甲型副伤寒238例临床分析

近年来,甲型副伤寒发病有增多趋势,而且早期缺乏典型临床表现,容易误诊。现将诸暨市人民医院2001年1月-2003年9月收治的血培养阳性的238例甲型副伤寒患者作一临床分析,以期对该病的早期诊断、治疗有所帮助。     

单份血清肥达凝集试验在甲型副伤寒诊断中的价值

目的：评价疑似甲型副伤寒病例单份血清肥达凝集试验(WAT)的诊断价值。方法：以甲型副伤寒沙门菌血培养阳性和／或血清鞭毛特异性抗原阳性的甲型副伤寒病例(n=76)、血培养阴性和／或血清抗原阴性的对照发热病人(n=92)和健康饮食从业人员(n=63)为检测对象,用WAT测定以上三种人群血清甲型副伤寒沙门菌O、H、A抗体,分析评价不同O、H、A判断值诊断甲型副伤寒的敏感性、特异性、阳性预测值和阳性似然比等指标。结果：获得三种人群O、H、A凝集价的分布及其几何平均滴度,20％对照发热病人O抗体效价≥160,而健康从业人员仅有3．2％的O抗体效价≥160,对照发热病人和健康人相应H抗体效价分别占17％和4．8％,A抗体效价分别占16％和1．6％。53％血培养阳性和血清鞭毛抗原阳性甲型副份寒病例O抗体效价≥160,相应H、A抗体效价分别占41％和51％。用敏感性、特异性、阳性预测值、阳性似然比等指标评价单份血清WAT诊断甲型副伤寒的价值,提出O或H或A≥160和O≥160或A≥80可作为WAT辅助诊断甲型副伤寒的标准。结论：单份血清WAT有助于甲型副伤寒的诊断,该试验对血培养阴性的临床疑似甲型副伤寒病例及其高危人群中甲型副伤寒病例的诊断有实用意义。     

广西桂林市1999—2008年甲型副伤寒病带菌者菌株的耐药性分析

目的了解甲型副伤寒病后带菌者菌株对常用抗生素耐药情况,指导临床合理规范用药。方法随访桂林市1999—2008年发病的甲型副伤寒病患者,采集其3次粪便标本培养甲型副伤寒菌,对培养出的菌株进行18种抗生素的耐药检测。结果 328名既往甲型副伤寒患者中检出恢复期病例20例,检出带菌6例,恢复期带菌率30.0%,95%CI(12.0%,54.0%),恢复期带菌者发病时用药不规范。病后3个月至9年的既往甲型副伤寒患者308例,检出慢性带菌1例,慢性带菌率为0.32%,95%CI(0.1%,5.6%)。所有菌株对喹诺酮类药物敏感率不高,对萘啶酸耐药率为100%。对氨卞西林、一代头孢、氨曲南、链霉素、磺胺等药物不同程度中介或耐药。慢性带菌者的菌株除萘啶酸耐药外,对其他抗生素均敏感。结论治疗甲型副伤寒患者时应做到抗生素的规范、合理使用,以减少病后带菌发生。     

异位妊娠早期超声的临床诊断分析

目的:评价超声在异位妊娠早期诊断中的应用价值,总结诊断经验。方法:回顾性分析确诊的早期异位妊娠超声诊断临床资料。结果:输卵管妊娠73例(89.02%),非输卵管妊娠9例(10.98%);胚囊类30(36.59%)例,实性包块30(36.59)例,不均质包块13(15.85%)例;伴有盆腔积液12例;确诊68(82.93%)例,漏诊4(4.88%)例;第1次、第2次、第3次诊断,阴道超声符合率90.91%、92.00%、100.00%,腹部超声诊断符合率58.33%、88.61%、98.65%;典型征象心血管搏动占13.41%、胚芽反射21.95%、双环征23.17%,不典型征象囊实性包块43.90%、积液14.63%、散在性包块9.76%。结论:异位妊娠早期超声征象多不典型,腹部超声诊断符合率较低,应尽量应用阴道超声,多次诊断,有助于提高诊断符合率;早期孕囊多表现为囊实性包块,若位置敏感,应提高警惕,详细确诊。     

