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Bacterial pneumonia and pandemic influenza could there be an Impact on a sewage treatment plant? http:// www.wordle.net/ Andrew Singer Centre for Ecology & Hydrology
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Bacterial pneumonia and pandemic influenza could there be an Impact on a sewage treatment plant?

Jan 14, 2016

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Bacterial pneumonia and pandemic influenza could there be an Impact on a sewage treatment plant?. Andrew Singer Centre for Ecology & Hydrology. http://www.wordle.net/. A gentle introduction to influenza pandemics!. What is an influenza pandemic?. - PowerPoint PPT Presentation
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Page 1: Bacterial pneumonia and pandemic influenza could there be an  Impact on a sewage treatment plant?

Bacterial pneumonia and pandemic influenza could there be an Impact on a sewage treatment plant?

http://www.wordle.net/

Andrew SingerCentre for Ecology & Hydrology

Page 2: Bacterial pneumonia and pandemic influenza could there be an  Impact on a sewage treatment plant?

A gentle introduction to influenza pandemics!

Page 3: Bacterial pneumonia and pandemic influenza could there be an  Impact on a sewage treatment plant?

What is an influenza pandemic?

• Pandemic Influenza = global spread of influenza infection in humans.

• Pandemic influenza is a rare but inevitable event:– 1918 “Spanish influenza” (H1N1)– 1957 “Asian influenza” (H2N2)– 1968 “Hong Kong influenza” (H3N3)

Page 4: Bacterial pneumonia and pandemic influenza could there be an  Impact on a sewage treatment plant?

Cases/Deaths Since 2003: 408/254 (62%)

Why are we interested in this now?

Page 5: Bacterial pneumonia and pandemic influenza could there be an  Impact on a sewage treatment plant?

One aim of the pandemic preparedness plan is to slow the spread of influenza, through:

1) vaccine development, stockpiling and distribution,

2) non-pharmaceutical measures, and

3) antiviral stockpiling and distribution 22 November 2007

Page 6: Bacterial pneumonia and pandemic influenza could there be an  Impact on a sewage treatment plant?

InfluenzaVirus

InfluenzaCases

AntiviralUse

Secondary Infection Cases

AntibioticUse

41

2 5

5 Treat with antibiotics

2 Treat with antivirals

1 Clinical cases of influenza

4 Secondary infections

3

3 Antiviral prophylaxis (outbreak and post exposure)

Schematic of a Pharmaceutical Preparedness Plan

Page 7: Bacterial pneumonia and pandemic influenza could there be an  Impact on a sewage treatment plant?

UK Guidelines

This document is intended for use in the UK in the event that the

World Health Organization declares

that an influenza pandemic has started

Page 8: Bacterial pneumonia and pandemic influenza could there be an  Impact on a sewage treatment plant?

What do we need to know to predict the arrival of antibiotics at a sewage treatment

plant during a pandemic? Part I

• The scale of influenza infection (R0)• The scale of prophylactic antiviral use (AVP)• The scale of antiviral use to combat actual

infections (AVT)• The likelihood of secondary infections

Page 9: Bacterial pneumonia and pandemic influenza could there be an  Impact on a sewage treatment plant?

Viral Infectivity (R0)

InfluenzaCases

AntiviralTreatment

(AVT)

Secondary Infection Cases

AntibioticUse

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

R0

2.3

2.7

3.1

1.9

AVP

5%

10%

0%30%

50%

70%

AVT

2%

40%

Antibiotic

Developing a Model for Pharmaceutical Use During an Pandemic Influenza

54% reduction in pneumonia with antiviral treatment

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

Robust Pandemic

EpidemiologyModel

AVP

Page 10: Bacterial pneumonia and pandemic influenza could there be an  Impact on a sewage treatment plant?

What do we need to know to predict the arrival of antibiotics at a sewage treatment

plant during a pandemic? Part II

• What antibiotics would be used during a pandemic (how does this compare to baseline)?

• How much of these would be excreted?• How much of these might be lost in the

sewer/sewage treatment plant?• How this predicted concentration (PEC)

compares to thresholds of microbial toxicity (NOEC)

Page 11: Bacterial pneumonia and pandemic influenza could there be an  Impact on a sewage treatment plant?

