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Joan Burke, Ph.D. Small Ruminant Integrated Parasite Control FAMACHA & Smart Drenching

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    Small Ruminant IntegratedSmall Ruminant Integrated

    Parasite ControlParasite ControlFAMACHAFAMACHA

    and Smart Drenchingand Smart Drenching

    Southern Consortium for Small Ruminant

    Parasite Control

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    TopicsTopics

    The problem

    The parasites; where we are and why

    Biology of important GI Parasites Dewormers a quick review

    What can we do?

    Smart Drenching

    FAMACHA

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    The Big Problem facingThe Big Problem facing

    producersproducers

    Anthelmintic (dewormer) resistance is

    considered a major threat to the

    current and future control of parasites

    of ruminants and horses

    Worldwide phenomena

    The prevalence ofmulti-drug resistantworms is extremely high in many areas

    of the world

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    What is Resistance?What is Resistance?

    The ability of certain worms in a population to

    survive drug treatments that are generally

    effective against the same worm species and

    stage of infection

    Caused by changes in levels of resistance

    genes carried by worms in a population

    Result of drug treatment that produces genetic

    selection of resistant worms in a population of

    worms

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    Dewormer ResistanceDewormer ResistanceHistory of the ProblemHistory of the Problem Age of modern dewormers

    Effective, broad-spectrum, cheap, safe

    Over-reliance on dewormers

    Addiction to drugs, improper use of dewormers Loss of common sense approaches

    Belief there will always be a new drug

    No new drug classes introduced since 1981

    We have what we have !!!!

    New anthelmintic announced by Novartis in 2007, but

    will not be available for many years to come

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    Where Do ResistantWhere Do Resistant

    Worms Come From ??Worms Come From ?? Resistance is an inevitable consequence of using any particular drug

    to kill worms

    Resistant worms worms that can survive drug treatment,

    actually exist prior to the first use of a drug

    Treatment eliminates worms whose genes render themsusceptible to the drug

    Parasites that are resistant survive and pass on their resistant

    genes to their offspring

    Over time with continued treatment, more and more resistant

    worms build up in the population

    High level of animal movement spreads resistant worms (Animals

    shipped from state to state or country to country carry their worm

    infections with them)

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    Parents

    R

    es

    ista

    nt

    Susce

    ptib

    leNext Generation

    Drug Treatment

    Res

    ista

    nt

    Selection forDrugResistance

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    Perc

    ent o

    f

    Worm

    sthat

    Are

    Resi s

    tan t

    Changes in Resistance GenesChanges in Resistance Genes

    in Response to Drug Selectionin Response to Drug Selection

    Worm Generations(exposed to repeated treatments)

    Detection level with tests

    Apparent as a clinical problem

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    Southern Consortium for SmallSouthern Consortium for Small

    Ruminant Parasite ControlRuminant Parasite ControlDr. Ray Kaplan, UGA, GAMr. Bob Storey, UGA, GA

    Ms. Sue Howell, UGA, GA

    Dr. Lisa Williamson, UGA, GA

    Dr. Tom Terrill, FVSU, GA

    Dr. Will Getz, FVSU, GA

    Dr. Seyedmehdi Mobini, FVSU, GA

    Dr. Jim Miller, LSU, LA

    Dr. Joan Burke, USDA-ARS, AR

    Dr. Jorge Mosjidis, AU, AL

    Dr. Elide Valencia, UPR, PR

    Dr. Anne Zajac, VT, VA

    Dr. Stephan Wildeus, VSU, VA

    Dr. Steve Hart, LU, OK

    Dr. Jean-Marie Luginbuhl, NC St, NC

    Dr. Jim Muir, TAMU, TX

    Dr. Dahlia Jackson, DSU, DE

    Dr. Niki Whitley, UMES, MDMs. Susan Schoenian, WMREC, MD

    Mr. Stuart Weiss, UVI, St. Croix

    Ms. Linda Coffey, NCAT, ATTRA

    Ms. Margo Hale, NCAT, ATTRA

    Dr. Adriano Vatta, OVI, South Africa

    Dr. Jan van Wyk, U Pretoria South Africa

    Dr. Gareth Bath, U Pretoria South Africa

    A Fresh Approach Is Needed!A Fresh Approach Is Needed!

