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The Bacillus Calmette-Guérin (BCG) vaccine was discovered a century ago and has since been clinically applicable. BCG can not only be used for the prevention of tuberculosis, but also has a non-specific protective effect on the human body called trained immunity that is mediated by innate immune cells such as monocytes, macrophages, and natural killer cells. Mechanisms of trained immunity include epigenetic reprogramming, metabolic reprogramming, and long-term protection mediated by hematopoietic stem cells. Trained immunity has so far shown beneficial effects on cancer, viral-infections, autoimmune diseases, and a variety of other diseases, especially bladder cancer, respiratory viruses, and type 1 diabetes. The modulation of the immune response by BCG has led to the development of a variety of recombinant vaccines. Although the specific mechanism of BCG prevention on diseases has not been fully clarified, the potential role of BCG deserves further exploration, which is of great significance for prevention and treatment of diseases.
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Mycobacterium bovis , Tuberculose , Humanos , Vacina BCG/uso terapêutico , Imunidade Treinada , Tuberculose/prevenção & controle , Macrófagos , Imunidade InataRESUMO
BACKGROUND: In areas where Lyme disease is endemic, bites from ticks are common, but no vaccine is currently available against Lyme disease for humans. Therefore, the feasibility of using antibiotic prophylaxis to prevent Lyme disease after a tick bite is worth further exploration. Previous meta-analyses lack sufficient power to demonstrate the efficacy of about antibiotic prophylaxis for the prevention of Lyme disease following a tick bite. In this study, we explored more precise evidence and attempted to identify and update optimum treatment strategies. METHODS: We searched PubMed, Embase, and the Cochrane Library for studies until March 23, 2021. We included studies if the enrolled patients were randomly allocated to a treatment or control group within 72 h following a tick bite and had no clinical evidence of Lyme disease at enrolment. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were followed for data abstraction. Two authors (GZZ and XX) independently reviewed the abstracts and identified articles for detailed assessment. We used a random-effects model to calculate the pooled results and reported the 95% confidence interval (CI). Study quality was assessed using a modified Jadad scale, and publication bias was assessed using Egger's test. We calculated the risk ratio (RR) for the rates of unfavorable events in patients who received intervention versus the control group. This study is registered with PROSPERO, number CRD42021245002. RESULTS: Six studies (3,766 individuals) were included. The pooled rate of unfavorable events in persons receiving treatment and the control group were 0.4% (95%CI: 0.1-1.1%) and 2.2% (95%CI: 1.6-3.0%), respectively. The pooled RR was 0.38 (95%CI: 0.22-0.66). Subgroup analysis revealed that the pooled RR was 0.29 (95%CI: 0.14-0.60) in the single-use 200-mg doxycycline group; 0.28 (95%CI: 0.05-1.67) in a 10-day course group (Amoxicillin, Penicillin or tetracycline); and 0.73 (95%CI: 0.25-2.08) in a topical antibiotic treatment group (Azithromycin). CONCLUSIONS: The available evidence supports the use of antibiotics for the prevention of Lyme disease, and reveals advantages of using single-dose; however, further confirmation is needed.
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Doença de Lyme , Picadas de Carrapatos , Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Antibioticoprofilaxia , Doxiciclina/uso terapêutico , Humanos , Doença de Lyme/tratamento farmacológico , Doença de Lyme/epidemiologia , Doença de Lyme/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Picadas de Carrapatos/tratamento farmacológicoRESUMO
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.
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Antibacterianos , Leptospirose , Humanos , Antibacterianos/efeitos adversos , Azitromicina/efeitos adversos , Doxiciclina/uso terapêutico , Leptospirose/tratamento farmacológico , Leptospirose/induzido quimicamente , Metanálise em Rede , Penicilinas/uso terapêuticoRESUMO
Periodontal disease (PD) and Alzheimer's disease (AD) are inflammatory diseases affecting the adult population of the world. PD is mainly caused by infection with Porphyromonas gingivalis (P. gingivalis) and by the synergistic action of various microorganisms. These microorganisms penetrate into the subgingival tissue and cause bacteremia, leading to disruption of the homeostasis of the internal environment of the body. Virulence factors known as gingipains, which are cysteine proteases and other toxins, including fimbria and lipopolysaccharides (LPS), are strongly associated with periodontitis and other systemic inflammation. PD has a known polymicrobial aetiology, and patients who eventually develop sporadic AD tend to have recurrent infections before a clinical diagnosis of dementia. AD, the most common neurodegenerative disease, is characterised by poor memory and specific hallmark proteins. An increasing number of studies have shown that periodontal pathogens are increasingly associated with this form of dementia. Many articles have shown that P. gingivalis infections directly increase the risk of PD and may indirectly lead to the development of AD. However, these links and probable pathogenesis remain to be explored. The aim of this review was to explore whether P. gingivalis periodontal infection is associated with AD and to provide possible mechanisms of association.
