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Clinical differences of influenza subspecies among hospitalized children.

Abstract

Aim: Clinical findings, mortality, and morbidity rates differ among influenza subspecies. Awareness of these differences will lead physicians to choose the proper diagnostic and therapeutic strategies and to foresee possible complications. The aim of this study was to evaluate the clinical differences of influenza subspecies among hospitalized children.

Material and Methods: Hospitalized children with proven influenza infection by polymerase chain reaction on nasopharyngeal swab specimens in our clinic, between December 2013 and March 2016, were enrolled. These children were divided into 3 groups as Influenza A/H1N1 (n=42), Influenza A/H3N2 (n=23), and Influenza B (n=35).

Results: The median age of the children was 51.5 months (range, 3-204 months). The most common presenting symptoms were fever (n=83), cough (n=58), and difficulty in breathing (n=25). The most common non-respiratory findings were lymphadenopathy (n=18) and gastrointestinal system involvement (n=17). Sixty-two percent of the patients (n=62) had chronic diseases. H1N1 and H3N2 were significantly more common among patients with chronic neurologic disorders and renal failure, respectively. Leukopenia (n=32) and thrombocytopenia (n=22) were the most common pathologic laboratory findings. Neutropenia, elevated CRP levels, and antibiotic use were significantly more common among patients with H1N1 infection. Seven patients were transferred to the intensive care unit with diagnoses of acute respiratory distress syndrome (n=4), encephalitis (n=2), and bronchiolitis (n=1). Two patients with chronic diseases and H1N1 infection died secondary to acute respiratory distress syndrome.

Conclusions: Influenza A/H1N1 infection represented more severe clinical disease. (Turk Pediatri Ars 2017; 52: 15-22)

Keywords: Influenza, influenza A/H1N1, influenza A/H3N2 and Influenza B

Introduction

Influenza is a significant acute respiratory tract disease that affects 5-20% of the world population and is characterized by high morbidity and mortality, especially in high-risk groups (1). In the United States of America (USA), approximately 250,000-500,000 cases of seasonal influenza are reported each year and about 200,000 of these patients require hospitalization (2). In children and patients with chronic disease, the attack rate may reach up to 40% during outbreaks (3). The agents that lead to morbidity in humans are mostly influenza A and B (4). However, influenza A is mostly responsible for seasonal epidemics and worldwide pandemics.

When the statistics of pandemic influenza in years were examined, it was observed that the clinical pictures, and morbidity and mortality rates showed variance between influenza subtypes (5-7). In the years during which the H3N2 type was generally predominant, the rates of pneumonia and mortality rates were reported higher compared with H1N1 epidemics (8). Studies reported that central nervous system (CNS) findings were mostly related with influenza A and myositis and digestive system symptoms were observed more frequently in influenza B infections (9-11). Knowledge of these clinical differences will be helpful for physicians to predict complications that may occur in relation with influenza. In this study, we aimed to compare the clinical pictures and complications of influenza subtypes by examining the clinical and laboratory findings of patients who presented to our clinic with respiratory tract infection findings, hospitalized, and were found to have influenza.

Material and Methods

This study is a retrospective archive screening study. Using polymerase chain reaction (PCR), influenza and non-influenza respiratory viruses were studied in nasopharyngeal swab samples of 3263 patients who presented to our Pediatric Emergency Outpatient Clinic between December 2013 and March 2016 and followed up in the emergency room. Influenza virus was found in 161 of these subjects (4.9%) and non-influenza respiratory tract virus was found in 1314 (40.3%).

One hundred patients who were found to have influenza virus in the viral respiratory tract panel examination and hospitalized after a 24-hour follow-up period in the emergency room because of different causes were included in this study. The age, sex, presentation symptoms, physical examination findings, laboratory results [complete blood count, C-reactive protein (CRP), procalcitonin (PCT), viral PCR examination result on respiratory tract swab sample], presence of antiviral drug use, hospitalization status, hospitalization period, and complications were recorded by retrospectively examining the patient files, computer records, and discharge summary epicrisis reports. The subjects were divided into three groups as influenza A/H1N1, influenza A/H3N2, and influenza B.

