Chlamydia pneumoniae and Mycoplasma pneumoniae

Mycoplasma pneumoniae infection occurs worldwide and is the most common cause of community-acquired pneumonia (CAP) in 5- to 20-year-olds. The most reliable diagnostic test is the enzyme immunoassay, which allows immunoglobulin (Ig)G and IgM titration and presents 92% sensitivity and 95% specificity on paired samples. Potentially active drugs are tetracyclines, macrolides, ketolides, lincosamides, streptogamines, chloramphenicol, and fluoroquinolones. Chlamydia pneumoniae accounts for 6 to 20% of CAP cases, depending on several factors such as setting of the studied population, age group examined, and diagnostic methods used. The current gold standard for serological diagnosis of acute infection is microimmunofluorescence testing. Tetracyclines and erythromycin show good in vitro activity and so far have been the most commonly employed drugs in the treatment of C. pneumoniae infection. New macrolides, ketolides, and new fluoroquinolones are other potentially effective drugs.     

Chlamydia pneumoniae infection and Mycoplasma pneumoniae infection in pediatric patients

We evaluated a total of 1104 pediatric patients with acute lower respiratory tract infection for C. pneumoniae infection and M. pneumoniae infection by serology during July 1995 to December 1998. A microimmunofluorescence test was used for diagnosis of C. pneumoniae infection and a high density particle agglutination test for that of M. pneumoniae infection. Acute C. pneumoniae infection was found in 149 patients (13.5%), acute M. pneumoniae infection in 118 patients (10.7%), and dual infection in 27 patients (2.4%). Among 305 patients with pneumonia, M. pneumoniae infection (83 patients, 27.2%) was more common than C. pneumoniae infection (47 patients, 15.4%). However among 799 patients with bronchitis. C. pneumoniae infection (102 patients, 12.8%) was more common than M. pneumoniae infection (35 patients, 4.4%). Patients with C. pneumoniae infection were more younger and more frequently wheezing than patients with M. pneumoniae infection. These findings demonstrate that C. pneumoniae infection in very common pathogen of pediatric lower respiratory tract infection as M. pneumoniae infection in Japan.     

Mycoplasma pneumoniae and Chlamydia pneumoniae in asthma: effect of clarithromycin

STUDY OBJECTIVES: To determine the effect of clarithromycin therapy in patients with asthma. DESIGN: Randomized, double blind, placebo-controlled trial. SETTING: A tertiary referral center. PATIENTS OR PARTICIPANTS: Fifty-five subjects with chronic, stable asthma recruited from the general Denver, CO, community. INTERVENTIONS: Patients underwent airway evaluation for Mycoplasma pneumoniae and Chlamydia pneumoniae by polymerase chain reaction (PCR) and culture, followed by treatment with clarithromycin, 500 bid, or placebo for 6 weeks. MEASUREMENTS AND RESULTS: Outcome variables were lung function, sinusitis as measured by CT, and the inflammatory mediators tumor necrosis factor (TNF)-alpha, interleukin (IL)-2, IL-4, IL-5, and IL-12 messenger RNA (mRNA) measured via in situ hybridization, in airway biopsies, and BAL. Mycoplasma or chlamydia were detected by PCR in 31 of 55 asthmatics. Treatment resulted in a significant improvement in the FEV(1), but only in the PCR-positive subjects (2.50 +/- 0.16 to 2.69 +/- 0.19 L, mean +/- SEM; p = 0.05). This was not appreciated in the PCR-negative subjects (2.59 +/- 0.24 to 2.54 +/- 0.18 L, p = 0.85) or the PCR-positive or PCR-negative subjects who received placebo. Sinus CTs revealed no change in sinusitis with clarithromycin treatment. In situ hybridization revealed no significant difference in baseline airway tissue or BAL-mediator expression between the PCR-positive and PCR-negative subjects. However, the PCR-positive subjects who received clarithromycin demonstrated a reduction in TNF-alpha (p = 0.006), IL-5 (p = 0.007), and IL-12 (p = 0.004) mRNA in BAL and TNF-alpha mRNA in airway tissue (p = 0.0009). The PCR-negative subjects who received clarithromycin only demonstrated a reduction in TNF-alpha (p = 0.01) and IL-12 (p = 0.002) mRNA in BAL and TNF-alpha mRNA in airway tissue (p = 0.004). There were no significant differences in cytokine expression in those subjects who received placebo. CONCLUSIONS: These observations support the hypothesis that clarithromycin therapy improves lung function, but only in those subjects with positive PCR findings for M pneumoniae or C pneumoniae.     

