M. Pneumoniae Pneumonia Research Articles

Model based on the automated AI-driven CT quantification is effective for the diagnosis of refractory Mycoplasma pneumoniae pneumonia

The prediction of refractory Mycoplasma pneumoniae pneumonia (RMPP) remains a clinically significant challenge. This study aimed to develop an early predictive model utilizing artificial intelligence (AI)-derived quantitative assessment of lung lesion extent on initial computed tomography (CT) scans and clinical indicators for RMPP in pediatric inpatients. A retrospective cohort study was conducted on patients with M. pneumoniae pneumonia (MP) admitted to the Children’s Hospital of Nanjing Medical University, China from January 2019 to December 2020. An early prediction model was developed by stratifying the patients with Mycoplasma pneumoniae pneumonia (MPP) into two cohorts according to the presence or absence of refractory pneumonia. A retrospective cohort of 126 children diagnosed with Mycoplasma pneumoniae pneumonia (MPP) was utilized as a training set, with 85 cases classified as RMPP. Subsequently, a prospective cohort comprising 54 MPP cases, including 37 instances of RMPP, was assembled as a validation set to assess the performance of the predictive model for RMPP from January to December 2021. We defined a constant Φ which can combine the volume and CT value of pulmonary lesions and be further used to calculate the logarithm of Φ to the base of 2 (Log2Φ). A clinical-imaging prediction model was then constructed utilizing Log2Φ and clinical characteristics. Performance was evaluated by the area under the receiver operating characteristic curve (AUC). The clinical model demonstrated AUC values of 0.810 and 0.782, while the imaging model showed AUC values of 0.764 and 0.769 in the training and test sets, respectively. The clinical-imaging model, incorporating Log2Φ, temperature(T), aspartate aminotransferase (AST), preadmission fever duration (PFD), and preadmission macrolides therapy duration (PMTD), achieved the highest AUC values of 0.897 and 0.895 in the training and test sets, respectively. A prognostic model developed through automated quantification of lung disease on CT scans, in conjunction with clinical data in MPP may be utilized for the early identification of RMPP.

A comparative study of general and severe mycoplasma pneumoniae pneumonia in children

ObjectivesThe increasing prevalence of severe Mycoplasma pneumoniae pneumonia (SMPP) poses a significant threat to the health of children. This study aimed to characterise and assess the outcomes in children with SMPP.MethodsWe retrospectively analysed children hospitalised for M. pneumoniae pneumonia (MPP) between January and December 2022. Retrospectively, demographic, clinical, underlying diseases, laboratory and radiological findings, and treatment outcomes were collected and analysed. Disease severity was defined as severe or general according to the Guideline for diagnosis and treatment of community-acquired pneumonia in children (2019 version).ResultsOver a 12-month observation period, 417 children with MPP were enrolled, 50.6% (211/417) of whom had SMPP, with the peak incidence observed in winter. Of the 211 children with SMPP, 210 were treated and discharged with improvement, while one child with congenital heart disease died of cardioembolic stroke. A significantly higher proportion of patients with SMPP had underlying diseases, extrapulmonary complications (myocardial and digestive system involvement), and bacterial co-infection. A total of 25 (12%) children with SMPP received mechanical ventilation. The median duration of mechanical ventilation was 3 days. All children were treated with macrolide antibiotic. A significantly higher proportion of patients with SMPP received antibiotic other than macrolides, methylprednisolone sodium succinate, intravenous immunoglobulin and anticoagulation, compared with patients with general MPP (GMPP). Children with SMPP had significantly higher levels of white blood cells, neutrophil percentage, C-reactive protein, procalcitonin, interferon-γ, interleukin (IL)-2, IL-5, IL-6, IL-8, IL-10 and significantly lower percentages of lymphocytes, monocytes, and natural killer cells, compared with GMPP group.ConclusionOur findings suggest that severely ill children have more pronounced inflammatory reaction and extrapulmonary complications. For effective management of children with SMPP, hormonal, prophylactic, anticoagulant therapy, as well as the use of antibiotics other than macrolides for bacterial co-infections, could be incorporated into treatment regimens.

The CARDS toxin of Mycoplasma pneumoniae induces a positive feedback loop of type 1 immune response.

