Efficacy and safety of antibiotics for treatment of leptospirosis: a systematic review and network meta-analysis.

BACKGROUND: Leptospirosis, an important zoonotic bacterial disease, commonly affects resource-poor populations and results in significant morbidity and mortality worldwide. The value of antibiotics in leptospirosis remains unclear, as evidenced by the conflicting opinions published. METHODS: We conducted a search in the PubMed, Web of Science, and Cochrane Library databases for studies. These studies included clinical trials and retrospective studies that evaluated the efficacy or safety of antibiotics for leptospirosis treatment. The primary outcomes assessed were defervescence time, mortality rate, and hospital stays. Subgroup analyses were performed based on whether there were cases involving children and whether there were cases of severe jaundice. Safety was defined as the prevalence of adverse events associated with the use of antibiotics. p scores were utilized to rank the efficacy of the antibiotics. RESULTS: There are included 9 randomized controlled trials (RCTs), 1 control trial (CT), and 3 retrospective studies (RS) involving 920 patients and 8 antibiotics. Six antibiotics resulted in significantly shorter defervescence times compared to the control, namely cefotaxime (MD, - 1.88; 95% CI = - 2.60 to - 1.15), azithromycin (MD, - 1.74; 95% CI = - 2.52 to - 0.95), doxycycline (MD, - 1.53; 95% CI = - 2.05 to - 1.00), ceftriaxone (MD, - 1.22; 95% CI = - 1.89 to - 0.55), penicillin (MD, - 1.22; 95% CI = - 1.80 to - 0.64), and penicillin or ampicillin (MD, - 0.08; 95% CI = - 1.01 to - 0.59). The antibiotics were not effective in reducing the mortality and hospital stays. Common adverse reactions to antibiotics included Jarisch-Herxheimer reaction, rash, headache, and digestive reactions (nausea, vomiting, diarrhea, abdominal pain, and others). CONCLUSIONS: Findings recommend that leptospirosis patients be treated with antibiotics, which significantly reduced the leptospirosis defervescence time. Cephalosporins, doxycycline, and penicillin are suggested, and azithromycin may be a suitable alternative for drug-resistant cases. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022354938.

Mapping of a recessive gene for all-stage resistance to stripe rust in a wheat line derived from cultivated einkorn (Triticum monococcum L.).

Stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is one of the most destructive fungal diseases of wheat. Cultivated einkorn (Triticum monococcum ssp. monococcum, 2n=2x=14, AmAm), one of the founder crops of agriculture, harbors unexploited genetic sources for wheat improvement. An advanced wheat line Z15-1949 with 42 chromosomes, selected from the hybrids of Pst-susceptible common wheat cultivar Crocus and resistant T. monococcum accession 10-1, exhibits high resistance to a mixture of the Chinese prevalent Pst races. Genetic analysis on F1, F2, and F2:3 generations of the cross between Z15-1949 and Pst-susceptible common wheat SY95-71 indicated that the resistance of Z15-1949 was conferred by a recessive gene, tentatively designated as YrZ15-1949. This gene was mapped to the short arm of chromosome 7D using the Wheat 55K SNP array, flanked by markers KASP-1949-2 and KASP-1949-10 within a 3.3 cM genetic interval corresponding to 1.12 Mb physical region in the Chinese Spring reference genome V2.0. The gene differs from previously reported Yr genes on 7D based on their physical positions, and is probably a novel gene. YrZ15-1949 would be a valuable resource for developing Pst-resistant wheat cultivars and the linked markers could be used for the marker-assisted selection.

The intricate role of CCL5/CCR5 axis in Alzheimer disease.

The morbidity and mortality associated with Alzheimer disease (AD), one of the most common neurodegenerative diseases, are increasing each year. Although both amyloid ß and tau proteins are known to be involved in AD pathology, their detailed functions in the pathogenesis of the disease are not fully understood. There is increasing evidence that neuroinflammation contributes to the development and progression of AD, with astrocytes, microglia, and the cytokines and chemokines they secrete acting coordinately in these processes. Signaling involving chemokine (C-C motif) ligand 5 (CCL5) and its main receptor C-C chemokine receptor 5 (CCR5) plays an important role in normal physiologic processes as well as pathologic conditions such as neurodegeneration. In recent years, many studies have shown that the CCL5/CCR5 axis plays a major effect in the pathogenesis of AD, but there are also a few studies that contradict this. In short, the role of CCL5/CCR5 axis in the pathogenesis of AD is still intricate. This review summarizes the structure, distribution, physiologic functions of the CCL5/CCR5 axis, and the progress in understanding its involvement in the pathogenesis of AD.