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Doença de Alzheimer , Doenças Neurodegenerativas , Doenças Periodontais , Periodontite , Adulto , Humanos , Porphyromonas gingivalis , Doença de Alzheimer/complicações , Doença de Alzheimer/epidemiologia , Doenças Neurodegenerativas/complicações , Periodontite/complicações , Inflamação/complicações , Doenças Periodontais/complicaçõesRESUMO
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].
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Hanseníase Multibacilar , Hanseníase , Humanos , Hansenostáticos/efeitos adversos , Rifampina/efeitos adversos , Clofazimina/efeitos adversos , Metanálise em Rede , Quimioterapia Combinada , Hanseníase/tratamento farmacológico , Dapsona/efeitos adversos , Hanseníase Multibacilar/tratamento farmacológicoRESUMO
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.
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Doença de Alzheimer , Quimiocina CCL5 , Humanos , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides , Quimiocina CCL5/metabolismo , Quimiocinas , Receptores CCR5/metabolismo , Receptores de Quimiocinas/metabolismoRESUMO
Lyme neuroborreliosis (LNB) is an infectious disease of the nervous system caused by Borrelia burgdorferi (Bb) infection. However, its pathogenesis is not fully understood. We used recombinant BmpA (rBmpA) to stimulate human microglia cell HMC3, then collected the culture supernatant and extracted total RNA from cells, and used the supernatant for cytokine chip, then ELISA and qPCR technology were used to validate the results from cytokine chip. After rBmpA stimulation of microglia, 24 inflammation-related cytokines showed elevated expression. Among them, six cytokines (IL-6, IL-8, CCL2, CCL5, CXCL1, and CXCL10) increased significantly in mRNA transcription, three cytokines (IL-6, IL-8, and CXCL10) concentrations in the cell supernatant increased significantly after the rBmpA stimulation, and CuIIa could inhibit expression of these cytokines. The BmpA can stimulate human microglia to produce large amounts of cytokines, leading to the occurrence of inflammation, which may be closely related to the development of LNB. CuIIa can inhibit BmpA-induced cytokine production in microglia, which may have potential therapeutic effects on LNB.
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Coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic and has severely affected socio-economic conditions and people's life. The lung is the major target organ infected and (seriously) damaged by SARS-CoV-2, so a comprehensive understanding of the virus and the mechanism of infection are the first choices to overcome COVID-19. Recent studies have demonstrated the enormous value of human organoids as platforms for virological research, making them an ideal tool for researching host-pathogen interactions. In this study, the various existing lung organoids and their identification biomarkers and applications are summarized. At the same time, the seven coronaviruses currently capable of infecting humans are outlined. Finally, a detailed summary of existing studies on SARS-CoV-2 using lung organoids is provided and includes pathogenesis, drug development, and precision treatment. This review highlights the value of lung organoids in studying SARS-CoV-2 infection, bringing hope that research will alleviate COVID-19-associated lung infections.
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COVID-19 , Pulmão , Modelos Anatômicos , Organoides , Humanos , Pulmão/virologia , Organoides/virologia , SARS-CoV-2RESUMO
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.
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Grupo Borrelia Burgdorferi , Borrelia burgdorferi , Doença de Lyme , Europa (Continente) , Humanos , Doença de Lyme/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos SoroepidemiológicosRESUMO
Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (MTB) infection, which has seriously endangered human health for many years. With the emergence of multidrug-resistant and extensively drug-resistant MTB, the prevention and treatment of TB has become a pressing need. Early diagnosis, drug resistance monitoring, and control of disease transmission are critical aspects in the prevention and treatment of TB. However, the currently available diagnostic technologies and drug sensitivity tests are time consuming, and thus, it is difficult to achieve the goal of early diagnosis and detection drug sensitivity, which results in limited control of disease transmission. The development of molecular testing technology has gradually achieved the vision of rapid and accurate diagnosis of TB. Droplet digital PCR (ddPCR) is an excellent nucleic acid quantification method with high sensitivity and no need for a calibration curve. Herein, we review the application of ddPCR in TB diagnosis and drug resistance detection and transmission monitoring.
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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.
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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.
