Attending:

Professor Simon Kroll (Chair)
Professor Karl Nicholson
Professor Lewis Ritchie
Dr Douglas Fleming
Dr Alan Hay

Scottish Executive
Dr Elizabeth Stewart

Welsh Assembly Government
Dr Richard Roberts
Neil Robins

Health Protection Agency
Dr John Watson
Prof Maria Zambon

Health Protection Scotland
Dr Jim McMenamin

DHSS Northern Ireland
Dr Lorraine Doherty

MHRA
Dr Jane Wooley
Shahin Kauser

Department of Health
Dr Jane Leese
Dr Alan Smith
Dr Dorian Kennedy
Dr Karen Noakes
Daniel Eghan (minutes)

Executive Summary

• More use should be made of the data on adverse reactions associated with influenza vaccines reported to and collated by the MHRA, in support of the annual immunisation campaign
• The Subgroup was updated on UK preparedness for an influenza pandemic.
• The Subgroup recommended, subject to agreement by the main JCVI, that pregnant women in the second and third trimesters who are expected to deliver in the flu season, i.e. those with an estimated date of delivery (EDD) between 1 November and 31 March be added to the list of 'at risk' groups who should be offered inactivated influenza vaccine.
• The Subgroup recommended, subject to agreement by the main JCVI, that a neurological 'at risk' category should be added to the list of 'at risk' groups to be offered influenza vaccine. Based on currently available evidence this would consist of:
  1. MS and related conditions (ICD 9 code 340);
  2. Hereditary and degenerative diseases of the CNS. (ICD 9 code 330-337)
  
  

1. Introduction: Purpose of meeting

Professor Simon Kroll kindly deputised for Professor Andrew Hall as chair. The main purpose of this subgroup is to evaluate, on an ongoing basis, scientific evidence that has the potential to impact on the seasonal influenza vaccination programme, and make appropriate recommendations. The subgroup was also expected to give expert advice on influenza vaccines and immunisation strategies for an influenza pandemic.

The main policy areas to be considered at this meeting were:

• A review of the 2005/06 influenza season and plans for the next influenza immunisation campaign
• Influenza immunisation and
  • pregnancy
  • patients with neurological disease
    o patients with mental illness, specifically schizophrenia and severe bipolar affective disorder
    

A paper was presented for discussion "Vaccination of children-are there indirect benefits to the community ?"

Dr Douglas Fleming declared a non-specific interest.

2. Apologies

Apologies were received from Prof Andy Hall, Dr John Wood, Dr John Edmunds and Karen Goodwin, and from Dr David Salisbury and Jeff Porter from the Department.

3. Minutes of the meeting on 8 September 2005

The minutes were agreed as a true record. There were no matters arising.

4. Review of the 2005/06 influenza season

Epidemiological (HPA)

he report covered the UK national surveillance data for influenza activity between week ending 2 October 2005 and week ending 19 February 2006.

Most indices of influenza activity in the UK remained low throughout the season so far, although a large number of outbreaks of Influenza B in school children across the country since mid-January did eventually impact on traditional activity indices (GP consultations and calls to NHS Direct) to some extent.

The outbreaks in schools have been in children aged 5-14 years old, but it would seem that much of the flu activity this winter was not severe enough to merit a general practice consultation.

A broadly similar pattern was seen in other European countries, while the USA reported moderate influenza A H3N2 activity.

Virological surveillance confirmed that influenza this year has been predominantly B with sporadic H3 and H1 cases. Two B lineages (Victoria and Yamagata) have been in circulation, but the lack of cases in the vaccinated population suggests that mismatch between vaccine and circulating strains was not a problem. Older people may have antibodies to similar viruses in circulation prior to the 1990s.

The influenza immunisation campaign and vaccine uptake

Manufacturers announced in late July 2005 that there would be delays of two to four weeks in the delivery of some influenza vaccines at the start of the campaign. The Department of Health secured additional contingency stock and directed supplies to surgeries. Despite the record number of doses of influenza vaccine available, shortages were reported in some areas.

The events of this year (flu season 05/06) prompted the Secretary of State for Health to instigate a review of the ordering, supply and distribution of seasonal influenza vaccine. The review is to be carried out by two independent assessors and is due to be completed by the end of June 2006. One assessor has been appointed and it is anticipated the second will be appointed soon.

Influenza vaccine uptake in England this season reached 75.3% in those aged 65 years and over and 48.0% in those under 65 years and at risk. There was wide variation between clinical risk groups: those with diabetes had the highest uptake (68.5%); the uptake in people with chronic respiratory disease was disappointingly low (42.2%).

In Scotland, uptake this year was 73.3% for those 65 years and over and 43.3% for at risk groups under 65 years. Scotland ordered 1.3 million doses of influenza vaccine but could only account for 1.15 million doses used.

Northern Ireland changed to a central supply and distribution system this year and reported no delays or interruptions to supplies.

The Subgroup discussed possible reasons for the poor uptake in people under 65 and the discrepancies between risk groups, and recommended that the Department's qualitative research continued to assess patient attitudes in 'at risk' groups with low uptake and in healthcare workers.

