Potential Game-Changer in Tracking Cholera

Serosurveillance model analyzes six serum markers to assess disease history, follow outbreaks.
A new method that identifies Vibrio cholerae O1 in just a drop of blood could be a game-changer in tracking the path and burden of disease. Researchers published their results in Science Translational Medicine (STM). “Currently, we use serological [blood antibody] assays for the diagnosis and surveillance of several infectious diseases, including HIV, viral hepatitis, and dengue. We now have a serological assay for the surveillance of cholera,” Daniel Leung, MD, MSc, an assistant professor in the Division of Infectious Diseases at University of Utah Health and study co-author, told CLN Stat.
Cholera infects 2 million to 3 million individuals around the world, killing more than 100,000 people annually. The disease is especially prevalent in Africa, South Asia, and Haiti. The World Health Organization Global Task Force for Cholera Control has a goal to eliminate cholera as a public health threat by 2030, yet an effective method to identify those with the disease has been out of reach.
Common cholera tests include bacterial culture, microscopy, antigen detection, and molecular methods such as polymerase chain reaction. “The problem with these methods is that you need a stool sample from a cholera patient, which may be logistically difficult in some settings,” according to Leung. Unless a patient has acute watery diarrhea, most cases go unreported and aren’t confirmed with laboratory testing, making it difficult to track the geographic path and prevalence of disease.
Leung and his colleagues theorized that surveying blood antibody profiles, a process known as serosurveillance, could accurately identify disease in patients. “Establishing a serosurveillance method overcomes many of the shortcomings of traditional surveillance approaches by providing a new way to track the spread of cholera in short-term outbreaks as well as assess long-term burden of cholera across different populations,” said Leung in a statement.
Leung and his colleagues developed an algorithm that uses data from antibody signatures in blood to monitor the concentration of six serum markers found in cholera patients. To identify recent Vibrio cholerae O1 infections, the team looked at more than 1,500 blood samples taken from cholera patients at the icddr,b hospital in Dhaka, Bangladesh and 58 of their uninfected contacts over a ten-year period. Going back at least a year, the algorithm was able to determine the time frame in which a cholera infection took place in a patient—whether it was 45 or even 100 days prior to giving their blood sample.
Among the antibodies they examined, the vibriocidal antibody marker was most predictive of recent infection. The marker “is the only one that is a measure of antibody function—it is an assay that measures how well the antibodies in blood kills Vibrio cholerae bacteria,” Leung explained.
The researchers were able to validate their method on two separate fronts. First, it had good results in a very different cohort of 38 North Americans who volunteered to be challenged with V. cholerae O1. “Furthermore, the model accurately estimated the annual incidence of cholera in simulated serosurveys with populations ranging from 500 to 3,000 individuals, indicating it could potentially help assess the burden of cholera across different population,” according to an STM summary of the study results.
Next steps are to try to find ways to distinguish between individuals with cholera infection and those vaccinated with the cholera vaccine. “We’re also working towards making the antibody assays (especially the vibriocidal) easier to perform in the field,” Leung said.