Global prevalence of alkhumra hemorrhagic fever virus infection: The first meta-analysis and systematic review.

Alkhumra hemorrhagic fever virus (AHFV) has spread beyond the Middle East. However, the actual global prevalence of the virus is yet unknown. This systematic review and meta-analysis, thus, followed the standard reporting guidelines to provide comprehensive details on the prevalence of Alkhumra virus infection globally. The pooled prevalence of AHFV globally was estimated at 1.3% (95% CI: 0.3-6.3), with higher prevalence in humans (3.4%, 95% CI: 0.4-25.0) compared to animals (0.7%, 95% CI: 0.3-1.8). The prevalence in ticks and camels were 0.7% and 0.2%, respectively. Overall, there was a high prevalence rate in Asia (2.6%) compared to Africa (0.5%), and a distinctly higher prevalence in Saudi Arabia (4.6%) compared to other parts of the world (<1%). Lower surveillance rate in humans was observed in recent years. These findings will aid public health preparedness, surveillance, and development of preventive measures due to AHFV's potential for outbreaks and severe health consequences.

A Review of the Resistance Mechanisms for ß-Lactams, Macrolides and Fluoroquinolones among Streptococcus pneumoniae.

Streptococcus pneumoniae (S. pneumoniae) is a bacterial species often associated with the occurrence of community-acquired pneumonia (CAP). CAP refers to a specific kind of pneumonia that occurs in individuals who acquire the infection outside of a healthcare setting. It represents the leading cause of both death and morbidity on a global scale. Moreover, the declaration of S. pneumoniae as one of the 12 leading pathogens was made by the World Health Organization (WHO) in 2017. Antibiotics like ß-lactams, macrolides, and fluoroquinolones are the primary classes of antimicrobial medicines used for the treatment of S. pneumoniae infections. Nevertheless, the efficacy of these antibiotics is diminishing as a result of the establishment of resistance in S. pneumoniae against these antimicrobial agents. In 2019, the WHO declared that antibiotic resistance was among the top 10 hazards to worldwide health. It is believed that penicillin-binding protein genetic alteration causes ß-lactam antibiotic resistance. Ribosomal target site alterations and active efflux pumps cause macrolide resistance. Numerous factors, including the accumulation of mutations, enhanced efflux mechanisms, and plasmid gene acquisition, cause fluoroquinolone resistance. Furthermore, despite the advancements in pneumococcal vaccinations and artificial intelligence (AI), it is not feasible for individuals to rely on them indefinitely. The ongoing development of AI for combating antimicrobial resistance necessitates more research and development efforts. A few strategies can be performed to curb this resistance issue, including providing educational initiatives and guidelines, conducting surveillance, and establishing new antibiotics targeting another part of the bacteria. Hence, understanding the resistance mechanism of S. pneumoniae may aid researchers in developing a more efficacious antibiotic in future endeavors.

Prevalence of Hepatocellular Carcinoma in Hepatitis B Population within Southeast Asia: A Systematic Review and Meta-Analysis of 39,050 Participants.

BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) is a significant complication of hepatitis B and still poses a global public health concern. This systematic review and meta-analysis provide adequate details on the prevalence of HCC in the HBV population within Southeast Asian countries. METHOD: Following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) criteria, a thorough search for literature discussing the prevalence of HCC in the HBV population within southeast Asia was performed. Eligible studies were subjected to a meta-analysis utilising a DerSimonian and Laird approach and a random effect model. A protocol was registered with PROSPERO (CRD42023423953). RESULT: Our study meticulously recovered 41 articles from seven countries in Southeast Asia, namely Cambodia, Indonesia, Malaysia, the Philippines, Singapore, Thailand, and Vietnam. A total of 39,050 HBV patients and 7479 HCC cases in southeast Asia were analysed. The pooled prevalence of HCC in HBV cases within southeast Asia was 45.8% (95% CI, 34.3-57.8%, I2 = 99.51%, p < 0.001). Singapore (62.5%, CI: 42.4-79.1) had the highest pooled prevalence of HCC in the HBV population compared to Vietnam, with the lowest estimate (22.4%, CI: 9.9-44.9). There was a drop in the pooled prevalence of HCC in HBV from 2016 until now (37.6%, CI: 19.2-60.5). CONCLUSION: The findings of this review reveal a high pooled prevalence of HCC in the HBV population and therefore stir the need for routine screening, management, and surveillance.

