Practical management of bacterial diseases in finfish aquaculture to minimize AMR

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FMM/RAS/298: Strengthening capacities, policies and national action plans on prudent and responsible use of antimicrobials in fisheries Final Workshop in cooperation with AVA Singapore and INFOFISH 12-14 December, Concorde Hotel, Singapore Practical management of bacterial diseases in finfish aquaculture to minimize AMR LARRY HANSON hanson@cvm.msstate.edu

ANTIMICROBIAL RESISTANCE MANAGMENT o AVOID DEVELOPMENT- Biosecurity Disease prevention Alternative treatments Judicious use o REDUCE PERSISTANCE of AMR Crop rotation/complete harvest Monitoring and disinfection? Antibiotic use restriction or rotation

Disease prevention- reduces need for antibiotics If you don t correct underlying cause disease will reoccur after treatment Pathogen Host Disease Environment

Disease prevention starts at the planning stage and is continuous o Site selection Soil type- Alkalinity, hardness (conditions stabilize algal populations and provide essential minerals) Water source- (biosecurity, temperature, volume, nutrients, contaminants) Location- local stressors, predatory bird roosting sites, flyways, proximity to aquaculture or wild fisheries, Cages-tidal flushing proximity to other aquaculture and prevalence of toxic algae o Fish Genetics- selection for disease and stress resistance

Disease prevention o Manage the environment to minimize stress and physical injury Water quality- Oxygen Ammonia Nitrite/chloride Handling Avoid rough handling- damage to mucus layer Avoid handling at critical temperatures or stages Manage predators Prevent aggression and cannibalism- remove dead fish from pond

Feeding management o Good quality feed, freshness and amount Nutritionally complete- protein vitamins and fatty acids Stored in dry place and used quickly o Physical- Proper size for fish- too large can damage mouth, too small wastage & nutrient loss o Amount and frequency- Want to evenly distribute to all fish for even growth Too much may bypass acid stomach barrier o Avoid pathogens- live feeds must be disease free and pasteurize any fresh feeds.

Prevent all diseaseso Actively manage to minimize viral and parasitic diseases (Predispose fish to bacterial disease and suppress feeding- resulting in subtherapeutic treatments)- o Vaccines-if effective for bacterial pathogens and viruses

Biosecurity- avoid obligate pathogens and introduction of AMR o Surveillance, quarantine and monitoring o Used of certified specific pathogen free stocks o Use pathogen free water, and processed feeds or SPF live/fresh feeds o Between farm security- On farm equipment, nets Limited access Cleaning/disinfecting trucks, trailers, boats entering facility o Within farm security Avoid water movement between ponds Disinfect nets and equipment Predator and scavenger control- mammals, birds and reptiles can shed fish pathogens

Biosecurity-Avoiding obligate pathogens and AMR strains o Fish source- critical factor Improper use of antibiotics during early stages can result in build up in system Fry and eggs sometimes given prophylactic bath treatments during handling- these may be critical during establishment of microbial flora and allow establishment of AMR. Know how fish produced and antibiotic usage- hatchery GAP Due to economics of hatchery systems and susceptibility of young- improper use of antibiotics at this stage is more common (also opportunity to spread pathogens and antibiotic resistance through industry) Disinfection of tanks and ponds between batches. Separation of eggs from brooders and disinfection of egg surface (iodine, formalin, potassium permanganate)

Alternatives to treatment o Many diseases do not need to be treated with antibiotics- disease and environment- evaluated by a professional who understands the system Many bacterial disease are secondary- correct predisposing factor or allow to run its course o Management to reduce pathogen load or transmission dose Fecal oral transmission- Allow time for gut to clear before feeding- reduces defecation where feeding- ESC every-other day feeding during peak disease season (feed restriction may help with others by reducing close contact) Probiotics or prebiotics?

