South Asian Clinical Toxicology Research Collaboration Relative toxicity of pesticides in the developing world A Dawson, M Fahim, I Gawarammana, N Buckley,

South Asian Clinical Toxicology Research Collaboration

Relative toxicity of pesticides Relative toxicity of pesticides in the developing world 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

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PesticidePesticide PoisoningPoisoning ProblemProblem

Asia 300,000 deaths /year

– Underestimate Sri Lanka

– 17000 admissions

– 35% ICU

– 10% Die

– (20% if symptomatic)


SACTRC: OverviewSACTRC: Overview Observational Cohort of

19,000 patients– Nested clinical trials

Community studies

15 postgraduate students

International Partners:– UK, USA, Denmark,

Germany, Portugal

Chilaw.


Anuradhapura District 2006Anuradhapura District 2006

Peripheral Hospitals1942 admissions

Peripheral Hospitals1942 admissions

11071107

Anuradhapura General Hospital1908 admissions

Anuradhapura General Hospital1908 admissions


BackgroundBackground 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 )

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Pesticide RestrictionPesticide Restriction

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


AimAim 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.

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MethodsMethods 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.

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ResultsResults 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%

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The case fatality for commonly ingested pesticides The case fatality for commonly ingested pesticides

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Dying is too easy for death to be a “Hard Dying is too easy for death to be a “Hard Outcome” in the developing world.Outcome” in the developing world.



Primary Rural HospitalsPrimary Rural HospitalsLalith Senarathna: Master’s Thesis 2007 www.sactrc.orgLalith 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


3 compounds: 60% of 3 compounds: 60% of mortalitymortality



Results: Pesticide WithdrawalResults: 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.

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Pesticide Restriction in Sri LankaPesticide Restriction in Sri Lanka

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

Bans 2008•Paraquat•Dimethoate•Fenthion


Results (2)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

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Projected CFR 95% CIProjected CFR 95% CI

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DiscussionDiscussion 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.

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When can we decide ?When can we decide ?



DiscussionDiscussion 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.

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Discussion (2)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.

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ConclusionConclusion

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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Documents

South Asian Clinical Toxicology Research Collaboration Relative toxicity of pesticides in the developing world A Dawson, M Fahim, I Gawarammana, N Buckley,