Case Report: Fatal Scorpion Envenomation in a Shuar Child by Tityus cisandinus from Amazonian Ecuador: A Call for Specific Antivenom Availability in the Amazon Basin

ABSTRACT.

Envenomation by scorpions belonging to the genus Tityus can be life threatening in the Americas, particularly in the Amazon Basin. We report a 4-month-old Ecuadorean boy of Shuar origin stung by a scorpion identified as Tityus cisandinus in the Amazonian province of Morona Santiago, presenting with pulmonary edema and systemic inflammation. We administered immunotherapy using the scorpion antivenom available in Ecuador, of Mexican origin (anti-Centruroides). Catecholamine discharge-related events such as hyperglycemia and thrombocytosis were resolved after treatment but leukocytosis did not, suggesting that factors associated with the sting-admission delay and specificity of antivenom played a role in the envenomation outcome. Cardiorespiratory arrest determined a fatal outcome, despite specific maneuvers. The case severity and the limited supply of nonspecific scorpion antivenoms in problematic areas of Amazonian Ecuador and elsewhere in northwestern Amazonia are discussed in regard to the need for specific therapeutic immunoglobulins in the area and in the Amazon Basin as a whole.

INTRODUCTION

Envenomation by scorpions in the family Buthidae can be life threatening, particularly in children under 10 years of age, depending, among other factors, on the species involved.¹ Scorpion stings are common in tropical and subtropical regions, with an estimated 1.2 million stings per year and over 2,600 deaths.² Lethality is associated with the rapid tissue distribution of low-molecular-mass toxins, which mainly target voltage-gated sodium and potassium channels located in excitable and immune cells with high-channel-isoform specificity, acting synergistically with hyaluronidases and metalloenzymes.^1,3 Systemic manifestations are characteristic of autonomic stimulation, both adrenergic and cholinergic, due to the postganglionic depolarizing action of scorpion neurotoxins, and also as a result of systemic inflammation associated with the release of proinflammatory cytokines from affected tissues.^4,5 As such, severe stings require intensive cardiorespiratory support and prompt treatment with specific antivenoms as therapeutic immunoglobulins effectively clear circulating scorpion venom antigens, particularly in patients where severe manifestations, mainly respiratory failure, are yet to develop.¹ In South America, the Amazon region has the highest envenomation incidence, with an estimated rate ranging between 30 and 200 cases per 100,000 inhabitants.⁶ These numbers are probably higher because large sections of Amazonia remain epidemiologically underreported, particularly in the northwestern section of the Amazon Basin, comprising Ecuador, Colombia, and Peru.⁶

Tityus is the buthid scorpion genus that contains species (N = 224 as of 2021) associated with most severe and fatal envenomation cases in lower Central America, the Caribbean, and South America, particularly in the Amazon region, where the genus reaches its highest species diversity.⁶ Despite such taxonomic diversity, only three specific scorpion antivenoms are produced in South America (Venezuela: anti-Tityus discrepans; Brazil: anti-Tityus serrulatus; Argentina: anti-Tityus carrilloi).⁷ In Amazonian Ecuador, scorpionism in the province of Morona Santiago has been associated with Tityus species genetically related to Tityus obscurus populations from Brazil and French Guiana, and affects the local main ethnic group, the Shuar, who consider scorpion stings as irredeemably lethal.⁸ We present a fatal sting case in a child from Morona Santiago and identify the culprit as Tityus cisandinus.