Amoxicillin

Doxycycline

Moxifloxacin

Clarithromycin

Levofloxacin

Erythromycin

Cefotaxime

Clavulanic acid

Cefuroxime

β-l

acta

mC

eph

alo

spo

rin

Mac

rolid

e

Tetracycline

Qu

ino

lon

e

Page 12: Bacterial pneumonia and pandemic influenza could there be an  Impact on a sewage treatment plant?

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000C

efu

roxi

me

Ce

fota

xim

e

Am

oxi

cilli

n

Ery

thro

myc

in

Cla

rith

rom

ycin

Le

voflo

xaci

n

Cla

vula

na

te

Mo

xiflo

xaci

n

Do

xycy

clin

e

Ta

mifl

u

Za

na

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

Page 13: Bacterial pneumonia and pandemic influenza could there be an  Impact on a sewage treatment plant?

Baseline Antibiotic Use (excreted in England)

1

10

100

1000

10000F

loxa

cilli

n

Am

oxic

illin

Cef

alex

in

Ery

thro

myc

in

Am

pici

llin

Cip

roflo

xaci

n

Pen

icill

in V

Trim

etho

prim

Cef

radi

ne

Cla

rithr

omyc

in

Cef

aclo

r

Cef

adro

xil

Cla

vula

nate

Oxy

tetr

acyc

line

Lym

ecyc

line

Sul

fam

etho

xazo

le

Min

ocyc

line

Cef

urox

ime

Azi

thro

myc

in

Dox

ycyc

line

Oflo

xaci

n

Nor

floxa

cin

Levo

floxa

cin

Mox

iflox

acin

ug

/he

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

Page 14: Bacterial pneumonia and pandemic influenza could there be an  Impact on a sewage treatment plant?

So as an example, today we might use 3.7 mg amoxicillin/d/capita (baseline), but

in a pandemic this would rise an additional 1.3 to 74 mg/d/capita (an

increase of 35 to 2000%)!

Page 15: Bacterial pneumonia and pandemic influenza could there be an  Impact on a sewage treatment plant?

Probable Excretion to Sewage Works

10

0

10

0

96

95

80

75

61

55

38

0

20

40

60

80

100

120

Ery

thro

my

cin

Mo

xif

lox

ac

in

Le

vo

flo

xa

cin

Ce

furo

xim

e

Do

xy

cy

clin

e

Am

ox

icill

in

Ce

fota

xim

e

Cla

rith

rom

yc

in

Cla

vu

lan

ate

% E

xc

rete

d a

s P

are

nt

or

Co

nju

ga

te

Page 16: Bacterial pneumonia and pandemic influenza could there be an  Impact on a sewage treatment plant?

Probable Loss in Sewage Works

92

%

54

%

22

%

22

%

22

%

7%

6%

2%

2%

0%

10%

20%30%

40%

50%

60%

70%80%

90%

100%C

lav

ula

na

te

Do

xy

cy

clin

e

Ce

furo

xim

e

Am

ox

icill

in

Ce

fota

xim

e

Cla

rith

rom

yc

in

Ery

thro

my

cin

Mo

xif

lox

ac

in

Le

vo

flo

xa

cin

% L

os

s in

ST

W

Estimates generated from STPWINTM and an average % removal from the literature

http://www.epa.gov/oppt/exposure/pubs/episuite.htm

Page 17: Bacterial pneumonia and pandemic influenza could there be an  Impact on a sewage treatment plant?

Where might the antibiotic concentrations start to hurt

bacteria?

Page 18: Bacterial pneumonia and pandemic influenza could there be an  Impact on a sewage treatment plant?

NOEC

0.01

0.1

1

10

Am

oxi

cilli

n

Cla

vulin

ate

Do

xycy

clin

e

Ce

furo

xim

e

Ce

foto

xam

ine

Ery

thro

myc

in

Cla

rith

rom

ycin

Le

voflo

xaci

n

Mo

xiflo

xaci

n

ug

/L A

nti

bio

tic NOEC

Threshold Toxicity for Pandemic Antibiotics against Model Clinical Microorganisms

Andrews JM (2001) J Antimicrob Chemother Reynolds et al. (1987) Chemosphere

Note: we see impacts between 0.1 and 2 ug/L concentrations

Page 19: Bacterial pneumonia and pandemic influenza could there be an  Impact on a sewage treatment plant?

