Short Communication
Pandemic influenza A vs seasonal influenza A in hospitalized children in Athens F. Stripeli1, I. Logotheti1, V. M. Vraila1, C. Balta1, A. Patsioura2, V. Papaevangelou1, I. Papadatos2, A. Baka3, S. Tsiodras3, M. N. Tsolia1 1
Second Department of Pediatrics, 2Intensive Care Unit, University of Athens School of Medicine, P. and A. Kyriakou Children’s Hospital, 3Hellenic Center for Disease Control and Prevention, Athens, Greece Background: Data on pandemic H1N1 influenza (pH1N1) virus infection in hospitalised children are limited. Aims and Objectives: To examine the epidemiological and clinical characteristics of children hospitalised with pH1N1 at a large tertiary-care centre in Athens and compare them with those of children hospitalised with seasonal influenza A in previous years. Methods: All children (n5146) admitted with confirmed pH1N1 between October 2009 to February 2010 and January 2011 to May 2011 were included. Data on children §6 months of age (n5109) were compared with those of 138 children admitted with seasonal influenza A who were examined during two previous influenza seasons (2002–2003 and 2004–2005). Results: The age distribution was similar between seasonal and pandemic H1N1. Bronchial asthma was significantly more common in the seasonal influenza group but the clinical presentation was similar in the two groups, except that fever was more common in patients with pH1N1. Children admitted with seasonal influenza were more likely to develop acute otitis media. There were no significant differences between the two groups for severe outcomes (admission to the ICU, mechanical ventilation or death). Only one child with seasonal influenza (0.6%) and three with pH1N1 influenza (2%) required admission to the ICU. Mean length of hospitalisation was longer in the seasonal influenza group. Conclusion: Clinical manifestations were similar between pH1N1 and seasonal influenza, and the pandemic virus did not appear to cause more severe disease in hospitalised children.
Keywords: Children, Hospitalisation, Pandemic H1N1 influenza, Seasonal influenza
Introduction In April 2009, a novel influenza A (H1N1) virus of swine-origin, pandemic H1N1 (pH1N1), spread rapidly worldwide. Until then, two subtypes of seasonal influenza A (H3N2 and (H1N1), as well as influenza B viruses, had been circulating in humans for many years. While pH1N1 had been more common than influenza in previous seasons, it is not clear how much they differed in severity of illness. Several paediatric studies1–5 comparing pH1N1 with seasonal influenza had demonstrated greater morbidity and mortality with pH1N14,5 while others had revealed a mild course comparable with seasonal influenza.1–3 Nowadays, pH1N1 is considered to be a seasonal influenza subtype. However, in clinical and epidemiological practice it is helpful to understand the differences between these two types. This study aimed to describe the clinical characteristics of children hospitalised with pH1N1 and to compare them with a Correspondence to: F Stripeli, Second Department of Pediatrics, University of Athens School of Medicine, P. and A. Kyriakou Children’s Hospital, 115 27 Athens, Greece. Fax z30 210 777 4383; email: [email protected]
ß W. S. Maney & Son Ltd 2015 DOI 10.1179/2046905513Y.0000000111
cohort of children hospitalised with seasonal influenza A studied in previous years.
Methods The study was conducted during two influenza seasons at the P. & A. Kyriakou Children’s Hospital, one of the two largest paediatric centres in the Athens area, serving a population of almost 512,000 children ,14 years (2002 data, National Statistical Service). Children admitted with laboratory-confirmed pH1N1 infection between 1 November 2009 and 28 February 2010 and 1 January to 31 May 2011 were studied. During these seasons, all children with fever and/or respiratory symptoms were examined for pH1N1 infection with real-time reverse transcription-polymerase chain reaction (RT-PCR) in nasopharyngeal aspirates. Pandemic H1N1 influenza was the only circulating influenza strain during the 2009– 2010 season and the predominant (97.7%) circulating strain during the next one.6 A standardised form was completed for each patient. For comparison, a cohort of children aged 6 months to ,14 years presenting with fever and/or
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P50.048). Only four children with pH1N1 and none with seasonal influenza were vaccinated against seasonal influenza. The commonest clinical symptoms among children with pH1N1 were fever (98%), rhinitis (60%) and cough (61%). Excluding fever (in 99% pH1N1 patients vs 89% of seasonal influenza patients, P50.002), there were no significant clinical differences between the two cohorts. Mean duration of symptoms prior to hospitalisation for pH1N1 children was 3.4 days compared with 2.5 days for those with seasonal influenza (P50.01). The complications seen in patients were similar between the two cohorts. The only significant difference was acute otitis media (AOM) which was more common in the seasonal group (8% vs 22%, P50.003) (Table 1). No statistically significant differences in complications, demographic characteristics or symptoms of pH1N1were seen between the children ,6 months and the older ones. A significant proportion of patients with pH1N1 were treated with antibiotics, mainly for pneumonia (25%) and AOM (20%); this proportion was significantly higher in those with seasonal influenza (64% vs 47%, P50.005).On the other hand, 97% of pH1N1 patients received oseltamivir while none of the patients in the seasonal cohort received antivirals. Mean duration of hospital stay for patients with pH1N1 was significantly shorter (3.2 vs 4.5 days, P50.01).
