The association between serological features of chronic Chlamydia pneumoniae infection and markers of systemic inflammation and nutrition in COPD patients

Introduction: Chlamydia pneumoniae is an obligatory human pathogen involved in lower and upper airway infections, including pneumonia, bronchitis. Asymptomatic C. pneumoniae carriage is also relatively common. The association of C. pneumoniae infections with the chronic obstructive pulmonary disease (COPD) course is unclear.

Objectives: The aim of the study was to investigate the association between chronic C. pneumoniae infection and clinical features of COPD, markers of inflammation and metabolic dysfunction.

Patients and methods: The study included 59 patients with stable COPD who had no, or had?≥2 acute exacerbations during last year. The level of IgA and IgG antibody against C. pneumoniae, IL-6, IL-8, resistin, insulin, adiponectin and acyl ghrelin was measured in serum by enzyme-linked immunosorbent assay (ELISA).

Results: No differences in clinical and functional data were observed between COPD patients without serological features of C. pneumoniae infection and chronic C. pneumoniae infection. The level of anti C. pneumoniae IgA significantly correlated with IL-8, IL-6, resistin concentration in group of frequent exacerbators. IgG level correlated negatively with acetyl ghrelin and body mass index (BMI) in patients without frequent exacerbations, in contrast to frequent COPD exacerbation group where significant correlations between IgG level and BMI was demonstrated. Serum IL-6 correlated positively with resistin and insulin and negatively with adiponectin in group of patients with serological features of chronic C. pneumoniae infection only.

Conclusions: Our study showed that chronic C. pneumoniae infection does not influence the clinical course of COPD in the both study groups. Chronic C. pneumoniae infections might be associated with a distinct COPD phenotype that affects metabolic dysfunction.     

Effect of Prolonged Treatment with Azithromycin, Clarithromycin, or Levofloxacin on Chlamydia pneumoniae in a Continuous-Infection Model

Persistent infections with Chlamydia pneumoniae have been implicated in the development of chronic diseases, such as atherosclerosis and asthma. Although azithromycin, clarithromycin, and levofloxacin are frequently used for the treatment of respiratory C. pneumoniae infections, little is known about the dose and duration of therapy needed to treat a putative chronic C. pneumoniae infection. In this study, we investigated the effect of prolonged treatment with azithromycin, clarithromycin, or levofloxacin on the viability of C. pneumoniae and cytokine production in an in vitro model of continuous infection. We found that a 30-day treatment with azithromycin, clarithromycin, and levofloxacin at concentrations comparable to those achieved in the pulmonary epithelial lining fluid reduced but did not eliminate C. pneumoniae in continuously infected HEp-2 cells. All three antibiotics decreased levels of interleukin-6 (IL-6) and IL-8 in HEp-2 cells, but this effect appeared to be secondary to the antichlamydial activity, as the cytokine levels correlated with the concentrations of microorganisms. The levels of IL-1β, IL-4, IL-10, tumor necrosis factor alpha, and gamma interferon were too low to assess the effect of antibiotics. These data suggest that the dosage and duration of antibiotic therapy currently being used may not be sufficient to eradicate a putative chronic C. pneumoniae infection.     

Comparison of complement fixation and microimmunofluorescence tests in respiratory infections caused by chlamydia and an evaluation of the serum amyloid a protein in chlamydial infections

