РЕЗУЛЬТАТИ ВИВЧЕННЯ МІКРОБНОГО СПЕКТРУ У ДІТЕЙ З РОЗЛАДАМИ СПЕКТРУ АУТИЗМУ, АСОЦІЙОВАНИМИ З ГЕНЕТИЧНИМ ДЕФІЦИТОМ ФОЛАТНОГО ЦИКЛУ

Обґрунтування. Результати п’яти мета-аналізів рандомізованих контрольованих клінічних досліджень свідчать про асоціацію генетичного дефіциту фолатного циклу (ГДФЦ) і розладів спектру аутизму (РАС) у дітей. В таких випадках формується імунодефіцит та імунна дисрегуляція, що знижує резистентність до деяких мікроорганізмів.Мета дослідження: вивчити структуру мікробного спектру у дітей з РАС, пов’язаними з ГДФЦ, згідно з накопиченою дотепер доказовою базою і вивчити асоціацію виявлених мікроорганізмів з показниками імунного статусу для покращення розуміння патогенезу енцефалопатії та удосконалення алгоритмів діагностики, моніторингу і лікування.Матеріали і методи. Ретроспективно проаналізовано медичні дані 225 дітей віком від 2 до 9 років з ГДФЦ, у яких відзначалися клінічні прояви за типом РАС (досліджувана група; ДГ; 183 хлопчиків і 42 дівчинки). До контрольної групи (КГ) віднесли 51 клінічно здорову дитину (37 хлопчиків та 14 дівчаток) аналогічного вікового розподілу, які не страждали на ГДФЦ. Спеціальне лабораторне обстеження дітей груп спостереження проводили з урахуванням сучасних уявлень щодо мікробного спектру у пацієнтів з РАС згідно з публікаціями в PubMed і Embase. Для вивчення асоціацій між досліджуваними показниками застосовували показник відношення шансів (odds ratio, OR) та 95% довірчий інтервал (95% СІ). Дослідження виконувалося як фрагмент науково-дослідної роботи на замовлення МОЗ України (№ держреєстрації 0121U107940).Результати та їх обговорення. TTV відзначався в 87%, HHV-7 – 79%, HHV-6 – 68%, EBV – 59%, Streptococcus pyogenes – 46%, Candida albicans – 41%, Borrelia – 34%, Mycoplasma pneumoniae – 27%, Chlamydia pneumoniae – 26%, Yersinia enterocolitica – 23%, Toxoplasma gondii – 19%, перенесена природжена CMV нейроінфекція – 7%, наслідки HSV-1/2-нейро-інфекції – 5% випадків в ДГ (р<0,05; Z<Z0,05). HHV-6, HHV-7 та EBV були асоційовані з дефіцитами NK-, NKT- та СD8+ цитотоксичних Т-лімфоцитів. ТТV також був асоційований з дефіцитами NK- та NKT-лімфоцитів, однак не з дефіцитом СD8+ цитотоксичних Т-клітин. Стрептококова інфекція була пов’язана з гіпо- і дисімуноглобулінемією, а також – дефіцитом мієлопероксидази. Кандидоз був асоційований тільки з дефіцитом мієлопероксидази. Токсоплазмоз відзначався при дефіциті СD4+ Т-хелперів та комбінованих порушеннях імунітету. Наслідки природженої CMV-нейроінфекції мали місце тільки при комбінованих порушеннях імунітету. Висновки. Для дітей з РАС, асоційованими з ГДФЦ, характерним є специфічний мікробний спектр з переважанням інтрацелюлярних опортуністичних та умовно патогенних мікроорганізмів, який визначається особливостями порушень в імунному статусі, спровокованих ГДФЦ, що має визначати алгоритм раціонального мікробіологічногопошуку, оцінки імунного статусу, проведення антимікробного та імунотропного лікування.

Mycoplasma pneumoniae and Chlamydia pneumoniae Coinfection with Acute Respiratory Distress Syndrome: A Case Report

Community-acquired pneumonia caused by Mycoplasma pneumoniae or Chlamydia pneumoniae is usually mild. Mycoplasma pneumoniae-related and C. pneumoniae-related acute respiratory distress syndromes (ARDSs) are rare. Moreover, to our knowledge, there are no published reports on ARDS caused by M. pneumoniae and C. pneumoniae coinfection. Here, we report a case of an immunocompetent young woman who was co-infected with M. pneumoniae and C. pneumoniae and was started on treatment with piperacillin and clarithromycin. Two days later, she developed ARDS. She recovered rapidly following a change of antibiotic treatment to levofloxacin and was discharged on day 12. We conducted exome sequencing followed by alternative filtering to search for candidate ARDS-related genes. We identified an intronic variant of unknown significance within leucine-rich repeat-containing 16A (LRRC16A), a gene previously identified as a significant locus for platelet count with a possible role in ARDS. This is a rare case of ARDS in a young adult caused by M. pneumoniae and C. pneumoniae coinfection. This case suggests that ARDS in young adults may be correlated with variants in LRRC16A. This requires confirmation by further case reports.

