Laboratory and Pilot Clinical Assessment of the Accuracy of Low-Cost, Point-of-Care Lateral Flow Detection Strips for Procalcitonin and Presepsin and a Clinical Strip Reader for the Early Detection of Puerperal Sepsis

Funding Agency:

Merck for Mothers

Overview:

Puerperal sepsis is a leading cause of maternal death, with an estimated 5 million cases worldwide annually and 62,000 deaths. While incidence may be low, the relative risk of mortality is much higher than other causes of maternal death, with a 10% mortality rate in high-income countries, and a 33% mortality rate in low-income countries due to inability to diagnose prior to hospital discharge. Rapid, point-of-care diagnostic tests that can diagnose sepsis prior to symptom onset have the potential to significantly decrease maternal mortality.

To meet this need, we are developing a rapid, low-cost, point-of-care diagnostic test for puerperal sepsis for low-resource settings. The lateral flow assay detects procalcitonin (PCT), C-Reactive Protein (CRP), and presepsin, three well characterized protein biomarkers of sepsis. PCT levels are increased in patients with bacterial infections leading to SIRS, and levels have been shown to exhibit a rapid 12-fold increase in septic patients over the first 4-12 hours of infection. CRP levels slowly increase in patients with inflammation due to bacterial infections after 6-8 hours, holding a steady maximum value after 24 hours that is at least 4-fold higher than baseline levels in healthy patients. Presepsin’s release into the bloodstream is induced by the phagocytosis of bacteria, making it a very specific marker to severe bacterial infections; levels increase 12-fold in septic patients and have shown a clinical sensitivity of 90%. By detecting these biomarkers together, we believe we can not only detect infections prior to symptomatic evidence, but also differentiate between mild infections and infections leading to sepsis. The test can be performed in minutes at the bedside with only 50uL of whole blood obtained from a finger-prick. We are currently optimizing the antibody selection for quantitative detection of presepsin, but our strips have demonstrated quantitative detection of PCT between [0.5 ng/mL] and [100 ng/mL] and CRP between [0.5 mg/L] and [100 mg/L] in serum samples spiked with protein. Quantitative analysis by signal-to-background results in an average PCT limit of detection at [0.5 ng/mL] and CRP limit of detection at [0.5 mg/L].