County launches program that can quickly track diseases

What started as an ad-hoc project shared by two of San Diego’s key research institutions is now a permanent part of the region’s public health infrastructure.

On Wednesday, San Diego County Public Health Services launched its own wastewater infectious disease surveillance system, publishing weekly data on SARS-CoV-2, influenza A and B and respiratory syncytial virus, or RSV, with plans to expand to M-pox, hepatitis A and measles in the near future. A $2.5 million federal grant is also funding work to begin looking for high-risk drugs, such as cocaine and methamphetamine.

The site, now live in the public health section of the county’s website, sandiegocounty.gov, presents an easy-to-read weekly summary of which viruses are on the rise in the community. In its inaugural posting on Wednesday, the signal is strongest for influenza A, which, supporting graphs show, has significantly increased in San Diego County as it has in other communities in recent weeks.

It’s exactly the scenario that wastewater has proven to be indispensable for. While the county’s weekly respiratory virus reports have not yet begun to detect a spike in cases, wastewater provides a more immediate signal when viral activity increases. While it may take some time for infected patients to get sick enough to get tested, and for that information to be reported to the county, everyone sheds viral material with each bathroom visit, delivering an immediate message on what’s going around.

“Sometimes we’re not always seeing the clinical cases right away,” said Dr. Seema Shah, the county’s medical director of epidemiology and immunization services. “Wastewater gives us a jumpstart in messaging to the community that, you know, even though we’re not seeing it clinically yet, it’s clearly here, and here are the actions that you can take.”

This work started during the COVID-19 pandemic, with UC San Diego and Scripps Research working to test the wastewater on campus, determining which buildings might house people infected by the virus before they developed strong enough symptoms to seek medical treatment and formal testing. The pandemic turned out to be the perfect proving ground for the early warning value of wastewater monitoring. In late 2021, UCSD researchers noticed a spike in the number of coronaviruses detected in local wastewater. That jump predicted a surge in cases as the Omicron variant exploded, outcompeting the previous Delta variant, and creating the pandemic’s largest spike of activity.

Those in the public interested in tracking that particular jagged line have grown accustomed to visiting searchcovid.info, a site run by Scripps and UCSD, initially as an ad-hoc project scraped together from available resources and eventually with financial contributions from the county’s public health department. But no permanent funding source was identified to keep this project running over the long term. Long-term monitoring of infectious diseases in communities is generally the function of public health departments rather than research labs, so when the county, using federal funding from the federal government’s Epidemiology and Laboratory Capacity Program, built a new, nearly $100 million public health lab, designers included the ability to surveil wastewater.

The process starts with daily samples collected from San Diego County’s largest wastewater treatment plant in Point Loma, which treats the waste of about 2.2 million county residents. Samples will also continue to be collected and analyzed from smaller plants in Carlsbad and South Bay, covering most of the county’s population.

Samples are processed in special rooms on the new public health building’s second floor, moving through concentration and extraction steps where viral ribonucleic acid is extracted and enzymes are used to convert this genetic material into a form of DNA. Molecules called primers bind only with the common sections of viral genetic code, but not with the many other types of DNA that are floating around in human wastewater.

This selective binding, then, selects only the genetic material from targeted viruses, and heat can then be used to massively duplicate these selected strands, making them more visible to analytic equipment. Visibility is enhanced by special “probe” molecules designed to connect only to a single type of viral genetic code, each emitting its own unique color of light that sensitive sensors can detect.

Called digital droplet polymerase chain reaction, this process is amazing for its ability to detect multiple targets simultaneously. From one tiny well, it is possible to differentiate between up to six discrete wavelengths, each corresponding to the tagged genetic material of a different virus.

Multiple wells, corresponding to different collection locations or different concentrations, are examined at the same time, quickly yielding an electronic scatter plot that estimates how much of each virus is present in the wastewater under examination.

From there, lab directors select the wells with the highest concentrations of each virus, subjecting a reserved portion to further genetic analysis, which shows which subtype of each virus is present. This allows epidemiologists and the public to see how the different types of virus make up the overall picture. This capability has been particularly useful during the COVID pandemic, making it possible to quickly discern which variants and subvariants are surviving and thriving.

Obtaining full genetic fingerprints for everything that’s circulating over time can also help epidemiologists track how new strains move within a geographic location, like a city or county or between different communities that are further away from each other.

The analysis of local wastewater has not been a purely local endeavor. WastewaterSCAN, a program run by Stanford University and Emory University in Atlanta, has been receiving and analyzing samples from San Diego’s Point Loma plant, and from nearly 150 sites across the country, since November 2020. This effort provides similar information compiled by the county’s new program.

While SCAN does do some subtyping of the viruses it detects, the county’s use of genetic sequencing provides a more fine-grained picture, as has the SEARCH coalition effort by Scripps Research and UCSD.

Lab director Jeremy Corrigan said the county decided that it was important to make wastewater analysis a core part of the public health department’s bedrock work because collecting and preserving a library of samples over time provides a deep trove of information that can potentially be analyzed looking back in time.

“The really big benefit of us doing this and having control in our hands versus other people’s hands is that we have the sample and we are extracting all of the nucleic acid that is present,” Corrigan said. “We may not know when we’re doing the extraction that we may be looking for measles or norovirus (in the future), but if we do start to see those types of cases popping up, we can take another look at those previous samples retrospectively.”

Having local wastewater analysis capabilities at the public health level, Shah added, also provides a capability to trace origins more easily in the community, potentially by taking samples from different locations in the larger wastewater system, as was the case in analyzing patterns on the UCSD campus.

The county has worked for months with UCSD and Scripps researchers to absorb the protocols created by local researchers, gradually fine-tuning models so that the data that the county’s process creates matches with what has already been collected and published by the research effort.

Kristian G. Andersen, a biologist and immunologist whose lab as Scripps Research was instrumental in spinning up local wastewater detection efforts, said in an email Wednesday that it is heartening to see a research method become a part of the overall infrastructure of public health.

“This is such a good example of projects that kick off on the academic side, become a strong collaborative program between academia and public health, and then, once mature, fully get integrated into the public health setting,” Andersen said. “It’s great to see and is going to be an important program for San Diego moving forward, both as it pertains to endemic diseases like COVID, flu and RSV, but also diseases that cluster more as outbreaks like (Hepatitis) A, M-pox and, of course, once the next novel virus and pandemic is on our doorstep.”