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Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System(BRICS)were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute(CLSI). WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period,9 035 strains of Gram-negative bacteria were collected from 51 hospitals,of which 7 895(87.4%)were Enterobacteriaceae and 1 140(12.6%)were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli( n=4 510,49.9%), Klebsiella pneumoniae( n=2 340,25.9%), Pseudomonas aeruginosa( n=534,5.9%), Acinetobacter baumannii complex( n=405,4.5%)and Enterobacter cloacae( n=327,3.6%). The ESBLs-producing rates in Escherichia coli, Klebsiella pneumoniae and Proteus spp. were 47.1%(2 095/4 452),21.0%(427/2 033)and 41.1%(58/141),respectively. The prevalence of carbapenem-resistant Escherichia coli(CREC)and carbapenem-resistant Klebsiella pneumoniae(CRKP)were 1.3%(58/4 510)and 13.1%(307/2 340);62.1%(36/58)and 9.8%(30/307)of CREC and CRKP were resistant to ceftazidime/avibactam combination,respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)complex was 59.5%(241/405),while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa(CRPA)was 18.4%(98/534). There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions,with statistically significant differences in the prevalence of CRKP and CRPA( χ2=20.489 and 20.252, P<0.001). The prevalence of CREC,CRKP,CRPA,CRAB,ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals( χ2=11.953,81.183,10.404,5.915,12.415 and 6.459, P<0.01 or <0.05),while the prevalence of CRPA was higher in economically developed regions(per capita GDP ≥ 92 059 Yuan)than that in economically less-developed regions(per capita GDP <92 059 Yuan)( χ2=6.240, P=0.012). Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend,and Escherichia coli is ranked in the top,while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different,and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.
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Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical bacterial isolates from bloodstream infections in China in 2021.Methods:The clinical bacterial strains isolated from blood culture from member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS) were collected during January 2021 to December 2021. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical Laboratory Standards Institute (CLSI). WHONET 5.6 was used to analyze data.Results:During the study period, 11 013 bacterial strains were collected from 51 hospitals, of which 2 782 (25.3%) were Gram-positive bacteria and 8 231 (74.7%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (37.6%), Klebsiella pneumoniae (18.9%), Staphylococcus aureus (9.8%), coagulase-negative Staphylococci (6.3%), Pseudomonas aeruginosa (3.6%), Enterococcus faecium (3.6%), Acinetobacter baumannii (2.8%), Enterococcus faecalis (2.7%), Enterobacter cloacae (2.5%) and Klebsiella spp (2.1%). The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus aureus were 25.3% and 76.8%, respectively. No glycopeptide- and daptomycin-resistant Staphylococci was detected; more than 95.0% of Staphylococcus aureus were sensitive to ceftobiprole. No vancomycin-resistant Enterococci strains were detected. The rates of extended spectrum B-lactamase (ESBL)-producing isolated in Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis were 49.6%, 25.5% and 39.0%, respectively. The prevalence rates of carbapenem-resistance in Escherichia coli and Klebsiella pneumoniae were 2.2% and 15.8%, respectively; 7.9% of carbapenem-resistant Klebsiella pneumoniae was resistant to ceftazidime/avibactam combination. Ceftobiprole demonstrated excellent activity against non-ESBL-producing Escherichia coli and Klebsiella pneumoniae. Aztreonam/avibactam was highly active against carbapenem-resistant Escherichia coli and Klebsiella pneumoniae. The prevalence rate of carbapenem-resistance in Acinetobacter baumannii was 60.0%, while polymyxin and tigecycline showed good activity against Acinetobacter baumannii (5.5% and 4.5%). The prevalence of carbapenem-resistance in Pseudomonas aeruginosa was 18.9%. Conclusions:The BRICS surveillance results in 2021 shows that the main pathogens of blood stream infection in China are gram-negative bacteria, in which Escherichia coli is the most common. The MRSA incidence shows a further decreasing trend in China and the overall prevalence of vancomycin-resistant Enterococci is low. The prevalence of Carbapenem-resistant Klebsiella pneumoniae is still on a high level, but the trend is downwards.
