Epidemiology and Clinical Features of Mycobacterium avium Complex Pulmonary Disease in a Brazilian Amazon Cohort

The incidence of Mycobacterium avium complex pulmonary disease (MACPD) has been globally increasing. The present study aims to provide a comprehensive analysis of clinical characteristics and treatment response among patients in the Amazon region of Brazil and conduct a retrospective cohort study at a prominent referral hospital in the State of Par, Brazil, from 2012 to 2020. The M. avium group represented 58.9% of cases, followed by M. intracellulare (35.7%), M. colombiense (3.6%), and M. chimaera (1.8%). The majority of patients (73.2%) were female and with an average age of 63 years. Primary clinical manifestations included persistent cough and sputum production. The Charlson comorbidity index (CCI) averaged 2.47, with 36.3% of patients having a CCI score equal to higher than 3. Notably, over 70% of patients had received treatment for pulmonary tuberculosis before initiating treatment for MAC infection. The fibrocavitary radiologic form was the most prevalent (55.4%), frequently exhibiting a bilateral distribution (53.6%). Antimicrobial susceptibility revealed a significant prevalence of MAC resistance to drugs in the therapeutic regimen. Despite this, most of the patients experienced clinical improvement (50%). In conclusion, this study highlights a higher prevalence of MAC infections among middle-aged women, with a history of pulmonary tuberculosis treatment and presenting the fibrocavitary radiological form was predominant.

Molecular isolation and identification of Mycobacterium avium subsp.hominissuis in Didelphis virginiana from Hidalgo,Mexico

Objective:To isolate and identify the exact species of the genus Mycobacterium from Didelphis(D.)virginiana,and the direct implications of this bacterium to public health and veterinary medicine.Methods:Thirty-one D.virginiana were captured and necropsied in Hidalgo,Mexico.Tissue samples were collected to culture mycobacteria present and examine individual specimens’histopathology.Mycobacterium identification was obtained through the application of amplification and sequencing of 16S rDNA techniques.Results:Three strains were isolated and identified as Mycobacterium(M.)avium subsp.hominissuis by utilizing M.avium complexspecific primers.Granulomatous lesions were observed in the subpleural zone(granuloma gradeⅡ)and bronchial(granuloma gradeⅠ)of the lungs of D.virginiana with positive isolation.Conclusions:Three strains of M.avium subsp.hominissuis,from lung tissue samples of D.virginiana were identified.This subspecies of M.avium has important implications in public health and veterinary medicine.

Mycobacterium avium subspecies paratuberculosis and its relationship with Crohn's disease

The hypothesis postulating that Mycobacterium avium paratuberculosis(MAP) is the cause of Crohn's disease(CD) has been circulating for many years.Advances in molecular techniques,such as polymerase chain reaction and culture methods,have enabled researchers to demonstrate that there is an association between MAP and CD.Recently,genome-wide association studies have identified novel susceptibility genes for CD,which are critical for generation of an adaptive immune response that is protective against intracellular pathogens,including M.tuberculosis infection.However,the role of MAP as a cause of CD suffered a setback with the report that administration of antimycobacterial therapy failed to lead to a sustained response in CD patients.Accordingly,this review sought neither to confirm nor refute this,but instead to survey recent literature on the role of MAP in CD.

Relationship between Crohn’s disease, infection with Mycobacterium avium subspecies paratuberculosis and SLC11A1 gene polymorphisms in Sardinian patients

AIM： To study the association between Crohn＇s disease （CD）, Mycobacterium avium subspecies paratubercuolsis （MAP）, and genetic factors by examining the role of natural resistance-associated macrophage protein 1 （NRAMP1） gene polymorphisms （now SLCllA1） in Sardinian patients with CD and controls. METHODS： Thirty-seven CD patients and 34 controls with no inflammatory bowel disease （IBD） were recruited at the University of Sassari after giving written consent. Six SCL11A1 polymorphisms previously reported to be the most significantly associated with IBD were searched. M, pafatubefculosis was identified by IS900 PCR and sequencing. Logistic regression was used to calculate odds ratios （OR） for the associations among CD, presence of MAP, and 6 loci described above.＇ RESULTS： For the first time, a strong association was observed between polymorphisms at NRAMP1 locus 823C/T and CD. While CD was strongly associated with both NRAMP1 and MAP, NRAMP1 polymorphisms and MAP themselves were not correlated. CONCLUSION： Combined with previous work on the NOD2/CARD15 gene, it is clear that the interplay of genetic, infectious, and immunologic factors in the etiology of CD is complex.