any respiratory symptoms and hospitalised with influenza A during two seasonal outbreaks (2002– 2003, 2004–2005) from a previous study was used.7 Nasopharyngeal aspirates from these patients were tested by a multiplex RT-PCR assay. Before admission, the attending physician was unaware of the viral diagnosis for both cohorts. Informed consent was obtained from patients’ parents.
Statistical analysis Data from the two cohorts were compared by means of the x2 test and Wilcoxon rank sum test, as appropriate, using SPSS (SPSS, Chicago, IL, USA).
Results Altogether, 146 children were hospitalised with confirmed pH1N1 infection and 37 of them (25%) were #6 months. The duration of the pH1N1 season each year was 17 weeks and the month of peak activity varied between December and February. The cohort with seasonal influenza A included 138 patients §6 months. Influenza A subtype H3N2 was the predominant circulating serotype (106/138, 77%) whereas subtype H1N1 was detected in 32/138 (23%) patients. Table 1 summarises the demographic characteristics of the two cohorts. Seventeen percent of pH1N1 children had an underlying condition which is similar to the proportion of patients with seasonal influenza (23%, P50.324). Bronchial asthma was commoner among children with seasonal influenza (19% vs 7%,
Table 1 General characteristics and complications of children hospitalized with seasonal or pandemic influenza Pandemic H1N1 n5146 Characteristics M/F Mean (SD) age, mths Greek nationality (%) Underlying illness: Bronchial asthma Other chronic illness* Mean (SD) duration of symptoms prior to hospitalisation, days Mean (SD) duration of hospitalisation, days Complications Acute otitis media Sinusitis Croup Bronchial asthma Pneumonia Bronchiolitis Encephalitis Bacteraemia{ Febrile seizures ICU admissions
Pandemic H1N1 (,6 mths) n537
Pandemic H1N1 (§6 mths) n5109
Seasonal influenza (§6 mths) n5138
P{
1.147 43.9 (47.9) 102 (70)
0.947 2.8 (1.1) 21 (57)
1.224 58 (48.4) 81 (74)
1.379 52.5 (42.9) 97 (70)
0.65 0.34 0.09
8 (5) 18 (12) 3.5 (2.4)
7 (19) 3.6 (2.6)
8 (7) 11 (10) 3.4 (2.3)
26 (19) 6 (4) 2.5 (3.0)
0.05 0.07 0.01
3.8 (7.9)
5.8 (14.4)
3.2 (2.2)
14 (10) 0 3 (2) 6 (4) 17 (12) 7 (5) 2 (1) 1/108 (1) 17 (12) 3 (2)
5 0 0 0 1 4 0 0 1 1
(14)
9 (8) 0 3 (3) 6 (6) 16 (15) 3 (3) 2 (2) 1/108 (1) 16 (15) 2 (2)
(3) (11)
(3) (3)
4.45 (4.9)
31 (22) 3 (2) 6 (4) 14 (9) 16 (10) 10 (7) 1 (0.7) 4/71 (6) 25 (18) 1 (0.7)
0.01
0.003 0.12 0.63 0.33 0.24 0.12 0.43 0.06 0.47 0.43
* Chronic illness in the seasonal cohort: congenital heart disease (1), seizures (3), others (2); chronic illness in the pandemic cohort: congenital heart disease (4), bronchopulmonary dysplasia (2), seizures (4), others (8); { comparison of children §6 months of age with pandemic vs seasonal influenza; { denominator indicates the number of patients for whom blood cultures results were recorded. Comparison between children §6 months and ,6 months of age with pandemic influenza showed no statistically significant difference. 1st pandemic season: 1 November 2009 – 28 February 2010; 2nd pandemic season: 1 January – 30 May 2011.
