Molecular Epidemiological Characterization of Staphylococcus aureus and Staphylococcus argenteus Clinical Isolates from a National Tertiary Care Hospital in Myanmar: Co-Isolation of Multiple Clones and Identification of Novel Staphylocoagulase Genotype.

Spread of antimicrobial resistance and virulence factors among Staphylococcus aureus/Staphylococcus argenteus poses a potential public health concern in Myanmar. In this study, a total of 226 clinical isolates of S. aureus (n = 211) and S. argenteus (n = 15) collected in Yangon General Hospital during a two-year period were analyzed for their antimicrobial susceptibility and genetic features. Methicillin-resistant S. aureus (MRSA) accounted for 19% of S. aureus isolates, associated with mostly staphylococcal cassette chromosome mec (SCCmec) type IV, or V. Panton-Valentine leukocidin (PVL) genes were detected in methicillin-susceptible S. aureus (MSSA) at significantly higher rate (39%) than in MRSA (22%). Among MRSA, ST361 (clonal complex [CC] 361), ST772 (CC1), and ST239 (CC8) were frequently identified, while the most common clone in MSSA was ST2990 (CC1), followed by ST121 and CC8 comprising five STs. Novel coagulase gene genotype XVI was identified in four MSSA isolates. All the S. argenteus isolates were assigned to ST2250 and mecA negative, including only one PVL-positive isolate. MSSA and S. argenteus were co-isolated from two patients, while two different MSSA clones were simultaneously identified in eight patients. This study revealed clonal diversity and genetic characteristics of current MRSA/MSSA/S. argenteus clinical isolates in the national tertiary care hospital in Myanmar.

Myiasis in Ulcerated Breast Carcinoma: First Case Record in Myanmar.

Myiasis is an infestation of maggot, which is frequently associated with poor personal hygiene and environmental sanitation. A 78-year-old female breast cancer patient visited clinic complaining of irritation, itching, and pain within the ulcerous cancer lesion for 3 weeks. Many maggots were found in the lesion. A total of 30 maggots were removed and identified to be 3rd stage of larvae of metallic fly. This is the first case of wound myiasis in advanced breast carcinoma as a complication of untreated or drug-induced ulcer.

Prevalence of Extended-Spectrum Beta-Lactamase/Carbapenemase Genes and Quinolone-Resistance Determinants in Klebsiella pneumoniae Clinical Isolates from Respiratory Infections in Myanmar.

In recent years, nosocomial infections due to multidrug resistant Klebsiella pneumoniae strains have been increasing, associated with growing trend of resistance to beta-lactams and fluoroquinolones (FQs) worldwide. In this study, prevalence of beta-lactamase genes and resistance mechanisms to FQ were analyzed in 191 clinical K. pneumoniae isolates derived from respiratory tract infections in a teaching hospital in Yangon, Myanmar. The major extended-spectrum beta-lactamase gene was blaCTX-M, which was detected in 33% of isolates, with CTX-M-15 being dominant. Fourteen isolates (7.3%) harbored carbapenemase genes that were genotyped as blaNDM-1, blaNDM-5, or blaNDM-7. The most common plasmid-mediated quinolone resistance (PMQR) gene was aac6'-Ib-cr (51.8%), followed by qnrB (41.9%), oqxAB (23%), and qnrS (15.2%). In quinolone-resistance determining region of GyrA, eight different types of mutation were identified for FQ-resistant isolates, with double mutations at two positions (S83F, D87A) being most common (54.6%). Isolates with double mutations (three patterns) showed higher minimal inhibitory concentration to levofloxacin (LVX) (≥64 µg/mL) than those with a single mutation. PMQR gene profiles, including aac6'-Ib-cr and any other gene(s), were generally related to higher resistance level to LVX. K. pneumoniae isolates with different profiles of beta-lactamase genes and FQ-resistance determinants were mostly classified into ST15 or its single-locus variant (SLV). The most common NDM gene, blaNDM-5, was detected in ST975 (ST15-SLV) isolates and an ST4000 isolate. The present study revealed the wide spread of FQ-resistant K. pneumoniae clinical isolates acquiring various FQ-resistance determinants and beta-lactamases that were presumably derived from a single clonal lineage in a hospital in Myanmar.