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Objective:To investigate the bacterial composition and antimicrobial resistance profile of clinical isolates from bloodstream infections in China.Methods:The clinical bacterial strains isolated from blood culture were collected during January 2020 to December 2020 in member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS). Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical Laboratory Standards Institute(CLSI, USA). WHONET 5.6 was used to analyze data.Results:During the study period, 10 043 bacterial strains were collected from 54 hospitals, of which 2 664 (26.5%) were Gram-positive bacteria and 7 379 (73.5%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (38.6%), Klebsiella pneumoniae (18.4%), Staphylococcus aureus (9.9%), coagulase-negative Staphylococci (7.5%), Pseudomonas aeruginosa (3.9%), Enterococcus faecium (3.3%), Enterobacter cloacae (2.8%), Enterococcus faecalis (2.6%), Acinetobacter baumannii (2.4%) and Klebsiella spp (1.8%). The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus aureus were 27.6% and 74.4%, respectively. No glycopeptide- and daptomycin-resistant Staphylococci were detected. More than 95% of Staphylococcus aureus were sensitive to rifampicin and SMZco. No vancomycin-resistant Enterococci strains were detected. Extended spectrum β-lactamase (ESBL) producing Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis were 48.4%, 23.6% and 36.1%, respectively. The prevalence rates of carbapenem-resistance in Escherichia coli and Klebsiella pneumoniae were 2.3% and 16.1%, respectively; 9.6% of carbapenem-resistant Klebsiella pneumoniae strains were resistant to ceftazidime/avibactam combination. The prevalence rate of carbapenem-resistance in Acinetobacter baumannii was 60.0%, while polymyxin and tigecycline showed good activity against Acinetobacter baumannii. The prevalence rate of carbapenem-resistance of Pseudomonas aeruginosa was 23.2%. Conclusions:The surveillance results in 2020 showed that the main pathogens of bloodstream infection in China were gram-negative bacteria, while Escherichia coli was the most common pathogen, and ESBL-producing strains declined while carbapenem-resistant Klebsiella pneumoniae kept on high level. The proportion and the prevalence of carbapenem-resistant Pseudomonas aeruginosa were on the rise slowly. On the other side, the MRSA incidence got lower in China, while the overall prevalence of vancomycin-resistant Enterococci was low.
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Objective:To investigate the distribution and antimicrobial resistance profile of clinical bacteria isolated from blood culture in China.Methods:The clinical bacterial strains isolated from blood culture from member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS) were collected during January 2018 to December 2019. Antibiotic susceptibility tests were conducted with agar dilution or broth dilution methods recommended by US Clinical and Laboratory Standards Institute (CLSI). WHONET 5.6 was used to analyze data.Results:During the study period, 14 778 bacterial strains were collected from 50 hospitals, of which 4 117 (27.9%) were Gram-positive bacteria and 10 661(72.1%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (37.2%), Klebsiella pneumoniae (17.0%), Staphylococcus aureus (9.7%), coagulase-negative Staphylococci (8.7%), Pseudomonas aeruginosa (3.7%), Enterococcus faecium (3.4%), Acinetobacter baumannii(3.4%), Enterobacter cloacae (2.9%), Streptococci(2.8%) and Enterococcus faecalis (2.3%). The the prevalence of methicillin-resistant S. aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus were 27.4% (394/1 438) and 70.4% (905/1 285), respectively. No glycopeptide-resistant Staphylococcus was detected. More than 95% of S. aureus were sensitive to amikacin, rifampicin and SMZco. The resistance rate of E. faecium to vancomycin was 0.4% (2/504), and no vancomycin-resistant E. faecalis was detected. The ESBLs-producing rates in no carbapenem-resistance E. coli, carbapenem sensitive K. pneumoniae and Proteus were 50.4% (2 731/5 415), 24.6% (493/2001) and 35.2% (31/88), respectively. The prevalence of carbapenem-resistance in E. coli and K. pneumoniae were 1.5% (85/5 500), 20.6% (518/2 519), respectively. 8.3% (27/325) of carbapenem-resistance K. pneumoniae was resistant to ceftazidime/avibactam combination. The resistance rates of A. baumannii to polymyxin and tigecycline were 2.8% (14/501) and 3.4% (17/501) respectively, and that of P. aeruginosa to carbapenem were 18.9% (103/546). Conclusions:The surveillance results from 2018 to 2019 showed that the main pathogens of bloodstream infection in China were gram-negative bacteria, while E. coli was the most common pathogen, and ESBLs-producing strains were in majority; the MRSA incidence is getting lower in China; carbapenem-resistant E. coli keeps at a low level, while carbapenem-resistant K. pneumoniae is on the rise obviously.
