|Year : 2018 | Volume
| Issue : 3 | Page : 401-407
Microbiological and chest X-ray studies on influenza B virus-associated pneumonia
Xiaoyun Wang, Yan Tian
Department of Neonatology, Jining No. 1 People's Hospital, Jining, Shandong, China
|Date of Web Publication||14-Nov-2018|
Prof. Yan Tian
Department of Neonatology, Jining No. 1 People's Hospital, Jining 272011, Shandong
Source of Support: None, Conflict of Interest: None
Introduction: The signs and symptoms of influenza B are commonly ignored. Therefore, very few clinical reports are available. This study is an attempt to evaluate the clinical features and characteristics of influenza B virus-associated pneumonia patients. Objective: The aim of this study is to investigate the microbiological and characteristics of influenza B virus-associated pneumonia patients. Methodology: Patients with <16 years old with a clinical diagnosis of influenza B virus infection and who had chest radiography within 2 days were enrolled. A total of 49 patients were categorised as the pneumonia group by clinical symptoms and chest X-ray (CXR) findings, whereas 107 patients were categorised as the non-pneumonia group based on the laboratory data and normal CXR findings. Results: The study observed that the age of the patients in the pneumonia group was significantly younger than the non-pneumonia group. The white blood cell (WBC) count of the pneumonia group was also higher. However, the haemoglobin (Hgb) level was lower in the pneumonia group. The C-reactive protein (CRP) level of the pneumonia group was also significantly high. The CXR findings revealed that 28.57% of patients had alveolar consolidation, 32.65% had interstitial infiltration and 40.82% had ground glass opacity. Conclusions: High clinical suspicion is required to detect pneumonia in influenza B virus patients. Based on the CXR findings, the study also suggests that patients with pleural effusion and positive bacterial culture need more attention for the severity of clinical outcome. Moreover, critical care should be given to paediatric patients having higher WBC count, higher CRP level and lower Hgb. These parameters would be helpful to differentiate primary pneumonia from non-pneumonic influenza.
Keywords: Chest X-ray findings, haemoglobin level, influenza B virus, influenza, white blood cell count
|How to cite this article:|
Wang X, Tian Y. Microbiological and chest X-ray studies on influenza B virus-associated pneumonia. Indian J Med Microbiol 2018;36:401-7
|How to cite this URL:|
Wang X, Tian Y. Microbiological and chest X-ray studies on influenza B virus-associated pneumonia. Indian J Med Microbiol [serial online] 2018 [cited 2020 Jul 13];36:401-7. Available from: http://www.ijmm.org/text.asp?2018/36/3/401/245398
| ~ Introduction|| |
Influenza A, B and C viruses cause influenza in humans. The host range for influenza B virus is limited to humans and seal and these limits for influenza virus B-caused influenza pandemics. In addition, the signs and symptoms of influenza B are commonly ignored and there are limited reports of pneumonia caused by influenza B pneumonia among children. Because of these reasons, there are very few clinical reports on the health complications caused by influenza B virus. In fact, influenza virus infection is common among paediatrics with an estimated attack rate at 20%–30% annually. The symptoms of the virus infection include persistent dry cough, fever, headache, nasal congestion, sore throat and muscle aches. Most people with influenza recover in <2 weeks, although a few people experience severe health complications as because of the flu such as pneumonia (myocarditis), brain encephalitis (brain) and myositis (muscle)., These complications commonly attack children of young age, pregnant women, adults above 65 years and people with severe chronic medical episodes.,, In fact, pneumonia is a major health threat worldwide that causes more deaths in children than AIDS, measles and malaria. This study is an attempt to investigate the clinical features and characteristics of influenza B virus-associated pneumonia patients. In this study, patients with <16 years old with a clinical diagnosis of influenza B virus infection between January 2012 and December 2015 and who had chest radiography within 2 days were enrolled and evaluated based on the clinical features, laboratory data and chest X-ray (CXR) findings.
| ~ Methodology|| |
Ethics approval and consent to participate
All procedures performed in studies involving human participants were in accordance with the ethical standards of the Institutional and/or National Research Committee and with the Declaration of Helsinki (1964) and its later amendments or comparable ethical standards. The protocol was approved by the Institutional Review Boards of the Jining Medical University Ethics Committee (NO-JPH/Neo/Aug2011). Written informed consent was obtained from all individual participants included in the study. Written informed consent was also obtained from the parents or guardians of the patients whose age is below 5 years. The confidential patient data are available from the corresponding author and can be shared on reasonable request.
