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

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

2. A gentle introduction to influenza pandemics!

3. 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)

4. Why are we interested in this now? Cases/Deaths Since 2003: 408/254 (62%)

5. One aim of the pandemic preparedness plan is to slow the spread of influenza, through: • vaccine development, stockpiling and distribution, 2) non-pharmaceutical measures, and 3) antiviral stockpiling and distribution 22 November 2007

6. Schematic of a Pharmaceutical Preparedness Plan Influenza Virus 1 Secondary Infection Cases 4 Influenza Cases 2 5 3 Antiviral Use Antibiotic Use 1 Clinical cases of influenza 2 Treat with antivirals 3 Antiviral prophylaxis (outbreak and post exposure) 4 Secondary infections 5 Treat with antibiotics

7. 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

8. 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

9. AVP R0 AVT Antibiotic 10% 3.1 70% 40% 5% 2.7 50% 2.3 30% 2% 0% 1.9 Developing a Model for Pharmaceutical Use During an Pandemic Influenza Influenza Cases Viral Infectivity (R0) Secondary Infection Cases AVP Robust Pandemic EpidemiologyModel Antiviral Treatment (AVT) Antibiotic Use R0 = number of secondary cases of influenza produced by 1 infected individual 54% reduction in pneumonia with antiviral treatment Kaiser (2003) Arch Intern Med; Nicholson (2000) Lancet; Treanor (2000) JAMA; Whitley (2000) Pediatr Infect Dis J

10. 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)

11. β-lactam Cephalosporin Macrolide Tetracycline Quinolone Amoxicillin Clavulanic acid Cefotaxime Cefuroxime Erythromycin Clarithromycin Doxycycline Levofloxacin Moxifloxacin

12. How much will be given to a patient? Moderately sick Severely sick Antivirals Lim (2007) Thorax

13. Baseline Antibiotic Use (excreted in England) Those highlighted in red to be used in a pandemic NHS BSA (2008) http://www.nhsbsa.nhs.uk/PrescriptionServices/Documents/NPC_Antibiotics_July_2008.ppt

14. 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%)!

15. Probable Excretion to Sewage Works

16. Probable Loss in Sewage Works Estimates generated from STPWINTM and an average % removal from the literature http://www.epa.gov/oppt/exposure/pubs/episuite.htm

17. Where might the antibiotic concentrations start to hurt bacteria?

18. Threshold Toxicity for Pandemic Antibiotics against Model Clinical Microorganisms Note: we see impacts between 0.1 and 2 ug/L concentrations Andrews JM (2001) J Antimicrob Chemother Reynolds et al. (1987) Chemosphere

19. A Realistic Scenario 2° Infection R0 AVP AVT 3.1 10% 70% 40% 2.7 5% 50% 2.3 1% 30% 2% 1.9 0% Will antibiotic concentrations in sewage get to harmful levels under a realistic scenario?

20. 2° Infection NOEC PEC Antibiotic risk assessment from modelled scenario PEC = Predicted environmental concentration (in Sewage) NOEC = Predicted no observable effect concentration > 1 Danger Level?

21. 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?

22. 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.

23. 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?

24. 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.

25. Thankyou to….. Epidemiology Model Team V. 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 Team V.D.J. Keller, R.J. Williams, Centre for Ecology & Hydrology, Wallingford, U.K

26. Role of AVP on Controlling Antibiotics in the Thames (Realistic Worst Case Scenario) 2° Infection R0 AVP AVT 3.1 10% 70% 40% 2.7 50% 5% 2.3 30% 2% 1.9 0%

27. Toxicity in Stretches of River (0% AVP) Where, Ro=2.7; AVP 0%, AVT 50%, p40%

28. Toxicity in Stretches of River (10% AVP) Where, Ro=2.7; AVP 10%, AVT 50%, p40%