Influenza vaccine ADRs update (MHRA)

The report provided an update on the safety of influenza vaccines from 1 September 2005 to 27 February 2006 using data extracted by the Medicines and Healthcare Products Regulatory Agency (MHRA) adverse drug reaction on-line information tracking (ADROIT) database.

A total of 95 reports were received during this period (when approaching 12 million doses of vaccine would have been administered), covering 240 adverse reactions in association with influenza vaccine. The majority of the ADR reports were defined as 'serious' (a 'serious' report contains at least one term that is considered to be serious according to the MedDRA dictionary). Most were reported in November/December.

The subgroup thought it would be helpful for future reports to analyse the data according to age group and vaccine brand, if possible.

An epidemiological study of selected serious adverse reactions since is proposed, which will also act as a pilot, and a base line, for monitoring ADRs to a future pandemic influenza vaccine.

It was suggested that the seasonal ADR data should be published nationally in support of the annual vaccination campaign. The annual CMO letter, Pulse or a British Medical Journal editorial were suggested options.

The Subgroup agreed with this recommendation.

5. Oral update on avian and pandemic influenza

Following an audit of NHS preparedness for an influenza pandemic, the Department of Health was considering how best to take forward work to improve preparedness in the NHS

The National Influenza Pandemic Committee (NIPC) and Scientific Advisory Group (SAG) continue to provide expert advice, together with other expert groups (including JCVI).

Two contracts have been awarded for around 3 million doses of an H5N1 vaccine. One is egg-based and the other cell-based. Both are adjuvanted. Initial deliveries are expected in May. The Department of Health has also tendered for 'sleeping contracts' with manufacturers for a pandemic vaccine for the UK population, once a pandemic virus has emerged.

Members of the Subgroup asked for more details on the H5N1 vaccines being purchased and emphasised the need to build up information on their immunogenicity and safety.

Experts, including Members of this Subgroup, continue to advise on vaccination strategy in the light of evolving scientific information.

DH and DEFRA are working on implementation plans for seasonal immunisation of poultry workers. The Subgroup was anxious that, in the event of an avian influenza incident or outbreak in the UK, immunisation against seasonal influenza did not interfere with the more immediate action needed to protect workers against avian influenza.

6. Influenza vaccine in pregnancy JCVI/RP/FLU(06)3

Recommendations on the use and safety of inactivated influenza vaccines during pregnancy

At the last meeting, the Influenza Subgroup agreed that pregnant women and their very young babies were at an increased risk from influenza. They were minded to recommend that:

1. influenza vaccine should be recommended for women expecting to deliver during the influenza season i.e. those in the second and third trimesters during the influenza immunisation programme
2. a vaccine without thiomersal would be preferable for pregnant women

but asked for a summary of the evidence that had been considered at previous meetings before coming to a final recommendation.

Much of the previously considered data were contained in a review carried out by The London School of Hygiene & Tropical Medicine (Tippi Mak) in November 2004.

Evidence that pregnant women are at an increased risk from influenza

The majority of published work showed that pregnant women are at higher risk of mortality and morbidity in influenza pandemic years. There were fewer published studies looking at an increased risk during pregnancy in non-pandemic years.

The main source of evidence that pregnant women are at an increased risk of influenza in non-pandemic years comes from an examination of cardiopulmonary hospitalisation rates during influenza seasons (1973-1994) in a retrospective study using Tennessee Medicaid historical cohort data (Neuzil et al, 1998).

Evidence that the foetus and newborn infant are at an increased risk from influenza and would benefit from maternal vaccination

In addition to the risk of influenza infection to pregnant women, there may be potential benefits in maternal vaccination to the foetus or newborn.

Although there are case reports, in utero infection appears to be a rare occurrence. However, morbidity from influenza is high in infants. There are no data on impact of infant morbidity from the vaccination of pregnant women.

The subgroup noted that the risk from influenza increased later in pregnancy and that there were additional benefits to vaccinating women who were expected to deliver during the influenza season as this would help to protect their newborn.

Evidence of vaccine efficacy in pregnancy

The few serologic studies on pregnant women (vaccinated in the second or third trimester) suggest that antibody response to influenza vaccine is similar to nonpregnant women.

Evidence of vaccine safety in pregnancy

In the original review by Tippi Mak it was noted that vaccine safety data were limited, particularly in the first trimester. More safety data has become available since this report (Munoz et al, 2005).

Passive reporting schemes for monitoring adverse reactions in the UK and the US (where pregnant women are recommended to receive flu vaccination and where around 0.5 million are vaccinated each year) note that a small number of serious reports have been received for women vaccinated during pregnancy.

7. Neurological disease JCVI/RP/FLU(06)4

The Subgroup previously agreed, confirmed by the main JCVI, that influenza immunisation should be recommended for people with multiple sclerosis, particularly relapsing MS. This would be in agreement with NICE guidance on MS. It was also agreed that any recommendation to add patients with MS to the list of 'at risk' groups should be considered in the wider context of a neurological disease category.