Patient selection and information
The study was conducted after getting the approval of the Institutional Review Board for the study. Between January 2012 and December 2015, patients with <16 years old with a clinical diagnosis of influenza B virus infection were selected for this study. The enrolment procedure begins from January 2012 to the data were recorded until December 2015. The medical records of these patients were reviewed and chest radiography was taken within 2 days for these patients who have a clinical diagnosis of influenza B virus infection. Written consent was obtained from those individual who re volunteer to participate in the study. Whereas for the individual whose age is <5 years, written informed consent was obtained from their parents and guardian. A total of 156 episodes were identified from a total of 207 patients and sorted them into two groups for comparison, with 49 episodes of pneumonia-based and 107 episodes of non-pneumonia based on CXR findings. The enrolment process is shown in [Figure 1].
In the present study for patient selection and categorisation of pneumonia and non-pneumonia, the pneumonia group was defined as follows:
- Patients with fever
- Clinical symptoms of respiratory tract infection
- Obvious infiltrations on CXR examination.
While the patients with the non-pneumonia group were defined as follows:
- Patients with fever
- Clinical symptoms of respiratory tract infection
- Having normal CXR finding.
The medical charts of both these groups were further reviewed by the paediatricians based on clinical presentations.
Specimen collection and processing
Nasopharyngeal specimens and viral throat swab culture were obtained by the same trained interns according to the Centres for Disease Control (CDC) manual. One nasopharyngeal specimen and one viral throat swab culture per child. The detection of influenza B virus infection was considered positive if it is confirmed by these tests, namely, rapid antigen test performed by nasopharyngeal swab, viral throat swab culture and blood sample polymerase chain reaction (PCR) which is conducted in accordance with the published guidelines of the US CDC and Prevention. For the nasopharyngeal specimen analysis, the swabs were placed immediately into Amies medium. Further, the samples were inoculated in blood agar media supplemented with gentamycin (5 mg/mL), and the specimen samples were streaked with the sterile loop. The medium was then incubated at 37°C for 48 h. The clinical courses which include fever days and survival outcome were assessed. Clinical management, including antimicrobial use, extracorporeal membrane oxygenation application and ventilation support were also investigated. The severity of illness was also assessed at presentation using a scoring system: the CURB-65 scoring system was used for all patients with pneumonia and the Acute Physiology and Chronic Health Evaluation II (APACHE II) scoring system was used for patients admitted to intensive care unit.
Data collection and study design
The demographic characteristic data in medical records included age, sex, clinical symptoms underlying diseases, invasive medical procedures and the duration of fever and oseltamivir use were analysed. The clinical reports of the patients and laboratory data which include the white blood cell (WBC) count, blood platelet count, level of haemoglobin (Hgb), C-reactive protein (CRP) level and positive bacterial culture were collected for the diagnosis and analysis.
Chest radiography was performed on every patient within 2 days of admission. The CXR films during the time of diagnosis in the pneumonia group were initially evaluated by the radiologist and further confirmed by the second radiologist. Both the radiologists were blind to the patient's clinical information and presentation.
The CXR findings were described depending on the following features
- The pattern of abnormal opacities
- Distribution of abnormal opacities
- Hilar abnormalities (unilateral or bilateral abnormal opacities) and
- Other extra-pulmonary changes.