Mycoplasma pneumoniae and Chlamydia pneumoniae in calcified nodules of aortic stenotic valves

Aortic Valve Stenosis (AVS) has been explained as an atherosclerotic process of the valve as they often exhibit inflammatory changes with infiltration of macrophages, T lymphocytes and lipid infiltration. The present study investigated whether the bacteria Chlamydia pneumoniae (CP) and Mycoplasma pneumoniae (MP), detected previously in atherosclerotic plaques, are also present in AVS. Ten valves surgically removed from patients with AVS were analyzed by immunohistochemistry, in situ hybridization, and electron microscopy. The mean and standard deviation of the percentage areas occupied by CP antigens and MP - DNA were respectively 6.21 +/- 5.41 and 2.27 +/- 2.06 in calcified foci; 2.8 +/- 3.33 and 1.78+/- 3.63 in surrounding fibrotic areas, and 0.21 +/- 0.17 and 0.12 +/- 0.13 in less injured parts of the valve. There was higher amount of CP and MP in the calcified foci and in the surrounded fibrosis than in more preserved valvular regions. In conclusion, the fact that there were greater amounts of CP and MP in calcification foci of AVS favors the hypothesis that AS is not an inevitable degenerative process due to aging, but rather that it may be a response to the presence of these bacteria, similarly to the morphology detected in atherosclerosis damage.     

Emerging role of Mycoplasma pneumoniae and Chlamydia pneumoniae in paediatric respiratory-tract infections

Increased use of specialised diagnostic techniques over the past 10 years has allowed considerable new information to be obtained concerning Mycoplasma pneumoniae and Chlamydia pneumoniae infections. In children, these pathogens seem to have a more important role in causing respiratory-tract infections than previously thought; they have been associated with wheezing, and they are also frequent in children aged under 5 years. Contrary to original belief, no clinical, laboratory, or radiological findings seem to be unique to M. pneumoniae or C. pneumoniae; furthermore, there is no rapid and cost-effective diagnostic test capable of identifying these pathogens. Appropriate antimicrobial treatment of the infections they cause is needed to reduce the recurrent episodes of wheezing and other respiratory symptoms, to decrease morbidity, and to avoid the spread of the pathogens. However, a number of therapeutic issues remain unsolved.     

Mycoplasma pneumoniae and Chlamydia pneumoniae cause lower respiratory tract disease in paediatric patients

New studies suggest that Mycoplasma pneumoniae and Chlamydia pneumoniae play a more significant role as causes of lower respiratory tract infections in childhood than was previously thought. In particular, the incidence of infections caused by these pathogens is high in children aged less than 5 years, the infections themselves seem to be a possible cause of wheezing, and may present a more complicated course when not treated with adequate antimicrobial agents. However, despite the increasing pathogenic significance of M. pneumoniae and C. pneumoniae, progress in fighting them is hampered by the lack of rapid and standardized diagnostic methods. This not only makes it practically impossible for practitioners to make a specific microbiological diagnosis, but has also had an adverse effect on treatment trials and has generated some questionable results. Carefully randomized and controlled trials are clearly needed to examine the effectiveness of different antibiotics against M. pneumoniae or C. pneumoniae and the optimal duration of therapy in various patient populations.     

Importance of acute Mycoplasma pneumoniae and Chlamydia pneumoniae infections in children with wheezing.

In order to evaluate the role of Mycoplasma pneumoniae and Chlamydia pneumoniae in reactive airway disease, 71 children aged 2-14 yrs with an acute episode of wheezing and 80 age-matched healthy children were studied. Sera for the determination of specific antibody levels and nasopharyngeal aspirates for the detection of M. pneumoniae and C. pneumoniae deoxyribonucleic acid were obtained on admission and after 4-6 weeks. All children with wheezing received a standard therapy with inhaled corticosteroids and bronchodilators for 5-7 days; when antibiotic was added on the basis of the judgement of the paediatrician in charge, clarithromycin 15 mg.kg body weight(-1).day(-1) for 10 days was used. Acute M. pneumoniae and C. pneumoniae infections were detected significantly more often in children with wheezing than in controls. In patients infected with one of the two pathogens, a history of recurrent wheezing was significantly more frequent than in those without either infection. During a 3-month follow-up period, among nonantibiotic-treated children, those with acute M. pneumoniae and/or C. pneumoniae infection showed a significantly higher recurrence of wheezing than those without acute M. pneumoniae and/or C. pneumoniae infection (p=0.03). These results highlight the apparently significant relationship of Mycoplasma pneumoniae and Chlamydia pneumoniae with wheezing in children, particularly in subjects with a history of recurrent episodes, and the possible improvement in the course of reactive airway disease within paediatric patients with acute Mycoplasma pneumoniae and/or Chlamydia pneumoniae infection.     

