Neurological manifestations of organophosphate exposure in animals: A one health approach to agrochemical toxicity

Introduction

Organophosphate poisoning is a significant concern in veterinary and human medicine due to its neurotoxic effects. organophosphates and carbamates, commonly used in agriculture for pest control, have been implicated in severe toxicity cases across species. More than 30,000 organophosphate (OP) insecticides have been identified. These compounds are organic esters of phosphoric acid (H₃PO₄) and its derivatives. Examples include Dichlorvos (Nogos, DDVP), an ester of phosphoric acid; Parathion (Agrofos), Methylparathion (Vofatox), and Diazinon, which are derivatives of thiophosphoric acid (H₃PO₃S); and Malathion (Karbofos, Metatox) and Dimethoate (Rogor), which are derived from dithiophosphoric acid [1] . As Organophosphates being most intoxicants for human and animals, it involves major public health risks and these compounds can enter through various routes like ingestion, inhalation, skin and mucous membranes [2,3] . Specifically, organophosphates exert their toxic effects by inhibiting the enzyme acetylcholinesterase, preventing it from breaking down of acetylcholine. As a result, they are considered the most potent group of anticholinesterase agents [4] . The One Health approach underscores the interconnectedness of human, animal, and environmental health, making it imperative to study the implications of OP poisoning comprehensively. In cases of chronic organophosphorus toxicity, the outcome often involves OP-induced delayed neuropathy (OPIDN), which is characterized by weakness, lack of coordination, unconsciousness, and primarily affects the pelvic limbs proprioception [5] . Whereas, the acute organophosphate poisoning shows clinical signs like bradycardia, bronchoconstriction, diarrhea, salivation, nasal discharge, apathy, prostration, motor incoordination, head pressing against objects, neck stiffness, paresis, flaccid paralysis of the limbs, permanent decubitus, pedaling movements in lateral decubitus, muscle tremors and death [6] .

Materials and Methods

A retrospective study was conducted at Veterinary Clinical Complex, Veterinary College and Research Institute, Orathanadu from February 2022 to July 2023. Neurological cases were identified and a subset of 32 cases with delayed Organophosphate poisoning symptoms was further analyzed. Clinical manifestations, diagnostic approaches and treatment outcomes were recorded. The cases suspected for OP poisoning, serum samples were collected and analyzed for Butyryl cholinesterase (Optimus®) using semi-autoanalyzer (SA-20-CLINDIAG)as per the standard protocol. Butyryl choline esterase acts as the biomarker in detecting and assessing the severity of OP poisoning in animals [7] .

Results and Discussion

Out of the 1023 neurological cases, 198 were suspected of having neurological disorders and 32 (47.06 per cent) cases were diagnosed with delayed OP (OPIDN) poisoning. Clinical symptoms included muscle tremors, weakness, respiratory distress, seizures and progressive neurological deterioration (Fig 3). The environmental impact of excessive pesticide use contributes significantly to OP poisoning in animals, as these chemicals persist in water and soil (Fig. 1). Moreover, OP compounds are known to interfere with acetylcholinesterase activity leading to overstimulation of the nervous system. Whereas, the delayed OP poisoning cases showed signs like generalized weakness, emaciation, tetraparesis/plegia, flaccid paralysis, Megaesophagus, urinary incontinence, spastic paralysis and laryngeal paralysis (Fig. 2). The clinical signs were depicted in the form of graph as per the percentage of occurrence (Fig 4). Here, all the cases showing clinical signs similar to OP poisoning showed decline in the level of butyryl cholinesterase below 3400 u/L indicative of OP poisoning (Fig. 5). The butyryl cholinesterase acts a early indicator in assessing the degree of OP poisoning [8] . Intermediate syndrome IMS presented as paralysis, occurring 7 to 96 hours post-ACC(Acute Cholinergic crisis), but before the typical onset time of OPIDP. It was clinically characterized by muscular weakness, predominantly of proximal limb muscles, neck flexors, muscles innervated by motor cranial nerves or respiratory muscles [9] . IMS was also characterized by prolonged cholinesterase inhibition [10] . Agricultural runoff containing pesticides and fertilizers contributes to water and soil pollution, fostering algal blooms that deplete oxygen levels and threaten aquatic life. The overuse of these chemicals not only disrupts ecosystems but also poses a severe risk to humans and animals through direct exposure and food chain contamination. Aluminium phosphide was the principal cause of fatal pesticide poisoning during the initial decade, but its occurrence declined markedly over time. In contrast, organophosphorus insecticides remained significant throughout the study period and emerged as the predominant toxic agents in the later decade. [11] . The One Health perspective emphasizes the need for integrated policies to regulate pesticide use, promote sustainable farming practices and enhance public awareness of OP poisoning risks. Collaborative efforts among veterinarians, medical professionals, environmental scientists and policymakers are essential to mitigating these challenges.