We retrospectively analyzed serum samples for antibodies to chlamydia species using the micro-immunofluorescence (MIF) test from 72 patients previously tested by the clamydia complement fixation (CF) test, which is used to detect pulmonary psittacosis. Nineteen patients were positive for chlamydia with the CF test. Of these, 9 patients (47.4%) were also positive forC. psittaci infection, and 7 patients (36.8%) were positive forC. pneumoniae infection by the MIF test. Five (9.4%) and (11.3%) of the 53 CF-negative patients were positive for psittacosis andC. pneumoniae infection by the MIF test, respectively. Our results indicate that the serum of patients suspected of pulmonary psittacosis should be examined by the MIF test as well as CF in order to distinguish between infections caused byC. psittaci, C. pneumoniae andC. trachomatis, and to improve the sensitivity of serodiagnosis. Serum samples of all 7 patients positive by both CF and the MIF test forC. pneumoniae infection showed a diagnostic IgG antibody change toC. pneumoniae without IgM antibody changes, which suggested a primary infection. These results suggest that the diagnostic CF antibody response occasionally appears in reinfection, especially inC. pneumoniae infection. There was a positive correlation (r=0.858) between C-reactive protein and serum amyloid protein A, a sensitive acutephase serum reactant, over a wide range of concentrations in 19 patients with chlamydia respiratory infections.     

Th2 cell hyporesponsiveness during chronic murine schistosomiasis is cell intrinsic and linked to GRAIL expression

Chronic infections are associated with progressively declining T cell function. Infections with helminth parasites, such as Schistosoma mansoni, are often chronic and characterized by the development of strong Th2 responses that peak during the acute stage of infection and then decline despite ongoing infection; this minimizes Th2-dependent immunopathology during the chronic stage of infection. We sought to understand the basis for the decline in Th2 responses in chronic schistosomiasis. Using IL-4 reporter mice (mice that express EGFP as a reporter for Il4 gene expression) to identify Th2 cells, we found that Th2 cell numbers plateaued during acute infection and remained constant thereafter. However, the percentages of Th2 cells proliferating during late infection were strikingly lower than those during acute infection. Th2 cell hyporesponsiveness was evident within 10 d of initiation of the Th2 response and became progressively ingrained thereafter, in response to repeated Ag stimulation. Gene expression analyses implicated the E3-ubiquitin ligase gene related to anergy in lymphocytes (GRAIL) in the hyporesponsive state. Consistent with this, suppression of GRAIL expression using retrovirally delivered siRNA prevented the development of hyporesponsiveness induced by repeated Ag stimulation in vitro or in vivo. Together, these data indicate that the decline in Th2 cell responsiveness during chronic schistosomiasis is the net result of the upregulation of GRAIL expression in response to repeated Ag stimulation.     

Chlamydia and chronic arthritis

Abstract

Certain bacterial infections have been demonstrated to be causative of reactive arthritis. The most common bacterial trigger of reactive arthritis is Chlamydia trachomatis. Chlamydia pneumoniae is another known cause, albeit far less frequently. Although Chlamydia-induced reactive arthritis will often spontaneously remit, approximately 30% of patients will develop a chronic course. Modern medicine has provided rather remarkable advances in our understanding of the chlamydiae, as these organisms relate to chronic arthritis and the delicate balance between host and pathogen. C. trachomatis and C. pneumoniae both have a remarkable ability to disseminate from the initial site of infection and establish persistently viable organisms in distant organ sites, namely the synovial tissue. How these persistent chlamydiae contribute to disease maintenance remains to be fully established, but recent data demonstrating that long-term combination antimicrobial treatment can not only ameliorate the symptoms but eradicate the persistent infection suggest that these chronically infecting chlamydiae are indeed a driving force behind the chronic inflammation. We are beginning to learn that this all appears possible even after an asymptomatic initial chlamydial infection. Both C. trachomatis and C. pneumoniae are a clear cause of chronic arthritis in the setting of reactive arthritis; the possibility remains that these same organisms are culpable in other forms of chronic arthritis as well.     

