1. Control of Aquatic Diseases

2. 6) External Treatments Controls pathogenic agents of fish/water Requires immersion Chemical effective but at lower-than-lethal level (e.g., chlorine not good for this use) Miscible in water Resist absorption by fish Usable for multiple treatments Cheap What fits THIS category?

3. Types of External Treatments: dips Characterized as high concentration for short time Used on small #’s of fish, often prophylactic Advantages: concentration easily established, requires small amount Disadvantages: have to handle all fish, can create situation where effective dose is higher than lethal dose

4. External Treatments: dip on the run, “Splash and go!” Strong chemical concentration via inflow water chemical rapidly enters water applicable to troughs, tanks, raceways advantage: don’t have to turn off water disadvantage: uneven distribution

5. External Treatments: bath Actually just a prolonged dip lower concentration, determined accurately by volume of tank, amount of chemical no water exchange advantage: concentration known, no fish handling disadvantage: oxygen can decrease, NH 3 can increase, hot-spots, must quickly remove chemical at end of treatment (this last one can be a real problem for large volume recirculation systems)

6. External Treatment: flow through Designed to maintain constant concentraton flowing into tank chemical dripped-in or siphoned advantages: no water shut-off, no handling disadvantages: must have even flow for even treatment, costly

7. External Treatment: indefinite Simple to treatment of most ponds very low concentration of chemical applied broken-down naturally or dissipates into air must break-down quickly (problem: few do) advantages: no handling of fish disadvantages: lot of chemical ($), adverse affects on pond (kills phytos), even application difficult

8. 7) Systematic Treatment of Diseases Compounds introduced orally thru feed problem: sick fish go off feed! drug must 1) control pathogen under internal conditions, 2) effective dose < lethal dose, and 3) be cost-effective Applied during manufacturing process, can be integrated into gelatin binder on pellet surface problem: even distribution difficult, pellets must be prepped daily Why not often used? Apathy, $$, FDA regs

9. Lack of Biosecurity??

10. Part 3. Regulatory Issues

11. Approval Requirements for New Drugs Approval from EPA or the FDA requires research/admin. tasks scientific research entails learning: efficacy of treatment (does the compound achieve the desired results?) can results be obtained w/out further jeopardizing health? Does its use pose danger to humans? Does the therapeutant harm the environment?

12. Efficacy or Effectiveness First step is to test the drug against potential pathogens (Are they sensitive to the drugs?) usually performed in vitro Minimum Inhibitory Concentrations (MIC’s) develop a standardized test battery of isolates isolates are representative bacterial strains + two references acceptable MIC’s are less than 2 ppm

13. Efficacy (continued) Second Step: assuming drug is determined safe, it must be effective in vivo a series of dose-titration studies disease intentionally induced (w/pathogen) followed by administration of drug at various levels if effective: dose response

14. Safety when used on Test Animal Lowest dose toxic to the test animal must be established toxicity is more than just the lowest level causing mortality death + any other deleterious effect (e.g., lethargy, poor growth, aesthetic considerations, etc.) levels established by: lethal concentration (LC), lethal dose (LD), effective concentration (EC), effective dose (ED)

15. Standardized Procedure?? Toxicity testing procedures for cattle are not that applicable to fish or shrimp Proposed method (Williams et al., 1992) Uses therapeutic index (TI) TI = (highest inhibitory level of drug/lowest level toxic to shrimp) if animals show a TI value (therapeutic index) of greater than 4, go on to more detailed studies in other stages

16. Human Safety Issues If the drug is shown to be effective against the pathogen, it is assumed that some is incorporated into tissue greatest concern: how long are effective levels in tissue maintained? Must establish withdrawal period definition: the amount of time a given drug persists in the edible flesh of treated fish/shrimp at detectable levels

