New Study Reveals Medication-Associated Diethylene Glycol Mass Poisoning as a Preventable Cause of Illness and Death

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Gambia has recently experienced medication-associated diethylene glycol mass poisoning (MDMP), despite increasing scrutiny of the pharmaceutical industry at both the national and international levels.

Public health authorities in low- and middle-income countries (LMICs) have inadequate resources to support core public health activities for MDMPs, such as surveillance for acute kidney injury of unknown origin and clinicians’ education about recognizing DEG poisoning and clinical follow-up of cases.   

According to a study published in The New England Journal of Medicine, DEG is responsible for an unusually high number of poisonings, owing to its consumption as an inappropriate excipient — an inert ingredient commonly used as a diluent or vehicle for delivering one or more biologically active ingredients in a medication. Hypotheses about the mechanism of these effects include tissue damage due to diglycolic acid (DGA) production by DEG metabolism.

Current management therapies for DEG poisoning include inhibiting DGA production by blocking alcohol dehydrogenase enzymes using a drug such as fomepizole or ethanol.

Promoting evidence-based public health practices, adherence to drug-manufacturing best practices and regulatory enforcement, establishing post-marketing surveillance programs, and encouraging reporting of adverse events may facilitate early detection, mitigating morbidity and mortality attributable to mass poisoning. Additionally, it is essential to address the more significant public health problem of global inequity in resources dedicated to preventing, controlling, and managing poisoning by toxins.   

Poison centers (PCs) play a significant public health role in poisoning-prevention activities, providing training and information to clinicians and the public on the recognition and management of poisoning, and supporting pharmacovigilance networks, and development of relevant laboratory capacity for toxicology.

Even though poisoning and chemical exposures are included in the International Health Regulations (2005) and the 70th World Health Assembly Roadmap, the WHO has estimated that only 47% of all WHO member states have a functioning PC.  

While nephrotoxicity is the most visible symptom of DEG poisoning, it is also thought to affect other organ systems. Diglycolic acid, a DEG metabolite, is most likely to account for nephrotoxicity; nevertheless, human data is limited (DGA).

DGA is a potent neurotoxin that accumulates in the proximal renal tubule and induces mitochondrial malfunction and cell death at high enough concentrations. 4 Long-term neurotoxic consequences that people who survive the early stages of poisoning are subjected to include facial paralysis on both sides, peripheral neuropathy, quadriparesis, and other neurological signs and symptoms.  

One possible explanation for these findings is tissue damage mediated by DGA generation via DEG metabolism. As a result, medicines such as fomepizole or ethanol are employed in traditional DEG poisoning treatment regimens to block alcohol dehydrogenase enzymes and decrease DGA synthesis. Extracorporeal techniques such as hemodialysis are examples of supplemental therapy regimens. Yet, regular access to assays that quantify DEG levels in blood serially remains a challenge.  

Although the International Health Regulations (2005) and the roadmap of the 70th World Health Assembly address the management of poisoning and chemical exposures, the WHO estimates that only 47% of all WHO member nations have a functioning PC. Clinical toxicologists may be more common in high-income countries such as North America, Europe, and others.

Formal toxicological education and “short-course” modular courses are urgently needed for health care practitioners and public health authorities in low and medium-income countries (LMICs). Although the sources of MDMPs are unknown, DEG has been found in medications that should not include DEG since they have acceptable excipients such as propylene glycol and glycerin manufactured to pharmaceutical standards.