The Subgroup had agreed to consider neurological disease in general at a subsequent meeting.

7.1 Association between influenza vaccination and reduced risk of stroke

The evidence and biological plausibility that chronic infections can induce atherosclerosis has been described (Meyers, 2003).

Three studies support the association between influenza vaccination and reduced risk of stroke (Lavellee et al, 2002, Nichol et al, 2003, Grau et al, 2005). A further study has provided evidence of a transient risk of vascular events, including stroke, following systemic respiratory tract infection.

The subgroup agreed that it was reasonable to assume that individuals who have already had a cerebrovascular incident are at an increased risk of another. Influenza vaccination would help to prevent another occurrence. It was suggested that ICD9 diagnostic group 'cerebrovascular disease' (430-438) could be used to define this group. The majority of this group are over 65 years (prevalence of 409/10,000). The prevalence in those 45-64 years is 57 per 10,000.

Inherited and degenerative diseases

A paper by Keren et al, 2005 identifies chronic medical conditions that are associated with respiratory failure in children hospitalised with laboratory confirmed influenza. This research supports ACIP's decision in 2005 to recommend the vaccination of 'adults and children who have any condition (e.g. cognitive dysfunction, spinal cord injuries, seizure disorders, or other neuromuscular disorders) that can compromise respiratory function or the handling of respiratory secretions or that can increase the risk for aspiration'.

The subgroup recommended the addition of ICD diagnostic group 'Hereditary and degenerative diseases of the CNS' (330-337).

Chronic Fatigue Syndrome

This was reviewed by Sleigh et al (2002). There is no clear evidence of an association between Chronic Fatigue Syndrome and a worsening of the condition following influenza infection.

Febrile Seizures

There is some published evidence that suggests a relationship between recurrent febrile seizures and influenza (van Zeijl et al, 2004). Considerable discussion took place on the topic of febrile seizures. The Subgroup agreed to incorporate this discussion into the planned agenda item of universal immunisation of children with seasonal influenza vaccine at the September 2006 meeting.

The Subgroup recommended that a neurological 'at risk' category should be added to the list of 'at risk' groups to be offered influenza vaccine. Based on currently available evidence this would consist of:

1. MS and related conditions (ICD 9 code 340 and 341);
2. Hereditary and degenerative diseases of the CNS (ICD9 code 330-337).
3. Cerebrovascular disease (ICD9 code 430-438)

The advice will be taken to the next main JCVI committee meeting for consideration for the 2007/08 immunisation programme.

8. Mental health JCVI/RP/FLU(06)5

The paper considered whether patients with schizophrenia and bi-polar affective disorder should be added to the list of 'at risk' groups for seasonal influenza vaccination.

Summary of evidence: The available papers do confirm a high level of co-morbidity and excess mortality in this group of patients but, critically, not necessarily from influenza. It is a consistent conclusion from the authors of these studies that it is the higher rate of preventable risk factors in this group (e.g. smoking, alcohol consumption, poor diet and lack of exercise) that contributes to the excess morbidity and mortality. There is no evidence at present to support a role for influenza vaccination.

The Subgroup was of the opinion that there was currently insufficient evidence to support the addition of patients with schizophrenia and bi-polar affective disorder to the at risk groups for seasonal influenza vaccine.

9. Vaccination of children - are there indirect benefits to the community? Paper for discussion JCVI/RP/FLU(06)6

The paper (Jordan et al, 2006) reviewed the evidence that there is an indirect benefits for adults if children are vaccinated with influenza vaccine.

The Subgroup agreed to incorporate this discussion into the planned agenda item of universal immunisation of children with seasonal influenza vaccine at the scheduled September 2006 meeting

10. Articles for Information JCVI/RP/FLU(06)7

The Committee's attention was drawn to the following papers for information.

• Antiviral letter to the profession
• Media Relations: CDC's Advisory Committee Recommends Expanded Influenza Vaccinations for Children 2006
  

11. Any other business

Three further items were tabled for discussion;

(a) Confirmation of the wording of the Multiple Sclerosis (MS) at risk group of patients.

The Subgroup agreed that "MS and related conditions" would be the wording used to describe this group of patients

(b) A draft outline of an operating procedure for the JCVI influenza subgroup. In summary, in future two meetings a year will be scheduled, in March and September, with different agendas, the March meeting concentrating on lessons from the previous year, and the September one of policy review. The aim is to structure the work efficiently in the context of an overall timetable that incorporates the work of other groups which impact on the seasonal flu campaign e.g. ordering flu vaccine supplies, negotiating with BMA GPC, CMO announcement. The Subgroup agreed that this was a good way forward.

(c) An enquiry as to whether Addison's disease and hypopituitarism have been considered as an at-risk group. This group of patients has not been considered as a separate 'at risk' group. The committee highlighted it as a topic to return to at a later date as part of the forward planning agenda.

12. Date of next meeting

Early September 2006. Members will be contacted with a suitable date.

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