The effect of inhaled corticosteroids on Chlamydophila pneumoniae and Mycoplasma pneumoniae infection in children with bronchial asthma

The purpose of this study was to clarify whether inhaled corticosteroids (ICSs) increased the infectious load of Chlamydophila pneumoniae and/or Mycoplasma pneumoniae in the respiratory tracts of asthmatic children. We studied a total of 310 outpatients with chronic stable asthma. Real-time polymerase chain reaction (PCR)-positive results for C. pneumoniae were obtained in 21 of 310 (6.8%) throat samples and 21 of 293 (7.2%) nasopharyngeal samples. There was no significant difference in the rate of detection or in the quantity of detection for C. pneumoniae between the ICS group and the non-ICS group, nor were there differences among groups classified by Japanese pediatric guidelines (JPGL) severity criteria. Real-time PCR-positive results for M. pneumoniae were obtained in 60 of 310 (19.4%) throat samples and 49 of 293 (16.7%) nasopharyngeal samples. There was no significant difference in the rate of detection or the quantity of detection between the ICS group and the non-ICS group, nor were there differences among age groups. The results of this research do not support the hypothesis that ICSs influence the infectious load of C. pneumoniae and M. pneumoniae. ICSs did not increase C. pneumoniae or M. pneumoniae infection in the upper respiratory tract, in contrast to the effect of ICSs in causing oral candidiasis. Our data exclude the concern that there is an increase in C. pneumoniae and M. pneumoniae infections due to ICS use, the use of ICSs being the gold standard in the long-term anti-inflammatory treatment of persistent asthma in children and adults.     

Predictors of mortality in multidrug-resistant Klebsiella pneumoniae bloodstream infections

The dramatic increase of antibiotic resistance in Klebsiella pneumoniae has been associated with fatal outcomes. First, bloodstream infections (BSIs) caused by extended-spectrum β-lactamases (ESBL) Enterobacteriaceae have been associated with treatment failure, more recently BSIs caused by carbapenem-resistant K. pneumoniae (CR-KP) have been reported to be fatal in approximately 50% of cases. Severity of underlying disease, intensive care unit stay at infection onset, infection with ESBL or CR-KP strain and delay in administration of appropriate therapy are among the most common risk factors for mortality in patients with K. pneumoniae BSI, while infection source control and early appropriate antimicrobial treatment have been associated with survival. Thus, risk assessment for ESBL and/or CR-KP is mandatory in patients with suspicion of K. pneumoniae BSI. Here, we examine current evidence regarding risk factors for mortality in patients with K. pneumoniae BSI and address the issue of a risk prediction model for CR-KP BSI.     

Evaluation of the diagnostic usefulness of real-time PCR for detection of Chlamydophila pneumoniae in acute respiratory infections

We investigated whether a real-time polymerase chain reaction (PCR) test is a useful diagnostic tool for identifying individuals with acute respiratory Chlamydophila pneumoniae infections. Nasopharyngeal swab specimens and peripheral blood mononuclear cells (PBMCs) from 100 patients with acute respiratory tract infections and 140 asymptomatic healthy subjects (controls) were analyzed using real-time PCR, culture, and serology for the detection of C. pneumoniae. Six patients had serological results indicating acute C. pneumoniae infections. C. pneumoniae DNA was detected in respiratory samples from eight patients (three of these cases were serologically confirmed as having C. pneumoniae infections) and four controls. The amount of C. pneumoniae DNA present in the real-time PCR for the samples was calculated, and no significant differences in the amount of DNA between symptomatic and asymptomatic subjects were found. On the other hand, traces of C. pneumoniae DNA were detected in PBMCs from eight patients, but this was confirmed in PBMCs from only seven of these patients. Only one patient had both respiratory and blood samples that were positive. C. pneumoniae DNA was also detected in samples from six controls, but no significant differences in the amount of C. pneumoniae DNA were observed between patients and controls. The present quantitative real-time PCR assay does not seem to be a useful method for differentiating between C. pneumoniae acute infections and persistent ones or nasopharyngeal carriage. In addition, the detection of C. pneumoniae DNA in PBMCs does not seem to be a suitable method for the diagnosis of acute respiratory C. pneumoniae infections.     

