Control of Aquatic DiseasesControl of Aquatic Diseases

6) External Treatments

Controls pathogenic agents of fish/waterRequires immersionChemical effective but at lower-than-lethal level (e.g., chlorine not good for this use)Miscible in waterResist absorption by fishUsable for multiple treatmentsCheap

What fits THIS category?

Types of External Treatments: dips

Characterized as high concentration for short timeUsed on small #’s of fish, often prophylacticAdvantages: concentration easily established, requires small amountDisadvantages: have to handle all fish, can create situation where effective dose is higher than lethal dose

External Treatments: dip on the run, “Splash and go!”

Strong chemical concentration via inflow waterchemical rapidly enters waterapplicable to troughs, tanks, racewaysadvantage: don’t have to turn off waterdisadvantage: uneven distribution

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, NH3 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)

External Treatment: flow through

Designed to maintain constant concentraton flowing into tankchemical dripped-in or siphonedadvantages: no water shut-off, no handlingdisadvantages: must have even flow for even treatment, costly

External Treatment: indefinite

Simple to treatment of most pondsvery low concentration of chemical appliedbroken-down naturally or dissipates into airmust break-down quickly (problem: few do)advantages: no handling of fishdisadvantages: lot of chemical ($), adverse affects on pond (kills phytos), even application difficult

7) Systematic Treatment of Diseases

Compounds introduced orally thru feedproblem: sick fish go off feed!drug must 1) control pathogen under internal conditions, 2) effective dose < lethal dose,

and 3) be cost-effectiveApplied during manufacturing process, can be integrated into gelatin binder on pellet surfaceproblem: even distribution difficult,pellets must be prepped dailyWhy not often used? Apathy, $$, FDA regs

Lack of Biosecurity??

Part 3. Regulatory Issues

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?

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 referencesacceptable MIC’s are less than 2 ppm

Efficacy (continued)

Second Step: assuming drug is determined safe, it must be effective in vivoa series of dose-titration studies disease intentionally induced (w/pathogen)followed by administration of drug at various levelsif effective: dose response

Safety when used on Test Animal

Lowest dose toxic to the test animal must be establishedtoxicity is more than just the lowest level causing mortalitydeath + 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)

Standardized Procedure??

Toxicity testing procedures for cattle are not that applicable to fish or shrimpProposed 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

Human Safety Issues

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

Human Safety Issues (continued)

Studies used to establish withdrawal period are referred to as “residue” or “depletion” studiestime 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

Environmental Safety

The FDA is primarily responsible for reviewing information to support the premise that the prospective drug does not harm the environmentthey 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

Environmental Safety

The FDA is really only concerned with the prospective drug harming the environment as a direct toxicantother 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

Administrative Procedures

Unfortunately, the previous scientific concerns are the only ones addressed for acceptance of newtherapeutic drugsadministrative tasks are more difficult than the scientific onesmyriad types of FDA applications and procedures that must be followed

What does the FDA Want?

review your protocol for testingfollow up with a visitmust 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...

Investigational New Animal Drug (INAD) Applications

If INAD’s approved, you can use an unapproved aquaculture drugINAD’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

INAD Applications

INAD’s lead to NAD’sNAD’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 expensiveUsually, NAD’s are submitted by pharmaceutical companies manufacturing the drug

Key ResourcesUSDA-APHIS fact sheets for various animal diseaseshttp://www.aphis.usda.gov/lpa/pubs/fsheet_faq_notice/fsfaqnot_animalhealth.html

APHIS’s Center for Emerging Issues (CEI) has various worksheets available on animal health and diseases of concernhttp://www.aphis.usda.gov/vs/ceah/cei/worksheets.htm

Aquatext.com -- a free, online aquaculture dictionaryhttp://www.pisces-aqua.co.uk/aquatext/dicframe.htm

34State Agricultural Response Team

Key ResourcesFlorida Department of Community Affairs, Division of Emergency Managementhttp://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

Key ResourcesFlorida Division of Aquaculture home pagehttp://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 Centerhttp://aquanic.org

36State Agricultural Response Team

Key ResourcesUSDA 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 linkhttp://www.cdc.gov/nasd/videos/v001401-v001500/v001433.html

37State Agricultural Response Team

Key ResourcesSpawn, Spat, and Sprains book produced by the Alaska Sea Grant College Program. The entire book can be downloaded from the following linkhttp://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 linkshttp://edis.ifas.ufl.edu/DEPARTMENT_VETERINARY_MEDICINEhttp://edis.ifas.ufl.edu/

DEPARTMENT_FISHERIES_AND_AQUATIC_SCIENCES

38State Agricultural Response Team