Mycobacterium avium subspecies paratuberculosis infects and multiplies in enteric glial cells

AIM: To establish the role of enteric glial cells during infection with Mycobacterium avium subspecies paratuberculosis (MAP) in Crohn's disease. METHODS: In order to establish the role of enteric glial cells during infection with M. avium subspecies paratuberculosis (MAP) in Crohn's disease, Map adhesion experiments on enteric glial cells were performed as well as expression analysis of Map sigma factors during infection. RESULTS: In this study, for the first time, we found a high affinity of MAP to enteric glial cells and we analyzed the expression of MAP sigma factors under different conditions of growth. CONCLUSION: The fact that Map showed a high affinity to the glial cells raises concerns about the complicated etiology of the Crohn's disease. Elucidation of the mechanisms whereby inflammation alters enteric neural control of gut functions may lead to novel treatments for Crohn's disease.

Mycobacterium avium subspecies paratuberculosis in the etiology of Crohn's disease, cause or epiphenomenon?

The origin of inflammatory bowel disease is unknown. Attempts have been made to isolate a microorganism that could explain the onset of inflammation, but no pathological agent has ever been identified. Johne’s disease is a granulomatous chronic enteritis of cattle and sheep caused by Mycobacterium avium subspecies paratuberculosis (MAP) and shows some analogies with Crohn’s disease (CD). Several studies have tried to clarify if MAP has a role in the etiology of CD. The present article provides an overview of the evidence in favor and against the “MAP-hypothesis”, analyzing the methods commonly adopted to detect MAP and the role of antimycobacterial therapy in patients with inflammatory bowel disease. Studies were identified through the electronic database, MEDLINE, and were selected based on their relevance to the objective of the review. The presence of MAP was investigated using multiple diagnostic methods for MAP detection and in different tissue samples from patients affected by CD or ulcerative colitis and in healthy controls. On the basis of their studies, several authors support a close relationship between MAP and CD. Although increasing evidence of MAP detection in CD patients is unquestionable, a clear etiological link still needs to be proven.

High prevalence of viable Mycobacterium avium subspecies paratuberculosis in Crohn's disease

AIM:To examine the detection rate of viable Mycobacterium avium subspecies paratuberculosis(MAP) in patients with inflammatory bowel disease [Crohn's disease(CD) and ulcerative colitis(UC)].METHODS:Thirty patients with CD(15 with at least one NOD2/CARD15 mutation),29 with UC,and 10 with no inflammatory bowel disease(IBD).were tested for MAP by polymerase chain reaction(specific IS900 fragment) and blood culture.RESULTS:MAP DNA was detected in all original blood samples and 8-wk blood cultures(CD,UC and non-IBD).Positive MAP DNA status was confirmed by dot blot assays.All 69 cultures were negative by acid-fast Ziehl-Neelsen staining.Viable MAP,in spheroplast form,was isolated from the 18-mo blood cultures of all 30 CD patients,one UC patient,and none of the non-IBD controls.No association was found between positive MAP cultures and use of immunosuppressive drugs or CDassociated single nucleotide polymorphisms.CONCLUSION:MAP is widely present in our area and MAP DNA can be recovered from the blood of CD,UC and non-IBD patients.However,MAP spheroplasts were only found in CD patients.