Maximum Lyapunov exponent-based multiple chaotic slime mold algorithm for real-world optimization.

Slime mold algorithm (SMA) is a nature-inspired algorithm that simulates the biological optimization mechanisms and has achieved great results in various complex stochastic optimization problems. Owing to the simulated biological search principle of slime mold, SMA has a unique advantage in global optimization problem. However, it still suffers from issues of missing the optimal solution or collapsing to local optimum when facing complicated problems. To conquer these drawbacks, we consider adding a novel multi-chaotic local operator to the bio-shock feedback mechanism of SMA to compensate for the lack of exploration of the local solution space with the help of the perturbation nature of the chaotic operator. Based on this, we propose an improved algorithm, namely MCSMA, by investigating how to improve the probabilistic selection of chaotic operators based on the maximum Lyapunov exponent (MLE), an inherent property of chaotic maps. We implement the comparison between MCSMA with other state-of-the-art methods on IEEE Congress on Evolution Computation (CEC) i.e., CEC2017 benchmark test suits and CEC2011 practical problems to demonstrate its potency and perform dendritic neuron model training to test the robustness of MCSMA on classification problems. Finally, the parameters' sensitivities of MCSMA, the utilization of the solution space, and the effectiveness of the MLE are adequately discussed.

Seventy years of evidence on the efficacy and safety of drugs for treating leprosy: a network meta-analysis.

OBJECTIVE: The World Health Organization (WHO) recommends multidrug therapy (MDT) with rifampicin, dapsone, and clofazimine for treating leprosy, which is based on very low-quality evidence. Here, we performed a network meta-analysis (NMA) to produce quantitative evidence to strengthen current WHO recommendations. METHOD: All studies were obtained from Embase and PubMed from the date of establishment to October 9, 2021. Data were synthesized with frequentist random-effects network meta-analyses. Outcomes were assessed using odds ratios (ORs), 95% confidence intervals (95% CIs), and P score. RESULTS: Sixty controlled clinical trials and 9256 patients were included. MDT was effective (range of OR: 1.06-1255584.25) for treating leprosy and multibacillary leprosy. Six treatments (Range of OR: 1.199-4.50) were more effective than MDT. Clofazimine (P score=0.9141) and dapsone+rifampicin (P score=0.8785) were effective for treating type 2 leprosy reaction. There were no significant differences in the safety of any of the tested drug regimens. CONCLUSIONS: The WHO MDT is effective for treating leprosy and multibacillary leprosy, but it may not be effective enough. Pefloxacin and ofloxacin may be good adjunct drugs for increasing MDT efficacy. Clofazimine and dapsone+rifampicin can be used in the treatment of a type 2 leprosy reaction. Single-drug regimens are not efficient enough to treat leprosy, multibacillary leprosy, or a type 2 leprosy reaction. AVAILABILITY OF DATA AND MATERIALS: All data generated or analyzed during this study are included in this published article [and its supplementary information files].

Efficacy and safety of antibiotic therapy for post-Lyme disease? A systematic review and network meta-analysis.

BACKGROUND: At present, the pathogenesis of post-treatment Lyme disease (PTLDS) is not clear, so the treatment scheme of PTLDS, especially antibiotic treatment, is still controversial. This study aims to evaluate the efficacy of antibiotics in the treatment of PTLDS using network meta-analysis (NMA). METHODS: Following PRISMA guidelines, a systematic literature search was conducted on randomized controlled trials in PubMed, EMBASE, Web of Science and Cochrane Library (the literature was published from database inception through December 16, 2022). Using random effect model and fixed effect model. STATA17.0 software was used to evaluate the quality and heterogeneity of the included research literature. RESULTS: The system included 4 randomized controlled trials (485 subjects). The network meta-analysis showed that ceftriaxone had better results than placebo [Mean = 0.87, 95% CI (0.02, 1.71)] and doxycycline [Mean = 1.01, 95% CI (0.03, 1.98)] in FSS scale scores. There was no statistical difference in FSS scale scores of other drugs after treatment. In terms of FSS score results, Ceftriaxone was the best intervention according to the SUCRA value of each treatment (97.7). The analysis of outcome indicators such as Beck Depression Inventory (BDI), Mental-health Scale and Physical-functioning scale showed that there was no statistically significant difference between the antibiotic group and placebo group. CONCLUSION: Ceftriaxone treatment may be the best choice for antibiotic treatment of PTLD, which provides useful guidance for antibiotic treatment of PTLD in the future.