Within the past 3-5 years, Mycoplasma pneumoniae has become a major pathogen of community-acquired pneumonia in children. The pathogenic mechanisms involved in M. pneumoniae infection have not been fully elucidated. Previous protein microarray studies have shown a differential expression of CXCL9 after M. pneumoniae infection. Here, we conducted a hospital-based study to explore the clinical significance of the type 1 immune response inflammatory factors interferon (IFN)-γ and CXCL9 in patients with M. pneumoniae pneumonia (MPP). Then, through in vitro experiments, we explored whether CARDS toxin stimulated F-DCs (dendritic cells incubated with Flt3L) to promote Th-cell differentiation; we also investigated the IFN-γ-induced CXCL9 secretion pathway in macrophages and the role of CXCL9 in promoting Th1 cell migration. The CXCL9 expression level was upregulated among patients with a higher fever peak, fever duration of greater than 7 days, an imaging manifestation of lobar or segmental, or combined pleural effusion (P<0.05). The peripheral blood levels of IFN-γ and CXCL9, which were higher in patients than in the healthy control group, were positively correlated with each other (r=0.502, P<0.05). In patients, the CXCL9 expression level was significantly higher in the bronchoalveolar lavage fluid (BALF) than in the peripheral blood, and the BALF CXCL9 expression level was higher than that in the healthy control group (all P<0.05). Our flow cytometry analysis revealed that M1-phenotype macrophages (CD16 + CD64 + CD163-) were predominant in the BALF from children with MPP. In in vitro experiments, F-DCs stimulated with CARDS toxin promoted the differentiation of CD4 + IFN-γ + Th (Th1) cells (P<0.05). Moreover, IFN-γ induced high levels of CXCL9 expression in M1-type macrophages in a dose-dependent and time-dependent manner. Additionally, macrophages transfection with STAT1-siRNA-1 downregulated the expression of CXCL9 (P<0.05), and CXCL9 promoted Th1 cell migration (P<0.05). Our findings suggest that CARDS toxin induces a type 1 immune response positive feedback loop during M. pneumoniae infection; this putative mechanism may be useful in future investigations of immune intervention approaches for M. pneumoniae pneumonia.

Clinical role of M. pneumoniae typing antibody detected by chemiluminescent immunoassay in the diagnosis of Mycoplasma pneumoniae pneumonia in children

ObjectiveThe levels of serum M. pneumoniae typing antibodies in children with community-acquired pneumonia (CAP) were detected by chemiluminescent immunoassay (CLIA) to explore the clinical role of M. pneumoniae typing antibody (MP-IgM, MP-IgG) in M. pneumoniae pneumonia. MethodsA total of 387 Child patients with CAP diagnosed at the Pediatric outpatient department of Zengcheng Branch, Nanfang Hospital, Southern Medical University, were enrolled between January 2020 to December 2021 and divided into M. pneumoniae pneumonia (MPP) group (n = 210) and non-M. pneumoniae pneumonia (NMPP) group (n = 177). Firstly, Clinical data, full blood count (WBC, NEU%, LYM%, MONO%, EOS%, BASO%, RBC, HGB, PLT) and biochemical tests (AST, LDH, ɑ-HBDH, CK, CKMB, CRP, PCT, IL-6) as well as laboratory diagnostic tests (MP-IgM, MP-IgG) were compared between the two groups. Secondly, we assessed the correlation between the average level of M. pneumoniae typing antibody detected by CLIA and the titer of anti-M. pneumoniae antibody (MP-Ab) tested by passive agglutination (PA) method. Thirdly, receiver operating characteristic (ROC) curve for the MP-IgM and MP-IgG was examined to evaluate the value of diagnosing M. pneumoniae pneumonia. Finally, we follow-up 120 cases of MPP group and analysis medication results. Results(1) Mean age, runny nose, expectoration, LYM%, NEU%, HGB, AST, MP-IgM and MP-IgG were statistically significant in the MPP group and NMPP group (all P < 0.05). (2) Correlation analysis showed that MP-IgM average level was linearly associated with MP-Ab titer (R2 = 0.84) and MP-IgG average level was exponentially correlated with MP-Ab titer under 1:640 (R2 = 0.96). (3) The ROC curve of MP-IgM and MP-IgG were significantly different (both P < 0.001). A serum MP-IgM level above 1 S/CO and MP-IgG level above 14.15 AU/mL were significant predictors for M. pneumoniae pneumonia: area under the curve (AUC) of 0.810, 0.815; standard error (SE) of 0.021, 0.022; 95 % confidence interval (CI) of 0.768–0.852, 0.773–0.858; the diagnostic sensitivity of 74.3 %, 62.1 %; and specificity of 72.9 %, 87.0 %; respectively. (4) Of the 120 children with M. pneumoniae pneumonia followed up, 79 (65.8 %) cases took azithromycin and 68 (86.1 %) cases were recovered. ConclusionsA series of our studies shown that, CLIA, speedy and automated clinical examination method, has higher specificity and sensitivity for the quantitative detection of MP-IgM and MP-IgG, playing an important role of early diagnosis as well as prompt intervention to reduces macrolide-resistant strains and sequelae of children with M. pneumoniae pneumonia.