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Analysis of the two pandemic seasons (2009–10 and 2010–2011) compared with the second season found that the mean (SD) age of the affected patients was higher in the first season [64.5 (6.0) months] than in the second season [50 (7) months], but the difference was not statistically significant. Similarly, separate comparison of the two pandemic seasons with the seasonal one demonstrated no differences in severity of the disease (data not shown). Three children (2%) in the H1N1 cohort required admission to the ICU. In addition, another four were referred to our ICU from other hospitals in the Athens area. The characteristics of ICU patients are shown in Table 2. Only one of the seven patients (14%) died. Only one of the 138 (0.7%) patients with seasonal influenza required admission to the ICU and none died (Table 2).
pH1N1 vs seasonal influenza
to seasonal influenza with regard to clinical characteristics, complications and the requirement for intensive care. In children §6 months, the mean age distribution was similar in the two groups, in contrast with previous studies which reported that children with pandemic influenza were significantly older.8,9 The largest number hospitalised was in children ,6 months, as in previous reports.10 Similar to other reports,1,3,5 the most common presenting clinical manifestations in children with pH1N1 were fever and cough. Asthma was the most common underlying illness in both cohorts, but it was considerably more prevalent in the seasonal influenza group. This is in contrast with most previous studies which reported higher rates of asthma in children with pH1N1 children, with percentages up to 50%.3,4 However, in a study in Argentina, only 6% of children hospitalised with pH1N1 had a history of asthma.11 Four of seven children in the ICU had an underlying illness and three of them a neurological disorder, which has been shown to be an important risk factor for admission to an ICU.4,12 Antibiotic administration was more common in children hospitalised with seasonal influenza, probably because of AOM. In addition, the results of PCR were available within 24 hours of admission during the pH1N1 season whereas in previous years they
Discussion To the best of our knowledge, this is one of the few studies comparing the characteristics of pH1N1 disease with those of seasonal influenza A in hospitalised children in Europe, and the only one conducted in a country in southern European. Conclusions of previous studies have been controversial since pandemic influenza seemed to present in various forms from mild to more severe. The main finding of the current study is that disease caused by pH1N1 in the paediatric population was comparable
Table 2 Summary of clinical findings in children with seasonal and pandemic H1N1 who required ICU admission
Influenza, Patients age, gender
Known co-morbidity
1
2009–2010 pH1N1, 7.5 y, F None
2*
pH1N1, 8 y, F
3*
pH1N1, 1 y, M
4*
pH1N1, 11 y, M None
5*
pH1N1, 9 y, M
6
2010–2011 pH1N1, 4 mths, F
7
pH1N1, 3 y, M
8
2002–2003 Seasonal, 6 y, F
Blood or other sterile fluid cultures
Presentation
Duration of ICU hospitalisation, days Progress
Respiratory distress, Negative pneumonia
5
None
Vomiting, diarrhoea
Negative
8
Epilepsy, neurodevelopental delay
Respiratory failure
Pseudomonas 23 aeruginosa in urine culture
Epilepsy
Respiratory distress, Negative pneumonia Status epilepticus Negative
Congenital nephrotic Febrile seizures Negative syndrome, congenital heart disease Menkes syndrome, Respiratory distress Negative tracheostomy, gastrostomy None
Respiratory distress, Negative lethargy, coma, 3rd nerve palsy
4 2
Pneumothorax, no ventilatory support, oxygen by nasal cannula Ventilatory support for 3 days Worsening ARDS, pneumothorax, prolonged ventilation, pulmonary haemorrhage, septic shock, death Oxygen by nasal cannula Ventilatory support for 4 hrs
2
No respiratory support
3
Ventilatory support for 1 day, hypovolaemic shock
10
Acute necrotising encephalopathy, i.v. corticosteroids, recovery with sequelae
* These patients were referred to our ICU from paediatric departments in other hospitals; ARDS, acute respiratory distress syndrome.
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seasonal influenza were available and therefore valid comparisons could be made. In conclusion, the findings indicate that clinical manifestations were similar in pandemic and seasonal influenza and that pH1N1 did not appear to cause more severe disease in hospitalised children.
