Treatment of a Large Multi-species Display Exhibit with Chloroquine and Mortality Associated with Treating the Water Containing Chloroquine with Ozone
Abstract
Chloroquine is a medication used to treat and prevent malaria in humans where it has a narrow margin of safety. It can treat aquarium fish for some protozoan parasites including Cryptocaryon, Amyloodinium and monogenetic trematodes.1,2,3 Unexpected mortalities sometimes occur and this case may demonstrate a mechanism for this toxicity. A 2800 m3 (750,000 gallon) exhibit system was diagnosed with Cryptocaryon irritans. Before treating that exhibit a smaller system was treated to perfect the treatment technique A 56.8 m3 (15,000 gallon) quarantine system using artificial sea water and containing cownose rays (Rhinoptera bonasus), bamboo sharks (Chiloscyllium plagiosum), and Wobbegong sharks (Orectolobus ornatus) was treated with Chloroquine at 10 mg/liter for two months. Chloroquine was measured with a UV spectrophotometer.2 During the treatment activated carbon was removed and ozone supplying the foam fractionator was turned off. None of the animals showed major side effects from this treatment so after one month the larger display system containing 750,000 gallons of synthetic saltwater was treated with Chloroquine. Animal population at the time consisted of 12 sand tigers (Carcharhias taurus), 4 sandbar sharks (Carcharhinus plumbeus), 3 nurse sharks (Ginglymostoma cirratum), 2 longcomb sawfish (Pristis zisjron), 1 roughtail stingray (Dasyatis centroura), 2 green sea turtles (Chelonia mydas) and a large number of teleosts.
The larger system was dosed with 2 ppm of chloroquine every other day until a level of 10 ppm of chloroquine was reached. Several animals developed anorexia and increased swimming speed. One animal showed more severe problems and the treatment was terminated 11 days after reaching 10 ppm.
Mortalities were seen following treatment in both systems. In the display tank for the 16 months prior to treatment mortality averaged about 1 per week. During the treatment there were 9 mortalities, which averages 1.6 mortalities per week. For weeks 3 to 6 after treatment the mortalities averaged 21 per week. In the larger system almost all the mortalities were teleosts. In the quarantine tank there were no mortalities during treatment but all 6 O. ornatus and three C. plagiosum died between 16 and 29 days after the end of treatment. The first death occurred when the measured chloroquine level was down to 5 ppm.
Why did mortalities increase after treatment? Ozone added to sea water produces hypobromous acid by reacting with bromide in the water 5 and sea water contains 65 mg per liter of bromide. Hypobromous acid can produce disinfection by-products by substitution reactions with hydrogen atoms on amino groups and other sites and by substitution for chlorine on chlorinated compounds. These disinfection by-products may be more toxic than the parent compound.4 Chloroquine has a narrow margin of safety so bromination might increase the toxicity and lead to the mortality seen. Systems containing elasmobranchs are supplemented with iodine to prevent goiter and iodine can also react with ozone similarly to bromine to form more toxic compounds.
Ozone should not be used in water containing chloroquine. Activated carbon and water changes may be safer.
* Presenting author
Literature Cited
1. Noga E. 2010. Fish Disease: Diagnosis and Treatment. 2nd ed. Ames, IA: Wiley-Blackwell. 536 p.
2. Hemdal JF. 2013. Chloroquine: a “new” drug for treating fish diseases. Advanced Aquarist. 12:(2).
3. Sowers K, Latson E, George R, Neal L. 2017. Chloroquine phosphate and praziquantel as a means to eradicate Decacoytle floridana in spotted eagle rays. Drum and Croaker. 48:16–20.
4. Plewa MJ, Muellner M, Richardson S, Fasano F, Buettner K, Woo Y, McKague B, Wagner E. 2008. Occurrence, synthesis, and mammalian cell cytotoxicity and genotoxicity of haloacetamides: an emerging class of nitrogenous drinking water disinfection byproducts. Environmental Science & Technology. 42(3):955–961.
5. Keaffaber JJ. 2009. Current perspectives in ozone chemistry in marine life support systems. AALSO Conference Proceedings, Seattle, WA; http://aalso.dreamhosters.com/oldsite/2009presentations/KeaffaberOzoneChemistryMarineLSSPaper.pdf