Toll-Like Receptor 2 Modulates Pulmonary Inflammation and TNF-α Release Mediated by Mycoplasma pneumoniae.

ObjectivesTo investigate the roles that Toll-like receptors (TLRs) play in lung inflammation mediated by Mycoplasma pneumoniae (MP).MethodsThe changes in TLRs and tumor necrosis factor alpha (TNF-α) in peripheral blood of children with M. pneumoniae pneumonia (MPP) were monitored, and the interactions of signaling molecules regulating TNF-α release in A549 cells and neutrophils after M. pneumoniae stimulation were investigated. In TLR2 knockout (TLR2-/-) mice, the levels of TNF-α in bronchial alveolar lavage fluid (BALF) and peripheral blood after mycoplasma infection and the pathological changes in the lung tissue of mice were detected.ResultsTNF-α levels in peripheral blood of children with MPP were higher than those in non-infected children, and children with refractory MPP had the highest levels of TNF-α and TLR2. TNF-α secretion and TLR2, myeloid differentiation primary response 88 (MyD88) and phospho-p65(p-p65) levels were increased in stimulated cells. TNF-α secretion was suppressed upon siRNA-mediated TLR2 silencing. Pharmacological inhibition of nuclear factor-kappa B (NF-κB) and MyD88 effectively reduced TNF-α expression. Compared with wild-type mice, the TNF-α in serum and BALF decreased, and lung pro-inflammatory response was partially suppressed in TLR2-/- mice.ConclusionWe concluded that TLR2 regulates M. pneumoniae-mediated lung inflammation and TNF-α release through the TLR2-MyD88-NF-κB signaling pathway.

Ribosomal RNA‑depleted RNA sequencing reveals the pathogenesis of refractory Mycoplasma pneumoniae pneumonia in children.

Pneumonia caused by Mycoplasma pneumoniae (M. pneumoniae) is a major cause of community-acquired pneumonia in children. In some cases, M. pneumoniae pneumonia (MPP) can develop into refractory MPP (RMPP), which shows no clinical or radiological response to macrolides, and can progress to severe and complicated pneumonia. However, the pathogenesis of RMPP remains poorly understood. The present study aimed to identify target genes that could be used as biomarkers for the clinical diagnosis of early-stage RMPP through high-throughput sequencing technology. The differences in long non-coding (lnc)RNAs, mRNAs and circular (circ)RNAs were examined between whole-blood samples from two patients with non-refractory MPP (NRMPP), two patients with RMPP and three healthy children using ribosomal (r)RNA-depleted RNA-sequencing techniques and an integrated mRNA/circRNA analysis. A total of 17 lncRNAs (four upregulated and 13 downregulated), 18 mRNAs (six upregulated and 12 downregulated) and 24 circRNAs (12 upregulated and 12 downregulated) were the most significantly differentially expressed (P<0.05) between the NRMPP and RMPP groups. Upon functional analysis, the significantly differentially expressed genes encoded by the targeting mRNAs (prostaglandin-endoperoxide synthase 2, IL-8 and fos-like antigen 1) were screened and identified to be enriched in the ‘IL-17 signaling pathway’. Furthermore, the key circRNAs in the NRMPP and RMPP comparative groups were primarily enriched in ‘herpes simplex virus 1 infection’, ‘viral carcinogenesis’ and ‘RNA transport’. In the present study, a comprehensive analysis of the differences between the NRMPP and RMPP cases was performed based on rRNA-depleted RNA-sequencing techniques, and the selected genes and circRNAs may be closely associated with the complex pathogenesis of RMPP.