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Hipersensibilidade , Sífilis , Humanos , Sífilis/tratamento farmacológico , Ceftriaxona/efeitos adversos , Doxiciclina/efeitos adversos , Minociclina/uso terapêutico , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Antibacterianos/efeitos adversos , Penicilinas/efeitos adversos , Tetraciclina , Eritromicina/uso terapêutico , Hipersensibilidade/tratamento farmacológico , Estudos Observacionais como AssuntoRESUMO
BACKGROUND: Lyme disease is a zoonotic disease caused by infection with Borrelia burgdorferi (Bb), the involvement of the nervous system in Lyme disease is usually referred to as Lyme neuroborreliosis (LNB). LNB has diverse clinical manifestations, most commonly including meningitis, Bell's palsy, and encephalitis. However, the molecular pathogenesis of neuroborreliosis is still poorly understood. Comprehensive transcriptomic analysis following Bb infection could provide new insights into the pathogenesis of LNB and may identify novel biomarkers or therapeutic targets for LNB diagnosis and treatment. METHODS: In the present study, we pooled transcriptomic dataset of Macaca mulatta (rhesus) from our laboratory and the human astrocyte dataset GSE85143 from the Gene Expression Omnibus database to screen common differentially expressed genes (DEGs) in the Bb infection group and the control group. Functional and enrichment analyses were applied for the DEGs. Protein-Protein Interaction network, and hub genes were identified using the Search Tool for the Retrieval of Interaction Genes database and the CytoHubba plugin. Finally, mRNA expression of hub genes was validated in vitro and ex vivo from Bb infected models and normal controls by quantitative reverse transcription PCR (qRT-PCR). RESULTS: A total of 80 upregulated DEGs and 32 downregulated DEGs were identified. Among them, 11 hub genes were selected. The pathway enrichment analyses on 11 hub genes revealed that the PI3K-Akt signaling pathway was significantly enriched. The mRNA levels of ANGPT1, TLR6, SREBF1, LDLR, TNC, and ITGA2 in U251 cells and/or rhesus brain explants by exposure to Bb were validated by qRT-PCR. CONCLUSION: Our study suggested that TLR6, ANGPT1, LDLR, SREBF1, TNC, and ITGA may be candidate mammal biomarkers for LNB, and the TLR6/PI3K-Akt signaling pathway may play an important role in LNB pathogenesis.
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Grupo Borrelia Burgdorferi , Borrelia burgdorferi , Neuroborreliose de Lyme , Animais , Biomarcadores , Borrelia burgdorferi/genética , Grupo Borrelia Burgdorferi/genética , Sistema Nervoso Central , Humanos , Macaca mulatta/genética , Mamíferos , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , RNA Mensageiro , Receptor 6 Toll-Like/genética , TranscriptomaRESUMO
Brain organoids, or brainoids, have shown great promise in the study of central nervous system (CNS) infection. Modeling Zika virus (ZIKV) infection in brain organoids may help elucidate the relationship between ZIKV infection and microcephaly. Brain organoids have been used to study the pathogenesis of SARS-CoV-2, human immunodeficiency virus (HIV), HSV-1, and other viral infections of the CNS. In this review, we summarize the advances in the development of viral infection models in brain organoids and their potential application for exploring mechanisms of viral infections of the CNS and in new drug development. The existing limitations are further discussed and the prospects for the development and application of brain organs are prospected.
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Encéfalo/citologia , Organoides/citologia , Técnicas de Cultura de Tecidos/métodos , Animais , Encéfalo/patologia , Encéfalo/virologia , Humanos , Organoides/virologia , Doenças Priônicas/patologia , Doenças Priônicas/prevenção & controle , Doenças Priônicas/terapia , Técnicas de Cultura de Tecidos/economia , Viroses/patologia , Viroses/prevenção & controle , Viroses/terapiaRESUMO
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.
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Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Doença de Lyme/tratamento farmacológico , Administração Oral , Adulto , Amoxicilina/efeitos adversos , Amoxicilina/uso terapêutico , Azitromicina/efeitos adversos , Azitromicina/uso terapêutico , Borrelia burgdorferi/efeitos dos fármacos , Grupo Borrelia Burgdorferi/efeitos dos fármacos , Cefotaxima/efeitos adversos , Cefotaxima/uso terapêutico , Ceftriaxona/efeitos adversos , Ceftriaxona/uso terapêutico , Criança , Doxiciclina/efeitos adversos , Doxiciclina/uso terapêutico , Humanos , Injeções/efeitos adversos , Metanálise em Rede , Penicilinas/efeitos adversos , Penicilinas/uso terapêuticoRESUMO
Background: Lyme neuroborreliosis (LNB) is one of the most dangerous manifestations of Lyme disease, but the pathogenesis and inflammatory mechanisms are not fully understood. Methods: Cultured explants from the frontal cortex of rhesus monkey brain (n=3) were treated with live Borrelia burgdorferi (Bb) or phosphate-buffered saline (PBS) for 6, 12, and 24 h. Total protein was collected for sequencing and bioinformatics analysis. In addition, changes in protein expression in the explants over time following Bb treatment were screened. Results: We identified 1237 differentially expressed proteins (DEPs; fold change ≥1.5 or ≤0.67, P-value ≤0.05). One of these, growth-associated protein 43 (GAP-43), was highly expressed at all time points in the explants. The results of the protein-protein interaction network analysis of DEPs suggested that GAP-43 plays a role in the neuroinflammation associated with LNB. In HMC3 cells incubated with live Bb or PBS for 6, 12, and 24 h, real-time PCR and western blot analyses confirmed the increase of GAP-43 mRNA and protein, respectively. Conclusions: Elevated GAP-43 expression is a potential marker for LNB that may be useful for diagnosis or treatment.