Efficacy and Safety of Treatments for Different Stages of Syphilis: a Systematic Review and Network Meta-Analysis of Randomized Controlled Trials and Observational Studies.

Parenteral penicillin is the first-line regimen for treating syphilis. However, allergic reactions and poor drug tolerance still present challenging problems with respect to use of this antibiotic. This study aimed to evaluate the efficacy and safety of ceftriaxone, erythromycin, minocycline, tetracycline, and doxycycline for syphilis treatment, compared with penicillin, to determine which antibiotic could be a better substitute for penicillin. This study included 17 articles, comprising 3 randomized controlled trials (RCTs) and 14 observational studies and involving 4,485 syphilis patients. Estimated risk ratios (RRs) and 95% confidence interval (CIs) were used to compare the serological response rates. At the 6- and 12-month follow-ups, the serological response rates were compared by direct meta-analysis and network meta-analysis (NMA). Based on direct meta-analysis, the serological response rates at the 3- and 24-month follow-ups were compared. Our NMA showed a higher serological response rate for ceftriaxone than for penicillin at the 6-month follow-up (RR of 1.12, 95% CI of 1.02 to 1.23). Ceftriaxone was equally effective as penicillin for syphilis in terms of serological response rates, and it was a better substitute for penicillin than ceftriaxone, erythromycin, minocycline, tetracycline, or doxycycline. However, more large-scale, high-quality, double-blind trials are still needed to determine whether ceftriaxone can safely replace penicillin for the treatment of syphilis when necessary. IMPORTANCE Parenteral penicillin is the first-line regimen for syphilis treatment. However, allergic reactions and poor drug tolerance still present emerging threatening problems with respect to use of this antibiotic. Our results showed a higher serological response rate for ceftriaxone than for penicillin at the 6-month follow-up. Sufficient data are not available for demonstrating significant differences in the efficacy of the other four antibiotics (erythromycin, minocycline, tetracycline, and doxycycline) for treating syphilis. In the clinical treatment of syphilis in patients who are allergic to penicillin or for whom penicillin is not available, ceftriaxone appears to be a better alternative treatment. This meta-analysis provides a reference for clinical treatment of syphilis. Currently, a lack of sufficient evidence to guide antibiotic treatment of syphilis exists, and a need for more high-quality RCTs is still present. This network meta-analysis can lay a foundation for further research.

Global seroprevalence and sociodemographic characteristics of Borrelia burgdorferi sensu lato in human populations: a systematic review and meta-analysis.

INTRODUCTION: Borrelia burgdorferi sensu lato (Bb) infection, the most frequent tick-transmitted disease, is distributed worldwide. This study aimed to describe the global seroprevalence and sociodemographic characteristics of Bb in human populations. METHODS: We searched PubMed, Embase, Web of Science and other sources for relevant studies of all study designs through 30 December 2021 with the following keywords: 'Borrelia burgdorferi sensu lato' AND 'infection rate'; and observational studies were included if the results of human Bb antibody seroprevalence surveys were reported, the laboratory serological detection method reported and be published in a peer-reviewed journal. We screened titles/abstracts and full texts of papers and appraised the risk of bias using the Cochrane Collaboration-endorsed Newcastle-Ottawa Quality Assessment Scale. Data were synthesised narratively, stratified by different types of outcomes. We also conducted random effects meta-analysis where we had a minimum of two studies with 95% CIs reported. The study protocol has been registered with PROSPERO (CRD42021261362). RESULTS: Of 4196 studies, 137 were eligible for full-text screening, and 89 (158 287 individuals) were included in meta-analyses. The reported estimated global Bb seroprevalence was 14.5% (95% CI 12.8% to 16.3%), and the top three regions of Bb seroprevalence were Central Europe (20.7%, 95% CI 13.8% to 28.6%), Eastern Asia (15.9%, 95% CI 6.6% to 28.3%) and Western Europe (13.5%, 95% CI 9.5% to 18.0%). Meta-regression analysis showed that after eliminating confounding risk factors, the methods lacked western blotting (WB) confirmation and increased the risk of false-positive Bb antibody detection compared with the methods using WB confirmation (OR 1.9, 95% CI 1.6 to 2.2). Other factors associated with Bb seropositivity include age ≥50 years (12.6%, 95% CI 8.0% to 18.1%), men (7.8%, 95% CI 4.6% to 11.9%), residence of rural area (8.4%, 95% CI 5.0% to 12.6%) and suffering tick bites (18.8%, 95% CI 10.1% to 29.4%). CONCLUSION: The reported estimated global Bb seropositivity is relatively high, with the top three regions as Central Europe, Western Europe and Eastern Asia. Using the WB to confirm Bb serological results could significantly improve the accuracy. More studies are needed to improve the accuracy of global Lyme borreliosis burden estimates. PROSPERO REGISTRATION NUMBER: CRD42021261362.