A review on current diagnostic tools and potential optical absorption spectroscopy for HFMD detection.

Hand, Foot, and Mouth Disease (HFMD) is an outbreak infectious disease that can easily spread among children under the age of five. The most common causative agents of HFMD are enterovirus 71 (EV71) and coxsackievirus A16 (CVA16), but infection caused by EV71 is more associated with fatalities due to severe neurological disorders. The present diagnosis methods rely on physical examinations by the doctors and further confirmation by laboratories detection methods such as viral culture and polymerase chain reaction. Clinical signs of HFMD infection and other childhood diseases such as chicken pox, and allergies are similar, yet the genetics and pathogenicity of the viruses are substantially different. Thus, there is an urgent need for an early screening of HFMD using an inexpensive and user-friendly device that can directly detect the causative agents of the disease. This paper reviews current HFMD diagnostic methods based on various target types, such as nucleic acid, protein, and whole virus. This was followed by a thorough discussion on the emerging sensing technologies for HFMD detection, including surface plasmon resonance, electrochemical sensor, and surface enhanced Raman spectroscopy. Lastly, optical absorption spectroscopic method was critically discussed and proposed as a promising technology for HFMD screening and detection.

Aberrant frequency of TNFR2-expressing CD4+ FoxP3+ regulatory T cells in nasopharyngeal carcinoma patients.

TNFR2 is a surface marker of highly suppressive subset of CD4+ FoxP3+ regulatory T cells (Tregs) in humans and mice. This study examined the TNFR2 expression by Tregs of nasopharyngeal carcinoma (NPC) patients and healthy controls. The proliferation, migration, survival of TNFR2+ Tregs, and association with clinicopathological characteristics were assessed. The expression levels of selected cytokines were also determined. The results demonstrated that in both peripheral blood (PB) (10.45 ± 5.71%) and tumour microenvironment (TME) (54.38 ± 16.15%) of NPC patients, Tregs expressed TNFR2 at noticeably greater levels than conventional T cells (Tconvs) (3.91 ± 2.62%, p < 0.0001), akin to healthy controls. Expression of TNFR2 (1.06 ± 0.99%) was correlated better than CD25+ (0.40 ± 0.46%) and CD127-/low (1.00 ± 0.83% ) with FoxP3 expression in NPC PB (p = 0.0005). Though there was no significant association between TNFR2 expression with the functional capacity (proliferation, migration and survival) of Tregs (p > 0.05), the proportions of PB and TME TNFR2+ Tregs in NPC patients showed more proliferative, higher migration capacity, and better survival ability, as compared to those in healthy controls. Furthermore, TNFR2+ Tregs from NPC patients expressed significantly higher amounts of IL-6 (p = 0.0077), IL-10 (p = 0.0001), IFN-γ (p = 0.0105) and TNF-α (p < 0.0001) than those from healthy controls. Most significantly, TNFR2 expression in maximally suppressive Tregs population were linked to WHO Type III histological type, distant metastasis, progressive disease status, and poor prognosis for NPC patients. Hence, our research implies that TNFR2 expression by PB and TME Tregs may be a useful predictive indicator in NPC patients.

A Recent Prevalence of Hepatitis B Virus (HBV) Genotypes and Subtypes in Asia: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIM: Despite introducing the hepatitis B virus (HBV) vaccine, the incidence of the Hepatitis B virus globally is still a major health concern. This systematic review and meta-analysis were conducted to provide detailed information on the prevalence of HBV genotypes and subtypes in circulation in Asia. METHODS: A systematic search for articles describing the prevalence of HBV genotypes and subtypes in Asia was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. RESULTS: Our search returned 207 eligible articles involving 49,279 genotypes and 7457 subtypes representing 28 Asian countries. A meta-analysis was performed on our eligible studies using the Random effect Model. The pooled prevalence of HBV genotypes showed that genotype C (30.9%) (95% CI, 27.5-34.5%; I2 = 97.57%; p < 0.001) was the most common HBV genotype in Asia, followed by genotype B (17.8%) (95% CI, 15.5-20.4%; I2 = 97.26%; p < 0.001) and genotype D (15.4%) (95% CI, 11.8-19.8%). Vietnam had the highest prevalence of genotype B, Lebanon had the highest prevalence of genotypes C, and Jordan had the highest prevalence of genotype D. There was variation in genotypic prevalence with respect to the target genes for HBV genotyping. Reverse dot blot hybridization had the highest estimate of genotypes B and C. HBV subtype C2 (40.0%) (95% CI, 33.3-47.0) is the most prevalent HBV subtype. CONCLUSION: Evidence from this study reveals that HBV genotypes C and B are the most dominant HBV genotypes in Asia, and HBV subtype C2 is more endemic in Asia.

