Neurotoxicity after poisonings with organophosphate pesticides in Nicaragua

In Nicaragua rates of acute human poisonings caused by pesticides, in spite of significant underreporting, are among the highest in the world. Hence the unrestricted availability of pesticides and their misuse, as well as the continuous increase in annual imports of pesticides are reasons for public health concern. Organophosphate insecticides (OPs) are responsible for more than 45 % of pesticide poisonings in Nicaragua. Severe poisonings caused by certain OPs have been associated with Organophosphate-induced Delayed Polyneuropathy (OPIDP), a persistent neurological impairment that may ensue a few weeks after recovering from acute poisoning.

Neuropathy was evaluated in relation to acute poisonings with some organophosphate pesticides (metamidophos, chlorpyrifos or fenthion) in Nicaraguan individuals hospitalized for acute OP poisoning between 1992 and 1996. Serial Lymphocyte Neuropathy Target Esterase (LNTE) was measured in a case of acute OP poisoning in order to evaluate this enzyme as a predictor of subsequent neuropathy. Motor function, as in grip and pinch strength, was evaluated among 62 patients immediately after hospital discharge and around 7 weeks later. Sensory function, as in vibrotactile thresholds, was evaluated among 56 patients immediately after hospital discharge and around 7 weeks later. Hand strength and vibrotactile thresholds were re-evaluated 2 years after poisoning among 48 patients. Nerve conduction velocity was measured on 3 occasions during a two-year period among 44 patients. Finally, long-term sensory neurological impairment was evaluated through a fixed protocol of clinical examination among 49 patients at the end of the follow-up.

Inhibition of LNTE was found to be a good predictor of the development of OPIDP in one poisoned individual. Hand strength was found to be reduced on both examinations in all exposure categories regardless of the OP type, but weakness was more marked among those with poisonings due to neuropathic OPs. Among these patients, those with intentional poisonings were the weakest and worsened with time, an unequivocal sign of OPIDP. Toe tactile vibration thresholds were impaired 7 weeks after poisoning among patients with severe intentional poisonings. This finding confirmed OPIDP. Two years after severe occupational and attempted suicide poisonings by neuropathic OPs patients had persistent sensory and motor impairment, predominantly motor impairment, which served as an indication of remaining OPIDP. In the same way, slowed conduction velocity in the tibial motor nerve that persisted two years after poisoning was found among all individuals poisoned by OPs regardless of whether the poisoning pesticide was considered as neuropathic or non-neuropathic, and this served as a possible indication of insufficient recovery from OPIDP. An increased number of reported symptoms and signs was detected among all patients, more evidently among those severely poisoned by neuropathic OPs two years earlier, which served as an indication of altered sensory function in contrast with our earlier findings of some recovery from motor dysfunction.

List of scientific papers

I. McConnell R, Delgado-Tellez E, Cuadra R, Torres E, Keifer M, Almendarez J, Miranda J, El-Fawal HA, Wolff M, Simpson D, Lundberg I (1999). Organophosphate neuropathy due to methamidophos: biochemical and neurophysiological markers. Arch Toxicol. 73(6): 296-300.
https://pubmed.ncbi.nlm.nih.gov/10447555

II. Miranda J, Lundberg I, McConnell R, Delgado E, Cuadra R, Torres E, Wesseling C, Keifer M (2002). Onset of grip- and pinch-strength impairment after acute poisonings with organophosphate insecticides. Int J Occup Environ Health. 8(1): 19-26.
https://pubmed.ncbi.nlm.nih.gov/11843436

III. Miranda J, McConnell R, Delgado E, Cuadra R, Keifer M, Wesseling C, Torres E, Lundberg I (2002). Tactile vibration thresholds after acute poisonings with organophosphate insecticides. Int J Occup Environ Health. 8(3): 212-9.
https://pubmed.ncbi.nlm.nih.gov/12358077

IV. Miranda J, McConnel R, Delgado E, Cuadra R, Torres E, Wesseling C, Keifer M, Lundberg I (2003). Muscular strength and vibraton thresholds during two years after acute poisoning with organophosphate insecticides. [Submitted]

V. Miranda J, Cuadra R, McConnel R, Borg K, Delgado E, Torres E, Wesseling C, Keifer M, Lundberg I (2003). Nerve conduction velocity after poisoning with organophosphate insecticides: A two-year follow-up study. [Manuscript]

VI. Miranda J, Borg K, Wesseling C, McConnel R, Lundberg I (2003). Occurance and severity of neuropathy during two years after organophosphate pestcide poisoning. [Manuscript]