甲型副伤寒沙门菌培养条件的优化

优化甲型副伤寒沙门菌的培养条件,提高菌体产量。方法通过单因素及正交试验,对影响甲型副伤寒沙门菌生长的培养温度、NaCl浓度和pH等条件进行优化。结果甲型副伤寒沙门菌在NaCl浓度0.75%、温度35℃、pH6.5时菌体产量最高。结论通过对甲型副伤寒沙门菌培养条件进行优化,获得较高的菌体产量,为后期诊断试剂盒的开发奠定了基础。     

甲型副伤寒沙门氏菌LPS提取和O-SP纯化

提取甲型副伤寒沙门氏菌脂多糖(LPS)和纯化特异多糖(O -SP),为制备副伤寒结合疫苗奠定基础。采用大罐培养,菌体热酚法提纯去蛋白,乙醇分级沉淀冷冻离心去核酸,乙酸水解脱毒,高速离心,柱层析等方法纯化。纯化O SP核酸含量低于 1%,蛋白含量低于 1. 5%,O 乙酰基含量 0. 5~0. 8mmol/L,与甲型副伤寒超免血清形成明显沉淀线,核磁共振图谱(NMR)显示甲型副伤寒O SP的特征谱。建立了实用的纯化甲型副伤寒O -SP工艺。     

甲型副伤寒并发浆膜腔积液

近年来温州地区甲型伤寒发病较前增多.甲型副伤寒是甲型副伤寒杆菌所致的败血症,常累及全身多部位,其临床表现多种多样,但出现浆膜腔积液者少见,往往不能及时被确诊.现将近五年来收住我院的甲型副伤寒并发浆膜腔积液患者8例报道如下.     

温州地区甲型副伤寒临床特征及耐药性分析

目的分析温州地区1997-2003年甲型副伤寒的临床特征及耐药性,提高对该病的认识,探讨合理使用抗生素。方法回顾性分析温州地区283例甲型副伤寒的临床特征,并采用ATB半自动细菌鉴定仪(法国生物梅里埃公司制造),进行细菌鉴定及药敏试验。结果甲型副伤寒临床表现以高热为主,伴畏寒234例(82．7％),伴头痛、头晕141例(49．8％),伴呼吸道症状105例(37．1％),伴消化道症状96例(33．9％)。血常规示嗜酸性粒细胞下降占74．1％,肝功能示SGPT升高占60．6％,SCOT升高占60．3％,SGOT升高占60．6％。肥达试验阳性率低。药敏分析：对培氟沙星、阿莫西林、阿莫西林．克拉维酸钾和头孢呋辛耐药率高,对头孢第3、4代,氨曲南,氨基糖甙类,喹诺酮类(除培氟沙星)与氯霉素敏感性强。结论温州地区甲型副伤寒的临床表现比较典型,治疗上需合理选用抗生素。     

全面与选择性腹部超声检查对急腹症诊断效果及满意度的影响

目的:探讨全面与选择性腹部超声检查对急腹症的诊断效果,评价患者对两种诊断方式的满意度。方法:选择2017年3月至2019年6月我院诊治的疑似急腹症患者146例为研究对象,所有患者均进行全面腹部超声检查和选择性腹部超声检查,比较两种检查方式的诊断符合率、敏感度、特异度、误诊率、漏诊率、超声检查时间、诊断时间、延迟诊断率、检查费用及满意度。结果:全面腹部超声检查诊断急腹症的符合率、敏感度、特异度高于选择性腹部超声,误诊率、漏诊率低于选择性腹部超声(P0.05)。与选择性腹部超声比较,全面腹部超声检查时间较长,诊断时间较短,延迟诊断率较低,检查费用较高(P0.05)。患者对全面腹部超声检查的满意度为97.26%,高于选择性腹部超声的71.92%(P0.05)。结论:与选择性腹部超声检查比较,全面腹部超声检查诊断急腹症时间较长,费用较高,但在准确性、漏诊、误诊、延迟诊断、患者满意度等方面优势明显,是诊断急腹症的有效方法。     