Prediction of risk factors of bronchial mucus plugs in children with Mycoplasma pneumoniae pneumonia

BackgroundRecently, many cases of pneumonia in children with Mycoplasma pneumoniae infection have been shown to have varying degrees of intrabronchial mucus plug formation. The clinical, laboratory, radiological characteristics, and treatment of patients with Mycoplasma infection are analyzed in this study. The risk factors for M. pneumoniae pneumonia (MPP) mucus plug formation in children are explored, and a risk factor scoring system is established.MethodsMPP patients treated with bronchoscopy were retrospectively enrolled in the study from February 2015 to December 2019. The children were divided into a mucus plug group and a control group according to the presence or absence of mucus plug formation. The clinical, laboratory, radiological characteristics, and treatment of the two groups of children were compared. Univariate and multivariate logistic regression models were used to identify the risk factors for MPP mucus plug formation. The receiver operating characteristic (ROC) curve was drawn to evaluate the regression model and establish the MPP mucous plug risk factor scoring system.ResultsA univariate analysis showed that the children in the mucous group were older and had a longer fever duration, longer hospital stay, higher fever peak, more cases of wheezing symptoms and allergies, and azithromycin or corticosteroids were administered later. In addition, neutrophil, C-reactive protein (CRP), lactate dehydrogenase (LDH), D-dimer (DD), sputum MP-DNA copy number, and total immunoglobulin A (IgA) levels were higher, while prealbumin (PA) levels were lower. The ROC curve analysis showed that children with MPP had PA ≤144.5 mg/L, had used corticosteroids during the course of the illness of ≥4.5 days, CRP ≥12.27 mg/L, an LDH ≥ 462.65 U/L, and there was a possibility of intra-airway mucus formation. The independent risk factors were scored according to their odds ratio (OR) value. Among the 255 children with MPP, the high-risk group had 44 (83.02%) mucus plugs out of 53; the middle-risk group had 35 (34.3%) mucus plugs out of 102; and the low-risk group had 11 (11%) mucus plugs out of 100.ConclusionsPA levels, timing of corticosteroid use (use in the first few days), CRP levels, and LDH levels were independent risk factors for MPP mucus plug formation. This provides a basis for the early identification of MPP in children combined with mucus plug formation.

Rational stepwise approach for Mycoplasma pneumoniae pneumonia in children.

Mycoplasma pneumoniae is a common pathogen that causes community-acquired pneumonia. In the past, M. pneumoniae was sensitive to macrolide antibiotics, and M. pneumoniae pneumonia (MPP) was usually a benign and self-limiting disease. However, despite use of the appropriate antibiotics, persistent fever and clinical deterioration may occur, leading to severe disease. Two major complicated conditions that may be clinically encountered are macrolide-resistant MPP and refractory MPP. Regarding the epidemics in Taiwan, before 2017, the mean rate of macrolide resistance was below 30%. Notably, since 2018, the prevalence of macrolide-resistant MPP in Taiwan has increased rapidly. Macrolide-resistant MPP shows persistent fever and/or no radiological regression to macrolide antibiotics and may even progress to severe and complicated pneumonia. Tetracyclines (doxycycline or minocycline) or fluoroquinolones are alternative treatments for macrolide-resistant MPP. Refractory MPP is characterized by an excessive immune response against the pathogen. In this context, corticosteroids have been suggested as an immunomodulator for downregulating the overactive host immune reaction. Overuse of macrolides may contribute to macrolide resistance, and thereafter, an increase in macrolide-resistant MPP. Delayed effective antimicrobial treatment is associated with prolonged and/or more severe disease. Thus, the appropriate prescription of antibiotics, as well as the rapid and accurate diagnosis of MPP, is important. The exact starting point, dose, and duration of the immunomodulator are yet to be established. We discuss these important issues in this review.

Severe Mycoplasma pneumoniae pneumonia requiring intensive care in children, 2010–2019

Despite the high prevalence of Mycoplasma pneumoniae infections, reports on severe life-threatening M. pneumoniae pneumonia (MPP) in children are limited. We retrospectively enrolled pediatric patients with PCR-positive MPP requiring ICU admission in a children's hospital in Taipei, Taiwan from Jun 2010 to October 2019. Clinical manifestations and laboratory data of severe MPP were analyzed. Macrolide susceptibility was determined by genotyping, and its relationship with clinical manifestations was also analyzed. Approximately 5% (34/658) children hospitalized for MPP required ICU admission. Compared with non-ICU cases (n=291), ICU cases (n=34) were associated with more underlying conditions, more pleural effusion, longer fever duration, longer hospital stay, the requirement of second-line antibiotic treatment, and delayed effective and second-line antibiotic treatment. Macrolide resistance was similar in ICU and non-ICU groups (53% vs 53%; p=0.986). In severe MPP, patients requiring endotracheal intubation were associated with more septic shock, empyema, ARDS, prolonged fever after effective antibiotic treatment, delayed second-line and effective antibiotic treatment. In 18 of the 22 patients with pleural fluid analysis, the pleural effusion was alkaline (pH>7.7) and lymphocyte-predominant. M. pneumoniae infection can cause severe life-threatening pneumonia in children. Delayed effective and second-line antibiotic treatments are associated with severe life-threatening MPP.

