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Runting/Stunting/Cystic Enteritis Syndrome

by 5m Editor
10 September 2008, at 12:00am

By John A. Smith, DVM, MS, MAM, ACVIM, ACPV, Director of Health Services of Fieldale Farms Corp. and presented at the North Carolina Broiler Supervisor's Short Course Conference. This article provides an update on the clinical features, temporal and geographic progression, and some research and field observations bearing on the possible aetiology, epizootiology and management of this syndrome.

Introduction

Disease syndromes characterized by diarrhoea and reduced growth have been recognized in commercial broilers since at least the 1970s, and have been variously referred to as runting, stunting, pale bird, malabsorption, brittle bone and helicopter wing syndromes. A variety of viruses have been associated with these syndromes, including reoviruses, parvoviruses, enterovirus-like viruses, rotaviruses, astroviruses, and other “small round viruses”, but a clear etiological relationship has rarely been established. Many of these viruses are commonly found in healthy chickens as well. With the exception of the reoviruses (whose association with these syndromes is tenuous at best) most of these viruses are difficult to propagate in the laboratory, and no vaccines and few diagnostic techniques are available.

A new wave of an enteric syndrome commonly referred to as “runting/stunting syndrome” (RSS) has emerged in the major broiler-producing areas of the United States (and possibly other areas) over the last four years. This syndrome is characterized by diarrhoea and severe stunting within the first one to two weeks of life, poor economic performance and specific gross and histological lesions, and appears in many cases to be followed by secondary problems highly suggestive of immunosuppression. The purpose of this paper is to update the clinical features, temporal and geographic progression, and some research and field observations with bearing on the possible etiology, epizootiology and management of this syndrome.

History, Temporal and Geographic Progression of the Current Syndrome

In the early spring of 2003, an integrated broiler company in northwestern Georgia (Company A) experienced a syndrome characterized by severe flushing and stunting during the first week of life and severe performance shortfalls in affected broiler flocks1. Gross and histological lesions similar to those described subsequently herein were noted in numerous cases. The syndrome abated somewhat during the summer of 2003. To our knowledge, this is the first well documented case of this particular syndrome. During the winter of 2003-2004, Company A was again severely affected and at least two other companies in Georgia and Alabama were sporadically affected. The problem again lessened somewhat in the summer of 2004.

Since 2004, the syndrome has been reasonably well documented in other complexes in Georgia as well as in complexes in Delmarva, North Carolina, South Carolina, Alabama, Arkansas, Louisiana, Mississippi, Virginia, Missouri and Tennessee. Some complexes appear to have recovered while others have continued to experience recurring seasonal episodes through 2007. Some complexes appear to have remained relatively unaffected. The author has consulted with colleagues who indicate the occurrence of a clinically similar syndrome in Great Britain, Jamaica, Mexico and Panama. The colleague in Mexico demonstrated the characteristic cystic enteropathy on histopathology.

Clinical Signs and Impact

Signs consist of a marked unevenness that is glaringly evident by 10 days of age. Experienced observers can detect definite signs by 6 days of age, and signs were initially reported in Company A as early as 3 days of age. A portion of chicks in affected flocks will display pasting of the perineum below the vent, often resulting in scalding of the skin. In the most severely affected houses, the litter and feed lids may become wet and slick, and there may be a sour odour in the house associated with the wet litter and feed. A few birds may experience cloacal impactions or prolapses. The down on the ventrum may appear matted from sitting in wet litter. The birds typically exhibit a transient phase of huddling as if they are febrile. Many of the stunted birds appear visibly ill with a ruffled, hunched-up, potbellied appearance and waddling gait. Feathering is poor, with some birds exhibiting protruding “helicopter” primary feathers on the wings. The flock will fall behind on feed and water consumption, often during the early starter phase. A number of affected complexes have noted that the syndrome is followed by a wide variety of secondary conditions such as severe colibacillosis, gangrenous dermatitis, inclusion body hepatitis, air sacculitis, cellulitis, purulent arthritis, osteomyelitis and adverse vaccine reactions (especially to Infectious Laryngotracheitis Virus Vaccine) leading to speculation that immune suppression is involved.