    www.scsrpc.orgwww.scsrpc.org

    www.wormx.orgwww.wormx.org

    http://www.scsrpc.org/http://www.scsrpc.org/http://www.wormx.org/http://www.wormx.org/http://www.wormx.org/http://www.scsrpc.org/
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    SCSRPC ProjectsSCSRPC Projectswww.scsrpc.org www.wormx.orgwww.scsrpc.org www.wormx.org

    FAMACHA validation and evaluation

    Copper-oxide wire particle bolus

    Condensed tannin containing forage

    Integrated approaches

    Host resistance studies

    Nematophagous fungi

    Vaccines

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    Gastrointestinal NematodesGastrointestinal Nematodes

    (Worms) of Sheep and Goats(Worms) of Sheep and Goats

    Most Important Species:

    1. Haemonchus contortus ***

    Barberpole worm1. Teladorsagia (Ostertagia) circumcincta

    Brown stomach worm

    1. Trichostrongylus colubriformis Bankrupt worm

    1. +/- Nematodirus

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    Life Cycle of GI Worms

    L2L3

    L1L3

    L3

    http://mirror-us-ga1.gallery.hd.org/_exhibits/natural-science/_more2007/_more04/ram-sheep-on-farm-in-grass-field-at-Neals-Farm-Checkendon-Oxfordshire-England-4-DHD.jpg
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    Haemonchus contortusHaemonchus contortus(Barber Pole Worm)(Barber Pole Worm)

    PUBLIC ENEMY NUMBER ONEfor small ruminant farmers

    Literally a blood sucking worm

    Very prolific one adult female can produce 5000 eggs per day

    Short life cycle about 3 weeks from time of infection until eggs are

    produced

    Preys on the weak, young, pregnant, or lactating animal

    Developing resistance to all classes of dewormers

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    Haemonchus contortusHaemonchus contortus

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    Bottle Jaw

    Anemia

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    Why isWhy is H. contortusH. contortusSuchSuch

    a Problem ???a Problem ???

    Evolved in tropics

    thrives in warm/wet climates

    Long transmission season in southern states Short life cycle

    Goats acquire only partial immunity

    Immunity is slow to develop in sheep Kids and Lambs are highly susceptible

    Immunity wanes around time of kidding/lambing

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    Why isWhy is H. contortusH. contortusSuchSuch

    a Problem ???a Problem ???

    Very prolific each female worms

    produces ~ 5,000 eggs per day

    500 worms 2.5 million epd per animal 50 goats 1 billion eggs per week

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    Goats Were Never Intended toGoats Were Never Intended to

    Live (and Graze) in a WarmLive (and Graze) in a Warm

    Humid ClimateHumid Climate

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    TeladorsagiaTeladorsagia((OstertagiaOstertagia)) circumcinctacircumcincta

    (Brown stomach worm)(Brown stomach worm)

    Most important parasite of sheep/goats in cool

    climates (e.g., Scotland, NZ)

    Tiny worms develop in gastric glands of

    stomach (abomasum)

    as worms grow they destroy the glands

    affects appetite, digestion and nutrient

    utilization Clinical symptoms

    diarrhea, reduced appetite, weight loss

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    TeladorsagiaTeladorsagiainin

    gastric glandsgastric glands

    Damage toDamage to

    stomach wallstomach wall

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    Resistance RevisitedResistance Revisited

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    So far.So far.

    Weve briefly discussed resistance

    Weve talked about parasite life cycles

    Weve talked about drugs in general

    and farms not having any dewormers

    that still work

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    So, How did we get here?So, How did we get here?

