Table 1

Candidate host biomarkers

Host biomarkerSummary of supportive data
Angiopoietin-1 and 2 (Ang-1 and Ang-2)Supportive data from Asia/SSA in children/adults, that Ang-2, Ang-1 and/or Ang-2:1 ratio predicts mortality in malaria, SBI and all-cause febrile illness.26 29 46–49
Soluble fms-like tyrosine kinase-1 and 2 (sFlt-1 and s-Flt-2)Supportive data from SSA that sFlt-1 predicts mortality in paediatric severe malaria and adults with all-cause febrile illness26 29 46; in Thailand sFlt-2 discriminates uncomplicated dengue from dengue associated with plasma leak in children.50
Soluble vascular adhesion molecule-1 (sVCAM-1)Supportive data from SSA that sVCAM-1 predicts mortality in children/adults with all-cause febrile illness.26 29
Soluble intercellular adhesion molecule-1 (sICAM-1)Supportive data from Uganda that sICAM-1 predicts mortality in paediatric severe malaria and all-cause febrile illness26 51; in Bangladesh, sICAM-1 predicts mortality in neonatal sepsis.52
Soluble tumour necrosis factor receptor-1 (sTNFR-1)Supportive data from Tanzania that sTNFR-1 predicts mortality in children/adults with all-cause febrile illness.26 29
Soluble thrombomodulin (sTM)Supportive data from Malawi that sTM predicts mortality in children with severe malaria.53
C-X-C motif chemokine-10 (CXCL-10)/interferon-y induced protein-10 (IP-10)Supportive data from Uganda that IP-10 predicts mortality in children with severe malaria.46
Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1)Supportive data from SSA that sTREM-1 predicts mortality in paediatric severe malaria and in adults/children with all-cause febrile illness26 29 46 51; in Asia, sTREM-1 predicted length of stay in infant febrile illness and in-hospital mortality in adults hospitalised with infection.54 55
Interleukin-6 (IL-6)Supportive data from India that IL-6 is predictive of mortality in children with dengue56; in Switzerland, supportive data that IL-6 predicts duration of antibiotic therapy for febrile children with lower respiratory tract infections.57
Interleukin-8 (IL-8)Supportive data from India that IL-8 is predictive of mortality in children with dengue56; in the UK, supportive data that IL-8 predicts disease severity in children with meningococcal disease.58
Interleukin-10 (IL-10)Supportive data from India that IL-10 is predictive of mortality in children with dengue.56
Chitinase-3-like protein-1 (CHI3L1)Supportive evidence from SSA that CHI3L1 is predictive of mortality in children/adults with all-cause febrile illness.26 29
Procalcitonin (PCT)Supportive evidence that PCT is predictive of severe illness in hospitalised children with suspected bacterial infections or meningococcal disease.59 60
LactateSupportive evidence that lactate is predictive of mortality in hospitalised children with febrile illness in East Africa.61 62
GlucoseSupportive evidence that hypoglycaemia is predictive of mortality in hospitalised children in Tanzania.63
HaemoglobinSupportive evidence that haemoglobin is predictive of mortality in hospitalised children with febrile illnesses in East Africa.62 64
C reactive protein (CRP)Although there is limited supportive evidence for the use of CRP as a prognostic marker for disease severity, as it is the most widely studied biomarker in our region, and numerous point-of-care tests already exist, further evaluation is warranted.
  • List is subject to review as new evidence comes to light during the conduct of the study. SBI = serious bacterial infection; SSA = sub-Saharan Africa.