Ivermectin is an endectoparasiticide and is the drug of choice in filariasis, scabies (crusted or if topical treatment has failed), and several other infestations [1]. It has a low rate of adverse reactions with toxicity occurring only with overdosing, resulting in adverse prognosis, as no specific antidotes are available [1,2]. Although rare in children, over 150 cases of serious neurological toxicities have been reported in adults [1]. We report a case of ivermectin toxicity with encephalopathy, shock and aspiration pneumonia in a young child and its successful management.

A 6-year-old previously healthy girl (weighing 20.5 kg) presented with a history of accidental consumption of 60 mL of 1% w/v (600 mg) ivermectin lotion (30 mg/kg). She was undergoing treatment for scabies. After four hours of consumption, she had two episodes of vomiting followed by generalized tonic-clonic movements and loss of consciousness. On arrival, she was unresponsive, with Glasgow Coma Scale (GCS) 6/15, with tachycardia, tachypnea, hypotension and oxygen saturation of 79% at room air. Pupils were equal bilaterally (3 mm) with sluggish reaction. There were no signs of meningeal irritation. There was generalized hypotonia with absent deep tendon reflexes and fundoscopic examination was normal. Excessive salivation and bilateral crepitations were present. The child was admitted to the pediatric intensive care unit. Given the poor GCS and respiratory failure, the child was intubated, ventilated, and started on parenteral antibiotics ceftriaxone and clindamycin, along with supportive measures. In view of continuing seizures, intravenous midazolam and phenytoin were given. In addition to saline bolus, noradrenaline infusion for hypotension was started and carefully titrated. Blood gas analysis showed respiratory and metabolic acidosis. The hemogram on admission showed hemoglobin 9.5 g/dL, platelet count 173×109/L; and total leucocyte counts 7.2×109/L (neutrophils, 76.7%). Liver function tests and renal function tests, coagulation profile and blood glucose were normal. C- reactive protein (CRP) was elevated 36.4 mg/L. Chest X-ray showed left upper lobe collapse and bilateral opacities. The National poison information centre was consulted and supportive management was advised as there was no specific antidote. Her urine output remained normal.

Patient started having high grade fever after 24 hours. Repeat investigations showed leucocytosis of 13.5×109/L (neutrophils 83%) and CRP of 67.8 mg/L. Blood culture and endotracheal secretions for culture showed no growth. In view of shock and hypotension, echocardiography was done, which showed normal left ventricular ejection fraction of 65%. Gradually, sensorium improved in the form of intermittent awakening after 48 hours, and GCS became 13/15 by day five. Patient became afebrile after four days. Hemodynamic improvement started only after day three, and vasopressors were slowly tapered off. Ventilatory requirements which were high initially, also decreased from day three and in view of neurological and hemodynamic stability, child was weaned off from ventilator on day five and extubated. Repeat hemogram, CRP and Chest X-ray became normal by eighth day. Neuroimaging could not be done initially as the child was critical, and was refused later by parents in view of clinical improvement. She was discharged after nine days of hospitalization in a stable condition on oral clindamycin (total duration of 14 days).

Ivermectin, in standard therapeutic doses, has both excellent parasiticidal efficacy and high tolerability [1]. Ivermectin does not readily cross the blood-brain barrier (BBB) in humans as it is effluxed by ATP-binding cassette subfamily B member 1 (ABCB1) transporter also called P-glycoprotein drug pump or mdr-1 located in the blood/brain barrier [1,3]. Hence, neurological adverse reactions are rare unless there is overdosage [1]. Our patient ingested 30 mg/kg of ivermectin, which was almost 100 times the recommended dose. Usually, a single oral dose of 150 to 300 mcg/kg is recommended, and 200 mcg/kg in scabies [4,5]. We suspected ivermectin poisoning due to the history, since encephalopathy and coma are well-documented side effects of ivermectin treatment in animals, and after ruling out other usual causes of coma. Severe neurological toxicities have been reported in public health programs in Africa, possibly due to concomitant infestations with high densities of loa loa, genetic predisposition, and co-infestations [1,6]. Additional intake of drugs that inhibit CYP3A4 and polymorphisms in the mdr-1 gene could also result in toxicity [1]. A recent case report of ivermectin taken in recommended dose, by a 13-year-old child, attributed the resulting neuro-toxicity, to human ABCB1　nonsense mutations, which had led to loss of the neurological protective ABCB1 activity [3].

In our patient, despite there being no specific antidote, vigorous monitoring, and supportive critical care treatment proved to be lifesaving.

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3. Baudou E, Lespine A, Durrieu G, et al. Serious lvermectin toxicity and human　ABCB1　nonsense mutations. N Engl J Med. 2020; 383:787-89.

4 Jans DA, Wagstaff KM. The broad spectrum host-directed agent ivermectin as an antiviral for SARS-CoV-2 ? Biochem Biophys Res Commun. 2021;538:163-72.

5. González Canga A, Sahagún Prieto AM, Diez Liébana MJ, et al. The pharmacokinetics and interactions of ivermectin in humans–A mini-review. AAPS J. 2008;10:42-6.

6. Boussinesq M, Gardon J, Gardon-Wendel N, Chippaux JP. Clinical picture, epidemiology and outcome of Loa-associated serious adverse events related to mass ivermectin treatment of onchocerciasis in Cameroon. Filaria J. 2003;2:S4.