Overall, 60 confirmed cases of influenza A/H1N1 and 180 controls were identified. The controls were admitted to the outpatient clinic or to hospital for a total of 270 diagnoses (table 1): four patients had four diagnoses, 13 had three, 52 had two, and the remainder (n=111) had one. The 10 most common reasons for admission were elective ear, nose, or throat surgery; asthma; obstructive sleep apnoea; chronic obstructive pulmonary disease; gastro-oesophageal reflux; tuberculosis; HIV/AIDS; arterial hypertension; interstitial pneumopathy; and diabetes.
Table 1 Admission diagnoses of 180 controls*
Controls who had been vaccinated against 2008-9 seasonal influenza were significantly more likely than cases to refer (table 2). Most of the cases (n=38, 63%) were aged 21-60 years. Frequency matching ensured that the cases and controls were balanced for socioeconomic status (table 2). Cases and controls were also similar for sex.
Table 2 Personal and clinical characteristics of influenza A/H1N1 cases and controls. Values are numbers (percentages) unless stated otherwise
The cases had more severe clinical manifestations than the controls; they were more likely to be admitted to hospital, undergo invasive mechanical ventilation, and die. Most of the cases had been previously healthy (n=45, 75%). Overall, the controls were significantly more likely than the cases to have underlying conditions conferring a higher risk of influenza related complications (table 2). With the exception of diabetes, which was three times more prevalent among cases than among controls (7 (12%) v 6 (3%), P=0.02), compared with cases the prevalence of other conditions among controls was higher or not significantly different.
The prevalence of underlying conditions conferring a higher risk of influenza related complications was similar among surviving and non-surviving cases (10/42 (24%) v 5/18 (28%), P=0.75). Conditions among the 10 surviving cases included chronic renal insufficiency, obesity, congenital thoracic deformity, and chronic obstructive pulmonary disease (one each); asthma (n=2); diabetes (n=3); and diabetes, obesity, and chronic renal insufficiency (n=1). Conditions among the five cases who died included chronic obstructive pulmonary disease, obstructive sleep apnoea, and HIV/AIDS (one each); diabetes and pulmonary arterial hypertension (n=1); and diabetes and obstructive sleep apnoea (n=1).
The proportion of patients who died among vaccinated cases was significantly lower than among unvaccinated cases (0/8 (0%) v 18/52 (35%), P=0.047). The proportion of patients requiring invasive mechanical ventilation was also lower among vaccinated cases than among unvaccinated cases, although this was not significant (1/8 (13%) v 25/52 (48%), P=0.058).
Table 3 shows the number of cases and controls and information on vaccination status and prevalence of underlying conditions by age group. With the exception of the age group 5-20 years, the crude odds ratio for vaccination during the previous season showed a protective effect for all age groups, although this was not statistically significant. The prevalence of underlying conditions conferring a higher risk of influenza related complications was significantly greater among controls aged <5, 41-60, and more than 60. When individual conditions were analysed by age group, asthma was significantly more prevalent among controls aged 5-20 and 21-40, whereas diabetes was significantly more prevalent among cases aged 21-40.
Table 3 Vaccination status and prevalence of underlying medical conditions conferring a higher risk of influenza related complications, by age group
In the multivariate model, vaccination status and underlying conditions were independently associated with influenza A/H1N1 (table 4). When the association of influenza A/H1N1 with vaccine status for each age group was modelled, the adjusted odds ratio continued to show a protective effect, although this was statistically significant only for the age group 41-60 (table 3). Vaccine effectiveness against laboratory confirmed cases of influenza A/H1N1 was 73% (95% confidence interval 34% to 89%).
Table 4 Variables associated with influenza A/H1N1, by conditional logistic regression analysis
We estimated the power of the study to be 88%, assuming a type I error probability of 0.05, 60 cases, three controls for each case, 29% prevalence of vaccination in the control group, a correlation coefficient for exposure between matched cases and controls of 0.21, and an adjusted odds ratio of 0.27.
When only the subset of cases (n=59) and controls (n=61) admitted to hospital was analysed the association between confirmed cases of influenza A/H1N1 and vaccination status was significant (table 4). Vaccine effectiveness was 77% (22% to 93%). When the association between influenza A/H1N1 cases and vaccination status was modelled among the subset of cases (n=45) and controls (n-60) without high risk underlying conditions, it continued to be significant (table 4). The estimated vaccine effectiveness for this subset was 86% (50% to 96%)