Trial of Respiratory Infections in Children for Enhanced Diagnostics
NCT ID: NCT03233516
Last Updated: 2020-11-23
Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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Recruitment Status
COMPLETED
Total Enrollment
376 participants
Study Classification
OBSERVATIONAL
Study Start Date
2017-11-20
Study Completion Date
2019-12-09
Brief Summary
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The overall aim of the TREND study is to improve the differential diagnosis of bacterial and viral etiology in children below 5 years of age with clinical community acquired pneumonia.
Specific objectives:
* To assess the diagnostic accuracy of MxA for viral CAP (sub-study I)
* To study etiologies in children with CAP (sub-study II)
* To evaluate sensitivity and specificity for MariPOC® Respi test versus PCR for detection of respiratory viruses (sub-study III)
* To assess sensitivity and specificity for a novel RPA-based point-of-care test versus PCR for detection of respiratory viruses (sub-study IV)
* To assess long-term complications in children with CAP (sub-study V
The study takes place at Sachs' Children and Youth hospital in Stockholm.
Specific objectives:
* To assess the diagnostic accuracy of MxA for viral CAP (sub-study I)
* To study etiologies in children with CAP (sub-study II)
* To evaluate sensitivity and specificity for MariPOC® Respi test versus PCR for detection of respiratory viruses (sub-study III)
* To assess sensitivity and specificity for a novel RPA-based point-of-care test versus PCR for detection of respiratory viruses (sub-study IV)
* To assess long-term complications in children with CAP (sub-study V
The study takes place at Sachs' Children and Youth hospital in Stockholm.
Detailed Description
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Background: Respiratory viral and bacterial infections are hard to distinguish clinically, and many children with viral infections receive unnecessary treatment with antibiotics, which contributes to development and spread of antibiotic resistance. Therefore, there is a need for new point-of-care diagnostic tests that better distinguish viral from antibiotic-requiring bacterial infections, particularly in children presenting with suspected clinical community-acquired pneumonia (CAP), and thus assist health-care workers decision making and improve rational use of antibiotics.
Myxovirus resistance protein A (MxA) is a promising biomarker for viral infection, but no studies have investigated MxA in children with CAP. Procalcitonin (PCT) is used as a biomarker for severe bacterial infection as the protein rapidly increases in plasma levels in response to stress and systemic infection. PCT has been reported to be more specific for bacterial infection as compared to CRP, but there are conflicting data on the clinical utility of PCT in children with CAP.
The role of viruses and atypical bacteria in childhood CAP Is increasingly recognized. Recent studies have reported an increasing incidence of B. pertussis and there have been several deaths in previously healthy infants associated with whooping cough in Sweden over the last ten years. Consequently, there is a need for new etiologic studies in childhood CAP.
Real-time PCR is currently considered gold-standard for detection of respiratory viruses in children with respiratory tract infection. Nevertheless, the turn-around time is usually long and the test results can rarely be used for decision making regarding treatment. There are currently several new antigen-based point-of-care tests of respiratory infections on the market, one is Multianalyte Point-of-care Antigen Detection Test System (MariPOC®) Respi. The sensitivity for respiratory syncytial virus (RSV) and influenza virus is as high as 90% as compared to PCR, the current gold-standard PCR, but, the sensitivity for less common respiratory viruses such as metapneumovirus (hMPV), parainfluenza virus (PIV), coronavirus and bocavirus have been insufficiently investigated.
Recombinase polymerase amplification (RPA) is a nucleic acid amplification method that doesn't require thermal cycling. As the test reaction can be carried out at room temperature it is a particularly interesting method for resource-limited settings where the need for new diagnostic tests is high.
Studies on long-term outcomes of radiologically confirmed bacterial CAP have indicated that the disease is associated with later development of asthma and decreased lung-function. Given the ongoing change in etiology of pediatric CAP, there is a need for new studies of long-term complications in pediatric CAP.
Overall Aim:
The overall aim of the TREND study is to improve the differential diagnosis of bacterial and viral etiology in children below 5 years of age with clinical CAP.
