Human intestinal spirochetosis in Japanese patients aged less than 20 years: Histological analysis of colorectal biopsy and surgical specimens obtained from 479 patients.

Human intestinal spirochetosis (HIS) is a condition in which spirochetes attach to and colonize the colorectal epithelium. To our knowledge, no comprehensive studies of HIS in young patient have been published in a developed country. This study aimed to determine the incidence and clinicopathological manifestations of HIS in Japanese patients aged less than 20 years. We retrospectively reviewed 3605 biopsy and 92 surgical specimens obtained from 479 patients admitted to Shinshu University Hospital between 1997 and 2014. All slides were reviewed independently by two pathologists to confirm the histological presence of spirochetes. Among 387 patients who underwent biopsy, the most common pathologic diagnosis was ulcerative colitis (12.6%, n = 49). Additionally, about half of the biopsy specimens showed non-specific, mildly inflamed mucosa (50.6%, n = 196); only one of these cases was HIS. On the other hand, among the surgical specimens, we found no cases of HIS. We concluded that the incidence of HIS in Japanese young patients was 0.2% (1/479 cases). The incidence of HIS in Japanese young patients was very low, and one HIS case was associated with colitis with abdominal pain.

Clinicopathologic study of intestinal spirochetosis in Japan with special reference to human immunodeficiency virus infection status and species types: analysis of 5265 consecutive colorectal biopsies.

BACKGROUND: Previous studies reported that the incidence of intestinal spirochetosis was high in homosexual men, especially those with Human Immunodeficiency Virus infection. The aim of the present study was to clarify the clinicopathological features of intestinal spirochetosis in Japan with special reference to Human Immunodeficiency Virus infection status and species types. METHODS: A pathology database search for intestinal spirochetosis was performed at Tokyo Metropolitan Cancer and Infectious Disease Center Komagome Hospital between January 2008 and October 2011, and included 5265 consecutive colorectal biopsies from 4254 patients. After patient identification, a retrospective review of endoscopic records and clinical information was performed. All pathology slides were reviewed by two pathologists. The length of the spirochetes was measured using a digital microscope. Causative species were identified by polymerase chain reaction. RESULTS: Intestinal spirochetosis was diagnosed in 3 out of 55 Human Immunodeficiency Virus-positive patients (5.5%). The mean length of intestinal spirochetes was 8.5 µm (range 7-11). Brachyspira pilosicoli was detected by polymerase chain reaction in all 3 patients. Intestinal spirochetosis was also diagnosed in 73 out of 4199 Human Immunodeficiency Virus-negative patients (1.7%). The mean length of intestinal spirochetes was 3.5 µm (range 2-8). The species of intestinal spirochetosis was identified by polymerase chain reaction in 31 Human Immunodeficiency Virus-negative patients. Brachyspira aalborgi was detected in 24 cases (78%) and Brachyspira pilosicoli in 6 cases (19%). Both Brachyspira aalborgi and Brachyspira pilosicoli were detected in only one Human Immunodeficiency Virus-negative patient (3%). The mean length of Brachyspira aalborgi was 3.8 µm, while that of Brachyspira pilosicoli was 5.5 µm. The length of Brachyspira pilosicoli was significantly longer than that of Brachyspira aalborgi (p < 0.01). The lengths of intestinal spirochetes were significantly longer in Human Immunodeficiency Virus-positive patients than in Human Immunodeficiency Virus-negative patients (p < 0.05). CONCLUSIONS: The incidence of intestinal spirochetosis was slightly higher in Human Immunodeficiency Virus-positive patients than in Human Immunodeficiency Virus-negative patients. However, no relationship was found between the Human Immunodeficiency Virus status and intestinal spirochetosis in Japan. Brachyspira pilosicoli infection may be more common in Human Immunodeficiency Virus-positive patients with intestinal spirochetosis than in Human Immunodeficiency Virus-negative patients with intestinal spirochetosis.

Human intestinal spirochetosis is significantly associated with sessile serrated adenomas/polyps.

