NEW STRATEGIES FOR COCCIDIOSIS MANAGEMENT

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NEW OPPORTUNITIES FOR MANAGING SUBCLINICAL ENTERITIS

SETTING STANDARDS FOR COCCIDIOSIS VACCINES

SOLVING THE GANGRENOUS DERMATITIS PUZZLEPLUS

NEW OPPORTUNITIES FOR MANAGING SUBCLINICAL ENTERITIS

SETTING STANDARDS FOR COCCIDIOSIS VACCINES

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2 WORKING UNDERCOVERSubclinical necrotic enteritis often goes undetected, slowly erodes profits

8 TECHNICALLY SPEAKING: ESSENTIAL ELEMENTSArkansas’ Dr. David Chapman presents new guidelines for coccidiosis vaccines

10 COVER STORYSOLVING THE GANGRENOUS DERMATITIS PUZZLEPreventing late coccidiosis cycling with vaccination may halt the growing problem of gangrenous dermatitis

16 COCCI NEWSTrends and research affecting coccidiosis management

Coccivac is a registered trademark and SprayCox is a trademark of Schering-Plough Animal Health Corporation.

1

Cover: Mortality, carcass condemna-tions and trimmed parts can resultfrom gangrenous dermatitis, a costlydisease in broilers. Now, new evidencesuggests that vaccinating for coccidiosismay be the missing piece of the controlpuzzle. For more informations see thearticle beginning on page 10.

Photo courtesy of Dr. Charles Broussard

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PAGE 10

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Agut disease that often goesunrecognized and preventsbroilers from achieving optimal

performance is more common thanthought and is certain to increase aspoultry operations reduce theirdependence on in-feed antibiotics.

The disease is subclinical necroticenteritis (NE), caused by the pathogenClostridium perfringens. Poultry veteri-narians familiar with subclinical NE saythe industry needs to intensify efforts todetect and manage the disease before iterodes performance and profits.

“It’s a big problem,” even though noone really knows the actual incidencebecause it is not easily detected ordiagnosed, says Dr. Steve Davis, presi-dent and chief executive officer ofColorado Quality Research, Wellington.

“The effect is subtle and additive.Performance deteriorates from flock toflock, especially if you aren’t cleaningout your houses. The clostridium in theenvironment increases over time,” hesays.

Conventional flocks at riskSubclinical NE is most likely to be seenin standard broilers that are receivingionophores for coccidiosis control butnot antibiotic growth promoters(AGPs), a pattern becoming more typi-cal in the US poultry industry, Davissays.

“Here at Colorado Quality Research,we saw the direction the industry washeading about 4 years ago and knewthat necrotic enteritis was going to be ahot research topic,” he adds. “That’swhy we developed and fine-tuned alive NE challenge model and, to date,have conducted over 30 NE studies.”

AGPs, Davis explains, have an inad-vertent side benefit. They not only pro-mote growth, they control clostridium.Overuse of ionophore anticoccidials,coupled with extended withdrawalperiods, has resulted in resistant coc-cidia and late cycling of the coccidialchallenge, which results in poor guthealth, setting the stage for develop-ment of NE.

In contrast to subclinical NE, full-blown clinical outbreaks of NE are eas-ily recognized and usually treated dueto high mortality. They are more likelyto occur in antibiotic-free birds and inbirds receiving chemical anticoccidialsor coccidiosis vaccines, which can doan excellent job controlling coccidiosisbut have no secondary antibiotic effectagainst NE, says Davis, who has expe-rience as a live production poultry vet-erinarian.

How C. perfringens affects a flockmight also differ with the isolate. SomeC. perfringens isolates tend to causerapid illness and mortality with lessimpact on the performance of survivingbroilers, while others rarely cause mor-tality but significantly decrease growthand feed conversion, he says.

Missed diagnosis“Producers tend to miss subclinical NEin part because they haven’t had itbefore,” he says. In other cases, there’sa gradual drop in feed efficiency andpoor weight gain that goes unnoticed.The problems may have gone on for solong that producers think it’s normal.There may be liver lesions that result incondemnation at processing. Some-times, subclinical NE isn’t recognizeduntil a change is made in the health

WORKING UNDERCOVERSubclinical necrotic enteritis often goes undetected, slowly erodes profits

Davis: ‘Producers tend to misssubclinical NE.’

3

program and they see improved per-formance.

Davis’ work has led him to believethat subclinical NE affects not only thegut, but also the joints in the form ofsynovitis and femoral head necrosis.“Generally, this problem is chalked upto an Escherichia coli infection, but ifyou culture the lesions anaerobically, Ithink you’d find clostridium is a muchbigger issue because it allows bacteriato become systemic and it ends up inthe joints,” he says, noting that he pre-sented the research supporting this the-ory at the 2006 American VeterinaryMedical Association annual meeting inJuly.

Dr. Scott Gustin, director of veteri-nary services for North America andAsia at Cobb-Vantress, the Arkansas-based poultry research and develop-ment company that sells broiler breed-ers, has similar comments about sub-clinical NE. “Unless you’re looking forit during routine posting sessions,you’ll miss it,” he says.

Does he believe that subclinical NEwill increase as less AGPs are used?“Absolutely.” There is still a lotunknown about subclinical NE, Gustinsays. “With the declining use of in-feedantibiotics and rise in intestinal dis-ease, we are realizing that gut health isan incredibly complex science.Diseases or syndromes such as ‘dys-bacteriosis’ and subclinical NE are per-fect examples of newly evolving dis-eases we don’t understand and controloptimally.”

He’s seen enough subclinical NE,however, to conclude that “it’s proba-bly much more of a significant issuethan we realize and is probably muchmore widespread than clinical NE.”

Cost of subclinical NEAn oft-quoted figure on the cost of sub-clinical NE is 5 cents per bird. Gustinsays that “Subclinical necrotic enteritiscan result in a 5- to 10-point increase in

feed conversion in controlled trials wehave funded. It can be very damagingto economic returns across an opera-tion due to that lost feed conversionratio.”

Dr. Charles Hofacre, a professor atthe University of Georgia, Athens whois considered in the poultry industry tobe a guru on the subject of NE, says,“Subclinical necrotic enteritis is proba-bly more expensive to the industry thanclinical NE because the acute form isobvious and gets treated while the sub-clinical form often goes unnoticed.

