Spirochetosis Research Articles

Colorectal problem in leptospirosis

Dear, Editor, leptospirosis is an important zoonotic leptospiral infection. This infection is common and endemic in several tropical countries. The patients with leptospirosis usually have high fever and other systematic clinical problems such as renal failure and jaundice. The colorectal manifestation of leptospirosis is possible but little mentioned. Sometimes, the colorectal presentation of leptospirosis might be missed or incorrectly diagnosed. The good example is the missed diagnosis of leptospirosis as colon cancer [1]. Colon ulcer might be detected by colonoscopy study [1]. The pathogenesis is according to colonic spirochetosis pathological process. Direct colonic involvement might be shown by histological study. Indeed, the gastrointestinal symptoms including diarrhea is observable in cases with leptospirosis [2]. The patient might also have severe abdominal pain [2]. In severe case, abdominal CT scan might reveal pancolitis [3]. In fact, colon might be an affected organ in leptospirosis. In rare case, ischemia of colon is observable [4 - 5]. In any case with atypical clinical problem, colorectal manifestation might be a clinical feature of leptospirosis. The practitioner should recognize and consider this problem in any case from or having history of visiting to tropical endemic area.

Isolates from Colonic Spirochetosis in Humans Show High Genomic Divergence and Potential Pathogenic Features but Are Not Detected Using Standard Primers for the Human Microbiota.

Colonic spirochetosis, diagnosed based on the striking appearance in histological sections, still has an obscure clinical relevance, and only a few bacterial isolates from this condition have been characterized to date. In a randomized, population-based study in Stockholm, Sweden, 745 healthy individuals underwent colonoscopy with biopsy sampling. Of these individuals, 17 (2.3%) had colonic spirochetosis, which was associated with eosinophilic infiltration and a 3-fold-increased risk for irritable bowel syndrome (IBS). We aimed to culture the bacteria and perform whole-genome sequencing of the isolates from this unique representative population sample. From 14 out of 17 individuals with spirochetosis we successfully isolated, cultured, and performed whole-genome sequencing of in total 17 isolates, including the Brachyspira aalborgi type strain, 513A. Also, 16S analysis of the mucosa-associated microbiota was performed in the cases and nonspirochetosis controls. We found one isolate to be of the species Brachyspira pilosicoli; all remaining isolates were of the species Brachyspira aalborgi Besides displaying extensive genetic heterogeneity, the isolates harbored several mucin-degrading enzymes and other virulence-associated genes that could confer a pathogenic potential in the human colon. We also showed that 16S amplicon sequencing using standard primers for human microbiota studies failed to detect Brachyspira due to primer incompatibility.IMPORTANCE This is the first report of whole-genome analysis of clinical isolates from individuals with colonic spirochetosis. This characterization provides new opportunities in understanding the physiology and potentials of these bacteria that densely colonize the gut in the individuals infected. The observation that standard 16S amplicon primers fail to detect colonic spirochetosis may have major implications for studies searching for associations between members of the microbiota and clinical conditions such as irritable bowel syndrome (IBS) and should be taken into consideration in project design and interpretation of gastrointestinal tract microbiota in population-based and clinical settings.

Hiding in Plain Sight: Colonic Spirochetosis in Humans.

In 1967, Harland and Lee made a startling discovery: in some humans, the colonic epithelium is covered with a "forest" of spirochetes (W. A. Harlan, and F. D. Lee, Br Med J 3:718-719, 1967, https://doi.org/10.1136/bmj.3.5567.718). In this issue of Journal of Bacteriology, Thorell et al. present a systematic analysis of the prevalence and diversity of the spirochetes Brachyspira aalborgi and Brachyspira pilosicoli in the human colon. These and prior studies provide avenues toward resolving important questions: what bacterial and host parameters contribute to this extensive colonization, and what impact does it have on human health?

