Pathologic anatomy of pneumonia caused by Legionella: on the materials of outbreak in town Verkhnyaya Pyshma

Data on postmortem examination of five patients deceased during Legionnaires' outbreak in town Verkhnyaya Pyshma are presented in the article. Feature of course of the disease was severe affection of the lungs with development of toxic shock. Pathomorphological picture in lungs was characterized by polymorphism, presence of shock reaction and ventilator-associated pneumonia (atelectases, distelectases, tracheobronchitis). In autopsy material from four fatal cases Legionella pneumophila serogroup 1 was detected. Causative agent of pneumonia was not determined in one fatal case although comparison of clinical and morphological characteristics of this case with other four cases as well as detection of Gram-negative bacillus in alveolar macrophages allowed to consider this case of pneumonia as caused by Legionella. In studied fatal cases postmortem diagnoses were ascertained in which main disease was bilateral pneumonia caused by Legionella pneumophila serogroup 1 complicated by toxic shock.     

Hyperoxia mediates acute lung injury and increased lethality in murine Legionella pneumonia: the role of apoptosis

Legionella pneumophila is a major cause of life-threatening pneumonia, which is characterized by a high incidence of acute lung injury and resultant severe hypoxemia. Mechanical ventilation using high oxygen concentrations is often required in the treatment of patients with L. pneumophila pneumonia. Unfortunately, oxygen itself may propagate various forms of tissue damage, including acute lung injury. The effect of hyperoxia as a cofactor in the course of L. pneumophila pneumonia is poorly understood. In this study, we show that exposure to hyperoxic conditions during the evolution of pneumonia results in a marked increase in lethality in mice with Legionella pneumonia. The enhanced lethality was associated with an increase in lung permeability, but not changes in either lung bacterial burden or leukocyte accumulation. Interestingly, accelerated apoptosis as evidenced by assessment of histone-DNA fragments and caspase-3 activity were noted in the infected lungs of mice exposed to hyperoxia. TUNEL staining of infected lung sections demonstrated increased apoptosis in hyperoxic mice, predominantly in macrophages and alveolar epithelial cells. In vitro exposure of primary murine alveolar epithelial cells to Legionella in conjunction with hyperoxia accelerated apoptosis and loss of barrier function. Fas-deficient mice demonstrated partial resistance to the lethal effects of Legionella infection induced by hyperoxia, which was associated with attenuated apoptosis in the lung. These results demonstrate that hyperoxia serves as an important cofactor for the development of acute lung injury and lethality in L. pneumophila pneumonia. Exaggerated apoptosis, in part through Fas-mediated signaling, may accelerate hyperoxia-induced acute lung injury in Legionella pneumonia.     

Etiology of acute pneumonias in an organized collective

In this work the immune structure of an organized group with respect to acute respiratory infections and the etiological structure of cases of acute pneumonia was studied. The sera taken from 602 persons were tested for the presence of antibodies to 14 infective agents of the viral, bacterial and mycoplasmal nature. The data indicate that all these agents circulate in the group under study with the prevalence of influenza A (H3N2), influenza B and group III parainfluenza viruses. Among etiological agents of acute pneumonia, the combination of Staphylococcus with Mycoplasma pneumoniae and adenovirus was noted. The Legionella etiology of some group cases of acute pneumonia among young persons was established on the basis of the increased titers of L. pneumophila antibodies in the indirect hemagglutination, indirect immunofluorescence and enzyme immunoassay. The source of this infection was highly dispersed water aerosol, containing the infective agent, in shower baths. This was bacteriologically confirmed by the isolation of three Legionella strains. The study showed that no transfer of Legionella infection in the group through contacts was possible.     

An outbreak of Legionella infection in Armavir

In March-April 1987 an outbreak of Legionella infection was registered among 236 workers at a rubber factory in Armavir. An ARD-like syndrome and acute alveolitis were the main variants of the clinical course of the infection. Legionella infection was diagnosed on the basis of a fourfold and greater increase in the titers of antibodies to L. pneumophila, serogroup 1, as determined in the indirect immunofluorescence test and enzyme immunoassay (EIA). In urine samples obtained from patients Legionella antigen was determined with the use of EIA techniques. The culture of L. pneumophila, serogroup 1, was isolated from the recycling-type water supply system of the factory. The outbreak was stopped by a complex of sanitary, hygienic and epidemic control measures.     

