Respiratory illnesses constitute at least half of the paediatric illnesses in any population (BioFire, 2021). Respiratory pathogens cause acute local and systemic disease, with the most severe cases occurring in young children, especially those less than 5 years of age (Monto, 2002; Andrea et al, 2017). Respiratory symptoms include cough, nasal discharge, fever, wheezing and shortness of breath. As a result of the similarity of diseases caused by many viruses and bacteria, diagnosis based on clinical symptoms alone is difficult. Identification of potential causative agents provides data to aid a physician in determining appropriate patient treatment and to direct a public health response for disease containment.
The author's hospital in the United Arab Emirates, has the facility to perform an approved and standardised respiratory viral panel polymerase chain reaction [PCR] test (real-time, nested multiplexed PCR test) designed to simultaneously identify nucleic acids from 23 different viruses and bacteria associated with respiratory tract infection using a single nasopharyngeal swab specimen. A respiratory virus panel (RVP) multiplex PCR test increases the ability to establish specific diagnosis within a wider range of potential pathogens by performing a single test but also increases diagnostic cost significantly (Andrea et al, 2017; BioFire, 2021). Debate exists over the utility and cost-effectiveness of testing for respiratory viruses, as there is currently specific antiviral therapy available only for influenza virus in the form of oseltamivir (Brendish et al, 2017; Landoll et al, 2017). A positive RVP result could potentially decrease antibiotic use and the need for hospitalisation when results are readily available. The objective of this study was to explore the characteristics and outcomes of children who had RVP and to identify its impact, if any, on the use of antibiotics, hospitalisation, revisit, and readmission rates.
Methods
The medical records of 100 children and young people aged under 18 years of age who had an RVP PCR test performed during December 2019 were reviewed using the Meditech health information system.
Ethical approval
The study had approval from the paediatric department and the Hospital Ethics and Research Committee. The study was supported by the staff in the pathology department, mainly to help identify the patient group.
Results
Out of 100 children, 15 had a negative RVP PCR test. None of the children had any other swabs in the preceding 2 weeks and the majority of the swabs (67%) were done in the emergency room department.
Table 1 shows details of the children's ages and the types of pathogens identified by the tests. Rhino/enterovirus was the single most common virus (28.8%) identified. Other viruses with high prevalence included influenza A, influenza B, respiratory syncytial virus and coronaviruses (not COVID-19). A total of 13 patients had mixed pathogens.
Table 1. Age and type of pathogen in children who received a PCR test
| Variable | Categories | Frequency, n (%) |
|---|---|---|
| Age (years) | <1 month | 1 (1) |
| 1 month – 1 year | 19 (19) | |
| 1–2 | 15 (15) | |
| 2–5 | 28 (28) | |
| 5–10 | 26 (26) | |
| >10 | 11 (11) | |
| Type of pathogen | Rhino/enterovirus | 21 (21) |
| Influenza A | 18 (18) | |
| Influenza B | 13 (13) | |
| Metapneumo virus | 5 (5) | |
| Respiratory syncytial virus | 4 (4) | |
| Coronavirus OC43 | 4 (4) | |
| Parainfluenza 3 | 3 (3) | |
| Coronavirus HJU1 | 3 (3) | |
| Parainfluenza 1 | 1 (1) | |
| Coronavirus NL 63 | 1 (1) |
The hospital admission rate was 9% and details of the patients who required hospital admission are shown in Table 2. Among admitted patients, 7 out of 10 (70%) and one baby in the neonatal intensive care unit received antibiotics. Among patients sent home, 10 out of 87 (11.5%) received antibiotics. Overall, three out of nine (33%) admissions had a negative PCR, which were treated as bacterial infections, two (22%) admissions were leukaemia patients, two (22%) admissions had an influenza A infection, one (11%) had an RSV infection and one (11%) had a febrile seizure.