1614 Asymptomatic Intestinal Spirochetosis With Colonic Ulcerations

INTRODUCTION: Both the origin and commensal or pathogenic nature of intestinal spirochetes (IS) in humans are poorly understood. Colonization is predominantly found in homosexual males and in HIV patients.1 Homosexual males have shown colonization rates up to 20.6-62.5% leading scientists to hypothesize that IS could be sexually transmitted.2 Colonization can be associated with severe clinical symptoms like persistent diarrhea and rectal bleeding, especially in children.3 Therefore, a greater understanding of clinical presentation and risk factors is needed. CASE DESCRIPTION/METHODS: A 51-year-old asymptomatic male with compensated alcoholic cirrhosis presented for a screening colonoscopy. He denied NSAID use and a personal or family history of inflammatory bowel disease. Colonoscopy revealed multiple clean-based ulcers in the cecum and ascending colon. Histologic examination of the specimens on H&E stain revealed colonic mucosa with focal, acute inflammation and microorganisms consistent with spirochetes. No granulomas, crypt architectural distortion, or dysplasia were identified. The fuzzy, basophilic fringe-like microorganisms were positive for GMS and PAS stains and negative for FITE stain. The findings were consistent with IS and the patient was treated with metronidazole. DISCUSSION: The clinical significance of IS in humans is not well defined. Presentation may vary from asymptomatic to causing chronic diarrhea, rectal bleeding, abdominal pain, and weight loss. IS can be associated with immunodeficiency, alcoholism and drug abuse, poor hygiene, sexual practices, and concomitant bowel content stasis. Pathology reveals presence of spirochetes in the brush border. Transmission electron microscopy reveals spirochetes attached to enterocytes with associated shortened or depleted microvilli. Often endoscopy in IS-infected patients is normal, but in this rare presentation of intestinal spirochetosis, ulcerations of colonic mucosa were noted. Metronidazole is an effective treatment.4-5

1555 Intestinal Spirochetosis: A Call to Unravel the “Spiral” of Undetermined Significance

INTRODUCTION: Intestinal Spirochetosis (IS) is a rare incidental finding on routine biopsies of the colon, thought to be a commensal organism more prevalent among those with HIV, immunocompromised, or those in developing countries. Anecdotally, it does not seem to be widely known among practicing gastroenterologists, and in those who have encountered it, their management has varied widely. The classic histologic finding is a fringe-like attachment of densely packed filamentous spirochetes on the surface epithelium of the large intestine. Identification can be done with H&E staining, but confirmation requires Warthin-Starry staining. Although clinical presentation varies, often patients are asymptomatic and have an endoscopically normal appearance. CASE DESCRIPTION/METHODS: In this case report, we present a 37 year old otherwise healthy homosexual female with intermittent hematochezia and RLQ pain and a family history remarkable for polyps in her sister (36), and father who was diagnosed with colon cancer in his 50s. Colonoscopy was remarkable for punctate ulcers on her IC valve and cecum, with biopsy findings of “chronic inflammation and architectural distortion” suspicious for Crohn's. She was started on Apriso BID, and on second read, the pathologist stated, ‘of note, we also identify organisms morphologically consistent with intestinal spirochetosis (Brachyspira), confirmed with a Warthin Starry stain, with an appropriately positive control. Intestinal spirochetosis usually is an incidental finding and the organisms are generally not considered pathogenic'. Consideration was given to treat the patient with a course of Flagyl, however, the patient was no longer symptomatic and on repeat colonoscopy the ulcers had resolved. Biopsies taken of the involved area again demonstrated Spirochetosis. DISCUSSION: While often regarded as a clinically insignificant finding, not enough is known about IS to make firm conclusions about the relevance of this organism. IS has been associated with IBS in a general population in Sweden1, and a retrospective case-control study in Japan demonstrated a strong association between IS and Sessile Serrated Adenomas/Polyps2. This case sheds light on the fact there is a lack of awareness and understanding of this organism among all involved sub-specialties. Further studies on this potentially pathogenic organism need to be carried out.

