cross-reactive antibodies to pandemic (H1N1) 2009 virus, Singapore [letter]
Tang JW, Tambyah PA, Wilder-Smith A, et al. Emerg Infect Dis. 2010 May; [Epub ahead of print]

This study assesses the potential serologic cross-reactivity to 2009 pandemic influenza A(H1N1) virus in Singapore, where serum samples were obtained during May–June 2009 from 50 randomly recruited, healthy volunteers born mostly before 1958 (i.e., potentially those with some natural exposure to the then circulating H1N1/1918-like subtype viruses), before widespread transmission of the 2009 pandemic influenza A(H1N1) virus took place in Singapore. The authors suggested there was partial cross-immunity due to humoral and cell-mediated immunity not detectable by haemagglutination-inhibition (HI) or micro-neutralization assays.

2009 Influenza A(H1N1) Seroconversion Rates and Risk Factors Among Distinct Adult Cohorts in Singapore
Chen M, Lee VJ, Lim W, et al. JAMA 2010; 303(14):1383-1391.

The objective of this study was to compare the risk and factors associated with A(H1N1) seroconversion (haemagglutination inhibition) in four different adult cohorts, during the period June - October 2009. These cohorts were the general population (n = 838), military personnel (n = 1213), staff from an acute care hospital (n = 558) and staff and residents from long-term care facilities (n = 300). Baseline titres of 40 or more were observed in 22 members (2.6%) of the general population, 114 military personnel (9.4%), 37 hospital staff (6.6%) and 20 participants from long-term care facilities (6.7%). In participants with 1 or more follow-up serum samples, 312 military personnel (29.4%) seroconverted compared with 98 community members (13.5%), 35 hospital staff (6.5%) and only 3 long-term care participants (1.2%). Increased frequency of seroconversion was observed for community participants from households in which 1 other member seroconverted (OR: 3.32), whereas older age was associated with reduced odds of seroconversion (OR: 0.77). Higher baseline titres were associated with decreased frequency of seroconversion in community (OR: 0.48), military (OR: 0.71) and hospital staff cohorts (OR: 0.50). The authors concluded that following the June-September 2009 wave about 13% of the general population seroconverted but that most of the adult population remained susceptible.

Acute lower respiratory infections due to RSV in young children:

Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis

Nair H, Nokes DJ, Gessner BD, et al. The Lancet, 16 April 2010

The purpose of this study was to estimate the global incidence of and mortality from episodes of acute lower respiratory infection (ALRI) due to Respiratory Syncytial Virus (RSV) in children younger than 5 years.  The authors estimated the incidence of RSV-associated ALRI in children younger than 5 years, stratified by age, using data from a systematic review of studies published between January 1995 and June 2009, and ten unpublished population-based studies. In the findings it is noted that, in 2005, an estimated 33.8(95% CI 19.3-46.2) million new episodes of RSV-associated ALRI occurred worldwide in children younger than 5 years (22% of ALRI episodes), with at least 3.4 (2.8-4.3) million episodes representing severe RSV-associated ALRI necessitating hospital admission. The authors also estimated that 66 000—199 000 children younger than 5 years died from RSV-associated ALRI in 2005, with 99% of these deaths occurring in developing countries. This mortality data suggest that RSV is an important cause of death in childhood from ALRI, after pneumococcal pneumonia and Haemophilus influenzae type b.

Continuing Debate - Hospitalizations due to 2009 pandemic influenza A (H1N1) versus those due to seasonal influenza:

Comparison of adult patients hospitalised with pandemic (H1N1) 2009 influenza and seasonal influenza during the "PROTECT" phase of the pandemic response - letter
Davies AR, Webb SA, Seppelt IM, Bellomo R. MJA 2010; 192 (6): 356-358

This editorial letter expresses concern that the true severity of the 2009 pandemic influenza A(H1N1) is being understated. It included findings that patients with pandemic influenza A(H1N1) infection were younger and less immunocompromised than those who usually suffer from seasonal influenza; both of these characteristics of the patients affected point to the suggestion that the pandemic virus is a more virulent strain. The authors argue that the real burden of the 2009 pandemic will be underestimated if these assumptions are not followed. They make the point that there is a real risk that the pandemic will affect Australia again next winter (2010) and that the medical community should not be misled into believing that the 2009 pandemic influenza A(H1N1) virus is not virulent and has not been responsible for significant mortality and morbidity in a population not normally affected.

PUBLIC HEALTH POLICY

Epidemiology of influenza pandemics and its use in informing Public Health Policy:
Influenza epidemiology-past, present, and future

Lagacé-Wiens, P.R.S., Rubinstein, E., Gumel, A.
Critical Care Medicine; Volume 38, Issue SUPPL. 4, 2010, Pages e1-e9

The 1918 influenza pandemic: Lessons for 2009 and the future
Morens, D.M., Taubenberger, J.K., Harvey, H.A. Critical Care Medicine; Volume 38, Issue SUPPL. 4, 2010, Pages e10-e20

These two papers in a journal of critical care summarise the biology that predisposes influenza to cause sudden pandemics, as well as summarising of the epidemiology of the 20th century pandemics.  The first  provides a mathematical model based on transmission dynamics of the 2009 influenza with special pertinence for hospital care.  The second discusses the origin of the 1918 pandemic, its unusual epidemiologic features and the causes and demographic patterns of fatality, and how this information should inform the response to the 2009 A(H1N1) and future pandemics.