Culture-negative bacteria: a blind spot in bacterial pathogen prioritization.

Area of Science:

• Infectious Diseases
• Microbiology
• Global Health

Background:

• Culture-negative bacteria (CNB) like Bartonella, Coxiella, Rickettsia, Orientia, and Leptospira cause significant febrile illness, particularly in low- and middle-income countries (LMICs).
• Standard diagnostic methods often fail to detect these pathogens, leading to underdiagnosis and underestimation of their public health impact.
• Limited diagnostic infrastructure and high pathogen diversity in LMICs exacerbate the problem.

Purpose of the Study:

• To evaluate current infectious disease guidelines for pathogen recognition and prioritization in the context of CNB.
• To identify diagnostic limitations and cognitive biases contributing to the neglect of CNB infections.
• To underscore the need for improved recognition and research investment for CNB in global health agendas.

Main Methods:

• Narrative review of existing infectious disease guidelines.
• Application of guideline criteria to CNB for assessing fit and identifying gaps.
• Discussion of diagnostic challenges, clinician biases, and epidemiological data fragmentation.

Main Results:

• Existing frameworks often fail to adequately incorporate or prioritize CNB detection.
• Diagnostic limitations and clinician biases significantly impede the recognition of CNB.
• The disproportionate burden of CNB in LMICs is compounded by fragmented data and limited research.

Conclusions:

• CNB are a neglected group of pathogens despite their significant impact on febrile illnesses globally, especially in LMICs.
• Systematic underdiagnosis stems from a combination of technical, cognitive, and systemic factors.
• Addressing the neglect of CNB requires revising diagnostic and prioritization frameworks, improving infrastructure, and increasing research investment.