Lethal methemoglobinemia in the invasive brown treesnake after acetaminophen ingestion

Abstract

the invasive brown treesnake (Boiga irregularis) has extirpated much of Guam's native birdlife and poses significant threats to other parts of the western Pacific. Acetaminophen (APAP) is a proven lethal oral toxicant in reptiles but the physiological mechanism is unknown. The effects of a lethal APAP oral dose on methemoglobin (MetHb, non-oxygen carrying form) levels and other blood parameters were examined in brown treesnakes. Co-oximetry was used to measure MetHb (%) and other hemoglobin species. Assessment of red blood cell integrity, white blood cell differential counts, and plasma biochemical analyses were conducted to evaluate tissue damage, stress, and liver function. Changes in oxygen carrying capacity were noted in APAP-treated snakes indicated by a 50-60% increase in methemoglobin levels and a 40% decrease in oxyhemoglobin (oxygen-carrying form) levels compared to controls. APAP-treated snakes had decreased lymphocyte and increased monocyte counts while also having increased levels of blood analytes associate with impaired liver function and muscle damage. the proximate cause of death in APAP-treated snakes was likely acute methemoglobinemia and respiratory failure due to severe hypoxia with no observed signs of distress or pain. An orally-ingested lethal dose of APAP appears to be a humane method for lethal control of this species.

Monitoring methaemoglobinaemia in birds using 5 μL of whole blood

“…In chicken, possum, dog and cat blood in vitro, declining Hb(Fe 2+ ) values determined by the Cera-Chek biosensor were strongly correlated with MetHb concentration determined by the CO-Oximeter. In all three mammals, the strong inverse relationship between MetHb and HbO determined by the CO-Oximeter corresponded with in vivo data reported for carnivores [10] and reptiles [28] orally dosed with MetHb-forming agents. Our data also accorded with prior in vitro experiments using a similar NaNO 2 gradient with coyote, duck and starling erythrocytes that were…”

“…While blood samples as small as 45 μL have been lysed, centrifuged and added to a phosphate buffer to permit MetHb analysis in the laboratory [26], several factors suggest that rapid analysis of avian blood at the point of collection should be preferred. Avian blood is difficult to preserve [27], moreover, changes in MetHb and HbO in response to MetHb-forming agents can be highly dynamic [10,28] and may alter due to changes in the induction of MetHb-reductases [29]. Accordingly, in order to facilitate investigations of the impact of MetHb-forming agents on a wide range of birds, we sought to develop methods able to analyse sequential whole blood samples no more than 5 μL in volume at their point of collection to provide markers of comparative hypoxaemia and hypoxia.…”

“…Methaemoglobinaemia, is a functional anaemia where MetHb displaces HbO, in a relationship that is strongly inversely correlated [10,28]. Individually, neither MetHb or HbO concentrations proved to be as successful at predicting bird survival as the MAI [17].…”

Brown Treesnake Mortality After Aerial Application of Toxic Baits

“…1). Acetaminophen is an approved toxicant for the lethal control of brown treesnakes (Savarie et al 2000, Johnston et al 2002, Sharp and Saunders 2011, van den Hurk and Kerkkamp 2019, Mathies and Mauldin 2020) and poses minimal risk to nontarget wildlife species (Johnston et al 2002, Clark et al 2012, Siers et al 2019 b ). Dead neonatal mice are attractive snake baits (Shivik and Clark 1997), but rodent‐based toxic baits more effectively target adults (Lardner et al 2013) because brown treesnakes exhibit an ontogenetic diet shift with juvenile snakes (<700 mm snout‐vent length [SVL]) consuming primarily lizards (Savidge 1988, Rodda et al 1999 b , Siers 2015) and exhibiting a strong prey preference for lizards (Lardner et al 2009).…”

“…Dead neonatal mice remain viable baits for brown treesnakes for approximately 48-72 hours post-deployment. Once baits are ingested, snakes may take an additional 24-48 hours (Mathies and Mauldin 2020) or longer for larger snakes (Siers et al 2021) to succumb to the toxin and another 24 hours following death for transmitters to broadcast a mortality signal. In accordance, we determined the effective treatment period to extend 7 days beyond the final application, or the 2-week period between 7 June through 21 June 2019.…”