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Research Article
Elena María Rincón-López
Hospital General Universitario Gregorio Marañón
Corresponding Author
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Background
Etiological diagnosis of fever in children with sickle cell disease (SCD) is often challenging. The aim of this study was to analyze the pattern of inflammatory biomarkers in SCD febrile children and controls, in order to determine predictors of severe bacterial infection (SBI).
Methods
A prospective, case-control study of febrile and steady-state SCD children was carried out during 3 years. Clinical characteristics and laboratory parameters, including 10 serum proinflammatory cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17a, IFN-γ and TNF-α) and comparisons among study subgroups were analyzed.
Results
A total of 137 patients (79 cases and 58 controls) were included in the study; 78.5% males, median age 4.1 (1.7-7.5) years. Four cases were diagnosed with SBI, 41 viral infection (VI) and 33 no proven infection (NPI). IL-6 was significantly higher in patients with SBI than in patients with VI or NPI (163 vs 0.7 vs 0.7 pg/ml, p < 0.001), and undetectable in all controls. The rest of the cytokines analyzed did not show any significant difference. The optimal cut-off value of IL-6 for the diagnosis of SBI was 125 pg/mL, with high PPV and NPV (PPV of 100% for a prevalence of 5, 10 and 15% and NPV of 98.7%, 97.3% and 95.8% for those prevalences, respectively).
Conclusion
We found that IL-6 (with a cut-off value of 125 pg/ml) was an optimal marker for SBI in this cohort of febrile SCD children, with high PPV and NPV. Therefore, given its rapid elevation, IL-6 may be useful to early discriminate SCD children at risk of SBI, in order to guide their management.
Keywords
Sickle cell disease, infection, fever, cytokines, interleukin-6
Figure 1
Figure 2
No competing interests reported.
This is a list of supplementary files associated with this preprint. Click to download.
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View the published article at BMC Infectious Diseases.
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Editorial decision: Major revision
On 05 May, 2021
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Received 01 May, 2021
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On 06 Apr, 2021
Reviews received
Received 12 Mar, 2021
Reviewers agreed
On 11 Mar, 2021
Reviewers invited
Invitations sent on 11 Mar, 2021
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On 11 Mar, 2021
Editor invited
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On 10 Mar, 2021
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Subject Areas
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A new preprint design is coming!
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See the published version of this preprint at BMC Infectious Diseases.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Elena María Rincón-López
Hospital General Universitario Gregorio Marañón
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at BMC Infectious Diseases.
Version 1
Posted 16 Mar, 2021
No community comments so far
Editorial decision: Major revision
On 05 May, 2021
Reviews received
Received 01 May, 2021
Reviewers agreed
On 06 Apr, 2021
Reviews received
Received 12 Mar, 2021
Reviewers agreed
On 11 Mar, 2021
Reviewers invited
Invitations sent on 11 Mar, 2021
Editor assigned
On 11 Mar, 2021
Editor invited
On 10 Mar, 2021
Submission checks complete
On 10 Mar, 2021
First submitted
On 02 Mar, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Infectious Diseases
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at BMC Infectious Diseases.
Background
Etiological diagnosis of fever in children with sickle cell disease (SCD) is often challenging. The aim of this study was to analyze the pattern of inflammatory biomarkers in SCD febrile children and controls, in order to determine predictors of severe bacterial infection (SBI).
Methods
A prospective, case-control study of febrile and steady-state SCD children was carried out during 3 years. Clinical characteristics and laboratory parameters, including 10 serum proinflammatory cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17a, IFN-γ and TNF-α) and comparisons among study subgroups were analyzed.
Results
A total of 137 patients (79 cases and 58 controls) were included in the study; 78.5% males, median age 4.1 (1.7-7.5) years. Four cases were diagnosed with SBI, 41 viral infection (VI) and 33 no proven infection (NPI). IL-6 was significantly higher in patients with SBI than in patients with VI or NPI (163 vs 0.7 vs 0.7 pg/ml, p < 0.001), and undetectable in all controls. The rest of the cytokines analyzed did not show any significant difference. The optimal cut-off value of IL-6 for the diagnosis of SBI was 125 pg/mL, with high PPV and NPV (PPV of 100% for a prevalence of 5, 10 and 15% and NPV of 98.7%, 97.3% and 95.8% for those prevalences, respectively).
Conclusion
We found that IL-6 (with a cut-off value of 125 pg/ml) was an optimal marker for SBI in this cohort of febrile SCD children, with high PPV and NPV. Therefore, given its rapid elevation, IL-6 may be useful to early discriminate SCD children at risk of SBI, in order to guide their management.
Figure 1
Figure 2
No competing interests reported.
This is a list of supplementary files associated with this preprint. Click to download.
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