Sewage epidemiology: potential and limitations of a …score-cost.eu/wp-content/uploads/sites/118/2014/09/140918-TS1... · Sewage epidemiology: potential and limitations of a novel

Sewage epidemiology: potential and

limitations of a novel approach

Ettore ZuccatoEttore Zuccato

“Mario Negri” Institute for Pharmacological Research, Milan, Italy

23/09/2014 1

Sewage epidemiology, a novel approach

• Sewage epidemiology is a new approach to population studies, which use wastewater analysis for assessing collective exposure of the members of a community to a wide range of chemicals.

• Chemicals that can be investigated include those that are voluntarily ingested (illicit drugs, pharmaceuticals) and those voluntarily ingested (illicit drugs, pharmaceuticals) and those to whom subjects are involuntarily exposed to (chemical contaminants ingested with food and water, atmospheric pollutants which are inspired, personal care products which can be absorbed transdermally).

• The rationale of this approach is that traces of almost everything we absorb, are excreted with urine or stool and end up in the sewage system.

23/09/2014 2


• Illicit drugs were the first application.

23/09/2014 3



• Residues of the illicit drugs consumed by a collectivity are

excreted in wastewater and their levels, knowing kinetic,

metabolism, and behaviour in wastewater, and characteristics

of the sewage system, such as flow rate and population size, of the sewage system, such as flow rate and population size,

can be used to back-calculate for the type and amount of illicit

drugs collectively consumed by a population

23/09/2014 4

Drugs

-cocaine

-cannabis

-heroin

-amphetamines

CONSUMER

Excretes residues of

the drugs with urine

after the intake

TREATMENT PLANT

The route of the drugs: from the consumer to the STP

The residues of the drugs

are transported to the STP

with the wastewater

DRUG RESIDUES

QUANTIFICATION

Wastewater is sampled and

the residues of the drugs at

the STP are quantified

CONSUMPTION ESTIMATE

Amounts of the residues

(g/day) are used to back-

calculate drug consumption in

the population served by the

STP (g/day of the parent drug)

23/09/2014 5

Urine testIndividual

(biomonitoring)

Collective

(sewage epidemiology)

23/09/2014 6

Metabolism and urinary excretion of cocaine

23/09/2014 7

Target residues selected for drug monitoring in wastewater

DRUG Target residue Relation of residue to parent drug

Cocaine benzoylecgonine (BE) Major metabolite of cocaine

Heroin morphine

6-acetylmorphine

Major metabolite of heroin

Minor but exclusive metabolite

Amphetamines

Amphetamine

Methamphetamine

Ecstasy

amphetamine

methamphetamine

MDMA (ecstasy)

Parent drugs and major excretion

products

Cannabis (THC) THC-COOH Major metabolite of THC

Zuccato et al., 2008

23/09/2014 8

Metabolism of MDMA (ecstasy) in man

23/09/2014 9

Highlights of this method

This method can provide

• Evidence-based and real-time estimates of drug collective consumption

It can be used to

• Estimate local consumptions

• Estimate spatial differences

• Estimate temporal differences

23/09/2014 10

Drug consumption (Milan, 2006)(Zuccato et al., 2008)

0

500

1000

1500

2000

Mo

nd

ay

Tue

sda

y

We

dn

esd

ay

Th

urs

da

y

Fri

da

y

Sa

turd

ay

Su

nd

ay

Cocaine g/day

0

2000

4000

6000

8000

Mo

nd

ay

Tue

sda

y

We

dn

esd

ay

Th

urs

da

y

Fri

da

y

Sa

turd

ay

Su

nd

ay

THC-cannabis (g/day)

23/09/2014 11

We

dn

esd

ay

0

100

200

Mo

nd

ay

Tue

sda

y

We

dn

esd

ay

Th

urs

da

y

Fri

da

y

Sa

turd

ay

Su

nd

ay

Heroin (g/day)