Non-antibiotic alternatives o Chemical treatments that interrupt transmission or stimulate resistant state in host Copper sulfate makes catfish less susceptible to columnaris disease Salt 1-5 ppt reduces F. columnare s ability to adhere to fish Potassium permanganate, chloramine T and other oxidizers kill surface bacteria and free bacteria in the water

Judicious Use of Antibiotics-medicated feeds- minimizes selective pressure o Use when needed and effective Must be diseased- no prophylactic use, no use for growth promotion must be susceptible bacteria pathogen- susceptibility testing Fish must feed well enough to get a therapeutic dose o Give for full treatment duration- antibiotic must persist long enough to kill pathogen o Use fresh good quality medicated feed- reliable licensed feed producer o Careful feeding practices- avoid wastage- AMR can develop in bacteria that grow in wasted feed

Eliminate improper use o Do not use on non- bacterial diseases o No prophylactic use- to prevent something that may happen o Do not use where non-therapeutic levels occur Bath treatment where poor uptake occurs and persistence of antibiotic is not adequate to kill the pathogen Medicated feed if not feeding fast enough or feeding poorly Medicated feed for less than recommended treatment period

REDUCE PERSISTANCE o Minimize use-amr is a natural process. There is cost to the bacteria to maintain this state, minimal antibiotic use will minimize selective pressure and result in lower numbers of AMR pathogens. o Complete harvest and disinfection of production system prevents build up in system. o o Crop rotation if practical- breaks pathogen cycle Voluntary antibiotic use restriction or rotation on a facility for 2-3 production cycles. o Impact of antibiotic use may be broad- many R-plasmids code for more than one resistance gene so use of any of these antibiotics helps maintain it in the population (characterize R-Plasmids?).

Examples in Channel catfish production o Major pathogens Flavobacterium columnare Edwardsiella ictaluri (Enteric septicemia of catfish) and E piscicida Aeromonas hydrophila o Approved antibiotics- All medicated feeds all by Veterinary prescription Terramycin-Oxytetracycline 10 days- 21 day withdrawal (rarely used- has been in past) Romet- Sulfadimethoxine-Ormetoprim 5 days- 3 day withdrawal (occasionally used) Aquaflor- Florfenicol 10 days- 15 day withdrawal (commonly used) o Cost $800 per ton vs. $390 for non-medicated- use of medicated feed affected by economics

Routine stress management o Dissolved oxygen intensely managed over summer months o Chlorides maintained above 100ppm to reduce nitrite toxicity o Use fresh, well formulated feeds o Stock fish in cool months to reduce handling stress

Columnaris disease Flavobacterium columnare produces necrotic lesions on skin and gills. Very often secondary to other pathogens or physical damage.

Management o Avoid damaging mucus layer- Handle during cool weather Use smooth surfaces or water cushion when handling Treat hauling tanks with 1-3 ppt salt Avoid damage to gills- particulates, ammonia, parasites o Manage ESC, Winter mortality, CCV o Vaccinate (effectiveness in fry not great, likely better in older fish) o Treatment with copper sulfate has been shown to help, don t restrict feed o Antibiotic medicated feed- Aquaflor (labelled), Terramycin not labelled effective but not used, Romet not labelled and may not be effective o AMR does not appear to be common (often not evaluated) but bystander effect-other bacteria become AMR

Enteric Septicemia of catfish o Gram- enteric bacterium Edwardsiella ictaluri invades the host through the intestinal mucosa. Facultatively intracellular. o High losses after stress or in naïve population (especially fingerlings) o Temp window 22-27 C. o E. piscicida infections similar

management o Avoid stress (DO and Nitrite) o While in temperature window- feed on alternate days This reduces transmission- enteric pathogen. Gut clearance before feeding reduces bacterial shedding when fish concentrated for feeding. (Wise & Johnson 1998. J. World Aquac Soc 29, 170-176). o Vaccination- helps in fingerlings but losses still occur o Antibiotic treatment- Aquaflor (labelled), Romet (labelled), Terramycin (not labelled) o AMR- relatively common often MDR- FloR and TetR found on self transmissible plasmid

AMR in catfish pathogens- Observations o Highest resistance seen in Aeromonas sobria This is a secondary pathogen, not usually the target of antibiotic treatment but often present during columnaris disease Also highest resistance to terramycin which is rarely used now o Second highest level of resistance seen in E. ictaluri If resistant, usually resistant to both Aquaflor and Terramycin Industry has seen increasing levels of Aquaflor resistance. May seriously impact treatment options. o Challenges- much of industry uses continuous production (partial harvest of population and restocking) allowing build up of AMR in system. Some systems now going to batch production

Summary o Management to minimize diseases is the most important component for AMR management o AMU only when necessary and effective The cost of treating now includes the loss of options in future o Antibiotic resistance will develop and may occur in non-target pathogens