Chronic central nervous system effects of acute organophosphate pesticide intoxication

1. Chronic central nervous system effects of acute organophosphate pesticide intoxication Rosenstock et al 1991 Presented by Michael Choi, Dalal Sulaihim and Soodtida Tangpraphaphorn

2. Introduction • Research question: Do single episodes of acute organophosphate intoxication lead to chronic neuropsychological dysfunction? • Exposure: hospitalization for acute organophosphate pesticide poisoning • Outcome: chronic neuropsychological dysfunction • Retrospective cohort study of farm workers in Nicaragua hospitalized for occupationally-related acute organophosphate poisoning testing for impaired neurological functions

3. Toxicology • Organophosphates are used as pesticides and chemical weapons • Organophosphates inhibit acetylcholinesterase enzyme • Symptoms include sweating, salivation, diarrhea, (SLUDGE) • Treatable in early stages via oxime therapy and atropine

4. Subjects • 36 matched pairs of men (n=72) ages 15-44 at time of hospitalization • no history of serious illness or neurological disorders • recruited from hospital discharge records in Leon, Nicaragua • matched by age to close male friend or sibling in same community

5. Methods • 6 (out of 7) WHO subtests modified • WAIS-R digit span and symbol • Spanish-translated standardized tests (including WAIS-R vocabulary) • Brief symptom inventory (self-reported) • Investigator-devised literacy test

6. Results • Cases had lower performance scores on 6 WHO subtests, 5 were stat. sig. • Reaction time, vocabulary and motor speed scores not stat. sig. different between groups • Cases tended towards greater number somatic complaints

7. Model: Pathways of Environmental Effects on Health “Source-Receptor Model” Susceptibility Oral, respira-tory or dermal intake Poor Ach reuptake, saturation of Ach on receptors Biologically Effective Dose Inhibition of AchE Neuro-psych Dysfunc-tion Organo-phosphate Chronic Neuro Sequelæ Environment Farmers working with pesticides, pesticide residues on food and clothing, education level

8. Strengths • Innovative study • Cases and control matched on age and alcohol consumption in the last month. • Neuropsychological deficit cannot be explained by any other factor • Found statistical differences in neuropsychological tests for acute exposure even with occupational exposure among the control group. • Neurological testing not conducted via computer keyboard

9. Weaknesses • Problems with sample selection (cases & controls) • 14 of the 36 claimed to have sought medical treatment for at least one pesticide poisoning. • 5 reported previous poisoning related admission to hospital. • Not enough information about how and where data were collected.

10. Weaknesses (continued) • The cases have higher percentage of working with solvents. • The control group has higher education level (17% of cases and 12% of the control have no formal education). • They reported that SES is not a confounder but they did not give any information about the SES of either group.

11. Measurement Bias • “Acutely poisoned” may have more background exposure compared to controls; may be partially responsible for observed associations • Experimenter bias unlikely since investigators were blinded • Recall bias unlikely as hospital records were used, but possible for other measured variables (e.g. drinking habits)

12. Selection Bias • Selection bias unlikely, criteria for exclusion does not suggest those excluded may have influenced the results. • Most of the people invited to take part in the study (95%) agreed to participate.

13. Confounding • Pre-morbid intelligence of study participants unknown • Traumatic effects of being hospitalized for acute organophosphate poisoning • Resulting psychiatric effects such as depression may have resulted in poorer performance on tests • Not all psychiatric problems would be reported because of a possible stigma. Also, access to care in Nicaragua is presumably poor.

14. Non-differential Misclassification • Not all those “acutely poisoned” sought treatment. Conversely, some less acutely poisoned may have sought treatment • Likely to some extent in general, as measurement techniques and instruments (e.g. WHO test battery) are imperfect

15. Discussion • Study not replicable, lacks info about stat. analyses, methodology • It is consistent with similar literature; study was unprecedented • Multicenter study would vastly improve generalizability of results • Future research should include prospective cohort studies

16. References • McConnell, R.; Keifer, M.; Rosenstock, L. (1994). Elevated Quantitative Vibrotactile Threshold Among Workers Previously Poisoned with Methamidophos and other Organophosphate Pesticides. American Journal of Industrial Medicine. 25:325-334. • Savage, E.; Keefe, T.J.; Mounce, L.; Heaton, R.K.; Lewis, J. A.; Burcar, P.J. (Chronic Neurological Sequelae of Acute Organophosphate Pesticide Poisoning. Archives of Environmental Health. 38-44. • Stallone, L.; Beselert, C. (2002. Pesticide illness, Farm Practice, and Neurological Symptoms among Farmers in Colorado. Environmental Research Section A/89-97. • Stephens, R. Spurgeon, A.; Calvert, I.; Jermey, B.; Levy, L.; Helen, B.; Harrington, J.M. (1995). Neuropsychological effects of long-term exposure to organophosphates in sheep dip. The Lancet. 345(8958):1135-1139. • Tai, C.K. (2002). Organophosphate Pesticides: Biochemistry and clinical toxicology. Therapeutic Drug Monitoring. 24(1):144-149.