Characterization of immune responses and immunopathology in turkeys experimentally infected with clostridial dermatitis-producing strains of Clostridium septicum.

Clostridium septicum is one of the major causative agents of clostridial dermatitis (CD), an emerging disease of turkeys, characterized by sudden deaths and necrotic dermatitis. Despite its economic burden on the poultry industry, the immunopathological changes and pathogen-specific immune responses are poorly characterized. Here, we used three strains of C. septicum, namely Str. A1, Str. B1 and Str. C1, isolated from CD field outbreaks, to experimentally infect turkeys to evaluate local (skin and muscle) and systemic (spleen) pathological and immunological responses. Results showed that while all three strains produced an acute disease, Str. A1 and B1 caused significantly higher mortality when compared to Str. C1. Gross and histopathology evaluation showed that birds infected with Str. A1 and B1 had severe inflammatory, edematous, granulomatous and necrotic lesions in the skin, muscle and spleen, while these lesions produced by Str. C1 were relatively less severe and mostly confined to skin and/or muscle. Immune gene expression in these tissues showed that Str. B1-infected birds had significantly higher expression of interleukin (IL)-1ß, IL-6 and interferon (IFN)γ genes compared to uninfected control, suggesting a robust inflammatory response both locally as well as systemically. The transcription of IL-1ß and IFNγ in the muscle or spleen of Str. A1-infected birds and IL-1ß in the skin of Str. C1-infected group was also significantly higher than control. Additionally, Str. A1 or B1-infected groups also had significantly higher IL-4 transcription in these tissues, while birds infected with all three strains developed C. septicum-specific serum antibodies. Furthermore, splenic cellular immunophenotyping in the infected turkeys showed a marked reduction in CD4+ cells. Collectively, it can be inferred that host responses against C. septicum involve an acute inflammatory response along with antibody production and that the disease severity seem to depend on the strain of C. septicum involved in CD in turkeys.

Clostridium Septicum Endogenous Endophthalmitis as the Initial Manifestation of Colorectal Carcinoma: Clinical Case Report and Literature Review.

PURPOSE: To describe the presentation and clinical course of a case of endogenous endophthalmitis caused by Clostridium septicum, an anaerobic and gram positive bacteria. METHODS: Observational report of a clinical case presented in Spain. CLINICAL CASE: A 61-year-old male patient was referred to our hospital with a diagnosis of endophthalmitis of his left eye since ten days prior to presentation, and a history of poor response to medical treatment. Evisceration was performed, and C. septicum was isolated from a sample of the vitreous humor. Fourteen days after surgery, the patient returned with orbital cellulitis, and exenteration was performed. Forty-two days after initial presentation, colonoscopy revealed an adenocarcinoma of the proximal colon. Surgical resection of the tumor was performed, and clinical recovery was achieved. CONCLUSIONS: iSystemic C. septicum infection without a traumatic cause has been associated with malignancy, although an initial presentation of endophthalmitis has rarely been reported. In cases of clostridial endogenous endophthalmitis, investigation for colorectal carcinoma is indicated.

Clostridium septicum endophthalmitis as the first manifestation of a colon adenocarcinoma: A case report.

Clostridium septicum endophthalmitis is an extremely rare infection with only a few cases reported in the literature. It has an endogenous origin and is associated with gastrointestinal and haematological malignancies. We present the case of a 62-year-old male who presented this infection as the first manifestation of a colon adenocarcinoma.

Colon Adenocarcinoma Associated With Clostridium Septicum Endophthalmitis Detected on 18F-FDG PET/CT.

Endogenous Clostridium septicum endophthalmitis is a rare and fulminant ocular infection, usually encountered in immunocompromised or diabetic patients. It is also highly associated with both gastrointestinal and hematologic malignancies. We describe herein the detection of an adenocarcinoma of the cecum on PET/CT with F-FDG in a patient with an active endogenous C. septicum endophthalmitis of the right eye. FDG PET/CT should be considered for all patients with endogenous endophthalmitis to exclude an occult malignancy, especially colorectal cancer.

Spontaneous C. septicum gas gangrene: A literature review.

As the infectious disease paradigm undergoes a subtle shift, unusual infections associated with malignancy and immunosuppression are being increasingly reported. Spontaneous or non-traumatic Clostridium septicum infection is one such unusual infection which has gained prominence. This article aims to understand the pathophysiology, clinical manifestations and current trends in diagnosing and treating this rare but deadly infection. To understand the multifactorial causation of this infection a review of published cases of spontaneous C. septicum gas gangrene was performed and a total of 94 such cases were identified. Several factors were analyzed for each case: age, infection location and underlying illness, presenting signs and symptoms, neutropenia, gross pathology of the colon, antibiotic use, surgical intervention, and survival. A known or occult malignancy was present in 71% patients and an overall mortality of 67% was observed.

Effects of dexamethasone immunosuppression on turkey clostridial dermatitis.