“You may have a large number offlocks affected before you realize youare losing feed efficiency and growthunless you conduct regular weeklyposting sessions, which most producersdo not,” he says.

Hofacre likewise expects to seemore acute and subclinical NE as theindustry backs off the use of in-feedantibiotics. He cites the experience inEurope, where the poultry industry hasseen a huge surge of NE in broilerssince AGPs were banned by regulators.

“In the US, the reduction in AGPs isbeing driven by consumers, not by reg-ulators as it is in Europe. I don’t know

Gustin: ‘Gut health is an incredi-bly complex science’

Multifocal yellowish necrotic plaques (A) may progress to complete necrosis ofthe intestinal mucosa (B), which has a "Turkish towel" appearance.

A

B

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that we’ll go to zero AGPs, but I thinkthe US poultry industry will go prettylow. Consumers don’t want AGPsused,” he says.

Causes of NEC. perfringens is a gram-positive, anaer-obic bacterium that is normally foundin the environment and gut of healthybirds. Although NE is caused by C. per-fringens, not all C. perfringens causesNE, Hofacre points out. A toxic strainof the pathogen must be present. Mostoccurrences of NE are thought to becaused by the alpha (α-toxin) pro-duced by C. perfringens.

A toxic strain of C. perfringens takeshold when the bird’s intestines aredamaged by other diseases, particularlycoccidiosis, he says.

“With intestinal damage, the normalbalance of bacteria is disrupted andmucus production increases. That’show the intestines respond, by coatingtheir surface. But mucus also providesa food source for C. perfringens. Thetoxin utilizes mucus and further dam-ages the intestines, and you get a dam-aging cycle,” Hofacre says.

Recent evidence about the impact ofcoccidiosis on the development of NEcomes from a study that was presentedin July 2006 at the annual conference ofthe American Association of AvianPathologists. It demonstrates that bothcoccidial pathogens Eimeria acervulinaand Eimeria maxima cause enoughintestinal damage to allow C. perfrin-gens to proliferate.

In the study, conducted by Dr. GregMathis of Southern Poultry Research,Athens, Georgia with co-investigatorHofacre, birds were inoculated with theEimeria species then challenged with C.perfringens. Those with Eimeria infec-tions were more susceptible to thedevelopment of NE compared to birdswithout coccidial infections. BothEimeria species were associated withan increased risk for NE, but the riskwas greatest with E. maxima.

Davis says that another contributorto NE is animal byproducts. “We haveconducted research showing there areliterally tens of thousands of clostridi-um spores per gram in some animalbyproducts found in blends. In onestudy we did, fish meal in the feed washeavily contaminated with C. perfrin-gens. We’ve also found the pathogen inbone meal. So, in some cases, flocksare getting clostridium from their food.”

There is a wrongful perception thatchemical anticoccidials and coccidiosisvaccination cause NE, he says. “In fact,the opposite is true. These products inno way cause NE. They just don’t havedirect efficacy against bacterium.There’s no secondary antibiotic effect,”he says.

A clinical impression No tests for C. perfringens are currentlyavailable, but researchers are hoping tochange that. Investigators in Europe,for instance, have been working on ablood test that would show antibodiesto toxic C. perfringens.

Hofacre cautions that there is alsono way to predict which farms are atincreased risk for NE based on littersamples. “Culturing C. perfringens fromthe litter is an exercise in futility,” heexplains, because there is no way totell if any clostridium that is isolatedhas the gene needed to produce thetoxin that results in NE.

In other words, “You can have ahigh level of clostridium in the envi-ronment, but that doesn’t prove it iscausing disease,” he says.

The lack of tests for identification oftoxic C. perfringens means that diagno-sis of subclinical NE depends on anastute clinician.

“It’s a clinical impression amongthose experienced with the disease,”says Hofacre. “There’s a certain amountof enteritis, but it never gets severeenough to call it clinical NE. The termsubclinical enteritis really reflects theseverity of NE.”

Hofacre: ‘You are loosing feedefficiency and growth.’

continued on page 7

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Understanding acute NEAcute or clinical necrotic enteritis (NE), caused by thepathogen Clostridium perfringens, results in necrosis ordeath of the intestinal lining and remains one of the mostcommon and costly diseases of modern broiler flocksaround the world.

In commercial flocks, acute NE has been relatively wellcontrolled — though inadvertently — with antibioticgrowth promoters (AGPs). However, with the use of in-feed antibiotics on the decline, the incidence of NE is certain to be on the rise.

Dr. Steve Davis, president and chief executive officer ofColorado Quality Research, Wellington, says that flocksmost at risk for acute NE are antibiotic-free birds such asthose not receiving AGPs and birds receiving coccidiosisvaccines or chemical anticoccidials, which have noantibiotic effects.

Dr. Scott Gustin, director of veterinary services for NorthAmerica and Asia at the Arkansas-based Cobb-Vantress,agrees that “For niche markets such as organic or antibi-otic-free flocks, acute NE is a significant problem.” Inlarge-scale broiler production, “acute NE is a naggingproblem that is sporadic in nature.”

Earlier onset notedDavis has noted that among some flocks, acute NE seemsto occur earlier than before. “It used to be at 3 to 4 weeksof age and now it’s between 2 and 3 weeks of age,” headds. “I think it may have to do with coccidiosis control;ionophore anticoccidials and the chemicals used areallowing more leakage faster than they used to.”

The earlier occurrence of acute NE may also be linked tobird genetics that allow for faster growth, says Davis,adding that “We have also found in our studies that acuteNE is more prevalent in males, which are more likely todie from the disease than females.”

MortalityWhen clinical NE strikes, it can cause mortality ranginganywhere from 5% to 50%; 10% mortality is a frequentlycited figure. Comments Davis, “We keep mortality fromclinical NE at around 10% because we recognize andtreat.”

Mortality is usually the first sign of the disease. In lessseverely affected flocks, birds may exhibit depression,

poor appetite, ruffled feathers and diarrhea.

Hofacre says an official diagnosis of clinical NE is madeupon necropsy of affected birds. “Once you see it, youwon’t forget it. The liver is firm and a dark mahoganycolor. The surface of the small intestines is thick andrough.”

