Prognostic markers of meningococcal disease in children: recent advances and future challenges

Abstract

Meningococcal disease is a life-threatening condition and a major cause of bacterial meningitis and sepsis worldwide. In many fatal cases, meningococcal disease is rapidly progressive and death occurs within hours of the initial symptoms. The early identification of patients at high risk of death would be useful in order to provide aggressive and more personalized clinical management with the proper level of supportive therapy required, contributing to an improvement in the survival rate and reduction in sequelae. The current study aims to review the current published literature about prognostic markers of meningococcal sepsis in children in order to elaborate conclusions and recommendations that could guide clinical practice and further research.

Keywords::

• children
• marker
• meningococcal
• prognosis
• score
• sepsis
• severity

Financial & competing interests disclosure

F Martinón-Torres’s research activities have been supported by grants from Instituto Carlos III (Intensificación de la actividad investigadora) and Fondo de Investigación Sanitaria (FIS; PI10/00540 and PI13/02382) del plan nacional de I+D+I and ‘fondos FEDER’. The authors received funding from the European Union’s seventh Framework program under ECGA no. 279185 (EUCLIDS) during the production of this manuscript. Dr Inwald is grateful for support from the NIHR Biomedical Research Centre funding scheme. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• There is strong enough evidence to affirm that procalcitonin is a useful biomarker for both, identifying children with meningococcal infection and predicting disease severity and mortality in these patients. Further research is needed to clarify the optimal cutoff value.

• The utility of C-reactive protein and blood count parameters as severity markers in meningococcal disease is currently unclear and controversial.

• Some coagulation factors (TAFI, TAFI-AP and TAFIa[i]) and chemokines (MCP-1, MIP-1α, GRO-α, IL-8, IL-6 and TNF-α) seem to be good predictors of severe disease and mortality in children with meningococcal sepsis, but further research is needed to confirm their utility.

• The quantification of cortisol and adrenocorticotropic hormone serum levels on admission may be potentially useful in identifying children with meningococcal disease at a high risk of severe disease or death.

• There is little evidence about the utility of lipoproteins, cholesterol and intestinal fatty acid binding protein as prognostic markers of meningococcal sepsis in children.

• The current evidence suggests that a specific polymorphism in the coding gene of PAI-1 (SERPINE1) and the FcγRIIIa-R/R131 allotype may be valuable prognostic markers in children with meningococcal disease.

• There is little evidence about the utility of TLR4 and TLR9 polymorphisms as prognostic markers of meningococcal disease in children.

• Pediatric risk of mortality score and Glasgow Meningococcal Septicaemia Prognostic Score are useful scores for identifying children at high risk of death and severe disease.

• The base excess and platelet count score and the platelets and neutrophils product are promising severity scales, recently developed, but further research is needed to assess their utility as prognostic markers in pediatric meningococcal disease.