1562 Rare Intestinal Spirochetosis Masquerading as a Colonic Polyp

INTRODUCTION: Spirochetosis in colonic mucosa is exceedingly rare in non-immunocompromised individuals. There have been less than 200 cases documented and more rare with the specific B. Pilosicoli genus. Spirochetosis is also seen in individuals who engage in high risk sexual encounters. This type of spirochetosis is found mosty in dogs, cats, pigs and chickens. Symptoms in humans include diarrhea, rectal bleeding, and abdominal cramps. Colonic spirochetosis is more common in third world countries. Even in immunocompromised state of health and with all other factors there is much unknown about colonic spirochetosis. Due to its infrequency the treatment is metronidazole and repeat colonoscopy and biopsy should symptoms persist. CASE DESCRIPTION/METHODS: Patient is a 62 year old male patient who presented as an outpatient consultation for screening colonoscopy. The patient complains of abdominal pain for several months that is localized in the right upper quadrant. The patient describes the pain as moderate to sharp and only last a few minutes after onset. Patient also reported post prandial fullness, abdominal bloating and distention. The patient denied rectal bleeding, melena, constipation, or pain on evacuation. The patient denies other symptoms. The patient has no medical history and only surgery was an elective laparoscopic cholecystectomy. The Decision was made to undergo screening colonoscopy. The patient had no history of immunocompromised state or HIV/AIDS. The patient denies anal sex. Colonoscopy revealed he had two polyps. One in the ascending colon and the other in the rectum. The specimens were sent for pathology for analysis. Ascending polyp was analyzed and it demonstrated colonic mucosa consistent with intestinal spirochetosis specifically Brachyspira pilosicoli. The rectal polyp was hyperplastic no adenomatous change. DISCUSSION: This case was chosen because only 200 known cases of colonic mucosa infected with spirochetosis have been documented. The patient is not immunocompromised, does not engage in anal sex, is not in a third world country, and does not have typical symptomatology of infection with Spirochetosis. In general colonic involvement with spirochetosis is very misunderstood due to its infrequency. The genus of B.pilosicoli. Is a spirochete genus that has limited data on how many cases have been documented. The presentation as a colonic polyp as a masquerade for actice spirochetosis infection prompts further study.

1480 Colonic Spirochetosis Causing Ulcerative Proctitis

INTRODUCTION: Intestinal spirochetosis is a rare infectious diarrheal illness. Here we present a case of colonic spirochetosis initially diagnosed and treated as ulcerative proctitis. CASE DESCRIPTION/METHODS: A 57-year-old male presented to the office with 2 months of diarrhea occurring over 10 times per day with urgency and bleeding. The patient had an unremarkable past medical and family history. On social history, he practiced high risk sexual behavior with unprotected anal intercourse. Initial work-up showed mild elevation of ESR/CRP and an elevated calprotectin. Colonoscopy revealed ulcerative proctitis extending to 15 cm with normal colonic mucosa proximally. Rectal biopsies showed moderately active chronic colitis, remaining biopsies of colon were normal. He was started on mesalamine with improvement and subsequent sigmoidoscopy showed remission. Eight weeks later the patient presented to the ED with blurry vision. He was seen by ophthalmology who identified left optic nerve edema. An RPR was sent and resulted with a titer of 1:1024. He was referred to Infectious Disease with high suspicion for ocular syphilis and completed 14 days of IV penicillin G. Lumbar puncture showed no neurologic involvement. His RPR titers downtrended and visual changes improved. One month later, the patient developed large volume loose stools. Again stool studies were negative. Pathology was contacted to conduct repeat histochemical stains on earlier specimens, which showed spirochetes in the colonic mucosa. He was given metronidazole for 14 days for intestinal spirochetosis with improvement. With suspicion that proctitis may have originally been infectious the mesalamine therapy was weaned. DISCUSSION: Clinical manifestations of colonic spirochetosis can vary from asymptomatic to watery diarrhea. Rectal ulcerations are an uncommon presentation of primary syphilitic infection when compared to other mucosal sites. A literature review revealed a range of endoscopic findings from normal mucosa to erythema, friability, and polypoid lesions. To our knowledge the development of multiple ulcers has not been reported. It is necessary to maintain a high clinical suspicion because the diagnosis can be missed on a histologic level without appropriate additional staining. Given the increasing prevalence of syphilis, this case highlights the importance of collecting a thorough sexual history as to not delay the diagnosis and prevent the progression of disease, especially since early disease can frequently be asymptomatic.

