Systematic review of clinical manifestations, management and outcome following accidental ingestion of liquid mosquito repellent vaporiser in children

Introduction

Mosquitoes represent a formidable public health challenge due to their role in transmitting diseases such as Zika, dengue, chikungunya and malaria. Mosquito repellents are key tools for preventing mosquito bites and reducing the risk of mosquito-borne diseases. While several types of mosquito repellents are available, pyrethroid-based repellents are commonly used because they have insecticidal, contact irritant and repellent properties.1 2 Pyrethroids are synthetic insecticides that are isolated from Chrysanthemum cineraria folium flowers.3 These compounds exert their insecticidal action by inactivating voltage-gated sodium channels in insect nerve cell membranes, resulting in paralysis and death of the insect.4 5

Pyrethroids are available in various forms and delivery methods, including sprays, coils, lotions and vaporisers, each with its own advantages and disadvantages tailored to the user’s needs and preferences.5 6 Sprays, available in aerosol and non-aerosol formulations, offer convenient applications for both indoor and outdoor spaces, effectively killing insects on contact and providing lasting protection. However, they may leave residues and emit strong odours, which some users may find unpleasant.7 8 Coils, composed of pyrethroid mixtures, release smoke when burned to repel and kill insects, making them cost-effective for treating large outdoor areas but requiring an ignition source and potentially irritating smoke.8–10 Lotions and creams, applied directly to the skin, offer targeted protection against insect bites but require frequent reapplication and may leave residues.9 10

Liquid mosquito-repellent vaporisers (LMRV) are a modern mode of pyrethroid delivery that works by heating a liquid pyrethroid solution and releasing it into the air as a vapour. They are effective at treating indoor spaces and are often used in areas where mosquitoes are prevalent.7 8 11 LMRVs typically contain a derivative of pyrethrin as a mosquito-repellent and a petroleum-based solvent. As a result, two types of effects can occur: those caused by the pyrethroid component and those caused by the hydrocarbon solvent.12–14

Despite their efficacy in mitigating mosquito-borne diseases, concerns persist regarding the potential hazards associated with mosquito repellents, particularly in cases of accidental ingestion or improper usage.2 5 15 According to the 38th annual report of the National Poison Data System, there were more than 19 191 reported cases of pyrethroid exposure in the USA in 2020, 3765 (approximately 20%) of which involved children under the age of 5.16 Existing literature has extensively investigated the adverse effects of pyrethroid poisoning, providing a foundational understanding of its clinical manifestations and management strategies.5 7 16–19 Acute poisoning can result in symptoms such as nausea, vomiting, headache and skin irritation.17 19 Neurological effects including dizziness, muscle twitching, altered awareness and convulsions have been reported following acute and chronic exposure to pyrethroids.17 20 Beyond acute toxicity, sublethal effects include neurobehavioral toxicity, oxidative damage, immune dysfunction, and endocrine disruption.17

LMRVs differ from other sources of pyrethroids in their formulation, often containing a distinct combination of pyrethroids and hydrocarbon solvents to facilitate vaporisation. While existing research has shed light on pyrethroid poisoning, there remains a notable gap in understanding the toxicity specifically associated with LMRVs. This knowledge gap is compounded by the limited availability of comprehensive data in the literature that can guide physicians in effectively managing cases of LMRV ingestion, particularly in paediatric patients.

Addressing poisoning resulting from LMRV ingestion requires timely initiation of appropriate treatment, including decontamination, provision of supportive care and the administration of specific antidotes. However, the lack of awareness among healthcare providers and parents regarding the risks associated with pyrethroid ingestion from mosquito-repellent vaporisers is concerning. This systematic review aimed to bridge this critical knowledge deficit by thoroughly examining the clinical presentation of LMRV ingestion in children and the diverse strategies employed in its management through an in-depth analysis of the available literature. By enhancing our understanding of clinical manifestations and treatment effectiveness, this study aimed to advance preventive measures and optimise clinical management practices.

Methods and materials

In conducting this research, we adhered to the reporting standards outlined in the PRISMA Statement for Systematic Reviews.21 This systematic review was prospectively registered with PROSPERO under record number CRD42023413937 to enhance transparency and minimise the risk of reporting bias.

Results

Using the above-mentioned three databases, we found 818 records; 66 duplicate records were excluded, and 752 were screened. All the records were in the English language. After the initial screening, 264 reports were assessed for eligibility, and 252 records were excluded because the studies did not provide primary data (n=45), because pyrethroid poisoning occurred from a source other than mosquito repellents (n=147), because the age of the study population was older than 18 (n=72) or because the full-text article was not available (n=2) (figure 1).

