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Relative toxicity of pesticides in the developing world

Relative toxicity of pesticides in the developing world. A Dawson, M Fahim, I Gawarammana, N Buckley, M Eddleston, G Manuweera South Asian Clinical Toxicology Research Collaboration, Faculty of Medicine, University of Peradeniya. Pesticide Poisoning Problem. Asia 300,000 deaths /year

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Relative toxicity of pesticides in the developing world

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  1. Relative toxicity of pesticides in the developing world A Dawson, M Fahim, I Gawarammana, N Buckley, M Eddleston, G Manuweera South Asian Clinical Toxicology Research Collaboration, Faculty of Medicine, University of Peradeniya

  2. PesticidePoisoningProblem • Asia 300,000 deaths /year • Underestimate • Sri Lanka • 17000 admissions • 35% ICU • 10% Die • (20% if symptomatic)

  3. SACTRC: Overview • Observational Cohort of 19,000 patients • Nested clinical trials • Community studies • 15 postgraduate students • International Partners: • UK, USA, Denmark, Germany, Portugal Chilaw.

  4. Anuradhapura District 2006 Peripheral Hospitals 1942 admissions 1107 Anuradhapura General Hospital 1908 admissions

  5. Background • Clinical impact of pesticide poisoning is a function of both: • the intrinsic toxicity of the pesticide • and availabilty of treatment resources • Effective pesticide regulation • can be threatened by illegal importation • considers agricultural and economic outcomes. • Effective regulation in Sri Lanka with targeted pesticide restrictions • reduced pesticide deaths • maintained agricultural production. • Do targeted bans of insecticides to prevent deaths from self-poisoning result in reduced agricultural output? (Manuweera G )

  6. Pesticide Restriction • Gunnell D, Fernando R, Heganawathna N et al Journal of Epidemiology 2007;1–8

  7. Aim • To provide information about the relative toxicity of pesticides that: • could inform regulatory policy • and may assist in the development of a minimum pesticide list • Eddleston,M. et al. Pesticide poisoning in the developing world--a minimum pesticides list. Lancet 360[9340], 1163-1167. 2002.

  8. Methods • Data was prospectively collected from a cohort of consecutive patients from April 2002 to April 2007. • Identification of pesticides was based on • history or positive identification of the container • and plasma assays in some cases. • Case fatality calculated.

  9. Results • 6449 patients who ingested a pesticide and were analysed. • Plasma assayed for pesticides • 60% of all patients • 90% of organophosphate admissions • Confirmed the history in over 90% patients. . • Overall mortality 11.2%

  10. The case fatality for commonly ingested pesticides

  11. Dying is too easy for death to be a “Hard Outcome” in the developing world. South Asian Clinical Toxicology Research Collaboration

  12. Primary Rural HospitalsLalith Senarathna: Master’s Thesis 2007 www.sactrc.org • Poor antidote stocking • Poor antidote utilisation • A gap between actual practice and perceived practice “We are like frogs in a well” • Clustered RCT Antidote Stocking & Academic Detailing

  13. 3 compounds: 60% of mortality South Asian Clinical Toxicology Research Collaboration

  14. Results: Pesticide Withdrawal • Assuming paraquat and dimethoate were removed from the market • and that people substituted the next most toxic compound in that class • Paraquat removal could lead to a 30% reduction in deaths • Dimethoate removal could lead to a 12% reduction. • Extrapolation of this data to the national figures of 3000 deaths per year from pesticides suggests a reduction in deaths of about 1200 per year.

  15. Pesticide Restriction in Sri Lanka • Bans 2008 • Paraquat • Dimethoate • Fenthion • Gunnell D, Fernando R, Heganawathna N et al Journal of Epidemiology 2007;1–8

  16. Results (2) • Pesticide Withdrawal November 2007 • Paraquat 6.5% Concentration • Model a 10 % reduction • Dimethoate & Fenthion to be withdrawn over 3 years from 2008 • Paraquat withdrawn from 2009 • Modeled Substitutions • Worst CFR within the class • Median CFR within the class

  17. Projected CFR 95% CI

  18. Discussion • Benefit of dimethoate restriction may be an underestimation • clinical research units has been shown to reduce mortality • Mortality from paraquat is likely to be a robust estimate as there is no treatment which clearly alters outcome.

  19. When can we decide ? South Asian Clinical Toxicology Research Collaboration

  20. Discussion • within a pesticide class there is a significant range of mortality. • The usefulness of point estimates of zero fatalities which have wide confidence intervals could be enhanced by • including other more sensitive clinical markers of toxicity • based on animal toxicity data • and known mechanisms of action.

  21. Discussion (2) • This data can inform a restricted pesticide policy that operates within the constraints of local health systems. • A cost-minimization approach could be explored, using models similar to those developed for drug regulation and subsidy.

  22. Conclusion • There is sufficient information to iteratively develop a minimum pesticide list. • Such implementation will require continuous sentinel monitoring of usage and clinical presentations.

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