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Central Register of Controlled Trials, MEDLINE, ClinicalTrials.gov) was performed to identify for published and unpublished randomized controlled trials comparing anti-TNF (etanercept, adalimumab, infliximab, certolizumab pegol, golimumab) with placebo in patients diagnosed with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.

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.

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.

A rare and unusual cause of Vibrio cholerae non-O1, non-O139 causing spontaneous peritonitis in a patient with cirrhosis.

Spontaneous bacterial peritonitis caused by Vibrio cholerae non-O1/ non-O139 is a rare phenomenon. V. cholerae is known as a common aetiology of epidemic diarrheal disease and rarely causes extra-gastrointestinal infections. In this report, a 52-year-old man presented to our hospital with a clinical scenario for chronic liver cirrhosis with low grade fever and loose stools. V. cholerae was isolated from peritoneal fluid culture, which was further confirmed as non-O1/ non-O139 strain by multiplex polymerase chain reaction. The patient was successfully treated with antimicrobial therapy and peritoneal drainage. This case represents the first isolation of V. cholerae non-O1/ non-O139 strain from peritoneal fluid.

A rare and unusual cause of Vibrio cholerae non-O1, non-O139 causing spontaneous peritonitis in a patient with cirrhosis

@#Spontaneous bacterial peritonitis caused by Vibrio cholerae non-O1/ non-O139 is a rare phenomenon. V. cholerae is known as a common aetiology of epidemic diarrheal disease and rarely causes extra-gastrointestinal infections. In this report, a 52-year-old man presented to our hospital with a clinical scenario for chronic liver cirrhosis with low grade fever and loose stools. V. cholerae was isolated from peritoneal fluid culture, which was further confirmed as non-O1/ non-O139 strain by multiplex polymerase chain reaction. The patient was successfully treated with antimicrobial therapy and peritoneal drainage. This case represents the first isolation of V. cholerae non-O1/ non-O139 strain from peritoneal fluid.

An ambient temperature stable and ready-to-use loop-mediated isothermal amplification assay for detection of toxigenic Vibrio cholerae in outbreak settings.

Cholera, caused by Vibrio cholerae is a foodborne disease that frequently reported in food and water related outbreak. Rapid diagnosis of cholera infection is important to avoid potential spread of disease. Among available diagnostic platforms, loop-mediated isothermal amplification (LAMP) is regarded as a potential diagnostic tool due to its rapidity, high sensitivity and specificity and independent of sophisticated thermalcycler. However, the current LAMP often requires multiple pipetting steps, hence is susceptible to cross contamination. Besides, the strict requirement of cold-chain during transportation and storage make its application in low resource settings to be inconvenient. To overcome these problems, the present study is aimed to develop an ambient-temperature-stable and ready-to-use LAMP assay for the detection of toxigenic Vibrio cholerae in low resource settings. A set of specific LAMP primers were designed and tested against 155 V. cholerae and non-V. cholerae strains. Analytical specifity showed that the developed LAMP assay detected 100% of pathogenic V. cholerae and did not amplified other tested bacterial strains. Upon testing against stool samples spiked with toxigenic V. cholerae outbreak isolates, the LAMP assay detected all of the spiked samples (n = 76/76, 100%), in contrast to the conventional PCR which amplified 77.6% (n = 59/76) of the tested specimens. In term of sensitivity, the LAMP assay was 100-fold more sensitive as compared to the conventional PCR method, with LOD of 10 fg per µL and 10 CFU per mL. Following lyophilisation with addition of lyoprotectants, the dry-reagent LAMP mix has an estimated shelf-life of 90.75 days at room temperature.

Development of multiplex loop mediated isothermal amplification (m-LAMP) label-based gold nanoparticles lateral flow dipstick biosensor for detection of pathogenic Leptospira.

In recent years extensive numbers of molecular diagnostic methods have been developed to meet the need of point-of-care devices. Efforts have been made towards producing rapid, simple and inexpensive DNA tests, especially in the diagnostics field. We report on the development of a label-based lateral flow dipstick for the rapid and simple detection of multiplex loop-mediated isothermal amplification (m-LAMP) amplicons. A label-based m-LAMP lateral flow dipstick assay was developed for the simultaneous detection of target DNA template and a LAMP internal control. This biosensor operates through a label based system, in which probe-hybridization and the additional incubation step are eliminated. We demonstrated this m-LAMP assay by detecting pathogenic Leptospira, which causes the re-emerging disease Leptospirosis. The lateral flow dipstick was developed to detect of three targets, the LAMP target amplicon, the LAMP internal control amplicon and a chromatography control. Three lines appeared on the dipstick, indicating positive results for all representative pathogenic Leptospira species, whereas two lines appeared, indicating negative results, for other bacterial species. The specificity of this biosensor assay was 100% when it was tested with 13 representative pathogenic Leptospira species, 2 intermediate Leptospira species, 1 non-pathogenic Leptospira species and 28 other bacteria species. This study found that this DNA biosensor was able to detect DNA at concentrations as low as 3.95 × 10(-1) genomic equivalent ml(-1). An integrated m-LAMP and label-based lateral flow dipstick was successfully developed, promising simple and rapid visual detection in clinical diagnostics and serving as a point-of-care device.