Anti-Tumor Necrosis Factor for Supplementary Management in Severe Asthma: A Systematic Review and Meta-analysis.

Tumor-necrosis factor (TNF) is recognized as a therapeutic target in inflammatory diseases, including asthma. In severe forms of asthma, biologics such as anti-TNF are rendered to be investigated as therapeutic options in severe asthma. Hence, this work is done to assess the efficacy and safety of anti-TNF as a supplementary therapy for patients with severe asthma. A systematic search of 3 databases (Cochrane Central Register of Controlled Trials, MEDLINE, ClinicalTrials.gov) was performed to identify for published and unpublished randomized controlled trials comparing anti-TNF (etanercept, adalimumab, infliximab, certolizumab pegol, golimumab) with placebo in patients diagnosed with persistent or severe asthma. Random-effects model was used to estimate risk ratios and mean differences (MDs) with confidence intervals (95% CIs). PROSPERO registration number is CRD42020172006. Four trials with 489 randomized patients were included. Comparison between etanercept and placebo involved 3 trials while comparison between golimumab and placebo involved 1 trial. Etanercept produced a small but significant impairment in forced expiratory flow in 1 second (MD 0.33, 95% CI 0.09-0.57, I2 statistic = 0%, P = 0.008) and a modest improvement of asthma control using the Asthma Control Questionnaire. However, using the Asthma Quality of Life Questionnaire, the patients exhibit an impaired quality of life with etanercept. Treatment with etanercept showed a reduced injection site reaction and gastroenteritis compared with placebo. Although treatment with anti-TNF is shown to improve asthma control, severe asthma patients did not benefit from this therapy as there is limited evidence for improvement in lung function and reduction of asthma exacerbation. Hence, it is unlikely to prescribe anti-TNF in adults with severe asthma.

Prevalence of Spontaneous Bacterial Peritonitis (SBP) in Hepatitis B (HBV), and Hepatitis C (HCV) Liver Cirrhosis: A Systematic Review and Meta-Analysis.

Background and Aim: Spontaneous bacterial peritonitis (SBP) is a common infection in liver cirrhosis. This systematic review and meta-analysis provide detailed information on the prevalence of SBP among hepatitis B virus (HBV) and hepatitis C virus (HCV)-related liver cirrhosis globally. Methods: A systematic search for articles describing the prevalence of SBP in HBV and HCV-related cirrhosis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Our search returned ten (10) eligible articles involving 1713 viral cirrhosis cases representing eight (8) countries. A meta-analysis was performed on our eligible studies using the random effect model. A protocol was registered with PROSPERO (CRD42022321790). Results: The pooled prevalence of SBP in HBV-associated cirrhosis had the highest estimate [8.0% (95% CI, 2.7−21.0%; I2 = 96.13%; p < 0.001)], followed by SBP in HCV-associated liver cirrhosis [4.0% (95% CI, 1.3%−11.5%; I2 = 88.99%; p < 0.001)]. China (61.8%, CI: 57.1−66.3%), the USA (50.0%, CI: 34.6−65.4%), and Holland (31.1%, CI: 21.6−42.5%) had the highest estimate for SBP in HBV associated liver cirrhosis, SBP in HCV associated liver cirrhosis and SBP in HBV + HCV associated liver cirrhosis respectively. There was a significant difference in the prevalence of SBP in viral hepatitis-associated liver cirrhosis with the year of sampling and method of SBP detection at P < 0.001. There was an increase in SBP incidence at the beginning of 2016 across the liver cirrhosis in this study. Conclusion: The findings of this review revealed a rise in the incidence of SBP in viral hepatitis over the last decade. The latter indicates a possible future rise in the global prevalence of SBP among HBV and HCV-related liver cirrhosis.

A GNAS Gene Mutation's Independent Expression in the Growth of Colorectal Cancer: A Systematic Review and Meta-Analysis.

