External validation and updating of clinical severity scores to guide referral of young children with acute respiratory infections in resource-limited primary care settings

Chandna, Arjun; Mwandigha, Lazaro; Koshiaris, Constantinos; Limmathurotsakul, Direk; Nosten, François; Lubell, Yoel; Perera-Salazar, Rafael; Turner, Claudia; Turner, Paul

doi:10.1101/2022.12.06.22283016

Cited by 3 publications

(5 citation statements)

References 41 publications

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“…The performance of the LqSOFA score is consistent with our broader analysis of the score in children with ARIs, 13 and comparable to that reported in the original derivation and validation study. 12 The LqSOFA score is the largest age-adapted version of the widelyendorsed qSOFA score for adults, 38 and was specifically designed for triaging children presenting from the community.…”

Section: Discussionsupporting

confidence: 86%

“…12 In a recent analysis we demonstrated that the LqSOFA score outperformed two other paediatric severity scores in Southeast Asian children with acute respiratory infections (ARIs), suggesting that the score has excellent generalisability and may be practical for use in resource-limited primary care settings. 13 A growing body of evidence indicates that final common pathophysiological pathways reflecting endothelial injury and immune activation are shared across a range of infectious diseases, 14,15 including in young children with pneumonia. [16][17][18] Markers of these pathways improve performance of clinical severity scores, 19 including qSOFA, 15,20 and consequently they have been proposed as adjuncts to paediatric triage tools.…”

Section: Introductionmentioning

confidence: 99%

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Defining the role of host biomarkers in the diagnosis and prognosis of childhood pneumonia – a prospective cohort study

Chandna

Lubell

Mwandigha

et al. 2022

Preprint

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Background Reliable tools to inform outpatient management of childhood pneumonia in resource-limited settings are needed. We investigated the value added by biomarkers of host infection response to the performance of the Liverpool quick Sequential Organ Failure Assessment score (LqSOFA), for triage of children presenting with pneumonia to a primary care clinic in a refugee camp on the Thailand-Myanmar border. Methods 900 presentations of children aged ≤ 24 months meeting WHO pneumonia criteria were included. The primary outcome was receipt of supplemental oxygen. We compared discrimination of a clinical risk score (LqSOFA) to markers of endothelial injury (Ang-1, Ang-2, sFlt-1), immune activation (CHI3L1, IP-10, IL-1ra, IL-6, IL-8, IL-10, sTNFR-1, sTREM-1), and inflammation (CRP, PCT), and quantified the net-benefit of including biomarkers alongside LqSOFA. We evaluated the differential contribution of LqSOFA and host biomarkers to the diagnosis and prognosis of severe pneumonia. Results 49/900 (5.4%) presentations met the primary outcome. Discrimination of LqSOFA and Ang-2, the best performing biomarker, were comparable (AUC 0.82 [95% CI 0.76-0.88] and 0.81 [95% CI 0.74-0.87] respectively). Combining Ang-2 with LqSOFA improved discrimination (AUC 0.91; 95% CI 0.87-0.94; p < 0.001), and resulted in greater net-benefit, with 10-30% fewer children requiring oxygen supplementation incorrectly identified as safe for community-based management. Ang-2 had greater prognostic utility than LqSOFA to identify children requiring supplemental oxygen later in their illness course. Conclusions Combining Ang-2 and LqSOFA could guide referrals of childhood pneumonia from resource-limited community settings. Further work on integration into patient triage is required.

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Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Defining the role of host biomarkers in the diagnosis and prognosis of childhood pneumonia – a prospective cohort study

Chandna

Lubell

Mwandigha

et al. 2022

Preprint

Self Cite

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show abstract

“…The performance of the LqSOFA score is consistent with our broader analysis of the score in children with ARIs 13 , and comparable to that reported in the original LqSOFA derivation and validation study 12 . The LqSOFA score is the largest age-adapted version of the widely-endorsed qSOFA score for adults 45 , and was specifically designed for triaging children presenting from the community.…”

Section: Discussionsupporting

confidence: 85%

“…Recently, an age-adapted version (the Liverpool-qSOFA [LqSOFA] score; Table 1 ) was developed specifically for febrile children presenting from the community 12 . In a recent analysis we demonstrated that the LqSOFA score outperformed two other paediatric severity scores in Southeast Asian children with acute respiratory infections (ARIs), suggesting that the score has excellent generalisability and may be practical for use in resource-limited primary care settings 13 .…”

Section: Introductionmentioning

confidence: 99%

Defining the role of host biomarkers in the diagnosis and prognosis of the severity of childhood pneumonia: a prospective cohort study