Abnormal opacities were defined as alveolar consolidation, interstitial infiltration and ground glass opacity [Figure 2]. The distribution of abnormal opacities was defined as diffuse and localised. Further the localised opacities are described as central [Figure 2], peripheral, upper and lower portions. The interpretation of the CXR characteristics and distribution of abnormal depended on the major finding by the one senior radiologist and two senior pulmonologists independently. The final interpretation was based on the consensus.
|Figure 2: Chest X-ray representative of (a) alveolar consolidation (b) interstitial infiltration (c) ground glass opacity (d) localised central distribution|
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The mean ± standard deviation was used for representing the continuous variables and evaluate using Mann–Whitney U-test. Categorical data from clinical presentations and outcomes were compared with the Chi-square test within the two groups. All the analysis was computed using IBM SPSS Statistics 19.0 (IBM Corp. Armonk, NY, USA). The level of statistical significance was defined as P < 0.05.
| ~ Results|| |
During the study, from a total of 156 patients which have undergone CXR examination, 49 patients were assigned to the pneumonia group, and 107 were assigned to the non-pneumonia group. Pneumonia was found in 19.14% (49/207) of influenza patients who have undergone CXR imaging. Among 49 patients, with pneumonia 45 patients was also confirmed by real time-PCR (RT-PCR) with nasopharynx or throat specimens by RT-PCR with bronchoalveolar lavage (BAL) fluid after a second negative RT-PCR with nasopharyngeal specimens in four patients. The age distribution of the pneumonia cases in the pneumonia group ranged from 2.4 years to 16.0 years. BAL was also performed in 16 pneumonia patients after taking consent from the patients and their guardian.
Clinical characteristics of influenza pneumonia
The demographic and clinical characteristics of patients with influenza B virus-associated pneumonia are presented in [Table 1]. All 156 patients were Chinese and their mean age was 5.5 ± 3.2 for the pneumonia group and 6.9 ± 4.1 for the non-pneumonia group. The median age of the pneumonia group (5.5 years) was found to be significantly younger than the non-pneumonia group (6.9) (P = 0.032). The average body weight distribution was 23.56 kg and 26.17, respectively, between the two groups. No significant difference was observed between the two groups at the time of the visit.
|Table 1: Clinical characteristics and features of influenza B virus-associated pneumonia patients|
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The majority of influenza patients which is categorised as non-pneumonia was 59 males over 48 females patients (55%) compared with those with pneumonic influenza 28 Males over 21 females (57%) (P = 1.00). The duration of fever before the hospital visit was longer in patients with the non-pneumonic group than the pneumonia group (P ≤ 0.542). Fever (>37.8°C) was noted in 91.84% of patients with pneumonia group and 82.24% of patients with the non-pneumonia group. Patients with pneumonic influenza also have fewer symptoms of myalgia, headache and nasal symptoms than patients with non-pneumonic influenza. Cough was more common in patients with pneumonia group (96%) than patients with non-pneumonic group (93%) (P = 1.00). There were no significant differences in age, body weight and height among the two groups. Moreover, there was no significant difference between the two groups based on the prescribed oseltamivir dosage before the admission (25.64% in the pneumonia group compared to 24.32% in the other group). The pneumonia group also observed a 23% sore throat and 71% rhinorrhoea compared to a 24% sore throat and 81% rhinorrhoea of the non-pneumonic group. The incidence of shortness of breath was 14% in the pneumonia group and 5% in the non-pneumonia group (P = 0.141). While the symptoms of abdominal distress which include pain, vomiting, nausea and diarrhoea were 41% for the pneumonia group and 22% for the other group (P = 0.061). The clinical scores on CURB-65 suggest that patients with the pneumonic group have a higher CURB-65 score 10 (20.41%). The APACHE II score, hypoxia (PO2<60 mmHg at room air) or mechanical ventilation scores 15.9 ± 2.8 in the pneumonia patient groups.
[Table 2] demonstrates the clinical outcome of the laboratory data of both the group of patients. The WBC count of the pneumonia group was observed to be significantly higher than the other group (7.8 × 109 against 5.9 × 109 cells/L, P = 0.016). The proportion of leukopenia (WBC <4.0 × 109 cells/L) was 6.2% in the pneumonia group, and 18.6% in the non-pneumonia group. Whereas the level of Hgb of the pneumonia group was observed to be slightly lower (12.3 against 13.1 g/dL, P = 0.028). The CRP level of the pneumonia group was observed to be significantly higher than the non-pneumonia group, 20.31 mg/L against 5.9 mg/L (P = 0.002).