Request permission

This review included 12 records of 61 patients who met the stipulated inclusion criteria.13–15 22–30 Predominantly, these records consisted of case reports from diverse regions: India (n=9), China (n=2) and the United Arab Emirates (n=1). Patient ages ranged between 11 and 50 months, with isolated instance in individual aged 14 years. The majority of the patients were male.

The clinical presentations among the patients exhibited considerable variability, with 27 individuals (44%) manifesting symptoms indicative of respiratory involvement, such as coughing, tachypnea or respiratory distress. Gastrointestinal complaints, notably nausea or vomiting, were documented in 23 patients (38%). Moreover, 19 patients (31%) remained asymptomatic during observation. Neurological symptoms, including altered sensorium or convulsions, were observed in 18 patients (29%), while fever was reported in 9 patients (15%). Additionally, rare instances of urticarial rash and acute kidney injury were noted in individual cases.28 29

The severity of the cases necessitated respiratory support for 73% of the patients, predominantly administered through oxygen delivery via nasal prongs or nasal continuous positive airway pressure. Furthermore, 65% of the patients required admission to the paediatric intensive care unit. Antiepileptic drugs were used for seizure control in 4 patients (6%), and mechanical ventilation was administered to 3 patients. Tragically, two fatalities occurred within the cohort, involving a 9-month-old infant initially treated for respiratory distress and altered sensation, and a 2-year-old female who presented with seizures followed by loss of consciousness. Notably, both children presented to the hospital approximately 3–5 hours post-incidence.

The review’s compiled data is shown in online supplemental table 1.

Discussion

The accumulation of research on LMRV in children underscores potential risks associated with these products, notably concerning child health and safety. Our systemic review included 12 studies and included a range of accidental LMRV ingestion in children. Notably, the study conducted by Reddy et al is a case series that primarily focused on liquid mosquito repellent intake. Their retrospective case series, covering 5 years, highlighted that accidental liquid mosquito repellent ingestion constituted a significant proportion (40%) of hydrocarbon exposures managed by the authors.15 This study identified vulnerable 1–2-year-old children exhibiting mouthing behaviours, inadvertently ingesting the repellent, coinciding with the increased prevalence of liquid repellents in urban households. The ingestion patterns, which typically occur during the summer months and are often mistaken for water due to attractive packaging, were associated with increased repellent usage and children’s heightened thirst.

The clinical manifestations primarily involved hydrocarbon-induced aspiration pneumonitis rather than neurological complications from the repellent’s synthetic pyrethroids. The predominant symptoms post-ingestion included vomiting and rapid breathing. Notably, induced vomiting or gastric lavage before referral heightened aspiration risks and exacerbated pulmonary symptoms.15 While Reddy et al observed neurological complications specifically linked to synthetic pyrethroids, our review reveals a broader spectrum of ingestions with varying clinical presentations.

The majority of the included studies reported adverse effects ranging from mild symptoms such as skin irritation to more severe manifestations, including neurological symptoms and respiratory distress. According to the largest reported case series of incidents of acute pyrethroid poisoning, which involved 573 people, 229 cases were caused by workplace exposure, and 344 cases were caused by accidental exposure, primarily through ingestion. The reported symptoms were facial paresthesia, skin itchiness, skin burning, nausea, vomiting and, in more severe cases, muscle fasciculations.31 These symptoms were also reported in the studies included in our review. The age range of patients described ranged from 11 to 50 months, indicating that the majority of the reported cases involved young children. These findings suggest that LMRV, while effective at repelling mosquitoes, may pose a risk to children’s health.

Animal research examining acute pyrethroid exposure has revealed two unique toxidromes. Type I pyrethroids (such as allethrin) lead to reflex hyperexcitability, fine tremors and the development of T syndrome or type I syndrome. On the other hand, type II pyrethroids (such as cyfluthrin) cause incoordination, choreoathetosis, seizures and direct effects on skeletal and cardiac muscles, as well as salivary glands, resulting in choreoathetosis-salivation or type II syndrome.20 The clinical features observed in our included studies are consistent with the aforementioned characteristics.

