Background
Methods
Study population and setting
Case definition and surveillance system
PCR confirmation of influenza
Statistical analysis
Ethical considerations
Results
Participating PICUs and recruitment of ARI patients
Frequency of PICU patients with PCR-confirmed influenza, by type and subtype
Influenza type/subtype | ||||||
---|---|---|---|---|---|---|
Seasons | All patients | A |
A(H1N1)pdm09
|
A(H3N2)
|
A (subtype n.a.)
| Ba
|
N (%) | N (%) |
N (%)
|
N (%)
|
N (%)
| N (%) | |
Season 1 (Oct 2010–Sep 2011) | 24 (100.0) | 23 (95.8) |
19 (79.2)
|
0 (0.0)
|
4 (16.7)
b
| 1 (4.2) |
Season 2 (Oct 2011–Sep 2012) | 7 (100.0) | 2 (28.6) |
1 (14.3)
|
1 (14.3)
|
0 (0.0)
| 5 (71.4) |
Season 3 (Oct 2012–Sep 2013) | 20 (100.0) | 16 (80.0) |
13 (65.0)
|
3 (15.0)
|
0 (0.0)
| 4 (20.0) |
Season 1–3 (Oct 2010–Sep 2013) | 51 (100.0) | 41 (80.4) |
33 (64.7)
|
4 (7.8)
|
4 (7.8)
| 10 (19.6) |
Incidence estimates for influenza-associated PICU admittance
Clinical characteristics of influenza-associated PICU admissions
Demographic characteristics, hospital admittance and length of stay
Influenza type/subtype | Comparison of seasons | ||||||
---|---|---|---|---|---|---|---|
A(H1N1)pdm09c
| |||||||
Characteristics | All patients | A |
A(H1N1)pdm09
|
A(H3N2)
|
A (subtype n.a.)
| B | S1 vs S3 |
N = 47 | N = 40 |
N = 32
|
N = 4
|
N = 4
| N = 7 |
p-value* | |
Male sex; n (%) | 28 (59.6) | 24 (60.0) |
18 (56.3)
|
3 (75.0)
|
3 (75.0)
| 4 (57.1) | 0.481 |
Age at ICU admission, in years (median, IQR) | 4.8 (1.6–11.0) | 4.7 (1.1–11.1) |
5.4 (1.6–11.3)
|
0.9 (0.6–4.4)
|
4.9 (2.3–10.4)
| 5.0 (2.3–9.4) | 0.020 |
Interval between onset of ARI symptoms and ICU admission, in days (median, IQR)b
| 3.0 (2.0–5.3) | 3.0 (1.0–6.0) |
3.5 (1.0–5.8)
|
2.5 (2.0–10.5)
|
3.0 (n.a.)
| 3.0 (1.5–5.0) | 0.041 |
Interval between onset of ARI symptoms and hospital admission, in days (median, IQR)b
| 3.0 (1.0–5.0) | 3.0 (1.0–5.0) |
3.0 (1.0–5.0)
|
2.5 (2.0–4.5)
|
2.0 (n.a.)
| 3.0 (1.5–4.0) | 0.217 |
Duration of ICU stay, in days (median, IQR) | 3.0 (1.0–11.0) | 3.5 (2.0–12.5) |
3.0 (1.3–12.3)
|
9.5 (7.3–29.0)
|
6.5 (2.0–16.3)
| 1.0 (1.0–11.0) | 0.837 |
Duration of hospital stay, in days (median, IQR) | 7.5 (4.0–16.3) | 8.0 (4.0–16.0) |
7.0 (4.0–16.0)
|
11.0 (8.8–59.0)
|
13.0 (7.3–20.3)
| 5.0 (3.0–22.0) | 0.953 |
Underlying chronic conditions
Influenza type/subtype | Comparison of seasons | ||||||
---|---|---|---|---|---|---|---|
A(H1N1)pdm09c
| |||||||
Underlying medical conditions | All patients | A |
A(H1N1)pdm09
|
A(H3N2)
|
A (subtype n.a.)