Clostridia represents a group of anaerobic spore-forming bacteria ubiquitous in the poultry environment. They are widely distributed in soil and survive for many years as highly resistant, inactive spores. They enter the body through wounds and contaminated feed as active bacteria or spores. Multiplication of clostridial bacteria occurs only in the absence of oxygen or in environments with very low concentrations of oxygen. During active multiplication, the clostridial organisms produce several toxins that are responsible for most of the clinical signs seen in clostridial diseases. Immunosuppression is a problem for the poultry industry. In modern, intensive poultry-rearing conditions, stress due to high population densities pose a considerable challenge for the immune system, and infectious agents can exploit this situation to cause disease. Immunosuppression may predispose turkeys to clostridial infection, resulting in clostridial dermatitis and mortality. The purpose of this study was to determine whether immunosuppression predisposes turkeys to clostridial infection and causes clostridial dermatitis. We immunosuppressed 10-wk-old turkey poults with dexamethasone. The birds immunosuppressed and not immunosuppressed were then challenged with Clostridium perfringens, Clostridium septicum, or both and examined for the development of clostridial dermatitis. The dexamethasone-treated birds were found to be more susceptible to C. peifingens/C. septicum challenge and developed clostridial dermatitis than the no-dexamethasone-treated birds through the subcutaneous route. However, oral inoculation of the same agents did not cause any dermatitis lesions in either of the groups.

Clostridium septicum can cause distant myonecrosis in patients with ovarian cancer.

A case report of lethal distant myonecrosis with gas gangrene is presented. Blood cultures and tissue biopsies revealed Clostridium septicum. The 55-year-old female patient presented with recurrent ovarian cancer of transitional cell type, initially diagnosed as FIGO IIb in January 2011, with hepatic metastasis and invasion of the ceacal wall. She underwent several operations, including partial bowel and liver resection in September 2011. Second-line therapy with topotecan three weekly was started in October 2011 while the patient was still in the hospital. During this chemotherapy, the patient revealed symptoms of severe pain and erythema of the skin. Within hours she died of sceptic shock after a debridement. The diagnosis was gas gangrene due to Clostridium septicum. Because it is a rare and severe disease and the time slot in which therapeutic measures can be taken is narrow, we discuss clinical symptoms and therapeutic options.

Genome-wide differential gene expression profiles in broiler chickens with gangrenous dermatitis.

Gangrenous dermatitis (GD) is a disease of poultry characterized by necrosis of the skin and severe cellulitis of the subcutaneous tissues caused by infection with Clostridium septicum (CS) and/or Clostridium perfringens (CP) type A. While GD causes significant morbidity, mortality, and economic loss to the poultry industry, the fundamental mechanisms underlying this host-pathogen interaction are relatively unknown. This study used comparative global gene expression microarray analysis of GD-affected and clinically healthy chickens from a recent GD outbreak to glean insights into the molecular and cellular changes associated with this disease process. Histopathologic and immunohistochemical analyses confirmed extensive muscle damage and prominent leukocyte infiltration in the skin of GD-affected birds but not in healthy controls. The levels of mRNAs in the skin and underlying muscle corresponding to 952 microarray elements were altered in GD-afflicted birds compared with healthy controls, with 468 being increased and 484 decreased. From these, a subset of 386 genes was identified and used for biologic function and pathway analyses. The biologic functions that were most significantly associated with the differentially expressed genes were "inflammatory response" and "cellular growth and proliferation" classified under the categories of "disease and disorders" and "molecular and cellular functions," respectively. The biologic pathway that was most significantly associated with the differentially expressed genes was the nuclear factor-erythroid 2-related factor 2 (NRF2)-mediated oxidative stress pathway. Finally, in vitro infection of chicken macrophages with CS or CP modified the levels of mRNAs encoding interferon (IFN)-alpha, IFN-gamma, interleukin (IL)-1beta, IL-6, IL-12p40, tumor necrosis factor superfamily 15 (downregulated), IL-8, and IL-10 (upregulated), thus confirming the suppressive effect of GD on the chicken immune system.

Molecular and cellular basis of microvascular perfusion deficits induced by Clostridium perfringens and Clostridium septicum.

Reduced tissue perfusion leading to tissue ischemia is a central component of the pathogenesis of myonecrosis caused by Clostridium perfringens. The C. perfringens alpha-toxin has been shown capable of inducing these changes, but its potential synergy with perfringolysin O (theta-toxin) is less well understood. Similarly, Clostridium septicum is a highly virulent causative agent of spontaneous gas gangrene, but its effect on the microcirculation has not been examined. Therefore, the aim of this study was to use intravital microscopy to examine the effects of C. perfringens and C. septicum on the functional microcirculation, coupled with the use of isogenic toxin mutants to elucidate the role of particular toxins in the resultant microvascular perfusion deficits. This study represents the first time this integrated approach has been used in the analysis of the pathological response to clostridial toxins. Culture supernatants from wild-type C. perfringens induced extensive cell death within 30 min, as assessed by in vivo uptake of propidium iodide. Furthermore, significant reductions in capillary perfusion were observed within 60 min. Depletion of either platelets or neutrophils reduced the alteration in perfusion, consistent with a role for these blood-borne cells in obstructing perfusion. In addition, mutation of either the alpha-toxin or perfringolysin O structural genes attenuated the reduction in perfusion, a process that was reversed by genetic complementation. C. septicum also induced a marked reduction in perfusion, with the degree of microvascular compromise correlating with the level of the C. septicum alpha-toxin. Together, these data indicate that as a result of its ability to produce alpha-toxin and perfringolysin O, C. perfringens rapidly induces irreversible cellular injury and a marked reduction in microvascular perfusion. Since C. septicum induces a similar reduction in microvascular perfusion, it is postulated that this function is central to the pathogenesis of clostridial myonecrosis, irrespective of the causative bacterium.