G. DONALD RITTER
DVM, Director of Health Services, Mountaire Farms, Inc., Millsboro, DE , U.S.A.
Gangrenous Dermatitis (GD) is a bacterial disease of chickens and turkeys primarily affecting the skin and subcutaneous tissues of the abdomen. Causative agents include Clostridium sp., usually Clostridium perfringens (CP) and/or Clostridium septicum (CS), although other species of Clostridia, Staphylococcus, E. coli and other bacteria may also be isolated from typical skin lesions associated with GD. The disease occurs in commercial poultry raised on deep litter systems used primarily in the United States.
Historically the occurrence of GD has been linked to viral immunosuppression caused by infectious bursal disease (IBDV) and/or chicken anemia virus (CAV) in broiler chickens. In the past differences in breed susceptibility were also observed under high GD challenge field conditions. However, the incidence of GD and other clostridial diseases in commercial poultry has been on the increase in recent years in the face of seemingly good control of viral immunosuppression in broilers.
Clinical presentation and gross lesions
Chickens with GD experience a sudden increase in mortality occurring from 5 to 7 weeks of age. Although morbidity in affected flocks is very low, mortality may peak as high as 10/1000 (1%) per day and losses can continue for up to two weeks. Turkey flocks experience a similar mortality pattern, usually occurring from 12 to 20 weeks of age. Surprisingly, finding live birds with GD lesions is a rare occurrence in affected flocks.
Because clostridia are spore-forming bacteria, they can persist in the environment for long periods of time and are resistant to most disinfection procedures. Many houses affected by GD thus evolve into endemic GD sites where the disease recurs in most flocks. There is also a seasonal pattern observed in the incidence of GD cases in chickens, with the most number of cases occurring during the spring and summer months. Penicillin prescribed by a licensed veterinarian is the treatment of choice for GD and is usually very effective.
Skin lesions are diagnostic of GD and consist of dark purple areas with excessive red thickened serous exudate ("jelly") with associated emphysema ("gas") in subcutaneous tissue around the hips, abdomen and occasionally the wings in chickens. Typical skin lesions are located in the tail head area of turkeys. Some lesions are proximate to skin scratches in defeathered hip areas.
Birds dying of GD decompose very rapidly, both externally and internally. Lame birds may be observed in affected flocks, and some birds have purulent arthritis/synovitis in leg joints. Internal lesions of GD are few, but liver pathology including micro abscesses, necrosis and emphysema may be seen.
Route of infection: "Outside--In" versus "Inside--Out" Theories
Because GD lesions are often found close to damaged or interrupted areas of skin due to toenail scratches, historically the presumed route of infection has been through this portal of damaged integument. The localized skin infection then produces bacterial toxins which quickly kill the bird (Outside-In Theory).
Conversely, many birds with GD lesions have intact skin in affected areas, or may have lesions on the wings or crop areas of the bird also unaffected by skin damage. Clostridia bacteria comprise part of the normal anaerobic intestinal flora of poultry. Thus the intestine affords another possible direct route of infection, whereby the clostridia enter the bloodstream via mucosal disruption in the gut, become systemic and produce typical lesions in the target tissues of the skin, joint spaces and liver (Inside-Out Theory).
A review of GD conditions in other species may provide insight into the true pathogenesis of this disease in poultry.
Outside-In: Damage to tissue caused by trauma provides a portal of entry for clostridia present in the environment. This occurs in horses (traumatic myonecrosis from puncture wounds and injection sites) and people (traumatic myonecrosis from puncture wounds and military injuries).
Inside-Out: Damage to gut tissue, especially in the lower intestinal tract, allows clostridia to enter the bloodstream, become systemic, and produce lesions in target tissues primarily in the skin. This occurs in cattle (Blackleg disease) and people (non-traumatic myonecrosis). In people this condition is almost always associated with mucosal disruption of the lower intestine caused by colon cancer, specifically adenocarcinoma. Skin lesions from this condition in people can occur anywhere on the body - on the trunk, shoulder, or extremities - and the condition is usually fatal unless aggressively treated when first noticed. GD lesions in people have been documented to expand at the rate of one inch per hour. Similarly rapid progression of lesions in chickens has been observed. To a much lesser degree in people, non-traumatic myonecrosis has also been reported to occur in children with neutropenic conditions that impair immune system protection from bacterial pathogens.
Role of Intestinal Microflora
Anecdotal observations in commercial chickens in several dense broiler growing areas in the U.S. point to a possible connection between intestinal microflora (bacterial and coccidial) and incidence of GD.
Bacterial Microflora: Dr. Margie Lee (UGA) and others have shown that poultry fed a basic corn-soy diet have very low levels of clostridia in their gastrointestinal tract (GIT). However, poultry fed antibiotic growth promotants (AGPs) and/or ionophorous anticoccidials such as monensin and salinomycin (ionophores) have a vastly different bacterial microflora pattern in their GIT. The AGP/Ionophore microflora supports much larger populations of many species of clostridia. Although not all clostridia are considered to be pathogens, this data supports a higher risk of "inside-out" origin GD occurring in flocks being fed AGPs and/or ionophores, which is precisely what is observed under field conditions. In fact, poultry reared without AGPs or ionophores (antibiotic free - ABF - type programs), even when grown in GD endemic sites, rarely if ever develop clinical GD. Similarly, use of chemical coccidiostats, which do not have the microflora shifting properties of traditional AGPs and ionophores, are often associated with reduced risk of clinical GD.