Specific objectives:
* To assess the diagnostic accuracy of MxA for viral CAP (sub-study I)
* To study etiologies in children with CAP (sub-study II)
* To evaluate sensitivity and specificity for MariPOC® Respi test versus PCR for detection of respiratory viruses (sub-study III)
* To assess sensitivity and specificity for a novel RPA-based point-of-care test versus PCR for detection of respiratory viruses (sub-study IV)
* To assess long-term complications in children with CAP (sub-study V)
Study Design:
The TREND study is a hospital-based prospective observational study of children with clinical CAP with asymptomatic controls at the emergency department at Sachs' Children and Youth hospital, Stockholm.
Case definition Children 1-59 months with clinical CAP according to WHO-criteria.
Bronchodilator challenge:
Inhalation with a rapid acting bronchodilator will be administered to children with wheezing and in-drawings to improve the specificity of the WHO clinical CAP criteria as suggested by the PERCH study team. Resolved in-drawings after bronchodilator challenge will be recorded but not considered an exclusion criteria to be able to exclude these patients in a sub-analysis.
Control definition:
Children 1-59 months at Sachs' Children and Youth Hospital treated for a minor orthopedic or minor surgical disease. The parents to the controls will be contacted via email/telephone 1-2 weeks after enrollment and be asked whether the child has developed respiratory symptoms or not. No matching will be performed but adjustments for age and season will be performed in the analyses.
Sampling:
A capillary blood sample and nasopharyngeal swabs/aspirates will be collected from all study subjects.
Microbiological and Biochemistry Analyses:
MariPOC® Respi as well as real-time PCR analysis (detecting: 16 respiratory viruses as well as Streptococcus pneumoniae, Bordetella pertussis, B. parapertussis and Mycoplasma pneumoniae) will be performed.
Biochemistry Analyses:
Serum MxA, procalcitonin and CRP levels will be analysed.
Study Variables:
Information regarding the study subject, number of siblings, days of illness, current symptoms, vaccinations, antibiotic treatment, medication, underlying diseases, heredity for asthma, previous hospitalization, recent stay abroad, allergies, smoking, recent travel abroad, recent contact with unwell individual, breastfeeding, preschool, origin of parents and socio-economic status will be collected through a standardized questionnaire based on previous studies.
Clinical parameters will be registered by the study doctor responsible for patient screening/enrolment in line with the study protocol of PERCH. Some of the clinical parameters included in the PERCH protocol are very rare in a Swedish context and to avoid overloading of the case report form, these will not be systematically registered at inclusion. However, information about these symptoms will be retrospectively collected from the medical records. Some clinical parameters are routinely recorded multiple times at the emergency unit. In these cases, the most extreme value (highest pulse/respiratory rate/body temperature/etc and lowest peripheral oxygen saturation) during the visit at the emergency unit until enrolment will be recorded. Information regarding admission, length of stay, radiological, routine clinical examination, microbiological and chemistry analyses, treatment, discharge diagnosis and complications will be retrospectively collected from the medical records.
All study subjects will be linked to the National Vaccination register to collect information regarding previous immunizations. To allow assessment of long-term complication, study subjects will also be linked to the National Patient Register, the National Death Register and the National Prescribed Drug Register for collection of discharge diagnoses according to ICD-10 as well as prescribed drugs.
Classification of Disease:
Etiology will be classified as probable or definitive based on clinical significance of the different microbiological test in the studies above. In TREND, the combination of probable and definitive etiology will be used in the main analysis, whereas children with definitive etiology will be assessed separately in a sub-analysis.
Definitive Viral Infection:
• PCR positive for influenza, RS virus, metapneumovirus or parainfluenza virus
Probable Viral Infection:
* PCR positive for adenovirus
* PCR positive for coronavirus, rhinovirus, bocavirus or enterovirus AND CRP \<20 AND reported fever \>24h.