2037 Intestinal Spirochetosis: An Unexpected Cause of Massive Gastrointestinal Bleed

INTRODUCTION: Human intestinal spirochetosis (HIS) is a condition characterized by the presence of spirochetal microorganisms attached to the apical cell membrane of the colorectal epithelium leading to chronic diarrhea. The invasive form of this disease is more often seen in HIV patients or homosexual individuals. Here, we present a rare case of HIS presenting as lower gastrointestinal (GI) bleed and abdominal pain in the absence of diarrhea. CASE DESCRIPTION/METHODS: A thirty-year-old male with a history of peptic ulcer disease (PUD) and HIV (CD4 >250) presented to the emergency department with a two-days duration of severe, generalized abdominal pain and bleeding per rectum. On presentation, the patient was hypotensive (mean arterial pressure < 65) and tachycardic (heart rate 120). Physical examination revealed generalized abdominal tenderness with normal bowel sounds but no rebound tenderness or guarding. Labs were significant for anemia (Hemoglobin 6.5 g/dl; baseline >14 g/dl). The rest of his labs including serum chemistry, white blood cells, amylase, lipase levels, were within normal limits. Due to the patient’s significant history of PUD and concern for rapid GI bleed, aggressive fluid resuscitation and proton pump inhibitor infusion were initiated. He also received two units of packed red blood cells with good toleration. CT scan of the abdomen/pelvis did not reveal any acute intraabdominal pathology. Despite the achievement of hemodynamic stability, the patient continued to have bright red blood per rectum. Extensive infectious workup (including blood cultures and stool tests such as stool culture, ova, and parasites) were negative. Esophagogastroduodenoscopy was performed and revealed well healed PUD without any signs of bleeding. Colonoscopy, however, revealed pan-colonic ulcers, most pronounced in the descending colon. Histopathology revealed spirochetal microorganisms attached all the way from the ascending colon to the rectum consistent with invasive HIS. Metronidazole was initiated with significant clinical improvement and he was subsequently discharged home with appropriate outpatient follow up. DISCUSSION: Most cases of HIS are asymptomatic and often diagnosed during screening/surveillance colonoscopy. Thus, data regarding symptomatic patients is scant. The few cases describing affected patients generally associate infection with chronic watery diarrhea, acute appendicitis or intermittent hematochezia. Metronidazole is an effective treatment of choice in symptomatic patients.

A survey on the occurrence of Brachyspira pilosicoli and Brachyspira hyodysenteriae in growing-finishing pigs

Background: The major pathogenic intestinal spirochetes affecting pigs during the growing- finishing stage of production include Brachyspira hyodysenteriae and Brachyspira pilosicoli. Infections by these pathogens, which affect the economics of pig production, can result in mortality, growth rate losses and substantial antibiotic costs. The aim of this study was to assess the current occurrence of B. hyodysenteriae and B. pilosicoli in Polish pig herds. Moreover, associations between the presence of diarrhea or other intestinal pathogens and occurrence of B. hyodysenteriae and B. pilosicoli in pigs were investigated. Methods: Between January 2017 and August 2019, a total of 401 samples of pig feces from 95 different herds were submitted to the National Veterinary Research Institute of Poland. These samples were obtained from pigs older than 7 weeks. All the received fecal samples were examined for the presence of B. hyodysenteriae, B. pilosicoli and Lawsonia intracellularis by real-time PCR. Results: For B. pilosicoli, 4.5% (95% CI, 2.5-7.0%) of samples and 13.7% (95% CI, 7.5-22.3%) of herds were positive. Out of 12 samples, B. pilosicoli was detected simultaneously with L. intracellularis, B. hyodysenteriae and B. pilosicoli were detected alone in two samples each. In terms of B. hyodysenteriae, 7.0% of samples (95% CI, 4.7-9.9%) from 18.9% of herds (95% CI, 11.6-28.3%) were positive in real time PCR. The presence of B. hyodysenteriae in fecal samples was associated with the presence of diarrhea in pigs. Conclusions: This study confirmed that B. pilosicoli infections occur in Polish pig herds, but the prevalence is at a low level and the presence of B. pilosicoli is not associated with the development of diarrhea in pigs. B. hyodysenteriae is still a common cause of diarrhea among pigs from Polish herds.