Nasopharyngeal swab samples were obtained by rotating swabs 360[degrees] after entering into both nostrils and proceeding up to the naspharyngeal area in order to detect viruses leading to respiratory tract disease. After the swabs were closed in covered boxes containing transport medium (Virocult, Medical Wire & Equipment, UK), full nucleic acid extraction was performed using an EZ1 virus mini kit V2.0 (Catalog number: 955134, Qiagen, Germany) in the virology laboratory. An FTD Respiratory Pathogens 21 kit (Fast-track diagnostics Ltd. Malta), which has the ability to differentiate influenza A (H3N2 and H1N1) and influenza B, was used with real-time and multiplex PCR to detect respiratory tract pathogens in the Rotor-Gene Q platform (Qiagen, Germany).

Statistical analysis

Statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS Inc.; Chicago, IL, USA) version 21 package program. Normality was tested using the Shapiro- Wilk and Kolmogorov-Smirnov tests. Data were given as median, minimum-maximum, frequency and percentage. Measurable data that did not show normal distribution were compared using the Kruskal-Wallis test in independent groups. Categorical data were evaluated using the Chi-square test and Fisher's exact test. A p value of <0.05 was considered significant.

Ethics committee approval was obtained from Istanbul University Faculty of Medicine Ethics Committee for this study (2016: 1479).

Results

One hundred patients with a median age of 5.5 months (range, 3-204 months) the majority of whom were male (65%) were included in the study. The clinical and laboratory characteristics of the patients are shown in Table 1. When examined by age group, eight patients were in the 0-6 years age group, 18 patients were in the 6 months-12 years age group, 35 patients were in the 2-5 years age group, and 39 patients were aged more than five years. Although patient distribution and influenza subtypes showed difference by years, congestion of patients was generally observed most frequently between the months of January and March (Figure 1).

Eighty-three percent of the patients presented with fever. Other presenting symptoms included cough (58%), respiratory distress (25%), sore throat (18%), rhinorrhea (18%), vomiting-diarrhea (17%), hoarse voice (8%), headache (6%), seizure (6%), redness in the eyes (4%), and eruption (4%). Two of the patients who had seizure were healthy previously and had a positive history of febrile convulsion. The remaining four patients had epilepsy. Although presentation because of fever and seizure was observed more frequently in patients who were found to have H1N1 infection, the difference was not statistically significant.

The median time period of symptoms was found as three days (1-13). There was no difference between the different influenza subtypes in terms of the time period of symptoms before presentation. The most common finding on physical examination was oropharyngeal hyperemia with a rate of 63%. Pathologic respiratory sounds were present in 29% of patients, postnasal discharge was present in 28%, and tachypnea was present in 20%. The most common non-respiratory findings included enlarged lymph nodes in the cervical region (18%) and gastrointestinal findings (17%). Influenza-related CNS involvement was present in seven patients who were healthy previously [encephalopathy (3%), febrile convulsion (2%), Guillain-Barre syndrome (2%)]. Other findings included myositis (6%), conjunctivitis (4%), eruption (4%), hepatitis (2%), and myocarditis (1%). Although enlarged lymph nodes and nervous system involvement were observed with a higher frequency in patients who were positive for H1N1, the difference was not statistically significant. All patients with neurologic symptoms who were healthy before the influenza infection recovered without sequela.

[FIGURE 1 OMITTED]

Sixty-two percent of the patients had chronic diseases including most commonly neurologic diseases [epilepsy (7%), cerebral palsy (5%), neuromotor retardation (4%)], metabolic disease (14%), asthma (10%), chronic renal failure (6%), chronic liver disease (5%), congenital heart disease (4%), malignancy (3%), diabetes mellitus type 1 (1%), familial Mediteranean fever (1%), juvenile idiopathic arthritis (1%), and congenital neutropenia (1%). Seventy percent (70.2%) of the patients who had chronic disease were aged more than two years. H1N1 positivity was found with a significantly higher frequency in patients who had chronic neurologic disease and H3N2 positivity was found with a significantly higher frequency in patients with chronic renal failure (p=0.007 and p=0.032, respectively) (Table 2).