| B | S1 vs S3 |
N = 47 | N = 40 |
N = 32
|
N = 4
|
N = 4
| N = 7 |
p-value* | |
At least one medical condition; n (%) | 36 (76.6) | 32 (80.0) |
24 (75.0)
|
4 (100.0)
|
4 (100.0)
| 4 (57.1) | 0.667 |
Selected conditions | |||||||
- Neurological disease; n (%) | 16 (34.0) | 14 (35.0) |
13 (40.6)
|
1 (25.0)
|
0 (0.0)
| 2 (28.6) | 1.000 |
- Chronic lung diseaseb; n (%) | 12 (25.5) | 12 (30.0) |
11 (34.4)
|
0 (0.0)
|
1 (25.0)
| 0 (0.0) | 1.000 |
- Pre-term birth; n (%) | 10 (21.3) | 9 (22.5) |
8 (25.0)
|
1 (25.0)
|
0 (0.0)
| 1 (14.3) | 0.210 |
- Cardiac malformation; n (%) | 8 (17.0) | 8 (20.0) |
3 (9.4)
|
3 (75.0)
|
2 (50.0)
| 0 (0.0) | 0.558 |
- Obesity; n (%) | 5 (10.6) | 5 (12.5) |
3 (9.4)
|
0 (0.0)
|
2 (50.0)
| 0 (0.0) | 0.245 |
- Genetic disorder; n (%) | 4 (8.5) | 3 (7.5) |
3 (9.4)
|
0 (0.0)
|
0 (0.0)
| 1 (14.3) | 0.558 |
- Immunocompromised; n (%) | 4 (8.5) | 2 (5.0) |
0 (0.0)
|
1 (25.0)
|
1 (25.0)
| 2 (28.6) | n.a. |
- Renal disease; n (%) | 1 (2.1) | 1 (2.5) |
1 (3.1)
|
0 (0.0)
|
0 (0.0)
| 0 (0.0) | 0.419 |
- Other underlying conditions; n (%) | 9 (19.1) | 8 (20.0) |
5 (15.6)
|
2 (50.0)
|
1 (25.0)
| 1 (14.3) | 0.134 |
Influenza vaccination status
Clinical diagnoses
Influenza type/subtype | Comparison of seasons | ||||||
---|---|---|---|---|---|---|---|
A(H1N1)pdm09b
| |||||||
Complications | All patients | A |
A(H1N1)pdm09
|
A(H3N2)
|
A (subtype n.a.)
| B | S1 vs S3 |
N = 47 | N = 40 |
N = 32
|
N = 4
|
N = 4
| N = 7 |
p-value* | |
At least 1 specific complication; n (%) | 42 (89.4) | 36 (90.0) |
29 (90.6)
|
3 (75.0)
|
4 (100.0)
| 6 (85.7) | 0.497 |
Influenza-associated pneumonia; n (%) | 29 (61.7) | 26 (65.0) |
22 (68.8)
|
1 (25.0)
|
3 (75.0)
| 3 (42.9) | 1.000 |
Bronchitis/bronchiolitis; n (%) | 15 (31.9) | 13 (32.5) |
8 (25.0)
|
3 (75.0)
|
2 (50.0)
| 2 (28.6) | 0.004 |
Secondary bacterial pneumonia; n (%) | 12 (25.5) | 10 (25.0) |
10 (31.3)
|
0 (0.0)
|
0 (0.0)
| 2 (28.6) | 0.452 |
ARDS; n (%) | 10 (21.3) | 9 (22.5) |
7 (21.9)
|
2 (50.0)
|
0 (0.0)
| 1 (14.3) | 0.099 |
Sepsis; n (%) | 6 (12.8) | 6 (15.0) |
4 (12.5)
|
1 (25.0)
|
1 (25.0)
| 0 (0.0) | 1.000 |
Febrile convulsions; n (%) | 3 (6.4) | 2 (5.0) |
2 (6.3)
|
0 (0.0)
|
0 (0.0)
| 1 (14.3) | 1.000 |
Encephalitis/encephalopathy; n (%) | 1 (2.1) | 1 (2.5) |
1 (3.1)
|
0 (0.0)
|
0 (0.0)
| 0 (0.0) | 1.000 |
Laryngitis/pseudocroup; n (%) | 1 (2.1) | 1 (2.5) |
1 (3.1)
|
0 (0.0)
|
0 (0.0)
| 0 (0.0) | 1.000 |
Otherc; n (%) | 6 (12.8) | 5 (12.5) |
5 (15.6)
|
0 (0.0)
|
0 (0.0)
| 1 (14.3) | 1.000 |
Co-infections
Patient treatment and outcome
Influenza type/subtype | Comparison of seasons | ||||||
---|---|---|---|---|---|---|---|
A(H1N1)pdm09c
| |||||||
Treatment | All | A |
A(H1N1)pdm09
|
A(H3N2)
|
A (subtype n.a.)
| B | S1 vs S3 |
N = 47 | N = 40 |
N = 32
|
N = 4
|
N = 4
| N = 7 |
p-value* | |
Antiviral drugsb; n (%) | 13 (27.7) | 12 (30.0) |
9 (28.1)
|
1 (25.0)
|
2 (50.0)
| 1 (14.3) | 1.000 |
Antibiotics i.v.; n (%) | 34 (72.3) | 31 (77.5) |
25 (78.1)
|
2 (50.0)
|
4 (100.0)
| 3 (42.9) | 0.676 |
Antipyretics; n (%) | 33 (70.2) | 28 (70.0) |
22 (68.8)
|
2 (50.0)
|
4 (100.0)
| 5 (71.4) | 0.452 |
Catecholamines; n (%) | 13 (27.7) | 13 (32.5) |
11 (34.4)
|
1 (25.0)
|
1 (25.0)
| 0 (0.0) | 1.000 |
Inhalation therapy; n (%) | 13 (27.7) | 13 (32.5) |
11 (34.4)
|
2 (50.0)
|
0 (0.0)
| 0 (0.0) | 1.000 |
Oxygen; n (%) | 31 (66.0) | 28 (70.0) |
20 (62.5)
|
4 (100.0)
|
4 (100.0.)