Definitive Bacterial Infection:
* positive bacterial blood culture in blood or pleura fluid
* positive pneumococcal antigen test in pleura fluid
Probable Bacterial Infection:
* CRP \>80 (children ≤2 years) / \>120 (children 2-5 years) AND/OR
* Radiographic evidence of empyema on X-ray or ultrasound AND/OR
* Large dense infiltrate or lobar consolidation on chest x-ray
Definitive Atypical Bacterial Infection:
• Positive PCR B. pertussis or B. parapertussis
Probable Atypical Bacterial Infection:
• Positive PCR M. pneumoniae
Undetermined:
• Cases not fulfilling any criteria above
Mixed Viral-bacterial Infection:
• Children fulfilling criteria for both viral and bacterial infection
Classification of Long-term Complications:
Long-term complications (asthma and number of hospital-requiring respiratory infections) will be assessed after 3, 7 and 10 years following study completion by linking to the National Patient Register. Asthma will be classified as ICD-10 diagnosis of J45 or ≥3 prescriptions of inhalation steroids, beta-2-agonists or leukotriene antagonists according to the Prescribed Drug Register.
Power Calculation:
For the sample size calculation, the investigators focused on the assessment of MxA-levels in cases with viral CAP as compared to cases with bacterial CAP/controls (study I). Two power calculations were made, one for viral CAP versus bacterial CAP and one for viral CAP versus controls. The following assumptions were made:
A difference in MxA-level of 500µg/l between the groups was considered clinically relevant. A standard deviation of 1000 and 300 was assumed in cases with viral CAP and bacterial CAP/controls respectively based on previous studies on MxA.
Using an alpha-level of 0.05 (two-sided) at an 80% power, with an additional 20% addition to account for non-parametric testing and multivariate analyses, 42 children in each group (viral CAP, bacterial CAP and controls) would be needed.
To ensure that enough of the included cases would fulfill the TREND definition of viral and bacterial CAP, the proportion of viral respectively bacterial CAP (TREND definition) was calculated in our previous study that assessed Swedish children with x-ray verified CAP. By doing this, the prevalence of viral and bacterial CAP was estimated to 45% and 14% respectively. Hence 300 cases and 42 controls would be needed to ensure sufficient collection of cases with viral and bacterial CAP respectively. The investigators also would like to compare cases with viral CAP with controls testing positive for one or more virus by PCR. In our previous study, 35.4% of asymptomatic children tested positive for one or more virus. To include a sufficient number of virus-positive controls, the investigators hence aim at including 300 cases and 119 controls (42/0.354=119) in the TREND-study.
Ethical Considerations:
The study will be conducted in accordance with the latest version of The Declaration of Helsinki and the fundamental principles of respect for the individual (Article 8), their right to self-determination and the right to make informed decisions (Articles 20, 21 and 22) regarding participation in research, both initially and during the course of the research.
Significance:
The findings from the TREND project can be an important step to improve the care of children with clinical CAP. Improved near-patient differential diagnosis is a prerequisite for rational antibiotic use and decreasing unnecessary antibiotic treatment. Further better diagnosis of the pathogens causing acute respiratory infections makes it easier to give advice to parents on how their children should be cared for and better surveillance in the society.
Myxovirus resistance protein A (MxA) is a promising biomarker for viral infection, but no studies have investigated MxA in children with CAP. Procalcitonin (PCT) is used as a biomarker for severe bacterial infection as the protein rapidly increases in plasma levels in response to stress and systemic infection. PCT has been reported to be more specific for bacterial infection as compared to CRP, but there are conflicting data on the clinical utility of PCT in children with CAP.
The role of viruses and atypical bacteria in childhood CAP Is increasingly recognized. Recent studies have reported an increasing incidence of B. pertussis and there have been several deaths in previously healthy infants associated with whooping cough in Sweden over the last ten years. Consequently, there is a need for new etiologic studies in childhood CAP.
Real-time PCR is currently considered gold-standard for detection of respiratory viruses in children with respiratory tract infection. Nevertheless, the turn-around time is usually long and the test results can rarely be used for decision making regarding treatment. There are currently several new antigen-based point-of-care tests of respiratory infections on the market, one is Multianalyte Point-of-care Antigen Detection Test System (MariPOC®) Respi. The sensitivity for respiratory syncytial virus (RSV) and influenza virus is as high as 90% as compared to PCR, the current gold-standard PCR, but, the sensitivity for less common respiratory viruses such as metapneumovirus (hMPV), parainfluenza virus (PIV), coronavirus and bocavirus have been insufficiently investigated.