Sometimes, warns Davis, “I’ve seen cases so acute thatthe gut starts to deteriorate rapidly and you may not seethe classic ‘Turkish towel’ lesions characteristic of NE,which could lead to a missed diagnosis.”

Conversely, a heavy growth of clostridium does notalways mean NE because after a bird dies, clostridium inthe gut balloons in great numbers since there are perfectanaerobic conditions with a lot of protein and mucus.Therefore, “in a full outbreak, you may need to necropsyquite a few birds before you see classic NE gut lesions,”he says.

PreventionThe risk factors that lead to acute NE are same as forsubclinical NE, since both are simply different degrees ofthe same disease, Hofacre says. The primary factors aredamaged intestines that can occur due to other diseases,such as coccidiosis, and a toxic strain of C. perfringens.Other factors linked to NE range from the level of littermoisture to certain feed ingredients.

Preventing acute or subclinical NE, say these veterinari-ans, requires good coccidiosis control and other methodsof promoting a healthy gut. In the future, NE control mayinclude vaccination against the disease as well as gener-al management measures that promote good gut healthand reduce the clostridium challenge. (See sidebar onmanagement).

Irritation in the gut can help C. perifringens produce tox-ins that cause necrotic enteritis.

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Necrotic enteritis (NE) is the same disease whether it hasan acute or subclinical presentation. Measures to preventNE, therefore, are similar for both forms of the disease,though the specifics may vary depending on the type ofbroiler production system in place.

One of the first steps that can be taken to control NE issound cleaning and disinfection of the environmentbetween flocks to decrease the bacterial load in the broil-er environment, especially in facilities with a history of NE,says Dr. Steve Davis, president and chief executive officerof Colorado Quality Research, Wellington. “More attentionto the efficacy of disinfectants and litter treatmentsagainst Clostridium perfringens will become important factors in controlling NE.”

Litter moisture should not be too high or low. Oat or ricehull may increase the risk for NE because it is less absorp-tive, he says.

Dr. Scott Gustin, director of veterinary services for NorthAmerica and Asia at Arkansas-based Cobb-Vantress,notes that some of his colleagues would disagree, but “Ihave found that reusing litter if possible helps stabilize theenvironmental and coccidial make-up of the house inorganic operations that continually struggle with NE.”

Dietary influencesGustin and Davis both emphasize that diet can influencethe development of NE. Grains that contain a lot of indi-gestible soluble fiber, such as wheat, barley, oats and rye,have been linked to intestinal disease in poultry. The use ofsome feed ingredients associated with NE, Gustin says, isunavoidable due to cost constraints, but producers may beable to at least limit their inclusion rate, especially duringtimes of heavy coccidia cycling when there is more stresson the gut.

Davis’ research has shown that broilers receiving highprotein diets are easier to challenge with C. perfringens;as are broilers receiving higher density diets, which maybe because nutrients remain available to the bacteria in

the intestine if they are fed at higher levels than the broilercan utilize. “Integrators raising broilers without feed gradeantibiotics may be able to decrease the incidence of NE byusing lower density formulations or concentrating onamino acid fortification and balance over feeding dietswith higher protein levels,” he says.

However, dramatic changes in diet, which are linked todevelopment of NE, should be avoided, Davis cautions.

Other factorsOvereating is yet another factor he has linked to NE. “Ifyou slow down feed consumption with measures such asdecreased lighting, you can decrease the incidence of NE,which is the opposite of what most people think,” Davissays.

Cooler temperatures that chill birds and increase feedconsumption are linked to NE mortality, he continues. “Itappears that increasing the environmental temperaturealso decreases feed intake in a broiler flock breaking withNE and will help curtail the severity of an outbreak.”

Another factor that can affect the severity of NE is thesource of chicks and their quality, Davis says. Flocks withexcellent chick quality and uniformity require a greaterchallenge to create disease, so continued improvements inchick quality should improve control of NE. It could be thatdifferent breeds have varying levels of maternal antibodyagainst C. perfringens, indicating that vaccinating breed-ers or broilers may be useful in preventing NE.

Gustin agrees that the broiler breed should be consideredand that some breeds seem to be more or less likely todevelop NE. “As a primary breeder, you try and stay aheadby breeding a bird that can withstand these industrychanges. As a producer, you need as many options andtools as possible to keep the feed conversion ratio and liveperformance competitive,” he says.

Last but not least, bird density is a critical factor in pre-venting NE, because density affects many of the othervariables involved, he says.

Management strategies for preventing NE in broilers

7

Recently he visited a farm withenteritis and liver lesions that appearedto be caused by NE. “This farm is onthe tip of flipping over into acute NE,but I won’t allow birds to go untreatedjust to prove I’m right. I think this hap-pens a lot.”

It was a conventional flock and hesuspects that their anticoccidial wasbeginning to lose efficacy and that toomuch coccidia was leaking through,Hofacre says.

Says Gustin, “The diagnosis of sub-clinical NE relies heavily on the qualityand frequency of technical service bythose with the ability to diagnosis sub-clinical NE. Routine posting sessionsconducted by individuals with specialtraining in diagnosis of the disease areneeded, and performance data must becorrelated to necropsy findings, espe-cially during times that coccidiosisprograms are transitioning.”

Davis adds, “To accurately diagno-sis subclinical NE, I think it’s veryimportant to get anaerobic cultures ofvery fresh, dead birds by euthanizingif necessary.”

Once familiar with the disease andthe intestinal lesions that characterizeNE, says Hofacre, subclinical NE canbe diagnosed upon necropsy. Thesmall intestinal surface is coveredwith mucus and may be thick andrough. The liver may be firm and isa dark, mahogany color.

Hofacre uses a scoring systemwith a range of zero to three forassessing necrotic enteritis, he says.Zero would be no intestinal lesions,one would be a mucus-covered intes-tine, characteristic of subclinical NE,while scores of two to three wouldindicate clinical NE because the intes-tines would be obviously diseased withbloody exudate in birds about to die orthat died.

NE control strategies To best control both clinical and sub-clinical NE in flocks, especially for pro-

ducers backing off antibiotic use, acombination approach will most likelybe needed, starting with good coc-cidiosis control, say these experts.