The question remains as to whether the syndrome itself is immunosuppressive or whether the syndrome is a consequence of another immunosuppressive condition such as Infectious Bursal Disease and/or Chicken Infectious Anemia. In the author’s opinion, this is clearly a distinct infectious disease and like any infectious disease, the clinical expression may be influenced by coexisting immunosuppressive diseases. Final feed conversion, daily gain and uniformity are severely impacted. Direct mortality from the disease itself appears to be fairly low in most (but not all) cases but mortality from culling and from the secondary conditions can be severe. Company A experienced weeks in 2004-2005 in which the complex average livability for a small bird was as low as 84 per cent and feed conversions suffered by at least 20 points1. The lack of uniformity may lead to increased condemnations due to “septicaemia-toxaemia” and contamination issues. Secondary septic conditions also increase condemnations.

Gross Lesions

Gross lesions include general paleness of the tissues, especially the shanks and intestinal serosa. The mid-gut serosa will often appear very white as opposed to the normal pink-grey color. The bone marrow is usually normal but some affected birds are anaemic. The bursa and thymus are variable but frequently normal during the acute phase, becoming atrophied in the chronic phase. The spleen is frequently very small. Livers are often small and dark, with enlarged gall bladders. Proventriculitis, pancreatic atrophy and mild hydropericardium seem to be a feature in some cases2. The hallmark lesion is a moderately to markedly distended, extremely thin, translucent gut with undigested feed suspended in clear, thin and watery mucus. There are no other gross serosal or mucosal lesions. The caecum is often distended with gas and brown-tinged clear watery fluid or foam. The kidneys may be mildly swollen in some cases.

Histopathology

Histopathological lesions include villous atrophy, clubbing and fusion and a remarkable crypt dilation and hypertrophy with accumulation of amorphous material, cyst formation and squamous metaplasia of the crypt epithelium. Pancreatic vacuolar degeneration and severe chronic lymphoplasmacytic enteritis have been noted in experimental cases2. Dr Fred Hoerr’s group at Auburn University has consistently identified microsporidian organisms resembling Myxospora in the amorphous debris filling the cystic crypts3. Dr Hoerr has also stressed that the most appropriate characterization of the microscopic lesion is the dramatic change in the crypt to villus ratio, with the crypt depth becoming markedly increased in relation to the villus height.

Clinical Pathology and Serology

Comparison of total protein, albumen, globulin, aspartate aminotransferase (AST), bile acids, lactic dehydrogenase (LDH) and uric acid between affected and ostensibly unaffected chicks in the same houses revealed some differences but none was considered clinically relevant and all could be attributed to general antigenic stimulation, dehydration, handling and/or inanition.

A comparison of affected and unaffected flocks for processing age ELISA titers to Infectious Bursal Disease Virus (IBDV), type I avian adenoviruses, Reovirus, Newcastle Disease Virus (NDV), Infectious Bronchitis Virus (IBV), Avian Encephalomyelitis Virus (AEV), Chicken Infectious Anemia Virus (CIAV), and Haemorrhagic Enteritis Virus (HEV) revealed no clinically meaningful differences.

Serum samples were obtained from hen flocks producing fewer or greater numbers of affected progeny flocks, before and after the peak of the syndrome in the spring of 2005. The hen flocks were selected based on an ongoing RSS scoring system in the broilers. Weighted average progeny scores were calculated for each hen flock during the peak period of the syndrome, and flocks with the highest (worst) and lowest scores were examined. No significant trends were noted for CIAV, IBDV or Reovirus titres in these hens. Interesting associations between RSS and seroconversion to HEV in both challenged broilers and in hen flocks associated with cases in broiler progeny have been noted but the meaning of these associations is still unclear.