Conclusion

Organophosphate poisoning remains a critical issue affecting animal, human, and environmental health. Addressing this issue requires a multidisciplinary approach, integrating veterinary and medical knowledge with environmental conservation efforts. Strengthening regulations on pesticide use, adopting sustainable agricultural practices and increasing awareness among farmers and pet owners can help reduce the prevalence and impact of OP poisoning. Whenever we are unaware about the history of poisoning, assessing butyryl cholinesterase will be a diagnostic tool to proceed with further treatment protocol.

Acknowledgement

AcknowledgementsThe author is thankful to the Dean, Veterinary College and Research Institute, Orathanadu.

References

1. Mshelia PC, Buba DM, Oziegbe SD. Management of Organophosphate Poisoning in a 3-Year Old Nigerian Local Breed of Dog (Case Report). Saudi J Med. 2019;4(7):554556.https://doi.org/10.36348/sjm.2019.v04i07.015
2. Wise CF, Hammel SC, Herkert NJ, Ospina M, Calafat AM, Breen M, et al. Comparative Assessment of Pesticide Exposures in Domestic Dogs and Their Owners Using Silicone Passive Samplers and Biomonitoring. Environ Sci Technol. 2022;56:11491161.https://doi.org/10.1021/acs.est.1c06819
3. Mavromati J, Prifti E. Organophospahte intoxication in dogs. European Academic Research. 2024;11(10):12251231.
4. Screbocan E, Hrlec G, Grabarevic Z, Pompe-Gotal J, Sabocanec R. Poisoning with acetylcholinesterase inhibitors in dogs: two case reports. Vet Med Czech. 2003;48(6):175-176.
5. Eddleston M. Novel clinical toxicology and pharmacology of organophosphorus insecticide self-poisoning. Annual Review of Pharmacology and Toxicology. 2019;59:341360.
6. Rizzo H, Silveria filho MEM, Jesus TKS, Soares LLS, Silva junior VA. Organophosphate poisoning in sheep-A case report. Arq Bras Med Vet Zootec. 2024;76(6):1-9.
7. Almeida SSR, Rayanne HSS, Oliveira LM, Alonso LB, Gonzaga BS, Barros ACM, et al. Serum Butyryl cholinesterase activity in helathy dogs with and without exposure to diazinon. An International Journal of Laboratory Medicine. 2023;52(4):646-653.
8. Klainbart S, Kelmer E, Sharabany E, Green I, Aroch I. Clinical Presentation, Consecutive Measurements of Serum ButyrylCholinesterase Activity and Treatment of a Dog Intoxicated by Anticholinesterase and Presented Acute Cholinergic Crisis Followed by Intermediate Syndrome. Case Report and Review of the Literature. Israel Journal of Veterinary Medicine. 2022;77(3):168-174.
9. Bleecker D, Neucker VDK, Colardyn F. Intermediate syndrome in organophosphorus poisoning: A prospective study. Crit Care Med. 1993;21:1706-1711.
10. Alahakoon C, Dassanayake TL, Gawarammana IB, Weerasinghe VS. Can we predict intermediate syndrome? A review. Neurotoxicol. 2018;69:209-216.
11. Karunarathne A, Bhalla A, Sethi A, Perera U, Eddlestone M. Importance of pesticides for lethal poisoning in India during 1999 to 2018: A systematic review. BMC Public Health. 2021;21:1441.