Initial reports of 208 deaths between 1 June and 8 November 2009 were received. Of these, 138 met the case definition as being related to pandemic A/H1N1. The others were excluded from analysis because the initial clinical suspicion was not borne out by investigation and hence the case definition was not met (n=56) or because they did not yet fulfil the case definition but death certification or results of postmortem tests were outstanding (n=14).
An estimated 540
000 people (range 240
000) in England had symptomatic pandemic A/H1N1 infection in the study period. With this denominator, the case fatality rate was 26 (11-66) deaths per 100
000 cases. On a general population basis over the same period, there were 1100 (400-2200) cases per 100
000 people and 2.7 (95% confidence interval 2.2 to 3.2) deaths per million (table 1). Fig 1 shows the number of deaths occurring in each week and the mid-point estimate of case numbers. The time distribution of cases follows a classic epidemic curve, with a peak in July, and a second wave in October and November. The time distribution of deaths is similar, with deaths in the first wave peaking two to three weeks after the peak of cases.
Age specific indices of incidence of and mortality from pandemic A/H1N1 in 2009. All population and case estimates rounded to nearest 1000
Fig 1 Weekly estimated incidence of pandemic A/H1N1 cases (mid-range estimates) and confirmed deaths in England (source: Health Protection Agency)
A sensitivity analysis censoring cases one week before death yielded a similar case fatality rate of 22 (range 9-56) deaths per 100
000 cases. Censoring at four weeks yielded a case fatality rate of 34 (14-90) deaths per 100
000. If we included all the 14 deaths currently under investigation, censoring at two weeks, the case fatality would rise to 28 (12-72).
Demographic and clinical characteristics
Patients who died ranged in age from 0 to 88 (median 39, interquartile range 17-57). Case fatality rates varied between age groups (table 1). The ≥65 age group had the lowest estimated incidence rate but the highest case fatality rate. Conversely, those aged 5-14 and 15-24 had the highest estimated incidence rates and the lowest estimated case fatality rates. There was no significant difference in the risk of death between males (3.0 deaths per million) and females (2.4 deaths per million) (Pearson χ2=1.7, df=1, P=0.22).
Before contracting pandemic A/H1NI, over a third of those who died were either previously healthy (ASA grade one, 19%, 26/138) or had mild systemic disease that did not limit their activity (ASA grade two, 17%, 24/138). Two thirds had severe (ASA grade three, 33%, 46/138) or incapacitating (ASA grade four, 30%, 42/138) underlying systemic disease. Patients at the extremes of age (<5 and ≥65) had poorer pre-morbid health as assessed by ASA grade (fig 2).
Fig 2 Age and pre-morbid health of patients who died from causes related to pandemic A/H1N1
Patients who died had a median of two long term conditions or risk factors (26 had no risk factors or long term conditions, 32 had one, 34 had two, 31 had three, 7 had four, 4 had five, 2 had six, and 2 had seven). Chronic respiratory disease and neurodevelopmental disorders were the most commonly reported long term conditions (table 2). The median age of patients was 8 (interquartile range 2-19, n=25) in those with a neurodevelopmental disorder, 30.5 (20-47, n=15) in those with asthma, and 64 (48-74, n=13) in those with COPD (chronic obstructive pulmonary disease). Of all those who died, 67% (92/138) fell into one of the risk categories eligible for the first phase of vaccination in England. The population risk of death for those falling into a vaccination group (9.9 per million people) was nine times that for those not in an at risk group (1.1 per million people, Pearson χ2=217, df=1, P<0.001). Those who were aged ≥65 were more likely to fall into a priority group for vaccination than those outside this age group (24/26 v 68/112, P=0.002, Fisher’s exact test).
Table 2 History of long term conditions and other risk factors among those dying from pandemic A/H1N1. Numbers in parentheses indicate number with single long term condition or risk factor
Time course of illness and treatment
In patients for whom a date of onset of symptoms was stated, death occurred a median of 12 days (interquartile range 5-19 days, n=114) after influenza-like symptoms began. A total of 125 patients were admitted to hospital, including one patient discharged who subsequently died in the community. A further four patients died in the ambulance or on arrival at hospital. The remainder (n=9) died in the community, having been solely cared for in the community.
In those admitted to hospital with pandemic A/H1N1, symptoms started a median of three days before admission (1-5 days, n=111). Two patients developed influenza-like symptoms while already in hospital. The date of onset of symptoms was missing or unclear for 12 patients admitted to hospital. After the exclusion of four patients (two with hospital acquired influenza, one discharged before death, and one with date of admission missing), patients spent a median of eight days in hospital (3-14 days, n=121). Most patients admitted to hospital (82%, 103/125), were treated in an intensive care unit at some stage, dying a median of six days (2-14 days, n=103) after admission to the unit.
Use of antiviral drugs
Of those who died, 78% (108/138) were prescribed antiviral drugs. In the 94 for whom a date of symptoms was reported, patients started taking the drugs a median of five days after symptoms began (interquartile range 2-8 days). Of those admitted to hospital, 9% (11/125) had started taking antiviral drugs before admission. Of those treated with antiviral drugs, 24% (26/108) received them within the recommended 48 hours after onset of symptoms. Greater use of antiviral drugs was observed in patients who died in acute hospitals than in those who died in the community (101/125 v 7/13, P=0.04, Fisher’s exact test,).
In 11 cases the death certificate had not yet been issued because a coroner’s investigation was ongoing (8%, 11/138). Table 3 reports the position of pandemic A/H1N1 on the 127 death certificates issued. When we analysed all available death certificates using the ICD-10 methods used to produce mortality data, the underlying cause of 39% of deaths (49/127) would be classified as influenza.
Table 3 Microbiological testing and death certification of included deaths
We further analysed death certificates that recorded pandemic A/H1N1 in the causal chain leading directly to death (n=74) (table 4). The direct cause of death was recorded as pandemic A/H1N1 (or some synonym) in 43% of these cases (32/74). In 11% of cases (8/74) pandemic A/H1N1 was the sole condition recorded on the death certificate. In most cases, the direct cause of death was a respiratory condition (76%, 56/74).
Table 4 Certification of direct cause of death in cases in which pandemic A/H1N1 infection was recorded within causal chain leading to death