Etiology of isolated terminal ileal ulcers in symptomatic patients

Introduction: Isolated terminal ileal ulcers (ITIUs) are being frequently encountered by the clinicians with the increasing numbers of ileal intubation during colonoscopies. This study was aimed at finding the etiologies of these ulcers in symptomatic patients and their association with various clinical features.
 Methods: This was a hospital based prospective, observational, descriptive study performed on all consecutive patients who underwent ileocolonoscopy for various gastrointestinal symptoms between 1 July 2018 and 30 June 2019. Clinical, endoscopic and histopathological findings were analyzed to determine the etiology of ITIUs in symptomatic patients. Statistical analysis was done by SPSS 20.
 Results: Among 60 (7.67%) of 782 symptomatic patients who had ITIUs on ileocolonoscopy, specific etiologies were established in 28 (46.67%) of them. Intestinal TB was the most common specific diagnosis, which was seen in 18 (30%) patients. Chronic abdominal pain with or without chronic diarrhea was the most common indication for ileocolonoscopy.
 Conclusions: Specific etiologies like tuberculosis, Crohn’s disease, NSAID-induced ulcer and intestinal spirochetosis were seen in 28 (46.67%) of patients with isolated terminal ileal ulcers. The most common clinical features were chronic abdominal pain (65%) and abdominal pain with diarrhea (16.7%). No clinical presentation was significantly associated with any specific etiology, thus emphasizing the need for routine ileal intubation and tissue sampling for histopathological examination in all symptomatic patients undergoing colonoscopy.

An atypical weakly haemolytic strain of Brachyspira hyodysenteriae is avirulent and can be used to protect pigs from developing swine dysentery

The anaerobic intestinal spirochaete Brachyspira hyodysenteriae colonises the large intestine of pigs and causes swine dysentery (SD), a severe mucohaemorrhagic colitis. SD occurs worldwide, and control is hampered by a lack of vaccines and increasing antimicrobial resistance. B. hyodysenteriae strains typically produce strong beta-haemolysis on blood agar, and the haemolytic activity is thought to contribute to the pathogenesis of SD. Recently, weakly haemolytic variants of B. hyodysenteriae have been identified in Europe and Australia, and weakly haemolytic strain D28 from Belgium failed to cause disease when used experimentally to infect pigs. Moreover, pigs colonised with D28 and then challenged with virulent strongly haemolytic strain B204 showed a delay of 2–4 days in developing SD compared to pigs not exposed to D28. The current study aimed to determine whether Australian weakly haemolytic B. hyodysenteriae strain MU1, which is genetically distinct from D28, could cause disease and whether exposure to it protected pigs from subsequent challenge with strongly haemolytic virulent strains. Three experimental infection studies were undertaken in which no diseases occurred in 34 pigs inoculated with MU1, although mild superficial lesions were found in the colon in 2 pigs in one experiment. In two experiments, significantly fewer pigs exposed to MU1 and then challenged with strongly haemolytic virulent strains of B. hyodysenteriae developed SD compared to control pigs not previously exposed to MU1 (p = 0.009 and p = 0.0006). These data indicate that MU1 lacks virulence and has potential to be used to help protect pigs from SD.

Brachyspira catarrhinii sp. nov., an anaerobic intestinal spirochaete isolated from vervet monkeys may have been misidentified as Brachyspira aalborgi in previous studies