CASE DESCRIPTION

A 6.8-kg, 4-month-old Shuar male with no previous medical history was stung by a black scorpion on the right heel inside the domicile in Macuma, province of Morona Santiago, eastern Ecuador (2.1648889 S, 77.6591111 W), at 15:30 on June 28, 2022. Given the lack of scorpion antivenom at the local health center, the child was transferred by road to the province capital’s Macas General Hospital, where he was admitted at 19:30 on the same day. The scorpion responsible for the accident was brought by the child’s parents, which was subsequently identified as a female T. cisandinus based on current taxonomic keys (Figure 1B).⁹ On physical examination, the patient was drowsy, with mucocutaneous pallor, sweaty, tachypneic (33 breaths per minute), and tachycardic (171 beats per minute), with a body temperature of 39°C and 89% blood oxygen saturation. Oral mucosa and lips were dry. Subcostal retractions were observed. Respiratory auscultation indicated bibasilar lung crackling rales; the abdomen was distended, with peristalsis preserved and palpable but weak distal pulses. Laboratory parameters indicated hyperglycemia (219 mg/dL), leukocytosis (27,640 cells/mm³) with a high neutrophil count (77.8%), significant thrombocytosis (618,000 cells/mm³), and hypokalemia (2.98 mEq/L). Serum urea, creatinine, and sodium levels were unremarkable. Chest X-ray revealed bilateral and patchy distribution of lung edema (Figure 1A). The case was classified as a level III envenomation according to the Ecuadorean Ministry of Health’s guidelines for treating scorpion-envenomed patients, where antivenom doses are calculated based on the clinical presentation.¹⁰ Therefore, the boy was administered intravenously two ampoules of scorpion antivenom (Alacramyn^®, Instituto Bioclon S.A., Mexico City, Mexico; lyophilized F[ab′]₂ immunoglobulin derivative, expiration date October 31, 2024) diluted each in 5 mL saline. The patient was hydrated with 5% dextrose in saline and received potassium chloride (6 mEq) intravenously. He was also treated with Ceftriaxone (340 mg), hydrocortisone (13 mg), Tramadol (6 mg), and calcium gluconate (250 mg) intravenously. His condition deteriorated 8 hours after admission, with worsening of respiratory distress that required mechanical ventilation with orotracheal intubation and also sedation (Midazolam, 13 μg/kg/minute). A significant increase in leukocytic count (33,350 cells/mm³) with 89.4% neutrophils, decreased hypokalemia (3.23 mEq/L), and glucose (100 mg/dL) and platelets (291,000 cells/mm³) within normal values, were recorded at this time. No additional doses of antivenom were available at the hospital for further treatment. Transfer to a hospital with an intensive care pediatric unit was recommended. On arrival, the patient experienced cardiac arrest corresponding to nonshockable asystole. Despite cardiopulmonary resuscitation maneuvers and adrenaline administration, the patient was pronounced dead at 22:40 on June 29, 2022.

Figure 1.

(A) Chest roentgenogram of a patient demonstrating bilateral and patchy distribution of lung edema. (B) The scorpion associated with the fatal sting, identified as a female Tityus cisandinus. The inset shows the geographical location of the village of Macuma, in the Amazonian province of Morona Santiago, western Ecuador (in red). The gray-shaded area corresponds to the reported distribution range for T. cisandinus in Ecuador and Peru.⁹

