Dr Kenneth bafundo - Rotations and Shuttles Effective Methods

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					    Rotations and Shuttles:
Effective Methods for Managing
 Coccidial Infection in Modern
        Broiler Production

      Kenneth Bafundo, Ph.D.
       Phibro Animal Health
        Ridgefield Park, NJ
               USA
THE STATE OF RESEARCH
 ON NEW PRODUCTS FOR
 COCCIDIOSIS CONTROL

COMPLETE REVIEW OF THE TOPIC IN
  PROCEEDINGS OF SIPAVI, 2007
 THE STATE OF COCCIDIOSIS
        RESEARCH

• SUMMARY
 – Chemotherapeutic research has stopped
   • Expect few new anticoccidial drugs
 – Vaccine research continues
   •   Live: new methods of administration
   •   Subunit
   •   Protein
   •   DNA vaccines
  CURRENT STATE OF COCCIDIOSIS
   DEVELOPMENTAL RESEARCH


• BIOTECH DEVELOPMENTS
 – PROVIDE NEW RESEARCH PLATFORM
 – NEW CONCEPTS
 – NEW METHODOLOGIES
• FUTURE PRODUCTS COULD BE
  SUBSTANTIALLY DIFFERENT THAN
  THE ONES WE USE TODAY
  NEW TECHNOLOGIES ARE
        POSSIBLE
• BIOTECH DEVELOPMENTS
 – PROVIDE NEW RESEARCH PLATFORM
 – NEW CONCEPTS
 – NEW METHODOLOGIES


• TECHNOLOGICAL ADVANCEMENTS
  SUGGEST THAT NEW PRODUCTS
  COULD BE ABOUT 10 YEARS AWAY
         FUNDING
WHO WILL FUND THE RESEARCH
 FOR THE NEXT GENERATION OF
   COCCIDIOSIS PRODUCTS?

     PHARMACEUTICAL INDUSTRY?
        POULTRY INDUSTRY?
          GOVERNMENTS?
            OTHERS?
              WHO?
    FUNDING
PHARMACEUTICAL INDUSTRY?
   POULTRY INDUSTRY?
     GOVERNMENTS?
       OTHERS?
    FUNDING
PHARMACEUTICAL INDUSTRY?
   POULTRY INDUSTRY?
     GOVERNMENTS?
       OTHERS?




     GOVERNMENT
               FUNDING
• WHILE GOVERNMENTAL FUNDING
  MAY SEEM LIKE THE BEST BET:
 – ONLY A FEW GOV’TS SUPPORT SUCH
   WORK
 – GOV’TS CHANGE PRIORITIES
   • E.G. : USDA

    WE ARE DEALING WITH AN ENDEMIC
     PARASITE THAT IS NOT OF HUMAN
         HEALTH SIGNIFICANCE
         FUNDING
GOVERNMENTAL FUNDING MAY BE
  ERRATIC, NON EXISTANT OR BE
  SUPERCEDED BY DISEASES OF
  PUBLIC HEALTH SIGNIFICANCE
             FUNDING
GOVERNMENTAL FUNDING MAY BE
  ERRATIC, NON EXISTANT OR BE
  SUPERCEDED BY DISEASES OF
  PUBLIC HEALTH SIGNIFICANCE


“…if commercial companies and governments are
    not prepared to invest in basic research on
   Eimeria, then success will not be achieved.”
             Dalloul and Lillehoj, 2006
 WHAT WILL WE RELY UPON
FOR COCCIDIOSIS CONTROL?
  WHAT WILL WE RELY UPON
 FOR COCCIDIOSIS CONTROL?

• WHAT WE HAVE TODAY
 – IONOPHORES
 – CHEMICALS
 – VACCINES
  CHALLENGES TO EXISTING
   ANTICOCCIDIAL USAGE

• PRACTICAL BIOLOGY
 – RESISTANCE
 – OVERUSE, ABUSE
 – MISUSE OF IONOPHORES
   • INAPPROPRIATE DOSAGE
   • FEEDING FOR INADEQUATE AMOUNT OF TIME
           RESISTANCE

• FOR CHEMICALS: WIDELY ACCEPTED
  – NICARBAZIN AN EXCEPTION


• FOR IONOPHORES:
  – EXTENSIVELY RESEARCHED
  – EARLY WORK SHOWED LITTLE CORRELATION
    TO FIELD SITUATIONS (CHAPMAN, 2005)
  – IN THE USA, RESULTS SINCE 2000 SUGGEST
    THAT CHANGES IN IONOPHORE EFFICACY ARE
    OCCURING
    MAJOR IONOPHORES