It remains unclear whether or not human intestinal spirochetosis (HIS) has any associated symptoms or lesions. In this study, we assessed the prevalence of HIS in sessile serrated adenomas/polyps (SSA/Ps) and their possible association. Following identification of early cecal cancer with SSA/P accompanied by a colonization of HIS, we went on to conduct a retrospective case-control study using endoscopically resected SSA/P specimens to examine the frequency of HIS infection in SSA/Ps. Nineteen SSA/P cases and 172 controls were obtained. The rate of HIS infection was significantly higher at 52.6% (10/19) in the SSA/P cases compared to the controls at 8.1% (14/172). Our SSA/P series were associated with a remarkably higher rate of HIS than controls or than previously reported. This is the first report to provide evidence for potential association between HIS and SSA/Ps.

Spirochetes in otology: are we testing for the right pathogens?

OBJECTIVE: To determine the prevalence rate of otosyphilis and Lyme-associated labyrinthine disease among patients presenting with idiopathic, progressive sensorineural hearing loss and, thus, to provide recommendations regarding the diagnostic workup. STUDY DESIGN: A prospective cohort study of patients presenting to a university hospital otology clinic with idiopathic, progressive sensorineural hearing loss between 1998 and 2006. SUBJECTS AND METHODS: Cases in which hearing loss was clearly attributable to other causes were excluded, leaving 181 patients (mean age 55.6 years). History, physical examination, autoimmune laboratory tests, syphilis and Lyme serology, audiometric assessment, and MRI were performed in all cases. RESULTS: Nine cases (4.9%) of otosyphilis and none of Lyme disease were diagnosed by serological tests. CONCLUSION: Routine serological testing for otosyphilis, but not Lyme disease, is recommended for all cases of idiopathic, progressive sensorineural hearing loss.

Human intestinal spirochetosis in Japan; its incidence, clinicopathologic features, and genotypic identification.

Human intestinal spirochetosis is a common condition in Western countries, but is not well recognized in Japan. To demonstrate the incidence and clinicopathologic findings of human intestinal spirochetosis in Japan, we retrospectively investigated biopsy, and endoscopically or surgically resected specimens of the large intestine. Among a series of 2556 samples, 11 cases of human intestinal spirochetosis were detected (0.4%). Together with additional nine cases sporadically found, 20 cases of human intestinal spirochetosis were subjected to molecular detection of two strains of spirochetes (Brachyspira aalborgi and Brachyspira pilosicoli) by amplifying species-specific portion of 16S ribosomal RNA and NADH oxydase gene by polymerase chain reaction. B. aalborgi was detected in all cases examined, three of which revealed dual infection of both species. Our results suggest that human intestinal spirochetosis infection is relatively rare, and B. aalborgi is the most prevalent species in Japan. Most of human intestinal spirochetosis were asymptomatic, although symptomatic in exceptional cases. In addition, we emphasize a usefulness of immunostaining with anti-Treponema pallidum and anti-Mycobacterium bovis polyclonal antibodies for detecting the spirochetes.

Human intestinal spirochetosis: analysis of the symptoms of 209 patients.

