Control of Aquatic Diseases

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” area No disease = fish moved Disease = rejected.

2) Q/R cont. Applies to whole animal, parts, or products Good on paper, hard to implement Why? 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 inspectors Sampling assumes 5% prevalence, or 95% chance of recovering one infected individual Infected? Who knows?

2) Q/R Programs not typically effective because farmers won’t pay for inspections if not required by law Interstate 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 (furunculosis r ), brown trout (whirling r ), L. vannamei (WSSV r ) 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 years elapsed time”

Federal Food, Drug and Cosmetic Act (1915) Revised in 1956 limited use of many substances until safety to animals established all compounds used must be registered as safe for use by FDA GRAS = generally recognized as safe testing: efficacy, toxicity, tissue residence time (food implications)

Federal Food, Drug and Cosmetic Act (Revised, 1956) Applied to previous, but also included section on food additives really targeting feeds feed 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/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?

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

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

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)

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

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

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

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 Guidelines Reduces vertically-transmitted pathogens: 1) import only eggs, never juveniles/adults 2) eggs should be from SPF/high health facilities 3) wild individuals should be prohibited or all water, etc. needs to be disinfected 4) disinfect all eggs prior to stocking hatching containers (also disinfect/destroy all shipping containers) chemicals: iodophores (Argentyne) 100 ppm for 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 grounds do not overlook any possible source of contamination proper 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 disease Due to severity of issue, parallel efforts were undertaken to design production systems to exclude diseases Such 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 diseases Critical to identify all known and potential vectors critical: use only seed from SPF or high- health facilities stocks monitored periodically for disease using rapid methodologies infection of facility = shut-down, complete disinfection (chlorine gas, formaldehyde, etc.)

Biosecurity: General Issues Other potential disease sources: incoming water facility should be isolated from other farms, processing plants, capture fisheries water should be recycled replacement water disinfected by chlorine, ozone, ultraviolet light avoid vectors: gulls, dogs, crabs, etc. feeds ( prepared vs. raw)

Biosecurity will reduce the likelihood that potential pathogens will be transferred from workers to the fish. Footbaths & hand disinfection required before entering 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 references acceptable MIC’s are less than 2 ppm

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

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)

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

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

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

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

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

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

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...

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

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

Key Resources USDA-APHIS fact sheets for various animal diseases alth.html APHIS’s Center for Emerging Issues (CEI) has various worksheets available on animal health and diseases of concern Aquatext.com -- a free, online aquaculture dictionary 34State Agricultural Response Team

Key Resources Florida Department of Community Affairs, Division of Emergency Management United States Department of Agriculture (USDA) Florida Department of Agriculture and Consumer Services (FDACS) 35State Agricultural Response Team

Key Resources Florida Division of Aquaculture home page Aquaculture Best Management Practices manual can be accessed directly at %20Manual% pdf Aquaculture Network Information Center 36State Agricultural Response Team

Key Resources USDA Animal and Plant Health Inspection Service (APHIS) World Organisation for Animal Health (OIE) Safety for Fish Farm Workers video on the National Ag Safety Database (NASD), English and Spanish versions available from the following link 37State Agricultural Response Team

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 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 State Agricultural Response Team