Article Text

Original research
Systematic review of clinical manifestations, management and outcome following accidental ingestion of liquid mosquito repellent vaporiser in children
  1. Babar Naeem1,
  2. Junaid Saleem2,
  3. Agha Syed Ali Haider Naqvi3,
  4. Sidra Kausar3,
  5. Aqdas Arshad4,
  6. Kantash Kumar5,
  7. Aashar Khalid2,
  8. Parkash Kumar6
  1. 1Allama Iqbal Medical College, Lahore, Pakistan
  2. 2Federal Medical and Dental College, Islamabad, Pakistan
  3. 3Pakistan Institute of Medical Sciences, Islamabad, Pakistan
  4. 4Mohi-ud-Din Islamic Medical College, Mirpur, Azad Kashmir, Pakistan
  5. 5Dow Medical College, Karachi, Pakistan
  6. 6Liaquat National Hospital and Medical College, Karachi, Pakistan
  1. Correspondence to Dr Babar Naeem; babar_naeem{at}hotmail.com

Abstract

Background Pyrethroid-based mosquito repellents are widely used to control mosquito-borne diseases. Liquid mosquito-repellent vaporisers are effective modes of pyrethroid delivery but can also pose significant health risks if ingested or used improperly.

Objective This systematic review was performed to assess the demographic distribution, clinical presentation, management strategies and outcomes in children resulting from accidental ingestion of liquid mosquito repellent vaporiser.

Methods The study adheres to the reporting standards outlined in the PRISMA Statement for Systematic Reviews and was prospectively registered with PROSPERO (record # CRD42023413937) to enhance transparency and minimise reporting bias. A comprehensive search was conducted on PubMed, Scopus and Google Scholar using specific MeSH terms related to insecticides, mosquito repellents, pyrethroids, ingestion, poisoning, toxicity and prevention. The reference lists of the included studies were also reviewed for additional relevant articles. The inclusion criteria involved studies published in peer-reviewed journals between 2000 and 2023 that focused on children under 18 years old with a history of mosquito-repellent ingestion based on primary data.

Results Twelve studies met the inclusion criteria; these were primarily case reports from India, China and the UAE. Male children were predominantly affected, and symptoms included vomiting, convulsions, cough and respiratory distress. Management primarily involved supportive and symptomatic measures, including atropine for salivation and antiepileptic drugs for seizures. Respiratory support was provided for respiratory complications.

Conclusion Despite the known risks and diverse presentations of pyrethroid poisoning caused by liquid mosquito repellent vaporiser in children, the limited substantial evidence in the literature underscores the urgent need for comprehensive research to refine management approaches and enhance preventive measures.

  • Toxicology
  • Epidemiology
  • Caregivers
  • Analgesia

Data availability statement

Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.

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This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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WHAT IS ALREADY KNOWN ON THIS TOPIC

  • Prior to this study, existing knowledge highlighted the potential risks of pyrethroid-based mosquito repellents, particularly when ingested, with scattered case reports indicating varied clinical presentations. However, a comprehensive understanding of liquid mosquito repellent vaporiser poisoning and effective management strategies is lacking. This study aimed to bridge this gap by systematically reviewing and synthesising the available literature to enhance comprehension and guide clinical management.

WHAT THIS STUDY ADDS

  • This study systematically reviews reported cases of liquid mosquito repellent vaporiser ingestion, offering a comprehensive overview of paediatric pyrethroid poisoning. It identifies a spectrum of clinical presentations, emphasising respiratory distress, gastrointestinal complaints and neurological symptoms as predominant manifestations. Additionally, it addresses associated mortality, complications and challenges linked to ingestion, offering a comprehensive understanding of the risks involved. Moreover, the findings highlight the inadequacy of current awareness among healthcare providers and parents regarding the dangers associated with pyrethroid ingestion, particularly from mosquito-repellent vaporisers.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

  • The findings underscore the need for heightened awareness among healthcare providers and caregivers regarding the potential risks of pyrethroid ingestion, especially among children. This study advocates for improved preventive measures, education and guidance on managing pyrethroid poisoning, thereby influencing policies on labelling, packaging and usage instructions. Furthermore, further research is needed to explore alternative carriers of mosquito repellents and enhance specific treatment protocols for pyrethroid poisoning.

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.

Search strategy

We searched PubMed, Scopus and Google Scholar using the following keywords: (Insecticide OR Mosquito repellent OR Pyrethroid OR Allethrin OR Transfluthrin) AND (Ingestion OR Intake OR Poisoning OR Toxicity OR Prevention). The keyword search was specifically confined to titles and abstracts to enhance precision. Filters were applied to confine the results to studies involving children aged between 0 and 18 years and studies published in English that focused exclusively on human subjects. Preprints and studies involving nonhuman species were excluded from the search to maintain the relevance and applicability to paediatric LMRV poisoning (online supplemental file 1).

Supplemental material

Furthermore, we systematically searched the reference lists of the included studies to identify any additional relevant articles.

Inclusion and exclusion criteria

The inclusion criteria for this systematic review included studies:

  1. From all countries and in the English language, provided they were published in peer-reviewed journals;

  2. With publication dates between 2000 and 2023;

  3. Involving children under the age of 18 years with a documented history of liquid mosquito-repellent vaporiser. The review also encompassed the inclusion of electric coils dipped in liquid mosquito repellent vaporiser, recognising their potential to expose children to both pyrethroid and hydrocarbon compounds.

Studies were excluded from the review if they:

  1. Presented unclear history or mixed poisoning cases;

  2. Lacked primary data;

  3. Reported toxicity occurring from sources other than mosquito repellents.

Data synthesis

The retrieved articles from all sources were exported to Mendeley, and all duplicates were removed. Two independent investigators screened the titles and abstracts of these articles for relevance based on the inclusion criteria. Next, the whole texts of the eligible papers were thoroughly evaluated, and relevant data were extracted using a standardised data extraction form. A summary of the selected studies was recorded, including the title of the study, first author name, sample size, age of the child, sex, country of origin, clinical findings, and outcome.

The findings of the included studies were synthesised, and a narrative synthesis of the literature was developed.

Quality assessment

Two independent reviewers assessed the quality of each included publication. The assessment was performed using the Joanna Briggs Institute Critical Appraisal Checklist, specifically designed to appraise the methodological quality of case reports and case series. Any disagreements between the reviewers were resolved through discussion or consultation with a third reviewer.

Quantitative analysis

Conducting a suitable meta-analysis was not feasible due to the insufficient research data available within the studies pertaining to this topic.

Patient and public involvement

The patients were not involved in the design, conduct, reporting or dissemination of our research.

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).

Figure 1

Flowchart of the systematic process of identifying, screening and including studies for a review. The numbers represent the count of records at each stage of the process.

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.

Supplemental material

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.

Abstract translation

This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

Data availability statement

Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.

Ethics statements

Patient consent for publication

Ethics approval

Not applicable.

Acknowledgments

The authors would like to acknowledge that there are no specific individuals, organisations, or institutions to whom they need to express any gratitude for their contribution to this systematic review.

References

Supplementary materials

Footnotes

  • Contributors BN designed the systematic review, developed the methodology and provided critical intellectual input throughout the manuscript preparation. JS led the writing process, managed references, conducted proofreading, records screening and data extraction. ASAHN contributed to the review’s design, collaborated with all authors, designed the PRISMA framework and assisted with proofreading. AA, SK, KK, AK and PK participated in records screening, data extraction and writing process. All authors critically reviewed and approved the final manuscript. BN is acting as guarantor.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.