When evaluated in terms of laboratory findings, the most common pathologic findings at the time of presentation were leukopenia (32%) and thrombocytopenia (22%). Anemia was present in 17% of patients, neutropenia in 16%, and leukocytosis was present in 7%. Neutropenia was statistically significantly more frequent in patients with H1N1 positivity compared with the other patients (p=0.021) (Table 2). At the time of presentation, the median CRP value was found as 6.9 mg/L (range, 0.1-86.7 mg/L) and the median PCT value was 0.33 ng/mL (range, 0.01-2.9 ng/mL). In patients who were found to have H1N1 infection, the CRP level at the time of presentation was statistically significantly higher compared with the other patients (p=0.026) (Table 2). Postero-anterior lung radiography revealed pathologic findings in 44% of patients including paracardiac infiltration (32%), increased aeration (7%), ground glass appearance (4%), and pleural effusion (1%). Although pathologic findings were observed with a higher frequency on postero-anterior lung radiographs in the H1N1 group, the difference was not statistically significant.

Oseltamivir treatment was given to 45 patients for a median period of 5 days (5-14 days). Antibiotic use was found in 54 patients with a median period of 7 days (3-21). Antibiotic use was found with a significantly higher frequency in patients with H1N1 positivity compared with the other patients (p=0.005) (Table 2). The median disease period was found as 10 days (range, 5-28 days) in all patients. During the follow-up period, seven patients were hospitalized in the intensive care unit (ICU) [acute respiratory distress syndrome (ARDS, n=4), encephalitis (n=2), bronchiolitis (n=1)] (Table 3). Although the frequency of H1N1 (n=4) was high among patients who were hospitalized in the neonatal intensive care unit, the difference was not statistically significiant. Two patients, one with glutaric aciduria type 1 and one with chronic liver disease died of ARDS. H1N1 was positive in both patients.

Discussion

Influenza virus, which is a significant agent of respiratory tract infections, frequently leads to an acute and self-limiting disease in previously healthy children; it may cause high morbidity and mortality in children with chronic disease and in children aged below 2 years. In the 2003-2008 National Survaillance Assessment of the USA, it was reported that hospitalization because of influenza in childhood occurred most commonly below the age of two years and especially below the age of six months (9). The Centers for Disease Control and Prevention reported that children below the age of two years carried risk in terms of the development of complications and recommended that they should be vaccinated (12). In our study, the majority of patients who were hospitalized because of influenza were above the age of 2 years in contrast to the literature information. This finding seemed to be related with the fact that our clinic is a tertiary healthcare institution and has a high rate of chronic disease in the group aged >2 years. It is known that influenza A virus causes hospital presentation with a higher frequency, especially in children aged below one year (9, 13). Similarly, the ages of patients who were found to have influenza A infection were younger in our study, but the difference was not statistically significant.

The clinical findings of influenza virus are variable and frequently characterized by cough and sore throat accompanying suddenly developing fever, headache, and myalgia. Higher fever, febrile convulsion, enlarged lymph nodes, a higher rate of gastrointestinal involvement and a lower rate of respiratory findings may be observed in children because they have not been exposed to the virus before (14). This causes difficulty in the diagnosis and increases unnecessary antibiotic use (14). In a study of 353 pediatric patients with confirmed influenza infection, fever was reported with a rate of 95%, cough as 77%, and coryza was reported as 78% (15). In the same study, headache (26%) and myalgia (7%) were reported more rarely. Gastrointestinal symptoms including vomiting, diarrhea, and abdominal pain may be observed with varying frequencies during the course of influenza infection. According to a meta-analysis compiled by Minodier et al. (16), this rate ranged between 2.8% and 30.9% for influenza A infection. There are also studies stating that abdominal pain and gastrointestinal symptoms are observed more frequently during influenza B infection (17). Although the pathophysiology of this state has not been elucidated fully, detection of viral RNA in stool suggests direct invasion by the virus and there are also publications proposing that the immune reaction created by growing viruses in lung mucosa might lead to gastointestinal findings (18, 19). In our study, gastrointestinal symptoms including vomiting-diarrhea were found with a rate of 17%, and no significant difference was found between H1N1, H3N2, and influenza B subtypes in terms of the frequency of gastrointestinal symptoms.