Recombinase polymerase amplification (RPA) is a nucleic acid amplification method that doesn't require thermal cycling. As the test reaction can be carried out at room temperature it is a particularly interesting method for resource-limited settings where the need for new diagnostic tests is high.
Studies on long-term outcomes of radiologically confirmed bacterial CAP have indicated that the disease is associated with later development of asthma and decreased lung-function. Given the ongoing change in etiology of pediatric CAP, there is a need for new studies of long-term complications in pediatric CAP.
Overall Aim:
The overall aim of the TREND study is to improve the differential diagnosis of bacterial and viral etiology in children below 5 years of age with clinical CAP.
Specific objectives:
* To assess the diagnostic accuracy of MxA for viral CAP (sub-study I)
* To study etiologies in children with CAP (sub-study II)
* To evaluate sensitivity and specificity for MariPOC® Respi test versus PCR for detection of respiratory viruses (sub-study III)
* To assess sensitivity and specificity for a novel RPA-based point-of-care test versus PCR for detection of respiratory viruses (sub-study IV)
* To assess long-term complications in children with CAP (sub-study V)
Study Design:
The TREND study is a hospital-based prospective observational study of children with clinical CAP with asymptomatic controls at the emergency department at Sachs' Children and Youth hospital, Stockholm.
Case definition Children 1-59 months with clinical CAP according to WHO-criteria.
Bronchodilator challenge:
Inhalation with a rapid acting bronchodilator will be administered to children with wheezing and in-drawings to improve the specificity of the WHO clinical CAP criteria as suggested by the PERCH study team. Resolved in-drawings after bronchodilator challenge will be recorded but not considered an exclusion criteria to be able to exclude these patients in a sub-analysis.
Control definition:
Children 1-59 months at Sachs' Children and Youth Hospital treated for a minor orthopedic or minor surgical disease. The parents to the controls will be contacted via email/telephone 1-2 weeks after enrollment and be asked whether the child has developed respiratory symptoms or not. No matching will be performed but adjustments for age and season will be performed in the analyses.
Sampling:
A capillary blood sample and nasopharyngeal swabs/aspirates will be collected from all study subjects.
Microbiological and Biochemistry Analyses:
MariPOC® Respi as well as real-time PCR analysis (detecting: 16 respiratory viruses as well as Streptococcus pneumoniae, Bordetella pertussis, B. parapertussis and Mycoplasma pneumoniae) will be performed.
Biochemistry Analyses:
Serum MxA, procalcitonin and CRP levels will be analysed.
Study Variables:
Information regarding the study subject, number of siblings, days of illness, current symptoms, vaccinations, antibiotic treatment, medication, underlying diseases, heredity for asthma, previous hospitalization, recent stay abroad, allergies, smoking, recent travel abroad, recent contact with unwell individual, breastfeeding, preschool, origin of parents and socio-economic status will be collected through a standardized questionnaire based on previous studies.
Clinical parameters will be registered by the study doctor responsible for patient screening/enrolment in line with the study protocol of PERCH. Some of the clinical parameters included in the PERCH protocol are very rare in a Swedish context and to avoid overloading of the case report form, these will not be systematically registered at inclusion. However, information about these symptoms will be retrospectively collected from the medical records. Some clinical parameters are routinely recorded multiple times at the emergency unit. In these cases, the most extreme value (highest pulse/respiratory rate/body temperature/etc and lowest peripheral oxygen saturation) during the visit at the emergency unit until enrolment will be recorded. Information regarding admission, length of stay, radiological, routine clinical examination, microbiological and chemistry analyses, treatment, discharge diagnosis and complications will be retrospectively collected from the medical records.
All study subjects will be linked to the National Vaccination register to collect information regarding previous immunizations. To allow assessment of long-term complication, study subjects will also be linked to the National Patient Register, the National Death Register and the National Prescribed Drug Register for collection of discharge diagnoses according to ICD-10 as well as prescribed drugs.
