Antiviral Drugs Zanamivir and Oseltamivir Found in Wastewater and Surface Water in Osaka, Japan

Abstract

Oseltamivir and zanamivir are the two most prescribed antiviral drugs against influenza in Japan. Oseltamivir and its metabolite are frequently detected in surface water bodies in Japan during the last few years particularly in seasonal influenza period posing a potential threat of emergence of drug-resistant genes in human pathogens. Despite the second largest use of zanamivir as an antiviral drug in Japan, its presence and fate in environmental waters is unknown until now. Accurate assessment on the presence and fates of these drugs in environmental waters is the very first step in countering the potential negative impact on human health. We have recently developed a novel solid-phase extraction (SPE) method for simultaneous recovery of oseltamivir and zanamivir in environmental waters. These antiviral drugs were quantified in Neya River water and a nearby conventional sewage treatment plant (STP) during the 2010/2011 seasonal influenza using the SPE method in this investigation. Oseltamivir and zanamivir concentrations in the river water and STP water samples are discussed and compared with those of the 2009/2010 pandemic influenza in this article. This successful simultaneous quantitation of zanamivir in wastewater and river water with high recovery ratios paves the way for its monitoring in environmental waters.

Resistance Mutation R292K Is Induced in Influenza A(H6N2) Virus by Exposure of Infected Mallards to Low Levels of Oseltamivir

“…Several studies have detected OC in the aquatic environment [12]–[15], and generally environmental levels in the magnitude of lower to mid ng/L have been found. Up to 865 ng/L of OC has been detected in river water which is 14-fold lower than the 12 µg/L of OC where we observed resistance development.…”

“…At least 75% of a given dose reaches the blood circulation as OC and is then excreted unchanged via the urine. OC is stable in sewage treatment processes and has been detected in effluents from sewage treatment plants (up to 1.21 µg/L) and in river water (up to 865 ng/L) [11]–[15]. Sampling in Germany suggests discharge from pharmaceutical industries as another contributing source [16].…”

Future perspectives of wastewater-based epidemiology: Monitoring infectious disease spread and resistance to the community level

“…) Takanami et al, 2012) (Funke et al, 2016;Prasse et al, (Huang et al, 2010;Roberts and Thomas, 2006) (Guerra et al, 2014;Roberts and Thomas, 2006) (Guerra et al, 2014;Kasprzyk-Hordern et al, 2009;Roberts and Thomas, 2006 (Munir et al, 2011;Wang et al, 2015) INF: Influent wastewater (U): Urine. PFU: Plaque forming units (measure of number of infectious particles).UTI: Urinary tract infection *Via sequencing…”

Compliance to Oseltamivir among Two Populations in Oxfordshire, United Kingdom Affected by Influenza A(H1N1)pdm09, November 2009 – A Waste Water Epidemiology Study

“…However, the bolus would appear completely unfeasible with sufficiently high sampling frequency as the quantity of drug passing per unit time would, in comparison to other time points, be unachievable on a per capita basis [30], [33]. Additional supporting evidence for the origin of OC in waste water can come from measuring the ratio of OC:OP, as described in a number of previous studies [17], [34], [35]. However, as OC (the active antiviral) is generated from the prodrug oseltamivir phosphate (OP), it can be assumed that all OC found in waste water in this study was the result of the consumption and ( in vivo ) metabolism of the prodrug.…”