Similarly, there are studies showing that myositis is observed more frequently in influenza B and H3N2 infections (9, 11). In another study in which 10 patients with acute benign childhood myositis in our clinic were examined, influenza B was detected in six patients and influenza A was detected in four (20). In our study, patients with influenza who were hospitalized were examined and myositis was found with rate of 6%; no difference was found in terms of influenza subtypes.

One of the most important non-respiratory findings of influenza is CNS involvement. Different neurologic findings, mainly including febrile convulsion, encephalopathy, encephalitis, aseptic meningitis, Guillain-Barre syndrome, extrapyramidal system involvement, and myelitis may be observed (21). In a study of 842 children with laboratory-confirmed influenza infection, the frequency of neurologic complications was reported as 4/100,000 person-year (21). However, it has been reported that the frequency of neurologic complications is increased in patients with chronic neurologic diseases. In a study in which the clinical findings in influenza A and B infections were compared, CNS involvement was found significantly high in the influenza A group (9). In our study, H1N1 positivity was more frequent in patients who were previously healthy and who had CNS involvement, but a statistically significant difference was not found when compared with the other influenza subtypes. In the group with chronic neurologic disease, H1N1 positivity was found more frequently. When examined in terms of other chronic diseases, it was found that influenza B infection occured more frequently and the complication rate was higher in individuals with chronic lung disease, chronic heart disease or immune system problems (9, 22). However, it is not known why influenza B virus leads to more serious findings in these patient groups. Similarly, influenza B was found with a higher frequency in patients with asthma in our study, though statistical significance was not shown.

Among patients with chronic renal failure, H3N2 was found with a higher frequency (p=0.032). During influenza infection, different hematologic findings, especially including reduction in bone marrow series may be observed (23). It is thought that hematologic findings occur as a result of cell migration from the circulation to tissues, cell death by way of necrosis or apoptosis, and supression of hematopoesis in the bone marrow (24). In the literature, there are different publications related with the hematologic findings of influenza subtypes.

In a study conducted in Japan in which 196 adult influenza cases were evaluated, the prevalence of leukopenia was found higher in patients with H3N2 positivity (11). In H1N1 infection, lymphopenia is generally observed in the first 1-3 days and neutropenia is observed after the fifth day. This is thought to be related with cell migration from the circulation to the infected respiratory mucosa during infection (25). It has been reported that hemaphagocytosis, which develops during influenza infection, causes reduction in bone marrow cell series (26). In our study, the most commonly observed abnormal laboratory findings included leukopenia and thrombocytopenia, in accordance with the literature. When the influenza subtypes were compared, presence of neutropenia was found with a significantly higher frequency in the H1N1 group.

The causes of mortality related with influenza mainly include pneumonia, ARDS, and encephalopathy (27). Although the H1N1 subtype has generlly been associated with more severe clinical prognosis, the frequency of complications and mortality rates may show variance in different patient groups during epidemics (28). In our study, a total of seven patients, two of whom were healthy previously, were hospitalized in the intensive care unit during the follow-up period because of ARDS (n=4), encephalopathy (n=2), and bronchiolitis (n=1). H1N1 was found positive in four of these patients. In addition, increased CRP and increased antibiotic use rates were found significantly more frequently in patients who were infected with H1N1.

In light of these findings, it can be stated that the clinical picture of H1N1 infection is more severe. It was observed that clearance of viral load was delayed and proinflammatory cytokines increased in the nasopharyngeal samples of patients who developed ARDS or died following H1N1 infection, but a correlation between viral load and disease severity has not been reported (29). Mortality is still high despite appropriate treatment in patients who develop ARDS (30). In our study, mortality occured in two patients following H1N1-related ARDS.

