Advancing diagnostic tests to distinguish bacterial from non-bacterial infections causes of fever

The challenge of antimicriobial resistance
Antibiotic resistance has become a major global health threat – and a problem that is being accelerated by hu-man behaviour. Antibiotics are precious medicines that have enabled us to survive bacterial infections that were frequently fatal in the past. However, the inappropriate use of these medicines now threatens their effective-ness. Already, infections such as pneumonia, tuberculosis and gonorrhoea are becoming harder to treat as the drugs used to treat them become less effective. Without urgent action to safeguard the antibiotics available to us, we risk returning to an era where common infections become deadly.

Limiting the use of antibiotics to cases where they will be effective is critical, but health workers need better tools to be able to promptly confirm bacterial infections. Three or more days is too long to wait for lab results. A new test that can quickly distinguish bacterial from non-bacterial causes of acute fever is urgently needed to guide appropriate patient treatment and to preserve the effectiveness of existing antibiotics in a context of rap-idly increasing antimicrobial resistance.

Meeting on Fever biomarkers for new diagnostic tests
A September 2015 meeting in Geneva convened by WHO, ReAct, MSF Access Campaign and FIND gathered together more than 50 biomarker scientists, policymakers, implementers, clinical researchers and industry prod-uct developers – a diversity of stakeholders representing the full “bench to bedside” pathway for biomarker test-ing to differentiate between bacterial and viral pathogens.

The meeting helped to identify the tools, resources and partnerships needed to accelerate the development of a point-of-care diagnostic assay for the detection of bacterial infections in patients with acute fever in low-resource settings. Strengthening multi-sectoral partnerships that include industry, academia, clinicians, NGOs and WHO will contribute to the accelerated development of needed tests. While several promising biomarkers have been identified for new tests, most of them are still in the proof-of-concept phase and have only been evaluated with a limited number of patients in high-income countries. Valida-tion with patients in low- and middle-income countries is needed.

Next steps
Meeting participants discussed the unique challenges of bringing biomarker diagnostics to low- and middle-income country settings and agreed on next steps for rapid action on the continued development and validation of potential biomarkers for new tests, including:

• development of a target product profile (TPP) to guide future diagnostics development;
• development of standardized guidelines for clinical trials of new fever tests;
• harmonization of reference standards; and
• agreement on specifications for building specimen banks to meet validation and evaluation needs.

Since the September meeting, a draft TPP has been developed and circulated to a subset of the experts who attended this meeting. It will then be further revised and shared with the larger group, and disseminated to stakeholders globally with a survey. The goal is to finalize the TPP in January 2016 at a consensus meeting. Concurrently, the convening partners are working on the development of standard protocols for clinical trials and specimen banking.