Yan-qing Liu, Xiao-xia Lu, Chun-yan Wang, Ming-fei Peng, Xiao-bo Peng, Yun Jiang, Le-xin Zheng, Dan-dan Yuan,Xi-gang Zhang, Ze-wu Qiu

Poisoning Treatment Department, Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital,Beijing 100071, China

The main toxic component of tetramine is tetramethylenedisulfotetramine (TETS).It is a sulfonamide derivative without special antidote, tasteless and tasteless,with high toxicity and high mortality.[1]It was first discovered by a German scientist Hagen in 1949.Although its use has been banned worldwide due to its high toxicity and mortality rate, it is still available in certain countries and has led to cases of intentional and unintentional poisoning.Tetramine blocks γ-neurons,leading to dizziness, fatigue, nausea, vomiting,convulsions, and other symptoms.[2-4]Due to the lack of recognized effective antidotes, many poisoned people suffocate and die as a result of continuous spasms of the respiratory muscles.[5-7]Tetramine poisoning sometimes occurs, but it is rare for vegetables grown in tetraminecontaminated soil to cause group poisoning after being eaten.

CASE

The patient, a 57-year-old male, had grown vegetables in a 10-year-old abandoned granary near his home in March 2018, which included fennel, lettuce,crowndaisy chrysanthemum, romaine lettuce, leeks,shallots, Chinese cabbage, and other vegetables.A total of 12 patients were found to have varying degrees of dizziness, nausea, sweating, fatigue, involuntary tremor of the limbs, and even convulsions and coma after eating vegetables (Table 1).

Table 1.Symptom onset time and type of vegetables eaten by the 12 patients and symptoms experienced afterward

On June 30, 2018, all 12 patients were transferred to our department.Patients A, D, J, K, and L had convulsive symptoms one after another, and familial epilepsy was excluded.Clinical manifestations are shown in Table 1.Laboratory findings were normal,including routine blood, urine, and stool, liver and kidney function, blood glucose, blood lipid, coagulation function, immune combination, electrocardiogram(ECG), chest and abdomen computed tomography (CT),and brain magnetic resonance imaging (MRI).However,creatine kinase increased to 567 U/L (normal <167 U/L) in the five patients with convulsions.Considering this evidence, diseases such as nervous system infection,cerebrovascular disease, psychosis, or metabolic disorders were excluded.During treatment, phenobarbital sodium was given to control body convulsions,rabeprazole sodium to protect the stomach, cerebroside and carnosine to nourish nerves, compound glycyrrhizicn to protect the liver, and creatine phosphate to nourish the myocardium.Different family members developed the disease successively.All the patients had eaten vegetables grown in the same field, and their clinical manifestations were similar.The degree of severity is related to the number of vegetables eaten.Those who had eaten a large quantity of vegetables had more serious symptoms.We considered that the patient’s symptoms were associated with eating these vegetables.The family members said that the seeds of vegetables as well as the vegetables had not been sprayed with pesticides.This does not rule out the possibility of rat poison stored in the location before the patient planted vegetables.In conclusion, there may be a strong possibility of convulsive rodenticide poisoning.

On July 1, 2018, a liquid chromatography-mass spectrometer (LC-MS) (API-3200, ABI, USA) was used for poison detection.Three patients (A, D, and F)ate two kinds of vegetables twice.The concentrations of TETS in venous blood were: patient A 988 ng/mL,patient D 820 ng/mL, and patient F (less food intake)265 ng/mL.Patient I ate a few boiled lettuce heads, and the test was taken 15 d later; TETS was not detected in the venous blood.Other patients ate one vegetable once, and the TETS concentration in venous blood was 110–602 ng/mL.Although TETS was still detectable in the blood when the patients came to our hospital, the symptoms of 10 patients were relieved, and only two patients had involuntary tremor of both upper limbs.Treatment was given to control limb tremor, nourish nerves, replenish body fluids, and promote the discharge of poisons.All twelve patients were cured after 3–15 d of hospitalization.The patients were followed up for 3 months after discharge, and all of them returned to normal.

DISCUSSION

To clearly determine the source of TETS, the poison detection center of our hospital examined fennel, lettuce,crowndaisy chrysanthemum, romaine lettuce, leek,shallot, Chinese cabbage, and soil.TETS was detected in the soil and all vegetables.

To determine the reason for convulsion in patients who ate lettuce and crowndaisy chrysanthemum, several vegetables grown in the soil were selected and made into vegetable juice.After the approval of the hospital ethics committee, the animal toxicity experiment was carried out by gavage in Wistar rats (body weight 200 g).On the first day, we took unwashed lettuce, leek, and shallot samples (7.4 g per vegetable; leaves, stems, and roots accounting for 1/3 each by mass).After grinding and mixing with 20 mL of water, 1 mL per 100 g body weight of the mixture was gavaged.There were two rats in each group.After 5–6 min of gavage, the rats in the lettuce group began to have convulsions, which lasted for 0.3–2.0 min and then relieved automatically, after which convulsions resumed intermittently.One rat died of continuous convulsions after 45 min, and the other one died of intermittent convulsions after 16 h.The rats in the leek group and the shallot group survived without convulsions.On the second day, we repeated the experiment.We took unwashed vegetables (lettuce, leek,shallot, romaine lettuce), washed vegetables (lettuce,leek, shallot, romaine lettuce), and soil in the planting area (20 g) as samples.After grinding and mixing with 20 mL of water, 1 mL per 100 g body weight of the mixture was gavaged.The rats in the unwashed and washed lettuce groups had convulsions and eventually died.The rats in the other groups survived.In the animal toxicity test, only the rats in the lettuce group had convulsive symptoms, which had nothing to do with whether the vegetables had been washed or not.There were no convulsive symptoms in rats fed with leek, shallot, romaine lettuce, or soil in the planting area,which indicated that the TETS content in soil was not too high, and the ability of different vegetables to enrich TETS was different.

The local authorities ruled out the possibility of patients being poisoned by others and further tested items in the patient’s home, such as flour, water in the drinking dispenser, and water in the bathtub.No TETS was detected.In the periphery of this land, no TETS was detected in vegetables or soil.TETS was detected only in vegetables and soil planted by patients.The patients had never purchased tetramine, and there was no factory producing tetramine near their home.By asking the former staff of the grain depot, the patients learned that rat poison had been stored in the place where the patients planted vegetables.It was found that tetramine used by the grain depot to eliminate mice 10 years ago polluted the soil.The patients planted vegetables on the polluted soil, and the vegetables became enriched with tetramine, resultingin tetramine poisoning after human consumption.After the incident, the local government sealed the abandoned grain depot and buried the incident site.

CONCLUSIONS

Tetramine is stable in nature and is not readily decomposable in the environment.Tetramine poisoning should be considered for cases of unexplained coma with convulsions.Daily necessities contaminated by tetramine should be destroyed promptly, and the contaminated soil should be buried deeply to prevent secondary poisoning.

Funding:This study was supported by a grant from the National Key R&D Program of China (2019YFC16063000).

Ethical approval:This study was approved by the Ethics Committee of the Fifth Medical Center of PLA General Hospital, Beijing, China.Informed written consent was obtained from the patients.

Conflicts of interest: None.

Contributors:YQL and XXL contributed equally to this work.YQL and XXL proposed and wrote the paper.All authors read and approved the final version.