Novel genetic variants of Hepatitis B Virus in fulminant hepatitis

Fulminant hepatitis (FH) is a life-threatening liver disease characterised by intense immune attack and massive liver cell death. The common precore stop codon mutation of hepatitis B virus (HBV), A1896, is frequently associated with FH, but lacks specificity. This study attempts to uncover all possible viral nucleotides that are specifically associated with FH through a compiled sequence analysis of FH and non-FH cases from acute infection. We retrieved 67 FH and 280 acute non-FH cases of hepatitis B from GenBank and applied support vector machine (SVM) model to seek candidate nucleotides highly predictive of FH. Six best candidates with top predictive accuracy, 92.5%, were used to build a SVM model; they are C2129 (85.3%), T720 (83.0%), Y2131 (82.4%), T2013 (82.1%),K2048 (82.1%), and A2512 (82.1%). This model gave a high specificity (99.3%), positive predictive value (95.6%), and negative predictive value (92.1%), but only moderate sensitivity (64.2%).We successfully built a SVM model comprising six variants that are highly predictive and specific for FH: four in the core region and one each in the polymerase and the surface regions. These variants indicate that intracellular virion/core retention could play an important role in the progression to FH

Colon Carcinogenesis: The interplay between diet and gut microbiota

Colorectal cancer (CRC) incidence increases yearly, and is three to four times higher in developed countries compared to developing countries. The well-known risk factors have been attributed to low physical activity, overweight, obesity, dietary consumption including excessive consumption of red processed meats, alcohol, and low dietary fiber content. There is growing evidence of the interplay between diet and gut microbiota in CRC carcinogenesis. Although there appears to be a direct causal role for gut microbes in the development of CRC in some animal models, the link between diet, gut microbes, and colonic carcinogenesis has been established largely as an association rather than as a cause-and-effect relationship. This is especially true for human studies. As essential dietary factors influence CRC risk, the role of proteins, carbohydrates, fat, and their end products are considered as part of the interplay between diet and gut microbiota. The underlying molecular mechanisms of colon carcinogenesis mediated by gut microbiota are also discussed. Human biological responses such as inflammation, oxidative stress, deoxyribonucleic acid (DNA) damage can all influence dysbiosis and consequently CRC carcinogenesis. Dysbiosis could add to CRC risk by shifting the effect of dietary components toward promoting a colonic neoplasm together with interacting with gut microbiota. It follows that dietary intervention and gut microbiota modulation may play a vital role in reducing CRC risk

Interstitial pulmonary fibrosis in a Malaysian captive Asian elephant (Elephas maximus)

A 14-year-old female captive Asian elephant in a Malaysian z oo with a history of positive sero-reactivity to Elephant TB STAT-PAK assay was humanely euthanized due to chronic weight loss and poor response to treatment. Postmortem revealed generalized congestion and emphysematous lungs. Microscopically, there were severe pulmonary emphysema, eosinophilic hyaline membrane and infiltration of mature fibrocytes in the alveolar walls. Based on the histopathological findings interstitial pulmonary fibrosis was diagnosed. The possible cause of which although not completely known, is most likely due to hypersensitivity. The allergic reaction could have been caused by exposure to antigens of avian origin or the Mycobacterium gilvum, an non-tuberculous mycobacterium (NTM), isolated from the lung. This is the second case reported in elephants globally, thought it has been well studied in humans and reported in horses. Providing good husbandry for elephants in captivity is important to reduce the occurrence of such condition

Tuberculosis in captive Asian elephants (Elephas maximus) in Peninsular Malaysia

A cross-sectional study was conducted from 10 January to 9 April 2012, to determine the seroprevalence of tuberculosis (TB) of all captive Asian elephants and their handlers in six locations in Peninsular Malaysia. In addition, trunk-wash samples were examined for tubercle bacillus by culture and polymerase chain reaction (PCR). For 63 elephants and 149 elephant handlers, TB seroprevalence was estimated at 20·4% and 24·8%, respectively. From 151 trunk-wash samples, 24 acid-fast isolates were obtained, 23 of which were identified by hsp65-based sequencing as non-tuberculous mycobacteria. The Mycobacterium tuberculosis-specific PCR was positive in the trunk-wash samples from three elephants which were also seropositive. Conversely, the trunk wash from seven seropositive elephants were PCR negative. Hence, there was evidence of active and latent TB in the elephants and the high seroprevalence in the elephants and their handlers suggests frequent, close contact, two-way transmission between animals and humans within confined workplaces