were available only after patients had been discharged. The availability of viral diagnosis has been shown to be associated with lower use of antibiotics.13 Duration of hospitalisation was shorter among pH1N1 patients, probably owing to treatment with oseltamivir. Few cases required ICU admission and only one child died. Similarly, according to unpublished data collected by the Hellenic Centre for Disease Control and Prevention, a total of 38 children with pH1N1 (21 and 17 each year) required admission to the ICU in the whole country and eight of them (5 and 3 each year, respectively) died. Population-based estimates of ICU admissions and deaths for influenza were 1.26 and 0.3/ 100,000 children ,14 years during the 2009–2010 period and 1.02 and 0.18/100,000 children during the 2010–2011 period, respectively. The above findings accord with other studies.3,4,8 The mortality reported is similar to that previously reported for seasonal influenza in the USA, ranging from 0.2 to 0.8/ 100,000.14 On the other hand, several paediatric studies comparing the two groups have demonstrated that, compared with seasonal influenza, pH1N1 patients were more likely to develop severe disease or die.4,5 There are several limitations to this study. One is that selection procedures were slightly different in the two cohorts. Children in the seasonal group may have been recruited more extensively for the purposes of a research protocol while children in the pandemic group were tested as a part of routine care. However, although there is a possibility of bias, this is towards the milder seasonal influenza which further supports our conclusions. Another limitation is that this was a single-centre study, but nevertheless it was in one of the two largest children’s hospital in the Athens area which serves a large population. Finally, although antivirals were used routinely in the pH1N1 group, which possibly affected disease severity in the two groups, the mean duration of symptoms before admission was longer than 3 days in children with pH1N1 and therefore the use of drugs could have limited the antiviral effect on the disease. Despite the above limitations, the study’s great advantage is that prospectively collected data on cases of PCR-confirmed
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References 1 Heininger U, Baer G, Ryser AJ, Li Y. Comparative analysis of clinical characteristics of pandemic influenza A/H1N1 and seasonal influenza A infections in hospitalized children. Pediatr Infect Dis J. 2013;32:293–6. 2 Chiu SS, Chan KH, Wong WH, Chan EL, Peiris JS. Agematched comparison of children hospitalized for the 2009 pandemic H1N1 influenza with those hospitalized for seasonal H1N1 and H3N2. PLoS One. 2011;6:e21837. 3 Ostovar GA, Rubin LG, Rajan S, Sood SK, Kohn N. Comparison of the clinical features of children hospitalized with pandemic 2009 A:H1N1 and seasonal influenza. Clin Pediatr (Phila). 2011;50:348–54. 4 Bagdure D, Curtis DJ, Dobyns E, Glode´ MP, Dominguez SR. Hospitalized children with 2009 pandemic influenza A (H1N1): comparison to seasonal influenza and risk factors for admission to the ICU. PLoS One. 2010;5:e15173. 5 Herberg JA, Jones KD, Paulus S, Gormley S, Muir D, Cooper M, et al. Comparison of pandemic and seasonal influenza reveals higher mortality and increased prevalence of shock in children with severe h1n1/09 infection. Pediatr Infect Dis J. 2011;30:438–40. 6 Hellenic Center for Disease Control and Prevention. Surveillance Data for Flu in Greece 2010–2011. Available at: http://www.keelpno.gr/el-gr/.aspx. 7 Sakkou Z, Stripeli F, Papadopoulos NG, Critselis E, Georgiou V, Mavrikou M, et al. Impact of influenza infection on children’s hospital admissions during two seasons in Athens, Greece. Vaccine. 2011;29:1167–72. 8 Gordon A, Saborı´o S, Videa E, Lo´pez R, Kuan G, Balmaseda A, et al. Clinical attack rate and presentation of pandemic H1N1 influenza versus seasonal influenza A and B in a pediatric cohort in Nicaragua. Clin Infect Dis. 2010;50:1462–7. 9 Tang JW, Tambyah PA, Lai FY, Lee HK, Lee CK, Loh TP, et al. Differing symptom patterns in early pandemic vs seasonal influenza infections. Arch Intern Med. 2010;170:861–7. 10 Neuzil KM, Mellen BG, Wright PF, Mitchel EF Jr, Griffin MR. The effect of influenza on hospitalizations, outpatient visits, and courses of antibiotics in children. N Engl J Med. 2000;342:225–31. 11 Libster R, Bugna J, Coviello S, Hijano DR, Dunaiewsky M, Reynoso N, et al. Pediatric hospitalizations associated with 2009 pandemic influenza A (H1N1) in Argentina. N Engl J Med. 2010;362:45–55. 12 Peacock BL, Cox C, Jhung M, Finelli L, Moore C. Neurologic disorders among pediatric deaths associated with the 2009 pandemic influenza. Pediatrics. 2012;130:3390–96. 13 Low D. Reducing antibiotic use in influenza: challenges and rewards. Clin Microbiol Infect. 2008;14:298–306. 14 Thompson WW, Sahy DK, Weintraub E, Brammer L, Cox N, Anderson LJ, et al. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA. 2003;289:179–86.