On deaf ears, Mycobacterium avium paratuberculosis in pathogenesis Crohn's and other diseases

The historic suggestion that Mycobacterium avium subsp. paratuberculosis(Map) might be a zoonotic pathogen was based on the apparent similarity of lesions in the intestine of patients with Crohn's disease(CD) with those present in cattle infected with Map, the etiological agent of Johne's disease. Reluctance to fully explore this possibility has been attributed to the difficulty in demonstrating the presence of Map in tissues from patients with CD. Advances in technology have resolved this problem and revealed the presence of Map in a significant proportion of patients with CD and other diseases. The seminal finding from recent investigations, however, is the detection of Map in healthy individuals with no clinical signs of disease. The latter observation indicates all humans are susceptible to infection with Map and lends support to the thesis that Map is zoonotic, with a latent stage of infection similar to tuberculosis, where infection leads to the development of an immune response that controls but does not eliminate the pathogen. This clarifies one of the reasons why it has been so difficult to document that Map is zoonotic and associated with the pathogenesis of CD and other diseases. As discussed in the present review, a better understanding of the immune response to Map is needed to determine how infection is usually kept under immune control during the latent stage of infection and elucidate the triggering events that lead to disease progression in the natural host and pathogenesis of CD and immune related diseases in humans.

The relative frequency of Mycobacterium tuberculosis and Mycobacterium avium infections in HIV positive patients,Ahvaz,Iran

Objective:To estimate the prevalence of Mycobacterium tuberculosis(M.tuberculosis) and Mycobacterium avium(M.avium) infections in HIV -positive patients suspected to have puimonar) and extrapulmonary mycobacterial co-infection using PCR technique.Methods: Totally 50 samples comprising sputum,pleural fluid and CSF taken from HIV positive patients suspected to have mycobacterial infection,were processed.The demographic information and results of acid fast staining and culture were recorded for each patient.The PCR for detecting of M.tuberculosis comprised of specific primers targeting IS6110 gene sequence.For detecting of M.avium,PCR with primers that amplifies the mig gene were used.Results:From 50 samples processed,45 were sputum(90%),3 pleural fluid(6%) and 2 CSK(4%).In total.8(16%) were culture positive,7 had positive acid fast staining 114%) and 13 samples(26%)were positive using PCR technique.All the positive samples were sputum and belonged to patients with pulmonary infection.01 these.9 were positive for M.tuberculosis(69.2%) and 4 were identified as 1/.avium (30.8%).which 2 out of 13 positive samples showed mixed infections by both mycobacteria. Conclusions:The PCR shows the highest detection rate(26%) of mycobacteria compared with culture and acid last staining.The majority of infections were with M.tuberculosis(18%) and this shows the importance of this mycobacterial co-infection in HIV positive patients in the region of study.

Mycobacterium avium subspecies paratuberculosis in the causation of Crohn's disease

Mycobacterium avium subspecies paratuberculosis(MAP),originally called Johne’s bacillus was firstdescribed from Germany in 1895 as the cause of achronic inflammatory disease of the intestine in acow.As the 20th century progressed,clinical andsub-clinical MAP infection in farm animals inWestern Europe appeared to become moreprevalent.Among the early reviews available

Pulmonary <i>Mycobacterium avium </i>Complex Disease Requiring Differentiation from Recurrence of Lung Cancer during the Follow-Up Period for Lung Cancer

Case 1 was a 49-year-old woman who visited with a dry cough. She had an underlying disease of lung adenocarcinoma and received cancer immunotherapy because of an ALK-positive response and several cancer chemotherapies. The clinical effect was a complete response. Chest CT was performed because of continuous dry cough, and a new tumor shadow was recognized in the lingula portion of the left upper lobe. We performed CT-guided lung biopsy and could aspirate pus-fluid. The culture test for acid-fast bacilli was positive and the causative microorganism was identified as Mycobacterium avium by the DDH method. The final diagnosis was pulmonary abscess due to M. avium. Treatment using combined chemotherapy including CAM was performed and a good clinical response was obtained. Case 2 was a 67-year-old man who had a past history of surgical resection of lung adenocarcinoma eight and two years ago and received several cancer chemotherapies and radiation therapy. Because a new nodular shadow appeared in the right middle lobe one year ago and showed strong positivity on PET/CT, surgical resection was performed with the suspected recurrence of lung cancer. Subsequently, the histological diagnosis was epithelioid granuloma and a culture test of acid-fast bacilli was positive, with the identification of Mycobacterium intracellulare by the DDH method. Combined chemotherapy was not performed because the lesion was completely resected. Afterwards, a new nodular shadow appeared in the left lower lobe again and bronchoscopy was performed. Because M. intracellulare was isolated from the local specimen, we diagnosed the patient with recurrence of pulmonary MAC disease and combined chemotherapy including CAM was performed for one year. Finally, the nodular lesion disappeared. It is difficult to differentiate pulmonary MAC disease from lung cancer. Therefore, careful follow-up of patients with lung cancer while keeping in mind the possible complication of pulmonary MAC disease is necessary.