Globally, colorectal carcinoma CRC is the third most common cancer and the third most common reason for cancer-associated mortality in both genders. The GNAS mutations are significantly linked with poor prognosis and failed treatment outcomes in CRC. A systematic review and meta-analysis of multiple studies executed following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) criteria and registered with PROSPERO (registration number: CRD42021256452). The initial search includes a total of 271 publications; however, only 30 studies that merit the eligibility criteria were eventually chosen. Data analysis via OpenMeta Analyst and comprehensive meta-analysis 3.0 (CMA 3.0) software were used to investigate the prevalence of GNAS gene mutation among CRC patients. The meta-analysis consisted of 10,689 participants with most being males 6068/10,689 (56.8%). Overall, prevalence of GNAS mutations was 4.8% (95% CI: 3.1−7.3) with I2 = 94.39% and (p < 0.001). In 11/30 studies, the frequency of GNAS gene mutations was majorly in codons R201C [40.7% (95% CI: 29.2−53.2%)] and in codon R201H [39.7% (95% CI = 27.1−53.8)]. Overall prevalence of GNAS mutations was highest among the male gender: 53.9% (95% CI: 48.2−59.5%: I2 = 94.00%, (p < 0.001), tumour location (colon): 50.5% (95% CI: 33.2−67.6%: I2 = 97.93%, (p < 0.001), tumour grade (Well): 57.5% (95% CI: 32.4−79.2%: I2 = 98.10%, (p < 0.001) and tumour late stage: 67.9% (95% CI: 49.7−84.3%: I2 = 98.%, (p < 0.001). When stratified according to study location, a higher prevalence was observed in Japan (26.8%) while Italy has the lowest (0.4%). Overall prevalence of GNAS gene mutations was 4.8% with codons R201C and R201H being the most mutated, and the results conformed with numerous published studies on GNAS mutation.

Effectiveness of Pulmonary Rehabilitation among COVID-19 Patients: A Systematic Review and Meta-Analysis.

Background: Many COVID-19 patients presented with detrimental features, such as impaired respiratory function, physical capacity, and overall poor quality of life. The present study evaluates the effectiveness of pulmonary rehabilitation on COVID-19 patients. Methods: We searched PubMed, Scopus, ScienceDirect, and Google Scholar from 2019 to 2021. The protocol was registered in PROSPERO with the registration number CRD42021273618. We performed statistical analyses via random effects and expressed the outcomes as standardized mean difference (SMD) for continuous variables, with 95% confidence intervals (CI). Results: We included six trials involving 432 patients. The primary outcome showed a significant improvement in physical function (SMD 0.83, 95% CI −0.58 to 1.09; p < 0.001; four trials, 266 participants; high-quality evidence). There was significant difference in anxiety (SMD −0.80, 95% CI −1.23 to −0.37; p = 0.003), physical activity intensity levels (SMD −1.27, 95% CI −2.23 to −0.32; p = 0.009), sleep quality (MD −0.05, 95% CI −0.83 to −0.16; p = 0.004), peripheral muscle performance of lower limbs (SMD 0.90, 95% CI −0.60 to 1.20; p < 0.001), and dyspnoea outcomes (SMD −0.55, 95% CI −0.87 to −0.23; p = 0.007). Conclusions: Pulmonary rehabilitation is an effective adjuvant therapy that minimizes COVID-19 severity in the intervention group compared to the conventional treatment. The findings of this study will need to be considered in the framework of the clinical outcome as observed in the intervention outcome. Additionally, safer data on guideline rehabilitation would be needed to examine whether pulmonary rehabilitation would be a fruitful intervention to reduce COVID-19 severity.

Effects of Circuit Training on Patients with Knee Osteoarthritis: A Systematic Review and Meta-Analysis.