Human adenovirus Coinfection aggravates the severity of Mycoplasma pneumoniae pneumonia in children

BackgroundMycoplasma pneumoniae (M. pneumoniae) is an important pathogen of community-acquired pneumonia (CAP) in children. The coinfection rate of M. pneumoniae pneumonia (MPP) can reach 52% in some areas, but the effects of coinfection with different pathogens have not been clearly recognized.MethodsThe cases of MPP hospitalized in Beijing Children’s Hospital from 1/1/2014 to 12/31/2016 were screened. MPP patients coinfected with Human adenovirus (HAdV) were categorized into the research group. Patients with single M. pneumoniae infection were categorized into the control group, matching the research group by age and admission time with a ratio of 1:3. Clinical manifestations, laboratory examinations, and disease severity were compared between these two groups.ResultsA total of 2540 hospitalized MPP cases were screened in Beijing Children’s Hospital, among which thirty cases were enrolled in the research group and ninety cases were enrolled in the control group. The results indicated that patients in the research group had longer hospital stays, longer fever durations and a higher rate of dyspnea, as well as a larger proportion applications of oxygen therapy and noninvasive continuous positive airway pressure (NCPAP). No obvious differences were found in lab examinations within the two groups. Regarding disease severity, the proportions of extremely severe pneumonia and severe disease defined by the clinical score system were higher in the research group than in the control group.ConclusionCompared with single M. pneumoniae infection, MPP coinfected with HAdV in children was relatively more serious.

High expression of miR-222-3p in children with Mycoplasma pneumoniae pneumonia

ObjectivesMycoplasma pneumoniae is a leading cause of community-acquired pneumonia in children. However, its mechanism of pathogenesis is not fully understood, and microRNAs might play a role. This study aimed to explore the microRNA-222-3p (miR-222-3p) expression and its possible role in children with M.pneumoniae pneumonia (MPP).MethodsThirty-six children with MPP and twenty-seven age-matched controls from Children’s Hospital of Soochow University were enrolled in this study. MiR-222-3p and cluster of differentiation 4 (CD4) mRNA were detected using real-time PCR in children’s peripheral blood plasma samples. THP-1 cells and mice were stimulated with M.pneumoniae lipid-associated membrane proteins(LAMPs).ResultsChildren with MPP had significantly higher levels of miR-222-3p and lower levels of CD4 in peripheral blood plasma (P < 0.05). Additionally, Sixteen children with MPP complicated with pleural effusion had higher miR-222-3p levels than those without pleural effusion. MiR-222-3p or CD4 in THP-1 cells increased or decreased, respectively, in a dose dependent manner after LAMP stimulation. In LAMP-stimulated mice massive inflammatory cells infiltrates surrounded the bronchioles, and miR-222-3p increased in the bronchoalveolar lavage fluid. In conclusion, miR-222-3p was highly expressed in children with MPP, especially those with pleural effusion.ConclusionSmall sample studies showed that M.pneumoniae or its LAMPs could increase miR-222-3p and decrease CD4 in macrophages,both in vitro and vivo.Thus, miR-222-3p might be an MPP biomarker for the diagnosis and prognosis.

Lung Microbiota and Pulmonary Inflammatory Cytokines Expression Vary in Children With Tracheomalacia and Adenoviral or Mycoplasma pneumoniae Pneumonia.