• SALINOMYCIN AND MONENSIN

• BOTH GENERIC FOR MANY YEARS
 – LOW PRICED
 – TENDENCY TO USE CONTINUOUSLY
   WITHOUT ROTATION
 – OVERUSE AND ABUSE (USA, EUROPE,
   ELSEWHERE)
   • COCCIDIOSIS PROBLEMS
      IONOPHORE USE: USA
• SINCE THE 1990s, OVERUSE AND
  FREQUENT ABUSE OF MAJOR
  IONOPHORES
  –   Cost driven lack of rotation
  –   Extended low dosage usage
  –   Minimal shuttle usage
  –   No consistent vaccine usage
• IN THE USA, EROSION OF MAJOR
  IONOPHORES IS NOW EVIDENT
• CONSISTENT WITH PUBLISHED
  RESEARCH (JEFFERS, 1989)
    IONOPHORE USE: USA
• INCREASE IN COCCIDIAL LESIONS
  AND RESULTANT CHANGES IN
  PERFORMANCE
 – E. acervulina, E. maxima
• SECONDARY COMPLICATIONS
  COMMON
 – Gangrenous dermatitis
Gross Lesions Scores for Field Isolates of Eimeria
   acervulina Collected during 1994-95 After
 Exposure to Non-Medicated, Semduramicin 25
          ppm or Salinomycin 66 ppm

  4
                             Eimeria acervulina
 3.5
                    1994-
  3                 95
 2.5

  2

 1.5

  1
                 SEM SAL
                 25  66

 Bafundo and Hopkins, 2000
Gross Lesions Scores for Field Isolates of Eimeria
 acervulina Collected during 1994-95 and 1998-
    2000 After Exposure to Non-Medicated,
 Semduramicin 25 ppm or Salinomycin 66 ppm

  4
                              Eimeria acervulina
 3.5
                    1994-              1998-
  3                 95                 2000
 2.5                                       Anticoccidial x year interaction (P<.05)


  2

 1.5

  1
                 SEM SAL         NMC SEM SAL
                 25  66              25  66

 Bafundo and Hopkins, 2000.
 DAY 18 LESION SCORES
      U.S. FLOOR PENS STUDY WITH
           IONOPHORES IN 2008

                 E. acervulina lesions
1.8
       ab                                 a


1.5                     ab
             b                      b

1.2



0.9
       Non   Sem       Mon          Sal   Nar
       Med    25       110          66     80
 DAY 18 LESION SCORES
      U.S. FLOOR PEN STUDIES WITH
            IONOPHORES IN 2008

                   E. tenella lesions
 1                       a
        a                                 a
0.8

0.6                                 ab

0.4          b

0.2

 0
       Non   Sem       Mon          Sal   Nar
       Med    25       110          66     80
  GANGRENOUS DERMATITIS
• Exact pathogenesis is unclear
• Clostridium perfringens and C. septicum
  involved
• Experimental models do not yet exist
• In the US, litter is not changed
• Onset >28 days of age
• According to Ritter (2009), GD is highly
  correlated with ionophore usage
  – Coccidiosis?
• Field reports indicate that chemical
  anticoccidials will prevent GD
  OVERUSE OF IONOPHORES

We must be realistic:
• IONOPHORES HAVE BEEN USED FOR
  NEARLY 40 YEARS
• FED TO HUNDREDS OF BILLIONS OF
  CHICKENS

• CAN WE REALISTICALLY EXPECT THEM TO
  PERFORM OPTIMALLY WHEN SUBJECTED
  TO ABUSE?
EFFECTS ON IONOPHORE
    COMBINATIONS


 DO CHANGES IN IONOPHORE SENSITIVITY
  AFFECT THE PERFORMANCE OF OTHER
               DRUGS?
  Mean Reduction in Coccidiosis
  Lesion Scores: Various Drugs
                Coccidiosis Vaccine Strains*
                         Used as a Control


                E. acervulina    E. maxima        E. tenella
                                % Reduction

NIC 125            93               100               90

NAR+NIC 80         79                83                93

SAL 66             86                89               83

NAR 80             76                83               80

SEM 25             83                89               93

*Based on coccidia collected from 1 complex using a live vaccine.
   Mean Reduction in Coccidiosis
    Lesion Scores: Ionophores
         21 U.S. Litter Samples Collected and Evaluated for
                   Ionophore Sensitivity in 2008*


                        E. acervulina             E. maxima           E. tenella

                               ------Percent Reduction After Challenge-------

  SAL 66                       29                       40                 35

  NAR 80                       28                       35                 17

  SEM 25                       42                       52                 50


*Each isolate tested in 3 reps of 8 broilers or 504 birds total.
   Mean Reduction in Coccidiosis
   Lesion Scores: Various Drugs
   21 US Coccidial Isolates Evaluated for Sensitivity