Detection of Legionella pneumophila at thermal spas

Water samples were collected at three therapeutic thermal spas in the area of Brescia, between February and October 2000: 34.8% of the samples contained Legionella pneumophila; the predominant isolates (30%) belonged to Legionella pneumophila serogroup 1. The microorganism was present in the spa water at high concentrations, generally higher than 10000 cfu/l. The large number of positive Legionella pneumophila samples indicates a potential risk of infection to patients, especially those undergoing inhalation treatment with thermal water, or those using a whirlpool or taking a shower even if, during the study, no clinical cases of Legionnaires' disease were observed. In some inhalators in use we detected Legionella pneumophila: after a treatment to eradicate the microorganism, no sanitary fittings currently show contamination. Thus, in our opinion, they are not sources of infection when they are mantained and serviced properly. Thermal disinfection and service checks at regular intervals are suggested for contaminated systems.     

Causes of atypical pneumonia: results of a 1-year prospective study.

In a protocol study of cases of atypical pneumonia over a 1-year period an etiologic agent was established in 16 cases: Legionella pneumophila in 8, Coxiella burnetii in 3, Chlamydia trachomatis in 2, Mycoplasma pneumoniae in 1, para-influenza 3 virus in 1 and cytomegalovirus in 1. In the remaining 11 cases no agent was identified; the illnesses in these cases tended to be less severe. The pneumonia took much longer to resolve in the patients with Legionnaires'' disease than in all the other patients (mean interval from onset of symptoms to clearing of the chest roentgenogram: 69 days v. an average of 16 days). However, the length of stay in hospital was similar for the three groups: those with Legionnaires'' disease, those with atypical pneumonia of unknown cause and those with atypical pneumonia of various other established causes. L. pneumophila infection may explain a proportion of atypical pneumonias that previously could not be diagnosed, although in this series the cause of 41% of the pneumonias remained unexplained.     

Fatal legionellosis in patients with malignant hematologic diseases

Pneumonia was present in 70/157 (44.6%) autopsied patients with malignant hematologic diseases. In 16/70 patients (22.9%), legionellae were found to be the causative agents by screening lung tissue specimens with the direct fluorescent antibody method. In 5/16 patients with Legionella pneumonia, in whom legionellosis had been suspected clinically, the diagnosis had already been established by serology, urinary Legionella antigen detection, and culture. These results provide evidence that legionellosis is an important pneumonia etiology in patients with malignant hematological diseases. Thus, Legionella diagnostics should be applied routinely, and antibiotics effective in the treatment of legionellosis should be added to the usual therapy in patients with etiologically unexplained pneumonias. In view of the common occurrence of relapses of Legionella pneumonia, antibiotic therapy should be continued for an extended period.     

Accelerated laboratory diagnosis of bacterial pneumonia

The effectiveness of countercurrent immunoelectrophoresis (CIE) used for the accelerated differential diagnosis of pneumococcal, staphylococcal, mycoplasmal and Legionella infections in cases of pneumonia has been shown. The presence of correlation between the results obtained in the bacterial study of sputa and bronchial washings and in CIE has been revealed, which gives grounds for recommending CIE for the accelerated diagnosis of pneumococcal pneumonia on the basis of the analysis of sputa, bronchial washings and blood sera obtained from patients. In Legionella infection the passive hemagglutination test with antigenic diagnostica has proved to be more effective for accelerated diagnosis than CIE.     

An epidemiological analysis of hemorrhagic fever with renal syndrome morbidity in the Republic of Bashkortostan in 1997

The outbreak of hemorrhagic fever with renal syndrome (HFRS) in the Republic of Bashkortostan, resulting in 10,057 registered cases of the disease (287 cases per 100,000 of the population), was analyzed. HFRS cases among the population were registered in 52 out of 54 regions of Bashkortostan. 31% of the total number of patients were the inhabitants of rural regions (170 cases per 100,000) and 69% were urban dwellers (295 cases per 100,000), mainly in Ufa (512 cases per 100,000). HFRS morbidity among males was fourfold higher than among females. In 70% of cases persons aged 20-49 years were affected. 5% of the total number of patients were children aged up to 14 years. In 34 cases (0.4%) the severe clinical course of the disease had a fatal outcome. Cases of HFRS were registered from April 1997 till March 1998 with the highest morbidity rate observed during the period of August-December. In most cases (46.8%) both urban and rural dwellers contacted infection during a short-term stay in the forest. As the result of the serological examination of the patients, all HFRS cases were etiologically attributed to hantavirus, serotype Puumala. The main natural reservoir of this virus and the source of human infection in Bashkortostan were bank voles (Clethrionomys glareolus), the domination species among small mammals in this region.     