Mycobacterium avium Paratuberculosis (MAP) and Cytomegalovirus (CMV) Are Frequently Detected in the Saliva of Patients Recently Diagnosed with Crohn Disease (CD) Whereas Oral Propionibacterium Acnes (PA) or Methylacetate (MA) in Their Breath Is Rare

We investigated the presence of MAP, CMV, or Epstein-Barr virus (EBV) in the saliva of patients presenting with periodontal disease, gingivitis or oral aphthosis. We also measured methylacetate in their breath and looked for the presence of PA on their tongue. All patients were prospectively enrolled into a two-year cohort study. We compared the group presenting with CD versus the group without CD. 167 patients were enrolled. 24 patients presented with CD. CMV and MAP were found concomitantly in 67% of CD patients (17 patients) whereas only 1 patient (<0.1%;p < 0.001) has these infectious agents in the comparative group. PA was rare in CD (25% versus 70.6%;p < 0.001). MA was low, especially with an empty stomach (0.59 ppm +/? 1.45 versus 5.14 ppm +/? 8.97;p < 0.001). It was concluded that the association MAP + CMV was frequently found in oral lesions of CD at an early stage. Detection of PA, MAP and CMV, as well as breath test could be easily performed and may participate to the early diagnosis of CD.

Concurrent pulmonary Mycobacterium avium complex (MAC) infection and active Hürthle cell thyroid carcinoma: is there a connection?

We present two cases of pulmonary MAC infection in women with Hürthle cell thyroid carcinoma. Both cases were asymptomatic octogenarian women with active Hürthle cell thyroid carcinoma and prolonged periods of hypothyroidism prior to diagnosis of pulmonary MAC. Mycobacterium avium complex has never been reported in association with any type of thyroid cancer, specifically Hürthle cell carcinoma. A review of the literature and possible associations between the two are discussed in this article.

The 19 kDa Protein from <i>Mycobacterium avium subspecies paratuberculosis</i>Is a Glycolipoprotein

This study characterizes the 19 kDa protein expressed by Mycobacterium avium subspecies paratuberculosis (MAP) as a glycolipoprotein, providing the foundation for future experiments regarding its antigenicity and role in disease pathogenicity. We have previously shown that a 4.8 kb insert from MAP will produce a 16 kDa recombinant protein when expressed in Escherichia coli and 19 kDa recombinant protein when expressed in M. smegmatis (smeg19K). The difference of 3 kDa in size of these expressed proteins may be related to post translational modifications that occur in Mycobacterium species. We hypothesized that smeg19K is a glycolipoprotein since BLAST analysis revealed approximately 76% amino acid identity between the MAP 19 kDa protein and a known lipoglycoprotein, the 19 kDa protein of M. tuberculosis. This prediction was confirmed by the following positive staining of smeg19K with Sudan Black 4B, a postelectrophoresis dye used to stain for lipids. Smeg19K has also stained positively for glycosylation with the lectin concavalin A, a highly specific stain for mannose residues. As expected, treatment with tunicamycin (an antibiotic known to inhibit N-glycosylation) and treatment with deglycosylation assay (non-specific for mannose), showed no reduction in size of 19 kDa glycolipoprotein.

