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EAPCCT 2021: Toxicology 2.0

Wastewater analysis to understand community consumption of opioids

May 2021

Claire Duvallet, PhD

Senior Data Scientist, Biobot Analytics

claire@biobot.io

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Wastewater epidemiology: Everybody pees. Every day.

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The opioid epidemic is the worst drug crisis in American history

190 opioid overdose deaths per day in the U.S. in 2019.

Despite government investment ($Bs) in public health interventions, problem continues to worsen.

Effective public health interventions are well established, but cities & states lack data to target their response.

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The best data we have is counting overdoses

Limited data drives billions of dollars of aid each year in the U.S.
Data is often delayed. In May 2021: CDC currently reports 2019 data; Massachusetts reports data from November 2020.
Doesn’t represent most people living with opioid use disorder (OUD): less than 1% of people with OUD die from overdoses each year.

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Massachusetts Department of Health (2017). “An Assessment of Fatal and Nonfatal Opioid Overdoses in Massachusetts (2011 – 2015).”

% of OUD population dying annually

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Sewage sampler

Lab chemical analysis

Data analysis & visualization

Robotic sewage sampler deployed in manholes.

Collects 7-day composite sample and pre-processes sample in situ.

HPLC-MS/MS method detects and quantifies 39 drugs and metabolites, including 8 glucuronide conjugates

Sewage concentrations are converted to estimated consumption & MME and visualized in PDF report.

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First pilot: Town of Cary, NC

June-Nov 2018 pilot
10 sampling locations
Monthly sampling

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Wastewater provides comprehensive and unbiased view of opioid exposure

MME = morphine milligram equivalent

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Substance

Endo et al. “Rapid Assessment of Opioid Exposure and Treatment in Cities Through Robotic Collection and Chemical Analysis of Wastewater.” Journal of Medical Toxicology. 2020.

Duvallet et al. “Mapping Community Opioid Exposure Through Wastewater-Based Epidemiology as a Means to Engage Pharmacies in Harm Reduction Efforts.”

Preventing Chronic Disease. 2020.

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Naloxone and treatments can also be detected in wastewater

Naloxone glucuronide

ρ_s = 0.58, p = 0.08

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Norbuprenorphine glucuronide

ρ_s = 0.79, p = 0.03

Endo et al. “Rapid Assessment of Opioid Exposure and Treatment in Cities Through Robotic Collection and Chemical Analysis of Wastewater.” Journal of Medical Toxicology. 2020.

You can also detect other substances in wastewater, for example treatments like buprenorphine and naloxone.
Naloxone is the main ingredient in the overdose reversal drug, Narcan. It’s also a component of a common long-term treatment, Suboxone.
Buprenorphine is the active ingredient in the long-term treatment, Suboxone.
Buprenorphine exposure can indicate areas of town which may benefit from additional outreach and education on Suboxone as a long-term treatment for opioid exposure.
You can also look at naloxone and compare it with overdose rates, for example, to get a sense of how well overdose data is capturing actual problematic usage.
For example, you could imagine identifying neighborhoods with low reported overdoses but high naloxone as places that might be experience a lot of bystander overdoses that never get reported to emergency responders.

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Town of Cary converted to full contract after the pilot

Overdoses decreased 40%

Prescription drug disposal increased more than 2.5x

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Smith. “Building smarter healthier communities through opioid wastewater monitoring.” NC Currents, NC AWWAWEA 99th Annual Conference. 2019. p. 81-84. https://www.kelmanonline.com/httpdocs/files/NC_AWWA_WEA/nccurrentsfall2019/

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Pilot deployed in 6 cities in Massachusetts in 2020

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City	Population (2010 census)	Rate of overdose incidence (by city of occurrence) in 2018 [/1000/year]	Rate of overdose death (by city of occurrence) in 2018 �[/1000/year]
A	100,000	11.5	0.68
B	180,000	9.4	0.74
C	40,000	4.3	0.87
D	30,000	3.1	0.46
E	80,000	1.6	0.11
F	30,000	0.25	0.03

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Correlations with reported opioid use

Spearman correlation between per capita MME reported by Prescription Monitoring Program (PMP) and average sewage concentration (Biobot data)
P-values corrected for multiple tests

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Parent drug	Analyte	Spearman R	Q-value
Buprenorphine	Buprenorphine	-0.38	0.0363
Buprenorphine	Norbuprenorphine glucuronide	0.61	0.000301
Fentanyl	Fentanyl	0.63	0.000181
Fentanyl	Norfentanyl	0.32	0.0834
Methadone	EDDP	0.58	0.000578