Epizootiology, Reproduction of the Syndrome and Transmission

Analysis of the hen population in two companies implicated progeny from younger flocks to a disproportionate degree. Company A sold eggs to several companies during the peak of the outbreak. These companies reported no signs of RSS in the progeny from these eggs, casting some doubt on vertical transmission. However, the existence of vertical transmission and the importance of maternal exposure or maternal antibody remain to be elucidated. The author has not been able to make any clear associations with breed.

The signs and/or lesions have been transmitted numerous times by several researchers using gavages of crude and filtered (0.22μ) gut homogenates, chloroform-treated filtrates, chick- and embryo-passaged materials, and by exposure to contaminated litter. The condition has been transmitted to SPF leghorns, broilers, late stage chicken embryos, and turkey poults. Dr John K. Rosenberger has transmitted signs and lesions with a pure culture of a single viral agent that appears to be a rotavirus.4 In these experiments, transmission to uninoculated contacts was extremely rapid and efficient, suggesting rapid and copious shed by the inoculated chicks and/or a very low infectious dose.

Dr Guillermo Zavala2 at the University of Georgia obtained contaminated litter and severely affected 13-day-old chicks from a broiler house and placed them in two isolated colony houses. The birds were kept for 13 more days and then removed. The following day, 150 new day-old chicks were placed in each house. These were kept for 13 days and removed and the process repeated using chicks from a single, young hen flock of the same breed each time. The chicks were derived from the same complex but the same specific hen flock was not used each time. Subsequent groups were kept for 10 to 18 days, with one or two days down time and no clean-out or other treatment. Beginning with the fourth batch, 150 controls from the same hen flock as the principals were placed in a clean house each time. This house was cleaned and disinfected between each successive batch. The body weights of the principals were repeatably approximately 50 per cent that of the controls, uniformity was terrible, and gross and microscopic lesions became increasingly apparent with each succeeding batch. At least 20 batches were placed in these houses for testing of various management interventions, with similar results each time. These findings strongly suggest that the agent takes up residence and persists in the house but that regular cleaning and disinfection may be able to exclude the agent(s). Most of the batches placed in these houses came from a complex experiencing widespread cases, and the donor hens were generally selected on the basis of association with field cases. The fact that the control house remained free of signs and lesions in all batches (except one described subsequently) also suggests that vertical shed is likely transient if it occurs at all.

Further examination of vertical transmission and possible maternal immunity:
Dr Zavala2 reared and housed 4 groups of 25 broiler breeders in clean facilities. After peak production, eggs were collected separately from each group to produce 9 progeny hatches every other week. Each group of progeny was reared to 10-14 days of age, at which time individual body weights were determined and post-mortem examinations performed. The first 4 hatches were produced without exposure of the hens or progeny to RSS. After the fourth hatch, the hens in two groups were gavaged with 1.5ml of intestinal contents from severely affected broilers from the contaminated colony houses on two consecutive days. The other two groups served as uninoculated controls. Five more hatches were produced. The first four of these hatches (numbers 5-8) were reared in clean facilities without exposure to RSS, while the fifth hatch (hatch 9 overall) was divided among the two highly RSS-contaminated colony houses and the clean control house. The objective of hatches 5-8 was to observe for signs of possible vertical transmission, while hatch 9 was designed to assess the effects of possible maternal immunity. Since the eggs for hatch 9 were produced approximately 10 weeks post-inoculation, it was hypothesized that any potential shedding should have stopped and maternal immunity might be present.

The progeny from the exposed hens in hatches 6 and 7 (the second and third hatches post inoculation) did exhibit weight depression compared to the progeny from the unexposed hens but the characteristic signs and lesions of RSS were not observed. Weights were comparable in hatch 8. It must be noted that the inoculum was derived from one of the later batches in the contaminated colony houses, which were likely heavily contaminated with not only the putative RSS agent(s) but also any number of other pathogens such as CIAV and Reoviruses. Any of these vertically transmitted agents could have been present in the crude inoculum and could have contributed to progeny weight depression without overt RSS.