We

dn

esd

ay

0

50

100

Mo

nd

ay

Tue

sda

y

We

dn

esd

ay

Th

urs

da

y

Fri

da

y

Sa

turd

ay

Su

nd

ay

Amphetamines (g/day)

Weekly pattern of consumption – Local consumption

Drug Consumption in Oslo (2009) (Reid et al., Drug Alcohol Dep, 2011)

23/09/2014 12

Cocaine consumption in Belgium(van Nuijs et al., 2009)

23/09/2014 13

Cocaine consumption in Italy

demographic and geographic distribution

0.7

0.8

0.9

1.0

g/d

ay

/10

00

in

ha

bit

an

ts

Cocaine

0.6

0.7

0.8

0.9

1.0

g/d

ay

/10

00

in

ha

bit

an

ts

0.0

0.1

0.2

0.3

0.4

0.5

0.6

Go

rizi

a

Ve

ron

a

Me

ran

o

Mil

an

Bo

log

na

Tu

rin

NO

RT

H

Pe

rug

ia

Te

rni

Flo

ren

ce

Ro

me

CE

NT

RA

L

Ba

ri

Ca

gli

ari

Nu

oro

Po

ten

za

Pe

sca

ra

Na

ple

s

Pa

lerm

o

SO

UT

H

g/d

ay

/10

00

in

ha

bit

an

ts0.0

0.1

0.2

0.3

0.4

0.5

Mil

an

Tu

rin

Ro

me

Na

ple

s

Pa

lerm

o

LAR

GE

CIT

IES

Ve

ron

a

Bo

log

na

Flo

ren

ce

Ba

ri

ME

DIU

M

Pe

sca

ra

Ca

gli

ari

Te

rni

Pe

rug

ia

ME

DIU

M-S

MA

LL

Go

rizi

a

Me

ran

o

Nu

oro

Po

ten

za

SM

ALL

g/d

ay

/10

00

in

ha

bit

an

ts

23/09/2014 14

Trends in drug consumption from wastewater analysis (2005-2009)

Cocaine consumption Cocaine consumption fell 45% in 2009

(p<0.05, Tukey-Kramer HSD test)Zuccato et al., 2011, Drugs and Alcohol

Dependence.

Cocaine

23/09/2014 15

… and from epidemiological surveys (2007-2010)Local survey Local survey -- MilanMilan

General Population Survey

National survey published 2011 National survey published 2011

23/09/2014 16



• Other potential applications include, for instance,

pharmaceuticals.

23/09/2014 17

Voluntary exposure (consumption)

illicit drugs

pharmaceuticals

Subjects

(population)

Excretion

metabolism

Sewage Epidemiology (in brief)

wastewater Wastewater analysis

Excretion

assessment

Intake

assessment

23/09/2014 18


• We know the amount of a given pharmaceutical which is

prescribed or sold in a given area, but we don’t know how

much is really taken by patients

• Frequently, patients do not comply to the treatment and this

is an important medical issueis an important medical issue

• Wastewater analysis of the pharmaceuticals can help in

elucidating the compliance of the patients to the treatment,

contributing to evaluate its efficacy.

23/09/2014 19

Consumption of pharmaceuticals in the city of Milan:

sewage epidemiology data compared to prescriptions

Prescriptions Milan 2005

Expectedloads

Measured loads(Milan 2005-2006)

mg/day/1000 inhabitants



23/09/2014 20

1000 inhabitants 1000 inhabitants 1000 inhabitants

Atenololo 1407 867 682-781

Atorvastatina 156 3 3

Codeina 0.026 0.012 0.017

Gemfibrozil 470 155 130-160

Enalapril 384 61 40-41

Sulfametossazolo 440 27 19-28

Claritromicina 898 209 236


• Illicit drugs were the first application, and pharmaceuticals is

another case study

• However, this approach has a much wider range of potential

applications.

• Practically every chemical our body enter in contact with, can • Practically every chemical our body enter in contact with, can

be absorbed, metabolized and excreted in wastewater of an

urban treatment plant.