In conclusion, influenza is characterized by various findings in childhood, and clinical differences may be observed between the subtypes. Awareness of these differences will prevent unnecessary investigations and antibiotic use by enabling better diagnosis of influenza cases, especially during the months when influenza infections are observed more frequently. Detection of influenza subtype will enable prediction of complications including ARDS and encephalopathy, which might have a fatal prognosis.

Ethics Committee Approval: Ethics committee approval was received for this study from Istanbul University School of Medicine Ethic Committee.

Informed Consent: Informed consent was not obtained due to retrospective nature of this study.

Peer-review: Externally peer-reviewed.

Author Contributions: Concept - M.A., M.S.; Design - M.A.; Supervision - A.S., N.S.; Data Collection and/or Processing - M.A., M.U., H.A., S.M.; Analysis and/or Interpretation - M.S., M.A.; Literature Review - S.H.T.; Writing - M.A.; Critical Review - A.S., N.S.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study has received no financial support.

References

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Manolya Acar (1), Murat Sutcu (1), Hacer Akturk (1), Selda Hancerli Torun (1), Metin Uysalol (2), Sevim Mese (3), Nuran Salman (1), Ayper Somer (1)

(1) Department of Pediatrics, Pediatric Infectious Diseases and Clinical Immunology Division, Istanbul University Istanbul School of Medicine, Istanbul, Turkey

(2) Department of Pediatrics, Division of Pediatric Emergency, Istanbul University Istanbul School of Medicine, Istanbul, Turkey

(3) Department of Microbiology and Clinical Microbiology, Istanbul University Istanbul School of Medicine, Istanbul, Turkey

Address for Correspondence: Manolya Acar E-mail: manolya_kara@yahoo.com

Received: 03.08.2016

Accepted: 11.01.2017
Table 1. Clinical and Laboratory Characteristics of Patients with
Influenza (4-204)

Sex [female, number, (%)]                         35 (35)

Age group (number, %)
 0-6 months                                        8 (8)
 6 months-2 years                                 18 (18)
 2-5 years                                        35 (35)
 >5 years                                         39 (39)
Symptom at the time of presentation (number, %)
 Fever                                            83 (83)
 Cough                                            58 (58)
 Respiratory distress                             25 (25)
 Sore throat                                      18 (18)
 Nasal discharge                                  18 (18)
 Vomiting-diarrhea                                17 (17)
 Hoarse voice                                      8 (8)
 Headache                                          6 (6)
 Seizure                                           6 (6)
 Redness in the eyes                               4 (4)
 Eruption                                          4 (4)
Period of symptoms [days, median (range)]          3 (1-13)
Presence of chronic disease (number, %)           62 (62)
 Neurologic disease                               16 (16)
 Metabolic disease                                14 (14)
 Asthma                                           10 (10)
 Chronic renal failure                             6 (6)
 Chronic liver disease                             5 (5)
 Congenital heart disease                          4 (4)
 Malignancy                                        3 (3)
 Diabetes mellitus type 1                          1 (1)
 Congenital neutropenia                            1 (1)
 Familial Mediteranean fever                       1 (1)
 Juvenile idiopathic arthritis                     1 (1)
Pathological finding on PALG (number, %)          44 (44)
 Paracardiac infiltration                         32 (32)
 Increased aeration                                7 (7)
 Ground-glass appearance                           4 (4)
 Pleural effusion                                  1 (1)
Laboratory [median (range)]
 Leukocyte count (/m[m.sup.3])                     6 550 (1 900-30 610)
 Neutrophil count (/m[m.sup.3])                    3 585 (400-26 650)
 Lymphocyte count (/m[m.sup.3])                    1 895 (400-6 800)
 Hemoglobin (gr/dL)                               12 (7.4-14.6)
 Platelet count (/m[m.sup.3])                    210 650 (19100-602000)
 CRP (mg/L)                                        6.9 (0.1-86.7)
 PCT (ng/mL)                                       0.33 (0.01-2.90)
Oseltamivir use (number, %)                       45 (45)
Period of oseltamivir use [days,                   5 (5-14)
median (range)]
Period of antibiotic use [days, median             7 (3-21)
(range)]
Hospitalization period [days, median (range)]      5 (2-94)