Prevalence of Borrelia burgdorferi in Ixodidae Tick around Asia: A Systematic Review and Meta-Analysis.

Lyme disease (LD) is a common arthropod-borne inflammatory disorder prevalent in the northern hemisphere. LD is caused by a spirochete named Borrelia burgdorferi s.l., which is transmitted to humans by ticks. Climate, environment, and other factors affect land use; recreational-behavior changes affect human contact with infected ticks. Studies in Europe and North America have looked at these aspects, but studies in Asia have not. We searched databases to identify all relevant abstracts published until March 2021. A meta-analysis was undertaken using the standard methods and procedures established by the Cochrane Collaboration. Ninety-one articles were included in our meta-analysis. The literature search identified data from nine countries (China, Japan, Malaysia, Mongolia, Pakistan, Russia Siberia region, South Korea, Thailand and Turkey). Furthermore, 53,003 ticks from six genera (Amblyomma, Dermacentor, Haemaphysalis, Hyalomma, Ixodes and Rhipicephalus) were inspected for infection with B. burgdorferi. The pooled prevalence was 11.1% (95% CI = 8.3-14.2%). Among the nine countries, China had the most studies (56) and Malaysia had the highest infection rate (46.2%). Most infected ticks were from the genera Ixodes and Haemaphysalis. Ticks of the genus Ixodes had the highest infection rate (16.9%). Obvious heterogeneity was noted in our meta-analysis. We analyzed the heterogeneity with regard to countries, genera, time points, and detection methods. This study suggests that Ixodes, Haemaphysalis and Dermacentor may be the most common tike of B. burgdorferi-positive in Asia. The highest proportion of ticks infected by B. burgdorferi were from the genus Ixodes. This meta-analysis is the first attempt to explain the B. burgdorferi infection of hard-body ticks in Asia. The infection rate for each country and infection rate of different tick genera were analyzed: there were large differences between them. The literature is concentrates mainly on East Asia, and data are limited. Our study can provide a reference for a more comprehensive and in-depth investigation of ticks in Asia infected by B. burgdorferi spirochetes.

Forty Years of Evidence on the Efficacy and Safety of Oral and Injectable Antibiotics for Treating Lyme Disease of Adults and Children: A Network Meta-Analysis.

Lyme disease (LD) is a heavy public health burden. The most common manifestations of LD include erythema migrans (EM), Lyme neuroborreliosis (LNB), and Lyme arthritis (LA). The efficacy and safety of antibiotics for treating LD is still controversial. Thus, we performed a network meta-analysis (NMA) to obtain more data and tried to solve this problem. We searched studies in the databases of Embase and PubMed from the date of their establishments until 22 April 2021. Odds ratios (ORs) were used to assess dichotomous outcomes. A total of 31 randomized controlled trials (RCTs) involving 2,748 patients and 11 antibiotics were included. Oral amoxicillin (1.5 g/day), oral azithromycin (0.5 g/day), injectable ceftriaxone, and injectable cefotaxime were effective for treating LD (range of ORs, 1.02 to 1,610.43). Cefuroxime and penicillin were safe for treating LD (range of ORs, 0.027 to 0.98). Amoxicillin was effective for treating EM (range of ORs, 1.18 to 25.66). Based on the results, we thought oral amoxicillin (1.5 g/day), oral azithromycin (0.5 g/day), injectable ceftriaxone, and injectable cefotaxime were effective for treating LD. Cefuroxime and penicillin were safe for treating LD. Amoxicillin was effective for treating EM. We did not observe evidence proving the advantage of doxycycline in efficacy and safety for treating LD, LA, LNB, and EM of children or adults. We did not have sufficient data to prove the significant difference of efficacy for treating LA and LNB in adults and LD in children, the significant difference of safety of oral drugs for treating LD, and the significant difference of safety of drugs for treating EM. IMPORTANCE Some previous studies investigated the efficacy and safety of antibiotics for treating Lyme disease (LD). However, due to technical limitations, several questions regarding the routes of drug administration and the dosages of drug are still unclear, which might be causing problems for clinicians. Hence, we performed network meta-analysis (NMA) to quantitatively analyze the clinical data published during the last 40 years. Here, we demonstrate the evidence regarding the efficacy and safety of antibiotics commonly used for treating LD in adults and children. We found that amoxicillin, azithromycin, ceftriaxone, and cefotaxime were effective for treating LD, but we did not observe significant efficacy and safety of doxycycline for treating LD.

