[Tuberculous orchiepididymitis and CNS complication]. / Die tuberkulöse Epididymoorchitis und die Zentralnervensystemkomplikation.

INTRODUCTION: Hydrocephalus as a complication of tuberculous orchiepididymitis is extremely rare. In this reported case, hydrocephalus was the consequence of a disseminated tuberculous process. CASE REPORT: A 28-year-old man was treated for a left-sided orchiepididymitis. He developed the signs of increased intracranial pressure. Computer tomography (CT) of the brain showed a hydrocephalus. The diagnostics that followed confirmed disseminated tuberculosis (Tbc). CONCLUSIONS: Urogenital system is at the present rarely affected by Tbc. Especially rare is disseminated Tbc, which affects at the same time three different organ systems. Disseminated Tbc presented with many different but non-specific clinical symptoms, sometimes mimicking neoplasm. This makes diagnosis and therapy more difficult. We point out that in any case of orchiepididymitis not responding to standard antimicrobial therapy Tbc must be taken into consideration as the one of the differential diagnostic possibilities.

Microbiological criteria in non-tuberculous mycobacteria pulmonary disease: a tool for diagnosis and epidemiology.

SETTING: The value of microbiological criteria in diagnosing non-tuberculous mycobacteria pulmonary disease (NTM-PD) and monitoring its epidemiology is unknown. OBJECTIVES: To correlate the rate of NTM-PD based on microbiological criteria (American Thoracic Society/Infectious Diseases Society of America [ATS/IDSA] or stricter microbiological criteria) compared with the full ATS/IDSA criteria, to assess the positive predictive value (PPV) of different microbiological criteria in predicting NTM-PD, and to evaluate the clinical relevance of different NTM species. DESIGN: Retrospective study of all patients with pulmonary NTM isolates in Croatia during an 8-year period. NTM species were divided into low, intermediate and high clinical relevance groups for additional analyses. RESULTS: Good correlation between both microbiological and full ATS/IDSA criteria was observed. The PPV of stricter and ATS/IDSA microbiological criteria was respectively 93.3% and 59.8%. The usefulness of microbiological criteria varied between groups. ATS/IDSA microbiological criteria had a PPV of 89.8% in the high relevance group, while in the intermediate relevance group, the PPV of stricter and ATS/IDSA microbiological criteria was respectively 94.3% and 63.4%. CONCLUSIONS: Microbiological criteria are useful in detecting NTM-PD, allowing laboratory-based monitoring. Stricter criteria should be used for species of low clinical relevance, and less stringent criteria for species of high relevance in the local setting.

Geographical distribution and clinical relevance of non-tuberculous mycobacteria in Croatia.

SETTING: The clinical relevance of non-tuberculous mycobacteria (NTM) in Croatia is unknown. OBJECTIVE: To estimate the isolation rate of NTM, record geographical differences and assess the burden of pulmonary NTM disease in Croatia. DESIGN: Nationwide retrospective cohort study of all Croatian residents with NTM isolated by culture in the period from 2006 to 2010. Microbiological criteria of the American Thoracic Society were used to establish a laboratory-based case definition of possible and probable NTM disease. RESULTS: Of 1187 individuals with pulmonary NTM isolates, 8.6% met the possible and 5.5% met the probable disease criteria. We estimated an annual incidence of probable pulmonary NTM disease of 0.23 per 100,000 population. This estimated annual incidence was 0.35/100,000 in the coastal region and 0.17/100,000 in the continental region. Species distribution differed between coastal and continental Croatia. NTM isolation frequency increased over the study period. CONCLUSION: Geography plays an important role in NTM species distribution and possible disease. The overall burden of NTM pulmonary disease in Croatia is still low compared to that of tuberculosis, but it is higher in the coastal region compared to the continental region.

Heterogeneity in intracellular replication and cytopathogenicity of Legionella pneumophila and Legionella micdadei in mammalian and protozoan cells.

