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Control of Aquatic DiseasesControl of Aquatic Diseases
http://www.flsart.org/library/index.htm
Various Methodolgies Allowing Control
◊ Test and Slaughter◊ Quarantine and Restriction of
Movement◊ Immunization and Disease Resistance◊ Destruction or Reduction of
Intermediate Hosts◊ Drug Therapy◊ External Treatments◊ Systemic Treatments◊ Hatchery Sanitation
1) Test and Slaughter◊ Requires testing population for pathogen◊ If found, entire group is destroyed◊ Carcasses buried or burned◊ Effective when absolute control is
needed:• agent has no known treatment• agent is exotic• fish have high levels of pathogen
◊ Often requires legislation to be effective• which agents require mandatory slaughter?• must include all policies• requires indemnification or won’t work
2) Quarantine and Restriction of Movement
Restricts all movements of fish between drainage systems and between hatcheries -or-Fish transport requires “Q” of fish in “suspected” areaNo disease = fish movedDisease = rejected.
2) Q/R cont.Applies to whole animal, parts, or productsGood on paper, hard to implementWhy? How can you practically hold fish outside your facility for the incubation period? Spoilage?? Death? Latent carriers?Q/R also applies to all fish/shrimp imports:Need certified inspectorsSampling assumes 5% prevalence, or 95% chance of recovering one infected individualInfected? Who knows?
2) Q/R
Programs not typically effective because farmers won’t pay for inspections if not required by lawInterstate transport laws are fairly “loose” (Idaho has no regulations)True inspections programs are best handled by large institutions (e.g., public aquaria)For permitting import of shrimp in Texas, you can only have one species (L. vannamei) and it must be SPF for TSV, white spot, IHHNV and Vibrio sp.
3) Immunization and Disease Resistance
Vaccines—good for terrestrials, not as much for fish
Fish not very immunocompetent at low temps
Time, $$$, limited methodologies
Breeding/genetics can increase disease resistance: rainbows (furunculosisr), brown trout (whirlingr), L. vannamei (WSSVr)
Common problem: breeding in resistance usually means breeding out growth...oops!
4) Destruction/Reduction of Other Hosts in Life Cycle
Can be effective against most metazoan parasites
You can try to eliminate some snails, keep birds out (Problems with permits?)
Difficult to eradicate vertebrates: most are “protected”
Herons, egrets, etc.
5) Drug Therapy: Cure, Crutch or Wheelchair??
Tried-and-true-method for fish/shrimp, but…
Resistance, cost, approval issues?
$$$$: limited potential volume of sales prohibits most companies from doing the R&D required to bring drugs to market
“Registration of a single compound for one type of use costs about $1.5 million and 1.5-3 years elapsed time”
Federal Food, Drug and Cosmetic Act (1915)
Revised in 1956limited use of many substances until safety to animals establishedall compounds used must be registered as safe for use by FDAGRAS = generally recognized as safetesting: efficacy, toxicity, tissue residence time (food implications)
Federal Food, Drug and Cosmetic Act (Revised, 1956)
Applied to previous, but also included section on food additivesreally targeting feedsfeed additives require additional registration: dosage (what is effective?) withdrawal time (last dose ---> market) (OTC=30
days) information on dose must appear on tags
real limitation on use, originally intended to curb only indiscriminate use
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
8) Hatchery Sanitation
Purpose 1: prevention of any foreign disease agents from getting into hatchery
Purpose 2: limits disease spread to tank of origin
Preventive GuidelinesReduces vertically-transmitted pathogens:1) import only eggs, never juveniles/adults2) eggs should be from SPF/high health facilities3) wild individuals should be prohibited or all water, etc. needs to be disinfected4) disinfect all eggs prior to stocking hatching containers (also disinfect/destroy all shipping containers)chemicals: iodophores (Argentyne) 100 ppm for 10-15 min
Guidelines for Limiting Spread
Disinfect all hatchery and personal equipment after or between use (equipment must be clean prior to disinfection)sports fishermen or farmers should never be allowed near facility (political issue)transfer/shipping equipment, vehicles must all be disinfected whenever leaving groundsdo not overlook any possible source of contaminationproper hatchery design limits spread
The fully outfitted lab is able to monitor water quality and fish pathology.
Part 2. Biosecurity
Recently, shrimp disease agents and associated problems have spread from foreign countries to the U.S.Major efforts established defense against diseaseDue to severity of issue, parallel efforts were undertaken to design production systems to exclude diseasesSuch systems are called “biosecure”Key issue: zero water exchange
Biosecurity: General Issues
Definition: the sum of all procedures in place to protect fish/shrimp from contracting, carrying and spreading diseasesCritical to identify all known and potential vectors critical: use only seed from SPF or high-health facilitiesstocks monitored periodically for disease using rapid methodologiesinfection of facility = shut-down, complete disinfection (chlorine gas, formaldehyde, etc.)
Biosecurity: General Issues
Other potential disease sources: incoming waterfacility should be isolated from other farms, processing plants, capture fisherieswater should be recycledreplacement water disinfected by chlorine, ozone, ultraviolet lightavoid vectors: gulls, dogs, crabs, etc.feeds ( prepared vs. raw)
Biosecurity will reduce the likelihood that potential Biosecurity will reduce the likelihood that potential pathogens will be transferred from workers to the fish.pathogens will be transferred from workers to the fish.Biosecurity will reduce the likelihood that potential Biosecurity will reduce the likelihood that potential pathogens will be transferred from workers to the fish.pathogens will be transferred from workers to the fish.
Footbaths & hand disinfection required before entering Footbaths & hand disinfection required before entering any fish rearing area.any fish rearing area.Footbaths & hand disinfection required before entering Footbaths & hand disinfection required before entering any fish rearing area.any fish rearing area.
Human Biosecurity
Don’t be afraid to keep folks out…
Your research or data is your livelihood!
You don’t want to be liable for someone’s injury either.
Human Biosecurity
Monitoring systems add redundancy to trained personnel.
Always good to have an extra set of eyes!
Walk-throughs before going home should be routine.
Human Biosecurity
Don’t assume folks will take precautions on their own.
You must establish a record and atmosphere of safety and maintain it.
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