Genetic Diversity of CMY Beta-Lactamase Genes in Clinical Isolates of Escherichia coli in Myanmar: Identification of Three Novel Types and Updated Phylogenetic Classification of blaCMY.

The dissemination of CMY-type enzymes, one of the plasmid-mediated AmpC beta-lactamases, among Enterobacteriaceae has become an important public health concern. In this study, genetic diversity of CMY beta-lactamase genes was investigated for 50 blaCMY-positive isolates detected from 426 clinical isolates of Escherichia coli in Yangon, Myanmar. CMY genes were differentiated into 9 types, with blaCMY-42 being predominant (22 isolates, 44%), followed by blaCMY-2, blaCMY-6, blaCMY-146, and included three novel types (CMY-156, CMY-158, CMY-159). Among E. coli harboring blaCMY, phylogenetic group D-sequence type (ST)405 and A-ST410 were the most common genotypes, and blaCTX-M-15 was detected in 72% (36/50) of isolates. blaCMY-42 was distributed to phylogenetic groups A, B1, and D E. coli with 11 STs, which included 10 isolates harboring carbapenemase genes (blaNDM-4, blaNDM-5, or blaNDM-7). Phylogenetic analysis of all the blaCMY genes reported to date, including the three novel types in the present study, revealed the presence of at least four distinct genetic groups, that is, CMY-1, CMY-2, CMY-70, and CMY-98 group, showing less than 91% nucleotide sequence identities among different groups. CMY-2 group beta-lactamase genes, which contained by far the largest number of CMY types (89.7%) with extensive diversity, were divided into two clusters (I and II). While eight CMY types identified in the present study were classified into CMY-2 group cluster I, novel type CMY-159 was assigned into CMY-98 group with a Citrobacter freundii strain in Thailand.

The Influence of Modernization and Disease on the Gastric Microbiome of Orang Asli, Myanmars and Modern Malaysians.

The present study explored the differences in gastric microbiome between three distinct populations of Southeast Asia. These include the isolated Orang Asli population and modern Malaysians, as well as patients from Myanmar, the least developed country in the region. All 79 subjects recruited in this study had Helicobacter pylori infection. Based on alpha diversity analysis, Orang Asli had the richest and most diverse gastric microbiome, followed by Myanmar and modern Malaysian groups. Beta diversity analysis revealed significant separation of samples between different populations. These observations are likely to be associated with the level of modernization of each population. Our data further suggested increased bacterial species richness and diversity of the gastric microbiome in individuals who were less modernized, particularly in the Orang Asli group, could suppress the growth of H. pylori. In addition, there were significant variations in the gastric microbiome between modern Malaysians with different types of gastric diseases. Notably, Cutibacterium acnes was present at significantly greater abundance level in patients with non-ulcerative dyspepsia than those with peptic-ulcer diagnosis. This suggests that C. acnes may also play a role in gastritis besides H. pylori, which merits further investigation.

Prevalence of Extended-Spectrum Beta-Lactamase and Carbapenemase Genes in Clinical Isolates of Escherichia coli in Myanmar: Dominance of blaNDM-5 and Emergence of blaOXA-181.