121株甲型副伤寒病原菌的噬菌体型和脉冲场凝胶电泳型

目的认识甲型副伤寒疫病区甲型副伤寒沙门菌的噬菌体型和脉冲场凝胶电泳（PFGE）型,确定噬菌体型和PFGE型之间的关系以及菌型的分布和流行率。方法采用沙门菌组合噬菌体和SpeI、XbaI消化染色体DNA的PFGE对来自玉溪市7县（区）的121株甲型副伤寒菌进行分型。结果121株菌存在4个完全噬菌体型或1个噬菌体型;用SpeI或XbaI消化产物分别得出以SpeI01、SpeI02或XbaI01占优势的5种或4种PFGE型,SpeI01型和SpeI02型分别占37．2％和57．9％,XbaI01型占95．1％。结论121株菌的噬菌体型与PFGE型之间无一致性联系,PFGE型的SpeI01和SpeI02或XbaI01是玉溪地区的主要流行型,采用SpeI和XbaI的PFGE是鉴别甲型副伤寒菌流行克隆的一项有用技术。     

Development and Evaluation of a Blood Culture PCR Assay for Rapid Detection of Salmonella Paratyphi A in Clinical Samples

Background

Enteric fever remains an important cause of morbidity in many low-income countries and Salmonella Paratyphi A has emerged as the aetiological agent in an increasing proportion of cases. Lack of adequate diagnostics hinders early diagnosis and prompt treatment of both typhoid and paratyphoid but development of assays to identify paratyphoid has been particularly neglected. Here we describe the development of a rapid and sensitive blood culture PCR method for detection of Salmonella Paratyphi A from blood, potentially allowing for appropriate diagnosis and antimicrobial treatment to be initiated on the same day.

Methods

Venous blood samples from volunteers experimentally challenged orally with Salmonella Paratyphi A, who subsequently developed paratyphoid, were taken on the day of diagnosis; 10 ml for quantitative blood culture and automated blood culture, and 5 ml for blood culture PCR. In the latter assay, bacteria were grown in tryptone soy broth containing 2.4% ox bile and micrococcal nuclease for 5 hours (37°C) before bacterial DNA was isolated for PCR detection targeting the fliC-a gene of Salmonella Paratyphi A.

Results

An optimized broth containing 2.4% ox bile and micrococcal nuclease, as well as a PCR test was developed for a blood culture PCR assay of Salmonella Paratyphi A. The volunteers diagnosed with paratyphoid had a median bacterial burden of 1 (range 0.1–6.9) CFU/ml blood. All the blood culture PCR positive cases where a positive bacterial growth was shown by quantitative blood culture had a bacterial burden of ≥ 0.3 CFU/ ml blood. The blood culture PCR assay identified an equal number of positive cases as automated blood culture at higher bacterial loads (≥0.3 CFU/ml blood), but utilized only half the volume of specimens.

Conclusions

The blood culture PCR method for detection of Salmonella Paratyphi A can be completed within 9 hours and offers the potential for same-day diagnosis of enteric fever. Using 5 ml blood, it exhibited a lower limit of detection equal to 0.3 CFU/ml blood, and it performed at least as well as automated blood culture at higher bacterial loads (≥0.3 CFU/ml blood) of clinical specimens despite using half the volume of blood. The findings warrant its further study in endemic populations with a potential use as a novel diagnostic which fills the present gap of paratyphoid diagnostics.     

Estimating the Burden of Paratyphoid A in Asia and Africa

Despite the increasing availability of typhoid vaccine in many regions, global estimates of mortality attributable to enteric fever appear stable. While both Salmonella enterica serovar Typhi (S. Typhi) and serovar Paratyphi (S. Paratyphi) cause enteric fever, limited data exist estimating the burden of S. Paratyphi, particularly in Asia and Africa.We performed a systematic review of both English and Chinese-language databases to estimate the regional burden of paratyphoid within Africa and Asia. Distinct from previous reviews of the topic, we have presented two separate measures of burden; both incidence and proportion of enteric fever attributable to paratyphoid. Included articles reported laboratory-confirmed Salmonella serovar classification, provided clear methods on sampling strategy, defined the age range of participants, and specified the time period of the study.A total of 64 full-text articles satisfied inclusion criteria and were included in the qualitative synthesis. Paratyphoid A was commonly identified as a cause of enteric fever throughout Asia. The highest incidence estimates in Asia came from China; four studies estimated incidence rates of over 150 cases/100,000 person-years. Paratyphoid A burden estimates from Africa were extremely limited and with the exception of Nigeria, few population or hospital-based studies from Africa reported significant Paratyphoid A burden.While significant gaps exist in the existing population-level estimates of paratyphoid burden in Asia and Africa, available data suggest that paratyphoid A is a significant cause of enteric fever in Asia. The high variability in documented incidence and proportion estimates of paratyphoid suggest considerable geospatial variability in the burden of paratyphoid fever. Additional efforts to monitor enteric fever at the population level will be necessary in order to accurately quantify the public health threat posed by S. Paratyphi A, and to improve the prevention and treatment of enteric fever.     

