Intestinal Spirochaetosis-A case series from the developing world.

Spirochaetes comprise a heterogenous group of gram negative, motile, spiral shaped bacteria. Some of these pathogens are known to cause numerous human diseases such as Lyme disease, relapsing fever, syphilis and leptospirosis. However, intestinal spirochetosis is a rare condition. Patients frequently present with long-term complaints of loose stools, abdominal pain and weight loss and rectal bleeding. Hence to establish a diagnosis an endoscopy with biopsy is required. In this article, we describe four such cases, having different ages and socio- economic background, successfully treated with a short course of metronidazole.

[Steroids in infection medicine]. / Steroide in der Infektionsmedizin.

Corticosteroids have been found as useful adjunctive therapy in patients with various infections and hyperinflammation-associated disease. They are recommended in practice guidelines for patients with tuberculous and pneumococcal meningitis and patients with immune reconstitution syndrome associated with antiretroviral therapy. A new indication is severe COVID-19. Evidence from clinical trials is insufficient to allow the routine use of steroids among patients with septic shock, community-acquired pneumonia or tuberculous pericarditis.

Human intestinal spirochetosis, a sexually transmissible infection? Review of six cases from two sexually transmitted infection centres in Barcelona.

Human intestinal spirochetosis (HIS) is a possible cause of chronic diarrhoea and affects mainly men who have sex with men (MSM) and people living with HIV. Diagnosis is based on colon biopsy, where spirochetes can be observed on the luminal surface, especially with the Warthin-Starry stain or similar silver stains. We conducted a retrospective descriptive study of all HIS cases diagnosed in two sexually transmitted infections (STI) centres in Barcelona from 2009 until 2018. The medical histories were reviewed to gather epidemiological, clinical, and diagnostic variables. Six patients were diagnosed with HIS. All the individuals were MSM, with a median age of 31.5 years (interquartile range [IQR] 29.5;49.25) and half of them were living with HIV. Five patients reported condomless anal intercourse and 4 patients had practised oro-anal sex previously. Concomitantly, two of them had rectal gonorrhoea, one had rectal Chlamydia trachomatis and none of them had syphilis. The predominant clinical symptom was diarrhoea (5 patients). All cases were diagnosed by a Warthin-Starry stain on a colon biopsy specimen, and mild inflammatory changes were found in 5 cases. Five patients were treated with metronidazole and one with benzathine penicillin G. Treatment was successful in all the patients. HIS should be considered in patients with chronic diarrhoea who report risky sexual practices and/or concomitant STI. HIS may also be sexually transmitted according to the context.

Intestinal Spirocheteosis in a Patient with Celiac Disease.

A young girl presented to us with recurrent diarrhea along with a history of 5 kg weight loss in one year. On examination, she appeared pale, while her laboratory reports showed a low hemoglobin, mean corpuscular volume (MCV) and serum albumin. Her erythrocyte sedimentation rate (ESR) was slightly raised with her iron profile suggestive of iron deficiency anemia. Viral markers, human immunodeficiency virus (HIV) serology along with thyroid profile were all unremarkable. There was no history of tuberculosis, and purified protein derivative (PPD) skin test was also negative. Computed tomography (CT) abdomen showed thickening of the terminal ileum with multiple enlarged lymph nodes. An esophagogastroduodenoscopy (EGD) along with colonoscopy was done. Multiple biopsies were taken, which were suggestive of sprue along with intestinal spirochetosis. Her tissue transglutaminase (TTG) was negative while deamidated gliadin peptide (DGP) was positive. She was kept on gluten-free diet and started on tablet metronidazole. This case shows that intestinal spirochetosis should be kept in mind in patients belonging to lower socio-economic status, who present with chronic diarrhea symptoms.

The Jarisch-Herxheimer Reaction After Antibiotic Treatment of Spirochetal Infections: A Review of Recent Cases and Our Understanding of Pathogenesis.

Within 24 hours after antibiotic treatment of the spirochetal infections syphilis, Lyme disease, leptospirosis, and relapsing fever (RF), patients experience shaking chills, a rise in temperature, and intensification of skin rashes known as the Jarisch-Herxheimer reaction (JHR) with symptoms resolving a few hours later. Case reports indicate that the JHR can also include uterine contractions in pregnancy, worsening liver and renal function, acute respiratory distress syndrome, myocardial injury, hypotension, meningitis, alterations in consciousness, seizures, and strokes. Experimental evidence indicates it is caused by nonendotoxin pyrogen and spirochetal lipoproteins. Mediation of the JHR in RF by the pro-inflammatory cytokines tumor necrosis factor (TNF), interleukin (IL)-6, and IL-8 has been proposed, consistent with measurements in patients' blood and inhibition by anti-TNF antibodies. Accelerated phagocytosis of spirochetes by polymorphonuclear (PMN) leukocytes before rise in cytokines is responsible for removal of organisms from the blood, suggesting an early inflammatory signal from PMNs. Rarely fatal, except in neonates and in pregnancy for African women whose babies showed high perinatal mortality because of low birth weight, the JHR can be regarded as an adverse effect of antibiotics, necessary for achieving a cure of spirochetal infections.

Intestinal spirochaetosis causing chronic diarrhoea in a patient with HIV infection.

A 36-year-old Caucasian homosexual man was found to have HIV infection on routine screening. He had an eight-year history of chronic diarrhoea, which pre-dated the HIV diagnosis and did not improve after the introduction of combination antiretroviral therapy. After referral to the Gastroenterology department, he underwent fibreoptic colonoscopy. Colonic biopsies revealed the presence of intestinal spirochaetosis. He received a two-week course of metronidazole, which led to complete resolution of his diarrhoea. Intestinal spirochaetosis should be considered in the differential diagnosis of patients with HIV infection and chronic diarrhoea without other apparent cause.