“One combination might be coc-cidiosis vaccination, natural productssuch as organic acids and NE vaccina-tion,” says Davis, who believes that akey to any successful combination willinvolve immunity.

“Consider dermatitis, which is acontinued on page 15

Checklist for necrotic enteritis control� Implement a good coccidiosis control program, which mayconsist of a properly administered vaccine or efficaciousin-feed products.

� Maintain good hygiene. Clean out and sanitize housesbetween flocks.

� Maintain appropriate flock density.� Use absorbent litter to help maintain proper litter moisture.

� Avoid food sources contaminated with toxic C. perfringens and consider monitoring ingredients for C. perfringens spores.� Eliminate or reduce food ingredients associated with anincreased risk for NE, such as wheat, barley, rye andother grains with a high level of indigestible soluble fiber,and animal byproducts.

� Avoid dramatic dietary changes.� Feed a low density, high-quality diet fortified with aminoacids; avoid high protein diets.� Vaccinate against NE when a vaccine becomes widely available.

� Consider administration of competitive exclusion and organic acid products to promote good gut health.� Consider bird breed and the source of chicks, since some may be more or less prone to development of NE.

Increased recognition that live vac-cines provide a valuable alternativeto chemotherapy for coccidiosis

control has encouraged researchersaround the world to consider develop-ment of coccidiosis vaccines for localuse. As with all products developed forthe poultry industry, it is essential thatvaccine development be carried outusing rigorous procedures and highprofessional standards that also complywith any official regulations that maybe applicable.

Guidelines have long been availableto help researchers satisfy standards fordrugs and many viral and bacterial vac-cines — but none have been producedfor vaccines against coccidiosis. Con-sequently, the author recently assem-bled a group of experts to participate ina joint project aimed at finding a reme-dy to this deficiency. The team includ-ed myself and the following esteemedexperts:

• Professor Martin Shirley, deputydirector of the Institute for AnimalHealth, United Kingdom, lead the

research team in the 1980s that devel-oped the world’s first attenuated coc-cidiosis vaccine. More recently, he wasinstrumental in organizing a successfulproject to sequence the entire genomeof Eimeria tenella, the most widespread,pathogenic species of Eimeria thatinfects the chicken.

• Dr. Ray Williams, of the UK, is oneof the world’s leading coccidiosisresearchers with vast experience in thepoultry industry. Dr. Williams has pub-lished numerous papers about aviancoccidiosis and vaccination.

• Dr. Brian Roberts, also of the UK, isan international authority with detailedknowledge of the registration require-ments necessary for obtaining market-ing authorization for poultry vaccines.

The project group’s goal was todevelop guidelines to assist scientistsand others in the design, implementa-tion and interpretation of studies forassessing the efficacy and safety of livecoccidiosis vaccines and to suggeststandards for manufacture and qualitycontrol. The resulting guidelines areintended to help researchers obtainspecific information for those involvedin the decision making process and tofacilitate the worldwide adoption ofconsistent, standard procedures.

The team received advice from vet-erinarians, researchers and those withpractical knowledge of poultry produc-tion. Scientists working in government,academia and industry around theworld were consulted, but the some-times controversial opinions expressedin the guidelines are the group’s own.A leading poultry veterinary journal,Avian Pathology, published the guide-lines1, which are shown on the follow-ing page.

ESSENTIAL ELEMENTSIndependent project group develops guidelines for coccidiosis vaccines

By H.D. Chapman, Ph.D.Department of Poultry Science,University of Arkansas, USA

KEY POINTS

� Rigorous procedures and high professional standards arenecessary to ensure safe and effective poultry products.

� Standards for evaluating coccidiosis vaccines have beenlacking.

� To remedy the deficiency, several top coccidiosis expertsrecently developed guidelines to facilitate the worldwideadoption of consistent standards for evaluating the efficacy,safety, manufacture and quality control of coccidiosis vac-cines for poultry.

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TECHNICALLY SPEAKING

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ProceduresBirds in vaccine development studiesshould be vaccinated under conditionsthat duplicate as closely as possible themanner in which vaccination will becarried out in the field. Subsequently,birds should be intentionally chal-lenged with the parasite to seewhether they have acquired protectiveimmunity.

An important aspect of experimen-tal design is that vaccinated birds mustbe reared in floor-pens to allow ade-quate exposure to infection followingvaccination; the challenge phase ofexperiments can be carried out in wire-floored cages or pens. The guidelinesas published in Avian Pathology providedetailed information about conductingthese studies.

Once satisfactory results have beenobtained from experimental studies,large-scale field tests can then be car-ried out; this is important to establishthat a vaccine is safe for use in thefield. Preferably, such trials should becarried out in all geographical regionswhere a vaccine is intended for use.

Criteria for efficacyThe criteria conventionally used toevaluate drug efficacy, such as weightgain, mortality, feed conversion and thepresence of intestinal lesions, may sim-ilarly be used to determine the extentof immunity development followingvaccination and subsequent challenge.However, in the opinion of the projectgroup, lesion scores are of question-able value. Lesion scoring requires con-siderable expertise. It is inherently sub-jective and, unfortunately, does notnecessarily correlate with protectionbecause lesions may be present in thegut of partially or completely immunebirds, even though their weight gain isnot depressed.

In some countries, guidelines foravian vaccines have been produced byregistration authorities, but specificstandards for anticoccidial vaccines in

poultry apparently have not been pub-lished so far. Detailed knowledge ofany local requirements is essential toobtain product approval.

The guidelines drafted by the proj-ect group provide information on thegeneral requirements of regulatoryauthorities based on regulations cur-rently applicable in the EU and the US.Topics covered in the guidelinesinclude efficacy requirements, safetyand environmental considerations,quality control in terms of purity, phar-

Guidelines for coccidiosis vaccines Ideally, any live anticoccidial vaccine should have the following 13characteristics:

� Induce protective immunity against economically important species of Eimeria

� Be safe for the target host, non-target animals and humans

� Not represent an environmental hazard

� Comprise parasites of normal or low virulence

� Comprise parasites that remain viable during storage for a reasonable period of time

� Protect against field strains in geographical areas where the vaccine is used

� Be administered by a commer-cially practical method to ensurethat as many birds as possiblereceive an immunizing dose

� Have no adverse effects on finalperformance or other production criteria

� Be compatible with other poultryvaccines

� Be free from viral, bacterial,mycoplasmal, fungal and chemi-cal contaminants

� Be cost effective compared withother methods of coccidiosis control

� Include drug-sensitive lines that may reduce drug resistance in field populations

� Raise no problems with residues or impose a need for mandatory withdrawal periods

continued on page 16

Good biosecurity helps ensure thatcoccidiosis vaccines are free fromcontaminants.