Water-borne outbreaks of rotavirus infections

The clinico-epidemiological characteristics of group rotavirus infection observed in one settlement in March-April is presented. 173 cases of infection were registered in all age groups (children under 7 years constituted only 10.4% of the patients). In most of the apartments found to be the foci of infection only one patient was registered. The virological study of fecal samples from 24 patients showed the presence of human rotaviruses in the feces of 10 patients (41.7%). Neutralizing antibodies in titers of 1:4 to 1:64 were detected in all taken paired sera (21). THe clinical study of 53 hospitalized patients showed that in all cases the infectious process had acute beginning. In most patients the disease took mild forms. The peculiarities of the distribution of the patients in different age groups, the location of the foci of infection and its seasonal character, as well as some objective data on the presence of pollutions in the water mains, indicated that this infection could spread through water via the system of centralized water supply.     

Coronavirus infection in immunodeficient patients with hemoblastosis and deficient hemopoesis

Coronavirus infection (CVI) was studied in 227 patients hospitalized in the clinic of the Research Institute of Hematology and Transfusiology in 1993-2003 with diagnosed acute and chronic leucosis, multiple myelogenic disease and aplastic anemia. Their blood sera and secretions of the nasal cavity were examined in the indirect hemagglutination (IHA) test with dried standard erythrocyte diagnostic preparations. CVI was shown to be activated in three year cycles in immunodeficient patients, which occurred, respectively, in 66.1, 56.9, 47.8 and 51.6% of cases in the above mentioned groups of patients. In 87% of cases CVI was associated with other respiratory pathogens, the following being prevailed: respiratory syncytial virus (37.9%), parainfluenza virus (32.2%) and Mycoplasma pneumoniae (36.8%). CVI was provoked by such factors as the course of the main disease and specific treatment, previous respiratory infections of other etiology with M. pneumoniae infection playing the leading role (60%). The most severe course of CVI was observed in patients with acute leucosis (in 75% of cases accompanied by lesions of lower respiratory tracts). The use of the highly sensitive IHA test made it possible to determine the potential for both serum and local antibodies production in the patients under observation.     

The clinical efficacy of ticarcillin/clavulanate in severe pneumonia]

Efficacy of ticarcillin/clavulanate was studied in the treatment of 11 patients with severe community- and hospital-acquired pneumonia in an open controlled trial. The drug was administered in a dose of 3.1 g every 4 or 6 hours depending on the infection severity. When pneumonia was due to Pseudomonas aeruginosa, amikacin was additionally used. The positive clinical effect of ticarcillin/clavulanate was stated in 73 per cent of the patients. The pathogen eradication was stated in all the patients. However, in 2 cases superinfection due to P.aeruginosa developed. Mild adverse effects were observed in 2 cases. It is concluded that ticarcillin/clavulanate is highly efficient in the treatment of patients with severe or complicated pneumonia. In cases with ventilator-associated pneumonia it is advisable to use ticarcillin/clavulanate in combination with an aminoglycoside.     

Streptococcus pneumoniae serotypes in children with acute pneumonia and pleurisy

The study of pneumococci of different serotypes, isolated from patients with acute pneumonia and pleuritis and from healthy children was carried out. Among the pneumococcal serotypes causing pneumonia and pleuritis in children serotypes 1, 6, 19, 14 and 3 were most widely spread and constituted 62.3% of all isolated pneumococci. In young children cases of acute pneumonia and pleuritis were more often induced by serotypes 6 and 14 and in older children, by serotypes 1 and 3. In patients with uncomplicated pneumonia and pleuritis differences in the detected serotypes of pneumococci were observed, and the disease course differed in severity. Serotypes 14, 3 and 3 induced destructive processes in the lungs more often than other serotypes. Monitoring of the sensitivity of pneumococci to antibiotics showed that most of the strains retained high sensitivity to penicillin and ampicillin. In most cases the detected resistant pneumococcal strains belonged to serogroup 19.     

Legionella, Legionnaires' disease

Legionella is the causative agent of Legionnaires' disease, a severe form of pneumonia. Detection of Legionella pneumophila serogroup 1 antigen in urine samples has shortened the delay of diagnosis and subsequent treatment initiation resulting in decreased mortality. Improved surveillance of potable water system reinforces the community prevention. In France, the National Reference Center for Legionella collects the strains responsible for sporadic or epidemic cases and crosslinks the data including epidemiological pattern, clinical presentation, and genetic analysis of the strains. Regarding host-pathogen interactions, major advances have been made recently in the understanding of L. pneumophila ability to subvert the host intracellular trafficking and the innate immune response leading to infection control.     

