Imaging of Non-tuberculous (Atypical) Mycobacterial Pulmonary Infection

Pulmonary infections due to mycobacterial organisms are increasing in incidence. Non-tuberculous (atypical) mycobacteria (NTM) represent a significant proportion of mycobacterial infections and may prove difficult to diagnose due to their non-specific clinical and radiographic presentations. An increasing volume of radiological data is now available for the more common non-tuberculous mycobacterial infections, and we have summarized the imaging features found in such cases, identifying radiographic features that would favour the diagnosis of a non-tuberculous mycobacterium and that, in some cases, suggest a specific organism.     

Molecular diagnosis of a Mycobacterium chelonae infection

A 23-year-old female presented with enlarged cervical lymph nodes, and a diagnosis of nonspecific lymphadenitis with formation of pyogranulomas was rendered. Despite an initial oral antibiosis and subsequent long-term intravenous and oral antibiosis under hospitalized conditions, the symptoms progressed. The lymph nodes became larger and then affected the cervical region bilaterally. Her general condition worsened, and an exanthema of the extremities accompanied by a reactive arthritis occurred. Serological assays of various viral and bacterial markers and blood cultures were negative. Application of a polymerase chain reaction (PCR) protocol allowing specific amplification of mycobacterial DNA revealed DNA of Mycobacterium chelonea in formalin-fixed, paraffin-embedded lymph node tissue. Sequencing of the PCR product showed a 97% homology with the known Mycobacterium chelonae sequence. Modification of the antibiotic therapy with clarithromycin, imipenem and amikacin resulted in a rapid regression of the symptoms. The clinical course, in combination with the difficulties in detecting the infectious agent, supports the usefulness of molecular pathological analyses specific for nontuberculous mycobacteria (NTM).     

T cell regulation of the chronic peritoneal neutrophilia during mycobacterial infections.

Intraperitoneal infection of mice with mycobacteria induces the persistent mobilization of neutrophils to the infected peritoneal cavities. The recruitment of the neutrophils was mediated by the immune system since it was enhanced by immunization and reduced in T cell-deficient nude and SCID mice. Anti-mitotic treatments with cyclophosphamide or X-rays led to a reduction in the number of mononuclear cells in the peritoneal cavity of infected mice, followed by a reduction in neutrophil numbers despite the presence of a normal circulating pool of neutrophils. The depletion of T cells with antibodies during mycobacterial i.p. infection led to a reduction in the number of neutrophils. Such a reduction was more extensive if the antibodies were administered early. Our data suggest that T cells are partially involved in the direct recruitment of neutrophils during chronic mycobacteriosis but they also play a role in the priming of other cell types for the mobilization of these phagocytes.     

Antibodies to mycobacterial 65-kD heat shock protein cross-react with the main mitochondrial antigens in patients with primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease associated with autoimmune disorders. The aetiology is unknown, although it has been suggested that the disease may be related to infectious agents. Previous studies revealed that sera from patients with PBC react against Mycobacterium gordonae . This specific reactivity, characterized by a recognition of two membrane polypeptides of 70–65 and 55 kD, cross-react with the two major mitochondrial autoantigens of PBC. As the most immunogenic components of mycobacteria are the heat shock proteins (hsp), which have been associated with autoimmunity, this study has been undertaken to characterize whether the reacting polypeptides in PBC are hsp from M. gordonae . Cultures of M. gordonae were incubated at 37 °C and 46 °C before sonication, protein extraction and separation by SDS-PAGE. Exposure of M. gordonae to heat shock treatment resulted in membrane protein overexpression, similar to the 70–65-kD polypeptide recognized by the sera from patients with PBC. Immunoprecipitation assays with a monoclonal antibody directed against the Hsp65 kD of mycobacteria and with sera from patients with PBC revealed similar reacting profiles characterized by the precipitation of the overexpressed 65-kD polypeptide from M. gordonae . Competitive immunoblotting showed that binding of the monoclonal antibody to the Hsp65 kD protein was prevented by preincubation with sera from patients with PBC, but not with sera from healthy subjects. Furthermore, monoclonal antibody to the Hsp65 kD protein recognized the main mitochondrial autoantigens of PBC (PDH-E2 and BCKDH-E2). These data indicate the existence of cross-reacting epitopes contained on M. gordonae Hsp65 kD and the main mitochondrial antigens in patients with PBC.     

Mycobacterium abscessus wound infection

We report an isolated case of wound infection due to Mycobacterium abscessus following minor cutaneous surgery. The patient had routine skin cancer surgery in a private dermatology practice setting. He presented 2 weeks later with a wound infection which failed to respond to cephalexin. The patient reported that he had walked through salt water and bushes with exposed surgical wounds 1 week postoperatively. Tissue cultures later grew M. abscessus. The patient was successfully treated with oral clarithromycin 500 mg qid of 6 months duration.     

Comparative genomics of the mycobacteria

The genus mycobacteria includes two important human pathogens Mycobacterium tuberculosis and Mycobacterium lepra. The former is reputed to have the highest annual global mortality of all pathogens. Their slow growth, virulence for humans and particular physiology makes these organisms extremely difficult to work with. However the rapid development of mycobacterial genomics following the completion of the Mycobacterium tuberculosis genome sequence provides the basis for a powerful new approach for the understanding of these organisms. Five further genome sequencing projects of closely related mycobacterial species with differing host range, virulence for humans and physiology are underway. A comparative genomic analysis of these species has the potential to define the genetic basis of these phenotypes which will be invaluable for the development of urgently needed new vaccines and drugs. This minireview summarises the different techniques that have been employed to compare these genomes and gives an overview of the wealth of data that has already been generated by mycobacterial comparative genomics.     

Non-tuberculous mycobacteriosis of the liver responsive to empiric therapy

This case demonstrates that clinical and pathological suspicion of NTM could be sufficient to start an empiric treatment even when microbiological isolation is unavailable. Moreover, disseminated mycobacteriosis may underlie an occult aggressive neoplasm.     

广州地区非结核分枝杆菌肺病微生物及临床特征分析

目的分析广州地区不同非结核分枝杆菌(NTM)与其所致肺病的临床特征。 方法选择2016年1月至2020年12月广州地区的112例NTM肺病患者,分析NTM患者的症状、影像学特征及易感因素。 结果112例NTM肺病患者中,男性年龄>50岁占78.7%(48/61),女性年龄>50岁占84.3%(43/51),NTM感染与患者年龄高度相关(r＝0.16,P＝0.018)。胞内分枝杆菌80例(71.4%)。男性患者更易出现咳嗽症状(48/61)(χ²＝3.27,P＝0.03),而女性患者更易出现咯血症状(14/51)(χ²＝5.39,P＝0.021)。年龄大的患者更易出现咯血(16/91)(r＝0.21,P＝0.015),而年轻患者更易出现气短症状(10/21)(r＝0.17,P＝0.023)。NTM肺部疾病最常见的影像学特征是支气管扩张,占40.2%(45/112),肺部结节占36.6%(41/112),多发空洞38.4%(43/112)。NTM感染最常见的易患因素为MTB,占66.1%(74/112);其次为支气管扩张占25.0%(28/112),合并COPD占17.9%(20/112)。与女性患者相比,男性患者更易合并COPD(OR＝5.23,95%CI 5.20~72.60);胞内分枝杆菌感染更易合并支气管扩张(OR＝0.13,95%CI 0.09~0.86)。 结论广州地区NTM感染最常见的病原体是胞内分枝杆菌。NTM感染与患者年龄相关,最常见的影像学表现是支气管扩张、结节影及多发性空洞。MTB感染及器官移植是NTM感染的高危因素。