Concentrated specimen smear microscopy utilising a polymer membrane sandwich filtration vessel for the detection of acid-fast bacilli in health facilities in Sabah, East Malaysia

A simple, ready-to-use concentrated specimen smear microscopy method employing a nanometer silicon polyvinylidene fluoride (PVDF) polymer membrane sandwich filtration vessel to concentrate acid-fast bacilli (AFB) in samples (SFV-CSSM, Hunan-Tech New Medical System Co. Ltd. China) was compared with direct sputum smear microscopy (DSSM) to determine its performance using culture on modified Ogawa agar as reference. The results for 4114 clinical samples collected from health facilities in Sabah were interpreted with reference to culture results, sample collection-transportation conditions and clinical data including responses to anti-TB drug treatment. The SFV-CSSM showed higher sensitivity than DSSM (79.4% versus 60.5%) and less background interference. Its ability to detect low levels of AFB at an affordable cost makes it an excellent tool for the screening of pauci-bacillary samples as well as for active case finding in TB control programs

Evidence and potential risk factors of tuberculosis among captive Asian elephants and wildlife staff in Peninsular Malaysia

Elephant tuberculosis (TB) caused by Mycobacterium tuberculosis is an important re-emerging zoonosis with considerable conservation and public health risk. We conducted prospective cohort and cross-sectional studies in elephants and wildlife staff respectively in order to identify potential risk factors associated with TB in captive Asian elephants and their handlers in Peninsular Malaysia. Sixty elephants in six different facilities were screened for TB longitudinally using the ElephantTB STAT-PAK and DPP VetTB assays from February 2012 to May 2014, and 149 wildlife staff were examined for tuberculosis infection using the QuantiFERON-TB Gold In-tube (QFT) assay from January to April, 2012. Information on potential risk factors associated with infection in both elephants and staff were collected using questionnaires and facility records. The overall seroprevalence of TB amongst the elephants was 23.3% (95% CI: 13.8–36.3) and the risk of seroconversion was significantly higher among elephants with assigned mahouts [p = 0.022, OR = 4.9 (95% CI: 1.3–18.2)]. The percentage of QFT responders among wildlife staff was 24.8% (95% CI: 18.3–32.7) and the risk of infection was observed to be significantly associated with being a zoo employee [p = 0.018, OR = 2.7 (95% CI: 1.2–6.3)] or elephant handler [p = 0.035, OR = 4.1 (95% CI: 1.1–15.5)]. These findings revealed a potential risk of TB infection in captive elephants and handlers in Malaysia, and emphasize the need for TB screening of newly acquired elephants, isolating sero-positive elephants and performing further diagnostic tests to determine their infection status, and screening elephant handlers for TB, pre- and post-employment

The identification of novel Mycobacterium tuberculosis DHFR inhibitors and the investigation of their binding preferences by using molecular modelling

It is an urgent need to develop new drugs for Mycobacterium tuberculosis (Mtb), and the enzyme, dihydrofolate reductase (DHFR) is a recognised drug target. The crystal structures of methotrexate binding to mt- and h-DHFR separately indicate that the glycerol (GOL) binding site is likely to be critical for the function of mt-DHFR selective inhibitors. We have used in silico methods to screen NCI small molecule database and a group of related compounds were obtained that inhibit mt-DHFR activity and showed bactericidal effects against a test Mtb strain. The binding poses were then analysed and the influence of GOL binding site was studied by using molecular modelling. By comparing the chemical structures, 4 compounds that might be able to occupy the GOL binding site were identified. However, these compounds contain large hydrophobic side chains. As the GOL binding site is more hydrophilic, molecular modelling indicated that these compounds were failed to occupy the GOL site. The most potent inhibitor (compound 6) demonstrated limited selectivity for mt-DHFR, but did contain a novel central core (7H-pyrrolo[3,2-f]quinazoline-1,3-diamine), which may significantly expand the chemical space of novel mt-DHFR inhibitors. Collectively, these observations will inform future medicinal chemistry efforts to improve the selectivity of compounds against mt-DHFR

