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Respiratory Research Jan 2024This study aimed to investigate the interactions among three core elements of respiratory infection-pathogen, lung microbiome, and host response-and their avocation with...
BACKGROUND
This study aimed to investigate the interactions among three core elements of respiratory infection-pathogen, lung microbiome, and host response-and their avocation with the severity and outcomes of Mycoplasma pneumoniae pneumonia (MPP) in children.
METHODS
We prospectively collected bronchoalveolar lavage fluid from a cohort of 41 children with MPP, including general MPP (GMPP) and complicated MPP (CMPP), followed by microbiome and transcriptomic analyses to characterize the association among pathogen, lung microbiome, and host response and correlate it with the clinical features and outcomes.
RESULTS
The lung microbiome of patients with CMPP had an increased relative abundance of Mycoplasma pneumoniae (MP) and reduced alpha diversity, with 76 differentially expressed species. Host gene analysis revealed a key module associated with neutrophil function and several inflammatory response pathways. Patients with a high relative abundance of MP, manifested by a specific lung microbiome and host response type, were more prone to CMPP and had a long imaging recovery time.
CONCLUSION
Patients with CMPP have a more disrupted lung microbiome than those with GMPP. MP, lung microbiome, and host response interacts with each other and are closely related to disease severity and outcomes in children with MPP.
Topics: Child; Humans; Mycoplasma pneumoniae; Transcriptome; Pneumonia, Mycoplasma; Lung; Nitrobenzenes; Organophosphorus Compounds
PubMed: 38238712
DOI: 10.1186/s12931-024-02687-4 -
Molecules (Basel, Switzerland) Oct 2023() is an atypical bacterial pathogen responsible for community-acquired pneumonia primarily among school-aged children and young adults. () has been used as a...
() is an atypical bacterial pathogen responsible for community-acquired pneumonia primarily among school-aged children and young adults. () has been used as a medicinal and edible plant in China for centuries, the constituents from which possessed various bioactivities. Notably, flavonoids existing in residues of defatted seeds exhibited significant anti-inflammatory activities. In the present study, we investigated the impact of total flavonoids from (TFCO) seed extract on pneumonia. TFCO was obtained using multiple column chromatography methods and identified as kaempferol glycosides via UPLC-HRESIMS. In a pneumonia mouse model, TFCO significantly reduced the lung damage, suppressed IL-1β, IL-6, and TNF-α production, and curbed TLR2 activation triggered by . Similarly, in RAW264.7 macrophage cells stimulated by lipid-associated membrane proteins (LAMPs), TFCO suppressed the generation of proinflammatory cytokines and TLR2 expression. Moreover, TFCO diminished the phosphorylation of IκBα, JNK, ERK, p38, and p65 nuclear translocation in vitro. In conclusion, TFCO alleviated -induced lung damage via inhibition of TLR2-mediated NF-κB and MAPK pathways, suggesting its potential therapeutic application in -triggered lung inflammation.
Topics: Animals; Child; Mice; Humans; NF-kappa B; Mycoplasma pneumoniae; Toll-Like Receptor 2; Flavonoids; Camellia; Lung Injury; Pneumonia
PubMed: 37894556
DOI: 10.3390/molecules28207077 -
Frontiers in Immunology 2023(MP) infection serves as a substantial cofactor in Kawasaki disease (KD) among patients. Although the dominant issue triggering KD has recently focused on MP infection,...
BACKGROUND
(MP) infection serves as a substantial cofactor in Kawasaki disease (KD) among patients. Although the dominant issue triggering KD has recently focused on MP infection, the complete demonstration of the relationship between MP infection and KD remains elusive. This study endeavors to scrutinize and compare the clinical manifestations and cardiac involvement between MP-triggered KD and non-infection-associated KD.
METHOD
This retrospective study (2023-039, approved by the Institutional Review Board of West China Second University Hospital of Sichuan University) encompassed 247 consecutive patients diagnosed with KD between June 2017 and December 2022. Patients were categorized into two groups: the MP group (n = 38) and the non-MP group (n = 209). Univariable analysis was utilized to discern differences in clinical features, severity of inflammation, and initial or persistent cardiac complications between the two groups.
RESULTS
The MP group exhibited a more intricate clinical profile compared with the non-MP group, characterized by prolonged hospital stays, a higher incidence of incomplete KD, and elevated comorbidities. In addition, MP infection correlated with severe hematological disorders, coagulation dysfunction, and myocardial injuries. Our findings revealed that MP infection led to prolonged inflammation after initial treatment with intravenous immunoglobulin. Although initial cardiac assessments failed to discern disparities between the two groups, MP infection notably exacerbated coronary artery aneurysms (CAAs), resulting in sustained dilation.