OBJECTIVE: Colonization of the colorectal mucosa with spirochetes is very rare. Owing to the small number of cases, it is not clear from the currently available publications whether spirochetes colonizing the colorectal mucosa are harmless commensals or pathogenic organisms. Furthermore, the reported complaints of these patients cannot be pooled to identify a characteristic complex of symptoms. The aim of the present work was to describe the symptoms associated with intestinal spirochetosis in a population of 209 patients, and to elucidate the effect of antibiotic treatment on these symptoms. MATERIAL AND METHODS: A total of 209 carefully processed questionnaires providing information on the symptoms, treatment and post-treatment symptoms of patients with spirochetosis were evaluated statistically and descriptively with the aid of the SPSS program, and the results were compared with those reported in the currently available literature. RESULTS: Of the 209 patients 168 (80.4%) were males, and the average age of the entire population at establishment of the diagnosis was 50.75 years. The most common symptoms reported were abdominal pain (46%), diarrhoea (51%) and alternating diarrhoea and constipation (13%). In this population, homosexuality and HIV infection played only a small role (6.5% homosexual patients, 3.8% HIV infected). In 72 of the 84 patients who received treatment (86%), the antibiotic employed was metronidazole, and the symptoms improved in 44 of the 84 patients (5%). Twenty-six of the 84 patients (30.9%) were investigated by colonoscopy/biopsy after receiving medical treatment. Biopsies in 20 of these patients no longer revealed infection with spirochetes, and symptoms were found to have improved in 11 of the 20 patients (55%). CONCLUSIONS: If intestinal spirochetosis is diagnosed to be the sole intestinal pathology in symptomatic patients, the bacteria should be eradicated with metronidazole and a colonoscopy/biopsy follow-up performed, where indicated, in patients with persisting symptoms. Significant results regarding symptoms and treatment of intestinal spirochetosis can be achieved only in a prospective, placebo-controlled, randomized, crossover study. In view of the low prevalence of this condition, such a study is difficult to implement.

Human intestinal spirochaetosis in Parma: a focus on a selected population during 2002-2005.

BACKGROUND AND AIM OF THE WORK: Human intestinal spirochaetosis (HIS) is a large bowel infection characterised by the colonization of the intestinal mucosa by spirochaetes belonging to the genus Brachyspira. The causative agents of HIS are Brachyspira aalborgi and Brachyspirapilosicoli. Symptoms of the infection, even if not specific, are long standing diarrhoea, abdominal pain, meteorism and rectal bleeding and sometimes they can suggest the clinical suspect of inflammatory bowel diseases or rectal carcinoma. Since poor data were available on the prevalence of this infection, the aim of our study was to describe the occurrence of this infection in our area in the period 2002-2005. METHODS: During a period of 4 years we analysed 297 faecal samples from 99 patients selected by potential risk factors and symptomatology suspected for HIS. The diagnosis of HIS was performed by isolation and a molecular assay based on 16S rDNA restriction fragment length polymorphism (RFLP)-polymerase chain reaction (PCR). RESULTS: From 2002 to 2005 we detected 12 cases of intestinal spirochaetosis, 7 caused by Brachyspira aalborgi, 4 by Brachyspirapilosicoli and one by both spirochaetes, which represented the first case of a mixed infection by 2 intestinal spirochaetes in our area. CONCLUSIONS: Despite the fact that HIS seems to be a low prevalence infection in our area, in a strongly selected population we found 12 cases of this infection (12.12%). These results stimulate us to extend the research of intestinal spirochaetosis in the general population, when long standing gastrointestinal disorders and potential risk factors are present.

Present status of tick-borne diseases in Sudan.

Ticks and tick-borne diseases are widespread in the Sudan, cause substantial economic losses and constitute major obstacles to the development of animal wealth. Most important among these diseases are tropical theileriosis, malignant ovine theileriosis, cowdriosis, babesiosis, anaplasmosis and avian spirochaetosis. However, knowledge about ticks and tick-borne diseases is still fragmentary and far from complete. The large number of tick species, the multplicity of transmitted agents and the diverse ecoclimatic zones of the Sudan provide a unique opportunity to host diverse research activities that could benefit other regions in Africa.

Colonic spirochetosis in children and adults.

We undertook a retrospective analysis of colonic spirochetosis in 14 cases: females, 3; males, 11; children, 4; adults, 10. Two men had HIV infections. All children and both HIV-infected men had abdominal complaints, diarrhea, or both. Most other adults underwent colonoscopy for polyp screening (n = 4) or follow-up of Crohn disease (n = 1) or had other indications (n = 2) or diarrhea (n = 1). Histologically, spirochetosis was identified in all parts of the colon and was not strongly associated with active inflammation, mucosal injury, or changes of chronicity. Genotype analysis of 13 cases showed that 11 resulted from Brachyspira aalborgi and 2 from Brachyspira pilosicoli infections. Only 2 patients were treated specifically with antibiotics, with complete resolution of abdominal symptoms in 1 patient with follow-up. Follow-up biopsy result were available for 2 patients who did not receive treatment; one showed persistent spirochetosis, and the other was negative. Spirochetosis in this series had a male predominance, was generally caused by B aalborgi, and occurred in 2 distinct clinical settings: children who often have abdominal symptoms and adults who typically are asymptomatic. While treatment information remains limited, treatment can lead to resolution of symptoms in some cases.

