Cholera rapid diagnostic tests at the host-microbe interface: Key Considerations for Global Deployments

Area of Science:

• Microbiology
• Infectious Diseases
• Diagnostic Technologies

Background:

• Effective cholera outbreak response relies on accurate bedside rapid diagnostic tests (RDTs) due to limited laboratory access.
• Cholera diagnostics face vulnerabilities, including antibiotic interference and bacteriophage (phage) predation specific to Vibrio cholerae (Vc).

Purpose of the Study:

• To investigate the impact of phage and antibiotics on RDT performance in cholera diagnosis.
• To characterize how diagnostic vulnerabilities affect RDT accuracy in a nationwide study.

Main Methods:

• Prospective nationwide study in Bangladesh involving over 2000 patients with diarrheal disease.
• Utilized culture, quantitative PCR (qPCR), and mass spectrometry (LC-MS/MS) for Vc detection and antibiotic analysis.

Main Results:

• No significant effect of phage on RDT performance was observed with current gold standards (culture/qPCR).
• Expanding diagnostic criteria to include phage slightly decreased RDT sensitivity.
• RDT sensitivity and specificity significantly increased in patients with moderate to severe dehydration.
• Antibiotics were detected in over 80% of samples, limiting assessment of their RDT impact.
• Restricting RDT use to severe cases without antibiotic exposure could increase sensitivity by 50%.

Conclusions:

• Cholera RDTs have critical limitations impacting global deployment.
• Further research is needed to explore the inclusion of phage detection in diagnostic criteria for improved cholera case detection.
• Findings may inform diagnostic development for other diseases with similar vulnerabilities.