In hatch 9, maternal exposure did not appear to offer any protection to exposure of progeny to the contaminated houses. The chicks from the exposed hens were as severely affected as those from the unexposed hens. Again, after approximately 20 batches in rapid succession, the challenge in the contaminated houses may have been overwhelming. Interestingly, the chicks from both the inoculated and uninoculated hens in the clean control house also developed characteristic signs and lesions of RSS in hatch 9. This house had been used for approximately 17 control batches, had been cleaned and disinfected each time, and until this batch had never produced signs or gross or microscopic lesions of RSS. These events suggest that the inoculated hens may have shed the agent at 10 weeks post inoculation, and that their progeny transferred the infection laterally to the progeny of the uninoculated hens. The questions of vertical transmission and maternal immunity therefore remain tantalizing ones.

Two batches of chicks were placed on the litter used for the RSS-challenged hens. The hens were removed approximately 20 weeks post challenge, and the first batch was placed within the week and held for 25 days. The second batch was placed within 48 hours of removal of the first batch and held for 11 days. No signs or lesions of RSS were noted, suggesting that any shedding that had occurred had stopped and the agent(s) had disappeared from the environment.

Aetiology

Bacteria:
E. coli carrying genes associated with attaching-effacing strains have been isolated from some cases. However, challenge of specific pathogen-free (SPF) and broiler chickens with these strains caused only minor alterations in weight gain, and did not reproduce any signs or lesions whatsoever. Some companies have claimed benefits from prestarter antibiotic programs, but the author has not been able to duplicate this response. Antibiotics, including neomycin/ oxytetracycline (Neo-Terra), ormetoprim/sulfadimethoxine (Rofenaid), enrofloxacin (Baytril), and penicillin seem to ameliorate the secondary complications, but do not significantly affect the progress of the syndrome itself. The consensus seems to be that the primary agent is likely viral, and while this may result in adverse alteration of the gut flora (“dysbacteriosis”), bacterial agents are probably only secondarily involved.

Viruses:
Reoviruses, coronaviruses, type I adenoviruses, and a putative rotavirus have been isolated, and EM and PCR studies have implicated rota, corona, reo, astro, and parvoviruses. Dr Zavala at the University of Georgia, using the contaminated colony house system described earlier, compared the responses of chicks with high maternal antibody titers for IBDV, Reovirus and CIAV, to those with low titres. Chicks with higher maternal titres fared no better than those with low titres2.

One company produced an autogenous vaccine to one of these novel Reoviruses. Chicks from hens that received the autogenous vaccine in addition to the company’s standard Reovirus program were compared to those from hens receiving the company’s standard Reovirus program only in the contaminated colony house system described earlier. The autogenous Reovirus vaccine offered no protection. A similar comparison was made in Horsfal isolation units using gavage with homogenized intestines, with a similar outcome5. These observations were supported by field observations in the company as well.

In the author’s opinion, the direct or primary involvement of a Reovirus appears unlikely. Extensive testing of affected broilers, associated breeders, and hatchery vaccines in one company has effectively ruled out a role for Avian Leukosis Virus. Again, Dr Rosenberger has transmitted the signs and lesions with a single virus that appears to be a rotavirus that appears to be a highly likely candidate. Dr Holly Sellers is also continuing investigations on novel reoviruses and astroviruses.

Interventions

The number of interventions attempted are literally too numerous to recall. Company A, which was severely affected for three years and has apparently recovered, made adjustments in IBDV, Reovirus and CIAV vaccination programs, including inclusion of autogenous IBDV and reovirus vaccines in the pullet programs. They also obtained additional housing to increase down-time, gave added attention to incubation, brooding, litter management, diet formulation and mill sanitation and maintenance. The breed cross was also changed. The manager admits that he cannot attribute the apparent success to any specific item although down-time is high on the list.

