Control of Aquatic DiseasesControl 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 pathogenic

agent• If found, entire herd is destroyed• Carcasses disposed in a manner preventing

further spread of agent• Effective when absolute control is needed:

• agent has no known treatment• agent is exotic• fish have high levels of agent

• Often requires legislation to be effective• which agents require mandatory slaughter?• must include all policies• requires indemnification or won’t be effective

2) Quarantine and Restriction of Movement

Restricts all movements of fish between drainage systems and between hatcheries -or-Fish transport requires detention of fish in “suspected” area for length of time equal to incubation period of suspected agentIf no disease develops, fish movedIf disease develops, fish are rejected.

2) Quarantine and Restriction of Movement

Applies to whole animal, parts, or productseasy to suggest on paper, hard to abide byWhy? How can you practically hold fish outside your facility for the incubation period?What about latent carriers?Q/R also applies to all fish/shrimp imports:inspections carried out by certified inspectorssampling assumes 5% prevalence in lotsampling level ensures 95% chance of recovering one infected individualcould be infected but probably not

2) Quarantine and Restriction of Movement

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 have proven useful to traditional agricultured species, humans, traditional speciesnot so effective for most aquacultured speciesfish not very immuno-competent at low tempslimited methodologies for mass immunizationbreeding/genetic programs in place for disease resistance: rainbows resistant to furunculosis at low temps (< 11 C), brown trout to whirling disease, new strains of L. vannamei resistant to WSSVcommon problem: breeding in resistance usually means breeding out growth

4) Destruction/Reduction of Other Hosts in Life Cycle

Can be effective against most metazoan parasitesyou can try to eliminate some snails, keep birds outdifficult to eradicate vertebrates: most are “protected”Belizean example of eradication

5) Drug Therapy

Typical method of dealing with outbreaks of infectious diseases in fish/shrimpunfortunate for various reasons: development of resistance, cost, approval issuesmoney: limited potential volume of sales prohibits most companies from doing the R&D required“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)

Revised Act (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) information on dose must appear on tags

real limitation on use, originally intended to curb only indiscriminate use

6) External Treatments

Controls pathogenic agents on outside surface of fish or from waterrequires immersion under quality environmental conditionschemical effective but at lower-than-lethal level (e.g., chlorine not good for this use)miscible in waterresist absorption by fishusable for multiple treatmentscheap

Types of External Treatments: dips

Characterized as high concentration for short period of timeused on small #’s of fish, often routine as a 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

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

Really just a prolonged diplower concentration, determined accurately by volume of tank, amount of chemicalno water exchangeadvantage: concentration known, no fish handlingdisadvantage: oxygen can decrease, NH3 can increase, hot-spots, must quickly remove chemical at end of treatment

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 feeddrug must 1) control pathogen under internal conditions, 2) have effective dose lower than lethal dose, and 3) be cost-effectiveapplied by feed company in feeds, can be integrated into gelatin binder on pellet surfaceproblem: even spread on pellet coat, pellets must be prepped dailywhy not often used? Apathy, money, stringent FDA regs

8) Hatchery Sanitation

Purpose 1: prevention of any foreign disease agents from getting into hatcheryPurpose 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

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 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)

Regulatory Issues

Approval Requirements for New Drugs• Approval comes from either the EPA or the

FDA• requires scientific research and

administrative 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 responsehard to show with shrimp because they have no obligate bacterial pathogens

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 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 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 Aquaculture Drug Applications (INADA’s)

If this is approved, you can use an unapproved aquaculture drugINADA’s are, however, used for specific purposes, many restrictions: meaningful data only under INADA protocol virtually no hazard to humans (rapid

degradation in test animals) minimum impact on the environment really restricted to certain user groups

New Animal Drug Applications (NADA)

INADA’s lead to NADA’sNADA’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, NADA’s are submitted by pharmaceutical companies manufacturing the drug