Classification of Disease:
Etiology will be classified as probable or definitive based on clinical significance of the different microbiological test in the studies above. In TREND, the combination of probable and definitive etiology will be used in the main analysis, whereas children with definitive etiology will be assessed separately in a sub-analysis.
Definitive Viral Infection:
• PCR positive for influenza, RS virus, metapneumovirus or parainfluenza virus
Probable Viral Infection:
* PCR positive for adenovirus
* PCR positive for coronavirus, rhinovirus, bocavirus or enterovirus AND CRP \<20 AND reported fever \>24h.
Definitive Bacterial Infection:
* positive bacterial blood culture in blood or pleura fluid
* positive pneumococcal antigen test in pleura fluid
Probable Bacterial Infection:
* CRP \>80 (children ≤2 years) / \>120 (children 2-5 years) AND/OR
* Radiographic evidence of empyema on X-ray or ultrasound AND/OR
* Large dense infiltrate or lobar consolidation on chest x-ray
Definitive Atypical Bacterial Infection:
• Positive PCR B. pertussis or B. parapertussis
Probable Atypical Bacterial Infection:
• Positive PCR M. pneumoniae
Undetermined:
• Cases not fulfilling any criteria above
Mixed Viral-bacterial Infection:
• Children fulfilling criteria for both viral and bacterial infection
Classification of Long-term Complications:
Long-term complications (asthma and number of hospital-requiring respiratory infections) will be assessed after 3, 7 and 10 years following study completion by linking to the National Patient Register. Asthma will be classified as ICD-10 diagnosis of J45 or ≥3 prescriptions of inhalation steroids, beta-2-agonists or leukotriene antagonists according to the Prescribed Drug Register.
Power Calculation:
For the sample size calculation, the investigators focused on the assessment of MxA-levels in cases with viral CAP as compared to cases with bacterial CAP/controls (study I). Two power calculations were made, one for viral CAP versus bacterial CAP and one for viral CAP versus controls. The following assumptions were made:
A difference in MxA-level of 500µg/l between the groups was considered clinically relevant. A standard deviation of 1000 and 300 was assumed in cases with viral CAP and bacterial CAP/controls respectively based on previous studies on MxA.
Using an alpha-level of 0.05 (two-sided) at an 80% power, with an additional 20% addition to account for non-parametric testing and multivariate analyses, 42 children in each group (viral CAP, bacterial CAP and controls) would be needed.
To ensure that enough of the included cases would fulfill the TREND definition of viral and bacterial CAP, the proportion of viral respectively bacterial CAP (TREND definition) was calculated in our previous study that assessed Swedish children with x-ray verified CAP. By doing this, the prevalence of viral and bacterial CAP was estimated to 45% and 14% respectively. Hence 300 cases and 42 controls would be needed to ensure sufficient collection of cases with viral and bacterial CAP respectively. The investigators also would like to compare cases with viral CAP with controls testing positive for one or more virus by PCR. In our previous study, 35.4% of asymptomatic children tested positive for one or more virus. To include a sufficient number of virus-positive controls, the investigators hence aim at including 300 cases and 119 controls (42/0.354=119) in the TREND-study.
Ethical Considerations:
The study will be conducted in accordance with the latest version of The Declaration of Helsinki and the fundamental principles of respect for the individual (Article 8), their right to self-determination and the right to make informed decisions (Articles 20, 21 and 22) regarding participation in research, both initially and during the course of the research.
Significance:
The findings from the TREND project can be an important step to improve the care of children with clinical CAP. Improved near-patient differential diagnosis is a prerequisite for rational antibiotic use and decreasing unnecessary antibiotic treatment. Further better diagnosis of the pathogens causing acute respiratory infections makes it easier to give advice to parents on how their children should be cared for and better surveillance in the society.
Conditions
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Community-acquired Pneumonia
Keywords
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Community-acquired pneumonia
Pediatrics
Etiology
Point-of-care test
MxA
CRP
Procalcitonin
Infectious diseases
Respiratory viruses
Pediatric asthma
Study Design
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Observational Model Type
CASE_CONTROL
Study Time Perspective
PROSPECTIVE
Study Groups
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Cases with clinical CAP
Children 1-59 months at Sachs' Children and Youth Hospital with clinical CAP (both severe and non-severe) according to WHO-criteria.