Other interventions by other companies include attempts at HEV vaccination of pullets, prestarter antibiotic programs, litter treatments, water acidification, dietary adjustments and supplements, etc. Of the long list, few have produced measurable results individually. At one company, heating of houses to extreme temperatures (up to 119º F) for extended periods (up to 5 days) appears to be helpful in many (but not all) cases, while clean-out has sometimes failed to prevent recurrence.

Specific Observations Bearing on Management of the Syndrome

Down-time and heat sensitivity:
The studies in the contaminated colony houses at the University of Georgia clearly indicate that built-up litter and short down-times exacerbate the syndrome2. In laboratory studies conducted by Dr Sellers at the University of Georgia, heat treatment of gut homogenates reduced the deleterious effects of the inoculum on body weight of gavage challenged chicks. Room temperature for 4 days and 37ºC for 24 hours had no effect, but 45ºC for 4 hours and 60ºC for 2 hours resulted in significant amelioration5.

Dr Zavala, using the contaminated colony house system described previously, held one contaminated house out for one 17 day cycle, and heated that house to 92-105ºF for days 11-15 of the down time. The house was otherwise not cleaned or disinfected. The other contaminated house grew an affected flock as usual, and the clean house also grew a flock as usual and was cleaned and disinfected as usual. On the subsequent flock, the heat-treated house had body weights of 90.6% and 60.5% of the controls at 5 and 14 days, respectively, while the untreated house had body weights of 73.9% and 53.9% of the controls. These differences were statistically significant2. On another occasion, both contaminated houses were allowed to sit empty for 22 days but with no further interventions (heating, cleaning, etc.). The body weight depression in these trials was roughly 35%, compared to about 50% in the other trials2. These results suggest that down-time and heating of the houses may be helpful but cannot be counted upon to eliminate the problem.

Age susceptibility:
In another experiment in the contaminated houses, Dr. Zavala held half of the chicks intended for the two contaminated houses in the clean control house until 11 days, at which time they were moved to the contaminated houses with their hatch mates that had been exposed since day 0. The delay in exposure significantly reduced (but did not abrogate) the effects of the exposure on body weight gain, uniformit, and expression of lesions2. These results suggest that delaying exposure, such as by cleaning and disinfecting the brood chamber, may be beneficial. The lack of significant signs (other than a transient diarrhoea) in the gavaged hens of the vertical transmission study suggests that there may be an age-associated immunity and therefore controlled exposure might be possible should vertical transmission or protection from maternal antibody appear important in control.

Treatment with Metronidazole:
Metronidazole is effective against anaerobic bacteria and protozoa. Half of the chicks in each of the contaminated houses were treated with this drug as a means of examining the role of anaerobes and protozoa in the syndrome. (Metronidazole is illegal in the United States and the objective was not to evaluate potential treatment with this particular drug.) The treatment offered no protection.

Management practices:
Because of the tendency to huddle due to fever, some managers increase the brooding temperature to 92-92ºF on affected flocks. This may be useful as long as it is not overdone and the chicks are not heat-stressed. In an effort to draw chicks away from the wet litter around the feeders, some managers have placed feed lids out in the middle of the house. Running a strip of paper down the middle of the house (as many managers now place under the drinkers to attract the chicks) and placing extra lids periodically on this strip may also help to lure chicks away from the wet litter. Higher light levels during the acute phase may also stimulate more movement, feeding and drinking. Increased ventilation, cake removal and top dressing with fresh shavings after the acute phase of flushing may also be necessary. Most managers turn chicks out of partial house brooding as soon as possible after the syndrome is noted.

Vaccination:
Several companies have commissioned production of killed oil emulsion vaccines from the putative rotavirus for administration either to pullets or hens in lay. The consensus appears to be that the vaccine has ameliorated the syndrome but has not eliminated it. In the author’s complex, the severe early huddling, flushing and stunting is less prevalent but a lesser degree of flushing and stunting persists. Although generally less severe, characteristic lesions are still observed in these birds. In some cases, it appears as though the maternal antibody has perhaps delayed the onset of the syndrome, and these older chicks handle the infection better, with less severe consequences. The apparent partial response suggests that this may indeed be a multifactorial syndrome, and has generated increased interest in the reoviruses and astroviruses.