Insights into the degradation and toxicity difference mechanism of neonicotinoid pesticides in honeybees by mass spectrometry imaging.

Honeybees are essential for the pollination of a wide variety of crops and flowering plants, whereas they are confronting decline around the world due to the overuse of pesticides, especially neonicotinoids. The mechanism behind the negative impacts of neonicotinoids on honeybees has attracted considerable interest, yet it remains unknown due to the limited insights into the spatiotemporal distribution of pesticides in honeybees. Herein, we demonstrated the use of matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) for the spatiotemporal visualization of neonicotinoids, such as N-nitroguanidine (dinotefuran) and N-cyanoamidine (acetamiprid) compounds, administered by oral application or direct contact, in the whole-body section of honeybees. The MSI results revealed that both dinotefuran and acetamiprid can quickly penetrate various biological barriers and distribute within the whole-body section of honeybees, but acetamiprid can be degraded much faster than dinotefuran. The degradation rate of acetamiprid is significantly decreased when piperonyl butoxide (PBO) is applied, whereas that of dinotefuran remains almost unchanged. These two factors might contribute to the fact that dinotefuran affords a higher toxicity to honeybees than acetamiprid. Moreover, the toxicity and degradation rate of acetamiprid can be affected by co-application with tebuconazole. Taken together, the results presented here indicate that the discrepant toxicity between dinotefuran and acetamiprid does not lie in the difference in their penetration of various biological barriers of honeybees, but in the degradation rate of neonicotinoid pesticides within honeybee tissues. Moreover, new perspectives are given to better understand the causes of the current decline in honeybee populations posed by insecticides, providing guidelines for the precise use of conventional agrochemicals and the rational design of novel pesticide candidates.

Efficacy and Safety of Antibiotics for Treatment of Scrub Typhus: A Network Meta-analysis.

Importance: Antibiotics have been used for many years to treat scrub typhus, but their efficacy and safety have not been studied thoroughly. Objective: To compare and rank different antibiotics to identify which one can safely eliminate Orientia tsutsugamushi and efficiently alleviate fever in patients with scrub typhus. Data Sources: An electronic search of PubMed and Embase was conducted, from database inception to July 12, 2019. The study was conducted from July 12 to September 2, 2019. Study Selection: Randomized clinical trials and retrospective studies that evaluated the use of antibiotics for treatment in patients diagnosed with scrub typhus caused by O tsutsugamushi were included. Records of articles in English were considered eligible. Studies were assessed independently by 2 reviewers, with disagreement resolved by consensus. Of 6408 studies initially identified, 10 randomized clinical trials and 4 retrospective study met the criteria for further analysis. Data Extraction and Synthesis: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension statement for systematic reviews incorporating network meta-analyses of health care interventions. Data were independently extracted by 2 reviewers and synthesized with frequentist random-effects network meta-analyses. Main Outcomes and Measures: The primary outcome was efficacy of the antibiotic, considered as the number of patients who achieved complete healing with an antibiotic. Safety, defined as the prevalence of adverse events associated with the antibiotics, was the secondary outcome, and defervescence time was the tertiary outcome. P scores (scale of 0 to 1, with 1 indicating superiority to other treatments) were used to rank the efficacy, safety, and defeverescence time of the antibiotics. Results: Three searches for articles in Embase and PubMed identified 10 randomized clinical trials (888 participants) and 4 retrospective studies (323 participants) for further analyses. No particular treatment regimen showed a significant advantage or disadvantage with regard to efficacy or safety. However, meta-analysis of retrospective studies indicated that clarithromycin (P score = 0.8730) alleviated fever more efficiently than other antibiotics. Conclusions and Relevance: No treatment regimen reported in this network meta-analysis showed a significant advantage or disadvantage with regard to efficacy or safety. However, clarithromycin might be a better choice than the other drugs for alleviating fever.