CONCLUSIONS
Recognizing MP infection as a significant infectious factor associated with KD is imperative. In patients with KD, MP infection significantly prolongs inflammation and causes hematological disturbances during the initial treatment phase. Moreover, the presence of MP infection exacerbates the progression of CAAs and myocardial injuries during the subacute phase of KD, consequently contributing to the persistence of CAAs.
Topics: Humans; Retrospective Studies; Mucocutaneous Lymph Node Syndrome; Heart Diseases; Coronary Aneurysm; Pneumonia, Mycoplasma; Inflammation
PubMed: 38304251
DOI: 10.3389/fimmu.2023.1310134 -
Frontiers in Cellular and Infection... 2023Omadacycline is a novel tetracycline antibiotic that exhibits good antibacterial activity against atypical pathogens such as . It is approved for the treatment of...
Omadacycline is a novel tetracycline antibiotic that exhibits good antibacterial activity against atypical pathogens such as . It is approved for the treatment of adults with community-acquired bacterial pneumonia. However, the safety and efficacy of omadacycline in pediatric patients under 18 years of age have not yet been established. In the present paper, we report a case of pediatric community-acquired pneumonia in which initial empirical anti-infective therapy had failed. The patient received empirical anti-infective therapy with azithromycin and other antimicrobial agents upon admission but showed a poor clinical response and developed secondary tinnitus and liver dysfunction. After the confirmation of infection through metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid, an antibiotic switch to omadacycline was made. Thereafter, the patient's condition improved, and no adverse reactions were observed. These findings demonstrate that mNGS enables the identification of infection-causing pathogens in patients with unresponsive pneumonia. Omadacycline can be considered as an alternative option for anti-infective therapy in pediatric pneumonia, especially when the presence of bacterial resistance, adverse drug reactions, or organ failure are taken into consideration.
Topics: Adult; Humans; Adolescent; Child; Macrolides; Mycoplasma pneumoniae; Drug Resistance, Bacterial; Anti-Bacterial Agents; Pneumonia, Mycoplasma; Tetracyclines; Community-Acquired Infections
PubMed: 37842004
DOI: 10.3389/fcimb.2023.1244398 -
Scientific Reports Mar 2024This study aimed to investigate differences in clinical characteristics and laboratory findings between children infected with Macrolide-Sensitive Mycoplasma pneumoniae... (Observational Study)
Observational Study
This study aimed to investigate differences in clinical characteristics and laboratory findings between children infected with Macrolide-Sensitive Mycoplasma pneumoniae (MSMP) and Macrolide-Resistant Mycoplasma pneumoniae (MRMP). Additionally, the research sought to identify laboratory markers for rapidly distinguishing refractory Mycoplasma pneumoniae pneumonia (RMPP) from ordinary Mycoplasma pneumoniae pneumonia (OMPP). In total, 265 Mycoplasma pneumoniae (MP) patients were included, with MRMP identified by specific point mutations in domain V of the 23S rRNA gene. A retrospective analysis compared the clinical courses and laboratory data, revealing that MRMP patients experienced prolonged febrile days (P = 0.004), elevated CRP levels (P < 0.001), and higher MP DNA loads than MSMP patients (P = 0.037). Based on clinical symptoms, MRMP was divided into RMPP (n = 56) and OMPP (n = 70), with RMPP demonstrating significantly increased IL-18, community-acquired respiratory distress syndrome (CARDS) toxins in nasopharyngeal aspirate, and serum CRP levels (P < 0.001; P = 0.006; P < 0.001). In conclusion, timely recognition of RMPP is crucial for enhancing prognosis. The identification of MRMP, coupled with proinflammatory cytokines such as IL-18, CARDS toxins, and CRP, emerges as promising markers with the potential to contribute significantly to diagnostic accuracy and prognosis assessment.
Topics: Child; Humans; Anti-Bacterial Agents; China; Drug Resistance, Bacterial; Interleukin-18; Macrolides; Mycoplasma pneumoniae; Pneumonia, Mycoplasma; Respiratory Distress Syndrome; Retrospective Studies
PubMed: 38453960
DOI: 10.1038/s41598-024-55311-2 -
Euro Surveillance : Bulletin Europeen... Jan 2024In 2023, through an ongoing respiratory pathogen surveillance system, we observed from mid-September onwards, an increase of respiratory illness among children aged...
In 2023, through an ongoing respiratory pathogen surveillance system, we observed from mid-September onwards, an increase of respiratory illness among children aged ≤ 15 years presenting at hospital outpatient clinics in Beijing, China. Data indicated that illness was caused by multiple pathogens, predominantly . Seasonality, periodicity and high prevalence of resistance to macrolide (30 of 30 strains sequenced with the A2063G mutation) were important characteristics of the epidemic, which resulted in a rise in consultations at specialised paediatric hospitals.