If you’re like many other modernpoultry operations, you probablyvaccinate at least a portion of your

broiler chicks for coccidiosis. Maybeyou do it to improve the performanceof broiler flocks when traditional in-

feed anticoccidials don’t seem to holdup to the challenge. Or maybe you doit to meet the growing consumerdemand for birds raised without drugs.

Now, early field trials and experi-ence indicate there’s one more reasonto vaccinate for coccidiosis: It can helpcontrol or eliminate the growing prob-lem of gangrenous dermatitis.

The coccidiosis vaccine itself is noteffective against the disease. However,vaccination prevents late coccidiosiscycling, an event that some veterinari-ans and production managers nowbelieve is the trigger for costly out-breaks of gangrenous dermatitis.

The consequences of gangrenousdermatitis include high mortality, car-cass condemnations and trimmed parts.Economic losses are an estimated $0.80to $1.31 per affected bird, which is sig-nificant because the disease occurs lateduring grow-out, when a lot hasalready been invested in birds that can’tbe saved, investigators say.1

Number one health problem“We’re hearing more people discussthis disease,” says Dr. CharlesBroussard, global technical servicesdirector for Schering-Plough AnimalHealth’s Poultry Business Unit.At some U.S. poultry companies, gan-

grenous dermatitis has become a veryserious problem, with 10% to 25% offlocks affected and mortality runningabout 2% to 4% — and sometimeshigher. The incidence seems severeenough that it’s on the minds of veteri-narians and has become a “numberone” health problem for some produc-ers, he says.

Broussard notes that when 17 U.S.broiler company veterinarians wereasked in a survey to list their top dis-ease concerns, 12 cited gangrenous

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SOLVING THE GANGRENOUS DERMATITIS PUZZLEPreventing late coccidiosis cycling with vaccination may halt this costly bacterial disease

Mortality, carcass condemnations and trimmed parts can result from gangrenousdermatitis, a costly disease in broilers. In the second photo, note the gas bubblesformed by clostridium, one of the pathogens that causes gangrenous dermatitis.

11

dermatitis. It was, in fact, “the mostconsistent and serious problem in theiroperations,” according to a 2005 Reportof the Committee on TransmissibleDisease of Poultry and other AvianSpecies.

It has long been thought that gan-grenous dermatitis starts with a scratchthat gets infected with a bacterium,which rapidly proliferates when birdsalso happen to be immunosuppresseddue to diseases such as infectious bur-sal disease (IBD) or chick anemia virus(CAV). The remedy was thought to begood control of IBD, CAV and otherimmunosuppressive diseases, as wellas management changes ranging fromlow lighting to special diets that are pri-marily aimed at keeping birds calm toprevent scratching.

But control of IBD, CAV and theenvironment has not resolved the prob-lem of gangrenous dermatitis, saysBroussard. In addition, recent experi-ence and trials indicate that an instiga-tor of gangrenous dermatitis may beone not considered before, and that’slate coccidiosis cycling.

“The remedy may be coccidiosiscontrol that prevents late coccidiosis

cycling — and there may be no need to make significant managementchanges,” he says.

Adds Broussard: “Coccidiosis mighthave been a cause of dermatitis allalong, but we’re approaching coccidio-sis control differently now. We aren’tusing as many anticoccidials and resist-ance has developed to some of them,which may be allowing dermatitis torear its head.”

Patterns of diseaseAlthough high mortality is the mostobvious sign of a gangrenous dermati-tis outbreak, says Broussard, producersmight also notice that affected birdshave a poor appetite, poor coordina-tion and leg weakness, skin lesions andedema. The pathogen most often asso-ciated with gangrenous dermatitis isclostridium of various species, butEscherichia coli and staph infections canalso be the culprits. The pathogens actas an opportunistic infection, which isset off by coccidiosis.

“Even though spring is often associ-ated with outbreaks of dermatitis, late-ly we’ve also seem problems with thedisease occurring in winter. Cold

Table 1. Gangrenous dermatitis control on three farms with and with-out coccidiosis vaccination to promote late coccidiosis control.

Farm Date Moved Mortality (%)A 05-Apr-05 10.29

10-Jun-05 12.12Coccivac-B Cycle 1 22-Mar-06 3.27Coccivac-B Cycle 2 06-May-06 2.28B 06-Apr-05 11.60

10-Jun-05 8.91Coccivac-B Cycle 1 21-Mar-06 3.37Coccivac-B Cycle 2 06-May-06 3.31C 05-Apr-05 11.94

09-Jun-05 6.94Coccivac-B Cycle 1 21-Mar-06 3.08Coccivac-B Cycle 2 06-May-06 2.96

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weather is a stress in and of itself, butthat’s also the same time that a lot offlocks experience a late coccidiosischallenge due to the anticoccidial con-trol program in use,” he says.

“The disease is occurring in birds onchemical-to-ionophore programs andon straight ionophore programs,” headds.

Broussard points to research con-ducted by Dr. Steve Collett of thePoultry Diagnostic and ResearchCenter, University of Georgia, Athens,which was presented at the GeorgiaVeterinary Medical Association 2006annual meeting. The results divergefrom standard gangrenous dermatitisdogma. Collett’s challenge model con-sistently induces gangrenous dermatitislesions in 100% of challenged birds andthe degree of mortality is dose-respon-sive. Most immune-competent broilersare able to contain the infection —become culture negative 7 days afterchallenge — and recover.