Interferon-γ release assays or tuberculin skin test for detection and management of latent tuberculosis infection: a systematic review and meta-analysis.

BACKGROUND: Use of an interferon-γ (IFN-γ) release assay or tuberculin skin test for detection and management of latent tuberculosis infection is controversial. For both types of test, we assessed their predictive value for the progression of latent infection to active tuberculosis disease, the targeting value of preventive treatment, and the necessity of dual testing. METHODS: In this systematic review and meta-analysis, we searched PubMed, Embase, Web of Science, and the Cochrane Library, with no start date or language restrictions, on Oct 18, 2019, using the keywords ("latent tuberculosis" OR "latent tuberculosis infection" OR "LTBI") AND ("interferon gamma release assays" OR "Interferon-gamma Release Test" OR "IGRA" OR "QuantiFERON®-TB in tube" OR "QFT" OR "T-SPOT.TB") AND ("tuberculin skin test" OR "tuberculin test" OR "Mantoux test" OR "TST"). We included articles that used a cohort study design; included information that individuals with latent tuberculosis infection detected by IFN-γ release assay, tuberculin skin test, or both, progressed to active tuberculosis; reported information about treatment; and were limited to high-risk populations. We excluded studies that included patients with active or suspected tuberculosis at baseline, evaluated a non-commercial IFN-γ release assay, and had follow-up of less than 1 year. We extracted study details (study design, population investigated, tests used, follow-up period) and the number of individuals observed at baseline, who progressed to active tuberculosis, and who were treated. We then calculated the pooled risk ratio (RR) for disease progression, positive predictive value (PPV), and negative predictive value (NPV) of IFN-γ release assay versus tuberculin skin test. FINDINGS: We identified 1823 potentially eligible studies after exclusion of duplicates, of which 256 were eligible for full-text screening. From this screening, 40 studies (50 592 individuals in 41 cohorts) were identified as eligible and included in our meta-analysis. Pooled RR for the rate of disease progression in untreated individuals who were positive by IFN-γ release assay versus those were negative was 9·35 (95% CI 6·48-13·49) compared with 4·24 (3·30-5·46) for tuberculin skin test. Pooled PPV for IFN-γ release assay was 4·5% (95% CI 3·3-5·8) compared with 2·3% (1·5-3·1) for tuberculin skin test. Pooled NPV for IFN-γ release assay was 99·7% (99·5-99·8) compared with 99·3% (99·0-99·5) for tuberculin skin test. Pooled RR for rates of disease progression in individuals positive by IFN-γ release assay who were untreated versus those who were treated was 3·09 (95% CI 2·08-4·60) compared with 1·11 (0·69-1·79) for the same populations who were positive by tuberculin skin test. Pooled proportion of disease progression for individuals who were positive by IFN-γ release assay and tuberculin skin test was 6·1 (95% CI 2·3-11·5). Pooled RR for rates of disease progression in individuals who were positive by IFN-γ release assay and tuberculin skin test who were untreated versus those who were treated was 7·84 (95% CI 4·44-13·83). INTERPRETATION: IFN-γ release assays have a better predictive ability than tuberculin skin tests. Individuals who are positive by IFN-γ release assay might benefit from preventive treatment, but those who are positive by tuberculin skin test probably will not. Dual testing might improve detection, but further confirmation is needed. FUNDING: National Natural Science Foundation of China and Natural Foundation of Yunnan Province.

Efficacy and Safety of Injectable and Oral Antibiotics in Treating Gonorrhea: A Systematic Review and Network Meta-Analysis.