• By monitoring metabolites and parent compounds in

wastewater we can back-calculate for the amount of a given

substance which has been collectively absorbed by a

community.

23/09/2014 21

Sewage Epidemiology:

Background

foodExposure

Exposure water

air

Skin contact

23/09/2014 22

ExcretionAbsorption

Alcohol consumption in Oslo. Analysis of ethyl sulfate in sewage

23/09/2014 23

Reid et al., 2011

Nicotine and smoking habit

23/09/2014 24

23/09/2014 25

Voluntary exposure (consumption)

Illicit drugs

Pharmaceuticals

Nicotine

Involuntary exposure

Environmental chemicals

Food chemicals

Subjects

(population)

Excretion

metabolism

Sewage Epidemiology (in brief)

wastewater Wastewater analysis

Excretion

assessment

Intake

assessment

23/09/2014 26

Assessment of the exposure to organophosphorous

pesticides

Exposure to pesticides

Diet

23/09/2014 27

Pesticide-related

health risk

Correlation with

specific diseasesAnalysis of food

Urinary

biomonitoring

Wastewater

analysis

Assessment of the exposure to organophosphorous pesticides

by biomonitoring (Lu et al., 2006)

23/09/2014 28

Potential applications of sewage epidemiology

• Illicit drugs

• Pharmaceuticals

• Pesticides

• Polycyclic Aromatic Hydrocarbons (PAH)• Polycyclic Aromatic Hydrocarbons (PAH)

• PCBs (OH-PCBs)/Dioxins

• Mycotoxins

• Food additives

23/09/2014 29

health parameter biomarkersLifestyle drug abuse

alcohol consumptiontobacco consumptioncaffeine consumption anabolic steroid abuse

drugs and their urinary metabolites ethyl sulphate cotinine, tobacco specific nitrosamines caffeine urinary metabolites synthetic steroids and their metabolites

Diet synthetic sweetener intake fruit and vegetable intake

sweetener metabolites phytoestrogens, flavonoids metabolites

Examples of Existing and Potential Wastewater Biomarkers

of Human Health (Thomas and Reid, 2011)

soya consumptionmeat consumption

iso-flavonoids metabolitescreatinine, taurine, 1-methylhistidine, and 3-methylhistidine

Environment pesticide exposure aflatoxin exposurePCB exposurePAH exposure

pesticide urinary metabolites aflatoxin N(7)-guanineOH-PCBsphenanthrol and other PAH metabolites

Health pharmaceuticalconsumption allergypolio surveillancedisease status

specific pharmaceuticals and their metabolites antihistaminespoliovirusurinary marker of specific diseases

Conclusion

• Sewage epidemiology needs a multidisciplinary

approach, with the interaction of experts of several

different fields, such as pharmacokinetic, medicine,

and analytical chemistry.

• Monitoring wastewater has the potential to extract

useful epidemiological information from qualitative

and quantitative profiling of biological indicators

entering the sewage system and might become a

useful tool to be used in population studies .

23/09/2014 31

Wastewater analysis VS. Epidemiology methods

• Advantages

• “Real time” estimates

• Quantitative consumption (pure drugs)

• Local consumption

• Limitations

• Consumers unknown (no data about

individuals patterns of drug use, routes of

administration, frequency of use, poly

drug use, effects on health)

• Difficult to estimate the amount of street • Local consumption

• Time trends

• Novel trends and new drugs

• Efficacy of preventive measures

• Difficult to estimate the amount of street

drugs consumed (size of a dose, purity)

• Potential sources of uncertainties

(sampling, metabolism, back calculation…)

23/09/2014 32

�Provide data difficult to be obtained by epidemiological methods

�Good potential to complement epidemiological methods

Sewage epidemiology: potential and limitations of a …score-cost.eu/wp-content/uploads/sites/118/2014/09/140918-TS1... · Sewage epidemiology: potential and limitations of a novel

Documents