Anti-staphylococcal of EW1, A traditional herbal remedy for carbuncles

A powder (EW1) made from a mixture of herbs used for the treatment of carbuncles by traditional medicine practitioners in China was investigated for anti staphylococcal activity by agar diffusion, time-kill studies and M.Le. determinations performed on 17 clinical isolates and a reference strain ATCC 29213. It was found that EW1 had little demonstrable ib vitro activity against the clinical isolates tested but inhibited the growth of the ATCC strain at 10 mg/l and retarded its growth in broth culture by an average of 1.5 log reduction in colony count

An Asian Study on the Prevalence of Atypical Respiratory Pathogens in Community-Acquired Pneumonia

Background:In many parts of Asia, the inaccessibility and high cost of diagnostic tests have hampered the study of community-acquired pneumonia ( CAP) caused by atypical respiratory pathogens. Objective: This surveillance study examined the frequency of infection with Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Legionella pneumophila in 1756 patients presenting with signs and symptoms of CAP at 12 medical centres in Asia, using standardised laboratory techniques and interpretation criteria in all participating centres. Methods: Diagnosis of current infection was based on significant changes in antibody titer or persisting high antibody titers, together with the presence of bacterial DNA in respiratory secretions , in the case of M. pneumoniae and C. pneumoniae infections, or bacterial antigen in urine, in the case of L. pneumophila serogroup 1 infection. Results: Using these criteria, results from 1374 patients with paired sera showed that, overall, 23.5% of CAP cases were associated with infection with atypical respiratory pathogens, with M. pneumoniae, C. pneumoniae, and L. pneumophila being found in 12.2%, 4.7%, and 6.6% of cases, respectively. Persisting high antibody titers indicative of past exposure to M. pneumoniae, C. pneumoniae, and L. pneumophila were seen in 10.2%, 4.8%, and 18.9% of patients, respectively. Conclusion : These data reflect the overall high prevalence of these atypical pathogens among Asian patients with CAP

Genetic Determinants of Tigecycline Resistance in Mycobacteroides abscessus

Mycobacteroides abscessus (formerly Mycobacterium abscessus) is a clinically important, rapid-growing non-tuberculous mycobacterium notoriously known for its multidrug-resistance phenotype. The intrinsic resistance of M. abscessus towards first- and second-generation tetracyclines is mainly due to the over-expression of a tetracycline-degrading enzyme known as MabTetX (MAB_1496c). Tigecycline, a third-generation tetracycline, is a poor substrate for the MabTetX and does not induce the expression of this enzyme. Although tigecycline-resistant strains of M. abscessus have been documented in different parts of the world, their resistance determinants remain largely elusive. Recent work on tigecycline resistance or reduced susceptibility in M. abscessus revealed the involvement of the gene MAB_3508c which encodes the transcriptional activator WhiB7, as well as mutations in the sigH-rshA genes which control heat shock and oxidative-stress responses. The deletion of whiB7 has been observed to cause a 4-fold decrease in the minimum inhibitory concentration of tigecycline. In the absence of environmental stress, the SigH sigma factor (MAB_3543c) interacts with and is inhibited by the anti-sigma factor RshA (MAB_3542c). The disruption of the SigH-RshA interaction resulting from mutations and the subsequent up-regulation of SigH have been hypothesized to lead to tigecycline resistance in M. abscessus. In this review, the evidence for different genetic determinants reported to be linked to tigecycline resistance in M. abscessus was examined and discussed