Clinical significance of human intestinal spirochetosis--a morphologic approach.

Intestinal spirochetosis (IS) is a condition defined morphologically by the presence of spirochetal microorganisms attached to the apical cell membrane of the colonic and rectal epithelium. Intestinal spirochetes comprise a heterogeneous group of bacteria. In humans Brachyspira aalborgi and Brachyspira pilosicoli predominate. Prevalence rates of IS are low where living standards are high, in contrast to poorly developed areas where IS is common. Homosexuals and HIV-infected individuals are at high risk of being colonized. Clinical significance in individual cases has remained unclear up to now. A review of the literature reveals that invasion of spirochetes beyond the surface epithelium is associated with gastrointestinal symptoms which respond to antibiotic treatment (metronidazole), whereas patients lacking this feature are mostly asymptomatic. Homosexual and HIV-positive men are more likely to be symptomatic irrespective of invasion. Rare cases of spirochetemia and multiple organ failure have been reported in critically ill patients.

[Human intestinal spirochetosis]. / Die intestinale Spirochätose des Menschen.

Whenever biopsy material obtained from endoscopically normal colorectal mucosa reveals the blue haematoxyphilic line between the microvilli of the covering epithelium, the rare condition of intestinal spirochetosis is diagnosed. The classification of the bacteria detected with the aid of special stains (e.g. the Warthin Starry silver stain) and in the electron microscope, continues to be something of a problem. A further point of contention is the question whether this spirochetal infection is of pathological significance or not. A point mitigating against pathogenicity is the fact that no histological signs of an inflammatory reaction are to be seen. Also, the symptoms of patients with intestinal spirochetosis are such that they provide no basis for a pronouncement on whether the infection is of a pathological or a pathological nature. On the other hand, however, a number of studies do seem to indicate that the spirochetes might be the cause of such symptoms as diarrhoea, constipation and abdominal pain. A point that would appear to support this view is the fact that such symptoms may disappear after successful treatment with metronidazole. The histological diagnosis is easily established when, faced by an apparently normal histological appearance of the colorectal mucosa, the pathologist considers the possibility of spirochetosis, and undertakes a specific search for the blue haematoxyphilic line in the covering epithelium of the colorectal mucosa.

Comparative prevalences of Brachyspira aalborgi and Brachyspira (Serpulina) pilosicoli as etiologic agents of histologically identified intestinal spirochetosis in Australia.

DNA from gastrointestinal biopsy specimens from 28 Australian patients with histologic evidence of intestinal spirochetosis (IS) was subjected to PCRs to amplify segments of the 16S rRNA and NADH oxidase genes of Brachyspira aalborgi and Brachyspira (Serpulina) pilosicoli. B. aalborgi was identified in specimens from 24 (85.7%) patients and B. pilosicoli in those from 4 (14.3%) patients (2 of whom were also positive for B. aalborgi). For two patients, no product was amplified. This study demonstrates that B. aalborgi is much more commonly involved in histologically identified IS in Australian patients than is B. pilosicoli. This is the first report of amplification of B. pilosicoli DNA from humans with IS.

The incidence of swine dysentery in pigs can be reduced by feeding diets that limit the amount of fermentable substrate entering the large intestine.