| 3 (42.9) | 0.275 |
Intratracheal ventilation; n (%) | 15 (31.9) | 14 (35.0) |
12 (37.5)
|
1 (25.0)
|
1 (25.0)
| 1 (14.3) | 1.000 |
CPAP; n (%) | 11 (23.4) | 9 (22.5) |
7 (21.9)
|
0 (0.0)
|
2 (50.0)
| 2 (28.6) | 0.084 |
Other; n (%) | 14 (29.8) | 13 (32.5) |
10 (31.3)
|
2 (50.0)
|
1 (25.0)
| 1 (14.3) | 0.247 |
Outcome | |||||||
Sequelae; n (%) | 5 (10.6) | 4 (10.0) |
3 (9.4)
|
1 (25.0)
|
0 (0.0)
| 1 (14.3) | 0.548 |
Death; n (%) | 5 (10.6) | 5 (12.5) |
5 (15.6)
|
0 (0.0)
|
0 (0.0)
| 0 (0.0) | 1.000 |
Fatalities and sequelae
Patient | PICU admittance (season) | Age (years) | Influenza type/subtype | Co-pathogen(s) detecteda
| Underlying chronic condition | Influenza vaccination | Complications | Antiviral treatment (days) | Antibiotics i.v. (days) | Cause of death |
---|---|---|---|---|---|---|---|---|---|---|
1 | 2010/11 | 10 | A(H1N1)pdm09 |
Escherichia coli
| Obesity | No | ARDS, sepsis, convulsion (encephalitis suspected) | Acyclovir (2) | Yes (2) | ARDS, Sepsis |
2 | 2010/11 | 4 | A(H1N1)pdm09 |
Streptococcus sp., Candida sp. | Neurologic | No | Pneumonia, secondary bacterial pneumonia, pleural effusion | No | Yes (10) | Circulatory insufficiency |
Pulmonal | ||||||||||
Pre-term birth | ||||||||||
3 | 2010/11 | 4 | A(H1N1)pdm09 | RSV Pseudomomas aeruginosa
| Neurologic | No | Pneumonia, secondary bacterial pneumonia, ARDS | No | Yes (19) | ARDS |
Pulmonal | ||||||||||
Pre-term birth | ||||||||||
Obesity | ||||||||||
4 | 2012/13 | 11 | A(H1N1)pdm09 | RSV, Candida sp. | Neurologic | No | Pneumonia, secondary bacterial pneumonia, bronchitis, ARDS, sepsis | Oseltamivir (5) | Yes (22) | ARDS, circulatory insufficiency |
Pulmonal | ||||||||||
5 | 2012/13 | 11 | A(H1N1)pdm09 | None | Neurologic | No | Pneumonia | No | Yes (4) | Respiratory failure |
Pulmonal |
Comparison of PICU patients infected with influenza A(H1N1)pdm09 in the first and the third post-pandemic season
Comparison of PICU patients infected with influenza in pre-pandemic and post-pandemic seasons
Key variables of PICU patients | Pre-pandemic (2005/06–2007/08) | Pandemic (2009/10) | Post-pandemic (2010/11–2012/13) | Pre-pandemic vs. post-pandemicb
|
---|---|---|---|---|
N = 20 |
N = 89a
|
N = 47 |
p-value | |
Male sex; n (%) | 12 (60) | 56 (60) | 28 (60) | 1.000 |
Age at ICU admission, in years (median, IQR) | 7.5 (0.5–12.75) | 4.5 (1.3–9.3) | 4.8 (1.6–11.0) | 0.727 |
Duration of ICU stay, in days (median, IQR) | 19 (12–38) | 8 (3–17) | 3 (1–11) | 0.006 |
Chronic underlying conditions; n (%) | 11 (55) | 63 (74) | 36 (77) | 0.089 |
Complications/diagnoses | ||||
Influenza-associated pneumonia; n (%) | 12 (60) | 66 (74) | 29 (62) | 1.000 |
Bronchitis/bronchiolitis; n (%) | 6 (30) | 11 (12) | 15 (32) | 1.000 |
Secondary bacterial pneumonia; n (%) | 5 (25) | 15 (17) | 12 (26) | 1.000 |
ARDS; n (%) | 5 (25) | 22 (25) | 10 (21) | 0.756 |
Sepsis; n (%) | 3 (15) | 5 (6) | 6 (13) | 1.000 |
Encephalitis/encephalopathy; n (%) | 5 (25) | 6 (7) | 1 (2) | 0.008 |
Co-infections; n (%) | 13 (65) | n.a. | 16 (34) | 0.030 |
Oseltamivir treatment; n (%) | 10 (50) | 51 (61) | 9 (19) | 0.017 |
Mechanical ventilation; n (%) | 10 (50) | 56 (65) | 22 (47) | 1.000 |
Death; n (%) | 2 (10) | 11 (12) | 5 (11) | 1.000 |
Influenza A(H1N1)pdm09; n (%) | 0 (0) | 89 (100) | 32 (68) | <0.001 |