Current dogma regarding the patho-genesis of gangrenous dermatitis isbased on the premise that when theskin’s barrier function is compromisedby scratches, contamination withClostridium perfringens commonlyoccurs and the progression of diseasefollowing wound contaminationrequires the bird to be immune-sup-pressed. Using his model, Collett

demonstrated that immunosuppressioncaused by IBD and CAV did notincrease the severity of gangrenousdermatitis lesions. From this, he sug-gested that immunosuppression ismore likely a predisposition to theprocess of infection (currently thoughtto be skin scratches) and not the con-sequence of infection (skin necrosis).This is important because it supportsCollett’s earlier hypothesis that the skinand scratches is not always the waythat clostridial organisms enter thebody and cause gangrenous dermatitis;an alternative route is mostly likely thegastrointestinal tract.

Collett went on to point out that, inthe field, gangrenous dermatitis typical-ly occurs in 4- to 6-week-old broilers.This coincides with the time betweenpeak coccidiosis challenge — peakoocyst output is around 28 days of age— and the development of solid immu-nity against Eimeria spp. challenge at 6weeks of age. Gut lesions caused byEimeria parasites, particularly latecycling Eimeria maxima, could easilyprovide a portal of entry for theclostridial organisms responsible forgangrenous dermatitis, as evidenced byhuman research on the pathogenesis ofgas gangrene.

Interestingly, the prevalence of gan-grenous dermatitis in flocks vaccinatedwith Coccivac appears to be extremely

Table 2. Paired house performance comparing coccidiosis vaccination against nicarbazin/monensin and salinomycin.

Mortality (%) Average Weight Adj. FCCoccivac-B 4.62 6.706 1.903Control 3.95 6.709 1.894

Paired house performance comparing coccidiosis vaccination against salinomycin 60 Gr.Coccivac-B 4.14 4.909 1.804Control 4.36 4.841 1.819

Note: Dermatitis was causing problems within the company during the trial period. Sisterflocks to these farms had to be treated for dermatitis-related mortality.

low when compared to vaccinatedflocks. It would seem that reducing theseverity of gut epithelial damage, orshifting the time at which it occurs,could be an important means of pre-venting or at least reducing the preva-lence of gangrenous dermatitis.

Major producer’s experienceConsider the experience at one largeUS broiler producer, where gangrenousdermatitis became a problem in severalcomplexes, particularly among smallbirds that had received nicarbazin/monensin for coccidiosis control.

“We had dermatitis coming in at 32to 35 days — toward the end of theanticoccidial control program cycle,”says the producer’s veterinarian, whospoke to CocciForum with the condi-tion that his company not be revealed.

“Gangrenous dermatitis can be dev-astating and, for some operations,results in mortality as high as 8% perweek. That’s very costly to individualgrowers,” the veterinarian says.

The producer followed the problemfor a while and realized that “we hadsome late-breaking coccidiosis,” hesays. When the birds received thechemical anticoccidial Clinacox after

nicarbazin/monensin, the dermatitisstopped.

The veterinarian has not been ableto link gangrenous dermatitis outbreakswith the traditional villains IBD norCAV. “We’ve had dermatitis in areaswith a good IBD program and in birdsthat I think are normal. We have alsohad dermatitis in chickens vaccinatedagainst CAV. The only link I’ve seen isthis late coccidiosis challenge.”

Some complexes with larger birdson the same nicarbazin/monensin pro-gram also experienced gangrenous der-matitis, which ceased when coccidiosiscontrol was managed with vaccinationadministered at the hatchery to initiateearly immunity and prevent a late coc-cidiosis challenge.

“I don’t want to sound too definitiveabout the association, but we see muchless dermatitis when we control coc-cidiosis late in the production cycle,”he says. “I think the vaccine helpedwith dermatitis because it did awaywith the late coccidiosis challenge.”

Based on his experience, this poul-try veterinarian believes that theobserved link between late coccidiosiscycling and gangrenous dermatitis rep-resents a changing pattern. He also

Coccivac-B

Chemical/Ionophore

IonophoreDays of Age

1 4 7 10 13 16 19 22 25 28 31 34 37 40 43 46 49

Oocysts excreted

1 4 7 10 13 16 19 22 25 28 31 34 37 40 43 46 49

Oocysts excreted

Der

mat

itis

Win

dow D

erm

atiti

sW

indo

w

Days of Age

1 4 7 10 13 16 19 22 25 28 31 34 37 40 43 46 49

Oocysts excreted

Der

mat

itis

Win

dow

Figure 1: Dermatitis outbreaks overlap with the late coccidiosis cycling thatoccurs when traditional coccidiosis control methods are used.

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thinks there may be a breed predispo-sition. Gangrenous dermatitis hasoccurred in three different bird breeds,but there have also been breeds thatseem highly resistant to dermatitis, henotes.

Integrator’s trialTo test the theory that gangrenous der-matitis may be triggered by a gut insultcreated by the late coccidiosis cyclingthat results with traditional in-feed anti-coccidial programs, another large broil-er integrator conducted a trial.

In January 2006, four farms ofstraight run broilers were immunizedwith one dose of the coccidiosis vac-cine Coccivac-B, which was sprayed onat one day of age in the hatcherybefore chicks were placed on farmswith the strongest history of gan-grenous dermatitis. All other manage-ment and vaccination procedures wereidentical to the standard company pro-gram. The trial was then replicated withthe same format in April 2006 for thenext sequential grow-out on the samefarms and houses.

On three of the farms, two cycles ofCoccivac-B vaccine were administeredin the spring, a peak time for gan-grenous dermatitis outbreaks. Duringthe same time period in 2005 — whencoccidiosis control comprised onecycle of nicarbazin/monensin then acycle of salinomycin — average mortal-ity exceeded 10%, but after coccidiosisvaccination in 2006, mortality was onlyabout 3% (see Table 1). The “sister”farms of the trial houses had gan-grenous dermatitis and a mortality of 3to 6 birds/1,000 per day for at least 4days.

At the fourth farm in the trial, pairedhouse performance was studied; coccidiosis vaccination was comparedagainst nicarbazin/monensin andagainst salinomycin (Table 2).

Performance in vaccinated birdswas very similar or better to perform-ance among birds receiving traditionalanticoccidial control, according to the

results. For instance, the averageweight in birds that received Coccivac-B vaccine was 4.9 lbs, compared to 4.8in birds receiving salinomycin.