              E. acervulina        E. maxima          E. tenella


                   -------Percent Reduction After Challenge-----

NIC 125            74                   78                87

NAR+NIC 80         40                   51                46

SAL 66             29                   40                35

NAR 80             28                   35                17

SEM 25             42                   52                50
   AVERAGE PERCENT REDUCTION IN
     LESION SCORES INVOLVING 61
   ISOLATES OF U.S. FIELD COCCIDIA*

                                E. acervulina     E. maxima      E. tenella



Nicarbazin 125                        70               76            94

Nar + Nic       80                    33               42            49



    *61 isolates produced from 47 litter samples from US farms. Based on
    comparison to non-medicated controls for 40 E. acervulina, 8 E. maxima
    and 13 E. tenella isolates
  OVERUSE OF IONOPHORES

We must be realistic:
• IONOPHORES HAVE BEEN USED FOR
  NEARLY 40 YEARS
• FED TO HUNDREDS OF BILLIONS OF
  CHICKENS

• WE MUST USE THESE PRODUCTS
  WISELY
               IN REPONSE
•   ROTATION
•   IN WINTER, INCREASE IN NICARBAZIN AND
    NICARBAZIN-BASED ANTICOCCIDIAL
    PROGRAMS
    –   INCLUDES LONGER FEEDING OF NICARBAZIN
•   IN WARM WEATHER, INCREASE IN
    VACCINATION
    –   VACCINE USE HAS DOUBLED THIS SUMMER
•   INCREASE IN LENGTH OF MEDICATED
    FEEDING
      ROTATION




IS ROTATION EFFECTIVE?
                        Effect of Rotation on Gross Coccidial
                          Lesions from One U.S. Complex
          140
                                                                                                               1.73
                Salinomycin                                                                      Salinomycin
          120                                                                                           2.08

          100
                 1.24                         Ionophore Rotation
                         1.13

          80
Percent




                                                                                                 1.2
                                       0.77                          0.56   0.91
          60                                          0.77   0.65                  0.53   0.56
                                0.44          0.43
          40

          20

           0
                 May     June   July   Aug    Aug      Aug    Sept    Oct   Oct    Nov    Feb    July   Aug    Dec

                                                     Monitoring Dates
    LOSS OF IONOPHORE
  SENSITIVITY AND ROTATION

• UNLIKE RESISTANCE TO CHEMICALS,
  IONOPHORE RESISTANCE IS:

 – UNSTABLE IN ABSENCE OF
   CONTINUOUS IONOPHORE USAGE
   (Chapman, 1984)


 – RESPONSIVE TO INCREASED DOSAGE
   (Jeffers, 1989)
SHUTTLE PROGRAMS

 DO THEY WORK?
     FROM IONOPHORE TO
      SHUTTLE PROGRAMS

• AGRISTATS
  – UP TO 2003-04, STRAIGHT IONOPHORE
    AT LOW DOSAGES
  – BETWEEN 2003 AND 2004,
    NICARBAZIN BASED SHUTTLES MORE
    THAN DOUBLED (225% INCREASE)
   FROM LOW DOSAGE TO
  TRADITIONAL PROGRAMS


• FROM: STRAIGHT SALINOMYCIN
  – 44 TO 55 PPM


• TO: NICARBAZIN 125 PPM  IONOPHORE
  – WINTER 2003-4 (DEC. TO MARCH)
  – MULTIPLE COMPANIES
  – OVER 1 BILLION BIRDS FED THIS SHUTTLE
    FROM LOW DOSAGE TO
       TRADITIONAL

• AGRI STATS RESULTS (ACROSS INDUSTRY):
  – GENERALLY, 3 POINT IMPROVEMENT IN F/G
    • E.G. 1.87  1.84; in a 2.2 Kg CHICKEN
    • ~68 g FEED / BIRD SAVED
  – FEED SAVINGS: ~68,000 TONS @ $143 US
    PER METRIC TON


• NET FEED SAVINGS: >$9,700,000
  INFLUENCE OF PROGRAM
        CHANGES

FOLLOWING STRAIGHT IONOPHORE
 USE, CHANGING TO A CHEMICAL 
   IONOPHORE SHUTTLE REDUCED
  DAYS TO 2.2 kg BY ALMOST 1 DAY



  D. Chapman, Poultry Sci. 80: 572-580, 2001.
    INFLUENCE OF PROGRAM
          CHANGES


  CHANGING FROM A CHEMICAL 
     IONOPHORE SHUTTLE TO A
       STRAIGHT IONOPHORE
   INCREASED DAYS TO 2.2 kg BY
          ABOUT 1 DAY