R0

2.3

2.7

3.1

1.9

AVP

1%

5%

10%

0%

30%

50%

70%

AVT

2%

40%

2° Infection

A Realistic Scenario

Will antibiotic concentrations in sewage get to harmful levels under a realistic scenario?

Page 20: Bacterial pneumonia and pandemic influenza could there be an  Impact on a sewage treatment plant?

Antibiotic risk assessment from modelled scenario

PEC = Predicted environmental concentration (in Sewage)NOEC = Predicted no observable effect concentration

0.1

1

10

100

1000

Am

oxi

cilli

n

Cla

vulin

ate

Do

xycy

clin

e

Ce

furo

xim

e

Ce

fota

xim

e

Ery

thro

myc

in

Cla

rith

rom

ycin

Le

voflo

xaci

n

Mo

xiflo

xaci

n

2%

40%

PE

C

NO

EC

2° Infection

> 1

DangerLevel?

Page 21: Bacterial pneumonia and pandemic influenza could there be an  Impact on a sewage treatment plant?

Under a realistic pandemic influenza scenario most of the individual predicted antibiotic

concentrations exceed the NOEC for laboratory bacteria

But what would it do to sewage bacteria?

Page 22: Bacterial pneumonia and pandemic influenza could there be an  Impact on a sewage treatment plant?

Conclusions

• Pandemic usage of total antibiotics will greatly exceed (50-1000%) that of baseline use

• It is important to note that increased antiviral prophylaxis might lower antibiotic use.

• Individual antibiotics in sewage are predicted to exceed concentrations required to inhibit laboratory test microorganisms.

Page 23: Bacterial pneumonia and pandemic influenza could there be an  Impact on a sewage treatment plant?

Key Scientific Questions

• Might high antibiotic concentrations harm the complex microbial consortium in a sewage works (rather than just laboratory bugs)?

• How important are additive effects of combined antibiotic usage (similar modes of action)?

• Are antibiotics in unlimited supply?

Page 24: Bacterial pneumonia and pandemic influenza could there be an  Impact on a sewage treatment plant?

Further Concerns

• Risk to sewage works failure & ‘downstream’ implications.

• Risk to drinking water under current models and after sewage treatment plant “failure.”

• Increasing antibiotic resistance problem.

Page 25: Bacterial pneumonia and pandemic influenza could there be an  Impact on a sewage treatment plant?

Epidemiology Model TeamV. Colizza, Complex Networks and Systems Group, ISI Foundation, Turin, Italy

D. Balcan, A. Vespignani, School of Informatics, Indiana University, Bloomington, IN, USA

River Flow Model TeamV.D.J. Keller, R.J. Williams, Centre for Ecology & Hydrology, Wallingford,

U.K

Thankyou to…..

Page 26: Bacterial pneumonia and pandemic influenza could there be an  Impact on a sewage treatment plant?

R0

2.3

2.7

3.1

1.9

AVP

5%

10%

0%

30%

50%

70%

AVT

2%

40%

2° Infection

Role of AVP on Controlling Antibiotics in the Thames

(Realistic Worst Case Scenario)

Page 27: Bacterial pneumonia and pandemic influenza could there be an  Impact on a sewage treatment plant?

Toxicity in Stretches of River (0% AVP)

Where, Ro=2.7; AVP 0%, AVT 50%, p40%

Page 28: Bacterial pneumonia and pandemic influenza could there be an  Impact on a sewage treatment plant?

Where, Ro=2.7; AVP 10%, AVT 50%, p40%

Toxicity in Stretches of River (10% AVP)

Page 29: Bacterial pneumonia and pandemic influenza could there be an  Impact on a sewage treatment plant?
Page 30: Bacterial pneumonia and pandemic influenza could there be an  Impact on a sewage treatment plant?