Clinical comparison of Chlamydia pneumoniae pneumonia, ornithosis, and Mycoplasma pneumoniae pneumonia]

To elucidate the differences between the clinical aspects of Chlamydia pneumoniae (C. pn) pneumonia and those of two other atypical pneumonias, Chlamydia psittaci (C. ps) pneumonia and Mycoplasma pneumoniae (M. pn) pneumonia, we analyzed the symptoms and laboratory data on the cases of these three types of pneumonia: 46 cases of C. pn pneumonia, 39 cases of C. ps pneumonia, and 131 cases of M. pn pneumonia. C. pn pneumonia was significantly more frequent among the elderly (mean 70 +/- 16 years, p < 0.01) and patients were significantly more likely to be male (76%, p < 0.05). A white blood cell count of over 10,000 was seen in 46% of C. pn pneumonia cases, a higher proportion than those of C. ps pneumonia (15%, p = 0.03) or M. pn pneumonia (18%, p = 0.006) cases. The proportions of patients with these infections who had an elevated GOT or GPT were not significantly different. Maximum body temperature was higher in M. pn pneumonia than in C. pn pneumonia (p = 0.003). Purulent sputa were seen in 44% of C. pn pneumonia cases and 50% of M. pn pneumonia cases, and these rates were higher than that of 13% in C. ps pneumonia cases (p = 0.002, p = 0.004). Dyspnea and anorexia symptoms were the most frequent in C. pn pneumonia cases (24% and 29%, respectively, the highest of all three pneumonias). There were clinical differences between C. pn pneumonia and the other two atypical pneumonias. However, there was some difficulty in differentiating between C. pn pneumonia and typical bacterial pneumonia because mixed infections were common (24%) in C. pn pneumonia cases.     

A case of pneumonia due to coinfection by Mycoplasma pneumoniae and Chlamydia pneumoniae]

Few cases of Mycoplasma pneumoniae and Chlamydia pneumoniae coinfection in pneumonia have been reported in adults. We report a case of such a double infection in a young adult. A 16-year-old boy was admitted to our hospital with dry cough and fever. Laboratory findings revealed elevated serum GOT and GPT levels. The patient had been administered a beta-lactam antibiotic before admission to our hospital. Antibodies to M. pneumoniae were significantly elevated. Titers of IgM and IgG specific for C. pneumoniae titer were high, as measured by the enzyme-linked immunosorbent assay method. The patient was treated with clarithromycin and discharged after a satisfactory recovery. M. pneumoniae and C. pneumoniae may act as cofactors in community-acquired pneumonia. Further studies are needed to clarify the relationships of these pathogens to community-acquired pneumonia.     

Mycoplasma pneumoniae and Chlamydia pneumoniae infections in children with pneumonia. Mowgli Study Group.

The most common clinical signs, host responses and radiographic patterns were studied in 203 Italian children hospitalized for community-acquired pneumonia in order to clarify the role of clinical and radiological characteristics in the diagnosis of Mycoplasma pneumoniae and/or Chlamydia pneumoniae infections. Antibody measurements in paired sera and polymerase chain reaction on nasopharyngeal aspirates were used to establish the diagnoses of acute M. pneumoniae and C. pneumoniae infection, and the aetiologic data were correlated with the clinical, laboratory and radiographic data obtained on admission. No significant association was observed between evidence of M. pneumoniae and/or C. pneumoniae infection and periods of episode during the year, mean age of the study subjects, individual symptoms, physical findings or laboratory test results. Furthermore, no significant correlation was observed in relation to the radiological findings and M. pneumoniae and/or C. pneumoniae infection. This study shows that neither clinical findings nor laboratory parameters distinguished Mycoplasma pneumoniae and/or Chlamydia pneumoniae infection in children with pneumonia. Radiological findings also have a limited capacity to differentiate aetiologic agents. The priorities for future research include the development of rapid, easily accessible and cost-effective diagnostic tests useful for each episode of pneumonia in children.     