Etiological structure of pneumonias in children and adults

The bacteriological study of sputa, nasopharyngeal smears and bronchial washings taken from pneumonia patients has shown that the leading etiological agent was Streptococcus pneumoniae isolated in the diagnostic titre (10(7) bacteria per ml) in 78.1% of the cases. Staphylococcus aureus, Haemophilus influenzae, enterobacteria and yeast-like fungi have been found to play an insignificant role in the etiology of acute pneumonia (2.5 +/- +/- 0.9%). The results of the serological diagnosis by means of the complement fixation test have revealed that, alongside S. pneumoniae, the following infective agents are of etiological importance in cases of acute pneumonia: respiratory viruses (more than 50%), Mycoplasma pneumonia (10%), Chlamydia psittaci (6.4%) and Legionella pneumophila (3.8%). The study has first revealed that, under the conditions of Alma-Ata, serotypes 19, 23, 8 and 4 prevail among circulating pneumococci. This study has also shown that the use of M. pneumoniae antibody erythrocyte diagnosticum enhances the detection rate of mycoplasma infections in pneumonia patients.     

Severe community-acquired pneumonia: etiology]

A complex microbiological (sputum, protected brush biopsy of the bronchial mucosa) and immunological examination of 40 male patients (the average age of 55.4 +/- 8.8 years) with severe community-acquired pneumonia (risk classes III-V according to Fine M.J. et al., 1997) revealed the disease etiology in 52.5 per cent of the cases. The leading pathogen was Streptococcus pneumoniae. It was detected in 61.6 per cent of the cases of the etiologically verified pneumonia. Staphylococcus aureus and Klebsiella pneumoniae were also among the actual pathogens (14.3 and 14.3 per cent respectively). The Legionnaires infection was not confirmed in any of the patients (enzyme-linked immunological analysis of urine for the serotype 1-6 Legionella pneumophila antigen). In the absolute majority of the patients the isolated pneumococci were susceptible (E-test) to benzylpenicillin. Only in 1 patients with severe pneumonia and secondary bacteriemia the pneumococcal isolates were moderately resistant to benzylpenicillin (the MIC of 0.125 mg/ml). Still, they were susceptible to ceftriaxone (the MIC of 0.023 mg/ml). The data are useful in the development of a national (regional) programme for empirical antibacterial therapy of severe community-acquired pneumonia.     

Standards for laboratory diagnostics of legionellosis and their application during epidemic outbreak of pneumonia in town Verkhnyaya Pyshma

High effectiveness of application of international standards for legionellosis laboratory diagnostics was confirmed during investigation of pneumonia outbreak in town Verkhnyaya Pyshma. Use of immunochromatographic method and enzyme immunoassay for detection of Legionella antigen in urine of patients allows to confirm diagnosis of Legionella infection during several hours, promptly begin etiologic antibacterial treatment and reveal possible sources of infection in potentially dangerous environmental objects.     

Laboratory diagnostics of infections caused by cytomegalovirus and parvovirus B19 in patients with secondary immunodeficiency

To improve the quality of diagnostics and treatment of patients with immunodeficient states, two groups of patients were examined for the presence of cytomegalovirus (CMV) infection, among them 1,348--with clinical manifestations of CMV infection (group 1) and 335 hematological patients (group 2); in addition, 36 patients with secondary immunodeficiency and 31 patients with aplastic and hemolytic anemia, or with anemia of unclear origin were examined for the presence of parvovirusinfection (B19). The results of enzyme immunoassay, polymerase chain reaction and immunofluorescence tests active CMV infection, confirmed by determination of IgM, low avidity IgG, antigen and DNAemia, was registered in group 2 more often than in group 1. Examinations on the presence of parvovirus infection revealed that in anemia patients with the low level of IgG or its absence IgM was also detected more often than in group 1. In mixed infection caused by CMV and parvovirus B19 the disease took a more severe course than in monoinfection, which was probably due to the parallel action exerted by parvovirus on erythrocyte production in hematopoiesis and by CMV on the monocytic and macrophagal row of cell.     

肺部铜绿假单胞菌感染前后肺组织角质细胞生长因子的变化研究

目的观察与分析肺部铜绿假单胞菌（PAE）感染前后患者肺组织角质细胞生长因子（KGF）的变化情况,并研究其临床意义。方法将2010年12月到2013年12月于沈阳军区总医院接受治疗的60例肺炎患者作为研究对象,分别于其感染前后收集肺组织标本,检测感染前后患者肺组织角质细胞生长因子的表达水平。结果在感染PAE后,患者肺组织角质细胞生长因子蛋白表达水平呈明显上升的态势,并于感染3 d后到达峰值。相较感染铜绿假单胞菌前,患者肺组织角质细胞生长因子蛋白表达水平明显提升,感染前后对比差异有统计学意义（P〈0.05）。结论在急性肺损伤的诊断与治疗中,重视对患者肺组织KGF蛋白表达水平的研究,及时实施KGF辅助干预,对抑制感染,控制肺炎的进展有十分重要的作用。