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The current document is based on a consensus reached by a panel of experts from the Chinese Society of Allergy and the Chinese Society of Otorhinolaryngology-Head and Neck Surgery, Rhinology Group. Chronic rhinosinusitis (CRS) affects approximately 8% of Chinese adults. The inflammatory and remodeling mechanisms of CRS in the Chinese population differ from those observed in the populations of European descent. Recently, precision medicine has been used to treat inflammation by targeting key biomarkers that are involved in the process. However, there are no CRS guidelines or a consensus available from China that can be shared with the international academia. The guidelines presented in this paper cover the epidemiology, economic burden, genetics and epigenetics, mechanisms, phenotypes and endotypes, diagnosis and differential diagnosis, management, and the current status of CRS in China. These guidelines—with a focus on China—will improve the abilities of clinical and medical staff during the treatment of CRS. Additionally, they will help international agencies in improving the verification of CRS endotypes, mapping of eosinophilic shifts, the identification of suitable biomarkers for endotyping, and predicting responses to therapies. In conclusion, these guidelines will help select therapies, such as pharmacotherapy, surgical approaches and innovative biotherapeutics, which are tailored to each of the individual CRS endotypes.
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Adult , Humans , Asian People , Biomarkers , China , Consensus , Diagnosis , Diagnosis, Differential , Drug Therapy , Eosinophils , Epidemiology , Epigenomics , Genetics , Hypersensitivity , Inflammation , International Agencies , Medical Staff , Neck , Phenotype , Precision MedicineABSTRACT
Objective@#To explore the temporal and spatial characteristics of search volume (SV) of allergic rhinitis (AR) and related search terms on Baidu Index, as well as the correlation between SV from Baidu Index and epidemiology of AR.@*Methods@#SV of AR and related search terms in mainland area of China from January 2012 to December 2016 were extracted from Baidu Index. Firstly, we investigated the temporal and spatial characteristics of SV of AR and related search terms ("pollen allergy" and" dust mite allergy", etc.), and explored the correlation between SV of AR and SV of related search terms. Secondly, the SV of specific search terms in Beijing and Guangzhou were compared with the actual pollen count in Beijing from April to September in 2016 and the monthly outpatient volume of AR patients in the Otorhinolaryngology Hospital, The First Affiliated Hospital of Sun Yat-sen University from 2014 to 2016 respectively to analyze the consistency between SV from Baidu Index and the real-world data. Spearman correlation analysis was used to explore the correlation between different search terms according to the normality and homogeneity of variance of the data. P<0.05 was considered statistically significant.@*Results@#SV of AR showed repetitively seasonal pattern, with the first peak in May and the second peak from August to September. SV of AR in northeast China, north China and northwest China were correlated with both SV of "pollen allergy" and "dust mite allergy" (r value was 0.533, 0.638, 0.609, 0.791, 0.517, 0.682, respectively, all P<0.05). In east China, central China, south China and southwest China, SV of AR showed significant correlation only with SV of "dust mite allergy" (r value was 0.897, 0.884, 0.799, 0.937, respectively, all P<0.05), but not with SV of "pollen allergy" (r value was 0.110, 0.171, 0.020, 0.265, respectively, all P>0.05). The correlation between pollen count and the SV of AR on the day and SV of "pollen allergy" on the next day was the highest (r value was 0.692 and 0.713, respectively, all P<0.05). The SV of AR was correlated with the monthly outpatient volume of AR patients one month and two months later (r value was 0.523 and 0.503, respectively, all P<0.05).@*Conclusion@#The SV of AR and related search terms show different trends in different times and regions which are consistent with the AR epidemiological survey, and significantly correlate with pollen count and AR outpatient volume.
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Objective@#To explore the clinical features, diagnostic methods and therapeutic strategy of silent sinus syndrome (SSS).@*Methods@#A retrospective study was made on eight SSS patients treated during 2013-2016 in Longgang ENT Hospital and Otorhinolaryngology Hospital of the First Affiliated Hospital of SUN Yat-sen University. The following clinical data, including demographic data, symptoms, history of trauma and surgery, signs, imaging examination, endoscopic surgery and postoperative outcomes, were analyzed to summarize the diagnosis and treatment experiences.@*Results@#Eight SSS patients showed the following clinical features: the proportions of both sexes and sinus sides were 4 to 4; seven cases (7/8) were adult, with an average of (48.1±11.8)y; seven cases (7/8) had long history of trauma or surgery, with an average of (17.9±10.5)y; seven cases (7/8) cannot recall the exact course of SSS; six cases (6/8) had no nasal symptoms; eight cases (8/8) had unilateral ocular discomforts; eight cases (8/8) had signs of unilateral enophthalmos (2-5 mm), accompanied with hypoglobus; and by CT and MRI scanning, eight cases (8/8) showed the unilateral maxillary sinus outlet obstruction, sinus full opacification, sinus wall bony rarefaction, sinus wall contraction, sinus volume loss, and the ipsilateral orbital floor bowing descent and orbital volume increase. After treated by endoscopic sinus surgery and followed-up for one year, four cases were cured, and the other four improved; no intra- or post-operative complications occurred; and no individual need a two-stage orbital plastic reconstruction.@*Conclusions@#SSS often develops in the unilateral maxillary sinus of adult patient with long history of trauma or surgery, but the nasal symptoms and signs are silent. Diagnostic for SSS depends on characteristic ocular sign and sinus CT imaging. Endoscopic sinus surgery helps to improve ocular and nasal signs and promote orbital self-reconstruction.
