Diagnostic Accuracy of Rapid Antigen Tests for COVID-19 Detection: A Systematic Review With Meta-analysis.

Introduction: Reverse transcription-polymerase chain reaction (RT-PCR) to detect SARS-CoV-2 is time-consuming and sometimes not feasible in developing nations. Rapid antigen test (RAT) could decrease the load of diagnosis. However, the efficacy of RAT is yet to be investigated comprehensively. Thus, the current systematic review and meta-analysis were conducted to evaluate the diagnostic accuracy of RAT against RT-PCR methods as the reference standard. Methods: We searched the MEDLINE/Pubmed and Embase databases for the relevant records. The QUADAS-2 tool was used to assess the quality of the studies. Diagnostic accuracy measures [i.e., sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratios (PLR), negative likelihood ratios (NLR), and the area under the curve (AUC)] were pooled with a random-effects model. All statistical analyses were performed with Meta-DiSc (Version 1.4, Cochrane Colloquium, Barcelona, Spain). Results: After reviewing retrieved records, we identified 60 studies that met the inclusion criteria. The pooled sensitivity and specificity of the rapid antigen tests against the reference test (the real-time PCR) were 69% (95% CI: 68-70) and 99% (95% CI: 99-99). The PLR, NLR, DOR and the AUC estimates were found to be 72 (95% CI: 44-119), 0.30 (95% CI: 0.26-0.36), 316 (95% CI: 167-590) and 97%, respectively. Conclusion: The present study indicated that using RAT kits is primarily recommended for the early detection of patients suspected of having COVID-19, particularly in countries with limited resources and laboratory equipment. However, the negative RAT samples may need to be confirmed using molecular tests, mainly when the symptoms of COVID-19 are present.

An overview on inactivated and live-attenuated SARS-CoV-2 vaccines.

After about 2 years since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first infections were detected in Wuhan city of China in December 2019, which was followed by a worldwide pandemic with a record of 5.41 million deaths. Due to urgent need for the development of a safe and effective vaccine for coronavirus disease 2019 (COVID-19), attempts for producing efficient vaccines are inexhaustibly continuing. According to a report by the World Health Organization (WHO) on COVID-19 vaccine tracker and landscape, there are 149 vaccine candidates all over the world. Inactivated SARS-CoV-2 vaccines as a conventional vaccine platform consist of whole virus particles grown in cell culture and inactivated by chemicals. Because of benefits such as antigenic similarity to real virion inducing humoral and cellular immune responses and ease for transport and storage, these vaccines, including the vaccines produced by Bharat Biotech, Sinopharm, and Sinovac, are in use at large scales. In this study, we have a review on inactivated SARS-CoV-2 vaccines that are passing their phase 3 and 4 clinical trials, population which was included in the trials, vaccine producers, the efficiency, adverse effects, and components of vaccines, and other vaccine features.

Diagnostic Accuracy of Pyrazinamide Susceptibility Testing in Mycobacterium tuberculosis: A Systematic Review with Meta-Analysis.

Introduction: Pyrazinamide (PZA) susceptibility testing plays a critical role in determining the appropriate treatment regimens for multidrug-resistant tuberculosis. We conducted a systematic review and meta-analysis to evaluate the diagnostic accuracy of sequencing PZA susceptibility tests against culture-based susceptibility testing methods as the reference standard. Methods: We searched the MEDLINE/PubMed, Embase, and Web of Science databases for the relevant records. The QUADAS-2 tool was used to assess the quality of the studies. Diagnostic accuracy measures (i.e., sensitivity and specificity) were pooled with a random-effects model. All statistical analyses were performed with Meta-DiSc (version 1.4, Cochrane Colloquium, Barcelona, Spain), STATA (version 14, Stata Corporation, College Station, TX), and RevMan (version 5.3, The Nordic Cochrane Centre, the Cochrane Collaboration, Copenhagen, Denmark) software. Results: A total of 72 articles, published between 2000 and 2019, comprising data for 8,701 isolates of Mycobacterium tuberculosis were included in the final analysis. The pooled sensitivity and specificity of the PZA sequencing test against all reference tests (the combination of BACTEC mycobacteria growth indicator tube 960 (MGIT 960), BACTEC 460, and proportion method) were 87% (95% CI: 85-88) and 94.7% (95% CI: 94-95). The positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and the area under the curve estimates were found to be 12.0 (95% CI: 9.0-16.0), 0.17 (95% CI: 0.13-0.21), 106 (95% CI: 71-158), and 96%, respectively. Deek's test result indicated a low likelihood for publication bias (p = 0.01). Conclusions: Our analysis indicated that PZA sequencing may be used in combination with conventional tests due to the advantage of the time to result and in scenarios where culture tests are not feasible. Further work to improve molecular tests would benefit from the availability of standardized reference standards and improvements to the methodology.