No interventions assigned to this group
Control subjects
Children 1-59 months at Sachs' Children and Youth Hospital treated for a minor orthopedic (elective (e.g. hand surgery) or acute) or minor surgical disease, e.g. minor trauma (excluding e.g. appendicitis, major burns, major trauma).
No interventions assigned to this group
Eligibility Criteria
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Inclusion Criteria
Cases:
* Age 28 days to 59 months
* Reported and/or observed breathing troubles OR cough
* Observed age-adjusted tachypnea (≥50 breaths/min in children 1-12 months, ≥40/min in children \>1year) OR chest in-drawings
* Written informed consent
Controls:
* Age 28 days to 59 months
* Minor surgical or orthopedic disease (elective (e.g. hand surgery) or acute) or minor surgical disease, e.g. minor trauma (excluding e.g. appendicitis, major burns, major trauma)
* Written informed consent
* Age 28 days to 59 months
* Reported and/or observed breathing troubles OR cough
* Observed age-adjusted tachypnea (≥50 breaths/min in children 1-12 months, ≥40/min in children \>1year) OR chest in-drawings
* Written informed consent
Controls:
* Age 28 days to 59 months
* Minor surgical or orthopedic disease (elective (e.g. hand surgery) or acute) or minor surgical disease, e.g. minor trauma (excluding e.g. appendicitis, major burns, major trauma)
* Written informed consent
Exclusion Criteria
Cases:
* Previously included as case in the study
* Hospitalized during last 14 days
Controls:
Symptoms of respiratory disease 7 days before enrollment
* Previously included as control in the study
* Hospitalized during last 14 days
* Previously included as case in the study
* Hospitalized during last 14 days
Controls:
Symptoms of respiratory disease 7 days before enrollment
* Previously included as control in the study
* Hospitalized during last 14 days
Minimum Eligible Age
28 Days
Maximum Eligible Age
59 Months
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
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Stockholm South General Hospital
OTHER
Sponsor Role
collaborator
Science for Life Laboratory
UNKNOWN
Sponsor Role
collaborator
Uppsala University
OTHER
Sponsor Role
collaborator
Astrid Lindgren Children´s Hospital
OTHER
Sponsor Role
collaborator
Sahlgrenska University Hospital
OTHER
Sponsor Role
collaborator
Turku University Hospital
OTHER_GOV
Sponsor Role
collaborator
Karolinska Institutet
OTHER
Sponsor Role
lead
Responsible Party
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Tobias Alfvén
Associate professor
Responsibility Role
PRINCIPAL_INVESTIGATOR
Locations
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Sachs' Children and Youth Hospital
Stockholm, , Sweden
Site Status
Countries
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Sweden
References
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Adams PF, Hendershot GE, Marano MA; Centers for Disease Control and Prevention/National Center for Health Statistics. Current estimates from the National Health Interview Survey, 1996. Vital Health Stat 10. 1999 Oct;(200):1-203.
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BACKGROUND
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BACKGROUND
Korppi M, Remes S, Heiskanen-Kosma T. Serum procalcitonin concentrations in bacterial pneumonia in children: a negative result in primary healthcare settings. Pediatr Pulmonol. 2003 Jan;35(1):56-61. doi: 10.1002/ppul.10201.
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BACKGROUND
Esposito S, Tagliabue C, Picciolli I, Semino M, Sabatini C, Consolo S, Bosis S, Pinzani R, Principi N. Procalcitonin measurements for guiding antibiotic treatment in pediatric pneumonia. Respir Med. 2011 Dec;105(12):1939-45. doi: 10.1016/j.rmed.2011.09.003. Epub 2011 Sep 29.
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BACKGROUND
Engelmann I, Dubos F, Lobert PE, Houssin C, Degas V, Sardet A, Decoster A, Dewilde A, Martinot A, Hober D. Diagnosis of viral infections using myxovirus resistance protein A (MxA). Pediatrics. 2015 Apr;135(4):e985-93. doi: 10.1542/peds.2014-1946.
