Wastewater an Early Warning System for Bird Flu Outbreaks

LOS ANGELES — Researchers found a biomarker for avian flu in Texas wastewater treatment plants more than a month before the first confirmed cases of H5N1 among Texas dairy cattle in 2024, according to new data presented at the Infectious Disease Week (IDWeek) 2024 Annual Meeting.

The retrospective finding demonstrates the power of wastewater monitoring in detecting pathogens that could alert public health departments earlier to impending outbreaks.

Outbreaks of H5N1 were seen regularly in poultry in the United States, but the latest outbreak “has been very concerning because of the spread in cattle and a few human cases,” presenting author Alessandro Zulli, PhD, postdoctoral fellow, Stanford University, Palo Alto, California, said.

As of October 11, 20 human cases of H5 bird flu have been reported in the United States since April of 2024, according to the Centers for Disease Control and Prevention. One other case was reported in 2022.

Researchers were looking to explain unseasonal spikes in influenza A virus seen in Texas wastewater treatment plants in early 2024. Zulli and colleagues turned to wastewater monitoring, which had been used historically to track viruses for cholera, typhoid, and polio but recently was used to track severe acute respiratory syndrome coronavirus 2. Zulli noted wastewater-based epidemiology is useful with tracking an array of other pathogens, such as influenza and respiratory syncytial virus.

Zulli is part of the Stanford WastewaterSCAN team, which operates in partnership with Emory University, Atlanta, and industry partner, Verily. The team monitors wastewater nationally to track more than a dozen pathogens across 190 wastewater locations three times a week and publicly displays the results on a dashboard at data.Wastewaterscan.org within 48 hours of readings.

Their data had shown an increase in H5N1 in poultry, mammals, and wild birds in late 2023 and early 2024, so they investigated whether the influenza increase in Texas could be H5N1.

They developed a hydrolysis probe digital droplet H5 reverse transcription polymerase chain reaction assay for detecting the H5 hemagglutinin gene found in bird flu and demonstrated it to be 100% specific and 90% sensitive, according to the data. They distributed the test to wastewater treatment plants and identified wastewater treatment plants that had registered increases in influenza A concentrations beyond seasonal variations.

During the monitoring period, after the seasonal influenza period had ended, 59 wastewater treatment plants showed increases in the H5 gene in bird flu that coincided with the recorded emergence of highly pathogenic avian influenza H5N1 in dairy cattle.

At a wastewater plant in Amarillo, Texas, he said, retrospective sampling by the Stanford team found that H5N1 had been detected on February 24, 2024, 2 weeks before cattle illnesses were reported in Texas. “The first cattle illness was reported on March 7, and at that point they didn’t know what it was,” Zulli said. The first confirmed detection of H5N1 in dairy cattle was on March 25. A month can give public health officials a good amount of time to develop a response, he said.

“We have the infrastructure and expertise necessary to deploy rapid responses to these emerging pathogens,” Zulli said. “We’ve demonstrated that — perhaps most convincingly — with H5N1, where we’ve been able to detect avian influenza markers well before clinical cases or the detection of cattle in 32 locations across eight states.”

He said with information ahead of time, public health officials can deploy staff to test poultry farms and cattle farms to test for the virus and medical facilities to look for increased cases of conjunctivitis, for example, which has been the primary symptom for humans infected by cattle.

“Wastewater monitoring remains the fastest, most unbiased method to actually measure the prevalence and spread of pathogens in a population. Leveraging this could have enormous implications for understanding the spread of illnesses and implementing interventions like the ones we have for H5N1,” Zulli said.

In the future, researchers need to better understand the shedding of the viruses — how much is from humans and how much from animals, Zulli said.

Karl Evans Henson, MD, an infectious disease physician and director of the Department of Advanced Medical Education at The Medical City in Pasig City, Philippines, who was not part of the study, said Zulli’s demonstration of 1 month of lead time in capturing the increase of the avian flu virus could have implications for a variety of diseases. In the Philippines, he said, wastewater is being used most prominently to track the polio virus.

He added that wastewater monitoring “has applicability in the One Health field,” a global health systems approach that aims to balance and integrate the health of people, animals, and ecosystems.

Zulli reported no relevant financial relationships.

Henson reported honoraria from BSV BioScience Philippines and Merck Sharp & Dohme; grant support from Cathay Drug Company, Inc.; and is an adviser for Pfizer.

Marcia Frellick is a freelance journalist based in Chicago. She has previously written for the Chicago Tribune, Science News, Northwestern Magazine, and Nurse.com and was an editor at the Chicago Sun-Times, The Cincinnati Enquirer, and St. Cloud Times. Follow her on X @MLfrellick