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Pandemic influenza A vs seasonal influenza A in hospitalized children in Athens F. Stripeli1, I. Logotheti1, V. M. Vraila1, C. Balta1, A. Patsioura2, V. Papaevangelou1, I. Papadatos2, A. Baka3, S. Tsiodras3, M. N. Tsolia1 1
Second Department of Pediatrics, 2Intensive Care Unit, University of Athens School of Medicine, P. and A. Kyriakou Children’s Hospital, 3Hellenic Center for Disease Control and Prevention, Athens, Greece Background: Data on pandemic H1N1 influenza (pH1N1) virus infection in hospitalised children are limited. Aims and Objectives: To examine the epidemiological and clinical characteristics of children hospitalised with pH1N1 at a large tertiary-care centre in Athens and compare them with those of children hospitalised with seasonal influenza A in previous years. Methods: All children (n5146) admitted with confirmed pH1N1 between October 2009 to February 2010 and January 2011 to May 2011 were included. Data on children §6 months of age (n5109) were compared with those of 138 children admitted with seasonal influenza A who were examined during two previous influenza seasons (2002–2003 and 2004–2005). Results: The age distribution was similar between seasonal and pandemic H1N1. Bronchial asthma was significantly more common in the seasonal influenza group but the clinical presentation was similar in the two groups, except that fever was more common in patients with pH1N1. Children admitted with seasonal influenza were more likely to develop acute otitis media. There were no significant differences between the two groups for severe outcomes (admission to the ICU, mechanical ventilation or death). Only one child with seasonal influenza (0.6%) and three with pH1N1 influenza (2%) required admission to the ICU. Mean length of hospitalisation was longer in the seasonal influenza group. Conclusion: Clinical manifestations were similar between pH1N1 and seasonal influenza, and the pandemic virus did not appear to cause more severe disease in hospitalised children.
Keywords: Children, Hospitalisation, Pandemic H1N1 influenza, Seasonal influenza
Introduction In April 2009, a novel influenza A (H1N1) virus of swine-origin, pandemic H1N1 (pH1N1), spread rapidly worldwide. Until then, two subtypes of seasonal influenza A (H3N2 and (H1N1), as well as influenza B viruses, had been circulating in humans for many years. While pH1N1 had been more common than influenza in previous seasons, it is not clear how much they differed in severity of illness. Several paediatric studies1–5 comparing pH1N1 with seasonal influenza had demonstrated greater morbidity and mortality with pH1N14,5 while others had revealed a mild course comparable with seasonal influenza.1–3 Nowadays, pH1N1 is considered to be a seasonal influenza subtype. However, in clinical and epidemiological practice it is helpful to understand the differences between these two types. This study aimed to describe the clinical characteristics of children hospitalised with pH1N1 and to compare them with a Correspondence to: F Stripeli, Second Department of Pediatrics, University of Athens School of Medicine, P. and A. Kyriakou Children’s Hospital, 115 27 Athens, Greece. Fax z30 210 777 4383; email: [email protected]
ß W. S. Maney & Son Ltd 2015 DOI 10.1179/2046905513Y.0000000111
cohort of children hospitalised with seasonal influenza A studied in previous years.
Methods The study was conducted during two influenza seasons at the P. & A. Kyriakou Children’s Hospital, one of the two largest paediatric centres in the Athens area, serving a population of almost 512,000 children ,14 years (2002 data, National Statistical Service). Children admitted with laboratory-confirmed pH1N1 infection between 1 November 2009 and 28 February 2010 and 1 January to 31 May 2011 were studied. During these seasons, all children with fever and/or respiratory symptoms were examined for pH1N1 infection with real-time reverse transcription-polymerase chain reaction (RT-PCR) in nasopharyngeal aspirates. Pandemic H1N1 influenza was the only circulating influenza strain during the 2009– 2010 season and the predominant (97.7%) circulating strain during the next one.6 A standardised form was completed for each patient. For comparison, a cohort of children aged 6 months to ,14 years presenting with fever and/or
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P50.048). Only four children with pH1N1 and none with seasonal influenza were vaccinated against seasonal influenza. The commonest clinical symptoms among children with pH1N1 were fever (98%), rhinitis (60%) and cough (61%). Excluding fever (in 99% pH1N1 patients vs 89% of seasonal influenza patients, P50.002), there were no significant clinical differences between the two cohorts. Mean duration of symptoms prior to hospitalisation for pH1N1 children was 3.4 days compared with 2.5 days for those with seasonal influenza (P50.01). The complications seen in patients were similar between the two cohorts. The only significant difference was acute otitis media (AOM) which was more common in the seasonal group (8% vs 22%, P50.003) (Table 1). No statistically significant differences in complications, demographic characteristics or symptoms of pH1N1were seen between the children ,6 months and the older ones. A significant proportion of patients with pH1N1 were treated with antibiotics, mainly for pneumonia (25%) and AOM (20%); this proportion was significantly higher in those with seasonal influenza (64% vs 47%, P50.005).On the other hand, 97% of pH1N1 patients received oseltamivir while none of the patients in the seasonal cohort received antivirals. Mean duration of hospital stay for patients with pH1N1 was significantly shorter (3.2 vs 4.5 days, P50.01).