17. Human Safety Issues (continued) Studies used to establish withdrawal period are referred to as “residue” or “depletion” studies time consuming, expensive, required detailed lab analyses, equip, etc. procedures must follow GLP: good laboratory practices (very rigid) requires FDA certified GLP lab (few in the U.S.) typical lab is owned by pharmaceutical company

18. Environmental Safety The FDA is primarily responsible for reviewing information to support the premise that the prospective drug does not harm the environment they like to see data indicating that the drug breaks down rapidly: short half-life in the system low effluent volume effluent that is highly diluted further dilution in the environment

19. Environmental Safety The FDA is really only concerned with the prospective drug harming the environment as a direct toxicant other factors should be of concern: direct/indirect effects on microflora in and outside the culture facility antimicrobials can shift things towards resistant species...oops! each successive use could increase proportion of drug-resistant microbes

20. Administrative Procedures Unfortunately, the previous scientific concerns are the only ones addressed for acceptance of newtherapeutic drugs administrative tasks are more difficult than the scientific ones myriad types of FDA applications and procedures that must be followed

21. What does the FDA Want? review your protocol for testing follow up with a visit must respond to your application within a certain time limit (sometimes up to 1/2 year) then they tell you that you forgot something!! Keep bugging them...

22. Investigational New Animal Drug (INAD) Applications If INAD’s approved, you can use an unapproved aquaculture drug INAD’s are, however, used for specific purposes, many restrictions: meaningful data only under INAD protocol virtually no hazard to humans (rapid degradation in test animals) minimum impact on the environment really restricted to certain user groups

23. INAD Applications INAD’s lead to NAD’s NAD’s provide for the submission of required data in support of a request to gain the approval of a new drug for use with animals. This process is very expensive Usually, NAD’s are submitted by pharmaceutical companies manufacturing the drug

24. Key Resources USDA-APHIS fact sheets for various animal diseases http://www.aphis.usda.gov/lpa/pubs/fsheet_faq_notice/fsfaqnot_animalhe alth.html APHIS’s Center for Emerging Issues (CEI) has various worksheets available on animal health and diseases of concern http://www.aphis.usda.gov/vs/ceah/cei/worksheets.htm Aquatext.com -- a free, online aquaculture dictionary http://www.pisces-aqua.co.uk/aquatext/dicframe.htm 34State Agricultural Response Team

25. Key Resources Florida Department of Community Affairs, Division of Emergency Management http://www.floridadisaster.org United States Department of Agriculture (USDA) http://www.usda.gov Florida Department of Agriculture and Consumer Services (FDACS) http://www.doacs.state.fl.us 35State Agricultural Response Team

26. Key Resources Florida Division of Aquaculture home page http://www.floridaaquaculture.com Aquaculture Best Management Practices manual can be accessed directly at http://www.floridaaquaculture.com/BAD/BMP%20Rule%20- %20Manual%206-9-04.pdf Aquaculture Network Information Center http://aquanic.org 36State Agricultural Response Team

27. Key Resources USDA Animal and Plant Health Inspection Service (APHIS) http://www.aphis.usda.gov World Organisation for Animal Health (OIE) http://www.oie.int Safety for Fish Farm Workers video on the National Ag Safety Database (NASD), English and Spanish versions available from the following link http://www.cdc.gov/nasd/videos/v001401-v001500/v001433.html 37State Agricultural Response Team

28. Key Resources Spawn, Spat, and Sprains book produced by the Alaska Sea Grant College Program. The entire book can be downloaded from the following link http://www.uaf.edu/seagrant/Pubs_Videos/pubs/AN-17.pdf University of Florida Institute of Food and Agricultural Sciences Electronic Data Information Source (EDIS) fact sheets for aquaculture, including diseases, can be found at the following links http://edis.ifas.ufl.edu/DEPARTMENT_VETERINARY_MEDICINE http://edis.ifas.ufl.edu/DEPARTMENT_FISHERIES_AND_AQUATIC_SCIENCES 38State Agricultural Response Team