To date nine species of anaerobic intestinal spirochaetes have been validly assigned to the genus Brachyspira. These include both pathogenic and non-pathogenic species. In the current study a genomic analysis of a novel spirochaete isolate was undertaken to determine whether it is a distinct species that previously has been misidentified as Brachyspira aalborgi. The genome of spirochaete strain Z12 isolated from the faeces of a vervet monkey was sequenced and compared to the genomes of the type strains of the nine assigned Brachyspira species. Genome to Genome Distance (GGD) values and Average Nucleotide Identity (ANI) values were determined. Single nucleotide polymorphisms (SNP) were used to create a phylogenetic tree to assess relatedness. The 16S rRNA gene sequences of the strains were aligned and the similarity amongst the Brachyspira species was recorded. Multilocus sequence typing (MLST) using five loci was conducted on Z12 and results compared with those for other Brachyspira isolates. Assembly of the Z12 sequences revealed a 2,629,108 bp genome with an average G + C content of 31.3%. The GGD, ANI, 16S rRNA gene sequence comparisons and the MLST results all indicated that Z12 represents a distinct species within the genus Brachyspira, with its nearest neighbour being B. aalborgi. Spirochaete strain Z12T was assigned as the type strain of a new species, Brachyspira catarrhinii sp. nov. The diagnostic PCR currently in use to detect B. aalborgi cross-reacts with Z12, but RFLP analysis of PCR product can be used to distinguish the two species. Previous reports of non-human primates being colonised by B. aalborgi based on PCR results may have been incorrect. The development of an improved diagnostic method will allow future studies on the distribution and possible clinical significance of these two anaerobic spirochaete species.

Diagnostic immunohistochimique de la spirochétose colique avec l’anticorps anti-tréponème chez les patients consultant pour une diarrhée chronique. Résultats d’une étude prospective menée chez 137 patients

To assess the incidence of colonic spirochetosis, diagnosed by immunohistochemical stain with anti-Treponema pallidum antibody, in a prospective study of colonic biopsies of patients presenting with chronic diarrhea. From March 2017 to March 2018 the colonic biopsies of patients presenting with chronic diarrhea were stained with Hematoxylin Eosin and anti-Treponema pallidum antibody. The positive cases were also stained with Steiner stain. A total of 137 colonic biopsies were assessed and 3 cases were positive for immunohistochemical stain with anti-Treponema pallidum antibody (2% of the patients). One case was easy to diagnose with HE stain but the 2 other cases were not. The bacteria were stained with Steiner stain, but less easily seen than with the immunohistochemical stain. No patient was treated with antibiotics. The colonic spirochetosis can be easily diagnosed by pathologists with immunohistochemical stain with anti-Treponema pallidum antibody. The bacteria are more easily diagnosed with immunohistochemical stain than with HE stain or Steiner stain. However, colonic spirochetosis is rarely diagnosed on colonic biopsies of patients presenting with chronic diarrhea (2% of the patients in our study). Due to the rarity of the entity, and the cost of immunohistochemical stain and the weak benefit for the patient (no patient in our study was treated with antibiotics for colonic spirochetosis) we cannot advise to perform systematic immunohistochemical stain with anti-Treponema pallidum antibody in all the colonic biopsies of patients presenting with chronic diarrhea.

The comparison of the intensity of human intestinal spirochetes between Brachyspira pilosicoli and Brachyspira aalborgi infections.

The agglutination titers of Brachyspira pilosicoli (B. pilosicoli) and Brachyspira aalborgi (B. aalborgi) were examined in colitis patients with human intestinal spirochetes. Among three cases of colitis patients, the titer of B. pilosicoli was extremely high in two cases while the titer of B. aalborgi was extremely high in one case. These three cases had symptoms of colitis, such as watery diarrhea, and we diagnosed the case as Brachyspira- related colitis. These findings suggest that the agglutination titers of Brachyspira may be useful in cases of Brachyspira- related colitis. Severe symptoms, such as abdominal pain and diarrhea, were observed in cases with high antibody titer of B. aalborgi, as well as B. pilosicoli, indicating that B. aalborgi could also cause symptomatic colitis.

Vaccination of chickens with the 34 kDa carboxy-terminus of Bpmp72 reduces colonization with Brachyspira pilosicoli following experimental infection