The Application of the Grey Disaster Model to Forecast Epidemic Peaks of Typhoid and Paratyphoid Fever in China

Objective

The objectives of this study were to forecast epidemic peaks of typhoid and paratyphoid fever in China using the grey disaster model, to evaluate its feasibility of predicting the epidemic tendency of notifiable diseases.

Methods

According to epidemiological features, the GM(1,1) model and DGM model were used to build the grey disaster model based on the incidence data of typhoid and paratyphoid fever collected from the China Health Statistical Yearbook. Model fitting accuracy test was used to evaluate the performance of these two models. Then, the next catastrophe date was predicted by the better model.

Results

The simulation results showed that DGM model was better than GM(1,1) model in our data set. Using the DGM model, we predicted the next epidemic peak time will occur between 2023 to 2025.

Conclusion

The grey disaster model can predict the typhoid and paratyphoid fever epidemic time precisely, which may provide valuable information for disease prevention and control.     

Combined rapid (TUBEX) test for typhoid-paratyphoid A fever based on strong anti-O12 response: design and critical assessment of sensitivity

Rapid diagnostics can be accurate but, often, those based on antibody detection for infectious diseases are unwittingly underrated for various reasons. Herein, we described the development of a combined rapid test for two clinically-indistinguishable bacterial diseases, typhoid and paratyphoid A fever, the latter fast emerging as a global threat. By using monoclonal antibodies (mAbs) to bacterial antigens of known chemical structures as probes, we were able to dissect the antibody response in patients at the level of monosaccharides. Thus, a mAb specific for a common lipopolysaccharide antigen (O12) found in both the causative organisms was employed to semi-quantify the amounts of anti-O12 antibodies present in both types of patients in an epitope-inhibition particle-based (TUBEX) immunoassay. This colorimetric assay detected not only anti-O12 antibodies that were abundantly produced, but also, by steric hindrance, antibodies to an adjoining epitope (O9 or O2 in the typhoid or paratyphoid bacillus, respectively). Sensitivity and, particularly, reaction intensities, were significantly better than those obtained using an anti-O9 or anti-O2 mAb-probe in the examination of paired sera from 22 culture-confirmed typhoid patients (sensitivity, 81.8% vs 75.0%) or single sera from 36 culture-confirmed paratyphoid patients (52.8% vs 28.6), respectively. Importantly, sensitivity was better (97.1% for typhoid, 75.0% for paratyphoid) if allowance was made for the absence of relevant antibodies in certain specimens as determined by an independent, objective assay (ELISA)--such specimens might have been storage-denatured (especially the older paratyphoid samples) or procured from non-responders. Benchmarking against ELISA, which revealed high concordance between the two tests, was useful and more appropriate than comparing with culture methods as traditionally done, since antibody tests and culture target slightly different stages of these diseases. Paired sera analysis was insightful, revealing 64% of typhoid patients who had no change in antibody titer over 4-16 days, and 14% with no IgM-IgG class-switching.     

18例新生儿李斯特菌病的母婴临床分析

本文旨在通过探讨新生儿李斯特菌病的临床特点、治疗及预后,明确母体危险因素,为新生儿产单核细胞李斯特菌(下称李斯特菌)感染的临床诊断和治疗提供依据。回顾性分析2011年5月-2018年4月西北妇女儿童医院新生儿科诊治的18例李斯特菌感染新生儿及其母亲的发病情况、临床表现、实验室指标、影像学检查、治疗及预后,发现18例产妇中15例有临床症状,以发热及不规则腹痛最为常见;患儿中13例有临床症状,多数表现为呼吸窘迫和发热;89%患儿发生血流感染(61%为化脓性脑膜炎、28%为肺炎);影像学检查提示,存活患儿中56%有神经系统后遗症,50%可能有先天性心脏病。14例在明确李斯特菌感染后调整抗生素治疗,所有产妇经治疗均预后良好;患儿除1例放弃治疗、3例要求出院外,其余14例均痊愈或好转出院。新生儿李斯特菌感染是一种严重的感染性疾病,因此对有发热、腹痛及早产症状的孕妇,应警惕李斯特菌感染,尽早进行病原学检测和目标性治疗,以改善预后。     