Acute poisoning with LMRV typically does not pose a significant life-threatening risk. However, there is a possibility of severe poisoning with a potential risk of mortality, especially when significant quantities of pyrethroids are consumed. This observation was also apparent in the studies we reviewed, as only two of these cases resulted in a fatality. The literature mentions life-threatening manifestations such as seizures, coma, pulmonary oedema and haemorrhage.5 Pyrethroid poisoning often presents with atypical manifestations. A study conducted in Korea with 59 individuals seeking care in the emergency room found that approximately 40% of the patients had unusual symptoms. These symptoms included altered mental status (34%), respiratory failure requiring ventilator assistance (18%), acute renal injury (11%), hypotension (10%), pneumonia (7%) and seizures (4%). Tragically, two patients from this series succumbed to the poisoning. The study revealed that consuming more than 250 mL of blood and having a serum lactate concentration higher than 3.5 mmol were risk factors for an unusual presentation.32 Recently, there has been a significant increase in the number of reports highlighting cases of pyrethroid poisoning in which individuals present with status epilepticus.33 There have been extremely rare published reports of pyrethroid poisoning associated with complete heart block34 and myelopathy.35 In a study including 104 individuals who had type II pyrethroid poisoning, hyperglycaemia was found to be linked to adverse effects such as respiratory failure, acidosis and hypotension. It is believed that the increase in adrenergic activity may be the underlying cause of hyperglycaemia in these patients.36 The diagnosis of LMRV poisoning is primarily established by assessing the patient’s clinical presentation and identifying the specific compound through the container provided by the patient or their relatives.

Another factor that can increase the toxicity of LMRV is the presence of additional solvents, such as hydrocarbons, which are frequently employed as carriers in pyrethroid-based mosquito repellents. These solvents are typically volatile in nature and can induce severe lung injury, even when the quantity of water ingested is minimal. Moreover, they have the potential to enhance the absorption of pyrethroids, consequently amplifying their toxic effects. These concerns have been reported by Chandelia S. et al.13 There are documented instances of fatal respiratory symptoms occurring even with the ingestion of small quantities of these compounds.24 37 Consequently, LMRV poisoning should be considered analogous to hydrocarbon solvent poisoning, as it warrants a regimen of supportive and symptomatic management. Further research is necessary to explore alternative substances that can be employed as carriers instead of hydrocarbons.

Management strategies for LMRV poisoning generally involve supportive and symptomatic measures addressing gastrointestinal, central nervous system and respiratory symptoms. No specific antidote exists that necessitates optimising the airway, breathing or circulation, similar to other poisonings. Atropine controls salivation, antiepileptic drugs manage seizures and respiratory problems are addressed with respiratory support. Caution is warranted with gastric lavage due to aspiration pneumonia risk associated with the solvent used.5 Although there is little research supporting the use of activated charcoal for treating LMRV, whether a patient arrives within an hour of consumption should be considered. In patients with LMRV, it is essential to effectively manage seizures through appropriate antiepileptic therapy. Experimental data in mice suggest that benzodiazepines may be more efficacious than phenobarbital in treating convulsions induced by type II pyrethroid compounds in comparison to type I compounds.38 Reports suggest that vitamin E has shown effectiveness in treating paraesthesia associated with pyrethroid poisoning, although the exact mechanism of its benefit remains unclear. Notably, since symptoms typically resolve within 12 to 24 hours, specific treatment is generally not needed.5 However, none of the studies included in our review reported the use of vitamin E for the management of paresthesia associated with LMRV. Researchers have explored the possibility of targeting the effects of pyrethroids on sodium and chloride channels. Animal studies have provided data on the potential advantages of lidocaine and tetracaine in reversing the effects on sodium channels, but cardiac toxicity limits their use. Phenytoin, phenobarbital and valproate may play a role in this process, as they have been shown to have equal effects on both pyrethroid-evoked and normal sodium currents in experimental animal models.39 While atropine may be considered to reduce salivation in cases of LMRV poisoning, caution is urged with its use due to reduced seizure thresholds.40

Future investigations exploring alternative carriers for pyrethroid-based LMRV, apart from hydrocarbons, are warranted. Additionally, enhancing the understanding and specific treatment protocols available for pyrethroid poisoning, encompassing both supportive and symptomatic management, are essential areas for future research and clinical practice improvements.

While the review encompassed a range of studies shedding light on LMRV, several limitations are worth noting. The reliance on case reports and the scarcity of large-scale studies might limit our comprehensive understanding of this topic. Moreover, retrospective studies could introduce biases and affect data accuracy, while underreporting might obscure the true scope and impact of pyrethroid poisoning. Standardised reporting criteria and enhanced surveillance systems are essential to better comprehend and address this health concern.

Conclusion

Despite our efforts to highlight the potential risks associated with pyrethroid-based LMRV, there is still a lack of substantial evidence regarding the management of pyrethroid poisoning caused specifically by LMRV use. While we have identified cases of LMRV ingestion and discussed supportive and symptomatic management measures, the current evidence is limited. There is a clear need for further research, particularly focused on the management of LMRV ingestion, to enhance our understanding and provide more comprehensive guidance in this area, especially regarding the utilisation of mosquito repellents and their potential effects on children’s health.