Management of bacterial infections in children with asthma

Respiratory viruses are the single most common causes of asthma exacerbations in children. Rhinovirus-induced wheezing is a risk factor for chronic asthma, but its mechanism has remained unknown. Human bocavirus is a common finding in wheezing children, but its role as a respiratory pathogen is still unclear. Mycoplasma pneumoniae may, like viruses, induce wheezing and asthma exacerbation. Chlamydia pneumoniae and, in recent studies, Chlamydia trachomatis, may not only induce asthma exacerbations but may also be involved in the pathogenesis of chronic asthma. Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis are often involved in respiratory infections associated with wheezing, but there is no evidence for their active role in asthma pathogenesis or exacerbation. This review summarizes current knowledge on the association between respiratory infections and asthma in children, with a special focus on the role of antibiotics in incipient asthma, asthma exacerbation and chronic stable asthma.     

Gene therapy for viral hepatitis

Hepatitis B and C infections are two of the most prevalent viral diseases in the world. Existing therapies against chronic viral hepatitis are far from satisfactory due to low response rates, undesirable side effects and selection of resistant viral strains. Therefore, new therapeutic approaches are urgently needed. This review, after briefly summarising the in vitro and in vivo systems for the study of both diseases and the genetic vehicles commonly used for liver gene transfer, examines the existing status of gene therapy-based antiviral strategies that have been employed to prevent, eliminate or reduce viral infection. In particular, the authors focus on the results obtained in clinical trials and experimental clinically relevant animal models.     

Doxycycline suppresses Chlamydia pneumoniae induced interferon-gamma responses in peripheral blood mononuclear cells in children with allergic asthma

Persistent respiratory infections caused by Chlamydia pneumoniae have been implicated in the pathogenesis of chronic diseases (e.g. asthma). Antibiotics are used to treat C. pneumoniae respiratory infections; however, the use of antibiotics as anti-inflammatory agents in treatment of asthma remains controversial. The current study investigated whether ciprofloxacin, azithromycin, or doxycycline can suppress C. pneumoniae-induced production of immunoglobulin (Ig) E or cytokines in peripheral blood mononuclear cells (PBMC) obtained from asthmatic children. Apart from blood, nasopharyngeal swab specimens were also collected to test for the presence of C. pneumoniae and/or M. pneumoniae (qPCR). PBMC (1.5 x 10⁶) from asthmatic pediatric patients (N = 18) were infected or mock infected for 1 h ± C. pneumoniae AR-39 at a multiplicity of infection (MOI) = 0.1, and cultured ± ciprofloxacin, azithromycin, or doxycycline (0.1 or 1.0 μg/mLmL) for either 48 h (cytokines) or 10 days (IgE). Interleukin (IL)-4, interferon (IFN)-γ and IgE levels in supernatants were measured (ELISA). When PBMC were infected with C. pneumoniae, IL-4 and IFNγ production increased (p = 0.06 and 0.03, respectively); IgE levels were low. The now-elevated levels of IL-4 didn't decrease significantly after addition of ciprofloxacin, azithromycin, or doxycycline. However, infected PBMC IFNγ formation decreased significantly when 0.1 μg/mL doxycycline was employed (p = 0.04); no dose of ciprofloxacin or azithromycin had any impact. This inhibitory outcome with doxycycline lends support to the use of tetracyclines as immune modulators and anti-inflammatory medications in treatment of C. pneumoniae-infected asthma patients.     

Characterization of children with <Emphasis Type="Italic">Mycoplasma pneumoniae</Emphasis> infection detected by rapid polymerase chain reaction technique

We used a new polymerase chain reaction (PCR) system to identify the 16S rRNA gene of Mycoplasma pneumoniae and to diagnose lower respiratory tract infections caused by the microorganism. Nasopharyngeal swabs collected from 21 patients (22 episodes) tested positive for M. pneumoniae with the PCR. The age distribution of the patients was between 2 and 13 years. The diagnosis, including concomitant infection, was as follows: pneumonia (n = 11), acute bronchitis (n = 10), bronchial asthma (n = 4), and acute otitis media (n = 1). Six patients had bacterial superinfections. Positive findings for M. pneumoniae were noted together with exacerbation of asthma symptoms, suggesting that M. pneumoniae infection may play the role of an inducer. The PCR system constructed by us will contribute to revealing the clinical features of M. pneumoniae infection, and as a result, an appropriate chemotherapeutic agent can be chosen. We propose the usefulness of this PCR system to detect the microorganism in younger children.     

