Organophosphorus & Carbamate Poisoning

• Organophosphorus (OP) and carbamate compounds are insecticides that can cause poisoning through accidental exposure or overdosing.

Epidemiology

• Outbreaks of OP and carbamate poisoning often result from overdosing or misuse of oil-based preparations.
• These preparations can be used on non-animal surfaces, dehydrated animals, or in orchards and fields.

Clinical Pathology

• OP and carbamate poisoning leads to a marked depression of blood cholinesterase levels, which are neurotransmitters.

Lesions

• Acute OP and carbamate poisoning typically does not cause diagnostic lesions.
• Chronic exposure can result in delayed neurotoxicity, causing degenerative lesions in peripheral nerves and the spinal cord.

Diagnosis

• Diagnosis is confirmed by detecting decreased cholinesterase levels in the blood.
• Presence of organophosphates or carbamates can be confirmed by testing feed or environmental samples.

Treatment

• Atropine is administered in large doses (0.5 mg/kg BW IV), followed by IM or SC injections every 3-4 hours for 1-2 days.
• Can administer atropine with 2-PAM (pralidoxime chloride) at 25–50 mg/kg BW IV as a 20% solution.
• Remove any residual toxin by washing the hair coat.
• Use activated charcoal and cathartics (laxatives) to prevent absorption of toxins from the gastrointestinal tract.

Etiology

• While OP compounds and carbamates share a similar mechanism, OP compounds bind irreversibly to esterase enzymes.
• Carbamates' bonding is spontaneously degradable and thus less dangerous.

Epidemiology: Sources of Toxin

• Grazing in recently sprayed areas or orchards is a common source of poisoning
• Sprays used on cereal crops and carried by wind onto pasture fields can also cause poisoning
• Other sources include hay or cubes made from sprayed plants, old insecticide containers used as feeding utensils, and contaminated water.

Risk Factors

• Young, stressed, water-deprived, and cooled animals are more susceptible.
• Pregnant females may have offspring with congenital defects.
• Brahman and Brahman-cross cattle appear more susceptible.

Environmental Risk Factors

• The use of these compounds to treat nematode, botfly, sheep nasal botfly, and warble fly infestations, as well as insecticidal sprays on plants and soil, increases poisoning risk.

Transmission

• Transmission is influenced by the formulation used and the method of application.
• Toxicity is delayed by 24 hours with pour-ons compared to sprays.

Pathogenesis

• OP compounds are highly toxic and easily absorbed through ingestion, inhalation, and skin.
• They are metabolized by mixed function oxidases (MFOs), increasing toxicity.

Types of Toxicity

• Cholinesterase inactivation & OP-induced, delayed neurotoxicity.
• Cholinesterase inactivation leads to increased acetylcholine levels and parasympathetic nervous system activity.

Symptoms

• Muscarinic effects include respiratory distress from decreased lung compliance and increased pulmonary resistance, bronchial constriction, increased mucus secretion, increased peristalsis, salivation, hypotension, bradycardia, pupillary constriction, sweating, and abortion.
• Nicotinic effects include muscle twitching, tremor, tetany, convulsions, weakness, and flaccid paralysis.

Organophosphorus-Induced Delayed Neurotoxicity

• Distal axonopathy starts 1-2 weeks after poisoning, causing flaccid paralysis, especially in long neurons.
• This is due to a toxic end product from the interaction of OP compounds and esterase

Clinical Findings (Acute Poisoning)

• Signs occur within minutes of inhalation or ingestion of toxic compounds.
• Death can occur within 2-5 minutes.
• With cutaneous application of dichlorvos, signs appear within 30 minutes, peak at 90 minutes, and disappear in 12-18 hours.

Acute Toxicosis in Cattle, Sheep, and Goats

• Early signs include salivation, lacrimation, restlessness, nasal discharge, cough, dyspnea, diarrhea, frequent urination, and muscle stiffness with staggering.
• Additional signs: tongue protrusion, pupil constriction with vision impairment, muscle tremor, bloat, collapse, and death. Sheep and goats may show abdominal pain.
• Signs disappear in 12-18 hours.

