Letter
A case of infant death due to chlorfenapyr poisoning
2024 Volume 49 Issue 12 Pages 549-553
Details
2024 Volume 49 Issue 12 Pages 549-553
Chlorfenapyr is a novel pyrrole compound with the chemical formula C15H11BrClF3N2O, exhibiting potent insecticidal and acaricidal effects. It primarily acts on the multi-functional oxidases in the mitochondria of insects, inhibiting the conversion of adenosine diphosphate to adenosine triphosphate, leading to cellular dysfunction due to energy depletion. With increased production and market availability, the population’s exposure to chlorfenapyr has risen, resulting in a growing number of fatal poisoning incidents. This report describes the clinical presentation, disease progression, and treatment outcomes of a 2-year and 11-month-old toddler poisoned with chlorfenapyr. The child exhibited symptoms of nausea and vomiting two hours post-poisoning, received gastric lavage and fluid replacement at the local hospital, and was subsequently transferred to our facility. On admission, the child's vital signs were stable for the first two days, with normal laboratory findings. On the third day, the child showed signs of fatigue and diaphoresis, followed by high fever, profuse sweating, altered consciousness, and muscle tremors on the fourth day. By the fifth day, the child displayed rigid muscles in the limbs and trunk, respiratory and circulatory failure, despite rescue efforts proving futile, leading to eventual demise.
Chlorfenapyr is a novel pyrrole insecticide and acaricide widely used globally, known for its broad spectrum and long-lasting efficacy (Yang et al., 2020; Rui and Qin, 2024). Classified as a moderately hazardous insecticide by the World Health Organization (https://www.who.int/publications/i/item/9789240005662), chlorfenapyr primarily acts by inhibiting the oxidative phosphorylation process of mitochondrial multi-functional oxidases, preventing the conversion of adenosine diphosphate to adenosine triphosphate, thus disrupting cellular energy production and exerting its insecticidal properties (Periasamy et al., 2017). Chlorfenapyr is mainly absorbed into the human body through the gastrointestinal tract, respiratory tract, and skin mucosa. Early symptoms of chlorfenapyr poisoning include nausea, vomiting, abdominal pain, dizziness, weakness, and lethargy. While reported cases of chlorfenapyr poisoning have predominantly involved adults, instances of pediatric chlorfenapyr poisoning are rare (Zhan et al., 2024; Wang et al., 2024). Here, we present a clinical case of a toddler poisoned with chlorfenapyr, detailing the clinical manifestations, disease progression, and treatment outcomes, with the aim of raising awareness among healthcare professionals.
Case ReportPatient: Female toddler, 2 years and 11 months old. Chief Complaint: Accidental ingestion of chlorfenapyr 2 hours ago. The toddler accidentally ingested chlorfenapyr at home (specific dosage unknown) and was immediately rinsed with water by family members upon discovery. Subsequently, she was taken to the local hospital for emergency treatment, where gastric lavage and fluid replacement were initiated before being transferred to our facility by ambulance. Upon arrival at our hospital, the patient exhibited symptoms of nausea and vomiting. Physical examination on admission revealed the following: Temperature: 36.7°C, Heart Rate: 100 beats per minute, Respiratory Rate: 28 breaths per minute, Blood Pressure: 118/81 mmHg, Oxygen saturation: 100% on room air. The patient was alert, responsive, with equal and round pupils measuring approximately 3 mm in diameter, showing sensitive light reflex. Clear breath sounds bilaterally without crackles, heart rate at 100 beats per minute with regular rhythm and no murmurs auscultated in all valve areas. Abdomen was soft with no tenderness or rebound tenderness, normal muscle tone in all extremities, negative Babinski sign bilaterally, and negative signs of meningeal irritation.