Antimicrobial susceptibility of porcine Brachyspira hyodysenteriae and Brachyspira pilosicoli isolated in Sweden between 1990 and 2010.

BACKGROUND: The anaerobic spirochetes Brachyspira hyodysenteriae and Brachyspira pilosicoli cause diarrheal diseases in pigs. Their fastidious nature has hampered standardization of methods for antimicrobial susceptibility testing. For monitoring of antimicrobial susceptibility wild type cutoff values are needed to define where the wild type distribution of MICs ends and no approved cutoffs are available for Brachyspira spp. In this study antimicrobial susceptibility data for both species (in total 906 isolates) were compiled and analyzed and wild type cut off values for B. hyodysenteriae proposed. METHODS: The MICs of tiamulin, valnemulin, tylosin, tylvalosin, doxycycline and lincomycin were determined by broth dilution in brain heart infusion broth supplemented with 10% fetal calf serum. RESULTS: The compiled MICs from the broth dilution tests of the B. hyodysenteriae type strain, B78T (ATCC® 27164T), showed that the method yields reproducible results. In an international perspective the frequencies of isolates with decreased antimicrobial susceptibility were low among both B. hyodysenteriae and B. pilosicoli. However, in B. pilosicoli a constant level of 10-15% isolates with tiamulin MICs >4 µg/ml was detected between 2002 and 2010 and in B. hyodysenteriae a gradual increase in tiamulin MICs was seen between 1990 and 2003 although this increase has ceased during the last years. The wild type cutoff values proposed for B. hyodysenteriae are: tiamulin >0.25 µg/ml, valnemulin >0.125 µg/ml, tylosin >16 µg/ml, tylvalosin >1 µg/ml, lincomycin >1 µg/ml and doxycycline >0.5 µg/ml. CONCLUSIONS: The broth dilution method used in this study has over the years generated tightly grouped MIC populations for the field isolates and reproducible results for the control strain B78T and is therefore a suitable antimicrobial susceptibility test method for monitoring of Brachyspira spp. Here we propose wild type cutoff values for six antimicrobial agents for B. hyodysenteriae tested by broth dilution based on MIC distributions and the current knowledge on mechanisms of resistance in this species. There are few studies on antimicrobial resistance mechanisms and MIC distributions in B. pilosicoli but to some extent the cutoff values proposed for B. hyodysenteriae may be applicable also for monitoring of antimicrobial susceptibility in B. pilosicoli.

Intestinal spirochetosis in children: five new cases and a 20-year review of the literature.

Intestinal spirochetosis (IS) is an unusual infection in children, one with no standard therapeutic options. This article reports the findings on 5 new cases in conjunction with a 20-year review of the pediatric literature. The diagnosis of IS in children requires a high degree of suspicion by the physician, as many cases present with abdominal pain, chronic diarrhea, and/or hematochezia associated with a normal endoscopic examination. Silver stains (Dieterle or Whartin-Starry) are the preferred confirmatory stains on tissue sections. Giemsa (Diff-Quik) and periodic acid-Schiff stains may also be of value. Current literature favors the use of metronidazole in adult patients with IS, yet little information is available regarding treatment options in pediatric cases. This review indicates that a macrolide antibiotic with or without metronidazole may represent the best therapeutic choice for children. Further investigations are needed to determine the correlation between IS and coexisting gastrointestinal diseases and/or immunodeficiencies.

Role of infection in the pathogenesis of Alzheimer's disease: implications for treatment.

While our understanding of the neuropathology of Alzheimer's disease continues to grow, its pathogenesis remains a subject of intense debate. Genetic mutations contribute to a minority of early-onset autosomal dominant cases, but most cases are of either late-onset familial or sporadic form. CNS infections, most notably herpes simplex virus type 1, Chlamydophila pneumoniae and several types of spirochetes, have been previously suggested as possible aetiological agents in the development of sporadic Alzheimer's disease but with little consistent evidence. However, peripheral infections may have a role to play in accelerating neurodegeneration in Alzheimer's disease by activating already primed microglial cells within the CNS. Potential pharmacological interventions could aim at modification of this peripheral inflammatory response through targeting various agents involved in this inflammatory pathway. However, benefit could also be gained clinically through the meticulous detection, treatment and prevention of infections in individuals either alone or in combination with anti-inflammatory therapy.

Assessment of the clinical significance of intestinal spirochaetosis.

BACKGROUND: Spirochaetes are well known causative agents of diarrhoea in veterinary medicine. However, there is no agreement as to whether or not they have any clinical significance in humans. AIMS: To assess the symptoms associated with intestinal spirochaetosis, their response to treatment and the natural history of untreated cases. METHODS: A retrospective review of all cases of intestinal spirochaetosis identified within an eight year period in a single university teaching hospital was performed. A chart review and follow up telephone interview was performed to assess the indications for colonoscopy that led to the diagnosis, treatment received, and duration and nature of symptoms. RESULTS: 18 cases were identified. The indications for colonoscopy were diarrhoea in 50% and rectal bleeding in 16.7%; also investigation of constipation, anaemia and abdominal pain, and in two cases reassessment of chronic proctitis. Two subjects were treated with metronidazole and two were treated with aminosalicylates. 69% had complete resolution of symptoms at follow-up, 15% had persistent symptoms and 15% had intermittent symptoms. Of the two patients treated with metronidazole, one had resolution of symptoms and one has persistent abdominal pain. CONCLUSION: Symptoms do not appear to parallel spirochaete persistence or eradication and therefore it seems appropriate to adopt a wait and see approach to treatment of patients in whom spirochaetes are identified, giving a trial of antimicrobial treatment only in those who have severe or persistent symptoms. Careful consideration of both host and pathogen should be undertaken.