|Table 2: Clinical reports and laboratory data of influenza B virus-associated pneumonia patients|
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Six patients (12.24%) had a positive result of the bacterial culture in specific media in the pneumonia group. Fours species were identified as Streptococcus pneumonia strains and the other two with Staphylococcus aureus strains. Two strains of S. pneumonia were detected form the blood samples whereas the other two strains of S. pneumonia and S. aureus were from the tracheal aspirates. Furthermore, the DNA of these six bacterial culture were isolated using standard protocol and amplified using specific universal primers 1100F and 1100R for 16s ribosomal RNA sequencing and deposited in the NCBI GenBank. The DNA sequences were assigned with the accession numbers MF805756, MF805757, MF805758, MF805759 for the S. pneumonia strains andMF805760, MF805761 for the S. aureus strains, respectively. A BLAST search analysis was carried out and the phylogenetic tree of the S. pneumonia strains and S. aureus strains were constructed whichisshown in [Figure 3]a and [Figure 3]b.
|Figure 3: Phylogenetic analysis of isolated bacterial culture of (a) Streptococcus pneumonia strain JNG-01, JNG-02, JNG-03, JNG-04 and (b) Staphylococcus aureus strain JNG-01 and JNG-02 |
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[Table 3] summarises the CXR findings of the pneumonia group. The findings on the abnormal opacity characteristics observed that 28.57% of the patients had alveolar consolidation, 32.65% had interstitial infiltration. In addition, six patients had pleural effusion in which one patient has S. aureus and another one with S. pneumoniae cultured from the tracheal aspirates. However, there were no reports of blood or pleural effusion from these two patients. In CXR the most common abnormal opacities distribution was mostly diffuse (40.82%) and in the localised zone the central zone was mostly involved covering about 12.24%.
|Table 3: Chest X-ray reports on 49 influenza B virus-associated pneumonia patients|
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In addition, further investigation was carried out for the duration of fever and the use of antibiotics in pneumonia patients with influenza B virus infection. Moreover, no significant difference was observed in 38 patients with fever after prescribing with and without antibiotic treatment.
Treatment and clinical outcome
Forty-nine patients of 156 patients with confirmed influenza B virus were hospitalised and anti-viral agent oseltamivir was given to 10 patients. For the patients with non-pneumonic influenza group, 27 were also treated with oseltamivir (80 mg bid, 5 days). For the patients with the pneumonic group, antiviral agents were given to 10 patients for 8.0 ± 2.4 days based on clinician's preference and fever usually disappeared within 2 days after antiviral treatment.
| ~ Discussion|| |
Chest radiography has been widely used for the diagnosis of pneumonia because of its convenience and ease of access. In addition, the identification of characteristic radiological opacities aid in early treatment and isolation of pneumonia cases with resultant better outcomes and spreading the illness., On the other hand, influenza B virus has also caused severe infection and invasive complications in the recent years. Earlier reports suggested that the influenza B virus as less virulent and less widespread compared to influenza A virus. Moreover hence, much emphasis was given to influenza A virus which was considered more pathogenic based on clinical studies and public health policy reports. Moreover, the 2009 pandemic of H1N1 influenza had triggered our mind about the importance of these viruses as the main cause of community-acquired pneumonia.,, In the present investigation, 19.5% who had undergone CXR were confirmed with pneumonia. Our data were also in agreement with the other reports by Lahti et al. and Fraaij and Heikkinen which varies from 5% to 20%.,
Because of the limited reports available on the on infection rates in the paediatric population, the assessment of the mortality rate of paediatric influenza B virus-associated pneumonia is difficult.,, In our study, a good number of patients recovered after getting proper treatment. In many cases, the mortality rate turns out to be high as 20%–80% if the condition of the patients gets worsened with acute respiratory distress syndrome. In our study, it was observed that many of the pneumonia patients were able to recover without any abnormalities; however, those patients who had developed acute respiratory distress syndrome were unable to get recovered and expired. There are also several reports of the influenza B virus infection in children that ranges from than 1 year to 6 years in different geographic areas.,, Our study also suggests that the median age of the pneumonia group (5.5 ± 3.2) was considerably younger than the non-pneumonia group (6.9 ± 4.1).