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    By doing what we thoughtBy doing what we thought

    was right, based on whatwas right, based on what

    we knewwe knew

    (what was recommended by(what was recommended bythe experts)the experts)

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    The Traditional ApproachThe Traditional Approach

    to Parasite Managementto Parasite Management

    Treated entire herd

    Dewormed by the calendar

    Rotated dewormers regularly

    One Pasture may be only option

    Over crowding/grazing

    If multiple pastures, dewormed at move to new

    pasture

    Unknowingly purchased resistant worms

    Wh t C R i t

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    What Causes ResistanceWhat Causes Resistance

    To Dewormers ???To Dewormers ???

    Lack of Refugia Refugia = the proportion of the worm population that

    is not selected by drug treatment

    Worms in untreated animals

    Eggs and larvae on pasture

    Provides pool of sensitive genes

    Dilutes resistant genes Considered the most important factor in the

    development of drug resistance

    Wh t C R i t

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    What Causes ResistanceWhat Causes Resistance

    To Dewormers ???To Dewormers ???

    1. Treatment strategies that refugia Examples:

    Treating and moving to clean pasture

    Treating when few larvae are on the pasture (drought) Treating all animals at same time

    1. Frequent Treatments > 3 treatments per year

    1. Under dosing

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    Resistance is InevitableResistance is InevitableWhat Can We Do ???What Can We Do ???

    Resistance is a natural biological

    consequence of drug treatment

    Rate of development of resistance is within

    our control and can be greatly reduced

    Goal = Preserve drug

    efficacy for as long as possible

    Increase refugia

    Selective treatment

    Cl f A th l i ti

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    Classes of AnthelminticsClasses of Anthelmintics

    (Dewormers)(Dewormers)

    1. Benzimidazoles (BZ) fenbendazole (FBZ; Panacur, Safegard)

    albendazole (ABZ; Valbazen)

    1. Avermectin / Milbemycins ivermectin (IVM; Ivomec)

    moxidectin (MOX; Cydectin)

    1. Imidazothiazoles / Tetrahydropyrimidines levamisole (LEV; Tramisole, Levasole), morantel

    (MOR; Rumatel, Golden Blend, others)

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    Resistance Occurs WithinResistance Occurs Within

    Classes of AnthelminticsClasses of Anthelmintics

    Resistance to one drug in a class

    confers resistance to all others

    same mechanism of action

    Exceptions to this are due to

    differences in potency and are onlytemporary

    f G

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    Prevalence of Resistance on Goarevalence of Resistance on Goa

    Farms in Georgia (2001)Farms in Georgia (2001)

    Albendazole (Valbazen) & Ivermectin (Ivomec) > 90%

    Levamisole (Tramisole)

    ~ 30%

    Moxidectin (Cydectin)

    none detected in 2001

    40% of farms in 2003 (where MOX was usedas predominant dewormer

    Evaluation of prevalence and clinical implications ofEvaluation of prevalence and clinical implications of

    anthelmintic resistance in gastrointestinal nematodes ofanthelmintic resistance in gastrointestinal nematodes of

    goats. Mortensen, et al.,goats. Mortensen, et al.,JAVMA,JAVMA, 223(4):495-500 (2003)223(4):495-500 (2003)

    P l f R i tP l f R i t

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    Prevalence of Resistance onPrevalence of Resistance on

    Sheep & Goat Farms (SE USA)Sheep & Goat Farms (SE USA)

    (Accumulated Data from 2002-2006)(Accumulated Data from 2002-2006)

    Dewormer Prevalence of

    ResistanceBenzimidazole 98

    Levamisole 54

    Ivermectin 76Moxidectin 24

    MDR all 3 classes 48

    MDR to all 3 classes + Moxidectin 17

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    Prevalence of AnthelminticPrevalence of Anthelmintic

    Resistance in Sheep:Resistance in Sheep:

    New Zealand and AustraliaNew Zealand and Australia Australia (WA)

    IVM 60%

    ABZ 99%

    LEV 99%

    New Zealand

    IVM 25%

    ABZ 41%

    LEV 24%

    Triple resistant 7%Moxidectin (Cydectin) resistance still is relatively

    uncommon (but it is being increasingly reported)

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    TotalTotal Anthelmintic FailureAnthelmintic Failure

    A near-term possibility on many sheep andgoat farms in many areas Many farms are down to their last drug

