Rheumatoid Arthritis (RA) has been increasingly associated with perturbations to the microbial communities that reside in and on the body (the microbiome), in both human and animal studies. To date, such studies have mainly focused on the microbial communities that inhabit the gut and oral cavity. Mounting evidence suggests that microbial DNA can be detected in the blood circulation using a range of molecular methods. This DNA may represent an untapped pool of biomarkers that have the potential to report on changes to the microbiome of distant sites (e.g., example, the gut and oral cavity). To this end, through amplification and sequencing of the bacterial 16S rRNA variable region four, we evaluated the presence and identity of microbial DNA in blood samples obtained from RA patients (both prior to and 3 months following the instigation of treatment) in comparison to a small number of healthy control subjects and samples obtained from patients with ankylosing spondylitis (AS) and psoriatic arthritis (PA). Bacterial-derived DNA was identified in the majority of our patient samples. Taxonomic classification revealed that the microbiome community in RA was distinct from AS, PA, and the healthy state. Through analysis of paired patient samples obtained prior to and 3 months following treatment (V0 vs. V3), we found the microbiome to be modulated by treatment, and in many cases, this shift reduced the distance between these samples and the healthy control samples, suggesting a partial normalization following treatment in some patients. This effect was especially evident in seronegative arthritis patients. Herein, we provide further evidence for the existence of a blood microbiome in health and identify specific taxa modulated in disease and following treatment. These blood-derived signatures may have significant utility as disease biomarkers and suggest this area warrants further investigation.

BackgroundIdentification of novel sources for developing new antibiotics is imperative with the emergence of antibiotic resistant bacteria. The fruits of Terminalia bellirica (Gaertn) Roxb., widely used in traditional medicine, were evaluated for antibacterial activity against multidrug-resistant (MDR) bacteria, antioxidant activity and cytotoxicity.MethodsTwelve solvent extracts of T. bellirica fruits were prepared by direct aqueous extraction and sequential extraction with dichloromethane, methanol and water using Soxhlet, bottle-shaker and ultrasound sonicator methods. Antibacterial activity of the extracts was tested against 16 strains MDR bacteria—methicillin-resistant Staphylococcus aureus (MRSA), extended spectrum β-lactamase (ESBL) producing Escherichia coli and MDR Acinetobacter spp., Klebsiella pneumoniae and Pseudomonas aeruginosa—and 4 control organisms, using the cut-well diffusion method. The minimum inhibitory concentration (MIC) was determined using an agar dilution method. The radical scavenging activity of six antibacterial extracts was screened against 2,2′-diphenyl-2-picrylhydrazyl (DPPH) and correlation was established between EC50 (50% effective concentration) values and the total phenolic content (TPC). Cytotoxicity was determined for the most potent antibacterial extract on baby hamster kidney (BHK-21) cells by Tryphan Blue exclusion method. Statistical analysis was carried out by one-way analysis of variance at significant level p < 0.05 using “SigmaPlot 10” and “R 3.2.0” software.ResultsAll aqueous and methanol extracts displayed antibacterial activity (MIC 0.25–4 mg/mL) against all strains of MRSA, MDR Acinetobacter spp. and MDR P. aeruginosa. The sequential aqueous extracts (MIC, 4 mg/mL) inhibited ESBL producing-E. coli. None of the extracts exhibited activity against MDR K. pneumoniae (MIC > 5 mg/mL). The sequential methanol extract (Soxhlet) recorded high antibacterial activity and the highest DPPH radical scavenging activity (EC50, 6.99 ± 0.15 ppm) and TPC content (188.71 ± 2.12 GAE mg/g).The IC50 (50% inhibition concentration) values of the most potent antibacterial extract—the direct aqueous extract from reflux method—on BHK-21 cells were 2.62 ± 0.06 and 1.45 ± 0.08 mg/ml with 24 and 48 h exposure, respectively.ConclusionsResults indicate that T. bellirica fruit is a potential source for developing broad-spectrum antibacterial drugs against MDR bacteria, which are non-toxic to mammalian cells and impart health benefits by high antioxidant activity.

BackgroundRickettsioses are emerging infections in Sri Lanka as shown by the increase in the number of clinically diagnosed rickettsial patients being reported to the Epidemiology Unit, Sri Lanka. However, mapping the disease for the whole island with laboratory confirmed cases has not been previously carried out.Methods615 samples received from 23 hospital representing 8 provinces were tested using ELISA or IFA methods and clinical data was collected using a validated questionnaire.ResultsRash was found among more spotted fever seropositive patients than scrub typhus seropositive patients while the opposite was true for the presence of eschar. Spotted fever and scrub typhus was found in a geographically restricted manner. Consistent temporal patterns were seen for the presentation of patients with rickettsioses in Kandy and Kurunegala districts for 2009 and 2010.ConclusionsThis study expanded knowledge on the distribution of rickettsioses in Sri Lanka and their clinical profiles which in turn helps in the clinical diagnosis of these infections.

BackgroundLeptospirosis is endemic in both urban and rural areas of Sri Lanka and there had been many out breaks in the recent past. This study was aimed at validating the leptospirosis surveillance case definition, using the Microscopic Agglutination Test (MAT).MethodsThe study population consisted of patients with undiagnosed acute febrile illness who were admitted to the medical wards of the Teaching Hospital Kandy, from 1st July 2007 to 31st July 2008. The subjects were screened to diagnose leptospirosis according to the leptospirosis case definition. MAT was performed on blood samples taken from each patient on the 7th day of fever. Leptospirosis case definition was evaluated in regard to sensitivity, specificity and predictive values, using a MAT titre ≥ 1:800 for confirming leptospirosis.ResultsA total of 123 patients were initially recruited of which 73 had clinical features compatible with the surveillance case definition. Out of the 73 only 57 had a positive MAT result (true positives) leaving 16 as false positives. Out of the 50 who didn't have clinical features compatible with the case definition 45 had a negative MAT as well (true negatives), therefore 5 were false negatives. Total number of MAT positives was 62 out of 123. According to these results the test sensitivity was 91.94%, specificity 73.77%, positive predictive value and negative predictive values were 78.08% and 90% respectively. Diagnostic accuracy of the test was 82.93%.ConclusionThis study confirms that the surveillance case definition has a very high sensitivity and negative predictive value with an average specificity in diagnosing leptospirosis, based on a MAT titre of ≥ 1: 800.

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