CRP: C-reactive protein; PALG: postero-anterior lung graphy; PCT:
procalcitonin

Table 2. Comparison of the clinical and laboratory findings of patients
in terms of different influenza subtypes

                                               Influenza A/H1N1
                                                    (n=42)

Age [months, median (range)]                       50 (3-158)
Presence of chronic disease (a)                    26 (61.9)
 Neurologic disease                                12 (28.6)
 Metabolic disease                                  7 (16.7)
 Asthma                                             0
 Chronic renal failure                              1 (2.4)
 Cronic liver disease                               3 (7.1)
 Congenital heart disease                           1 (2.4)
Symptom at the time of presentation (n, %)
 Fever                                             39 (92.9)
 Cough                                             22 (52.4)
 Respiratory distress                              11 (26.2)
 Sore throat                                        6 (14.3)
 Nasal discharge                                   10 (23.8)
 Vomiting-diarrhea                                  7 (16.7)
 Seizure                                            5 (11.9)
Non-respiratory findings (n, %)
 Lymphadenopathy                                    9 (21.4)
 Neurologic                                         4 (9.5)
 Myositis                                           3 (7.1)
 Eruption                                           2 (4.8)
 Conjunctivitis                                     2 (4.8)
 Hepatitis                                          1 (2.4)
 Myocarditis                                        0
Laboratory (n, %)
 Leukocytosis                                       4 (9.5)
 Neutropenia                                       11 (26.2)
 Leukopenia                                        15 (35.7)
 Anemia                                            11 (26.2)
 Thrombocytopenia                                  10 (23.8)
 Increased CRP                                     28 (66.7)
 Increased procalcitonin                            5 (11.9)
Radiologic finding (n, %)                          24 (57.1)
Antibiotic use (n, %)                              30 (71.4)
Hospitalization in intensive care unit (n, %)       4 (9.5)
Mortality                                           2 (4.8)

                                               Influenza A/H3N2
                                                    (n=23)

Age [months, median (range)]                      58 (5-204)
Presence of chronic disease (a)                   15 (65.2)
 Neurologic disease                                0
 Metabolic disease                                 4 (17.4)
 Asthma                                            4 (17.4)
 Chronic renal failure                             4 (17.4)
 Cronic liver disease                              1 (4.3)
 Congenital heart disease                          0
Symptom at the time of presentation (n, %)
 Fever                                            17 (73.9)
 Cough                                            15 (65.2)
 Respiratory distress                              5 (21.7)
 Sore throat                                       6 (26.1)
 Nasal discharge                                   5 (21.7)
 Vomiting-diarrhea                                 5 (21.7)
 Seizure                                           0
Non-respiratory findings (n, %)
 Lymphadenopathy                                   4 (17.4)
 Neurologic                                        1 (4.3)
 Myositis                                          1 (4.3)
 Eruption                                          1 (4.3)
 Conjunctivitis                                    1 (4.3)
 Hepatitis                                         1 (4.3)
 Myocarditis                                       0
Laboratory (n, %)
 Leukocytosis                                      2 (8.7)
 Neutropenia                                       0
 Leukopenia                                        7 (30.4)
 Anemia                                            1 (4.3)
 Thrombocytopenia                                  6 (26.1)
 Increased CRP                                    10 (43.5)
 Increased procalcitonin                           2 (8.7)
Radiologic finding (n, %)                          7 (30.4)
Antibiotic use (n, %)                             12 (52.2)
Hospitalization in intensive care unit (n, %)      2 (8.7)
Mortality                                          0