The most prevalent joint disease is osteoarthritis (OA), which affects an estimated 240 million individuals worldwide. Knee osteoarthritis (KOA) is one of the top 10 causes of disability worldwide. The aim of this study is to systematically evaluate the effect of circuit training (CT) on patients with KOA. We searched through PubMed, Scopus, ScienceDirect, Cochrane, and Google Scholar up to 12 February 2022. We used random-effects statistical analysis for continuous variables and reported the results as a standardized mean difference (SMD) with 95 percent confidence intervals (CI). Seven trials involving 346 patients were included. A significant improvement in the intervention group was observed for the parameter, pain level (SMD -0.96, 95% CI -1.77 to -0.14; p = 0.02; seven trials, 346 participants; high quality evidence), while no significant improvement was found in physical function (SMD 0.03, 95% CI -0.44-0.50; p = 0.89; five trials, 294 participants; high-quality evidence), quality of life (SMD -0.25, 95% CI -1.18-0.68; p = 0.60; three trials, 205 participants; high-quality evidence), the activity of daily living (SMD 0.81, 95% CI -0.85-2.48; p = 0.34; three trials, 223 participants; high-quality evidence), and knee stiffness (SMD -0.65, 95% CI -1.96-0.66; p = 0.33; two trials, 71 participants; high-quality evidence). The findings in this meta-analysis suggest that CT could effectively complement the conventional treatment of KOA, particularly in alleviating pain. However, comprehensive data on the guidelines for the CT approach would be needed to adequately examine the effects of CT on quality of life and biochemical markers in patients with KOA.

SARS-CoV-2 viral shedding and susceptibility: perspectives on gender and asymptomatic patients.

Despite efforts to contain and manage the SARS-CoV-2 outbreak which was declared a public health emergency of international concern in January 2020 by the World Health Organization (WHO), the COVID-19 pandemic still remains a major global challenge. Patients who display the classical symptoms of the infection are easily identified, tested, isolated and monitored. However, many cases of infected asymptomatic patients have been documented. These patients are not easily identified even though many evidences suggest that they can spread the virus to others. How and why these COVID-19 asymptomatic presentations occur remain unclear. The many theories and views are conjectural, and supporting evidences are still needed. In this review, we described the trend in SARS-CoV-2 viral shedding and susceptibility, providing perspectives on gender differences and asymptomatic patients. We further discussed how genetics, gender, viral inoculum, and pre-existing immunity may influence asymptomatic presentations in COVID-19 infections. We hope that this article improves our understanding of asymptomatic SAR-CoV-2 infection and it sheds light on some salient areas that should be considered as the search for a potent vaccine continues.

Prognostic Epstein-Barr Virus (EBV) miRNA biomarkers for survival outcome in EBV-associated epithelial malignancies: Systematic review and meta-analysis.

BACKGROUND: The EBV-associated epithelial tumours consist 80% of all EBV-associated cancer, where the nasopharyngeal cancer (NPC) and EBV-associated gastric carcinoma (EBVaGC) are considered as the most frequent EBV-associated epithelial tumours. It has been shown that the BART-encoded miRNAs are abundantly expressed in EBV-associated epithelial tumours, hence, these miRNAs may serve as diagnostic and prognostic biomarkers for EBV-associated epithelial tumours. Therefore, the purpose of this systematic review and meta-analysis is to assess these EBV miRNAs as prognostic biomarkers for NPC and GC. METHOD: This systematic review was developed based on PRISMA guidelines and utilizing PubMed, Web of Science, Scopus, Cochrane, and Google scholar databases. The retrieved articles were thoroughly screened in accordance with the selection criteria. The hazard ratio (HR) and 95% confidence interval (CI) for patient survival outcomes were used to evaluate EBV miRNA expression levels. To assess the risk of bias, funnel plot symmetry and Egger's bias test were employed. RESULT: Eleven studies met the selection criteria for inclusion, and four were included in the meta-analysis. Most of the articles considered in this study were from China, with one study from South Korea. The overall pooled effect size estimation (HR) for upregulated EBV miRNAs was 3.168 (95% CI: 2.020-4.969), demonstrating that upregulated EBV miRNA expression enhanced the mortality risk in NPC and GC patients by three times. CONCLUSION: To the best of our knowledge, this is the first meta-analysis that investigates the significance of EBV miRNAs as prognostic biomarkers in NPC and GC patients. The pooled effect estimates of HR of the various studies revealed that higher EBV miRNA expression in NPC and GC may result in a worse survival outcome. To assess the clinical significance of EBV miRNAs as prognostic biomarkers, larger-scale prospective studies are needed.

Prevalence of EBV infection in 1157 diseased cohorts in Nigeria: A systematic review and meta-analysis.