D. Chapman, Poultry Sci. 80: 572-580, 2001.
      RATIONALE FOR SHUTTLE
            PROGRAMS

•   IMPROVED COCCIDIOSIS CONTROL
•   BETTER PERFORMANCE
•   BETTER FINANCIAL RETURN
•   REDUCED RESISTANCE
    DEVELOPEMENT
  IMMUNITY AND
WITHDRAWAL TIMES
              THE BELL CURVE OF COCCIDIOSIS
                        VACCINATION
          8

          6
LESIONS




          4

          2

          0
               7   14   21    28   35      42   49   54
                             DAYS OF AGE
              THE BELL CURVE OF COCCIDIOSIS
                        IONOPHORE
          8

          6
LESIONS




          4

          2

          0
               7   14   21     28   35     42   49   54
                             DAYS OF AGE
    THE BELL CURVE OF COCCIDIOSIS
8

6

4

2

0
     7   14   21     28   35     42   49   54
                   DAYS OF AGE
               COCCIDIOSIS BELL CURVE
          AS AFFECTED BY EARLY WITHDRAWAL
          8

          6
LESIONS




          4

          2

          0
              7   14   21     28   35     42   49   54
                            DAYS OF AGE
      TIMING OF LESIONS

• COCCIDIAL LESIONS ARE AFFECTED BY THE
  IMMUNE STATUS OF THE FLOCK
• OCCUR UNDER VACCINATION AND DRUG
  PROTECTION
• WITHDRAWAL OF ANTICOCCIDIAL DRUGS
  SHOULD BE COORDINATED WITH IMMUNE
  ONSET
• STRONG ANTICOCCIDIAL PROGRAMS
  (STARTER PRODUCTS) INFLUENCE LESIONS
  AT 35 DAYS OR GREATER
    1.6 TO 1.8 Kg BROILER
• NORMALLY REQUIRES HIGHER LEVEL OF
  DRUG PROTECTION
• NOT MUCH CHANCE (TIME) FOR
  IMMUNITY TO BE A MAJOR INFLUENCE
  ON THE PROGRAM
• RELIANCE ON NICARBAZIN-BASED
  SHUTTLES AND SHORT WD TIMES
     2 to 2.5 Kg BROILER

• MORE TIME FOR IMMUNITY TO PLAY A
  ROLE
• POTENTIAL FOR LOWER DOSAGES AND
  STEP UP PROGRAMS
• MAY BE ABLE TO USE LONGER WD
  PERIODS
       3.2 Kg OR GREATER
• IMMUNITY SHOULD BE A KEY PART OF
  THE PROGRAM
• VACCINE USE CAN BE CONSIDERED, IF
  NE CAN BE MANAGED
• LONGER WD PERIODS
• LOWER DOSAGES OF ALL DRUGS WILL
  PROMOTE IMMUNITY
    RECOMMENDATIONS
1. UNDERSTAND THE FUTURE OF
  CHEMOTHERAPY IS NOT BRIGHT
 – IONOPHORES, WHILE STILL EFFECTIVE,
   SHOW SIGNS OF WEAR, ESPECIALLY
   WHEN ABUSED
 – THEY WILL NEED SUPPORT AND
   PRUDENT USE
   • PROPER DOSAGE
   • APPROPRIATE DURATION OF USE
    RECOMMENDATIONS

2. SHUTTLE PROGRAMS AND
  ROTATIONS ARE EFFECTIVE MEANS
  OF:
 – MINIMIZING RESISTANCE
 – MAINTAINING OPTIMAL PERFORMANCE
 – MAXIMIZING PROFITABILITY
    RECOMMENDATIONS

3. PRUDENT USE OF VACCINES
 – WILL REPOPULATE HOUSES WITH DRUG
   SENSITIVE STRAINS OF COCCIDIA
 – A VALUABLE PRINCIPLE OVER THE LONG
   TERM
    RECOMMENDATIONS

4. APPROPRIATE TIMING OF
  WITHDRAWAL PERIODS
 – TIMING WD FEED TO COINCIDE WITH THE
   ONSET OF COCCIDIAL IMMUNITY
 – IMPROVES PROFITABILITY
 – REDUCES LATE COCCIDIOSIS PROBLEMS
    RECOMMENDATIONS

5. ENVIRONMENTAL MANAGEMENT
 – MINIMIZE STRESS
 – EFFECTIVE VACCINATION
 – AIR AND WATER MANAGEMENT
 – LITTER MANAGEMENT
   • COMPOSTING