    Malaysia and South America Some farms reporting TOTAL drench failure

    20% death losses per year

    First case in USA diagnosed by Dr. Kaplanslaboratory in 2005 now seeing more cases Recent study -- TAF on 17% of farms in SE

    Future viability of SR industries is threatened

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    Total Anthelmintic Failureon a Meat Goat Farm in Arkansas, USA

    Drench Control Levamisole Albendazole Ivermectin Moxidectin

    Number 15 14 14 11 15

    Arith. Mean 2490 557 979 2018 563

    % Reduction 78 61 19 77

    Upper 95% CL 88 79 57 88

    Lower 95% CL 57 26 0 57

    Drench effectiveness Resistant Resistant Resistant Resistant

    Wh D t it S AWh D t it S A

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    Why Doesnt it Seem AsWhy Doesnt it Seem As

    Bad As it Sounds ???Bad As it Sounds ??? Your neighbor may be worse off than you US Data is from the southern states

    may be less resistance in the north and west

    Resistance as defined is a population measure Not all worms on farm are resistant

    Killing some worms will relieve disease symptoms Removing 50% of worms gives clinical improvement

    This gives the appearance that treatment was effective Animals will require treatment again very soon

    Obvious treatment failure only recognized onceresistance is severe

    Wh t D Thi M F ThWh t D Thi M F Th

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    What Does This Mean For TheWhat Does This Mean For The

    Small Ruminant Industry ???Small Ruminant Industry ???

    Dewormers can no longer be thought of as a cheap input to

    maximize productivity

    Extremely valuable and limited resources

    Requires a medically-based approach to treatment Control ofHaemonchus must be practiced with an eye to the

    future

    Reality = long-term control ofHaemonchus will only be

    possible if dewormers are used intelligently withprevention of resistance as a goal

    Reduced-chemical and non-chemical approaches are

    needed

    Sl i dSl i d

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    Slowing downSlowing down

    ResistanceResistance

    Given that resistance is inevitable and

    resistance is forever, how do we slow it

    down?

    Reduce genetic selection pressure

    Maintaining a pool of sensitive genes

    REFUGIA Treat individuals, not herds

    Concept known as..

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    Smart DrenchingSmart Drenching

    Using what we have learned to

    develop deworming strategies that

    maximize the effectivenessoftreatments while at the same time

    decreasing the rate at which we

    create drug resistance

    C t f S tComponents of a Smart

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    Components of a SmartComponents of a Smart

    Drenching ProgramDrenching Program

    Know the resistance status of theherd/flock

    Sound pasture management Keep resistant worms off the farm

    Administer the proper dose

    Utilize host physiology Selective treatment -- FAMACHA

    K th R i tKnow the Resistance

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    Know the ResistanceKnow the Resistance

    Status of the FlockStatus of the Flock

    Perform FECRT or DrenchRite

    Repeat every 2 years

    When resistance is recognized in earlystages

    Drug can still be used

    Must be managedappropriately

    Use ProperUse Proper

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    Use ProperUse Proper

    TechniqueTechnique

    Ensure proper dose is delivered

    Proper technique when drenching

    sheep and goats is very important

    drench should be delivered over the back of

    the tongue

    critical that full dose lodges in the rumen

    drench delivered to the mouth maystimulate esophageal groove to close

    significant drench bypasses the rumen

    efficacy is reduced

    Images courtesy ofpremier1supplies.com

    D SD S

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    Dewormer SavvyDewormer SavvyGive theGive the RightRightDoseDose

    Goats: 2X sheep dose

    exceptions

    Levamisole (1.5X)

    Moxidectin

    injectable (1X)

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    Dose According to WeightDose According to Weight

    Weigh scales

    Weight tapes Only accurate

    for dairy goats

    inaccurate inmeat breeds

    Utili H t Ph i l tUtilize Host Physiology to

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    Utilize Host Physiology toUtilize Host Physiology to

    Maximize Drug EfficacyMaximize Drug Efficacy

    Restrict feed intake for 24 hours prior totreatment (BZ and ivermectin)

    Withholding feed decreases digesta flow rate

    leading to an increase in drug efficacy Never in late pregnancy

    Repeat dose in 12 hours (BZ)

    These simple measures can substantiallyimprove efficacy when resistance is present and

    can help to delay resistance if not yet present

    R t ti f DR t ti f D

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    Rotation of DewormersRotation of Dewormers

    Is This a Good Idea ???Is This a Good Idea ???