Mycoplasma pneumoniae and Chlamydia pneumoniae are associated to inflammation and rupture of the atherosclerotic coronary plaques

In this review we report recent findings of our lab showing that Mycoplasma pneumoniae and Chlamydia pneumoniae are present in higher amount, associated with adventitial inflammation and positive vessel remodeling, in thrombosed coronary artery segments (CAS) of patients who died due to acute myocardial infarction. CD8T cell was the predominant lymphocytes in the plaque and CD24(B) cell in the adventitia. The mean numbers of lymphocytes were significantly higher in adventitia than in the plaque. Vulnerable plaques were usually associated with focal positive vessel remodeling and large lipidic atheromas. Mycoplasma is the only bacterium that needs cholesterol for proliferation. We hypothesized that the association of Mycoplasma pneumoniae and Chlamydia pneumoniae increases virulence of both bacteria, inducing inflammation and rupture of the plaque. The search of CMV and Helicobacter pylori resulted negative.     

Role of Mycoplasma pneumoniae and Chlamydia pneumoniae in children with community-acquired lower respiratory tract infections.

In order to evaluate the role of Mycoplasma pneumoniae and Chlamydia pneumoniae, we studied 613 children aged 2-14 years who were hospitalized for community-acquired lower respiratory tract infections (LRTIs). The patients were enrolled in the study by 21 centers in different regions of Italy from May 1998 through April 1999. Paired serum samples were obtained on admission and after 4-6 weeks to assay the titers of M. pneumoniae and C. pneumoniae antibodies. Nasopharyngeal aspirates for the detection of M. pneumoniae and C. pneumoniae were obtained on admission. Acute M. pneumoniae infections in 210 patients (34.3%) and acute C. pneumoniae infections in 87 (14.1%) were diagnosed. Fifteen of the 18 children with M. pneumoniae and/or C. pneumoniae infections whose treatments were considered clinical failures 4-6 weeks after enrollment had not been treated with macrolides. Our study confirms that M. pneumoniae and/or C. pneumoniae plays a significant role in community-acquired LRTIs in children of all ages and that such infections have a more complicated course when not treated with adequate antimicrobial agents.     

Chlamydia pneumoniae and Mycoplasma pneumoniae in children with acute respiratory infection in general practices in The Netherlands

In this retrospective study Chlamydia pneumoniae and Mycoplasma pneumoniae infections were detected by polymerase chain reaction (PCR) in samples (n = 457) from children presenting with acute respiratory infection to general practitioners during 1992-97. Samples were collected in autumn and winter, and from 1994 onwards in spring and summer also. Overall, C. pneumoniae and M. pneumoniae were detected in throat or nasal samples by PCR in 3.1% and 2.4% of the cases, respectively. The proportion of both C. pneumoniae and M. pneumoniae infections varied between 0% and 6.9% over the years studied, whereas seasonal proportions varied from 1.8 to 9.1% and 1.2 to 4.5%, respectively. For both microorganisms the lowest proportion was detected during winter and the highest in summer. C. pneumoniae could already be detected by PCR in patients under 4 y of age, an observation not made in sero-epidemiological studies. In conclusion, both C. pneumoniae and M. pneumoniae infections play a minor role in children presenting with acute respiratory infection.     

A case of Chlamydia trachomatis and Mycoplasma pneumoniae coinfection in a child]

Mycoplasma pneumoniae infection is often experienced as community-acquired pneumonia, whereas Chlamydia trachomatis pneumonia is sometimes experienced as a vertical infection from mother to child through delivery, but is rare after six months of age. We reported the first case to date of a seven-year-old boy with coinfection of C. trachomatis and M. pneumoniae. The patient, who was referred to our hospital because of suspected pneumonia, had had severe cough and pyrexia for four days before his admission. The coinfection was confirmed because the antibodies to both bacteria were significantly increased. In addition the PCR for C. trachomatis detected the presence of C. trachomatis in the throat even after treatment. The PCR from a cervix swab of his mother and from a throat swab of his father were negative, but their antibodies to C. trachomatis were positive. We think that this may have been community-acquired pneumonia or due to persistent infection after a vertical transmission.     

Bordetella pertussis, Bordetella parapertussis, Mycoplasma pneumoniae, Chlamydia pneumoniae and persistent cough in children.