DISCUSSION

The case presented attests to the severity of scorpion envenomation in Amazonian Ecuador for the pediatric population, a situation shared by neighboring areas in Colombia and Peru,^6,11 and confirms the involvement of T. cisandinus in the Ecuadorean case. Notably, hyperglycemia, thrombocytosis, and high leukocytic count at the expense of neutrophilia, as recorded in this case, are established poor prognostic factors with severe scorpion envenomation worldwide, which statistically correlate with multiorgan failure, including lung injury.^12–15 Hyperglycemia can be due to the increase in glycogenolysis, as a result of the massive release of catecholamines, or a resistance to insulin, because adrenaline storms inhibit glucose-induced insulin secretion from pancreatic β cells.¹² Increased neutrophil mobilization is related to the production of inflammatory mediators, chiefly the platelet aggregation factor, via NK-1 receptor activation of mast cells and macrophages through neuropeptides released by venom action.¹⁶ Thrombocytosis in scorpionism is secondary to platelet α-adrenergic receptor activation by increased catecholamines, and also to upregulation of liver thrombopoietin induced by hyperglycemia.¹⁵ According to the current national guidelines for treatment of scorpion-envenomed victims in Ecuador, four levels of severity are established, namely level I (local effects [edema] and mild pain), level II (psychomotor agitation, anxiety, and mild to moderate pain), level III (lung edema, cardiogenic shock, and severe neuromuscular excitation), and level IV (multiorgan failure and convulsions).¹⁰ Diagnosis of pulmonary edema and the lack of convulsions in this case determined its classification as a level III envenomation and the administration of two doses of the available antivenom, produced in Mexico against species of the genus Centruroides. According to the manufacturer, each antivenom ampoule neutralizes 150 medium lethal doses (1.8 mg) of venom from American scorpions.¹⁷ Tityus species belonging to the same subgenus (Atreus) as T. cisandinus (i.e., Tityus pachyurus)⁹ yield 0.3–1 mg of venom per sting,¹⁸ and thus the antivenom administered should be sufficient to neutralize over 3-fold the maximum amount of injected venom, provided that antigenic recognition of T. cisandinus venom components by anti-Centruroides antibodies exists and that antivenom is applied with the least sting-admission delay.¹⁹ Antivenom here was administered after 4 hours of evolution, and it is known that the delay in seeking treatment (i.e., time to intensive care unit admission > 5 hours) contributes to most rural deaths in endemic areas of scorpionism.²⁰ In this case, a combination of factors associated with the sting-admission delay^15,20 and specificity of antivenom²¹ may have played a role in the clinical outcome. In the study by Mazzei de Dàvila et al.,²² where children stung by Tityus zulianus were treated with specific anti-Tityus antivenom, a reduction in plasmatic catecholamine levels was demonstrated up to 8 hours of elapsed sting/treatment time, with the absolute negative change in plasma norepinephrine progressively decreasing as such time increases. Clinical evidence in the present case indicates that hyperglycemia and thrombocytosis, both related to the catecholamine discharge, subsided after antivenom treatment, but leukocytosis did not, suggesting that some T. cisandinus venom activities and/or envenomation secondary mediators were probably not neutralized as a result of treatment. The use of anti-Centruroides antibodies in children stung by Centruroides spp. is reported to normalize electrolyte alterations and significantly decrease circulating venom antigens within 30 minutes after immunotherapy.¹⁴ Also, the use of the Brazilian antivenom effectively reduces leukocyte counts, together with glycemia and kalemia, within 6–18 hours of treatment in children envenomed by T. serrulatus.^23,24 Experimental evidence indicates that anti-Centruroides antibodies are significantly less reactive toward Tityus toxins from several origins in South and Central America compared with available anti-Tityus antivenoms in these regions.^7,25,26 Notably, in an envenomation case from southern Colombia treated with anti-Centruroides antibodies, autonomic manifestations did not subside upon antivenom administration up to 96 hours after immunotherapy.¹¹ In this context, further support for the use of paraspecific antivenoms to treat the envenomation syndrome produced by Tityus species endemic to Ecuador is needed to validate their neutralizing ability and determine the antivenom doses to be administered depending on the case severity.

A unique envenomation syndrome produced by Amazonian Tityus species, particularly T. obscurus, has been described, comprising neurological manifestations associated with cerebellar dysfunction, some of which are refractory to treatment with therapeutic antivenoms produced against non-Amazonian scorpions.^6,27 Neurological manifestations were not observed in this case but have been reported (i.e., dysarthria) in other envenomations from the same geographical area where T. cisandinus is prevalent.⁸ Taking into account the different clinical outcome of envenomation by Tityus spp. inhabiting western and Amazonian Ecuador,^8,28 we suggest that current national guidelines for treating patients in the country are revised to include species-specific manifestations and supportive treatment. Genetic and physiopathological data suggest that Amazonian Tityus species share toxin homologs, indicating the feasibility of preparing specific antidotes for the Amazon region including Ecuador, urgently needed by local ethnic communities, considering the reported structural variability in scorpion toxin antigenic epitopes, which limits neutralization by nonspecific antivenoms.⁶ The two antivenom ampoules administered here are deemed sufficient to treat severe envenomations²⁹; however, lack of additional antivenom doses precluded further immunotherapy, as recommended previously when worsening to higher degrees of envenomation occurs within 6 hours of the first dose.³⁰ The severity of this case and the local antivenom shortage demand implementation of appropriate health measures, including adequate supplies of specific antivenoms in remote endemic areas of eastern Ecuador and elsewhere in the Amazon Basin, to reduce the time elapsed between sting and antivenom administration for treatment of envenomed children and pregnant women.