any respiratory symptoms and hospitalised with influenza A during two seasonal outbreaks (2002– 2003, 2004–2005) from a previous study was used.7 Nasopharyngeal aspirates from these patients were tested by a multiplex RT-PCR assay. Before admission, the attending physician was unaware of the viral diagnosis for both cohorts. Informed consent was obtained from patients’ parents.
Statistical analysis Data from the two cohorts were compared by means of the x2 test and Wilcoxon rank sum test, as appropriate, using SPSS (SPSS, Chicago, IL, USA).
Results Altogether, 146 children were hospitalised with confirmed pH1N1 infection and 37 of them (25%) were #6 months. The duration of the pH1N1 season each year was 17 weeks and the month of peak activity varied between December and February. The cohort with seasonal influenza A included 138 patients §6 months. Influenza A subtype H3N2 was the predominant circulating serotype (106/138, 77%) whereas subtype H1N1 was detected in 32/138 (23%) patients. Table 1 summarises the demographic characteristics of the two cohorts. Seventeen percent of pH1N1 children had an underlying condition which is similar to the proportion of patients with seasonal influenza (23%, P50.324). Bronchial asthma was commoner among children with seasonal influenza (19% vs 7%,
Table 1 General characteristics and complications of children hospitalized with seasonal or pandemic influenza Pandemic H1N1 n5146 Characteristics M/F Mean (SD) age, mths Greek nationality (%) Underlying illness: Bronchial asthma Other chronic illness* Mean (SD) duration of symptoms prior to hospitalisation, days Mean (SD) duration of hospitalisation, days Complications Acute otitis media Sinusitis Croup Bronchial asthma Pneumonia Bronchiolitis Encephalitis Bacteraemia{ Febrile seizures ICU admissions
Pandemic H1N1 (,6 mths) n537
Pandemic H1N1 (§6 mths) n5109
Seasonal influenza (§6 mths) n5138
P{
1.147 43.9 (47.9) 102 (70)
0.947 2.8 (1.1) 21 (57)
1.224 58 (48.4) 81 (74)
1.379 52.5 (42.9) 97 (70)
0.65 0.34 0.09
8 (5) 18 (12) 3.5 (2.4)
7 (19) 3.6 (2.6)
8 (7) 11 (10) 3.4 (2.3)
26 (19) 6 (4) 2.5 (3.0)
0.05 0.07 0.01
3.8 (7.9)
5.8 (14.4)
3.2 (2.2)
14 (10) 0 3 (2) 6 (4) 17 (12) 7 (5) 2 (1) 1/108 (1) 17 (12) 3 (2)
5 0 0 0 1 4 0 0 1 1
(14)
9 (8) 0 3 (3) 6 (6) 16 (15) 3 (3) 2 (2) 1/108 (1) 16 (15) 2 (2)
(3) (11)
(3) (3)
4.45 (4.9)
31 (22) 3 (2) 6 (4) 14 (9) 16 (10) 10 (7) 1 (0.7) 4/71 (6) 25 (18) 1 (0.7)
0.01
0.003 0.12 0.63 0.33 0.24 0.12 0.43 0.06 0.47 0.43
* Chronic illness in the seasonal cohort: congenital heart disease (1), seizures (3), others (2); chronic illness in the pandemic cohort: congenital heart disease (4), bronchopulmonary dysplasia (2), seizures (4), others (8); { comparison of children §6 months of age with pandemic vs seasonal influenza; { denominator indicates the number of patients for whom blood cultures results were recorded. Comparison between children §6 months and ,6 months of age with pandemic influenza showed no statistically significant difference. 1st pandemic season: 1 November 2009 – 28 February 2010; 2nd pandemic season: 1 January – 30 May 2011.