A Large-Scale Community-Based Outbreak of Paratyphoid Fever Caused by Hospital-Derived Transmission in Southern China

Background

Since the 1990s, paratyphoid fever caused by Salmonella Paratyphi A has emerged in Southeast Asia and China. In 2010, a large-scale outbreak involving 601 cases of paratyphoid fever occurred in the whole of Yuanjiang county in China. Epidemiological and laboratory investigations were conducted to determine the etiology, source and transmission factors of the outbreak.

Methodology/Principal Findings

A case-control study was performed to identify the risk factors for this paratyphoid outbreak. Cases were identified as patients with blood culture–confirmed S. Paratyphi A infection. Controls were healthy persons without fever within the past month and matched to cases by age, gender and geography. Pulsed-field gel electrophoresis and whole-genome sequencing of the S. Paratyphi A strains isolated from patients and environmental sources were performed to facilitate transmission analysis and source tracking. We found that farmers and young adults were the populations mainly affected in this outbreak, and the consumption of raw vegetables was the main risk factor associated with paratyphoid fever. Molecular subtyping and genome sequencing of S. Paratyphi A isolates recovered from improperly disinfected hospital wastewater showed indistinguishable patterns matching most of the isolates from the cases. An investigation showed that hospital wastewater mixed with surface water was used for crop irrigation, promoting a cycle of contamination. After prohibition of the planting of vegetables in contaminated fields and the thorough disinfection of hospital wastewater, the outbreak subsided. Further analysis of the isolates indicated that the origin of the outbreak was most likely from patients outside Yuanjiang county.

Conclusions

This outbreak is an example of the combined effect of social behaviors, prevailing ecological conditions and improper disinfection of hospital wastewater on facilitating a sustained epidemic of paratyphoid fever. This study underscores the critical need for strict treatment measures of hospital wastewater and the maintenance of independent agricultural irrigation systems in rural areas.     

全球伤寒和副伤寒的流行强度区域及其预防策略

伤寒和副伤寒流行强度与区域人口数、发病率、病死率、高危人群、污水系统及卫生设施、地表水系及环境污染、健康教育与人群习惯的关系密切。美国疾病预防控制中心提出、世界卫生组织报道、国际学者引用的流行区域划分法是根据伤寒和副伤寒每年发病率的高、中、低水平来划分的,该划分法不能真实反映100万、100~1 000万、1 000万人口数的伤寒和副伤寒高、中、低流行强度和相应区域。本研究对全球伤寒和副伤寒流行强度区域文献作一综述,分析伤寒和副伤寒流行强度、流行强度区域及其指标体系,为查明相应流行强度区域危险因素、进行风险评估和制定防控策略提供科学依据。     

Pan-Genomic Analysis Provides Insights into the Genomic Variation and Evolution of Salmonella Paratyphi A

Salmonella Paratyphi A (S. Paratyphi A) is a highly adapted, human-specific pathogen that causes paratyphoid fever. Cases of paratyphoid fever have recently been increasing, and the disease is becoming a major public health concern, especially in Eastern and Southern Asia. To investigate the genomic variation and evolution of S. Paratyphi A, a pan-genomic analysis was performed on five newly sequenced S. Paratyphi A strains and two other reference strains. A whole genome comparison revealed that the seven genomes are collinear and that their organization is highly conserved. The high rate of substitutions in part of the core genome indicates that there are frequent homologous recombination events. Based on the changes in the pan-genome size and cluster number (both in the core functional genes and core pseudogenes), it can be inferred that the sharply increasing number of pseudogene clusters may have strong correlation with the inactivation of functional genes, and indicates that the S. Paratyphi A genome is being degraded.     

Genetic Diversity of <Emphasis Type="Italic">Salmonella enteric</Emphasis> serovar Typhi and Paratyphi in Shenzhen,China from 2002 through 2007

Background  

Typhoid and paratyphoid fever are endemic in China. The objective of this investigation was to determine the molecular features of nalidixic acid-resistant Salmonella enteric serovar Typhi (S. typhi) and Paratyphi (S. paratyphi) from blood isolates in Shenzhen, China.