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Andrew Singer acsi@ceh.ac.uk

How influenza pandemic control can lead to unpreparedness: modelling the ecotoxicity of pharmaceutical usage. Andrew Singer acsi@ceh.ac.uk. Centre for Ecology & Hydrology Wallingford, UK. “Dilution is the Solution to Pollution”. Many drugs are minimally metabolised in the body.

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Andrew Singer acsi@ceh.ac.uk

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  1. How influenza pandemic control can lead to unpreparedness: modelling the ecotoxicity of pharmaceutical usage Andrew Singer acsi@ceh.ac.uk Centre for Ecology & Hydrology Wallingford, UK

  2. “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. • Is there enough water available to dilute projected drug use during an influenza pandemic? • If not, what’s the potential impact?

  3. What is Pandemic Preparedness? … to slow the spread of influenza, through: • vaccines, 2) non-pharmaceutical measures 3) antivirals

  4. O O O HN NH2 • H3PO4 O O O OH HN NH2 O 2 x 75 mg/d for 5 days ? Impact Assessment ? ?

  5. 1. epidemic model GLEaM – 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 around • transportation hubs www.epiwork.eu Balcan et al. PNAS (2009) extended to the entire globe

  6. R0 Secondary Infection Rate 40% 2.3 15% 1.9 1.65 2% Pharmaceutical Use Model During an Influenza Pandemic Influenza Cases Viral Infectivity (R0) Secondary Infection Cases AVP “GLeAM”: Global Epidemiology Model Antiviral Treatment (AVT) Antibiotic Use R0 = number of secondary cases of influenza produced by 1 infected individual AVT/AVP • No prophylaxis • Early stage Prophylaxis • - 2w • - 4w • Treatment 30% cases 54% reduction in pneumonia with antiviral treatment Kaiser (2003) Arch Intern Med; Nicholson (2000) Lancet; Treanor (2000) JAMA; Whitley (2000) Pediatr Infect Dis J

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

  8. from body to waste

  9. 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

  10. results: antibiotics in WWTPs 300% 252% 200% relative increase to baseline 2007/2008 100% 13% 1% R0 = 1.65 R0 = 1.9 (AVT) R0 = 2.3 (AVT)

  11. 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 • Output in GIS format

  12. Determining Impact No acute toxicity Inhibition of microbial biofilms Tamiflu Microbial growth inhibition (WWTP & rivers) Antibiotics toxicity (0-100%) ‘Potentially affected fraction’ of sewage or river microbial species

  13. Ecotoxicity: Species sensitivity distributions based on Minimum Inhibitory Concentrations

  14. results: toxicity in WWTPs

  15. Spatial distribution of toxicity in WWTPs & Rivers % of sewage plants >5% PAF ≤ 85 ≤100 % of Thames River length >5% PAF ≤ 10 ≤ 40

  16. 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.

  17. Impact disruption of WWTPs widespread river pollution • contamination of rivers • degradation of drinking water • spread of antiviral and antibiotics resistance • eutrophication : • loss of acquatic ecosystem (fish kill) • temporary loss of ecosystem function

  18. Solutions ? VACCINATION!!

  19. 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.

  20. Pandemic usage of Pharmaceuticals www.prepare.org.uk

  21. Thanks to Collaborators...and you! Vittoria Colizza Heike Schmitt Duygu BalcanAlessandro Vespignani Indiana University, Bloomington, USA Virginie D. J. Keller Richard J. Williams Centre Ecology & Hydrology vcolizza@isi.it ISI, Turin Italy h.schmitt@uu.nl Inst. Risk Assessment Sciences, Univ. Utrecht Johanna Andrews Wei E. Huang Dept Civil Structural Engineering, Univ Sheffield, UK

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