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Analysis of the two pandemic seasons (2009–10 and 2010–2011) compared with the second season found that the mean (SD) age of the affected patients was higher in the first season [64.5 (6.0) months] than in the second season [50 (7) months], but the difference was not statistically significant. Similarly, separate comparison of the two pandemic seasons with the seasonal one demonstrated no differences in severity of the disease (data not shown). Three children (2%) in the H1N1 cohort required admission to the ICU. In addition, another four were referred to our ICU from other hospitals in the Athens area. The characteristics of ICU patients are shown in Table 2. Only one of the seven patients (14%) died. Only one of the 138 (0.7%) patients with seasonal influenza required admission to the ICU and none died (Table 2).
pH1N1 vs seasonal influenza
to seasonal influenza with regard to clinical characteristics, complications and the requirement for intensive care. In children §6 months, the mean age distribution was similar in the two groups, in contrast with previous studies which reported that children with pandemic influenza were significantly older.8,9 The largest number hospitalised was in children ,6 months, as in previous reports.10 Similar to other reports,1,3,5 the most common presenting clinical manifestations in children with pH1N1 were fever and cough. Asthma was the most common underlying illness in both cohorts, but it was considerably more prevalent in the seasonal influenza group. This is in contrast with most previous studies which reported higher rates of asthma in children with pH1N1 children, with percentages up to 50%.3,4 However, in a study in Argentina, only 6% of children hospitalised with pH1N1 had a history of asthma.11 Four of seven children in the ICU had an underlying illness and three of them a neurological disorder, which has been shown to be an important risk factor for admission to an ICU.4,12 Antibiotic administration was more common in children hospitalised with seasonal influenza, probably because of AOM. In addition, the results of PCR were available within 24 hours of admission during the pH1N1 season whereas in previous years they
Discussion To the best of our knowledge, this is one of the few studies comparing the characteristics of pH1N1 disease with those of seasonal influenza A in hospitalised children in Europe, and the only one conducted in a country in southern European. Conclusions of previous studies have been controversial since pandemic influenza seemed to present in various forms from mild to more severe. The main finding of the current study is that disease caused by pH1N1 in the paediatric population was comparable
Table 2 Summary of clinical findings in children with seasonal and pandemic H1N1 who required ICU admission
Influenza, Patients age, gender
Known co-morbidity
1
2009–2010 pH1N1, 7.5 y, F None
2*
pH1N1, 8 y, F
3*
pH1N1, 1 y, M
4*
pH1N1, 11 y, M None
5*
pH1N1, 9 y, M
6
2010–2011 pH1N1, 4 mths, F
7
pH1N1, 3 y, M
8
2002–2003 Seasonal, 6 y, F
Blood or other sterile fluid cultures
Presentation
Duration of ICU hospitalisation, days Progress
Respiratory distress, Negative pneumonia
5
None
Vomiting, diarrhoea
Negative
8
Epilepsy, neurodevelopental delay
Respiratory failure
Pseudomonas 23 aeruginosa in urine culture
Epilepsy
Respiratory distress, Negative pneumonia Status epilepticus Negative
Congenital nephrotic Febrile seizures Negative syndrome, congenital heart disease Menkes syndrome, Respiratory distress Negative tracheostomy, gastrostomy None
Respiratory distress, Negative lethargy, coma, 3rd nerve palsy
4 2
Pneumothorax, no ventilatory support, oxygen by nasal cannula Ventilatory support for 3 days Worsening ARDS, pneumothorax, prolonged ventilation, pulmonary haemorrhage, septic shock, death Oxygen by nasal cannula Ventilatory support for 4 hrs
2
No respiratory support
3
Ventilatory support for 1 day, hypovolaemic shock
10
Acute necrotising encephalopathy, i.v. corticosteroids, recovery with sequelae
* These patients were referred to our ICU from paediatric departments in other hospitals; ARDS, acute respiratory distress syndrome.
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pH1N1 vs seasonal influenza
seasonal influenza were available and therefore valid comparisons could be made. In conclusion, the findings indicate that clinical manifestations were similar in pandemic and seasonal influenza and that pH1N1 did not appear to cause more severe disease in hospitalised children.