ABSTRACTThe anaerobic intestinal spirochaete Brachyspira pilosicoli colonizes the large intestine of a variety of species of mammals and birds, and may result in colitis, diarrhoea and reductions in growth rate. Naturally occurring infections in chickens are largely confined to adult laying and breeding birds. In this study, the 34 kD carboxy-terminus of the prominent outer membrane protein Bmp72 of B. pilosicoli was expressed as a histidine-tagged recombinant protein and used to immunize two groups (B and C) of 15 individually housed layer chickens. Vaccination was with either 100 μg (B) or 1 mg (C) protein emulsified with Freund’s incomplete adjuvant delivered into the pectoral muscles, followed three weeks later by 1 mg of protein in phosphate buffered saline delivered via crop tube. Two weeks later these and 15 non-vaccinated positive control birds (group A) housed in the same room were challenged via crop tube with B. pilosicoli avian strain CPS1. B. pilosicoli was detected in the faeces of all control birds and in 14 of the vaccinated birds in each vaccinated group at some point over the 30-day period following challenge. Colonization was delayed and the duration of excretion was significantly reduced (P = 0.0001) in both groups of vaccinated birds compared to the non-vaccinated control birds. Fewer immunized birds had abnormal caecal contents at post mortem examination compared to non-vaccinated birds, but the difference was not statistically significant. This study indicates that recombinant Bmp72 C-terminus has potential to be developed for use as a vaccine component to provide protection against B. pilosicoli infections.RESEARCH HIGHLIGHTSLaying chickens were immunized with recombinant Brachyspira pilosicoli membrane protein Bpmp72.Immunized birds had a highly significant reduction in the duration of colonization.Fewer immunized than control birds had abnormal caecal contents after infection.Bpmp72 showed potential for use as a novel vaccine component for B. pilosicoli.

Histochemistry in the diagnosis of non-neoplastic gastrointestinal disorders.

The alimentary tract serves as host to a large number of diseases. In the non-neoplastic group of disorders, conventional histochemistry continues to play an important diagnostic role. It is particularly important in recognizing specific infectious diseases, such as Helicobacter gastritis, Whipple disease, intestinal tuberculosis and other forms of mycobacteriosis, malakoplakia, intestinal spirochetosis, fungal enteritides, amebiasis, cryptosporidiosis, isosporiasis, and microsporidiosis. Those conditions and their histochemical properties are discussed in this review, along with the use of histochemistry in the characterization of structural gastrointestinal disorders. The latter include mucosal metaplasias, amyloidosis, glycogenic acanthosis of the esophagus, lymphocytic-collagenous colitis, gastric neuroendocrine hyperplasia, and pill gastritis.

Intestinal Spirochetosis

A 61-year old man was admitted for a 2-day history of watery diarrhea and RLQ pain, a day after he ate a pork sandwich. He had AAA endovascular repair 2 months PTA. On exam he was afebrile, with a tender RLQ. WBC count was 11k, 70% N. CT showed colitis of the cecum and ascending colon, patent SMA and intact endoprosthesis (Img1a). Stool culture, O/P, and C.diff were negative. Diarrhea and pain improved with IVF and he was discharged 3 days later. A previously scheduled surveillance colonoscopy 18 days after admission, showed cecal and IC valve healing ulcers (Img1b), otherwise normal TI and colonic mucosa. Biopsies of the ulcers and normal appearing mucosa showed spirochetosis confirmed with multiple stains (Img2). HIV and RPR were negative.1654_A Figure 1. A. CT showing colonic wall thickening from the cecum to the hepatic flexure with mucosal edema and infiltration of the pericolonic fat, representing acute segmental colitis. B. Colonoscopy showing a healing Ileocecal valve ulcer.1654_B Figure 2. A. H&E: Fringe formation attached to the luminal surface of the colonic mucosa (Biopsy of normal endoscopic transverse colonic mucosa) B. Steiner/ Silver Stain: (Biopsy of normal endoscopic transverse colonic mucosa C. Polyclonal Treponema pallidum immunohistochemical stain: Cross reactivity of Anti-Treponema immunohistochemistry with Non-Treponema spirochetes (Biopsy of normal endoscopic transverse colonic mucosa) D. Polyclonal Treponema pallidum immunohistochemical stain: Mucosal and possible submucosal involvement (Biopsy of cecal ulcer)Intestinal spirochetosis (IS) is caused by the gram-negative bacteria Brachyspira aalborgi and Brachyspira pilosicoli. B pilosicoli induces disease in humans and animals, whereas B aalborgi affects humans and higher primates. It can be transferred to humans after contact with infected animal feces, ingestion of meat from infected animals or food contaminated by food handlers. IS is prevalent in areas with low living standards and amongst HIV patients. It affects different animals but mainly pigs and chicken. Our patient lives on a farm but does not have such animals. In most reported cases, IS was an incidental finding on random colonic biopsies. It was also reported in patients with diarrhea and abdominal pain. Our patient had an infectious colitis as ischemia was unlikely 2 months after AAA repair. We think that our patient's infectious colitis was attributed to an acute form of IS after consuming infected pork. An incubation period has never been reported. In our case, it would have been around 24 hours. Alternatively, our patient could have been colonized as he lives on a farm, but then experienced acute symptoms after ingestion of a large load of Brachyspira. We speculate that non-carriers and asymptomatic carriers could present with an acute self-limiting colitis after ingestion of a large spirochetal load or if they become immunocompromised. The patient still had IS on biopsies obtained 21 days after ingestion at a time when he was asymptomatic. Possibly, one's body is able to partially clear the organism over time to a point where IS could exist without causing symptoms. We suggest that stool culture and PCR for Brachyspira be performed in patients with acute colitis especially if immunocompromised.

