Transcript Control of Fish Diseases

Control of Aquatic
Diseases
Various Methodolgies Allowing
Control
• Test and Slaughter
• Quarantine and Restriction of Movement
• Immunization and Disease Resistance
• Destruction or Reduction of
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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 orFish 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.
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
2) Quarantine and Restriction
of Movement
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 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 (< 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
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
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
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 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)
Revised Act (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)
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 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
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
External Treatments: dip on
the run
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
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
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) 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
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
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 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)
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:
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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
hard 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
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 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
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 Aquaculture Drug
Applications (INADA’s)
If this is approved, you can use an
unapproved aquaculture drug
INADA’s are, however, used for specific
purposes, many restrictions:
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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’s
NADA’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, NADA’s are submitted by
pharmaceutical companies manufacturing the
drug