Ecotoxicity Risks During an Influenza Pandemic

Andrew Singeracsi@ceh.ac.uk

Centre for Ecology & HydrologyWallingford, UK

“Dilution is the Solution to Pollution”

• Many drugs are minimally metabolised in the body.

• As a general rule, if a drug persists in the body it will likely persist in the environment.

• The problem is when a drug is used in sufficient quantity, such that its dilution in rivers is insufficient to lower its potential toxicity.

Dilution of Acutely Toxic Drugs

Cytotoxics (Chemotherapy)

Cocaine, etc

Estrogen (Oral contraceptive)

% Remaining of Parent

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Cef

alex

in

Cef

tria

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Am

anta

dine

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tam

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carb

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ate

Cef

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ime

Levo

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cin

Cip

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xaci

n

Pen

icill

in G

Dem

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Tet

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Van

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ycin

Trim

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tam

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Oflo

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Imip

enem

Pen

icill

in V

Cod

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Flu

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Cla

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Co-

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Met

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/Ace

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hen

Amount excreted as % of ingested%

Exc

rete

d

AntibioticsAntiviralsAnalgesics

The unique situation of an influenza pandemic

0%

10%

20%

30%

40%

50%

60%

Indo

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a

Bra

zil

Cyp

rus

Sou

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orea

Ital

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Gre

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Tai

wan

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Ger

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Sw

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Fin

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Alg

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Mal

ta

Can

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Sta

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ong

Bel

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gdom

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(% o

f P

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n)

Relenza (% of pop)

Tamiflu (% of pop)

Research Question

Is there enough water in sewage works and the Thames River to dilute

projected drug use during an influenza pandemic?

If not, what’s the potential impact?

What is Pandemic Preparedness?

… to slow the spread of influenza, through:

1) vaccines,

2) non-pharmaceutical measures

3) antivirals

NH2 • H3PO4

O

HN

O

O

O

NH2

O

HN

O

OH

O

2 x 75 mg/d for 5 days

?

??

Impact Assessment

1. epidemic modelGLEaM – Global Epidemic and Mobility model

air mobility layer 3400 airports in 220 countries 20,000 connections traffic data (IATA, OAG) >99% commercial traffic

commuting mobility layer daily commuting data >30 countries in 5 continents universal law of mobility

demographic layer cells ¼° x ¼° tessellation aroundtransportation hubs

extended to the entire globe Balcan et al. PNAS (2009)www.epiwork.eu

Viral Infectivity (R0)

InfluenzaCases

AntiviralTreatment(AVT)

Secondary Infection Cases

AntibioticUse

R0 = number of secondary cases of influenza produced by 1 infected individual

Pharmaceutical Use Model During an Influenza Pandemic

54% reduction in pneumonia with antiviral treatment

Kaiser (2003) Arch Intern Med; Nicholson (2000) Lancet; Treanor (2000) JAMA; Whitley (2000) Pediatr Infect Dis J

“GLeAM”: Global Epidemiology Model

AVP

R0

1.9

2.3

1.65 2%

40%

Secondary Infection Rate

15%

• No prophylaxis• Early stage Prophylaxis - 2w - 4w• Treatment 30% cases

AVT/AVP

Amoxicillin

Doxycycline

Moxifloxacin

Clarithromycin

Levofloxacin

Erythromycin

Cefotaxime

Clavulanic acid

Cefuroxime

β-la

ctam

Ceph

alos

porin

Mac

rolid

e

Tetracycline

Qui

nolo

ne

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000C

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me

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miv

ir

Do

se

(m

g d

-1)

CURB 0-2

CURB 3-5

How much will be given to a patient?

Lim (2007) Thorax

Antivirals

Moderately sick

Severely sick

Baseline Antibiotic Use (excreted in England)

1

10

100

1000

10000F

loxa

cilli

n

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illin

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line

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line

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ad

/d

NHS BSA (2008) http://www.nhsbsa.nhs.uk/PrescriptionServices/Documents/NPC_Antibiotics_July_2008.ppt

Those highlighted in red to be used in a pandemic

from body to waste

LF2000-WQX works

• Estimates water quality on a reach by reach basis – starting at the top

• Makes a mass balance of the inputs to the reach – Sewage treatment plants,

industrial discharges, tributaries

• New concentrations calculated at the end of the reach allowing for degradation of the compound of interest

Uses Monte Carlo approach to predict downstream concentrations of contaminant and assign a probability distribution

Qup

Probability

Downstream predicted concentration

Drug d = Qup*Drugup + Qe*Druge

Sample from Distributions and do this mass balance calculation many times (shots)

Upstream Flow and Quality

Probability

Downstream Quality

Drugup

ProbabilityEffluent Flow and Quality

Qe Druge

Qd

Downstream concentration

Overview of how model works for a catchment

STP locations &Type, human PE& flow

Equation to predict drugload

Relevant catchmentdata such as area,all major discharges &abstractions

LF2000-WQXGIS maps withdrugconcentrations forevery reach

GIS maps withconcentrations can be converted to risk levels for every reach

Determining Impact

Antibioticsgrowth inhibitionof microbial species(WWTP & rivers)

toxicity (0-100%) :

‘Potentially affected

fraction’ of sewage

or river microbial

species

Tamiflu Low projected ecotoxicityImpact microbial biofilms

results: antibiotics in WWTPs

R0 = 1.65 R0 = 1.9(AVT)

R0 = 2.3(AVT)

1%13%

252%

rela

tive incr

ease

to b

ase

line 2

007

/2008

100%

200%

300%

results: toxicity in WWTPs

results: toxicity in rivers (by length)

Spatial distribution of toxicity in WWTPs & Rivers

General Conclusions

• A mild pandemic with a low rate of secondary infections is not projected to result in problems for sewage works or most UK rivers.

• A pandemic with an R0 > ~2.0 is likely to pose operational challenges to sewage works which could result in the release of untreated sewage into receiving rivers.

Impact

disruption of WWTPswidespread river pollution

contamination of rivers degradation of drinking water spread of antiviral and antibiotics resistance leading to:

potential loss of key antiviral potential loss of key antibiotics

eutrophication – leading to: loss of acquatic ecosystem (fish kill) temporary (?) loss of ecosystem function

Solutions ?

VACCINATION!!

Priority Research

• Empirically determine vulnerability of sewage works.

• Assess the short and long term risks to widespread antiviral and antibiotic release into the environment.

• Empirically determine vulnerability of drinking water to contamination.

Watch this space: www.prepare.org.uk

Thanks to Collaborators...and you!

Vittoria Colizzah.schmitt@uu.nlInst. Risk AssessmentSciences, Univ. Utrecht

Duygu BalcanAlessandro VespignaniIndiana University, Bloomington, USA

Virginie D. J. KellerRichard J. WilliamsCentre Ecology &Hydrology

Heike Schmittvcolizza@isi.itISI, Turin Italy

Johanna AndrewsWei E. HuangDept Civil Structural Engineering, Univ Sheffield, UK