                                               Influenza B
                                                 (n=35)       p

Age [months, median (range)]                   65 (3-178)  0.066 (b)
Presence of chronic disease (a)                21 (60)     0.92 (c)
 Neurologic disease                             4 (11.4)   0.007 (d)
 Metabolic disease                              3 (8.6)    0.51 (d)
 Asthma                                         6 (17.1)   0.058 (d)
 Chronic renal failure                          1 (2.9)    0.032 (d)
 Cronic liver disease                           1 (2.9)    0.20 (d)
 Congenital heart disease                       3 (8.6)    0.68 (d)
Symptom at the time of presentation (n, %)
 Fever                                         27 (77.1)   0.079 (c)
 Cough                                         21 (60)     0.57 (c)
 Respiratory distress                           9 (25.7)   0.91 (c)
 Sore throat                                    6 (17.1)   0.48 (c)
 Nasal discharge                                3 (8.6)    0.19 (d)
 Vomiting-diarrhea                              5 (14.3)   0.75 (c)
 Seizure                                        1 (2.9)    0.096 (d)
Non-respiratory findings (n, %)
 Lymphadenopathy                                5 (14.3)   0.71 (d)
 Neurologic                                     2 (5.7)    0.68 (d)
 Myositis                                       2 (5.7)    0.89 (d)
 Eruption                                       1 (2.9)    0.42 (d)
 Conjunctivitis                                 1 (2.9)    0.24 (d)
 Hepatitis                                      0          0.49 (d)
 Myocarditis                                    1 (2.9)    0.39 (d)
Laboratory (n, %)
 Leukocytosis                                   1 (2.9)    0.41 (d)
 Neutropenia                                    5 (14.3)   0.021 (d)
 Leukopenia                                    10 (28.6)   0.78 (c)
 Anemia                                         5 (14.3)   0.070 (d)
 Thrombocytopenia                               6 (17.1)   0.67 (c)
 Increased CRP                                 13 (37.1)   0.026 (c)
 Increased procalcitonin                        2 (5.7)    0.63 (d)
Radiologic finding (n, %)                      13 (37.1)   0.070 (c)
Antibiotic use (n, %)                          12 (34.3)   0.005 (#)
Hospitalization in intensive care unit (n, %)   1 (2.9)    0.48 (d)
Mortality                                       0          0.24 (d)

(a) Patients with chronic diseases (n=62); comparison of patients with
malignancy (n=3), diabetes mellitus type 1 (n=1), congenital
neutropenia (n=1), familial Mediteranean fever (n=1), and juvenile
idiopathic arthritis (n=1) could not be performed because they had
inappropriate numbers for statistical comparison.
(b) Kruskal-Wallis test; (c) Pearson's Chi-square test; (d) Fisher's
exact test

Table 3. Clinical characteristics of patients hospitalized in the
intensive care unit


                     Chronic
Sequence  Age/Sex    disease         Symptoms            Diagnosis

1            50     Malignancy    Fever, cough,       Pneumonia/ARDS
          months/M                 respiratory
                                     distress
2           112         -             Fever,          Encephalopathy
          months/M                  sonmolance
3            55      Chronic          Fever,          Pneumonia/ARDS
          months/M    liver        respiratory
                     disease         distress
4             8         -       Fever, respiratory  Acute bronchiolitis
          months/                    distress
5            59     Metabolic   Fever, respiratory    Pneumonia/ARDS
          months/M   disease         distress
6            46     Neurologic        Fever,          Encephalopathy
          months/M   disease       sonmolance,
                                     seizure
7            29      Chronic          Fever,          Pneumonia/ARDS
          months/M     lung        respiratory
                     disease         distress

                             ICU
           Influenza   hospitalization
Sequence     type       period (days)

1            H3N2             4


2            H1N1             4

3            H1N1            10


4            H3N2             3

5            H1N1            76

6         Influenza B         7


7            H1N1            14



                        Antiviral
          Mechanical   treatment/     Final
Sequence  ventilation   duration     status

1              -            -       Discharge


2              -       Oseltamivir  Discharge
                          7 days
3              4            -       Mortality


4              -       Oseltamivir  Discharge
                          5 days
5             76       Oseltamivir  Mortality
                         14 days
6              -            -       Discharge


7              9       Oseltamivir  Discharge
                         10 days


ARDS: acute respiratory distress syndrome; ICU: intensive care unit
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Title Annotation:Original Article
Author:Acar, Manolya; Sutcu, Murat; Akturk, Hacer; Torun, Selda Hancerli; Uysalol, Metin; Mese, Sevim; Salm
Publication:Turkish Pediatrics Archive
Article Type:Report
Date:Mar 1, 2016
Words:5190
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