Delayed Neurotoxicity

• Signs appear 8-90 days post-poisoning and include posterior incoordination and paralysis. Specific example is chlorpyrifos.
• Other signs include anorexia, depression, recumbency, distended abdomen, ruminal stasis, diarrhea, and fluid splashing sounds, can result in death.

Acute Toxicosis in Horses

• Include abdominal pain, grossly increased intestinal sounds, very fluid diarrhea, muscle tremors, ataxia, circling, weakness, and dyspnea.
• Transient fluid diarrhea in foals may indicate severe gastroenteritis with heavier doses.

Delayed Neurotoxicity in Horses

• Occurs as syndrome and bilateral laryngeal paralysis which occurs in foals after dosing with an OP anthelmintic.

Clinical Pathology (Laboratory Diagnosis)

• Cholinesterase estimation in body tissues is the most satisfactory diagnosis method
• Normal controls should be used.
• Convincing figures are of the order of 50% to 100%
• Blood cholinesterase levels are depressed for much longer than clinical signs are apparent.
• Unlike organophosphate insecticides, carbamate insecticide cholinesterase inhibitors may spontaneously reverse binding, and cholinesterase depression may not be detectable in recently poisoned animals.
• Suspected food material can be assayed for its content of OP compounds

Necropsy Findings

• There are no gross or histologic lesions at necropsy in acute cholinesterase.
• Inactivation cases, but tissue specimens could be collected for toxicologic analysis.
• Material sent for laboratory analysis for cholinesterase should be refrigerated but not deep frozen.

Differential Diagnosis

• Outbreaks of a syndrome of dyspnea, salivation, muscle stiffness, and constriction of the pupils after exposure plus a history of exposure and depressed blood levels of cholinesterase suggest intoxication with these organophosphorus compounds,
• In cattle the morbidity and case-fatality rates are approximately 100% and residual defects,
• Including blindness and paralysis, occur in a proportion of the survivors.

Differential Diagnosis List

• Cattle: Early stages of nicotine poisoning, acute bovine pulmonary emphysema, sporadic anaphylaxis cases.
• Horses: Lead toxicosis, arsenic toxicosis, avitaminosis A, mercury poisoning, sodium chloride poisoning NOTE: Other disease can be a differential diagnosis

Treatment

• Wash animals that have been dipped or sprayed with water and soap to remove residual OP material.
• If oral intake occurred, use activated charcoal to adsorb residual toxin with laxative
• Primary treatment is critical, particularly in cattle due to the case-fatality rate.
• Atropine is the antidote for muscarinic effects, but does not reverse the nicotinic effects of OP compounds.
• Recommended dose of atropine in sheep and goats is 0.5 mg/kg BW IV, repeated every 3-4 hours for 1-2 days. Atropine is less effective in sheep.

Treatment (cont.)

• Dose of atropine in horses is 0.02 to 0.2 mg/kg BW, but it needs to be given with care because horses are very susceptible to the gastrointestinal effects of atropine.
• Oximes (e.g., pralidoxime chloride/2-PAM) are useful early in OP poisoning.
• Dose rate for 2-PAM in ruminants is 25 to 50 mg/kg BW IV as a 20% solution over 6 minutes.

Doses for Ruminants:

• Atropine sulfate: 0.5 mg/kg BW with 1/4 IV and the remainder IM or SC every 3–4 hours for 1–2 days.
• Pralidoxime chloride (2-PAM): 25–50 mg/kg BW IV as a 20% solution over 6 minutes, repeat as needed.

Doses for Horses:

• Atropine sulfate: 0.02 to 0.2 mg/kg BW IV; repeat SC every 1.5-2 hours.
• Pralidoxime chloride (2-PAM): 20 mg/kg BW IV; repeat every 4–6 hours as needed.

Control

• Address accidental access to compounds.
• Provide ample fresh drinking water beforehand.
• Chlorpyrifos use is restricted to beef cattle, not in calves under 12 weeks or bulls over 8 months.