THE ROLE OF IMMUNITY IN THE PATHOGENESIS OF EXPERIMENTAL HEMATOGENOUS PYELONEPHRITIS

Hematogenous pyelonephritis was produced in rats utilizing multiple strains of Escherichia coli, a strain of Klebsiella pneumoniae, and a strain of Proteus mirabilis. Three patterns of hematogenous pyelonephritis occurred which represent an interrelationship between an immune response to the infecting bacteria and the development of obstructive uropathy as a consequence of infection. First, the course of pyelonephritis due to strains of Escherichia coli was acute, self-limited, and associated with the development of circulating agglutinins. Following healing, this pattern of infection was associated with acquired resistance to reinfection with the same bacterial strain. Second, the course of pyelonephritis due to a strain of Klebsiella pneumoniae type C was chronic. This infection was not associated with the production of circulating agglutinins against encapsulated strains. Acquired resistance to reinfection by the homotypic strain could not be demonstrated following eradication of infection but was produced by the passive transfer of concentrated antiserum. Third, pyelonephritis due to Proteus mirabilis was associated with circulating agglutinins and resistance to reinfection with the same organism following eradication of infection, yet the course was chronic. The chronicity appeared to be the consequence of obstructive uropathy resulting from calculi which developed during the course of the infection. Resistance to reinfection was demonstrated in infections with strains of E. coli and P. mirabilis. The resistance is associated with specific immunity as demonstrated by the observation that: (a) it is type-specific, (b) it is of at least 3 months' duration, and (c) it can be passively transferred by means of rabbit antiserum. Since K. pneumoniae failed to evoke capsular antibodies in the rat, resistance to infection with K. pneumoniae was produced only by means of passively transferred concentrated rabbit antiserum and not by prior infection. Immunity can be demonstrated to have a significant role in the pathogenesis of experimental hematogenous pyelonephritis only in the absence of obstructive uropathy.     

Prevalence of Chlamydophila pneumoniae among Bangladeshi children under age 5 years with acute respiratory infections

Despite major improvements in the diagnosis of pathogenic organisms causing acute respiratory infections (ARIs), details of infections caused by atypical pathogens are not well understood, particularly in developing countries. This clinical and epidemiological research was conducted in Bangladesh to explore the prevalence of atypical pathogens in causing childhood pneumonia. Sixty-four children with ARI were studied at the Pediatric Outpatient Department of Dhaka Medical College Hospital, Bangladesh, during September through December 2000. In addition to clinical examination, hematological, radiological, and bacteriological examinations were performed. Antibody titers from paired sera against Mycoplasma pneumoniae and Legionella spp. in the acute and convalescent phases revealed that none of these children were infected with M. pneumoniae, while only one serum sample was positive for L. pneumophila serogroup 4. Antibody titers against Chlamydophila (Chlamydia) pneumoniae, determined by an indirect microimmunofluorescence method, and by an enzyme-linked immunosorbent assay (ELISA) kit (HITAZYME C. pneumoniae kit) indicated that 13 children (20.3%) were infected with C. pneumoniae. Our results indicate a high prevalence rate of C. pneumoniae, suggesting it is as an important causative pathogen of childhood pneumonia in Bangladesh.     

T-regulatory lymphocytes and chronic viral hepatitis

Both hepatitis B virus (HBV) and hepatitis C virus (HCV) can cause persistent viral infection in humans. Chronic infection is associated with a risk of cirrhosis and hepatocellular carcinoma. The cause of chronic infection is unknown. A large body of evidence suggests that a failure of the adaptive immune response is critical in the establishment of chronic infection. Recently a new group of T cells (T-regulatory cells), that express CD4⁺CD25⁺ and Foxp3, which can inhibit the cellular (CD4⁺/CD8⁺) immune response have been described. In this review the authors explore the thoughts regarding immune responses to HBV and HCV infections and the role of these T-regulatory cells in relation to the pathogenesis of chronic HBV and HCV infection and the potential for therapeutic intervention.     