Limited microbial community data from live birds with GD and non-GD control birds from the same poultry house also indicate differences in GIT microflora present in these two subpopulations of birds.
Clues from Penicillin Treatment of Clinical GD Flocks: Penicillin is an antibiotic which is very effective in treating outbreaks of clostridial diseases in poultry (both NE and GD). However, this medication is mostly ineffective as a "preventive" treatment on endemic farms. The reason for this is that while the birds are actively consuming penicillin the intestinal counts of CP/CS drop to virtually zero. However, when the medication is removed the intestinal CP/CS counts quickly return to pretreatment levels on endemic GD sites, and clinical disease can return. This recurrence of clinical GD commonly occurs in longer lived turkey flocks following removal of penicillin treatment.
Coccidial Microflora: Coccidial infections stimulate mucin production in the intestines. Clostridial bacteria thrive in mucous rich environments. Thus, there may be a causal relationship between coccidiosis and elevated CP/CS numbers in the GIT.
Most (>90%) of commercial poultry companies rely on anticoccidials for the control of coccidiosis in their flocks. Typical cocci control programs for broilers include the use of ionophorous compounds fed from 0-35 days of age (straight ionophore program) or fed from 18-35 days of age following a starter diet containing a chemical coccidiostat (chemical/ionophore shuttle program). Either of these methods of coccidiosis control results in a peak of intestinal cycling of coccidia at approximately 28-30 days of age or later.
ABF type poultry production relies on either attenuated live coccidial vaccination or straight chemical anticoccidial programs (0-35 days of age) to provide cocci control. Coccidial vaccines are administered at hatch and produce early cycling of oocysts with peak infections in chickens occurring at 16-18 days of age. The resulting immunity from this early controlled exposure to attenuated strains of coccidian successfully prevents later cycling of oocysts in the intestine. Curiously, ABF raised poultry have increased incidence of NE problems, but seem "protected" from clinical GD. It has been speculated that early infection with CP induces immunity to clostridial toxins that are then protective to subsequent or repeated clostridial challenge later in the growout cycle. Coccidial vaccine usage has been associated with decreased risk to GD under field conditions.
Chemical coccidiostats are more coccicidal in activity than ionophores and thus prevent cycling of oocysts to a large degree when they are included in the diet. NE is also more frequently observed when this cocci control program is used, again perhaps inducing immunity to clostridial challenges later in the poultry growing cycle and thus acting as "protective" for GD. Unfortunately, coccidia develop resistance to direct chemical control rapidly and thus chemical coccidiostats have limited or short term uses in commercial poultry.
Timing of intestinal mucosal damage: Early (< 3 weeks) vs. Late (>4 weeks)
Early (<3 weeks) Gut Damage: CP and other clostridial species have long been associated with causing direct mucosal damage in the form of necrosis and/or ulceration of the intestinal lining in poultry. In broilers the disease caused by CP is necrotic enteritis (NE) and in many cases this disease of young birds is linked to early cycling of coccidia. Companies with ABF growing programs routinely battle both clinical and subclinical outbreaks of NE in their production systems. However, flocks recovering from the early gut damage caused by NE grow to market age without symptoms of GD as earlier described.
Late (>4 weeks) Gut Damage: Straight ionophore or chemical/ionophore shuttle coccidiostat programs allow coccidia to cycle and peak infections to occur closer to the age of natural GD outbreaks in broilers. This late cycling of coccidian has been directly linked to increased incidence of GD in traditional broiler growing programs.
Conversely, when straight chemical or ionophore/chemical shuttle coccidiostat programs are utilized for control of coccidiosis, late cycling of cocci oocysts is prevented. Such programs have been directly linked to decreased incidence of GD in broilers.
Plane of nutrition and susceptibility of different genetic stocks
Poultry selected for high breast meat yield used in the industry today require higher planes of nutrition (more protein and amino acids) to perform up to their genetic potential. Such relatively protein rich diets result in protein traveling lower down the GIT, down to where CP/CS colonize normal intestines. Clostridia thrive in protein rich environments. It is speculated that this protein rich environment may create a "bloom" of pathogenic clostridia numbers in the gut and thus increases the risk for clinical GD to occur.
Certain breeds and genetic lines of broilers are associated with increased risk of clinical GD. Often this is observed in the field as differences in age of GD onset. A "GD susceptible breed" may develop GD reliably at 32 days of age, while a "GD resistant breed" reared in the same GD endemic site may not develop clinical GD symptoms until 42 days of age. This difference in age of onset can be economically significant to companies that have the luxury of raising birds of different ages in the same geographic location.