No significant difference in symptoms was also observed based on the percentage with the underlying disease between the two groups. In our study, two of previously healthy patients expired after developing chronic conditions. Hence, due to care and greater observation are required in patients associated with a chronic medical condition. Moreover, previously healthy patients should not be with lower risks of morbidity and mortality rate.
The drug history, dosage study also suggests that there was no significant difference in the usage of oseltamivir between pneumonia (25.64%) and non-pneumonia (24.32%) patients before the onset. However in some cases, the usage of oseltamivir has also shown to have a relative clinical effect.,, In the current study, gastrointestinal symptoms accounted for the largest proportion of symptoms in the pneumonia group. These symptoms were common in children with pneumonia. Our findings are also consistent with other data reported by Tang et al. The clinical data outcome of the patients also suggests that the median WBC was higher in pneumonia group (7.8 × 109 cells/L) compared to the non-pneumonia group (5.9 × 109 cells/L). However, the rate of leukopenia was lower in the pneumonia group. No significant difference was observed in the neutrophil (%) and lymphocyte (%) level between the investigated two groups. It may be noted that the deficiency of red blood cells is associated with lower respiratory tract infection and for more serious influenza infection as reported by Chavez et al. and Wonodi et al. Besides, Ruuskanen et al. reported that a higher level of CRP is believed to be a sign of bacterial infection among influenza patients. In this study, the CRP level in the pneumonia group was higher even though no significant difference was observed in the level of the Hgb in both the groups. These findings suggest that patients with higher WBC, lower Hgb, and higher the CRP level should not be neglected with proper observations in patients with influenza B virus-associated pneumonia.
In the present investigation, the findings of the CXR pattern were also varied among the paediatric pneumonia patients with influenza B virus. Moreover in fact, there are several reports which described the inconsistency in CXR findings of influenza patients associated with pneumonia., Our findings also evidenced that two patients associated with pleural effusion with confirmed S. aureus and S. pneumonia cultures from tracheal aspirates which were cannulated had expired. To the contrary, Kim et al. reported that paediatric patients with swine flu (H1N1) pneumonia associated with pleural effusion and without bacterial infection had a mild clinical course. These findings deduced that patient associated pleural effusion and confirmed bacterial culture from tracheal aspirates had a high risk of the death rate. In this study, there was no clear-cut consensus that patients with viral pneumonia need to treat with antibiotics or not. In addition, no significant difference was observed pneumonia patients having fever having administered with and without antibiotic. However, the study also suggests that further investigation should be carried out to those patients with a positive bacterial culture report of blood or tracheal aspirates.,,, In our study, two patients cannulated with endotracheal tube died due to severe respiratory distress. Another patient with pleural effusion and confirmed bacterial culture from tracheal aspirates also died due to acute respiratory distress syndrome after a week of admission. The lack of a worldwide consensus guideline for pneumonia means that the diagnosis is usually based on clinical signs and symptoms such as fever, cough, dyspnoea, history-taking and physical examination. The diagnosis of pneumonia is usually a new infiltrate seen on a chest radiograph.
| ~ Conclusions|| |
The author's would like to highlight the fact that appropriate care should be given to paediatric patients with influenza B virus-associated pneumonia. In fact, high clinical suspicion is required to detect this type of pneumonia and more attention should be given patients, which have lower Hgb with higher WBC and CRP level. Because these parameters would be helpful to differentiate influenza B virus-associated pneumonia from non-pneumonia. The CXR finding also indicates that pleural effusion patients with confirmed bacterial culture are likely to have a severe clinical outcome. However, the present study has some limitations such as the study only considered the initial clinical features, and CXR findings, which might change with the clinical course. In fact, the study has made a generalised and assumes influenza-associated pneumonia as only those with fever, radiographic signs of consolidation and clinical symptoms of respiratory tract infection. Furthermore, the study period was 4 years and, different strains of influenza B virus may have already been circulated in different seasons. Further studies with a larger number of patients with longer duration necessitate elucidating the precise function of these studied parameters.
The author's would like to thank the hospital authority of Jining No. 1 People's Hospital and Jining Medical University for the necessary support.
Financial support and sponsorship
The project was funded by the Jining Medical University Project Number – JMU/JPH/AN-27851-S.
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3]