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Objective@#To summarize the surgical techniques, benefits and limitations of transnasal endoscopic resection and optic nerve decompression for patients with optic neuropathy caused by fibro-osseous lesions.@*Methods@#Eight patients with optic neuropathy caused by fibro-osseous lesions who accepted endoscopic surgery of either resection of the lesion or decompression of optic nerve in Otorhinolaryngology Hospital, First Affiliated Hospital of Sun Yat-sen University from 2007 to 2016 were retrospectively reviewed and followed until April, 2017. Analyses were performed on the pathology type, disease extent and disease duration, especially on the visual acuity and visual field changes before and after surgery.@*Results@#Eight patients (5 male and 3 female) were included in this study, with a median age of 12 years old (8-19 years old). The median disease duration was 12 months (1-72 months). The visual acuity (VA) of five patients (40 cm/FC, 0.2, 0.1, 0.2, 10 cm/FC, respectively) improved after surgery (0.1, 0.3, 1.2, 0.1, 0.6, respectively), and one patient had no change of VA after the surgery. Two patients (0.02, hand movement, before surgery) became deprived of light perception (VA=0) immediately after surgery. One patient complicated with intra orbital hemorrhage because of anterior artery injury. No complications of cerebral spinal fluid leak, intra-ocular muscle injury, intra-cranial hemorrhage or brain tissue injury occurred.@*Conclusion@#For the treatment of optic neuropathy caused by fibro-osseous lesions, transnasal endoscopic surgery might have a good outcome.
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There is a strong association between chronic rhinosinusitis (CRS) and asthma. Approximately 10%-50% of CRS patients also have comorbid asthma. These patients are more likely to have severe CRS and asthma and higher recurrence rates after sinus surgery. Also there may be acute asthma attack during the perioperative period. Therefore, we should pay more attention to these patients. Assessment of the control level of asthma and pulmonary function should be performed preoperatively. And asthma needs to be fully managed in the perioperative period to avoid acute asthma attack. Extensive sinus surgery is recommended in these patients to reduce the inflammation load. Long-term medical treatment and regular follow-up are suggested to achieve well control of CRS and asthma.
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Humans , Asthma , Therapeutics , Chronic Disease , Inflammation , Therapeutics , Rhinitis , Therapeutics , Sinusitis , TherapeuticsABSTRACT
The purpose of this review is to explain the relationship between chronic rhinosinusitis (CRS) and lower respiratory tract inflammation, especially asthma and introduce the new advances in the treatment of CRS patient with asthma. We also introduce our treatment strategy for these patients, including surgery technique and perioperative management.
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Humans , Asthma , Pathology , Chronic Disease , Inflammation , Pathology , Otolaryngology , Methods , Respiratory System , SinusitisABSTRACT
PURPOSE: Chronic rhinosinusitis (CRS) is characterized by the excessive production of mucus. However, the molecular mechanism underlying mucin overproduction in CRS with or without nasal polyps (CRSwNP and CRSsNP, respectively) is poorly understood. This study was conducted to assess the importance of the transcription factor FoxA2 in mucin production and to investigate the targeting of FoxA2 as a potential therapeutic strategy for mucus hypersecretion in CRS patients. METHODS: We enrolled 15 CRSwNP patients, 15 CRSsNP patients, and 10 normal controls in this study. The expression levels of FoxA2, MUC5AC, and MUC5B in inflamed and healthy nasal tissues were examined via immunohistochemistry and quantitative reverse transcription-polymerase chain reaction, and the levels of several proinflammatory cytokines in nasal secretions were measured via FlowCytomix analysis. In addition, the expression of MUC5AC and FoxA2 was determined in polyp-derived epithelial cells and NCI-H292 cells after in vitro stimulation. RESULTS: FoxA2 was significantly down-regulated, and MUC5AC and MUC5B were significantly up-regulated in both the CRSwNP and CRSsNP patients compared to the controls (P<0.05), and the protein level of FoxA2 was negatively associated with the IL-6 level in the CRS patients (P<0.05). IL-6 significantly increased MUC5AC expression but inhibited FoxA2 expression in vitro (P<0.05). Transfection with a FoxA2 expression plasmid significantly decreased MUC5AC promoter activity (P<0.05) and inhibited IL-6-induced MUC5AC production (P<0.05). In addition, clarithromycin significantly alleviated IL-6-induced FoxA2 suppression and decreased MUC5AC expression in vitro (P<0.05). CONCLUSIONS: Our findings suggest that FoxA2 may be considered a therapeutic target for the modulation of mucus hypersecretion in CRS patients.