CHLAMYDIAL INFECTIONS

SUMMARY Chlamydiae are among the most successful bacterial pathogens, and there are few branches of medicine on which chlamydial infection and its sequelae do not impinge. Chlamydia trachomatis is responsible for many million cases of blindness, pelvic inflammatory disease, urethritis, epididymitis, infertility and ectopic pregnancy annually; it also causes lymphogranuloma venereum, reactive arthritis, ophthalmia neonatorum and infantile pneumonia. C. pneumoniae is among the most common causes of community-acquired pneumonia, and recent evidence suggests that it may play a part in the pathogenesis of coronary heart disease. C. psittaci is a highly prevalent zoonotic infection with a wide host range. It is of great economic importance, and causes sporadic but sometimes devastating disease in humans. Most chlamydial infections are subclinical, but even if the initial illness is mild there may be serious long-term sequelae. It is therefore important to identify and treat chlamydial infections in their early stages, but diagnosis usually depends on laboratory tests. Recent trials have shown that single doses of the long-acting macrolide azithromycin are effective in the treatment of genital and ocular C. trachomatis infection, but longer courses of antimicrobials remain the mainstay of treatment for C. pneumoniae and C. psittaci infections.     

Diagnosis of Legionella pneumophila,Mycoplasma pneumoniae,or Chlamydia pneumoniae lower respiratory infection using the polymerase chain reaction on a single throat swab specimen

Diagnosis of Mycoplasma pneumoniae and Chlamydia pneumoniae lower respiratory infections using DNA amplification by polymerase chain reaction (PCR) on throat swab specimens has been reported. In this study we determined the sensitivity of the detection of Legionella pneumophila in simulated throat swab specimens by PCR. Next, we compared the sensitivity and specificity of a single throat swab PCR with the current tests for diagnosis of Legionella spp., M. pneumoniae, and C. pneumoniae in patients with lower respiratory tract infections. Patients' work-up included: (a) throat swab speciment for Legionella spp., M. pneumoniae, and C. pneumoniae PCR; (b) throat swab specimen for C. pneumoniae, culture; (c) sputum specimen for L. pneumophila direct fluorescent antibody and culture; (d) urine specimen for L. pneumophila serogroup 1 antigen detection; and (e) serum specimen for L. pneumophila, M. pneumoniae, and C. pneumoniae acute and convalescent antibody titers. A total of 155 patients with lower respiratory infection were enrolled in this prospective study. Throat swab PCR was positive for Legionella spp. in five of the six patients with legionellosis, indicating the presence of this organism in the oropharynx of patients with Legionnaires disease. Mycoplasma pneumoniae PCR was positive in eight of the nine patients with mycoplasma infection. Chlamydia pneumoniae PCR was positive in the two patients with C. pneumoniae infection. None of the other 138 patients with negative PCR had other positive confirmatory tests for respiratory infection by these three organisms (100% specificity). PCR was able to detect 15 of the 17 infected (88.2%). Results of this investigation indicate that PCR on a single throat swab specimen is a rapid, sensitive, and specific test that may greatly simplify the diagnosis of lower respiratory infection caused by Legionella spp., Mycoplasma pneumoniae, or C. pneumoniae.     

Streptococcus pneumoniae serotype 6C presenting as recurrent prosthetic knee joint infection in a patient with a history of congenital asplenia and underlying autoimmune disease: a case report and literature review

This report describes a case of primary Streptococcus pneumoniae bacteremia with prosthetic joint infection caused by serotype 6C with recurrent infection in a patient with a history of congenital asplenia and underlying autoimmune disease. Isolates from the primary and recurrent infections were determined to be indistinguishable by pulsed-field gel electrophoresis. This study expands the conditions associated with recurrent invasive pneumococcal disease caused by serotype 6C.