牛副结核病的病原学和防控研究进展

牛副结核病是一种由副结核分枝杆菌引起的主要影响反刍动物的慢性消耗性疾病,也是一种潜在的人兽共患病。该病可导致腹泻、渐进性消瘦,甚至死亡,增加生产成本,是影响全球奶牛业最严重的传染病之一。牛副结核病难以诊断,病原分离周期长,我国相关研究报道较少且存在误区。因为潜伏期长,患病动物在感染早期体液免疫水平低,排菌量低,导致细菌分离培养和抗体检测都很难做出诊断;即使最灵敏的实时荧光定量聚合酶链式反应(qPCR)检测方法也只能在部分感染动物的粪便样品中检出副结核分枝杆菌;皮肤变态反应试验和γ干扰素释放试验等方法易受其他结核分枝杆菌的影响,也难以普及。本文旨在提炼性的阐述牛副结核病的病原学研究进展,总结其流行病学和防控策略等信息,以期为该病的预防和控制工作提供参考。

肾脏移植受者非结核分枝杆菌病临床诊疗指南

近年来,非结核分枝杆菌(NTM)感染呈快速增多趋势,受到广泛关注。肾脏移植受者由于免疫抑制药物等因素的影响,其NTM的感染率升高更为明显,但是由于缺乏充分的研究基础,肾脏移植术后NTM的诊治缺乏规范指引。为进一步规范我国肾脏移植受者NTM病的诊断和治疗,提高我国器官移植领域医务工作者对NTM病的认识和诊治水平,中华医学会器官移植分会组织相关专家,参考美国胸科协会及欧洲呼吸协会发布的最新版《非结核分枝杆菌病治疗指南》,我国《非结核分枝杆菌病诊断与治疗专家共识》《器官移植受者非结核分枝杆菌病临床诊疗技术规范(2019版)》等,结合肾脏移植受者的特点,进行指南制订。

空洞是鸟分枝杆菌感染患者治疗失败的危险因素

目的探讨单一感染鸟分枝杆菌患者治疗失败的危险因素。方法选取上海市肺科医院2016年1月-2020年12月符合非结核分枝杆菌病诊断与治疗指南的鸟分枝杆菌感染患者,采用Logistic回归模型分析其治疗失败的危险因素。结果53例纳入研究的鸟分枝杆菌感染患者有26例(49%)治疗失败,治疗失败组有更高比例的发热、贫血和肺部空洞患者,中性粒细胞数和直接胆红素显著升高、前白蛋白显著降低。多因素Logistic回归分析证明空洞是鸟分枝杆菌感染患者治疗失败的独立危险因素,Kaplan-Meier分析显示空洞患者12个月累积治愈率显著降低。结论鸟分枝杆菌感染患者治疗失败率较高,研究发现空洞是鸟分枝杆菌感染患者治疗失败的危险因素。提示临床医生应重视合并空洞的鸟分枝杆菌感染患者的监测和治疗,以提高患者治愈率。

基于CT特征和机器学习的鸟-胞内分枝杆菌复合群肺病和初治肺结核鉴别诊断模型的构建与验证

目的基于胸部CT特征和机器学习构建并验证鸟-胞内分枝杆菌复合群肺病与肺结核的鉴别诊断模型。资料与方法回顾性收集2021年5月—2022年8月于首都医科大学附属北京市胸科医院确诊为鸟-胞内分枝杆菌复合群肺病及肺结核患者作为训练集,并前瞻性收集2022年9月—2023年5月河南中医药大学第一附属医院患者作为外部验证集。分析患者临床资料及影像学征象,分别采用逻辑回归、随机森林和支持向量机方法建立模型,并在验证集中进行外部验证。使用受试者工作特征曲线和精确率-召回率曲线评估模型的诊断效能,比较各模型曲线下面积的差异。结果两组患者年龄和咯血率差异有统计学意义(t=30.414,P<0.001;χ^(2)=6.186,P=0.013)。两组空洞类型和形态差异有统计学意义(χ^(2)=6.546,P=0.011;χ^(2)=24.113,P<0.001),空洞病灶分布和特征差异无统计学意义(P>0.05)。两组支气管扩张类型和分布差异有统计学意义(χ^(2)=4.634,P=0.031;χ^(2)=23.113,P<0.001)。3种机器学习模型中,支持向量机模型较逻辑回归、随机森林模型的鉴别诊断效能更好,训练集和验证集中,受试者工作特征曲线下面积、敏感度、特异度、准确度、阳性预测值和阴性预测值分别为0.960、0.857、0.936、0.905、0.933、0.880和0.885、0.767、0.800、0.783、0.793、0.774。精确率-召回率曲线显示支持向量机模型的精确率高且召回率低,即模型的性能良好。结论基于临床特征和CT征象构建的机器学习模型具有较高的诊断效能,有助于提高鸟-胞内分枝杆菌复合群肺病和肺结核的鉴别诊断。