Reference Type
BACKGROUND
Sambursky R, Shapiro N. Evaluation of a combined MxA and CRP point-of-care immunoassay to identify viral and/or bacterial immune response in patients with acute febrile respiratory infection. Eur Clin Respir J. 2015 Dec 10;2:28245. doi: 10.3402/ecrj.v2.28245. eCollection 2015.
Reference Type
BACKGROUND
Toivonen L, Schuez-Havupalo L, Rulli M, Ilonen J, Pelkonen J, Melen K, Julkunen I, Peltola V, Waris M. Blood MxA protein as a marker for respiratory virus infections in young children. J Clin Virol. 2015 Jan;62:8-13. doi: 10.1016/j.jcv.2014.11.018. Epub 2014 Nov 18.
Reference Type
BACKGROUND
Rhedin S, Lindstrand A, Rotzen-Ostlund M, Tolfvenstam T, Ohrmalm L, Rinder MR, Zweygberg-Wirgart B, Ortqvist A, Henriques-Normark B, Broliden K, Naucler P. Clinical utility of PCR for common viruses in acute respiratory illness. Pediatrics. 2014 Mar;133(3):e538-45. doi: 10.1542/peds.2013-3042. Epub 2014 Feb 24.
Reference Type
BACKGROUND
Lindstrand A, Bennet R, Galanis I, Blennow M, Ask LS, Dennison SH, Rinder MR, Eriksson M, Henriques-Normark B, Ortqvist A, Alfven T. Sinusitis and pneumonia hospitalization after introduction of pneumococcal conjugate vaccine. Pediatrics. 2014 Dec;134(6):e1528-36. doi: 10.1542/peds.2013-4177. Epub 2014 Nov 10.
Reference Type
BACKGROUND
Rhedin S, Lindstrand A, Hjelmgren A, Ryd-Rinder M, Ohrmalm L, Tolfvenstam T, Ortqvist A, Rotzen-Ostlund M, Zweygberg-Wirgart B, Henriques-Normark B, Broliden K, Naucler P. Respiratory viruses associated with community-acquired pneumonia in children: matched case-control study. Thorax. 2015 Sep;70(9):847-53. doi: 10.1136/thoraxjnl-2015-206933. Epub 2015 Jun 15.
Reference Type
BACKGROUND
Barger-Kamate B, Deloria Knoll M, Kagucia EW, Prosperi C, Baggett HC, Brooks WA, Feikin DR, Hammitt LL, Howie SR, Levine OS, Madhi SA, Scott JA, Thea DM, Amornintapichet T, Anderson TP, Awori JO, Baillie VL, Chipeta J, DeLuca AN, Driscoll AJ, Goswami D, Higdon MM, Hossain L, Karron RA, Maloney S, Moore DP, Morpeth SC, Mwananyanda L, Ofordile O, Olutunde E, Park DE, Sow SO, Tapia MD, Murdoch DR, O'Brien KL, Kotloff KL; Pneumonia Etiology Research for Child Health (PERCH) Study Group. Pertussis-Associated Pneumonia in Infants and Children From Low- and Middle-Income Countries Participating in the PERCH Study. Clin Infect Dis. 2016 Dec 1;63(suppl 4):S187-S196. doi: 10.1093/cid/ciw546.
Reference Type
BACKGROUND
He Q, Viljanen MK, Arvilommi H, Aittanen B, Mertsola J. Whooping cough caused by Bordetella pertussis and Bordetella parapertussis in an immunized population. JAMA. 1998 Aug 19;280(7):635-7. doi: 10.1001/jama.280.7.635.
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BACKGROUND
van den Brink G, Wishaupt JO, Douma JC, Hartwig NG, Versteegh FG. Bordetella pertussis: an underreported pathogen in pediatric respiratory infections, a prospective cohort study. BMC Infect Dis. 2014 Sep 30;14:526. doi: 10.1186/1471-2334-14-526.
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DERIVED
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
2017/958-31
Identifier Type: -
Identifier Source: org_study_id