Community-acquired pneumonia (CAP) is a worldwide infectious disease caused by bacteria, viruses, or a combination of these infectious agents. Mycoplasma pneumoniae is an atypical pneumonia pathogen that causes high morbidity and mortality in children, and adenovirus can lead to severe pneumonia. However, the etiology of different types of pneumonia is still unclear. In this study, we selected a total of 52 inpatients with M. pneumoniae pneumonia (MPP) (n = 21), adenovirus pneumonia (AVP) (n = 16), or tracheomalacia (n = 15) to serve as a disease control. Bronchoalveolar lavage fluid (BALF) samples that had been obtained for clinical use were analyzed. We compared the differences in microbiota and the expression of 10 inflammatory cytokines in samples between MPP, AVP, and tracheomalacia. We found that the bacterial diversity in MPP was lower than that in AVP and tracheomalacia. Mycoplasma, Streptococcus, and Pseudomonas were predominant in samples of MPP, AVP, and tracheomalacia, respectively. The expression levels of IL-6, IL-8, and IL-10 were significantly higher in inpatients with AVP compared to children hospitalized with tracheomalacia or MPP. The lung microbiota in MPP was remarkably correlated with IL-2, IL-4, IL-5, IL-6, TNF-α, and IL-1α expressions, while this was not found in tracheomalacia and AVP. Microbiota analysis identified a high load of multi-drug resistant Acinetobacter baumannii in the lung microbiota of several inpatients, which might be associated with the long hospitalization length and intra-group differences at the individual level. This study will help to understand the microbial etiology of tracheomalacia, AVP, and MPP and to identify effective therapies for these diseases.

Rapid Detection of the Macrolide Sensitivity of Pneumonia-Causing Mycoplasma pneumoniae Using Quenching Probe Polymerase Chain Reaction (GENECUBE®).

Macrolide-resistant Mycoplasma pneumoniae (MR-MP) have been reported worldwide. Strategies for the treatment of MR-MP are a key focus of research. The GENECUBE® is a novel, fully automated rapid genetic analyzer. The goals of this study were to assess the macrolide sensitivity of M. pneumoniae (MP) isolates by analyzing 23S ribosomal RNA (rRNA) gene sequences using a GENECUBE®-based system and to determine the validity of this system in determining clinical treatment options for MP pneumonia. This was an observational retrospective study including 150 children with MP pneumonia. We used quenching probe polymerase chain reaction (Q-probe PCR) as implemented in the GENECUBE® system to detect macrolide resistance-causing mutations in the MP 23S rRNA gene. We compared the duration of fever between patients receiving initial empirical antibiotic treatment (Empirical T group) and those receiving treatment after Q-probe PCR (PCR First group) diagnosis. Selecting antibiotic treatment after Q-probe PCR significantly shortened the duration of fever compared to empirical antibiotic treatment (PCR First group, median: 6.0days [n = 32]; Empirical T group, median: 7.5days [n = 66]; p = 0.002). Comparison of macrolide sensitivity using Q-probe PCR and clinical diagnosis showed that the reliability of Q-probe PCR was nearly validated for macrolide sensitivity. Q-probe PCR as implemented by GENECUBE® is a useful tool for the diagnosis of MP pneumonia and enables optimization of the selection of antibiotics in order to rapidly improve the clinical course of disease.

The changes of prevalence and etiology of pediatric pneumonia from National Emergency Department Information System in Korea, between 2007 and 2014.

PurposeUnderstanding changes in pathogen and pneumonia prevalence among pediatric pneumonia patients is important for the prevention of infectious diseases.MethodsWe retrospectively analyzed data of children younger than 18 years diagnosed with pneumonia at 117 Emergency Departments in Korea between 2007 and 2014.ResultsOver the study period, 329,380 pediatric cases of pneumonia were identified. The most frequent age group was 1–3 years old (48.6%) and the next was less than 12 months of age (17.4%). Based on International Classification of Diseases, 10th revision diagnostic codes, confirmed cases of viral pneumonia comprised 8.4% of all cases, pneumonia due to Mycoplasma pneumoniae comprised 3.8% and confirmed cases of bacterial pneumonia 1.3%. The prevalence of confirmed bacterial pneumonia decreased from 3.07% in 2007 and 4.01% in 2008 to 0.65% in 2014. The yearly rate of pneumococcal pneumonia also decreased from 0.47% in 2007 to 0.08% in 2014. A periodic prevalence of M. pneumoniae pneumonia (MP) was identified.ConclusionThe increased number of patients with pneumonia, bacterial pneumonia, pleural effusion, and empyema in 2011 and 2013–2014 resulted from an MP epidemic. We provide evidence that the frequency of confirmed cases of bacterial pneumonia and pneumococcal pneumonia has declined from 2007 to 2014, which can simultaneously reflect the effectiveness of the pneumococcal conjugate vaccine.

Clinical Features of Severe or Fatal Mycoplasma pneumoniae Pneumonia.