Says Broussard, “These trial resultsconfirm our anecdotal observations thatthe prevailing trigger for dermatitis canbe correlated to late coccidiosis cycling.Traditional anticoccidial programs thatshift coccidiosis cycling into peak der-matitis periods may compound theeffect or even create it.

“Coccidiosis vaccination shifts coc-cidiosis cycling out of the dermatitis‘window’ to eliminate what nowappears to be the predominant predis-posing factor for dermatitis,” he says.(See Figure 1).

In addition, control of gangrenousdermatitis by preventing a late coc-cidiosis challenge has not requiredmanagement changes traditionally nec-essary to rid an operation of this dis-ease, Broussard says.

Vaccine is cost competitiveEconomic data from the trial was alsoconsidered as well as data from othersources. Compared to other methods ofanticoccidial control in the trial,Coccivac-B was less costly for control-ling coccidiosis. This was the case evenbefore other benefits of vaccination,such as reduced mortality and fewermedication costs, were considered, hesays.

“Most exciting is the ability toreduce or eliminate dermatitis by shift-ing coccidiosis cycling, which givescoccidiosis vaccination added value,”Broussard says.

“We’re on to something here thatcould really help broiler producers getrid of the dermatitis problem, the stag-gering losses caused by this diseaseand, at the same time, provide goodcoccidiosis control,” he says.

Reference1 Norton, RA et al. Gangrenous der-matitis reemerges in broilers. WattPoultry USA. March: 38.

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clostridial disease that occurs later inthe life of birds, unlike NE, whichoccurs early in the bird’s life. I havenever seen or met another poultry vet-erinarian who has seen a flock of broil-ers with NE that get dermatitis later, andthe reason for that is immunity,” hesays. In short, birds that survive NEbuild immunity against dermatitis.

That observation indicates that vac-cinating for NE could be helpful inflocks at risk. This would include notjust antibiotic-free birds, but birdsreceiving chemicals or vaccines to pre-vent coccidiosis and birds on a rotationprogram during times they transition offionophores, he says.

A C. perfringens type A toxoid vac-cine for NE has been developed bySchering-Plough Animal Health and, atthis writing, is being used in the USwith a conditional license granted lastyear by the USDA. It is administered tobreeders, which convey passive immu-nity against NE to their broiler progeny.

The vaccine has obvious benefits forantibiotic-free birds at risk for acute NEoutbreaks and might also benefit pro-ducers still using AGPs by enablingthem to lower the amount of antibioticused, says Davis. When his firm vacci-nated birds with the type A toxoid thenchallenged their progeny with clostridi-um, they performed just as wellwhether they received 25 grams/ton ofbacitracin methylene disalicylate (BMD)or twice that amount. “There seemed tobe some synergistic effect between thevaccine and BMD.”

Gustin couldn’t comment specifical-ly on the new vaccine but says, “If youlook at many of the diseases we vacci-nate for in poultry, it is obvious that wetake advantage of passive immunity.We should do so for other diseases ifwe can do so effectively.

“One would assume that if clinicalnecrotic enteritis can be prevented witha vaccine, the same mechanism couldimprove control of subclinical NE. Since

subclinical NE is much more wide-spread than clinical NE, the benefits toconventional sectors would be there,”he says.

Hofacre says, “When anticoccidialsstart to fail, a vaccine may have a role”and it may also have a role in birdsreceiving AGPs, since antibiotics arenot always 100% effective against NE.Producers, however, will have to weighthe cost of the vaccine against otherfactors.”

To improve NE control, he advisesthat producers “look at ways to main-tain good gut flora and overall intestin-al health, perhaps by feeding competi-tive exclusion products and organicacids. If a coccidiosis vaccine is used,make sure it’s managed well” andadministered properly so that birds donot get overexposed to coccidia.

Control of NE also relies on goodbasic management, these expertsemphasize. Litter moisture, house tem-perature, the diet fed to flocks as wellas bird density and other factors mustbe considered and will play an increas-ingly important role in the control ofNE (see article, page 6).

NECROTIC ENTERITIS continued from page 7

Severe necrosis of the intestinal lining (mucosa).

COCCI NEWS

Late production E. maxima problemslinked to anticoccidial resistanceProblems with Eimeria maxima infections late in the pro-duction cycle appear to be linked to extensive use ofionophore antibiotics and resulting ionophore-resistant E. acervulina, says Dr. Greg F. Mathis of Southern PoultryResearch, Inc., Athens, Georgia.

An earlier study suggested that E. acervulina can interferewith E. maxima colonization. Consequently, Mathis designeda battery cage study to examine the relationship of E. acervulina sensitivity to the ionophore salinomycin andsubsequent infection levels with E. maxima.

Birds were fed nonmedicated feed or salinomycin at therate of 60 grams/ton and were then challenged with either asalinomycin sensitive strain of E. acervulina, a resistant strainof E. acervulina and/or an E. maxima field isolate.

The oocyst per bird challenge levels were as follows:

• None (control)

• E. acervulina (sensitive strain) 50,000

• E. acervulina (resistant strain) 50,000

• E. acervulina (sensitive strain ) 50,000 plus E. maxima 5,000

• E. acervulina (resistant strain) 50,000 plus E. maxima 5,000

• E. maxima 5,000

E. maxima alone caused a 20% weight reduction and 2.70lesion score, says Mathis.

Salinomycin controlled the sensitive strain with 5% weightreduction and 1.25 lesion score. It did not control the resist-ant strain, resulting in a 22% weight reduction and 2.75

lesion score. Birds infected with E. maxima and the sensitive E.

acervulina strain had E. maxima lesion scores of 2.25. Thebirds infected with E. maxima and the resistant E. acervuli-na strain had E. maxima lesion scores of 1.30.

“From the results it can be inferred that E. acervulinainterfered with development of E. maxima,” Mathis says.“Higher anticoccidial resistance allows more E. acervulinacolonization, which appears to interfere with colonization ofE. maxima, and thus indirectly slows E. maxima immunitydevelopment.”

This increases the chance for late problems with E. maxi-ma, possibly explaining an increase in field reports of late E.maxima infections where salinomycin has been extensivelyused, Mathis adds.