Parent drug	Analyte	Spearman R	Q-value
Codeine	Codeine	-0.021	0.906
Codeine	Codeine glucuronide	0.5	0.00467
Codeine	Norcodeine	-0.098	0.648
Hydrocodone	Hydrocodone	0.87	1.52E-10
Hydrocodone	Norhydrocodone	0.87	1.52E-10
Hydromorphone	Hydromorphone	0.15	0.453
Hydromorphone	Hydromorphone glucuronide	-0.75	1.61E-06
Morphine	Morphine	0.35	0.0547
Morphine	Morphine glucuronide	0.4	0.0324
Oxycodone	Noroxycodone	1	0
Oxycodone	Oxycodone	0.09	0.648
Tramadol	N-Desmethyl-cis-tramadol	0.63	0.00015
Tramadol	O-Desmethyl-cis-tramadol	0.67	3.99E-05
Tramadol	cis-Tramadol	0.83	4.82E-09

Treatments & fentanyl

Prescription opioids

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Other emerging drugs are included in Biobot’s panel

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Cocaine

Benzoylecgonine (cocaine)

Methamphetamine

THC-COOH

THC-OH

Δ9-THC

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Rapid deployment & scaling for Covid-19

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Wu, Zhang, Xiao et al. “SARS-CoV-2 Titers in Wastewater Are Higher than Expected from Clinically Confirmed Cases.” mSystems. 2020.

Wu, Xiao, et al. “Wastewater surveillance of SARS-CoV-2 across 40 U.S. states.” biorXiv. 2020

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Pro-bono campaign

March 2020

Full service offering

June 2020

Variant add-on

April 2021

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Wu, Zhang, Xiao et al. “SARS-CoV-2 Titers in Wastewater Are Higher than Expected from Clinically Confirmed Cases.” mSystems. 2020.

Wu, Xiao, et al. “Wastewater surveillance of SARS-CoV-2 across 40 U.S. states.” biorXiv. 2020.

Lee et al. “Quantitative detection of SARS-CoV-2 B.1.1.7 variant in wastewater by allele-specific RT-qPCR.” bioRxiv. 2021.

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Legend

Wastewater concentration

3-sample average

New cases per 100k

7-day average

In preparation

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Sewers as population health observatories

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High-risk substances

Platform for population health monitoring powered by wastewater

Infectious disease

Health & wellness

Methamphetamine

Heroin

Fentanyl & fentanyl analogs

Influenza

Antimicrobial resistance

Emerging pathogens

Stress markers

Nutritional biomarkers

Pharmaceuticals

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Thank you!

Claire Duvallet, PhD

claire@biobot.io

Biobot research team

Noriko Endo, PhD
Katelyn Foppe
Mariana Matus, PhD
Newsha Ghaeli

Our partners:

Town of Cary: Donald Smith, Nicole Raimundo, Gerald Mitchell, Maria VanderLoop, Sandal Abid, and Town of Cary DPW
MDPH: Sarah Ruiz, Hermik Babakhanlou-Chase, participating DPW and municipalities

Biobot scientific advisors

Peter Chai, MD
Tim Erickson, MD
Liz Kujawinski, PhD
Eric Alm, PhD

We’re hiring!

Analytical chemist
Chemical data analyst

https://jobs.lever.co/biobot

claire@biobot.io

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LC-MS method quantifies multiple categories of substances in wastewater

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	Prescription opioids	Illicit opioids	Treatment drugs	Positive Control
Substances	Codeine, Fentanyl, Hydrocodone, Hydromorphone, Morphine, Oxycodone, Oxymorphone, Sufentanil, Tramadol	Heroin, Carfentanil, Fentanyl precursor	Methadone Naloxone Buprenorphine Naltrexone	Caffeine Nicotine* Serotonin* Acetaminophen*

Limit of quantification < 5 ng/mL for all analytes

Foppe et al. “Analysis of 39 drugs and metabolites, including 8 glucuronide conjugates, in an upstream wastewater network via HPLC-MS/MS.” Journal of Chromatography B. In press.

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Chemical analysis provides granular view of prescription opioid exposure

Detection rate

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Duvallet et al. “Mapping Community Opioid Exposure Through Wastewater-Based Epidemiology as a Means to Engage Pharmacies in Harm Reduction Efforts.” Preventing Chronic Disease. 2020.

Relative MME