Gonorrhea is the second most frequently reported sexually transmitted infectious disease of bacterial origin in the world. Current empiric therapies rely on broad-spectrum antibiotics. However, treatment options are becoming limited due to the rise of drug-resistant gonorrhea. To control the rise of drug-resistant gonorrhea and to identify alternative treatment options, clinicians will have to increasingly rely on experimental evidence for the treatment of gonorrhea patients. Thus, we performed a systematic review and network meta-analysis of all randomized clinical trials about the efficacy and safety of various antibiotic regimens in adults with gonorrhea. We searched all references in Embase and PubMed from the date of their inception to January 2019, and then an updated search was performed in March 2019. Of the 28,843 identified references, 44 fulfilled our selection criteria. We used a network meta-analysis based on a frequentist approach to evaluate the efficacy and safety of 12 injectable and 11 oral antibiotics. The efficacy of treatments was ranked by p score and inconsistency was assessed by a back-calculation method. Certainty of evidence was evaluated by the GRADE system. For injectable drugs, there was no difference in efficacy between a reference antibiotic and other drugs. However, ceftriaxone had significantly better efficacy than cefuroxime (OR, 12.03; 95% CI 3.73-38.79), cephaloridine (OR, 42.41; 95% CI 8.77-205.07), kanamycin (OR, 5.45; 95% CI 1.25-23.70), penicillin (OR, 13.11; 95% CI 4.48-38.37), and spectinomycin (OR, 4.70; 95% CI 1.62-13.62). Thus, ceftriaxone was the most effective injectable drug (p score of 0.924). As for oral drugs, azithromycin was the most effective compound (p score of 0.8633). There were no significant differences in safety between injectable and oral treatments. In our systematic review of randomized controlled trials, we found azithromycin and ceftriaxone to be the most effective antibiotics for the treatment of gonorrhea. This is in line with current guidelines which recommend a combination therapy of azithromycin and ceftriaxone for the treatment of gonorrhea due to increased antimicrobial resistance. Our analysis identified gentamicin and ofloxacin as alternative therapeutics to treat drug-resistant gonorrhea.

Seroprevalence of Tick-Borne Anaplasma phagocytophilum Infection in Healthy Adult Population and Patients with Acute Undifferentiated Fever from the Yunnan Province of China.

Anaplasma phagocytophilum-the causative agent of human granulocytic anaplasmosis (HGA)-is a tick-borne pathogen transmitted by Ixodid ticks infecting wild and domestic mammals as well as humans. Despite the availability of evidence regarding this emerging infection among vectors, host animals, and individuals in China, there is limited knowledge on the prevalence and distribution of A. phagocytophilum in the Yunnan Province. The aim of this study was to assess the seroprevalence of A. phagocytophilum in healthy adults and patients with acute undifferentiated fever from four regions in the Yunnan Province. The enzyme-linked immunosorbent assay and indirect immunofluorescence assay were used to detect immunoglobulin (Ig) G and IgM antibodies against A. phagocytophilum in sera obtained from 1185 healthy blood donors and 245 patients with acute undifferentiated fever, respectively. Demographic variables were assessed as potential risk factors using the chi-squared test. The rates of seropositivity rates were 7.59% and 4.49% in healthy donors and fever patients, respectively. Analysis of risk factors such as gender, age groups, and place of residence showed statistically significant differences. Infections with A. phagocytophilum occur widely among individuals residing in southwestern China. Our results indicate that there is serological evidence of HGA in this population and presence of acute A. phagocytophilum infections in patients with undifferentiated fever in the Yunnan Province.

Macrophage migration inhibitory factor-794 CATT microsatellite polymorphism and risk of tuberculosis: a meta-analysis.

Tuberculosis (TB) is a chronic infectious disease that has been threatening public health for many years. Several studies have shown the relationship between the macrophage migration inhibitory factor (MIF)-794 CATT (MIF-794 CATT) microsatellite polymorphism and susceptibility to TB. However, the results remain inconclusive. Therefore, we aim to find out the impact of MIF-794 CATT microsatellite polymorphism on risk of TB by a comprehensive meta-analysis. We conducted a systematic study search in PubMed, Embase, the Cochrane Library, and the China National Knowledge Infrastructure (CNKI) up to October 2017. Five studies involving 836 cases and 678 controls were included in the current meta-analysis. We calculated the pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) to estimate the association between the MIF-794 CATT microsatellite polymorphism and risk of TB. The reliability of the results were evaluated with trial sequential analysis (TSA). The results suggested that the MIF-794 CATT microsatellite polymorphism was significantly associated with the susceptibility of TB in all comparisons for allele (7 + 8 compared with 5 + 6, OR = 1.56, 95% CI = 1.31-1.87, P<0.00001) and genotype (7/X + 8/X compared with 5/X + 6/X, OR = 1.81, 95% CI = 1.39-2.36, P<0.0001). Therefore, the meta-analysis indicated the MIF-794 allele CATT7 and CATT8 may be a risk factor to increase the susceptibility of TB, which was confirmed by TSA.