Severe Human Intestinal Spirochetosis: An Unusual Cause of Diffuse Colonic Ulcerations in a Patient Living With HIV

Colonic ulceration in HIV infected individuals is commonly attributed to infectious colitis (viral, bacterial and fungal) and inflammatory bowel disease. Among bacterial causes, pathogens like salmonella, shigella, campylobacter, Yersinia and Neisseria gonorrhea predominate. Intestinal spirochetosis is however gaining clinical significance as an infectious cause of colonic ulceration in this population. Normal colonic mucosa is visualized in most cases and data on cases with colonic ulcerations remains sparse. Herein, we present a unique case of a HIV-infected male with diffuse colonic ulcerations attributed solely to intestinal spirochetosis. A 30-year-old male with a medical history of HIV infection, not on ARTs, and irritable bowel syndrome presented with a 2-week history of left lower abdominal pain and severe watery diarrhea. He initially had 4 stools daily, which were non-bloody, but became bloody one day prior to his presentation with an increased frequency of 10-12 stools. No identifiable precipitating factor. Colonoscopy done 2 years prior was normal. On admission, his vital signs were: BP 111/88 mmHg, HR 101 bpm and Temp 37.4 ° C. He had dry oral mucous membranes and a tender left lower abdominal quadrant. The rest of his exam was unremarkable. He was admitted for volume resuscitation. Stool ova and parasite, Clostridium difficile toxin, stool culture, RPR, Cryptosporidium, rotavirus and Giardia antigens were all negative. No leukocytosis or anemia. CD4 count was 246. An abdominopelvic CT scan was unrevealing. Colonoscopy was performed which revealed severe diffuse punctate ulcerations involving entire colon but worse in left colon (Figure 1, 2). Pathologic analysis of biopsy specimens revealed intestinal spirochetes in the entire colon and rectum, forming a false brush border over surface epithelium (Figure 3). No other pathogen was identified. A diagnosis of intestinal spirochetosis was made. He received ARTs and a 14-day course of oral Metronidazole. His clinical course was marked by complete resolution of diarrhea and abdominal pain. Repeat colonoscopy was not pursued given symptom resolution. Our patient had severe diffuse colonic ulcerations, a colonic pathology less commonly described in Intestinal spirochetosis. Interestingly, severity of ulcerations correlated with symptom severity. Hence, intestinal spirochetosis should be considered in cases of colonic ulcerations in HIV infected patients after excluding alternate causes.1608_A Figure 1. Colonoscopy showing diffuse severe colon ulcerations1608_B Figure 2. Colonoscopy showing diffuse severe colon ulcerations1608_C Figure 3. Intestinal spirochetes forming false brush border over surface epithelium and staining red with Treponema Pallidum immunostain

Intestinal Spirochetosis: Incidental Finding or Clinically Significant?

Intestinal Spirochetosis: Incidental Finding or Clinically Significant?

An Unusual Case of Intestinal Spirochetosis in a Patient with Ulcerative Colitis

An Unusual Case of Intestinal Spirochetosis in a Patient with Ulcerative Colitis