Current Progression of the Syndrome

In the author’s experience, as determined by a flock scoring system in place since February 20055, there is a definite seasonal pattern, with overt clinical cases appearing in December, peaking in February-March, declining in April, and finally abating in June. Overt signs reach a nadir in October. Additionally, it appears that clinical severity decreased after the first year (winter of 2004-05) but more flocks were affected with a milder form of the disease. In other words, it appeared that severity has decreased but prevalence had increased.

After use of the vaccine for the winter of 2007-08, it appears that both the incidence and severity may have decreased but it is mainly the severity that has been reduced. The effects on economic performance (livability, weight gain, feed conversion) were equally as severe in the second and third years as in the first year, and the secondary effects were possibly worse. The imposition of ILT vaccination on flocks that had experienced RSS was frequently problematic.

As another example, we track the incidence of gangrenous dermatitis (GD) via a reporting system by the broiler flock supervisors. The three winters of RSS (2004-05, 2005-06, and 2006-07) were some of the worst on record for GD, and 2005-2006 was slightly worse than 2004-2005. In addition, cases of Inclusion Body Hepatitis were seen in the winters of 2005-06 and 2006-07, the first time this disease had been noted since an outbreak in 1998. Condemnations for septicaemia-toxaemia have been steadily increasing since the onset of the clinical RSS outbreak in late 2004.

There was a spike in air sacculitis condemnations in the late winter of 2005-2006 that did not occur in the previous winter, and as mentioned, the use of ILT vaccine the past year was more problematic than ever. These secondary problems have continued into the winter of 2007-2008 but the apparent incursion of a variant IBV, an effective intervention for GD and use of vectored LT vaccines in place of CEO vaccine have made direct comparisons to previous years difficult. In the earlier years, multiple houses were observed with a combination of these problems (GD, IBH and adverse vaccine reactions).

This pattern suggests immune suppression. Indeed, other immunosuppressive diseases would be expected to make this syndrome worse. However, due to the extremely early onset of signs, it is difficult to conceive that immune suppression developing before 6 days of age is a prerequisite for development of this condition. The author is of the opinion that the agent(s) causing clinical RSS may be directly and profoundly immunosuppressive themselves. The putative rotavirus has been found in bursas4.

The reason for the eventual disappearance in some complexes is unknown, as a literal 'shotgun' approach has generally been taken. One might speculate that gradual spread eventually leads to population immunity, particularly in the hens, leading to either decreased shed and/or maternal immunity, but there is currently insufficient information about either vertical shed or maternal immunity to draw any conclusions regarding the plausibility of this hypothesis.

It has been observed that the syndrome often seems worse and persists longer in small bird complexes. One might further speculate that the cycle length, irrespective of actual down time, may play a role. With a disease that strikes so early in the life of the bird, assuming the birds do seroconvert, become immune as a group, and stop shedding, the later part of a long large-bird growing cycle may be tantamount to down time. In any case, should this syndrome eventually disappear (as similar syndromes have tended to do in the past), we should continue to seek answers to this problem. Our knowledge of enteric viruses in broilers is woefully inadequate. Similar syndromes are likely to recur in the future, and we do not need to be starting from scratch each time.

References

  1. Dufour-Zavala, L. Cystic enteritis: reproduction of the disease and attempted control measures. Proceedings of 40th National Meeting on Poultry Health and Processing, 19-21 October 2005, 20-21.
  2. Zavala, G. Personal communication.
  3. Hoerr, F.J. Personal communication.
  4. Rosenberger, J.K. Personal communication.
  5. Sellers, H. Personal communication.
  6. Smith, J.A. Runting and stunting syndrome (cystic enteritis): a field perspective. Proceedings of 40th National Meeting on Poultry Health and Processing. 19-21 October 2005. 6-19.

September 2008