Material collected during a prospective pertussis vaccine trial in 1992-95 was examined for Bordetella pertussis (culture and serology), Bordetella parapertussis (culture), Mycoplasma pneumoniae and Chlamydia pneumoniae (PCR). From 64% (99/155) of episodes with cough for less than 100 d, 115 aetiological agents were identified in one southern and one northern subset of DT-recipients. The most common single agent was B. pertussis, representing 56%(64/115), with a median cough period of 51 d, followed by M. pneumoniae 26%(30/115), 23 d, C. pneumoniae 17% (19/115), 26 d, and B. parapertussis 2% (2/115). For co-infections, the median duration of cough was about 60 d. Spasmodic cough for 21 d or more (clinical WHO criteria for pertussis) was present in 82% (41/50) of infections with B. pertussis as single agent, 38% (17/45) with B. parapertussis, 38% (5/13) with C. pneumoniae, 26% (5/19) with M. pneumoniae and 30%(17/56) in cases where no aetiology was found. In children with cough for more than 100 d (n = 78) using all vaccine arms, B. pertussis was responsible in 83% (65/78), in 21%(16/78) together with other agents. Acellular vaccines were more efficient against serious disease than whole cell vaccine. Antibiotic treatment was more common at the southern (34%) study site than at the northern one (12%). The findings indicate that diagnosis should rely on laboratory confirmation, both for rational treatment of an individual case and for monitoring outbreaks.     

Multiplex PCR for the simultaneous detection of Chlamydia pneumoniae, Mycoplasma pneumoniae and Legionella pneumophila in community-acquired pneumonia

A multiplex polymerase chain reaction (PCR) was developed for the simultaneous detection of Chlamydia pneumoniae, Mycoplasma pneumoniae and Legionella pneumophila. Oligonucleotide primers for the amplification of the DNA of these three organisms were optimized for use in combination in the same reaction. PCR products were detected by the Micro-Chip Electrophoresis Analysis System. Clinical samples were obtained from 208 community-acquired pneumonia (CAP) patients who were participants in a multicenter CAP surveillance study performed at seven medical schools and their affiliate hospitals in Japan. No significant differences in the sensitivity of each primer set were observed when tested in both the multiplex and monoplex PCR assays. Our multiplex PCR was able to reliably detect 10 copies/100 microl of each of the three pathogen DNAs. Of the panel of 208 samples, 14 of 15 C. pneumoniae, 10 of 10 M. pneumoniae, eight of eight L. pneumophila and 165 of 176 negative samples were correctly identified. Eleven cases who were the multiplex PCR positive and conventional method negative were observed. The PCR findings were of possible significance in at least four of these patients. Our multiplex PCR assay could potentially be used as a diagnostic and epidemiological tool. Further prospective studies are needed to establish its clinical usefulness.     

Chest radiograph of atypical pneumonia: comparison among Chlamydia pneumoniae. Pneumonia, ornithosis, and Mycoplasma pneumoniae pneumonia

No report has been found comparing Chlamydia pneumoniae (C. pneumoniae) pneumonia radiographically with other atypical pneumonias, Chlamydia psittaci (C. psittaci) pneumonia and Mycoplasma pneumoniae (M. pneumoniae) pneumonia. We described the chest radiographs of three kinds of pneumonia cases: 46 cases of C. pneumoniae pneumonia, 39 cases of C. psittaci pneumonia, and 131 cases of M. pneumoniae pneumonia. Radiographic shadows were categorized into main shadows and sub-shadows. The main shadows are classified from the viewpoint of the characteristics; air space consolidation(AS), ground-glass opacity(GG), reticular shadow(RS), bronchopneumonia(BP), and small nodular shadows (SN). The size, the site, and the number of the main shadows were also analyzed. In comparison among the three pneumonias, BP was the most frequent in M. pneumoniae pneumonia (0.40/case). AS predominated in C. pneumoniae pneumonia (0.67/case), and GG in C. psittaci pneumonia (0.62/case). The number of main shadows was equal, about 1.4/case in three pneumonias. Large shadows were less frequent in M. pneumoniae pneumonia than C. pneumoniae pneumonia (p = 0.02) and C. psittaci pneumonia (p = 0.01). Main shadows were more frequent in the outer zone in M. pneumoniae pneumonia than C. psittaci pneumonia (p = 0.01), and in the middle zone in C. psittaci pneumonia than in M. pneumoniae pneumonia (p = 0.02). Cases with bilateral main shadows were less common in M. pneumoniae pneumonia (9%) than C. pneumoniae pneumonia(33%, p = 0.001) and C. psittaci pneumonia(30%, p = 0.005). Thickening of bronchovascular bundles as a sub-shadow was most frequently noted in M. pneumoniae pneumonia. Some differences among the three atypical pneumonias were seen in the chest radiograph. However, no specific findings of C. pneumoniae pneumonia were shown radiographically in this study.