The resistance mechanisms of bacteria against ciprofloxacin and new approaches for enhancing the efficacy of this antibiotic.

For around three decades, the fluoroquinolone (FQ) antibiotic ciprofloxacin has been used to treat a range of diseases, including chronic otorrhea, endocarditis, lower respiratory tract, gastrointestinal, skin and soft tissue, and urinary tract infections. Ciprofloxacin's main mode of action is to stop DNA replication by blocking the A subunit of DNA gyrase and having an extra impact on the substances in cell walls. Available in intravenous and oral formulations, ciprofloxacin reaches therapeutic concentrations in the majority of tissues and bodily fluids with a low possibility for side effects. Despite the outstanding qualities of this antibiotic, Salmonella typhi, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa have all shown an increase in ciprofloxacin resistance over time. The rise of infections that are resistant to ciprofloxacin shows that new pharmacological synergisms and derivatives are required. To this end, ciprofloxacin may be more effective against the biofilm community of microorganisms and multi-drug resistant isolates when combined with a variety of antibacterial agents, such as antibiotics from various classes, nanoparticles, natural products, bacteriophages, and photodynamic therapy. This review focuses on the resistance mechanisms of bacteria against ciprofloxacin and new approaches for enhancing its efficacy.

Prevalence of SARS-CoV-2 in Patients with Severe Pneumonia in Khuzestan Province, Iran.

The emergence of a highly pathogenic virus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) accounts for severe pneumonia throughout the world. More than 7 million world population have been infected with SARS-CoV-2, and the number of deaths is increasing every day. This study aimed to evaluate the frequency of SARS-CoV-2 in hospitalized patients with an acute respiratory infection (ARI). During an outbreak of the SARS-CoV-2, the nasopharyngeal and oropharyngeal swabs were collected from 909 hospitalized patients with severe pneumonia, including 517 (56.9%) males and 392 (43.1%) females. All the collected samples were from different cities of Khuzestan province from 19 February to- 27 March 2020. The RNA was extracted from samples and subjected to real-time polymerase chain reaction (PCR) tests for the detection of the SARS-CoV-2. Simultaneously, the computerized tomography (CT) scan was tested for the presence of ground-glass opacity in the lung among the patients. Of the total number of 909 specimens, 328 (36.08%) cases, including 185 (20.35%) females and 143 (15.73%) males, were positive for the SARS-CoV-2 while, 581 (63.9%) cases, including 374 (41.14%) males and 207 (22.77%) were negative for the SARS-CoV-2 by real-time PCR (p=0.001).Four hundred sixteen (45.76%) cases were positive for ground-glass opacity in the lung by CT scan, while 328/909 (36.08%) trials proved positive for SARS-CoV-2 by the real-time PCR (p=0.003).  In this study, 36.08% of patients were positive for SARS-CoV-2. Although the results of positive cases by CT scan showed higher than real-time PCR, screening the SARS-COV-2 with a real-time PCR method is the first line of choice.

Epidemiological linkage of vancomycin-resistant Enterococcus faecium from different sources in Ahwaz, Iran.

This study was set to determine the genetic linkage and the clonal relationship between vancomycin-resistant Enterococcusfaecium (VREfm) isolates in three hospitals of Ahwaz city. In this study, 1050 samples were collected from various rectal swabs, hands of health care workers, environmental surfaces, medical equipment and 146 enterococci isolates from clinical sources of three hospitals from March to September 2015. Antimicrobial resistance patterns in VREfm were detected by disk diffusion method. Genetic linkages of VREfm strains were investigated by pulse field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) methods. Out of 366 enterococcal isolates, 163 Enterococcus faecium isolates were found to be resistant to vancomycin. PFGE and MLST analysis showed the presence of 79 pulsotypes and 11 sequence types (ST), respectively. In total, 90% of the isolates belonged to clonal complex 17 (CC17). Three new STs were reported for the first time in this study and ST80 was the predominant ST. We found a high prevalence of diverse VREfm with threatening antibiotic resistance patterns in all the studied sources with the dominance of CC17 VREfm strains in Ahwaz hospitals. Also, the results of typing method showed inter- and intra-hospital circulation of VREfm and similar pulsotypes and STs among different sources.

Virulence Determinants and Antimicrobial Resistance Patterns of Vancomycin-resistant Enterococcus faecium Isolated from Different Sources in Southwest Iran.