Mycoplasma pneumoniae is one of the most common causes of community-acquired pneumonia in children and young adults. The incidence of fulminant M. pneumoniae pneumonia (MPP) is relatively rare despite the high prevalence of M. pneumoniae infection. This literature review highlights the clinical features of fulminant MPP by examining the most recent data in epidemiology, clinical presentation, pathogenesis, and treatment. Fulminant MPP accounts for 0.5–2% of all MPP cases and primarily affects young adults with no underlying disease. Key clinical findings include a cough, fever, and dyspnea along with diffuse abnormal findings in radiological examinations. Levels of inflammatory markers such as white blood cells and C-reactive protein are elevated, as well as levels of lactate dehydrogenase, IL-18, aspartate transaminase, and alanine transaminase. The exact pathogenesis of fulminant MPP remains unclear, but theories include a delayed hypersensitivity reaction to M. pneumoniae and the contribution of delayed antibiotic administration to disease progression. Treatment options involve pairing the appropriate anti-mycoplasma agent with a corticosteroid that will downregulate the hypersensitivity response, and mortality rates are quite low in this treatment group. Further research is necessary to determine the exact pathogenesis of severe and fulminant types of MPP.

Role of the Mycoplasma pneumoniae/Interleukin-8/Neutrophil Axis in the Pathogenesis of Pneumonia.

Neutrophil infiltration is the characteristic pathological feature of M. pneumoniae pneumonia (MPP). This study aimed to explore the associations among neutrophil activity, clinical presentation, and role of the M. pneumoniae/interleukin-8 (IL-8)/neutrophil axis in the pathogenesis of MPP. A total of 42 patients with MPP were prospectively enrolled in the study. Neutrophil activity, including matrix metalloproteinase-9 (MMP-9), myeloperoxidase (MPO), and neutrophil elastase (NE), were measured. Clinical information was collected for all patients and control group. In vitro, IL-8 production was measured at different time points after M. pneumoniae infection of bronchial epithelial cells, and neutrophil activity was analyzed after IL-8 stimulation. The percentage of neutrophil in the bronchoalveolar lavage fluid was higher in the group of patients with high levels of M. pneumoniae DNA than in those with low levels of M. pneumoniae DNA (P < 0.05). IL-8, MMP-9, and NE in patients with MPP significantly increased compared with controls and decreased after treatment (P < 0.05). MPO and MMP-9 were associated with duration of fever (r = 0.332, P < 0.05) and length of stay (r = 0.342, P < 0.05), respectively. In vitro, M. pneumoniae induced IL-8 production by bronchial epithelial cells in a time dependent manner. MPO, MMP-9 and NE production by neutrophils significantly increased compared with medium controls after IL-8 stimulation. In summary, the M. pneumoniae/IL-8/neutrophil axis likely plays a vital role in the pathogenesis of MPP.

Relationships between the varied ciliated respiratory epithelium abnormalities and severity of Mycoplasma pneumoniae pneumonia.

The pathogenesis of Mycoplasma pneumoniae infection involves cytoadherence of M. pneumoniae to the ciliated respiratory epithelium (CRE), followed by CRE injury caused by the M. pneumoniae. However, whether CRE abnormalities are related to the severity of M. pneumoniae pneumonia (MP) remains to be determined. Thirty-eight patients with MP and 8 controls who underwent fiber-optic bronchoscopy with bronchial biopsy were included in this study. Patients with MP were divided into 2 groups: a mild disease group (12 patients) and a severe disease group (26 patients). The clinical features, laboratory findings, chest radiographic findings, and CRE abnormalities were characterized. Patients with severe pneumonia had a higher epithelial integrity score than those with mild pneumonia (5.1 ± 0.76 vs 3.8 ± 0.75; p < 0.01). Patients with severe CRE abnormalities had a longer duration of fever (p < 0.01), higher C-reactive protein (p < 0.01), and lower proportion of blood lymphocytes (p < 0.05) compared to those with mild abnormalities. Patients with a positive bacteria culture had a higher epithelial integrity score compared to those with a negative culture (6.0 ± 0.44 vs 4.8 ± 0.71; p < 0.01). CRE abnormalities are closely related to the severity of MP. These findings extend our current knowledge of MP.

