A Global Mutational Profile of SARS-CoV-2: A Systematic Review and Meta-Analysis of 368,316 COVID-19 Patients.

Since its first detection in December 2019, more than 232 million cases of COVID-19, including 4.7 million deaths, have been reported by the WHO. The SARS-CoV-2 viral genomes have evolved rapidly worldwide, causing the emergence of new variants. This systematic review and meta-analysis was conducted to provide a global mutational profile of SARS-CoV-2 from December 2019 to October 2020. The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA), and a study protocol was lodged with PROSPERO. Data from 62 eligible studies involving 368,316 SARS-CoV-2 genomes were analyzed. The mutational data analyzed showed most studies detected mutations in the Spike protein (n = 50), Nucleocapsid phosphoprotein (n = 34), ORF1ab gene (n = 29), 5'-UTR (n = 28) and ORF3a (n = 25). Under the random-effects model, pooled prevalence of SARS-CoV-2 variants was estimated at 95.1% (95% CI; 93.3-96.4%; I2 = 98.952%; p = 0.000) while subgroup meta-analysis by country showed majority of the studies were conducted 'Worldwide' (n = 10), followed by 'Multiple countries' (n = 6) and the USA (n = 5). The estimated prevalence indicated a need to continuously monitor the prevalence of new mutations due to their potential influence on disease severity, transmissibility and vaccine effectiveness.

Multilocus sequence types of clinical Burkholderia pseudomallei isolates from peninsular Malaysia and their associations with disease outcomes.

BACKGROUND: Previous studies on the Burkholderia pseudomallei genetic diversity among clinical isolates from melioidosis-endemic areas have identified genetic factors contributing to differential virulence. Although it has been ruled out in Australian and Thai B. pseudomallei populations, it remains unclear whether B. pseudomallei sequence types (STs) correlate with disease in Malaysian patients with melioidosis. METHODS: In this study, multi-locus sequence typing (MLST) was performed on clinical B. pseudomallei isolates collected from Kelantan state of Malaysia, patients' clinical data were reviewed and then genotype-risk correlations were investigated. RESULTS: Genotyping of 83 B. pseudomallei isolates revealed 32 different STs, of which 13(40%) were novel. The frequencies of the STs among the 83 isolates ranged from 1 to 12 observations, and ST54, ST371 and ST289 were predominant. All non-novel STs reported in this study have also been identified in other Asian countries. Based on the MLST data analysis, the phylogenetic tree showed clustering of the STs with each other, as well as with the STs from Southeast Asia and China. No evidence for associations between any of B. pseudomallei STs and clinical melioidosis presentation was detected. In addition, the bacterial genotype clusters in relation with each clinical outcome were statistically insignificant, and no risk estimate was reported. This study has expanded the data for B. pseudomallei on MLST database map and provided insights into the molecular epidemiology of melioidosis in Peninsular Malaysia. CONCLUSION: This study concurs with previous reports concluding that infecting strain type plays no role in determining disease presentation.

A Combination of Trimethoprim-sulfamethoxazole and Ceftazidime Showed Good In Vitro Activity against Stenotrophomonas maltophilia.

BACKGROUND: Stenotrophomonas maltophilia has emerged as an important nosocomial pathogen, capable of causing a wide spectrum of infections. Treatment is difficult because it is resistant to many antimicrobial agents, thus reducing the treatment options. The aims of this study were to describe the antimicrobial susceptibility patterns and synergistic effect of selected antimicrobial combinations against S. maltophilia isolates. METHODS: This was a descriptive cross-sectional study undertaken in the Hospital Universiti Sains Malaysia from April 2011 to March 2012. S. maltophilia isolated from various clinical specimens were included in the study. Antimicrobial susceptibility testing was done using the epsilometer test (E-test) and interpreted according to the guidelines of the Clinical and Laboratory Standards Institute. In the synergy test, the isolates were tested against six different antimicrobial combinations. RESULTS: In total, 84 S. maltophilia isolates were collected and analysed. According to the E-test, the antimicrobial susceptibility of trimethoprim-sulfamethoxazole (TMP-SMX), tigecycline, and ciprofloxacin was 100%, 91.1%, and 88.9% respectively. The antimicrobial combination of TMP-SMX and ceftazidime showed the highest synergistic effect. CONCLUSION: TMP-SMX remains the antimicrobial of choice to treat S. maltophilia infection. TMP-SMX and ceftazidime was the most effective combination in vitro.

The epidemiology and clinical spectrum of melioidosis in a teaching hospital in a North-Eastern state of Malaysia: a fifteen-year review.