    Has been promoted for many years

    Although recommended for many years

    there are new arguments against usingrotation

    Rotation is NOT a replacement for properresistance prevention measures

    On many farms, rotation is not possiblebecause of resistance

    Rotation of De ormers IsRotation of Dewormers Is

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    Rotation of Dewormers IsRotation of Dewormers Is

    A Bad IdeaA Bad Idea

    Creates a false presumption among vetsand livestock owners that they have a

    bona-fide resistance prevention program

    Rotation will mask resistance Resistance develops slowly to all drugs

    simultaneously

    1 effective drug will cover for another Few livestock owners realize they have

    resistance problems until it is too late

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    Drug CombinationsDrug Combinations

    Use of combinations of drugs simultaneously have been

    shown to

    Decrease rate with which resistance develops

    Increase the effectiveness of treatment

    Drugs not useful on their own can achieve reasonable

    therapeutic results if combined

    BUT very dangerous if:

    Do not build refugia into system

    Do not do efficacy testing to monitor resistance situation

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    Selective TreatmentSelective Treatment

    FAMACHA

    ForH. contortus only

    For other GI worms

    FEC Age

    Body condition

    Production level Symptoms

    Short term weight gain

    Concept BehindConcept Behind

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    Concept BehindConcept Behind

    Selective TreatmentSelective Treatment

    Parasites are not equally distributed ingroups of animals

    Overdispered / aggregated distributions

    20-30 % of animals harbor most of worms Few animals are responsible for most of egg

    output

    Number of Worms

    Freq

    Di t ib ti f FEC i G t H d

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    Distribution of FEC in Goat Herds

    0

    4000

    8000

    12000

    16000

    20000

    FEC

    0

    1000

    2000

    3000

    4000

    Individual Goats

    FEC

    33% of Goats

    80% of Eggs

    Treating high 33%

    Greatly ReducesDaily Pasture

    Contamination With

    Eggs

    Treating 1/3 ofgoats gives just

    as good control

    as treating the

    entire herd

    230 M

    33%

    46 Million

    66%

    Wh t H If W T t O l th Hi h 33% ???

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    33% of Goats

    < 5% of Eggs

    0

    400

    800

    1200

    1600

    2000

    FEC

    0

    100

    200

    300

    400

    Individual Goats

    FE

    C

    Treating high 33% with a

    drug that causes a 99%FECR reduces daily

    pasture contamination

    with eggs by 80%

    Following treatment

    > 95% of eggs are being

    shed by untreated goats

    = REFUGIA

    Less Resistance

    What Happens If We Treat Only the High 33% ???

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    So, how do we easilydetermine who to treat?

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    FAMACHAFAMACHA

    FaFafafaMaMalanslansChaChartrt

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    The FAMACHAThe FAMACHA SystemSystem

    Eye color chart with five

    color categories

    Compare chart with color of

    mucous membranes ofsheep or goat

    Classification into one of five

    color categories: 1 not anemic

    5 -- severely anemic

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    How Does FAMACHA Work ??How Does FAMACHA Work ??

