- Research article
- Open Access
- Open Peer Review
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
© Tateishi et al.; licensee BioMed Central. 2015
- Received: 12 September 2014
- Accepted: 22 December 2014
- Published: 13 January 2015
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.
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.
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).
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.
- Intestinal spirochetosis
- Human Immunodeficiency Virus (HIV) infection
- Colorectal biopsies
- Brachispira pilosicoli
- Brachyspira aalborgi
Previous studies reported that the incidence of IS was high in homosexual men, especially those with Human Immunodeficiency Virus (HIV) [7-10]. Although IS is generally considered to be associated with immunocompromised states such as HIV infection, it has also been detected in patients with a normal immune status [5,11-13]. The incidence of IS in HIV-positive patients has not yet been reported in Japan. Furthermore, the prevalence of these species in HIV-positive patients remains unclear [11,13-15]. Therefore, the aim of the present study was to clarify the clinicopathological features of IS in Japan with special reference to HIV infection status and species types.
This study was approved by the Research Ethics Committees at the Tokyo Metropolitan Cancer and Infectious Disease Center Komagome Hospital, and performed according to its guidance. Informed consent was obtained from all participants. A pathology database search for IS was performed at the Tokyo Metropolitan Cancer and Infectious Disease Center Komagome Hospital between January 2008 and October 2011, and included 5265 consecutive colorectal biopsies from 4254 patients. Patients consisted of 2558 men and 1696 women, whose age ranged between 9 and 93 years with a mean age of 64 years. Fifty-five of these patients were HIV-positive (1.3%) and 4199 were HIV-negative (98.7%). After patient identification, a retrospective review of endoscopic records and clinical information was performed.
The database search identified 76 patients with IS. All pathology slides were collected and reviewed by two pathologists (YT and NF). All specimens were stained with hematoxylin and eosin and examined under X 400 magnification. IS was identified by characteristic basophilic fringes on the surface epithelium . Immunostaining for spirochetosis was performed an antibody against Treponema pallidum (polyclonal, dilution 1:300; Concord CA, Biocare Medical) where necessary to confirm or refute the diagnosis. The lengths of spirochetes were measured using a digital microscope (Leica DMD 108).
Sequences of primers to detect the gene for 16S rRNA, NADH oxydase (nox) of Brachyspira aalborgi and Brachyspira pilosicoli
Size of products (bp)
B. aalborgi 16S rRNA
B. aalborgi nox
B. pilosicoli 16S rRNA
B. pilosicoli nox
All statistical analyses were performed using the JMP statistics software package (SAS; version 9.0.2). The relationship between IS and clinicopathological characteristics was assessed. Comparisons between two groups were analyzed with the Chi-square test. Differences were considered significant when the probability value was < 0.05.
Relationship between Clinicopathological Findings and IS
n = 76
n = 4178
Mean age, y (range)
p < 0.01
Men (n = 2558)
p < 0.01
Women (n = 1696)
Positive (n = 55)
p = 0.09
Negative (n = 4199)
IS was identified by characteristic 2–11 -μm-thick basophilic fringes on the luminal surface of the epithelium. The mean lengths of IS were 8.5 μm in HIV-positive patients and 3.5 μm in HIV-negative patients. The length of IS was significantly longer in HIV-positive patients than in HIV-negative patients (p < 0.05).
Relationship between size of IS and species identified by PCR analysis
Size of IS
Case of B. aalborgi
Case of B. pilosicoli
Case of both B. aalborgi and B. pilosicoli
n = 25
n = 9
n = 1
Characteristics of IS patients with clinical symptoms
Ages as ranges
Length of IS (μm)
Results of PCR
Abdominal pain, diarrhea
The prevalence of IS was previously reported to be between 2 and 7% in Western countries and 11-34% in less developed countries [18,19]. Our study revealed that the incidence of IS in Japan was 1.7%, which was similar to that in Western countries. The prevalence of IS was previously reported to be approximately 54% in men who have sex with men (MSM) and HIV-positive patients [9,18,20]. On the other hand, Orenstein et al. identified four patients with IS among 82 HIV-positive patients . Our study revealed that the incidence of IS was slightly higher in HIV-positive patients than in HIV-negative patients; however, no correlation was found between the HIV status and IS in Japan. Fifty-five HIV-positive and 4199 HIV-negative patients were evaluated in our study, which was one of the largest reported series of IS in HIV-positive and HIV-negative patients at a single institution.
Previous studies showed that the length of B. aalborgi was 2 to 6 μm and B. pilosicoli was 4 to 20 μm [1,2]. In patients in which the species was identified by PCR amplification, the length of B. aalborgi was 2 to 4.5 μm and B. pilosicoli was 2.5 to 11 μm. The length of B. pilosicoli was significantly longer than that of B. aalborgi (p < 0.01), which was consistent with the findings of previous studies. Furthermore, the length of IS in HIV-positive patients was significantly longer than that of IS in HIV-negative patients (p < 0.05).
B. aalborgi has been confirmed as the most prevalent species in Western countries and Japan, while B. pilosicoli is rare [6,13]. In the present study, B. pilosicoli was detected in all 3 HIV-positive patients. The results of the present study suggest that B. pilosicoli infections were more common in HIV-positive patients with IS while B. aalborgii infections may be more common in HIV-negative patients with IS in Japan. The prevalence of these species in HIV-positive patients has not yet been examined in detail [11,13-15]. To the best of our knowledge, this is the first study to show that B. pilosicoli infections may be more common in HIV-positive patients with IS based on one of the largest series composed of HIV-positive and HIV-negative patients examined at a single institution.
All 3 HIV-positive patients with IS in this study were male, less severely immunosuppressed, and had watery diarrhea. Anthony et al. reported that three HIV-positive IS patients were symptomatic with diarrhea . A previous study demonstrated that IS caused chronic diarrhea in HIV-positive men who have sex with men, but were not severely immunosuppressed (CD4 lymphocyte cells >200/ μL) . The clinicopathological findings of IS cases in our study were similar to these findings.
B. aalborgi is generally considered to be a non-pathogenic commensal, while B. pilosicoli is an opportunistic pathogen . All three HIV-positive patients with B. pilosicoli in our study had watery diarrhea. In HIV-negative patients, B. pilosicoli was more commonly detected in patients with clinical symptoms (50%) than in patients without clinical symptoms (16%). Furthermore, the prevalence of B. pilosicoli was markedly higher in patients with clinical symptoms than in patients without clinical symptoms (p = 0.02). This result supports the pathogenic potential of B. pilosicoli. Since the number of patients was too small to clarify the clinical significance of B. pilosicoli infection, further investigations are required.
In this study, we revealed the clinicopathological features of IS in Japan. The incidence of IS was slightly higher in HIV-positive patients than in HIV-negative patients. However, no relationship was found between the HIV status and IS. Brachyspira pilosicoli infection may be more common in HIV-positive patients with IS than in HIV-negative patients with IS.
The authors are grateful to staff of Tokyo Metropolitan Cancer and Infectious Disease Center Komagome Hospital for their unreserved help and facilitation of this study.
Presented at the 2012 American Society of Clinical Pathology Annual Meeting, October 31 to November 2, and was a finalist in the Best poster Submitted From Outside the U.S. Award Competition.
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