Topics: Child; Humans; Pneumonia, Mycoplasma; Beijing; Drug Resistance, Bacterial; Mycoplasma pneumoniae; Anti-Bacterial Agents; Macrolides; China
PubMed: 38214078
DOI: 10.2807/1560-7917.ES.2024.29.2.2300704 -
Italian Journal of Pediatrics Sep 2023Tuberous sclerosis complex (TSC) is an autosomal dominant disorder with different initial symptoms and complex clinical manifestations. A 14-year-old female patient... (Review)
Review
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder with different initial symptoms and complex clinical manifestations. A 14-year-old female patient presented with persistent fever and severe headache. Medical imaging examinations revealed multiple abnormal intracranial lesions. The patient had previously been misdiagnosed with "encephalitis and acute disseminated encephalomyelitis" after visiting numerous hospitals. Eventually, by combing the characteristics of the case and genetic testing results, the patient was diagnosed with TSC accompanied by Mycoplasma pneumoniae infection. The purpose of this case report and literature review is to improve understanding of the clinical diagnosis and treatment of TSC so as to avoid misdiagnosis, missed diagnosis, and overtreatment.
Topics: Female; Humans; Adolescent; Tuberous Sclerosis; Encephalitis; Hospitals; Physical Examination; Pneumonia, Mycoplasma
PubMed: 37679848
DOI: 10.1186/s13052-023-01490-z -
International Journal of Infectious... Aug 2024The prevalence of respiratory infectious diseases has changed in the post-COVID-19 epidemic era, and mycoplasma pneumoniae (MP) infection in children has attracted wide...
OBJECTIVES
The prevalence of respiratory infectious diseases has changed in the post-COVID-19 epidemic era, and mycoplasma pneumoniae (MP) infection in children has attracted wide attention.
METHODS
Children hospitalized for pneumonia in Wuhan, China, in 2023 were enrolled. Respiratory secretions were obtained for the targeted next-generation sequencing (tNGS) including mutation of MP. Pulmonary inflammation was divided into bronchopneumonia and pulmonary consolidation/atelectasis according to lung computed tomography imaging.
RESULTS
Of the 667 pediatric pneumonia, 478 were MP positive (72%). The positive rate of MP detected by tNGS increased from April, and MP had become the primary pathogen of pneumonia in children in 2023. The 23S rRNA mutations were all A2063G, accounting for 85% of detected MP. The clinical symptoms of the mutant and wild-type strains were similar, with half of them experiencing atelectasis and lung consolidation. Early bronchoscopic lavage combined with azithromycin in pediatric pulmonary consolidation was an effective therapy strategy, which could be an alternative selection to MP pneumonia treatment.
CONCLUSIONS
A2063G mutant strain MP was the primary pathogen of mycoplasma pneumoniae in children recently, which was often complicated by extra-pulmonary symptoms and complications.
Topics: Humans; Pneumonia, Mycoplasma; China; Mycoplasma pneumoniae; Female; Child; Male; Child, Preschool; Mutation; Infant; RNA, Ribosomal, 23S; Anti-Bacterial Agents; Azithromycin; COVID-19; High-Throughput Nucleotide Sequencing; Adolescent
PubMed: 38734057
DOI: 10.1016/j.ijid.2024.107074 -
European Journal of Pediatrics Oct 2023Benign acute childhood myositis (BACM) is a self-limited childhood illness, and viral infections mainly cause it. Clinical and laboratory alterations usually normalize...