Laboratory Investigations: WBC 8.31×10^9/L (Reference Range: 4.4-11.9 ×10^9/L), Neutrophil Percentage 87% (Reference Range: 22-65%), Hb 110 g/L (Reference Range: 112-149 g/L), PLT 141×10^9/L (Reference Range: 188-472×10^9/L); Blood Gas Analysis: pH 7.43 (Reference Range: 7.35-7.45), PCO2 34 mm Hg (Reference Range: 35-45 mm Hg), PO2 114 mm Hg (Reference Range: 83-108 mm Hg), Lactate 0.7 mmol/L (Reference Range: 0.5-1.6 mmol/L), HCO3- 23 mmol/L (Reference Range: 22-26 mmol/L); Liver function, renal function, electrolytes, cardiac enzymes, troponin I, coagulation profile, and amylase levels were all within normal ranges; ECG and chest X-ray showed no abnormalities.
Due to the clear identification of the toxic substance and its nature, and the prior gastric lavage and fluid replacement conducted at the external hospital, the patient’s family declined to provide blood and gastric content samples for toxicological analysis and drug concentration testing. Upon admission, the patient received fluid replacement, acid suppression (intravenous omeprazole 0.8 mg/kg once daily), and diuresis (intravenous furosemide 1 mg/kg every 12 hr) treatments, leading to the resolution of the patient’s nausea and vomiting symptoms. On the second day of admission, repeat tests, including blood routine, ECG, cardiac enzyme profile, and troponin I, were within normal ranges. The patient was transferred to a general ward at 9 AM on the third day of admission. However, at 9 PM on the third day of admission, the patient exhibited fatigue, diaphoresis, and polydipsia. By 8 AM on the fourth day of admission, the patient developed fever, drowsiness, and dyspnea, prompting a transfer back to the Pediatric Intensive Care Unit (PICU).
Upon transfer to the PICU, the vital signs of the patient were as follows: temperature 37.6°C, respiratory rate 50 breaths per minute, heart rate 150 beats per minute, and SPO2 of 96% under nasal cannula oxygen supplementation. Physical examination revealed the patient to be lethargic, diaphoretic, with bilateral pupils dilated and isocoric, measuring 2 mm in diameter, and showing sensitive light reflexes. Clear bilateral lung breath sounds were heard without rales, strong heart sounds with regular rhythm, and a Glasgow Coma Scale score of 10 (E4V3M3), with mild tremors in the limb muscles. Laboratory investigations showed the following results: blood gas analysis revealed a pH of 7.469 (Reference Range: 7.35-7.45), PCO2 27.1 mmHg (Reference Range: 35-45 mmHg), PO2 110 mmHg (Reference Range: 83-108 mmHg), lactate 1.0 mmol/L (Reference Range: 0.5-1.6 mmol/L), bicarbonate 19.7 mmol/L (Reference Range: 22-26 mmol/L), K+ 2.7 mmol/L (Reference Range: 3.5-4.5 mmol/L), Na+ 134 mmol/L (Reference Range: 136-146 mmol/L), Ca2+ 0.66 mmol/L (Reference Range: 1.15-1.29 mmol/L), and blood glucose 16.4 mmol/L (Reference Range: 3.89-5.83 mmol/L). Coagulation parameters included an APTT >170s (Reference Range: 22.7-31.8s), PT 19.5s (Reference Range: 9.8-12.1s), TT >160s (Reference Range: 14-21.0s), INR 1.72 (Reference Range: 0.84-1.04), FIB 2.45g/L (Reference Range: 2.0-4.0g/L), and D-Dimer 0.24 (Reference Range: 0.00-0.55g/L). BNP was elevated at 1092 pg/mL (Reference Range: 0-125.2 pg/mL), and creatine kinase was elevated at 145 ng/mL (Reference Range: 14.3-65.8 ng/mL). Liver and kidney function, troponin I, ECG, and echocardiography showed no abnormalities.