Chandna

Lubell

Mwandigha

et al. 2023

Sci Rep

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Reliable tools to inform outpatient management of childhood pneumonia in resource-limited settings are needed. We investigated the value added by biomarkers of the host infection response to the performance of the Liverpool quick Sequential Organ Failure Assessment score (LqSOFA), for triage of children presenting with pneumonia to a primary care clinic in a refugee camp on the Thailand-Myanmar border. 900 consecutive presentations of children aged ≤ 24 months meeting WHO pneumonia criteria were included. The primary outcome was receipt of supplemental oxygen. We compared discrimination of a clinical risk score (LqSOFA) to markers of endothelial injury (Ang-1, Ang-2, sFlt-1), immune activation (CHI3L1, IP-10, IL-1ra, IL-6, IL-8, IL-10, sTNFR-1, sTREM-1), and inflammation (CRP, PCT), and quantified the net benefit of including biomarkers alongside LqSOFA. We evaluated the differential contribution of LqSOFA and host biomarkers to the diagnosis and prognosis of pneumonia severity. 49/900 (5.4%) presentations met the primary outcome. Discrimination of LqSOFA and Ang-2, the best performing biomarker, were comparable (AUC 0.82 [95% CI 0.76–0.88] and 0.81 [95% CI 0.74–0.87] respectively). Combining Ang-2 with LqSOFA improved discrimination (AUC 0.91; 95% CI 0.87–0.94; p < 0.001), and resulted in greater net benefit, with 10–30% fewer children who required oxygen supplementation incorrectly identified as safe for community-based management. Ang-2 had greater prognostic utility than LqSOFA to identify children requiring supplemental oxygen later in their illness course. Combining Ang-2 and LqSOFA could guide referrals of childhood pneumonia from resource-limited community settings. Further work on test development and integration into patient triage is required.

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“…The LqSOFA could be very useful in low-resource settings, for it consists of easy- and quick-to-score clinical parameters (heart rate, respiratory rate, capillary refill time, consciousness level) and no laboratory tests. The LqSOFA showed promising results in a primary care setting with limited resources in Thailand [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Identifying critically ill children in Malawi: A modified qSOFA score for low-resource settings

Kumwenda,

Assies,

Snik

et al. 2024

PLOS Glob Public Health

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In low-resource settings, a reliable bedside score for timely identification of children at risk of dying, could help focus resources and improve survival. The rapid bedside Liverpool quick Sequential Organ Failure Assessment (LqSOFA) uses clinical parameters only and performed well in United Kingdom cohorts. A similarly quick clinical assessment-only score has however not yet been developed for paediatric populations in sub-Saharan Africa. In a development cohort of critically ill children in Malawi, we calculated the LqSOFA scores using age-adjusted heart rate and respiratory rate, capillary refill time and Blantyre Coma Scale, and evaluated its prognostic performance for mortality. An improved score, the Blantyre qSOFA (BqSOFA), was developed (omitting heart rate, adjusting respiratory rate cut-off values and adding pallor), subsequently validated in a second cohort of Malawian children, and compared with an existing score (FEAST-PET). Prognostic performance for mortality was evaluated using area under the receiver operating characteristic curve (AUC). Mortality was 15.4% in the development (N = 493) and 22.0% in the validation cohort (N = 377). In the development cohort, discriminative ability (AUC) of the LqSOFA to predict mortality was 0.68 (95%-CI: 0.60–0.76). The BqSOFA and FEAST-PET yielded AUCs of 0.84 (95%-CI:0.79–0.89) and 0.83 (95%-CI:0.77–0.89) in the development cohort, and 0.74 (95%-CI:0.68–0.79) and 0.76 (95%-CI:0.70–0.82) in the validation cohort, respectively. We developed a simple prognostic score for Malawian children based on four clinical parameters which performed as well as a more complex score. The BqSOFA might be used to promptly identify critically ill children at risk of dying and prioritize hospital care in low-resource settings.

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External validation and updating of clinical severity scores to guide referral of young children with acute respiratory infections in resource-limited primary care settings

Cited by 3 publications

References 41 publications

Defining the role of host biomarkers in the diagnosis and prognosis of childhood pneumonia – a prospective cohort study

Defining the role of host biomarkers in the diagnosis and prognosis of childhood pneumonia – a prospective cohort study

Defining the role of host biomarkers in the diagnosis and prognosis of the severity of childhood pneumonia: a prospective cohort study

Identifying critically ill children in Malawi: A modified qSOFA score for low-resource settings

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