The increasing trend of Escherichia coli producing extended-spectrum beta-lactamases (ESBLs) and carbapenemases is a global public health concern. In this study, prevalence and molecular characteristics of E. coli harboring ESBL and carbapenemase genes were investigated for 426 isolates derived from various clinical specimens in a teaching hospital in Yangon, Myanmar, for the 1-year period beginning January 2016. A total of 157 isolates (36.9%) were ESBL producers and harbored CTX-M-1 group genes (146 isolates; blaCTX-M-15, blaCTX-M55) or CTX-M-9 group genes (11 isolates; blaCTX-M-14, blaCTX-M-27). Carbapenem resistance was detected in 35 isolates (8.2%), among which 26 isolates had carbapenemase genes encoding NDM-1 (2 isolates), NDM-4 (6 isolates), NDM-5 (14 isolates), NDM-7 (3 isolates), and OXA-181 (2 isolates). blaNDM-5 was identified in phylogenetic groups A, B1, and D isolates belonging to various genotypes (ST101, ST354, ST405, ST410, ST1196) associated with blaTEM-1, blaCTX-M-15, blaOXA-181, blaCMY-2, blaCMY-6, blaCMY-42, qnrB, qnrS, or aac6'-Ib-cr. While two isolates with blaOXA-181 belonged to phylogenetic group A-ST410, one isolate had also blaNDM-5, as well as blaCTX-M-15 and blaCMY-2, and the other harbored blaCMY-42 and aac6'-Ib-cr, showing different resistance patterns. Phylogenetic group B2 isolates examined were classified into mostly ST131 and had solely blaCTX-M-15 or blaCTX-M-27, harboring more virulence factors than other phylogenetic groups. The present study revealed high prevalence of ESBL genes represented by blaCTX-M-15 and dominance of blaNDM-5 among NDM genes, disseminating to various E. coli clones. Notably, carbapenemase gene encoding OXA-181 was first identified in Myanmar, suggesting its spread together with NDM genes.

A 26-week feasibility study comparing the efficacy and safety of modified-release prednisone with immediate-release prednisolone in newly diagnosed cases of giant cell arteritis.

OBJECTIVE: A feasibility study to assess efficacy and safety of modified release (MR) prednisone (Lodotra™) compared to immediate release (IR) prednisolone in patients with newly diagnosed giant cell arteritis (GCA). METHODS: Twelve patients with new diagnosis of GCA were initially treated with high-dose prednisolone (40-60 mg) daily for 4 weeks and then randomized to two open arms to continue tapering steroid treatment with either standard IR prednisolone or MR prednisone. Patients were reviewed every 2 weeks either face to face or by telephone, for a total of 26 weeks. Disease activity, steroid-related side effects, sleep disturbance, fatigue scores and blood tests were systematically monitored. The primary endpoint (efficacy) was defined as the proportion of patients achieving persistent clinical disease control (without features of active disease and remaining flare free at 26 weeks) in each arm. RESULTS: At 26 weeks, 6/7 patients taking MR prednisone were in persistent control, compared with 4/5 receiving IR prednisone. One patient in each group suffered a disease flare necessitating an increased steroid dose. There were no statistically significant differences between the groups in terms of reduction in inflammatory markers, Health Assessment Questionnaire, visual analogue scale, fatigue and improvement in EuroQol 5D scores. CONCLUSION: This trial shows that MR prednisone appears to be a safe and effective treatment for GCA with a similar outcome profile to standard IR prednisolone.

Prevalence and Genetic Characteristics of Staphylococcus aureus and Staphylococcus argenteus Isolates Harboring Panton-Valentine Leukocidin, Enterotoxins, and TSST-1 Genes from Food Handlers in Myanmar.

Asymptomatic carriers of toxigenic Staphylococcus aureus are potential source of diseases, including food poisoning. Toxigenic potential and genetic traits of colonizing S. aureus were investigated for 563 healthy food handlers in Myanmar. Carriage of S. aureus was found in 110 individuals (19.5%), and a total of 144 S. aureus isolates were recovered from nasal cavities (110 isolates) and hands (34 isolates). Panton-Valentine leucocidin genes (pvl) were detected in 18 isolates (12.5%), among which 11 isolates were classified into coa-VIa, agr type III, and ST1930 (CC96) that had been also detected in pvl-positive clinical isolates in Myanmar. A pvl-positive, ST2250 nasal isolate was identified as S. argenteus, a novel coagulase-positive staphylococcus species. Toxic shock syndrome toxin-1 (TSST-1) gene was detected in five pvl-negative isolates. All of the 144 isolates harbored at least one of the 21 enterotoxin(-like) gene(s). The most prevalent enterotoxin(-like) gene was selw (98%), followed by selx (97%), sei (28%), sely (28%), sem (26%), sel (24%), and sea and sec (22% each). Considerable genetic diversity with five groups was detected for selw. The present study revealed the relatively high rate of pvl, as well as the wide distribution of enterotoxin(-like) genes among colonizing S. aureus in Myanmar.

