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Control of Aquatic Diseases

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Title: Control of Aquatic Diseases


1
Control of Aquatic Diseases
2
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

3
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 wont be effective

4
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 agent
  • If no disease develops, fish moved
  • If disease develops, fish are rejected.

5
2) Quarantine and Restriction of Movement
  • Applies to whole animal, parts, or products
  • easy to suggest on paper, hard to abide by
  • Why? 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 inspectors
  • sampling assumes 5 prevalence in lot
  • sampling level ensures 95 chance of recovering
    one infected individual
  • could be infected but probably not

6
2) Quarantine and Restriction of Movement
  • Programs not typically effective because farmers
    wont 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.

7
3) Immunization and Disease Resistance
  • Vaccines have proven useful to traditional
    agricultured species, humans, traditional species
  • not so effective for most aquacultured species
  • fish not very immuno-competent at low temps
  • limited methodologies for mass immunization
  • breeding/genetic programs in place for disease
    resistance rainbows resistant to furunculosis
    at low temps (lt 11 C), brown trout to whirling
    disease, new strains of L. vannamei resistant to
    WSSV
  • common problem breeding in resistance usually
    means breeding out growth

8
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
  • difficult to eradicate vertebrates most are
    protected
  • Belizean example of eradication

9
5) Drug Therapy
  • Typical method of dealing with outbreaks of
    infectious diseases in fish/shrimp
  • unfortunate for various reasons development of
    resistance, cost, approval issues
  • money limited potential volume of sales
    prohibits most companies from doing the RD
    required
  • registration of a single compound for one type
    of use costs about 1.5 million and 1.5-3 years
    elapsed time

10
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)

11
Revised Act (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 ---gt market)
  • information on dose must appear on tags
  • real limitation on use, originally intended to
    curb only indiscriminate use

12
6) External Treatments
  • Controls pathogenic agents on outside surface of
    fish or from water
  • requires immersion under quality environmental
    conditions
  • 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

13
Types of External Treatments dips
  • Characterized as high concentration for short
    period of time
  • used on small s of fish, often routine as a
    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

14
External Treatments dip on the run
  • Strong chemical concentration via inflow water
  • chemical rapidly enters water
  • applicable to troughs, tanks, raceways
  • advantage dont have to turn off water
  • disadvantage uneven distribution

15
External Treatments bath
  • Really 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

16
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

17
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

18
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) have effective dose lower than
    lethal dose, and 3) be cost-effective
  • applied by feed company in feeds, can be
    integrated into gelatin binder on pellet surface
  • problem even spread on pellet coat, pellets
    must be prepped daily
  • why not often used? Apathy, money, stringent FDA
    regs

19
8) Hatchery Sanitation
  • Purpose 1 prevention of any foreign disease
    agents from getting into hatchery
  • Purpose 2 limits disease spread to tank of
    origin

20
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
    10-15 min

21
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

22
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

23
Biosecurity General Issues
  • Definition the sum of all procedures in place
    to protect 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.)

24
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)

25
  • Regulatory Issues

26
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?

27
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 (MICs)
  • develop a standardized test battery of isolates
  • isolates are representative bacterial strains
    two references
  • acceptable MICs are less than 2 ppm

28
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
  • hard to show with shrimp because they have no
    obligate bacterial pathogens

29
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)

30
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

31
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 shrimp at
    detectable levels

32
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

33
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

34
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
  • each successive use could increase proportion of
    drug-resistant microbes

35
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

36
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

37
Investigational New Aquaculture Drug Applications
(INADAs)
  • If this is approved, you can use an unapproved
    aquaculture drug
  • INADAs 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

38
New Animal Drug Applications (NADA)
  • INADAs lead to NADAs
  • NADAs 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, NADAs are submitted by pharmaceutical
    companies manufacturing the drug
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