Benign acute childhood myositis (BACM) is a self-limited childhood illness, and viral infections mainly cause it. Clinical and laboratory alterations usually normalize rapidly; generally, the only medical intervention required is supportive (hydration and analgesic medication). The low awareness about BACM often led to delayed diagnosis and unneeded ancillary investigations. This study aims to better characterize the clinical and laboratory features of BACM to improve the diagnostic process and inpatient and outpatient management. We conducted a retrospective study selecting all children admitted to Meyer's Children's Hospital-IRCCS (Florence, Italy) with a diagnosis of BACM over the last 5 years, both those visited at Emergency Department (ED) and those admitted to the Pediatric Unit. Clinical, laboratory, and instrumental data were collected from electronic clinical records and analyzed. Overall, sixty-five patients were enrolled; 49 children were visited and discharged directly from ED, whereas 16 were admitted in the Pediatric or Neurologic Wards. The median age was 6.56 years (IQR 4.9-9.1). Male gender (66.1%) and Caucasian ethnicity (70%) were prevalent. Most patients were admitted during winter, and a second peak was found in autumn. All patients had bilateral calf pain, most of them (87.7%) associated with asthenia and refuse to walk (93.8%). Prodromal symptoms were fever (75.3%), cough (32.3%), coryza (26.1%), sore throat (26.1%), and vomiting (15.3%). The median value of CPK was 1827 U/L (IQR 915.5-2462) at peak. CPK median time to normalization was 7 days (IQR 7-8.5) from the nadir. Influenza B was the virus most frequently BACM associated, followed by Influenza A; a novel association with Sars-CoV-2 has been detected. Two patients had pathogenic variants at the Next Generation Sequencing myopathies panel. Conclusion: School-aged children admitted to the hospital with walking difficulty and myalgia, generally after an upper respiratory tract infection with a moderate CPK elevation, should remind at first of BACM. Rapid complaint resolution and biochemical markers normalization will prevent unnecessary tests and inappropriate therapies. What is Known: • BACM is a self-limited syndrome associated with acute infections. Influenza A and B viruses are the main etiological agents, but BACM may be related to many other microorganisms like Parainfluenza virus, Epstein-Barr virus, Cytomegalovirus, Human herpesvirus 6, Respiratory syncytial virus, Coxsackieviruses, Mycoplasma pneumoniae, Streptococcus pyogenes, Legionella, and Salmonella spp. • Clinical and laboratory alterations usually normalize rapidly; generally, the only medical intervention required is supportive (hydration, analgesic medication). Evolution in rhabdomyolysis and kidney damage is possible but rarely reported. What is New: • Sars-CoV-2 could be an emerging possible cause of BACM. During and after the Sars-CoV-2 outbreak, virus infection seasonality has changed, and so has BACM seasonality. • Screening tests for muscular and metabolic disorders are recommended in recurrent myositis and/or cases with marked CPK elevation (≥ 5000 U/L).
Topics: Humans; Child; Male; Influenza, Human; Retrospective Studies; Epstein-Barr Virus Infections; Hospitals, Pediatric; Tertiary Healthcare; Herpesvirus 4, Human; Acute Disease; Myositis; Analgesics
PubMed: 37462800
DOI: 10.1007/s00431-023-05115-9 -
Cancer Immunology, Immunotherapy : CII Nov 2023Immune checkpoint inhibitors (ICI) substantially improve outcome for patients with cancer. However, the majority of patients develops immune-related adverse events...
BACKGROUND
Immune checkpoint inhibitors (ICI) substantially improve outcome for patients with cancer. However, the majority of patients develops immune-related adverse events (irAEs), which can be persistent and significantly reduce quality of life. Neurological irAEs occur in 1-5% of patients and can induce severe, permanent sequelae or even be fatal. In order to improve the diagnosis and treatment of neurological irAEs and to better understand their pathogenesis, we assessed whether previous neurotropic infections are associated with neurological irAEs.
METHODS
Neurotropic infections that might predispose to ICI-induced neurological irAEs were analyzed in 61 melanoma patients from 3 countries, the Netherlands, Australia and Germany, including 24 patients with neurotoxicity and 37 control patients. In total, 14 viral, 6 bacterial, and 1 protozoal infections previously reported to trigger neurological pathologies were assessed using routine serology testing. The Dutch and Australian cohorts (NL) included pre-treatment plasma samples of patients treated with neoadjuvant ICI therapy (OpACIN-neo and PRADO trials; NCT02977052). In the Dutch/Australian cohort a total of 11 patients with neurological irAEs were compared to 27 control patients (patients without neurological irAEs). The German cohort (LMU) consisted of serum samples of 13 patients with neurological irAE and 10 control patients without any documented irAE under ICI therapy.
RESULTS
The association of neurological irAEs with 21 possible preceding infections was assessed by measuring specific antibodies against investigated agents. The seroprevalence of all the tested viral (cytomegalovirus, Epstein-Barr-Virus, varicella-zoster virus, measles, rubella, influenza A and B, human herpes virus 6 and 7, herpes simplex virus 1 and 2, parvovirus B19, hepatitis A and E and human T-lymphotropic virus type 1 and 2), bacterial (Borrelia burgdorferi sensu lato, Campylobacter jejuni, Mycoplasma pneumoniae, Coxiella burnetti, Helicobacter pylori, Yersinia enterocolitica and Y. pseudotuberculosis) and protozoal (Toxoplasma gondii) infections was similar for patients who developed neurological irAEs as compared to control patients. Thus, the analysis provided no evidence for an association of described agents tested for seroprevalence with ICI induced neurotoxicity.
CONCLUSION
Previous viral, bacterial and protozoal neurotropic infections appear not to be associated with the development of neurological irAEs in melanoma patients who underwent therapy with ICI across 3 countries. Further efforts are needed to unravel the factors underlying neurological irAEs in order to identify risk factors for these toxicities, especially with the increasing use of ICI in earlier stage disease.
Topics: Humans; Immune Checkpoint Inhibitors; Seroepidemiologic Studies; Quality of Life; Antineoplastic Agents, Immunological; Australia; Melanoma; Retrospective Studies
PubMed: 37606856
DOI: 10.1007/s00262-023-03498-0