#17,019
Nearly 16 years, and almost 17,000 blogs ago, in The Law of Unintended Consequences (Jan ‘07), I wrote about growing concerns over what effects the large-scale use of Oseltamivir (Tamiflu ®) might have on the environment and the evolution of avian flu viruses (see study Potential Risks Associated with the Proposed Widespread Use of Tamiflu).
Tamiflu, like many antivirals and antibiotics, is excreted almost 100% intact in one’s urine, and can eventually make its way through wastewater treatment plants and end up in the environment where it could potentially impact the evolution of viruses carried by wildlife.
Supplemental Table 4. Assessing the Ecotoxicologic Hazards of a Pandemic Influenza Medical Response. Environ Health Perspect :-. doi:10.1289/ehp.1002757
We revisited the topic again in 2009 (see Everything Old Is News Again) when researchers at Kyoto University tested wastewater discharge from three local sewage treatment plants and water from two rivers into which they drained during the 2008-09 flu season looking for signs of the active ingredient in Tamiflu, oseltamivir carboxylate (OC).
For years Japan had been the largest consumer of antivirals for seasonal flu, and they found exactly what they were looking for; substantial levels of the Tamiflu metabolite in the environment.
A couple of years later, in Pandemics & The Law Of Unintended Consequences, we looked at not only the potential effects of antivirals in our sewage system, but also how the consumption (and excretion) of antibiotics during a pandemic might affect wastewater treatment plants (WWTPs).
Specifically that antibiotics in the sewage could inhibit microbial activity, resulting in the failure of WWTPs and the discharge of under-treated wastewater into the environment (see Centre for Ecology & Hydrology 2-Mar-2011 Effectiveness of wastewater treatment may be damaged during a severe flu pandemic).
Carrying the WWTP story one step further, in WWTPs As `Mixing Vessels’ For Resistant Bacteria, UK scientists discovered that sewage plants were actually amplifying the number of resistant bacteria that entered the plant.
The idea that we can `flush it and forget it' is, unfortunately, dangerously naive.
As we approach COVID's 3rd anniversary, many of the initial monoclonal antibody treatments are no longer effective, and we are becoming more reliant upon antivirals like Molnupiravir (Lagevrio) and nirmatrelvir/ritonavir (Paxlovid).
We are similarly highly dependent upon oseltamivir and baloxavir marboxil for the treatment of both seasonal, and novel (or even pandemic) influenza. And anything that contributes to antibiotic resistance is a perennial concern.
All of which brings us to a preprint, published this month in EcoEcoRxiv, that looks at the potential risks of antiviral spillover into the environment via wastewater. I've only excerpted the Abstract, and the conclusion from this 28-page report, so follow the link to read it in its entirety.
I'll have a brief postscript after the break.
Spillover of human antivirals may promote resistant pathogens in animal reservoirs
Emma J. Rosi 1 , Jerker B. Fick 2 , Barbara A. Han 1
Abstract
Novel viral pathogens are causing diseases to emerge in humans, a challenge to which society has responded with technological innovations such as antiviral therapies.
Antivirals can be rapidly deployed to mitigate severe disease, and with vaccines, save human lives and provide a long-term safety net against new viral diseases. Yet with these advances come unforeseen consequences when antivirals are inevitably released to the environment. Using SARS-CoV-2 as a case study, we identify global patterns of overlap between bats and elevated pharmaceutical concentrations in surface waters. We model how freshwater contamination by antivirals could result in exposure to insectivorous bats via consumption of emergent insects with aquatic larvae, ultimately risking the evolution of antiviral-resistant viruses in bats. The consequences of widespread antiviral usage for both human and ecosystem health underscore urgent frontiers in both scientific research and sustainable development.
Keywords: antivirals, bats, emerging aquatic insects, wastewater
In a nutshell
• Humans have developed antiviral therapies that are often repurposed for multiple viral diseases.
• Antiviral compounds are incompletely metabolized during human use and enter surface waters via wastewater effluents.
• Although aquatic insects are known to bioaccumulate some pharmaceuticals by multiple orders of magnitude, antiviral bioaccumulation has not been quantified.
• When insect predators such as bats are also reservoirs of viral pathogens, exposure to bioconcentrated antivirals may result in viruses that are resistant to antiviral drugs.
• We outline a research frontier to examine the potential for these effects and a call to action to minimize risks for human health.
(SNIP)
Conclusions
In an increasingly connected world, novel infectious diseases can spread rapidly to every country of the world. Widespread use and uncontrolled release of antiviral may pose unforeseen and potentially serious consequences to human health. Bioaccumulation of antivirals in aquatic insects and potential transfer to bats represents a gap in our understanding about the consequences of antiviral contamination of the environment. We need to exercise caution with our current arsenal of antiviral compounds to ensure that our actions today do not render treatments ineffective for the diseases of tomorrow.
Last week we saw a warning from the FDA On The Potential For Monkeypox To Evade TPOXX (tecovirimat) Antivirals, and this comes even before this experimental drug has seen much use.
Two months ago, in CDC: COVID-19 Reverses Progress in Fight Against Antimicrobial Resistance in U.S., we looked at how the overuse of antibiotics in treating COVID patients has made matters demonstrably worse since the pandemic began.
While many people worry that a hyper-virulent novel virus will emerge and kill hundreds of millions of people, the reality is - if we don't protect our limited armamentarium of antibiotics and antivirals - something relatively ordinary, and previously treatable, could do the job equally as well.