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Humans , Clarithromycin , Cytokines , Epithelial Cells , Immunohistochemistry , Interleukin-6 , Mucins , Mucus , Nasal Polyps , Plasmids , Transcription Factors , TransfectionABSTRACT
<p><b>OBJECTIVE</b>To investigate the application of Chinese guideline for the diagnosis and treatment of chronic rhinosinusitis (2008, Nanchang) on a national scale.</p><p><b>METHODS</b>The contents of the guideline and its relevant applied indicators were designed into an initial questionnaire and, after a pre-survey, revised into a formal questionnaire. Then a stratified sampling was selected out of otolaryngology practitioners in the different level hospitals across the country. After a uniform training, the investigators were sent to these different hospitals to conduct questionnaire survey by face to face interview with otolaryngology respondents. Based on the summarized data, statistical analyses on the awareness and practice status of the guideline, together with their influencing factors, were made. SPSS 16.0 software was used to analyze the data.</p><p><b>RESULTS</b>Issuing and withdrawing questionnaires were performed from December 2012 to June 2013 and 1 240 respondents in 350 hospitals from 30 different provinces, municipalities or autonomous regions were effectively investigated. An average awareness and practice rate of 48.7% and 40.8% upon the guideline was acquired, respectively. There was a significant correlation (r = 0.280, P = 0.000) between the two indicators. With linear regression, county-level hospitals, junior practitioners, non-rhino professionals were the risk factors of poor guideline adherence. In addition, respondents form western region showed lower awareness and practice rate than that of ones from central and eastern region.</p><p><b>CONCLUSION</b>The adherence on Chinese guideline for the diagnosis and treatment of chronic rhinosinusitis is nationally low, so popularization of activities should be urgently strengthened, especially in focus areas, focus hospitals, and focus groups.</p>
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Humans , Chronic Disease , Therapeutics , Guideline Adherence , Practice Guidelines as Topic , Risk Factors , Sinusitis , Therapeutics , Surveys and QuestionnairesABSTRACT
Objective To investigate the PCR-based evaluation of prednisolone-induced relapse of asymptomatic Toxoplasma gondii infection and the therapeutic efficacy of azithromycin.Methods A total of 36 of female ICR mice,about 20 g,were randomly divided into 6 groups:contrast group (C),prednisolone group (P),infection group(I),infection plus prednisolone group (IP),infection plus azithromycin group(IA),infection plus prednisolone and azithromycin group (IPA).The infection group (I),infection plus prednisolone group(IP),infection plus azithromycin group(IA),infection plus prednisolone and azithromycin group (IPA)were challenged at week 0 with 10 cysts of Toxoplasma gondii Prugniaud strain per injection intraperitoneally.The prcdnisolone group (P),infection plus prednisolone group (IP) infection plus prednisolone and azithromycin group (IPA)were injectied with prednisolone 1 mg into hind medial subcutaneous every day from the 6th week to 7th week.The infection plus azithromycin group(IA),infection plus prednisolone and azithromycin group (IPA) were injectied with azithromycin 250 mg/kg intraperitoneally every day from the 6th week to 7th week.The serum samples were collected and DNAs extracted at week 0,1,2,3,4,5,6 and 7 for amplification of Toxoplasma gondii of specific B1 gene by PCR.All the mice were sacrificed 7 weeks after the challenge to calculate the number of cysts in brain tissues.Results Compared with the primer of AF146527 gene,the primer of B1 gene was more sensitive and specific.The method of PCR could amplify the productions of specific B1 gene Toxoplasma gondii 5 weeks before the challenge,while it could not amplified 5 weeks after the challenge.All the mice of the IP group were dead 2 weeks after the injection of prednisolone (week 7),and the only two mice of the IPA group were dead at the same time (P <0.05),respectively.Compared with the I group,IA group and IPZ group,the number of cysts in brain tissues of the IP group significantly increased (P <0.01).Conclusions B1 as target gene is more suitable for diagnosis of Toxoplasma gondii infection by PCR.Prednisolone could induce the relapse of asymptomatic Toxoplasma gondii infection of mice and the mice are finally dead.Azithromycin is effective but it can not completely cure the Toxoplasma gondii infection.