Two experiments were conducted to test the hypothesis that feeding diets which limit the amount of fermentable substrate entering the large intestine would protect pigs against experimental infection with Serpulina hyodysenteriae, the causative agent of swine dysentery. Experiment 1 examined the effect of grain processing (hammer milling vs. steam flaking) and grain type (barley, groats, corn, sorghum and wheat) on indices of fermentation in the large intestine and the incidence of swine dysentery. Experiment 2 examined the role of five diets, steam-flaked corn, steam-flaked sorghum, hammer-milled wheat, extruded wheat and cooked white rice, on these same measures. All diets contained an animal protein supplement and no antibiotics. Pigs fed diets based on steam-flaked corn and steam-flaked sorghum had a lower incidence of disease (11-33%) than pigs fed diets based on other grains (75-100%). Pigs fed the diet based on cooked white rice were fully protected against swine dysentery. Both the soluble non-starch polysaccharide (NSP) concentration and the total NSP concentration of the diets explained a significant proportion of the variation in swine dysentery (R2 = 0.56, P = 0.016, and R2 = 0.71, P = 0.002, respectively), such that pigs eating diets containing <1.0 g/100 g soluble NSP showed reduced disease. However, pigs fed corn, sorghum and steam-flaked sorghum (Experiment 2), which contained only 0.4-0.5 g/100 g soluble NSP, still had a high incidence of disease (>50%). This was attributable to a higher level of resistant starch present in these grains. These data provide evidence that the expression of swine dysentery is associated with an increased concentration of fermentable substrate entering the large intestine.

Intestinal spirochetosis: first cases reported in Brazil and the use of immunohistochemistry as an aid in histopathological diagnosis.

Colonization of the colon and rectum by intestinal spirochetes is detected for the first time in Brazil in 4 of 282 (1.41%) patients who had undergone sigmoidoscopy and/or colonoscopy with a histopathological diagnosis of chronic non specific-colitis. This frequency is probably underestimated, since surgically obtained specimens were not considered in the present study. Histopathological diagnosis was performed using routine stains like hematoxylin-eosin which showed the typical, of 3-microns thick hematoxyphilic fringe on the brush border of the surface epithelium, and by silver stains like the Warthin-Starry stain. Immunohistochemical procedures using two, polyclonal, primary antibodies, one against Treponema pallidum and the other against Leptospira interrogans serovar copenhageni serogroup Icterohaemorrhagiae cross-reacted with spirochetal antigen/s producing a marked contrast of the fringe over the colonic epithelium, preserving the spiral-shaped morphology of the parasite. In one case with marked diarrhea, immunohistochemistry detected spirochetal antigen/s within a cell in an intestinal crypt, thus demonstrating that the infection can be more widely disseminated than suspected using routine stains. Immunohistochemical procedures, thus, greatly facilitate the histological diagnosis of intestinal spirochetosis and may contribute to a better understanding of the pathogenesis of the disease. Transmission and scanning electron microscopy performed in one case showed that the spirochete closely resembled the species designated as Brachyspira aalborgi.

Human intestinal spirochaetosis in mid-Norway. A retrospective histopathological study with clinical correlations.

Among 1205 mid-Norwegian patients who underwent colorectal biopsies during 1990, 30 cases (2.5%) with human intestinal spirochaetosis (HIS) were found. In only two cases were the spirochaetes mentioned in the biopsy reports. Cases with HIS showed a 7:3 male preponderance, but the mean age did not differ from that in the whole material. The spirochaetes were slightly more frequent in the rectum than in other parts of the large bowel. There was no indication of seasonal or geographical clustering of HIS and no association with occupation, use of certain drugs or underlying diseases. Most cases had HIS as the only positive biopsy finding, but the condition was also seen in connection with adenocarcinomas, Crohn's disease, and metaplastic and granulation polyps. The predominant symptoms of patients with HIS were faecal blood, diarrhoea, abdominal pain and constipation.

Infectious agents and disease of peripheral nerve.

An organism by organism review is presented of infectious agents that may result in focal, multifocal, or diffuse peripheral neuropathy by either direct or, more often, indirect means. Therapy is discussed and is directed at the primary infection as well as at the indirect cause if possible (for example, replacement therapy in vitamin deficiency).