NF­κB is a key modulator in the signaling pathway of Borrelia burgdorferi BmpA­induced inflammatory chemokines in murine microglia BV2 cells.

Lyme disease, caused by the bacterial spirochete Borrelia burgdorferi, is a tick­borne zoonosis. Lyme neuroborreliosis is a principal manifestation of Lyme disease and its pathogenesis remains incompletely understood. Recent studies have demonstrated that Borrelia burgdorferi lipoproteins caused similar inflammatory effects as exhibited in Lyme neuroborreliosis. Basic membrane protein A (BmpA) is one of the dominant lipoproteins in the Borrelia burgdorferi membrane. In addition, nuclear factor κ­B (NF­κB) modulates the regulation of gene transcription associated with immunity and inflammation; however, in unstimulated cells, NF­κB is combined with the inhibitor of NF­κB (IκB­ß). Therefore, it was hypothesized that NF­κB may be associated with BmpA­induced inflammation and the occurrence of Lyme neuroborreliosis. Therefore, the aim of the present study was to investigate the role that NF­κB serves in the signaling pathway of rBmpA­induced inflammatory chemokines. The present study measured the expression levels of NF­κB, IκB­ß and inflammatory chemokines following recombinant BmpA (rBmpA) stimulation of murine microglia BV2 cells. Following stimulation with rBmpA, concentrations of pro­inflammatory cytokines including C­X­C motif chemokine 2, C­C motif chemokine (CCL) 5 and CCL22 were determined by ELISA analysis. Reverse transcription­quantitative polymerase chain reaction and western blotting were used to detect the expression levels of NF­κB p65 and IκB­ß. The data demonstrated that concentrations of these chemokines in cell supernatants increased significantly following rBmpA stimulation. NF­κB was overexpressed, but IκB­ß expression was significantly decreased. In conclusion, these results suggested that NF­κB serves an important stimulatory role in the signaling pathway of rBmpA­induced inflammatory chemokines in BV2 cells.

The dominance of bacterial genotypes leads to susceptibility variations under sublethal antibiotic pressure.

AIM: To investigate the collective resistance of the bacteria population with resistant horizontal gene transfer under sublethal bactericide pressure. MATERIALS & METHODS: By employing qualitative analysis of ordinary differential equations, particularly bifurcation theory and several numerical simulations, a modified 4D ordinary differential equation model describing antibiotic susceptibility variations induced by sublethal antibiotic pressure is analyzed in detail. RESULTS: The long-term behaviors and collective resistance of different bacterial genotype populations in different sublethal bactericide concentration subintervals exhibit high levels of heterogeneity and are determined by the protection provided by resistant genes on chromosome or plasmid, their fitness costs, plasmid segregation rate and sublethal bactericide pressure. CONCLUSION: First, the possible mechanism of antibiotic susceptibility variations is the dominance of different bacterial genotypes under sublethal bactericide pressure, rather than persistence, tolerance or resistance. Additionally, the combination of vertical genetic transfer, horizontal genetic transfer and plasmid segregation can lead to unique switch between two states of different bacterial genotypes.

Isoforskolin downregulates proinflammatory responses induced by Borrelia burgdorferi basic membrane protein A.

The plant Coleus forskohlii is distributed primarily in India, Thailand, China, Egypt and Brazil and has a history of use in the treatment of multiple diseases. Isoforskolin (ISOF) is the principle active component of C. forskohlii native to China and has previously been studied for its biological effects. The aim of the present study was to evaluate the effect of ISOF on the proinflammatory responses induced by recombinant Borrelia burgdorferi basic membrane protein A (rBmpA). In in vitro experiments, the proinflammatory effects of rBmpA and the anti-inflammatory function of ISOF were evaluated in murine macrophages, human macrophages and dendritic cells by detecting the transcription and expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6. In in vivo experiments, mean arthritis index and X-ray and histopathological examinations were used to verify the role of ISOF in experimental Lyme arthritis in mice. The results indicated that rBmpA, which induced the transcription and expression of TNF-α and IL-6, activated proinflammatory responses in murine macrophages, human macrophages and dendritic cells. In turn, ISOF downregulated the transcription and expression of TNF-α and IL-6 induced by rBmpA. Additionally, the in vivo experiments demonstrated that ISOF could also inhibit the symptoms of experimental Lyme arthritis. These results suggest that ISOF may have a potential application as an anti-inflammatory agent for the treatment of Lyme arthritis.