In resource limited settings malaria-negative patients are often treated empirically. This contributes to the indiscriminate use of antimicrobial drugs but also results in poor patient management and poor outcomes. This review aimed to identify host biomarkers capable of differentiating bacterial from non-bacterial infections, to guide patient care at the point of first contact. Next steps are also explored to move from biomarkers to diagnostic tests. English language studies, published in 2015-2017, evaluating the performance of relevant host biomarkers were included. Study quality was assessed using stringent criteria and biomarkers were categorized into hematology, inflammatory and genetic markers. In total, 37 out of 144 studies were included, evaluating 95 new markers compared to the earlier 2010-2015 review. Most (31/37, 84%) studies still involved populations from high-income countries and did not therefore consider malaria infections as a confounding factor. The most frequently evaluated biomarkers were still: C-reactive protein (19/37, 51%), procalcitonin (12/37, 32%) and white blood cell count (7/37, 19%). While the basic research in the biomarker area continues, limited data are available on how these markers perform in settings with multiple other co-infections, such as malaria. While transforming biomarkers into useful commercial tests is challenging, FIND and partners have launched multiple evaluation studies as well as development projects aiming at improving the management of malaria negative patients in diverse settings. This work presents an overview about recent developments in host biomarker research globally and in malaria-endemic areas and provides a gap analysis as the basis for prioritizing efforts for point-of-care test development. Further the aim is to provide long and short term approaches to tackle this challenging topic with single or multiplexed tools (for host biomarkers or/and specific pathogens including malaria) and to explore the study needs to bridge these gaps.