BACKGROUND: Epstein-Barr virus (EBV) is a member of the herpesvirus family that is known to ubiquitously infect people worldwide. However, the actual prevalence of EBV infection in diseased patients in Nigeria, remains unknown. This study was thus conducted to ascertain the true prevalence. METHODS: A systematic review and meta-analysis of published data was conducted according to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Electronic databases including PubMed, Scopus, ScienceDirect, and Google Scholar were searched for studies reporting the occurrence of EBV infection among patients with established diseases. Studies were included if they assessed EBV infection in diseased patients in Nigeria. Data were extracted and subsequently analysed using R software. Funnel plot and Egger's regression test was used to assess publication bias, while JBI prevalence tool was used to assess study quality. RESULTS: A total of 13 studies covering 228 cases of EBV infection among 1157 diseased patients were included. Summary estimates were computed using random-effects model. The pooled prevalence of EBV infection was 20.3% (95% CI: 10.8-34.9, I2 â€‹= â€‹92.26, p â€‹< â€‹0.001). When stratified according to the type of disease, higher estimates were obtained for patients suffering from Kaposi's sarcoma (98.7%, 95% CI: 82.2-99.9) and Nasopharyngeal malignancy (85.7%, 95% CI: 70.0-93.9). A prevalence of 13.4% (95% CI: 6.0-27.4) and 12.2% (95% CI: 4.8-27.8) was derived for the most reported patient populations, lymphoma and HIV, respectively. CONCLUSION: This first meta-analysis on the prevalence of EBV among Nigerian patients suffering from various diseases reveals a prevalence that emphasises the need to routinely monitor EBV infection in all EBV-associated diseases in Nigeria.

Global prevalence of dengue and chikungunya coinfection: A systematic review and meta-analysis of 43,341 participants.

Dengue and chikungunya virus are important arboviruses of public health concern. In the past decades, they have accounted for numerous outbreaks of dengue and chikungunya in different parts of the world. Several cases of concurrent infection of dengue and chikungunya have been documented. However, the true burden of this concurrent infection is unknown. Here, a systematic review and meta-analysis of published data on the prevalence of dengue and chikungunya coinfection in the human population was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. Six electronic databases (Web of science, Embase, PubMed, ScienceDirect, Scopus, and Google Scholar) were searched without year or language restrictions for relevant studies. The study protocol was registered with PROSPERO (CRD42020175344). Eighty-three studies involving a total of 43,341 participants were included. The random-effects model was employed to calculate the summary estimates. A pooled global prevalence of 2.5% (95% CI: 1.8-3.4) was obtained for dengue and chikungunya coinfection. Males and females appear to be coinfected at a fairly similar rate. Among the regions, Asia accounted for the highest prevalence (3.3%, 95% CI: 2.3-4.6) while North America was the least (0.8%, 95% CI: 0.3-2.4). The prevalence estimates varied across different countries. A much higher prevalence rates were obtained for Colombia (37.4%, 95% CI: 9.1-78.1), Madagascar (18.2%, 95% CI: 10.1-30.6), Laos (12.5%, 95% CI: 5.3-26.7), Maldives (4.5%, 95% CI: 1.5-13.0) and Thailand (3.7%, 95% CI: 0.4-26.3). This first extensive systematic review and meta-analysis reveals dengue and chikungunya coinfection as a global problem worthy of consideration. It is therefore pertinent that both infections be assessed during diagnosis, mosquito vector control practices be implemented, and vaccine development strides be supported globally.

Antivirals against HCV infection: the story thus far.

Remarkable scientific breakthroughs have been made in the stride towards the development of potent and tolerable hepatitis C regimens within the last three decades. Earlier approaches involved the use of pegylated interferon alfa and ribavirin as standard-of-care treatment. Treating genotype 1a infection with this regimen which was at that time considered the gold standard for hepatitis C virus therapy was rife with challenges; safety and toxicity issues necessitated a rigorous quest for alternative regimens. Deeper understanding of the pathogenesis of hepatitis C virus ushered in the era of direct acting antiviral agents. These agents have been the subject of intensive research in the last two decades, leading to the development of drug classes such as protease inhibitors (e.g., grazoprevir), NS5A inhibitors (e.g., daclatasvir) and NS5B inhibitors (e.g., sofosbuvir). While many are still under development, several have been approved for hepatitis C therapy. A number of studies investigating the combination of direct acting antiviral agents with or without pegylated interferon and/or ribavirin for the treatment of chronic hepatitis have demonstrated sustained virologic response of > 90%. Given the array of direct acting antiviral agents currently available, the present landscape of hepatitis C therapy is now characterized by a gradual transition to all-oral interferon-free regimens. Despite these milestones, the WHO global target of eliminating hepatitis C as a public health problem by 2030 seems uncertain. In this review, we provide a concise account of the evolution and advancements in the development of anti-HCV regimens.