Treatment included fluid resuscitation, potassium and calcium supplementation, anti-inflammatory therapy (intravenous methylprednisolone sodium succinate 1 mg/kg every 12 hours), and blood filtration with hemoperfusion. On the fourth night of admission, the patient fell into a deep coma, with pinpoint pupils, hyperpyrexia (41°C), necessitating cooling measures with cooling blankets. By the morning of the fifth day of admission, the patient exhibited trismus, limb rigidity, muscle stiffness in the limbs and trunk, followed by cardiac and respiratory arrest. Immediate cardiopulmonary resuscitation, endotracheal intubation, multiple doses of intravenous adrenaline, and aggressive resuscitation efforts were initiated, but unfortunately, the resuscitation was unsuccessful, and the patient succumbed to the condition.
With the increase in production capacity and market distribution, the population is increasingly exposed to chlorfenapyr, leading to a rise in clinical poisoning-related fatalities (Huang et al., 2020; Gong et al., 2021; Lije et al., 2022; Chien et al., 2022; Zhao et al., 2022; Tie et al., 2023; Qu et al., 2023). In this study, the child’s family grows mango trees, and they live in a small house next to the mango orchard. The pesticide is used for insect control. The child’s father did not store the pesticide properly. He transferred it to a beverage bottle because the instructions indicated that the pesticide needed to be diluted with water before use, but he did not inform the other family members. Unfortunately, the child mistakenly ingested the pesticide thinking it was a beverage. The child’s mother discovered that the child had ingested powder from a beverage bottle, immediately made the child vomit, and performed oral cleaning. It is estimated that the child ingested a dose of pesticide of around 3 g. A study in Ethiopia revealed that among pesticide users, 63.8% exhibited poor pesticide handling and storage practices. Knowledge, attitude, and educational status were significantly associated with pesticide handling and storage practices (Mequanint et al., 2019). Training and extensive information dissemination can enhance the knowledge of pesticide handling and storage practices among relevant populations.
According to a previous study, the median lethal dose of chlorfenapyr in mice is 45 mg/kg (Metruccio and Boobis, 2012). The European Union recommends an acceptable daily intake of chlorfenapyr based on animal studies at 0.015 mg/kg/day and an acute reference dose of 0.03 mg/kg/day, with no specific toxicological reference values available (European Food Safety Authority, 2019). The child is 88 cm tall and weighs 13.5 kg. Based on the data provided by the above-mentioned animal experiment, although species differences exist, we believe that this patient ingested a dose of chlorpyrifos far exceeding the lethal dose (222 mg/kg).
Chlorfenapyr primarily inhibits the mitochondrial oxidative phosphorylation process, preventing the conversion of ADP to ATP within the mitochondria. In the early stages of poisoning, the remaining ATP can sustain the body’s basic metabolism. As the condition progresses, high-energy-demanding organs such as the brain, skeletal muscles, and heart may be compromised, leading to symptoms such as coma, high fever, muscle rigidity, and cardiac arrest. In this case, the child exhibited normal liver, kidney, and heart functions on the first day of post-ingestion. On the third night, the child experienced fatigue and excessive sweating, followed by drowsiness and high fever on the fourth day. By the fifth day, the child was presented with coma, generalized muscle rigidity, and cardiac and respiratory arrest. Laboratory tests revealed elevated creatine kinase levels and significant abnormalities in coagulation function.
Currently, there are no published studies on the relationship between delayed symptoms of chlorfenapyr poisoning and patient height and weight. A study on the metabolic characteristics of chlorfenapyr indicated that mice rapidly convert chlorfenapyr to tralopyril in the liver after ingestion, with tralopyril having significantly higher values for half-life (t1/2) and peak concentration (Cmax) compared to chlorfenapyr (P<0.05). In vitro metabolism studies showed a metabolic half-life of 62 min for chlorfenapyr in human liver microsomes, while tralopyril had a metabolic half-life of over 120 min (Zhang et al., 2024). Despite species differences, it is speculated that similar metabolic characteristics may exist in humans after chlorfenapyr ingestion.
