Transcript Control of Fish Diseases

Control 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 orFish 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, $$$, limited methodologies
Breeding/genetics can increase disease resistance:
rainbows (furunculosisr), brown trout (whirlingr), L.
vannamei (WSSVr)
Common problem: breeding in resistance usually
means breeding out growth...oops!
4) Destruction/Reduction of
Other Hosts in Life Cycle
Can be effective against most metazoan
parasites
You can try to eliminate some snails, keep
birds out (Problems with permits?)
Difficult to eradicate vertebrates: most are
“protected”
Herons, egrets, etc.
5) Drug Therapy: Cure, Crutch
or Wheelchair??
Tried-and-true-method for fish/shrimp, but…
Resistance, cost, approval issues?
$$$$: 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 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:
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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, 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 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 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 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 highhealth 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:
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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:
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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:
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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:
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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
http://www.aphis.usda.gov/lpa/pubs/fsheet_faq_notice/fsfaqnot_animalhe
alth.html
APHIS’s Center for Emerging Issues (CEI) has various
worksheets available on animal health and diseases of
concern
http://www.aphis.usda.gov/vs/ceah/cei/worksheets.htm
Aquatext.com -- a free, online aquaculture dictionary
http://www.pisces-aqua.co.uk/aquatext/dicframe.htm
State Agricultural Response Team
34
Key Resources
Florida Department of Community Affairs, Division of
Emergency Management
http://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
State Agricultural Response Team
35
Key Resources
Florida Division of Aquaculture home page
http://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 Center
http://aquanic.org
State Agricultural Response Team
36
Key Resources
USDA 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 link
http://www.cdc.gov/nasd/videos/v001401-v001500/v001433.html
State Agricultural Response Team
37
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
http://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 links
http://edis.ifas.ufl.edu/DEPARTMENT_VETERINARY_MEDICINE
http://edis.ifas.ufl.edu/DEPARTMENT_FISHERIES_AND_AQUATIC_SCIENCES
State Agricultural Response Team
38