Granulomas as a disease process are used by some host organisms to wall off infectious agents, and may occur as a result of persistence of inflammatory stimuli for extended periods of time. In poultry, granulomas in visceral organs can be caused by a number of agents - Mycobacterium avium (which causes avian tuberculosis), granulomatogenic mucoid E. coli (which can cause coligranulomas), Yersinia pestis (pseudotuberculosis), Eubacterium tortuosum, Aspergillus fumigatus, and the parasites Histomonas meleagridis, larval migrations of the nematode Ascaridia, and by the cestode Raillietina echinobothridia. Another etiological agent that cause granulomatous reactions in poultry that often mimics the ones described above is Tetratrichomonas gallinarum.
In a guest editorial in the journal ‘Avian Pathology’ titled ‘Coligranulomatosis (Hjarre and Wramby’s disease) reconsidered’, authors Landman and van Eck give several reasons for why the diagnosis of Hjarre’s disease/coligranulomatosis in large outbreaks of granulomatous disease in poultry flocks is often actually a misdiagnosis (Ref 1). They posit that the parasitic protozoa Tetratrichomonas gallinarum must be considered on the differential list in such cases. Some of the reasons they list include:
a. Coligranulomas generally occur sporadically in individual adult birds, with low flock prevalence, and are generally not of economic significance for poultry farming.
b. Koch's postulates were never fulfilled for Hjarre's disease. The authors discuss several research studies that have successfully reproduced coligranulomatosis by infecting birds by injections of the infectious agent (by artificial routes - intravenous, intramuscular) but never by the natural oral route.
c. Several reports that the authors deem as misdiagnoses have highly variable mortality rates with several causing economic losses in the flocks, but none of these studies were able to reproduce coligranulomatosis experimentally by orally inoculating E.coli isolates from diseased birds [and most were able to rule out tuberculosis as the cause].
d. The authors also cite reports of granulomatous disease in the caecum and liver in North American poultry flocks in which the etiology was described as unknown, because Koch postulates could not be fulfilled. These outbreaks had lesions consistent with a 2013 outbreak of granulomatous disease in poultry flocks in the Netherlands in which Landman et al. (Ref 2) fulfilled Koch’s postulates to demonstrate that the agent that caused upto 11% mortality in layers between 21 and 35 weeks of age was Tetratrichomonas gallinarum and not Escherichia coli.
In their impressive study, Landman et al. (Ref 2) started with an investigation of seven affected layer flocks that showed a high incidence of mortality which were all linked to one rearing farm. They isolated and cultured the protozoa from affected birds, and identified it by morphology and PCR, and also use FISH probes to rule out bacterial and fungal agents. They undeniably proved the infectious nature of the agent by using sentinel hens on the affected farms that subsequently developed the same lesions as in the original outbreak. The authors fulfil another one of Koch’s postulates by experimentally inoculating material from the outbreak into specific pathogen free Leghorns intracloacally or intravenously, re-isolating the protozoa and confirming protozoan identity by PCR.
The importance of both coligranulomatosis and Tetratrichomonas gallinarum mainly stems from the resemblance of the granulomas they produce to avian tuberculosis. Tetratrichomonas gallinarum as the sole causative agent has been subject to controversies because of subclinical infections, co-infections with Histomonas and age-related pathology due to which birds are affected only in the egg producing period. However, the paper and editorial by Landman et al. show that Tetratrichomonas gallinarum must be included in the differential diagnosis list in future outbreaks of graunulomatous disease alongside other well-known bacterial culprits.
References:
1. W. J. M. Landman & J. H. H. van Eck (2017) Coligranulomatosis (Hjärre and Wramby’s disease) reconsidered, Avian Pathology, 46:3, 237-241, DOI: 10.1080/03079457.2017.1291903
2. W.J.M. Landman, R.J. Molenaar, A. Cian, H.M.J.F. van der Heijden & E. Viscogliosi (2016) Granuloma disease in flocks of productive layers caused by Tetratrichomonas gallinarum , Avian Pathology, 45:4, 465-477, DOI: 10.1080/03079457.2016.1163325