Chung et al. reported a case of suicide involving the oral ingestion of 200 mL of 10% chlorfenapyr. Their findings revealed low serum levels of chlorfenapyr at 4 hr post-exposure (77.4 ng/mL), which became undetectable at 113 and 156 hr. However, a late increase in serum tralopyril levels was observed, rising from 723.6 to 9654.2 ng/mL (Chung et al., 2022). Both chlorfenapyr and its metabolite tralopyril are lipophilic. Given the high peak concentration and long half-life of tralopyril, it is believed to be the main reason for the prolonged poisoning window in chlorfenapyr patients.
Based on previous reports of chlorfenapyr poisoning cases, most patients exhibit neurological manifestations, with imaging studies showing involvement of the brain white matter, demyelinating lesions, and diffuse brain edema (Zhan et al., 2024; Wang et al., 2024; Gong et al., 2021). In a case reported by Zhan et al., a child with chlorfenapyr poisoning developed headaches on the fifth day of poisoning and fell into a coma on the ninth day (Zhan et al., 2024). In another case reported by Wang et al., a child with chlorfenapyr poisoning experienced headaches on the eleventh day of poisoning and fell into a deep coma on the seventeenth day (Wang et al., 2024). In the present case, involving a toddler, drowsiness occurred on the fourth day of poisoning, followed by deep coma on the fifth day. All three of the aforementioned pediatric cases ultimately resulted in fatalities.
A previous study has shown that chlorfenapyr primarily accumulates in the stomach, lungs, and liver of mice and does not distribute to the heart, spleen, or brain. After 8 hours, chlorfenapyr was rapidly cleared from all tissues and blood except the stomach. In contrast, tralopyril not only forms rapidly in the body but also widely distributes to all organs and tissues, including the heart, liver, spleen, lungs, kidneys, stomach, intestines, muscles, brain, and plasma (Zhang et al., 2024). We believe that continuous assessment of tralopyril concentration is crucial in managing chlorfenapyr poisoning, determining the monitoring duration based on tralopyril levels in the body. Due to the extensive distribution of tralopyril in various organs, it is also necessary to assess organ function in patients during hospitalization, including coagulation function, complete blood count, liver and kidney function, troponin I, creatine kinase, etc.
In this case, the child’s vital signs were stable on the first and second days of hospitalization, with no significant abnormalities in laboratory tests observed, leading to a lack of aggressive interventions such as plasma exchange or blood perfusion. However, on the third night of hospitalization, the child exhibited fatigue and excessive sweating, indicative of organ dysfunction. By the fourth day of admission, the patient’s condition worsened, manifesting as coma, high fever, and organ failure, indicating a missed optimal treatment window. On the fifth day of admission, the child passed away. Based on this case, we recommend early and proactive interventions for chlorfenapyr poisoning patients, such as plasma exchange and blood perfusion. According to literature reports, the time to fatality from chlorfenapyr poisoning ranges from 1 to 21 days after exposure (Zhan et al., 2024), suggesting the need to extend the observation period for children in the hospital, dynamically monitor toxin concentrations and organ function, and promptly provide symptomatic treatment.
In terms of treatment, due to the lack of specific antidotes, clinical management of chlorfenapyr poisoning patients often involves symptomatic treatment such as gastric lavage, fluid replacement, diuresis, ATP supplementation, and coenzyme Q10 administration. Chlorfenapyr, with its small molecular weight, low water solubility, strong lipophilicity, and electron affinity, is easily absorbed by organs. According to the consensus of experts on the diagnosis and treatment of acute poisoning in China (Chinese Medical Doctor Association Emergency Medical Branch; Chinese Society of Toxicology Poisoning and Treatment of Specialized Committee, 2016), clinicians should consider factors such as the molecular weight of the toxin, solubility, half-life, volume of distribution, and protein binding rate when deciding whether to pursue blood purification therapy and selecting the appropriate modality.
In summary, this article presents a clinical case of a toddler with chlorfenapyr poisoning, detailing the clinical manifestations, disease progression, and treatment outcomes. Proper storage and handling of pesticides are crucial for individuals involved in agricultural production.
Thanks to the healthcare professionals involved in the treatment of the child.
Conflict of interestThe authors declare that there is no conflict of interest.