In contrast to Legionella pneumophila, little is known about the pathogenesis of other legionellae species that are capable of causing Legionnaires' disease. In this report, we contrast L. pneumophila and L. micdadei for their cytopathogenicity and intracellular replication within mammalian and protozoan cells. We show by transmission electron microscopy that L. micdadei replicates within an endoplasmic reticulum (RER)-free phagosome within human macrophages, alveolar epithelial cells, and within the protozoan Hartmannella vermiformis. In contrast, L. pneumophila replicates within a RER-surrounded phagosome within the same host cells. In contrast to replication of L. pneumophila within Acanthamoebae polyphaga, L. micdadei does not replicate within this protozoan host. Despite the prolific intracellular replication, L. micdadei is less cytopathogenic to all host cells than L. pneumophila. Since both species replicate intracellularly to a similar level, we have examined whether the reduced cytopathogenicity of L. micdadei is due to a reduced capacity to induce apoptosis or pore formation-mediated necrosis, both of which contribute to killing of the host cell by L. pneumophila. The data show that both species induced apoptosis-mediated killing of mammalian cells to a similar level. In contrast to L. pneumophila, expression of the pore-forming toxin by L. micdadei and its necrotic effect on macrophages and alveolar epithelial cells is undetectable. This has been further confirmed showing that L. micdadei is completely defective in contact-dependent haemolysis of RBCs, an activity mediated by the pore-forming toxin. Finally, in contrast to L. pneumophila, there was no significant intrapulmonary replication of L. micdadei in the A/J mice animal model. Our data show dramatic differences between L. pneumophila and L. micdadei in intracellular replication, cytopathogenicity, and infectivity to mammalian and protozoan cells.

Legionella pneumophila infection in intratracheally inoculated T cell-depleted or -nondepleted A/J mice.

The inflammatory response and influence of T cell depletion on the pathogenesis of an experimental Legionella infection were studied. A/J mice were infected with 10(6) CFU of Legionella pneumophila intratracheally. With this dose all infected animals survived the infection and bacteria were cleared from lung, spleen, liver, and kidney within 10 to 11 days, leaving no residual changes in the affected organs. Inflammatory cells were recruited into the lung on the second day of infection, reaching a maximum on the third day and filling out predominantly the interstitial areas. During the first 3 days after inoculation, mainly macrophages, B cells, NK cells, and large mononuclear cells of an unknown phenotype were attracted into the lung interstitium, whereas T lymphocytes infiltrated subsequently. During the early phase of infection, serum concentrations of IFN-gamma, TNF-alpha, IL-1beta, IL-4, and IL-6 but not IL-2 increased dramatically. The cytokine secretion decreased on the third day after infection although bacteria were still present in the lung or even disseminated in different organs. Successful clearance of bacteria from the lung was not observed before recruitment of T cells into the lung. In mice depleted of both CD4+ and CD8+ T cells, control of infection was impaired and lethality of infection increased. Depletion of either subset left residual antibacterial mechanisms, which, however, were not sufficient to clear the Legionella as rapidly as in undepleted mice.

Protective effect of antilipopolysaccharide monoclonal antibody in experimental Klebsiella infection.

An O-antigen-specific murine monoclonal antibody (MAb) directed against an immunodominant epitope expressed on Klebsiella O1, O6, and O8 lipopolysaccharides (LPS) was examined with respect to its binding to nonencapsulated and encapsulated bacterial cells and its ability to protect against lethal murine Klebsiella sepsis. While the MAb (clone Ru-O1, mouse immunoglobulin G2b) bound well to nonencapsulated organisms of the O1 serogroup, binding was significantly, but not completely, abolished by the presence of the K2 capsule. In a model of experimental Klebsiella peritonitis and sepsis induced by a virulent O1:K2 serogroup strain, higher doses of anti-LPS MAb Ru-O1 than of a previously described anticapsular MAb specific for the K2 capsular polysaccharide were needed to provide protection. However, high-dose (40 microg/g of body weight) pretreatment with anti-LPS MAb Ru-O1 significantly reduced bacterial dissemination to various organs as well as macroscopic and histologic pulmonary alterations. Thus, since the number of Klebsiella capsular antigens occurring in clinical material is too large to be completely "covered" by a K-antigen-specific hyperimmunoglobulin preparation, O-antigen-specific antibodies may supplement K-antigen-specific immunoprophylaxis and -therapy of clinical Klebsiella infection.