CP/CS in the GIT: Quantity (numbers) vs. Pathotype (strain)
- Studies and comparisons of endemic (GD) vs. non-endemic (no-GD) sites have attempted to determine which of the following hypotheses are true.
GD sites have more numbers of CP/CS in the litter/soil. Overwhelming numbers of CP/CS in the GIT produce systemic disease when late mucosal disruption of intestinal lining occurs and clostridia escapes the gut to produce GD (numbers). - GD sites have uniquely virulent pathogenic strains of CP/CS in the litter soil. These virulent pathotypes invade systemically through the GIT when late mucosal disruption of the intestinal lining occurs and GD is produced (strains).
To date, data on the "numbers" hypothesis is supportive in turkey studies and non-supportive in chickens. Data on the "strain" hypothesis suggests a minor trend towards certain areas of a diverse dendrogram associated with especially severe GD endemic sites. However, data from samples collected from clinically affected farms may have been influenced by penicillin antibiotic treatment in most cases, and thus further work in this area is needed to get a clearer picture of bacterial strain affects on incidence of GD.
Attempts at experimental reproduction of clinical GD in chickens
Experimental broiler studies have been completed to try to prove the theories presented herein. While additional work remains to be done, and additional experiments are currently underway with more planned, much has been learned about this complex disease in the research lab.
Outside-In Studies: Experimental inoculation of poultry with CP/CS strains under the skin (usually via subcutaneous injection) has been reported on by others at scientific meetings. This method was attempted as follows with results described.
- SQ injection of CP/CS: Different ages of cultures (18-24 hours best), different culture media (Cooked Meat best), different ages of birds (4-7 weeks best), different cultures (CP alone, CS alone, CP mixtures, CS mixtures, CP/CS mixtures, CP/CS + Staph. aureus, different origins of CP/CS cultures - skin, gut, liver - and GD "soups" [undefined anaerobic cultures of skin lesions]. Best results were obtained with a "6-way" culture consisting of a mixture of 3CP/3CS from different tissues spread out across the dendrograms created with isolates from clinical cases on endemic GD sites. Some GD soup cultures also reproduced GD, but seemed to lose their effectiveness after "aging" on the bench top.
- This work confirms that "outside-in" theory is possible.
Inside-Out Studies: Experimental challenge of poultry with CP/CS strains to attempt to reproduce the gut-bloodstream-skin "order of pathogenesis" were attempted as follows with results described.
- IV injection of CP/CS: "6-way" blend of CP/CS and some GD soups worked best. This work confirms that "inside-out" theory is possible.
- Oral gavage of CP/CS: Oral dosing of various mixtures of clostridia occurred on days 4 thru 8 after inoculation of various strains of coccidia to produce GIT mucosal damage. Diets fed during the oral studies included ABF, High Protein/High Fiber, and AGP/Ionophore feeds. In addition, Lomotil was also administered to birds to slow gut transit times in one experiment.
Results of oral experiments to date are NE production only in some birds first administered a pathogenic strain of E. maxima prior to clostridial gavage. No GD has been produced via oral challenge of CP/CS so far, although others have reported limited success with this oral challenge method at recent scientific meetings.
Missing Link 1: "Hole Puncher" Helper Pathogen: It is possible that there is an unknown intestinal pathogen (bacterial, viral or coccidial) required to "help" CP/CS escape the GIT and produce systemic disease. Such a pathogen may be capable of "punching holes" in the GIT to open a portal for CP/CS to enter the bloodstream. Such a pathogen may also open the door in the GIT wide enough to result in a "jail break" type scenario for all CP/CS strains residing in the intestine to exit the gut and end up in target tissues. Thus, the CP/CS isolates obtained from GD skin lesions when administered orally may not be capable of escaping the intestine without such helper organisms. This may be one problem associated with the creation of successful oral reproduction models of clinical GD.
Missing Link 2: Immunosuppressive Agents: It is possible that some degree of immunosuppression is required for CP/CS to become a systemic pathogen outside of the intestine. Studies of birds from GD and non-GD endemic sites indicate that CP/CS can become systemic in birds at various ages (as young as 2 weeks). Perhaps viral immunosuppressors, environmental stresses or other unknown factors affecting the bacterial protection mechanisms of poultry are required for overt GD disease to develop from circulating CP/CS organisms. Viruses such as CAV and Marek's Disease Virus (MDV), both of which affect heterophil numbers and function in chickens, are candidates for such helper agents.
Conclusions and future studies
GD is a complex disease process that is just now beginning to be better understood by the poultry industry.
The Author believes that GD will be proven to be a primary "gut disease" when all field and research data has been collected and carefully scrutinized.
Pathogenesis research is ongoing in several public and private research environments and answers will eventually be forthcoming from these efforts. Future studies will include intestinal microflora comparisons (both bacterial and coccidial), enteric and immunosuppressive virus interactions, affect of feed formulation, and molecular evaluation of bacterial strains from field cases.
From Proceedings of the "Midwest Poultry Federation Convention", St. Paul, Minnesota, U.S.A.