副结核分枝杆菌免疫原蛋白的筛选及免疫保护效果评价

【背景】副结核病(paratuberculosis,PTB)是由副结核分枝杆菌(Mycobacterium avium subsp.paratuberculosis,MAP)主要引起反刍动物的一种慢性消耗性传染病。患病动物表现为肉芽肿性肠炎和肠道的功能失调、顽固性腹泻、渐进性消瘦、营养不良、贫血、嗜睡甚至死亡。PTB给畜牧业造成巨大的经济损失,并且严重威胁公共卫生安全。由于目前临床上对于PTB的检测和控制手段不够完善,现有的PTB疫苗保护效果不佳,并且干扰牛结核病的诊断,因此亟需研发免疫原性强、保护效果佳的疫苗以用于PTB的防控。【目的】通过筛选MAP免疫原蛋白,并对其免疫保护效果进行评价,为PTB的防控提供数据支持。【方法】根据MAP的p22、map1272c、map3531c、map3783、map3701c以及map3527这6个基因,分别构建5种重组质粒,在获得5种重组蛋白基础上,联合MONTANIDE ISA 61 VG佐剂皮下多点注射免疫小鼠,通过IFN-γELISPOT试验筛选出最佳免疫原;随后将最佳免疫原和已报道的66NC融合蛋白混合,经皮下多点注射免疫小鼠,在二免3周后用1×10^(8)CFU的MAP K-10菌株腹腔感染小鼠。通过IFN-γELISPOT试验,抗体监测和细胞因子检测,分析感染后小鼠的体重、肝脏病理学和组织病理学变化及其荷菌数差异,综合评价候选亚单位疫苗的免疫原性和免疫保护效果。【结果】以MAP p22、map1272c、map3531c、map3783以及map3701c为基础成功构建和表达了5种融合蛋白58F、62F、69F、46F和52F,其中免疫58F后产生的IFN-γ水平最高,是更具潜力的候选免疫原,且以融合蛋白组合66NC+58F诱导持久高滴度的IgG、IgM、IgG1和IgG2a水平,诱导特异性的IFN-γ、TNF-α和IL-17A的释放;在保护效果评价中,融合蛋白组合66NC+58F抵抗MAP感染造成的体重下降,显著减轻肝脏的病理损伤,降低MAP在肝脏中的定植。【结论】融合蛋白组合66NC+58F诱导小鼠产生Th1和Th17型免疫反应,对MAP感染有着一定免疫保护作用,是PTB重要的候选亚单位疫苗。

牛源副结核分枝杆菌MAP3732c基因的原核表达与多克隆抗体的制备

为表达副结核分枝杆菌MAP3732c蛋白,研究构建原核表达质粒pET28a-MAP3732c,诱导表达鉴定后采用His标签亲和层析纯化获得MAP3732c重组蛋白,多次免疫Balb/c小鼠制备多克隆抗体,采用间接ELISA方法检测其抗体效价。结果表明,成功构建克隆重组质粒T1-MAP3732c与表达重组质粒p ET28a-MAP3732c;在IPTG终浓度为0.5 mmol·L^(-1)、37℃条件下成功诱导MAP3732c重组蛋白表达;SDS-PAGE结果表明,MAP3732c重组蛋白大小约为28 ku,且以包涵体形式存在;Western blot鉴定结果显示,重组蛋白与His抗体和牛源副结核病阳性血清均有良好免疫反应、阴性血清无非特异性结合;ELISA方法检测结果显示,抗MAP3732c多克隆抗体效价为1:204800。研究为副结核分枝杆菌MAP3732c蛋白免疫原性分析及副结核病检测方法建立提供理论参考。