Characteristics of suppressor macrophages induced by mycobacterial and protozoal infections in relation to alternatively activated M2 macrophages.

In the advanced stages of mycobacterial infections, host immune systems tend to change from a Th1-type to Th2-type immune response, resulting in the abrogation of Th1 cell- and macrophage-mediated antimicrobial host protective immunity. Notably, this type of immune conversion is occasionally associated with the generation of certain types of suppressor macrophage populations. During the course of Mycobacterium tuberculosis (MTB) and Mycobacterium avium-intracellulare complex (MAC) infections, the generation of macrophages which possess strong suppressor activity against host T- and B-cell functions is frequently encountered. This paper describes the immunological properties of M1- and M2-type macrophages generated in tumor-bearing animals and those generated in hosts with certain microbial infections. In addition, this paper highlights the immunological and molecular biological characteristics of suppressor macrophages generated in hosts with mycobacterial infections, especially MAC infection.

The International Infections in Pregnancy (IIP) study: variations in the prevalence of bacterial vaginosis and distribution of morphotypes in vaginal smears among pregnant women.

OBJECTIVE: The objective of the study was to determine the prevalence of bacterial vaginosis and the distribution of associated morphotypes among asymptomatic pregnant women in different countries. STUDY DESIGN: In 8 institutions participating in the Global Network for Perinatal and Reproductive Health (www.gnprh.org) from July 1999 to September 2001, 1466 women were enrolled. Vaginal smears were Gram stained and scored with Nugent's method at a reference laboratory. The prevalence of bacterial vaginosis and bacterial morphotype distributions were compared. RESULTS: Overall, 12.3% of women had bacterial vaginosis according to Nugent's criteria. Zimbabwe had the highest prevalence (24.4%) when compared with all other sites, except Myanmar (P < .05). Among bacterial vaginosis cases, 98.9% of vaginal smears had more than 30 Gardnerella/Bacteroides morphotypes present per oil immersion field. Individual centers showed significant differences in the number of Mobiluncus and lactobacillus morphotypes (P < .01). CONCLUSION: The prevalence of bacterial vaginosis and distribution of bacterial morphotypes in vaginal smears among asymptomatic pregnant women vary significantly in populations from different countries.

Roles of tumor necrosis factor-alpha and transforming growth factor-beta in regulating intercellular adhesion molecule-1 expression on murine peritoneal macrophages infected with M. Leprae

Profiles of intercellular adhesion molecule-1 (ICAM-1) expression on murine peritoneal macrophages (M phi s) infected with Mycobacterium leprae during cultivation were examined with special reference to the regulatory effects of tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta). When M phi s were infected with M. leprae or stimulated with heat-killed M. leprae at day 0, their ICAM-1 expression, measured in terms of the ratio of M phi s positively stained with anti-ICAM-1 antibody (Ab), rapidly increased, peaking during days 1 to 3 and thereafter fell, returning to the normal level by day 7. The addition of TNF-alpha or anti-TGF-beta Ab inhibited the middle phase (day 7) downregulation of M phi ICAM-1 expression, although the late-phase (day 14) downregulation of ICAM-1 was not prevented by them. M. leprae-infected M phi s released small amounts of TNF-alpha and significant amounts of TGF-beta into the culture medium. This may indicate that M. leprae-infected M phi s produced the majority of TNF-alpha in a membrane-bound form. Alternatively, endogenous TNF-alpha might upregulate M phi ICAM-1 expression even at very low concentrations. In any case, these findings indicate the central roles of TNF-alpha and TGF-beta in the early phase upregulation and the middle-to-late phase downregulation, respectively, of ICAM-1 expression by M. leprae-infected M phi s.