Mathis: ‘Increases the chance for late problems’

macopoeial sterility, potency, quantifi-cation and stability etc., manufacturingpractice and, last but not least, neces-sary documentation.

PurposeIn the foreseeable future, new vaccinesare likely to be introduced for protect-ing poultry against coccidiosis. Some ofthese vaccines will be produced bycompanies with an established trackrecord in providing high quality vac-cines to the poultry industry but, aspointed out at the 2005 InternationalCoccidiosis Conference held in Brazil,many smaller companies lacking suchexperience are also likely to beinvolved. It is important that all com-mercial vaccines, whatever theirsource, be produced to the same highstandards. For example, in the US,

source flocks used to produce poultryvaccines must be serologically tested toensure freedom from at least 11 kindsof virus, not to mention Mycoplasmaand Salmonella species.

To reiterate, the purpose of the proj-ect group’s guidelines is to facilitate theworldwide adoption of consistent, stan-dard procedures for evaluating the effi-cacy, safety, manufacture and qualitycontrol of coccidiosis vaccines for poul-try. The poultry industry deserves noless.

Reference1 Chapman, HD, Shirley, MW, Williams,

RB. Guidelines for evaluating the efficacy

and safety of live anticoccidial vaccines,

and obtaining approval for their use in

chickens and turkeys. Avian Pathology

2005;34: 279-290.

ESSENTIAL ELEMENTS continued from page 9

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CocciForum is published by the Worldwide Poultry Business Unit ofSchering-Plough Animal Health Corporation, Summit, NJ. The editors welcome your ideas and suggestions for news articles concerning coccidiosismanagement. Send correspondence to CocciForum, PO Box 9000, PMB239, Edgartown, MA 02539-9000, USA. E-fax: 928-569-2491, E-mail:JFeeks@prworks.net. Back issues are available online atwww.thepoultrysite.com/cocciforum

© Copyright 2006, Schering-Plough Animal Health Corporation.

Executive Editors: Stephen P. CollinsMarcelo Lang

Managing Editor: Joseph Feeks

Associate Editor: Diana Delmar

Design & Production: Deborah Sottile

Proofreader: Marisa Kane

Lesser known Eimeriaspecies underestimatedOne of the lesser-known Eimeriaspecies in poultry may be underesti-mated in importance.

Dr. Steve H. Fitz-Coy, of Schering-Plough Animal Health, explains thatE. mivati is a coccidial species thatsome researchers have consideredto be a variant of E. acervulina or amixture of E. acervulina and E.mitis, but not a unique species.

To further determine whether E.mivati is unique, Fitz-Coy obtainedseveral field isolates from Georgia

and the Delmarva Peninsula that fit descriptions of the species.He selected three of the isolates and sent them with 10 otherEimeria species samples to an independent lab for polymerasechain reaction (PCR) assay. The identity of each sample was notknown by the lab.

“The only isolates that could not be identified by PCR assaywere the E. mivati samples,” he reports. The current primers foridentification of Eimeria species include E. acervulina and vir-tually all the other Eimeria species known to affect chickens —except E. mivati.

The PCR test indicates that E. mivati is, in fact, a valid andunique Eimeria species, he said.

E. mivati is also “moderately pathogenic” in chickens and, onsome occasions, can cause mortality, according to Fitz-Coy. Inone study, mortality was 40% in naive chickens, but there wasno pathology in hyper-immunized hatch-mates.

Sanderson: Organic going mainstreamThe all-natural food trend is gaining momentum and attractingthe attention of larger poultry producers, according to Joe FrankSanderson, chairman and CEO of Sanderson Farms.

He says the trend is not only showing up in the company’sresearch, it is in evidence elsewhere, according to a report inWatt Poultry USA’s July 2006 issue. Sanderson points to the suc-cessful development of the Whole Foods grocery chain. In addi-tion, most traditional grocery stores now offer organic productsand promotion and even Arby’s fast food chain is promoting all-natural chicken.

All-natural products were considered a small niche marketthat now appears to be burgeoning and “I predict this trend willcontinue,” he says.

Fitz-Coy: Closing in onmivati

Water potential carrier of coccidia Drinking water may be a potential carrier of coccidia to chick-ens, according to a French study.

The study focused on 24 farms that used forage or surfacewater and did not include farms supplied by treated water.

Fecal samples from the farms showed that 75% of the flockswere positive for coccidia. When filters were placed to captureoocysts where water entered the buildings, four of the sampleswere positive for coccidia.

The species of coccidia found in the water was Eimeriaacervulina, which was also present in litter from farms in thestudy.

These preliminary results suggest that water can be a poten-tial carrier of coccidia for chickens.

Study shows Coccivac antigens protectagainst recent field isolates The antigens in Coccivac vaccines provide good protectionagainst coccidia in the field, according to the results of acontrolled study.

Chickens were orally immunized with one dose of eitherCoccivac-B, a coccidiosis vaccine for broilers, or Coccivac-D, a coccidiosis vaccine for breeders and layers.

There were 70 birds in each group and a third group,comprised of unimmunized hatch mates, served as positivecontrols for the study, which was designed to compare theantigenicity of coccidia in the field against the antigenicityof antigens in the vaccine.

After immunization, birds in the study were placed intofloor pens on clean wood shavings and grown to about 35days of age. They were then challenged with three predom-inant species of coccidial field isolates that were collectedfrom 60 broiler and breeder pullet farms across the UnitedStates.

From 144 to 156 hours after challenge, the birds wereeuthanized and examined for gross coccidial lesions. Inaddition, mucosal scrapings from multiple intestinal siteswere taken and examined microscopically with a com-pound light microscope and the severity of parasitic infection was scored.

The average level of protection provided by the vaccineswas determined to be 97% for Eimeria acervulina, 86% forEimeria maxima and 91% for Eimeria tenella.

Compared to the unimmunized birds, the birds vaccinat-ed with Coccivac-B or Coccivac-D demonstrated substantialimmunity as determined by the level of parasitism.

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Coccivac is a registered trademark of Schering-Plough Veterinary Corporation.Copyright © 2005, Schering-Plough Animal Health Corporation. All rights reserved.

For additional information, call 1-800-219-9286 or visit us on-line at www.coccivac.com