Childhood poisoning is a significant health concern in South Africa – especially in densely populated informal housing settlements where children are frequently exposed to various household poisons – and accounts for 4%- 5% of paediatric hospital admissions in the country.
Common household mothballs pose a significant danger, and have resulted in a number of tragic, avoidable paediatric deaths.
Writing in the SA Medical Journal, a team of leading specialists from Wits present the findings of their recent study highlighting the importance of toxicological testing in instances of suspected poisoning, to enable accurate feedback to families, and to inform surveillance and preventive strategies.
They write:
The most common causes of childhood poisoning are fuels, pesticides and medicines, although many cases have unidentifiable causes. In this case series, three children, aged three to five-years-old, were declared dead on arrival at public healthcare facilities. Their symptoms had included vomiting of a foam-like substance and distress (crying, shaking, fatigue).
Postmortem, fine-needle liver biopsies were obtained and underwent atmospheric pressure matrix-assisted laser desorption/ionisation mass spectrometry imaging (AP-MALDI-MSI) analysis.
MSI analysis identified the presence of naphthalene-associated metabolites, the active component in household mothballs, suggesting death due to accidental ingestion.
These cases highlight the urgent need for novel toxicology screening tools to accurately determine causes of death and guide targeted preventive strategies.
Strategic efforts are needed to reduce childhood poisoning through robust toxico-vigilance to monitor and regulate the sale of toxic substances and enhance access to toxicology testing.
Global issue
Worldwide, childhood poisoning is a major public health concern, contributing significantly to hospitalisation, disability and mortality. The Institute for Health Metrics and Evaluation reported 1.88m cases globally in 2019, of which 830 000 occurred in young people under 20.
In South Africa, in 2021, poisoning accounted for 0.13% of deaths in children under five, with common causes in children hospitalised at the Red Cross War Memorial Children’s Hospital in Cape Town including pharmaceutical poisoning (49%), followed by industrial products (22%), household products (11%) and pesticides (11%), with naphthalene accounting for 2% and unspecified pesticides for 14%.
At Chris Hani Baragwanath Academic Hospital, Johannesburg, the main causes of poisoning were organic solvents (including paraffin) (37.6%), pharmaceuticals (32.9%)m and pesticides (17.5%), with unspecified and other poisons cumulatively at 10.2%.
Similarly, at a regional hospital in KwaZulu-Natal, the main types of poisoning included pharmaceuticals (45.2%), hydrocarbons (23.4%) and pesticides (10.2%).
In most parts of the country, there is limited access to laboratory services with the capacity to identify the poison in children hospitalised with suspected toxicity. Toxidromes (a constellation of clinical signs that infer a type of poison) are used by clinicians to guide management of children where a history of the type of poison is not forthcoming.
Online toxicology programmes (like AfriTox) and call centres are available to support clinicians, but toxidromes may be incomplete, and not sensitive or specific, and many poisons overlap in clinical presentation.
Furthermore, in children who have died from unknown causes or suspected poisoning, there are markedly prolonged delays in obtaining postmortem toxicology testing results, and families are often not provided with closure.
The need, therefore, for effective toxico-vigilance to identify and manage cases of poisoning, and to inform targeted public health strategies to reduce childhood mortality and morbidity, is evident.
As part of the Child Health and Mortality Prevention Surveillance (CHAMPS) study in Soweto, minimally invasive tissue sampling (MITS) was undertaken to determine the cause of death in children whose parents consented to the study.
As part of a pilot collaboration, liver biopsy samples were analysed using atmospheric pressure matrix-assisted laser desorption/ionisation (AP-MALDI) mass spectrometry imaging (MSI) to identify possible toxins in a child whose death was suspected to be from poisoning.
Here we present three cases in which naphthalene, a substance commonly found in mothballs, was identified.
CASE ONE
A four-year-old boy presented with a history of vomiting and suspected poisoning, and from the verbal autopsy, the mother reported he had been well until the day of death, when he ate some food, after which he began to vomit a foam-like substance: she said it seemed as though he had been poisoned, and he was taken to the nearest healthcare facility.
However, there were no significant findings, and the forensic provisional report indicated that the history preceding death was consistent with aldicarb poisoning.
CHAMPS histopathology of the liver noted mild sinusoidal inflammation with a finding of sinusoidal leucocytosis, while the lungs and heart histology were unremarkable.
CASE TWO
A three-year-old girl with no past medical history, had begun vomiting until a foam-like substance started to appear before she was taken to hospital. She died before arrival.
From the clinical history and gross autopsy findings, the death was assessed as possible aldicarb poisoning. CHAMPS histopathology of the liver noted extramedullary haematopoiesis, and interstitial pneumonitis of the right and left lung, with no other findings or diagnosis noted.
CASE THREE
A three-year-old girl presented with a history of being ‘shaky’ and wanting to sleep after playing with other children outside.
On examination at the clinic, a fine white powder was noted on her. The formal forensic report noted that the brain was swollen, with a small subarachnoid haemorrhage in the cerebellum and a spiderweb appearance of blood vessels.
