Pandemic influenza 2009: Impact of vaccination coverage on critical illness in children, a Canada and France observational study

Table 1 Characteristics of critically ill children with influenza A(H1N1)pdm09 virus at admission to the pediatric intensive care unit in two countries

	Canada (n = 160)	France (n = 125)	OR (95%CI) Canada/France	P value
Incidence rate (/100000 children)	2.6	1·1	2.3 (1.8-2.9)	< 0.001
Age, mean (SD), yr	6.6 (0.40)	5.5 (0.48)	NA	0.09
Weight, mean (SD), kg	25.9 (1.62)	20.1 (1.45)	NA	0.01
Female gender, n (%)	68 (42)	56 (45)	0.91 (0.57-1.46)	0.70
Vaccination H1N1, n (%)	34 (21)	2 (2)	16.6 (3.90-70.6)	< 0.001
Underlying chronic conditions, n (%)
Any underlying conditions	102 (64)	93 (74)	0.60 (0.36-1.01)	0.05
Infant < 1 years old	21 (13)	32 (25)	0.44 (0.24-0.81)	0.007
Lung disease	65 (40)	29 (23)	2.26 (1.34-3.82)	0.002
Asthma	42 (26)	16 (13)	2.40 (1.29-4.56)	0.005
Chronic lung disease	33 (20.6)	14 (11.2)	2.06 (1.05-4.05)	0.03
Cystic fibrosis	0 (0)	2 (2)	NA	NA
BPD	4 (2)	4 (3)	0.78 (0.19-3.16)	0.731
Tracheostomy	5 (3)	1 (1)	4.00 (0.46-33.3)	0.241
Congenital heart disease	24 (15)	3 (2)	7.18 (2.11-24.4)	< 0.001
Neurological disease	31 (19)	19 (15)	1.33 (0.71-2.50)	0.36
Seizure disorder	19 (12)	5 (4)	3.23 (1.18-9.09)	0.02
Immunosuppressive disorder	11 (7)	9 (7)	0.95 (0.38-2.37)	0.91
Diabetes mellitus	6 (3.8)	0 (0)	NA	0.041
Renal insufficiency	7 (4)	1 (1)	5.56 (0.69-50.0)	0.081
Others diseases	32 (20)	28 (22)	0.87 (0.95-1.54)	0.62
PELOD score, mean (SD)2	6.67 (0.82)	7.80 (1.47)	NA	0.47
PIM2 score, mean (SD)3	8.47 (1.05)	9.74 (2.77)	NA	0.67
Clinical presentation at admission
Lower respiratory infection, n (%)	101 (63)	90 (72)	0.67 (0.40-1.10)	0.11
CNS infection	2 (1)	7 (6)	0.21 (0.04-0.99)	0.04
Shock	13 (8)	6 (5)	1.75 (0.65-4.76)	0.26
Other	48 (30)	35 (29)	1.10 (0.67-1.85)	0.90
Bacterial infection at admission	22 (14)	27 (22)	0.58 (0.31-1.07)	0.08

¹Fisher’s exact test;

²Missing values PELOD: 42.4% in France, 1.9% in Canada;

³Missing values PIM2: 37.6% in France, 0% in Canada. Chronic lung disease = chronic restrictive lung syndrome and chronic upper airway disease and tracheo/bronchomalacia and obstructive sleep apnea and recurrent aspiration into lungs and others; Immune deficit = oncologic disorder and HIV and hemoglobinopathy. CI: Confidence interval; NA: Not applicable; BPD: Broncho-pulmonary dysplasia; PELOD: Pediatric logistic organ dysfunction; PIM2: Paediatric index of mortality revised version; OR: Odds ratio; SD: Standard deviation.

Table 2 Hospital course of critically ill children with influenza A(H1N1)pdm09 infection in two countries

	Canada (n = 160)	France (n = 125)	OR (95%CI), difference	P value
Time-dependent variables, median (25th 75th percentile), d
PICU length of stay	2.9 (2.1-3.6)	3.0 (1.8-4.2)	0.1	0.03
Duration of mechanical ventilation	4.0 (2.8-5.2)	5.0 (3.2-6.8)	1	0.07
Duration of invasive ventilation	4.0 (2.9-5.1)	6.0 (4.6-7.4)	2	0.02
Categorical variables, n (%)
Mortality	7 (4.4)	8 (6.5)	0.67 (0.24-1.90)	0.45
Respiratory dysfunction
ARDS	29 (18)	40 (32)	0.48 (0.27-0.81)	0.007
Mechanical ventilation	86 (54)	66 (53)	1.04 (0.67-1.67)	0.87
Invasive ventilation	78 (49)	50 (40)	1.43 (0.91-2.50)	0.14
Pneumothorax	19 (12)	10 (8)	1.17 (0.67-3.33)	0.32
ECMO	3 (2)	8 (6)	0.28 (0.07-1.07)	0.05
Neurologic dysfunction
Seizures	2 (1)	9 (7)	0.16 (0.03-0.13)	0.01
ADEM	3 (2)	7 (6)	0.32 (0.08-1.26)	0.09
Renal dysfunction
Dialysis/hemofiltration	10 (6)	4 (3)	2.00 (0.63-6.67)	0.24
Nosocomial infections
Nosocomial infection	15 (9)	26 (21)	0.39 (0.20-0.78)	0.006
Ventilator-associated pneumonia	9 (6)	21 (17)	0.29 (0.13-0.67)	0.002
Antiviral treatment
Oseltamivir	148 (93)	111 (89)	1.55 (0.69-3.49)	0.28
Oseltamivir within 48 h	102 (63)	99 (79)	0.46 (0.27-0.79)	0.004

A bivariate analysis compared mortality, organ dysfunction, nosocomial infection and anti-viral treatment between the two countries. OR: Odds ratio; CI: Confidence interval; PICU: Pediatric intensive care unit; ARDS: Acute respiratory distress syndrome: ECMO: Extracorporeal membrane oxygenation; ADEM: Acute demyelinating encephalo-myelitis or demyelinating disorder.

Table 3 Critically ill patient-based factors associated with risk of invasive ventilation in Canada

Included variables	n = 157	OR	95%CI	P value
PIM2 > 7.5	39	6.26	2.43-16.4	< 0.001
Age, years < 1	21	1.88	0.51-6.94	0.35
1-4	52	1.50	0.51-4.35	0.46
5-9	46	2.42	0.45-6.93	0.10
> 10	38	1	(Ref)
H1N1 vaccine	32	0.30	0.11-0.83	0.02
Asthma	41	0.23	0.09-0.64	0.004
Lung diseases (not asthma)	22	0.99	0.32-3.08	0.99
Neurologic diseases	31	2.51	0.92-6.90	0.07
Cardiologic diseases	28	1.13	0.43-2.97	0.76
Others diseases	47	0.87	0.37-2.05	0.76
Oseltamivir within 48 h	102	1.02	0.47-2.24	0.95

H1N1 vaccine, children vaccinated against H1N1; lung diseases, chronicle lung diseases without asthma; Neurologic disease, neurologic and muscular disorder; Cardiologic diseases, cardiologic diseases before admission; other diseases, all comorbities without lung, cardiologic or neurologic diseases. OR: Odd ratio; CI: Confidence interval; PIM2: Paediatric index of mortality revised version.