The following article is the third in a series authored by Marmar Nekoro and James Mount from the Department of medicinal products in veterinary use at the Swedish Medical Products Agency, to address the different elements of the One Health approach. This article argues for incorporation of One Health and ecopharmacovigilance in decision making regarding policy and pharmaceutical legislation to safeguard public health, as evidenced by ecological crisis involving the effects of diclofenac on the vulture population in Asia and consequent rise in rabies. Read the second article here.
In the intricate web of ecosystems, the loss of a single species can trigger cascading effects affecting the environment, public and animal health, and economies. The near extinction of vultures on the Indian subcontinent due to the veterinary use of the anti-inflammatory drug diclofenac is such an example. While the ecological impact of this collapse was devastating, the broader public health implications – particularly the resurgence of rabies driven by a rapid growth in feral dog populations – is equally alarming. It is a stark reminder of the need for ecopharmacovigilance, the monitoring of pharmaceuticals in the environment.
Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) widely used in human medicine for its analgesic and anti-inflammatory properties. Introduced for veterinary use in India, Pakistan, and Nepal during the 1990s, it was widely administered for treating pain and inflammation in livestock. As its environmental risks were not assessed prior to its approval for veterinary use, its toxicity to wild species – in this case, endemic vulture populations – was unknown. Their story provides a vivid illustration of the unintended consequences of introducing pharmaceutical products into an ecosystem.
Ecological collapse and the rise of rabies
Vultures play a vital role in scavenging, but in so doing, unintentionally consumed diclofenac while feeding on the carcasses of treated livestock, leading to kidney failure and death. The scale of the impact was staggering. Vulture populations plummeted by over 95 per cent in the early 2000s, with some species experiencing losses of 91-98 percent, making it one of the fastest and most dramatic population crashes of any bird species in recorded history. The disappearance of vultures had immediate and far-reaching consequences. In South Asia, where carcass disposal infrastructure is limited, vultures had long served as a natural waste management system. Through their ability to rapidly consume animal carcasses, vultures were key in preventing the spread of pathogens and limiting food sources for other scavengers like stray dogs.
When vulture populations collapsed due to diclofenac poisoning, carcasses remained in the environment longer, giving rise to both the proliferation of bacteria and infectious diseases and a surge in feral dog population growth in rural and peri-urban areas. Compared to vultures, who are evolutionarily adapted to be scavengers, dogs were ineffective in cleaning the rotting remains of dead livestock, leaving flesh on the carcasses. As a result, levels of bacteria and pathogens grew, spreading into drinking water through runoff and poor disposal methods. This led to rising human death rates.
In addition, dogs account for the majority of rabies cases, with infections transmitted to humans through their bites. As feral or stray dog numbers increased, this led to more frequent interactions between dogs and humans and the occurrence of rabies in the human population subsequently increased.
Recent research on social costs of keystone species collapse suggests that the loss of vultures in India caused around 100,000 additional human deaths annually coupled to an increase in feral dog populations and rabies. This resulted in more than USD 69bn per year in mortality damages (the economic costs associated with premature deaths).
Ecopharmacovigilance: A framework for prevention
This public health crisis was not just a consequence of ecological imbalance—it was a failure of pharmacovigilance as the toxic effects on non-target species were not adequately assessed before its widespread use in veterinary practices. In response to mounting scientific evidence and international pressure, the governments of India, Nepal, and Pakistan banned the veterinary use of diclofenac in 2006. Captive breeding and reintroduction programs were launched to save the remaining vulture populations. While some recovery has been observed, the road to ecological restoration is long. Vultures are slow to reproduce, and illegal use of diclofenac persists in some areas. The presence of other pharmaceuticals, such as ketoprofen, which also has toxic effects on vultures, also continue to threaten the birds.
This chain of events, beginning with a pharmaceutical intervention in livestock and culminating in a human health crisis, highlights the urgent need for the One Health approach and ecopharmacovigilance (EPV). The One Health approach, which recognises the interconnectedness of human, animal, and environmental health, aligns closely with the goals of EPV. EPV extends the principles of pharmacovigilance beyond human and animal health to include ecosystem health and underscores the need for a more holistic approach to drug safety, one that includes environmental impact assessments as a standard part of the drug approval process. EPV offers a framework for the detection, assessment, understanding, and prevention of adverse effects of pharmaceuticals on the environment, particularly on non-target species. If EPV would have been implemented in the above case, the collapse of the Asian vulture population and subsequent rabies crisis might have been prevented.
Protecting the environment from pharmaceutical harm is not just about saving wildlife—it is about safeguarding human health and ensuring a sustainable future for all.
Incorporating One Health and ecopharmacovigilance in legislation
Legislation regarding the environmental impact of pharmaceuticals differs (and is sometimes lacking completely) across jurisdictions. Since 2006, EU legislation requires all human and veterinary medicines to undergo an environmental risk assessment (ERA) before approval. An ERA uses standardised tests to evaluate the potential risk posed to the environment from exposure to pharmaceutical substances by analysing ecotoxicological data.
This data is, unfortunately, only available for a very small percentage of pharmaceuticals. This is true both for pharmaceuticals approved before (so called legacy APIs/substances) and for those approved after implementation of the ERA requirements, as there is no legal requirement for companies to update the ERAs with new information about environmental effects. Furthermore, while identified environmental risk can be used as a reason to deny the granting of marketing authorisation for a veterinary medicinal product, this is not the case for human medicinal products.
However, as part of the revision of the EU pharmaceutical legislation, the European Commission intends to incorporate the One Health approach both to address antimicrobial resistance and broaden the scope of ERAs, and to impose stricter requirements regarding environmental pollution from pharmaceuticals in the environment. For example, the Swedish Medical Products Agency has pushed to integrate stricter requirements at both the European and national level, not least for substances with a known negative effect on non-target species.
Protecting the environment from pharmaceutical harm is not just about saving wildlife—it is about safeguarding human health and ensuring a sustainable future for all. As we face growing challenges from climate change, biodiversity loss, and emerging infectious diseases, the lessons of the diclofenac crisis are more relevant than ever. By integrating EPV into One Health strategies, policymakers can better anticipate and mitigate the unintended consequences of pharmaceutical interventions.
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