Global secretome characterization of A549 human alveolar epithelial carcinoma cells during Mycoplasma pneumoniae infection

BackgroundMycoplasma pneumoniae (M. pneumoniae) is one of the major etiological agents for community-acquired pneumonia (CAP) in all age groups. The early host response to M. pneumoniae infection relies on the concerted release of proteins with various biological activities. However, no comprehensive analysis of the secretory proteins has been conducted to date regarding the host response upon M. pneumoniae infection.ResultsWe employed the liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based label-free quantitative proteomic technology to identify and characterize the members of the human alveolar epithelial carcinoma A549 cell secretome during M. pneumoniae infection. A total of 256 proteins were identified, with 113 being differentially expressed (>1.5-fold change), among which 9 were only expressed in control cells, 10 only in M. pneumoniae-treated cells, while 55 were up-regulated and 39 down-regulated by M. pneumoniae. The changed expression of some of the identified proteins was validated by RT-PCR and immunoblot analysis. Cellular localization analysis of the secretome data revealed 59.38% of the proteins were considered as “putative secretory proteins”. Functional analysis revealed that the proteins affected upon M. pneumoniae infection were mainly related to metabolic process, stress response, and immune response. We further examined the level of one up-regulated protein, IL-33, in clinical samples. The result showed that IL-33 levels were significantly higher in the plasma and bronchoalveolar lavage fluid (BALF) of M. pneumoniae pneumonia (MPP) patients.ConclusionsThe present study provided systematic information about the changes in the expression of secretory proteins during M. pneumoniae infection, which is useful for the discovery of specific biomarkers and targets for pharmacological intervention.

Clinical significance of different bacterial load of Mycoplasma pneumoniae in patients with Mycoplasma pneumoniae pneumonia

ObjectiveThis retrospective study was conducted to investigate the clinical significance of different Mycoplasma pneumoniae bacterial load in patients with M. pneumoniae pneumonia (MP) in children. MethodsPatients with MP (n=511) were identified at the Children's Hospital Affiliated to Soochow University database during an outbreak of MP between January 2012 and February 2013. ResultsComparing patients with high and low bacterial load those with higher loads were significantly older (p<0.01) and had fever significantly more frequently (p=0.01). Presence of wheezing at presentation was associated with low bacterial load (p=0.03). Baseline positive IgM was present in 93 (56.4%) patients with high bacterial load compared to 46 (27.8%) patients with low bacterial load (p<0.001). Co-infection with viruses was found significantly more frequent among patients with low bacterial load (24.2%) than those with high bacterial load (8.5%) [p<0.001]. Bacterial co-infection was also more frequently detected among patients with low bacterial load (22.4%) than in those with high bacterial load (12.1%) [p=0.01]. ConclusionM. pneumoniae at a high bacterial load could be an etiologic agent of respiratory tract disease, whereas the etiologic role of MP at a low bacterial load remains to be determined.

Epidemiological characteristics and meteorological factors of childhood Mycoplasma pneumoniae pneumonia in Hangzhou

Mycoplasma pneumoniae (M. pneumoniae) is an important pathogen of pediatric respiratory infections and the relation of M. pneumoniae pneumonia (MPP) with meteorological factors remains obscure. This study aims to investigate the epidemiological characteristics of childhood MPP and observe if there is a relationship between epidemiological characteristics and meteorological factors in Hangzhou. M. pneumoniae DNA in nasopharyngeal aspirates of hospitalized pneumonia children were detected by polymerase chain reaction from January 1, 2007 to December 31, 2009. The positive rates of MPP (MPP rates) in different years, seasons and ages were compared. The relationship between MPP rates and meteorological data, including mean air temperature (°C), mean relative humidity (%), monthly precipitation (mm) and raining days were analyzed. In 14 799 pneumonia cases found from 2007 to 2009, the MPP rate was 18.5%. Altogether 1610 boys (16.9%) and 1134 girls (21.4%) suffered from MPP with a significant difference between both genders (χ(2)=45.68, P<0.001). In children younger than 1 year, 1-2 years, 3-6 years, and older than 7 years, the MPP rates were 9.8%, 21.1%, 44.4% and 61.6%, respectively. The MPP rates were significantly higher in older children than in younger ones (trends test χ(2)=46.72, P<0.001). In a descending order, the MPP rates in summer, autumn, spring, and winter were 27.8%, 23.9%, 18.0% and 11.6%, respectively (χ(2)=372.75, P<0.001). The MPP rates in 2007 to 2009 were 12.9%, 19.3% and 23.6%, respectively (trends test χ(2)=13.72, P<0.001). Of the four meteorological factors, only monthly mean air temperature was included in the multiple linear regression model (P<0.001). This study showed that the MPP rate was higher in older children than in younger ones. Girls had a higher positive rate of MPP than boys. In Hangzhou, MPP was more prevalent in summer and autumn. Air temperature was the only meteorological factor affecting the prevalence of MPP.