BACKGROUND: Over the last two decades, many epidemiological studies were performed to describe risks and clinical presentations of melioidosis in endemic countries. METHODS: We performed a retrospective analysis of 158 confirmed cases of melioidosis collected from medical records from 2001 to 2015 in Hospital Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia, in order to update the current status of melioidosis clinical epidemiology in this putatively high risk region of the country. RESULTS: Principal presentations in patients were lung infection in 65 (41.1 %), skin infection in 44 (27.8 %), septic arthritis/osteomyelitis in 20 (12.7 %) and liver infection in 19 (12.0 %). Bacteremic melioidosis was seen in most of patients (n = 121, 76.6 %). Focal melioidosis was seen in 124 (78.5 %) of patients and multi-focal melioidosis was reported in 45 (28.5 %) cases. Melioidosis with no evident focus was in 34 (21.5 %) patients. Fifty-four (34.2 %) patients developed septic shock. Internal organ abscesses and secondary foci in lungs and/or soft tissue were common. A total of 67 (41 %) cases presented during the monsoonal wet season. Death due to melioidosis was reported in 52 (32.9 %) patients, while relapses were occurred in 11 (7.0 %). Twelve fatal melioidosis cases seen in this study were directly attributed to the absence of prompt acute-phase treatment. Predisposing risk factors were reported in most of patients (n = 133, 84.2 %) and included diabetes (74.7 %), immune disturbances (9.5 %), cancer (4.4 %) and chronic kidney disease (11.4 %). On multivariate analysis, the only independent predictors of mortality were the presence of at least one co-morbid factor (OR 3.0; 95 % CI 1.1-8.4), the happening of septic shock (OR 16.5; 95 % CI 6.1-44.9) and age > 40 years (OR 6.47; 95 % CI 1.7-23.8). CONCLUSIONS: Melioidosis should be recognized as an opportunistic nonfatal infection for healthy person. Prompt early diagnosis and appropriate antibiotics administration and critical care help in improved management and minimizing risks for death.

Brief communication genotyping of Burkholderia pseudomallei revealed high genetic variability among isolates from a single population group.

Burkholderia pseudomallei is a soil dwelling Gram-negative bacteria predominates in Southeast Asia zone and the tropical part of Australia. Genetic diversity has been explored among various populations and environments worldwide. To date, little data is available on MLST profiling of clinical B. pseudomallei isolates in peninsular Malaysia. In this brief report, thirteen culture positive B. pseudomallei cases collected from a single population of Terengganu state in the Western Peninsular Malaysia and were confirmed by In-house TTS1-PCR. Isolates were subjected for multi-locus sequence typing (MLST) to explore their genotypic diversity and to investigate for possible clonal clustering of a certain sequence type. Patient's clinical information was examined to investigate for clinical correlation among the different genotypes. In spite of small sample set, MLST results indicated predictive results; considerable genotypic diversity, predominance and novelty among B. pseudomallei collected over a single geographically-located population in Malaysia. Massive genotypic heterogeneity was observed; 8 different sequence types with predominance of sequence type 54 and discovery of two novel sequence types. However, no clear pathogenomic or organ tropism clonal relationships were predicted.

Detection of blaIMP4 and blaNDM1 harboring Klebsiella pneumoniae isolates in a university hospital in Malaysia.

Background : Antibiotic resistance among Enterobacteriaceae posts a great challenge to the health care service. The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) is attracting significant attention due to its rapid and global dissemination. The infection is associated with significant morbidity and mortality, thus creating challenges for infection control and managing teams to curb the infection. In Southeast Asia, there have been limited reports and subsequent research regarding CRKP infections. Thus, the study was conducted to characterize CRKP that has been isolated in our setting. Methods : A total of 321 K. pneumoniae were included in the study. Each isolate went through an identification process using an automated identification system. Phenotypic characterization was determined using disk diffusion, modified Hodge test, Epsilometer test, and inhibitor combined disk test. Further detection of carbapenemase genes was carried out using polymerase chain reaction and confirmed by gene sequence analysis. Results : All together, 13 isolates (4.05%) were CRKP and the majority of them were resistant to tested antibiotics except colistin and tigercycline. Among seven different carbapenemase genes studied (blaKPC, bla IMP, bla SME, bla NDM, bla IMI, bla VIM, and bla OXA), only two, bla IMP4 (1.87%) and bla NDM1 (2.18%), were detected in our setting. Conclusion : Evidence suggests that the prevalence of CRKP in our setting is low, and knowledge of Carbapenem-resistant Enterobacteriaceae and CRKP has improved and become available among clinicians.