were available only after patients had been discharged. The availability of viral diagnosis has been shown to be associated with lower use of antibiotics.13 Duration of hospitalisation was shorter among pH1N1 patients, probably owing to treatment with oseltamivir. Few cases required ICU admission and only one child died. Similarly, according to unpublished data collected by the Hellenic Centre for Disease Control and Prevention, a total of 38 children with pH1N1 (21 and 17 each year) required admission to the ICU in the whole country and eight of them (5 and 3 each year, respectively) died. Population-based estimates of ICU admissions and deaths for influenza were 1.26 and 0.3/ 100,000 children ,14 years during the 2009–2010 period and 1.02 and 0.18/100,000 children during the 2010–2011 period, respectively. The above findings accord with other studies.3,4,8 The mortality reported is similar to that previously reported for seasonal influenza in the USA, ranging from 0.2 to 0.8/ 100,000.14 On the other hand, several paediatric studies comparing the two groups have demonstrated that, compared with seasonal influenza, pH1N1 patients were more likely to develop severe disease or die.4,5 There are several limitations to this study. One is that selection procedures were slightly different in the two cohorts. Children in the seasonal group may have been recruited more extensively for the purposes of a research protocol while children in the pandemic group were tested as a part of routine care. However, although there is a possibility of bias, this is towards the milder seasonal influenza which further supports our conclusions. Another limitation is that this was a single-centre study, but nevertheless it was in one of the two largest children’s hospital in the Athens area which serves a large population. Finally, although antivirals were used routinely in the pH1N1 group, which possibly affected disease severity in the two groups, the mean duration of symptoms before admission was longer than 3 days in children with pH1N1 and therefore the use of drugs could have limited the antiviral effect on the disease. Despite the above limitations, the study’s great advantage is that prospectively collected data on cases of PCR-confirmed
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References 1 Heininger U, Baer G, Ryser AJ, Li Y. Comparative analysis of clinical characteristics of pandemic influenza A/H1N1 and seasonal influenza A infections in hospitalized children. Pediatr Infect Dis J. 2013;32:293–6. 2 Chiu SS, Chan KH, Wong WH, Chan EL, Peiris JS. Agematched comparison of children hospitalized for the 2009 pandemic H1N1 influenza with those hospitalized for seasonal H1N1 and H3N2. PLoS One. 2011;6:e21837. 3 Ostovar GA, Rubin LG, Rajan S, Sood SK, Kohn N. Comparison of the clinical features of children hospitalized with pandemic 2009 A:H1N1 and seasonal influenza. Clin Pediatr (Phila). 2011;50:348–54. 4 Bagdure D, Curtis DJ, Dobyns E, Glode´ MP, Dominguez SR. Hospitalized children with 2009 pandemic influenza A (H1N1): comparison to seasonal influenza and risk factors for admission to the ICU. PLoS One. 2010;5:e15173. 5 Herberg JA, Jones KD, Paulus S, Gormley S, Muir D, Cooper M, et al. Comparison of pandemic and seasonal influenza reveals higher mortality and increased prevalence of shock in children with severe h1n1/09 infection. Pediatr Infect Dis J. 2011;30:438–40. 6 Hellenic Center for Disease Control and Prevention. Surveillance Data for Flu in Greece 2010–2011. Available at: http://www.keelpno.gr/el-gr/.aspx. 7 Sakkou Z, Stripeli F, Papadopoulos NG, Critselis E, Georgiou V, Mavrikou M, et al. Impact of influenza infection on children’s hospital admissions during two seasons in Athens, Greece. Vaccine. 2011;29:1167–72. 8 Gordon A, Saborı´o S, Videa E, Lo´pez R, Kuan G, Balmaseda A, et al. Clinical attack rate and presentation of pandemic H1N1 influenza versus seasonal influenza A and B in a pediatric cohort in Nicaragua. Clin Infect Dis. 2010;50:1462–7. 9 Tang JW, Tambyah PA, Lai FY, Lee HK, Lee CK, Loh TP, et al. Differing symptom patterns in early pandemic vs seasonal influenza infections. Arch Intern Med. 2010;170:861–7. 10 Neuzil KM, Mellen BG, Wright PF, Mitchel EF Jr, Griffin MR. The effect of influenza on hospitalizations, outpatient visits, and courses of antibiotics in children. N Engl J Med. 2000;342:225–31. 11 Libster R, Bugna J, Coviello S, Hijano DR, Dunaiewsky M, Reynoso N, et al. Pediatric hospitalizations associated with 2009 pandemic influenza A (H1N1) in Argentina. N Engl J Med. 2010;362:45–55. 12 Peacock BL, Cox C, Jhung M, Finelli L, Moore C. Neurologic disorders among pediatric deaths associated with the 2009 pandemic influenza. Pediatrics. 2012;130:3390–96. 13 Low D. Reducing antibiotic use in influenza: challenges and rewards. Clin Microbiol Infect. 2008;14:298–306. 14 Thompson WW, Sahy DK, Weintraub E, Brammer L, Cox N, Anderson LJ, et al. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA. 2003;289:179–86.
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