BACKGROUND: This study aimed to investigate the incidence of antibiotic-resistance and virulence genes in vancomycin-resistant Enterococcus faecium isolated from different sources in southwest Iran from Mar to Sep 2015. METHODS: Overall, 120 E. faecium isolates (80 VRE and 40 vancomycin-susceptible enterococci [VSE] isolates) were obtained from four hospitals. The resistance of the VRE isolates was determined by disk diffusion method. Multiplex PCR was performed to detect the virulence genes carried by the E. faecium isolates, namely, enterococcal surface protein (esp), hyaluronidase (hyl), and collagen-binding adhesin (acm). RESULTS: All the VRE isolates exhibited multidrug resistance, with the rates of resistance to ampicillin, erythromycin, and ciprofloxacin reaching high levels. The isolates were least resistant to chloramphenicol and nitrofurantoin, but all of them were susceptible to linezolid. 46.6%, 20.8%, and 86.6% of the E.faecium isolates carried the esp, hyl, and acm genes, respectively. CONCLUSION: There is a significant difference between the prevalence of esp and hyl genes in the VRE and VSE isolates. In the VRE isolates, the high prevalence of multidrug resistance were found and the difference in the prevalence of esp among various sources was significant. The findings reflected a relationship between the prevalence of esp and hyl and resistance to certain antibiotics.

Prevalence of virulence genes and their association with biofilm formation in VRE faecium isolates from Ahvaz, Iran.

INTRODUCTION: Vancomycin-resistant Enterococcus faecium (VREfm) is a common cause of nosocomial infections. Biofilm formation is an important factor in recurrence of infections, facilitating transfer of genetic elements, leading to treatment failures. The aim of this study was to investigate the virulence genes in biofilm producing isolates and to determine possible association between biofilm formation and the presence of these genes; also to determine association between antibiotic susceptibility patterns of VREfm isolates and their biofilm formation ability. METHODOLOGY: A total of 57 isolates of VREfm were recovered from different sources of hospitals under Ahvaz University, Iran. The isolates were examined by conventional microbiological methods and molecular test using PCR. The antibiotic susceptibility patterns of the isolates were determined by disk-diffusion and E-test. The biofilm formation ability of the isolates was investigated by Modified Congo red agar and microtiter plate techniques. The presence of virulence genes was examined using Multiplex-PCR method. RESULTS: Out of 57 VREfm isolates, 63.15% of isolates were biofilm producers. The frequency of biofilm producing isolates from clinical specimens, colonized patients and environmental sources were 78.26%, 60%, and 42.85%, respectively. The prevalence of acm, esp and hyl genes among biofilm producing isolates was 86.10%, 55.56% and 52.77%, respectively. There was statistically significant association between esp gene and biofilm formation among isolates from the clinical specimens. CONCLUSION: Clinical isolates producing biofilms showed a positive association with the presence of the esp. Our study further suggests that the link between virulence genes and biofilms is affected by the environmental context.

High prevalence of diverse vancomycin resistance Enterococcus faecium isolates in clinical and environmental sources in ICU wards in southwest of Iran.

This study aimed at determining the prevalence, antibiotic resistance patterns, and genetic linkage of Vancomycin Resistant Enterococcus faecium (VREfm) from different sources in the southwest of Iran. A total of 51 VREfm isolates were obtained and subjected to antibiotic susceptibility testing, carriage of virulence genes, and pulsed-field gel electrophoresis (PFGE) method. All the VRE isolates exhibited a high level of resistance to teicoplanin, ampicillin, erythromycin, ciprofloxacin, and gentamicin, also carried the vanA gene. A total of 59% and 34% of the VREfm strains harbored esp and hyl genes, respectively. The results from PFGE showed 31 PFGE patterns including 10 common types (CT) and 21 single types (ST) among the VRE isolates. Furthermore, isolates from different sources in each common type revealed cross transmission between clinical and environmental sources. Overall, the study showed a high prevalence of diverse VRE faecium strains with threatening resistance phenotypes in the environment and clinical sections among different ICU wards of Ahvaz hospitals.

Drug Resistance Pattern of Mycobacterium tuberculosis Isolates From Patients Referred to TB Reference Laboratory in Ahvaz.

OBJECTIVES: Tuberculosis remains one of the top three infectious disease killers. The prevalence of multidrug-resistant tuberculosis (MDR-TB) has increased substantially in the past 20 years. When drug resistance is not detected, MDR-TB patients cannot access life-saving treatment; this puts their communities at risk of ongoing MDR-TB transmission. We aimed to determine the patterns of resistance to antituberculosis drugs among Mycobacterium tuberculosis isolates from Khuzestan province in Iran. METHODS: A total of 850 clinical specimens from patients suspected of active TB were cultured in 2015. Drug susceptibility testing to the first line antiTB drugs for culture positive MTB was performed on Lowenstein-Jensen medium using the proportion method. RESULTS: Of 850 cultured specimens, 272 (32%) were culture positive for mycobacteria. Of 64 MTB isolates that were analyzed by the proportion method, 62 (96.8%) were pan-susceptible and two (3.1%) were MDR. CONCLUSION: An important way to prevent the emergence of MDR and XDR TB, and the principles of full implementation of the strategy is directly observed treatment, short-course (DOTS). The efficient diagnosis and timely treatment of MDR-TB patients can prevent disease transmission, reduce the risk of drug resistance developing, and avoid further lung damage.