At the nose, there was oozing, dried brownish mucus, and both kidneys appeared congested. There were no other abnormalities detected.
The stomach contained ~100 mL of partially digested food mixed with green granules, and the report concluded that the death may be consistent with aldicarb poisoning.
The CHAMPS histopathology examinations of the liver and lungs were unremarkable.
Investigations
From the MITS procedures performed, for all three cases, polymerase chain reaction screening of up to 116 pathogens on a custom-designed syndromic TaqMan Array cards (Thermo Fisher Scientific Inc USA) and standard postmortem cultures showed no significant infectious CoD.
During the DeCoDe panel, the underlying cause of death was suspected to be poisoning for all three cases. Liver biopsy samples were prepared and analysed using AP-MALDI MSI. An untargeted MSI analysis approach was used to detect a wide range of biomolecules of interest.
This technique may provide a novel screening tool for the rapid identification of toxins, and has been identified as a method to aid forensic toxicology.
For the mass spectrometry imaging analysis, frozen liver biopsies were embedded in a 250 mM sucrose solution and sectioned to a thickness of 12 μm using a Leica CM1860 cryostat.
AP-MALDI MSI provides the unique advantage of being able to detect drugs, metabolites and biomolecules in their native state without the need for labelling or chemical modification.
In this study, we were able to detect naphthalene-1,2-diol.Naphthalene, an aromatic hydrocarbon, and its metabolites were detected in all three liver samples.
Additionally, bile-associated metabolites and a high number of different lipid species, suggesting possible dysfunctional lipid metabolism, were identified.
Unrestricted sales
Mothballs are a household item sold without restrictions in supermarkets and by street vendors in South Africa: their shape and colour resemble a hard candy, and they can easily be ingested by unsupervised children.
Although not frequently reported, previous studies have shown that naphthalene toxicity may occur after ingestion, inhalation or dermal exposure, and may be fatal. There is no known toxidrome for naphthalene poisoning.
The fatal dose of naphthalene in children is unknown, and although uncommon, there are reports of death following ingestion of naphthalene.
There are few data describing the histological features in children with fatal naphthalene poisoning.
Pathological manifestations are thought to be driven by the production of oxygen free radicals, resulting in lipid peroxidation and subsequent DNA damage. The increased oxidative stress leads to the formation of methaemoglobin, an oxidised form of haemoglobin that does not bind oxygen and increases the affinity of oxygen for the partially oxidised portion of haemoglobin.
This process impairs the delivery and release of oxygen, leading to tissue hypoxia. Oxidative and mechanical trauma to red blood cells results in the release of free haemoglobin into plasma, which is filtered in the kidney.
In this case series, all three cases were attributed to aldicarb poisoning by the forensic pathologist, but this was in the absence of formal toxicology testing and was based on clinical history and gross autopsy findings.
From the history, the first two cases had a history of vomiting and the third had an altered mental status.
The manifestations of naphthalene poisoning are not specific and heterogenous, and it is unlikely that a clinician or pathologist will be able to differentiate between naphthalene poisoning vs other toxidromes.
Notably, aldicarb was not identified in any of these cases using AP-MALDI MSI testing.
This case series has some limitations. For the MSI analysis, frozen temperatures render enzymes metabolically inactive, and therefore time from sampling to freezing should be minimised. In our study, the time to freezing was not documented.
Another limitation is that we were unable to detect the parent compound of naphthalene, but only its biologically active metabolite.
Under-reporting of fatalities from naphthalene – because of a lack of specific toxin testing – has consequences. The assumption that this is a rare cause of accidental poisoning leads to mismanagement of cases, and missed opportunities during public health interventions to prevent it.
Mothball poisoning is likely to be of greater public health concern than reported. In settings where this household item is still commonly used, and supervision of children may be limited owing to social circumstances, this toxin should be suspected in children with suspected poisoning.
The case series highlights the importance of toxicological testing in instances of suspected poisoning, to enable accurate feedback to families and to inform surveillance and preventive strategies.
Novel detection methods are necessary to identify and target interventions in children with suspected poisoning. The application of AP-MALDI MSI aids the identification of poisons, and has the potential to assist strategic efforts in reducing childhood poisoning rates through robust toxico-vigilance.
M Dempster,1 BBusSci, MD; L Erasmus,1 MMed, MSc; S Johnstone,1 MSc, PhD; K Storath,1 BCMP; O Letlhake,1 BCMP; S van der Merwe,1 BCMP; S G Lala,2 MMed (Paed), PhD; S A Madhi, 1 MMed (Paed), PhD; A M E Millen, 3 MBA, PhD; S Baijnath,3 MSc, PhD; Z Dangor,1 MMed (Paed), PhD1
1 South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, University of the Witwatersrand, Johannesburg, 2 Department of Paediatrics and Child Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 3 Wits Integrated Molecular Physiology Research Initiative, Department of Physiology, School of Biomedical Sciences, Faculty of Health Sciences, and Wits Health Consortium, University of the Witwatersrand
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