    Since the primary impact ofH.

    contortus is anemia, one can indirectly

    measure parasite burden (and need fortreatment) by measuring anemia

    Only useful where H. contortus is theprimary parasite species

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    AnemiaAnemia

    Definition a reduction below normal in thenumber or volume of red blood cells in theblood

    Symptoms depend on degree/severity

    Sub-mandibular Edema (Bottle Jaw)

    Unthrifty Condition

    Poor BCS

    Broken coatExercise/Heat intolerance

    Pale mucus membranes

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    Severe AnemiaSevere Anemia

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    Haemonchus contortusHaemonchus contortus

    Heavy burden can result in the loss of cup

    or more of blood per day

    The total blood volume of a goat makes up

    approximately 1/12th its total body weight. A 120 pound goat => 10 pounds of blood => 4.5

    kg of blood => 4.5 liters or 4,500 ml of blood

    volume. 120 ml in cup => 50% blood loss in 37

    days

    Conjunctiva colorConjunctiva color

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    Conjunctiva colorConjunctiva color

    relationship to Anemiarelationship to Anemia

    28Red1

    Hematocrit

    Range (%)

    Color

    Classification

    Clinical

    Category

    1)

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    2) Pull down lower eyelid with other thumb

    1) Place gentle downwardpressure on eye with upper

    thumb

    3) Read color ofeye on mucousmembranes of

    lower eyelid

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    FAMACHAFAMACHA System rulesSystem rules

    Score using the chart

    Evaluate in bright light

    (sunlight)

    Be quick

    Score both eyes

    Use higher score if eyes

    differ

    What Do I Do With TheWhat Do I Do With The

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    What Do I Do With TheWhat Do I Do With The

    Results?Results?

    Always treat goats

    and sheep in

    categories4 and 5

    Dont treat 1s and

    2s

    When should youtreat the 3s?

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    Animals in Category 3Animals in Category 3

    Treat when

    >10% of herd scores in categories 4 or 5

    Young animals

    Ewes/does (pregnant or lactating) Animals in poor body condition

    If any concern about animals general health

    and well being

    Consider using less effective drugs

    H Oft D I M it

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    How Often Do I MonitorHow Often Do I Monitor

    If

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    How oftenHow often

    If>10% of flock/herd scores in

    categories 4 and 5:

    Recheck weekly

    Treat the 3s

    Change pastures (if possible)

    P ti

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    PrecautionsPrecautions

    FAMACHA only applicable where

    Haemonchus is the main worm

    causing clinical disease Conjunctival redness can be

    caused by eye disease,

    environmental irritants, andsystemic disease

    P ti

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    Precautions.Precautions.

    Dont use it as a sole criteria for

    whether or not to drench

    If you see other symptoms such as bottle

    jaw, you know you need to drench

    Look at all available signs

    Body condition score

    Coat condition Consistency of feces

    Heat/exertion intolerance

    Th F h C dTh F h C d

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    The Famacha CardThe Famacha Card

    Store in dark placewhen not in use

    Replace card after 12months use

    Keep a spare card in

    a light protectedplace

    Wh FAMACHAWh FAMACHA

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    Why use FAMACHAWhy use FAMACHA

    Decreased Worm burdens

    Creates Refugia

    Decreased development of

    resistance Saves money

    Identifies animals that need less frequent

    deworming -- keep for breeding

    Identifies animals that need more frequent

    deworming -- cull

    R b R f i (I R f )R b R f i (I R f )

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    Remember Refugia (In Refuge)Remember Refugia (In Refuge)

    Untreated animals

    harbor susceptible

    worms

    Dilutional effect

    Resistance

    develops more

    slowly

    Keep Herd and IndividualKeep Herd and Individual

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    Keep Herd and IndividualKeep Herd and Individual

    Records!!!!Records!!!!

    Example Herd AnemiaExample Herd Anemia

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    Example Herd AnemiaExample Herd Anemia

    RecordRecord

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    Control Parasites by Determining

    Which parasites are present

    When they are being transmitted

    How they survive

    Which anthelminthics are effective

    What dose is required for host species

    When is the most appropriate time to

    administer anthelminthics or use otheralternative control methods

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    Thanks to The 2004 World Sheep and Wool

    Congress For Use of the Slide Design

    Produced by

    Ray Kaplan, DVM, PhD, Dip EVPC,

    Bob Storey, MS, RVTLisa Williamson, DVM, MS, Dip ACVIM

    University of Georgia

    Jim Miller, DVM, MPVM, PhD

    Louisiana State University

    With contributions from other members of the SCSRPC

    Questions ???

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    Questions ???