Table 2. Details of children who required hospital admission
| Age (years) | Problem(s) | Test result |
|---|---|---|
| 3.5 | Acute leukaemia neitropenia | Coronavirus NL63 |
| 9 months | Pneumonia otitis media | Influenza A |
| 3 | Pneumonia | Influenza A |
| 6 | Pneumonia | Negative |
| 4 | Tonsillitis | Negative |
| 15 | Pneumonia | Negative |
| 1 | Bronchiolitis | RSV positive |
| 2 | Febrile seizure | Coronavirus OC43 |
| 1.5 | Acute myeloid leukaemia | Coronavirus HKU1 |
A total of 14 out of 87 patients (16%) revisited the hospital within a week. Initial attendance at the paediatric clinic followed by paediatric clinic follow-up visit included two patients. Initial emergency room attendance followed by paediatric clinic follow-up visit included 12 patients.
No patients required the use of antibiotics at follow-up and no patients who were sent home required hospital readmission.
Discussion
Diagnosing and treating respiratory tract infections in children can be very challenging. Due to the difficulty in differentiating viral versus bacterial respiratory tract infections on clinical assessment alone, clinicians often resort to unnecessary investigations and interventions. Inappropriate use of antibiotics for viral respiratory tract infections is a main contributor to increasing antimicrobial resistance worldwide. It is estimated that more than 50% of antibiotic prescriptions for respiratory tract infections in outpatients or emergency room departments are unnecessary (American Academy of Pediatrics, 2018). It is known that respiratory viral panel PCR study offers a high degree of sensitivity and specificity. Previously used rapid antigen tests such as RSV and influenza antigen testing have high specificity rate, but lower sensitivity rates [approximately 75.3% for RSV antigen test and 61.1% for the influenza antigen tests], thereby resulting in high false negative results (Charles, 2008; Ferronato et al, 2012; Krause et al, 2014; Brendish et al, 2017; Bruning et al, 2017; Kitano et al, 2020; BioFire, 2021). The processing time for the RVP PCR is comparable to RSV and influenza antigen testing. In our institution it takes only about couple of hours for the RVP PCR to be reported. It is more expensive than the conventional RSV and influenza antigen tests. However, considering the overall diagnostic, therapeutic and economic advantages, RVP PCR is a much better and superior investigation for children presenting with respiratory illnesses (Rogers et al, 2015; Minejima et al, 2016; Subramony et al, 2016; Landoll et al, 2017; McFall et al, 2018).
This study indicates that a positive RVP PCR result can lead to beneficial outcome such as low rates of hospitalisation and use of antibiotics. Antibiotic Stewardship Program (ASP) in the ambulatory setting is a relatively new concept that is gathering momentum. Rapid diagnostic tests (RDTs) including the RVP PCR test with short turn around time enhance diagnostic accuracy and the speed of diagnosis. Successful ASP should incorporate these promising technological advances to rationalise clinician thinking and decison making, modify prescribing habits, optimise cost-effective patient care and mitigate adverse global public health outcomes such as development of multi-drug resistant bacteria and superbugs (Fong and Timbrook, 2020).
Limitations
Although the numbers in the study are small and the author is unable to compare with a study on the clinical outcomes in the absence of RVP PCR testing; it seems reasonable that with thoughtful clinical correlation, the RVP PCR can be a useful and overall cost-effective tool for clinical management.
Conclusions
In light of the results of this study, the author would recommend the use of RVP PCR as a single routine swab test for children presenting with upper or lower respiratory tract symptoms, rather than subjecting them to multiple swab tests for influenza and RSV. In our clinical practice, it was also observed, though difficult to quantify, that having a clear diagnosis alleviates parental anxiety and reduces frequent hospital attendances. This in turn has positive benefits and implications on the health economy and public health. The RVP PCR test provides a lot more specific diagnostic information, and it is even more relevant in the current pandemic situation as the test done in our hospital now also includes the COVID-19 PCR, thus providing rapid results with an average turnaround time of only couple of hours. This helps the clinician in rapid decision-making and evidence-based clinical management to the best satisfaction of patients and families.