Global Prevalence of Nosocomial Multidrug-Resistant Klebsiella pneumoniae: A Systematic Review and Meta-Analysis.

The emergence of nosocomial multidrug-resistant Klebsiella pneumoniae is an escalating public health threat worldwide. The prevalence of nosocomial infections due to K. pneumoniae was recorded up to 10%. In this systematic review and meta-analysis, which were conducted according to the guidelines of Preferred Reporting Items for Systematic Review and Meta-Analysis, 1092 articles were screened from four databases of which 47 studies fulfilled the selected criteria. By performing a random-effect model, the pooled prevalence of nosocomial multidrug-resistant K. pneumoniae was estimated at 32.8% (95% CI, 23.6-43.6), with high heterogeneity (I2 98.29%, p-value < 0.001). The estimated prevalence of this pathogen and a few related studies were discussed, raising awareness of the spread of multidrug-resistant K. pneumoniae in the healthcare setting. The emergence of nosocomial multidrug-resistant K. pneumoniae is expected to increase globally in the future, and the best treatments for treating and preventing this pathogen should be acknowledged by healthcare staff.

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.

One-step, multiplex, dual-function oligonucleotide of loop-mediated isothermal amplification assay for the detection of pathogenic Burkholderia pseudomallei.

This study highlights the development of a multiplex real-time loop-mediated isothermal amplification assay. The developed assay employed a dual-function oligonucleotide (DFO) which simultaneously monitors the emitted amplification signals and accelerates the amplification process. The DFO was a modification of loop primer (LP); the 5'-end and 3'-end of the LP was tagged with fluorophore and quencher, respectively. The DFO was quenched in its unbound state and fluoresces only when it anneals to the specific target during the amplification process. With the same working mechanism as LP, DFO allowed the detection of target genes in less than 1 h in a real time monitoring system. We demonstrated this detection platform with Burkholderia pseudomallei, the causative agent of melioidosis. An internal amplification control (IAC) was incorporated in the assay to rule out false negative result and to demonstrate that the assay was successfully developed in a multiplex system. The assay was 100% specific when it was evaluated against 96 B. pseudomallei clinical isolates and 48 other bacteria species. The detection limit (sensitivity) of the developed assay was 1 fg/µl of B. pseudomallei genomic DNA and 18.2 CFU/ml at the bacterial cell level. In spiked blood samples, the assay's detection limit was 14 CFU/ml. The assay's diagnostic evaluation showed 100% diagnostic sensitivity, diagnostic specificity, positive predictive value, and negative predictive value. An integrated multiplex LAMP and real-time monitoring system was successfully developed, simplifying the workflow for the rapid and specific nucleic acid diagnostic test.

Prevalence of HCV genotypes and subtypes in Southeast Asia: A systematic review and meta-analysis.

Known for its high genetic diversity and variation in genotypic presence in different regions of the world, hepatitis C virus (HCV) is estimated to infect about 71 million people globally. Selection of an appropriate therapeutic regimen largely depends on the identification of the genotype responsible for the infection. This systematic review and meta-analysis was conducted to provide a comprehensive view of HCV genotype and subtype distribution in Southeast Asia (SEA). The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). We searched five databases without year and language restrictions. Data from 90 eligible studies involving 15,089 genotypes and 9,646 subtypes representing 10 SEA countries were analyzed. The pooled estimates showed that genotype 1 (46.8%) [95% CI, 43.2-50.4; I2 = 92.77%; p < 0.001] was the most dominant HCV genotype in the region, followed by genotype 3 (23.1%) [95% CI, 19.4-27.2; I2 = 93.03%; p < 0.001], genotype 6 (16.5%) [95% CI, 13.8-19.6], genotype 2 (4.6%) [95% CI, 3.5-5.9], genotype 4 (1.1%) [95% CI, 0.7-1.5] and genotype 5 (0.8%) [95% CI, 0.4-1.3]. Philippines had the highest prevalence of genotypes 1 and 2. Genotype 6 became more prevalent after year 2000. Over 40 different subtypes were identified, with subtypes 1b (26.3%), 1a (21.3%), and 3a (14.3%) being the most prevalent of all the reported subtypes. Although on a global scale, genotype 6 is considered highly prevalent in SEA, evidence from this study reveals that it is the third most prevalent genotype within the region.