Lefamulin in Patients with Community-Acquired Bacterial Pneumonia Caused by Atypical Respiratory Pathogens: Pooled Results from Two Phase 3 Trials

Lefamulin was the first systemic pleuromutilin antibiotic approved for intravenous and oral use in adults with community-acquired bacterial pneumonia based on two phase 3 trials (Lefamulin Evaluation Against Pneumonia [LEAP]-1 and LEAP-2). This pooled analysis evaluated lefamulin efficacy and safety in adults with community-acquired bacterial pneumonia caused by atypical pathogens (Mycoplasma pneumoniae, Legionella pneumophila, and Chlamydia pneumoniae). In LEAP-1, participants received intravenous lefamulin 150 mg every 12 h for 5–7 days or moxifloxacin 400 mg every 24 h for 7 days, with optional intravenous-to-oral switch. In LEAP-2, participants received oral lefamulin 600 mg every 12 h for 5 days or moxifloxacin 400 mg every 24 h for 7 days. Primary outcomes were early clinical response at 96 ± 24 h after first dose and investigator assessment of clinical response at test of cure (5–10 days after last dose). Atypical pathogens were identified in 25.0% (91/364) of lefamulin-treated patients and 25.2% (87/345) of moxifloxacin-treated patients; most were identified by ≥1 standard diagnostic modality (M. pneumoniae 71.2% [52/73]; L. pneumophila 96.9% [63/65]; C. pneumoniae 79.3% [46/58]); the most common standard diagnostic modality was serology. In terms of disease severity, more than 90% of patients had CURB-65 (confusion of new onset, blood urea nitrogen > 19 mg/dL, respiratory rate ≥ 30 breaths/min, blood pressure <90 mm Hg systolic or ≤60 mm Hg diastolic, and age ≥ 65 years) scores of 0–2; approximately 50% of patients had PORT (Pneumonia Outcomes Research Team) risk class of III, and the remaining patients were more likely to have PORT risk class of II or IV versus V. In patients with atypical pathogens, early clinical response (lefamulin 84.4–96.6%; moxifloxacin 90.3–96.8%) and investigator assessment of clinical response at test of cure (lefamulin 74.1–89.7%; moxifloxacin 74.2–97.1%) were high and similar between arms. Treatment-emergent adverse event rates were similar in the lefamulin (34.1% [31/91]) and moxifloxacin (32.2% [28/87]) groups. Limitations to this analysis include its post hoc nature, the small numbers of patients infected with atypical pathogens, the possibility of PCR-based diagnostic methods to identify non-etiologically relevant pathogens, and the possibility that these findings may not be generalizable to all patients. Lefamulin as short-course empiric monotherapy, including 5-day oral therapy, was well tolerated in adults with community-acquired bacterial pneumonia and demonstrated high clinical response rates against atypical pathogens.

Neuroprotective effects of some epigenetic modifying drugs’ on Chlamydia pneumoniae-induced neuroinflammation: A novel model

Chlamydia pneumoniae (Cpn) is a gram-negative intracellular pathogen that causes a variety of pulmonary diseases, and there is growing evidence that it may play a role in Alzheimer’s disease (AD) pathogenesis. Cpn can interact functionally with host histones, altering the host’s epigenetic regulatory system by introducing bacterial products into the host tissue and inducing a persistent inflammatory response. Because Cpn is difficult to propagate, isolate, and detect, a modified LPS-like neuroinflammation model was established using lyophilized cell free supernatant (CFS) obtained from infected cell cultures, and the effects of CFS were compared to LPS. The neuroprotective effects of Trichostatin A (TSA), givinostat, and RG108, which are effective on epigenetic mechanisms, and the antibiotic rifampin, were studied in this newly introduced model and in the presence of amyloid beta (Aβ) 1–42. The neuroprotective effects of the drugs, as well as the effects of CFS and LPS, were evaluated in Aβ-induced neurotoxicity using a real-time cell analysis system, total ROS, and apoptotic impact. TSA, RG108, givinostat, and rifampin all demonstrated neuroprotective effects in both this novel model and Aβ-induced neurotoxicity. The findings are expected to provide early evidence on neuroprotective actions against Cpn-induced neuroinflammation and Aβ-induced neurotoxicity, which could represent a new treatment option for AD, for which there are currently few treatment options.

Detection of Chlamydia Pneumoniae in Lung Tissues Derived from Lung Tumor-Bearing Iraqi Patients

Chlamydia pneumoniae is an intracellular gram-negative bacteria associated with lower and upper respiratory tract infections. Several studies, mostly achieved by serological assays, proposed a role for this bacteria in lung cancer risk. Therefore, this study aimed to evaluate the prevalence of Chlamydia pneuomoniae in fresh lung tissues of a sample of Iraqi patients with lung tumors, utilizing polymerase chain reaction (PCR) technique. . Chlamydia pneumoniae DNA was detected in 86.67% of samples. Besides, DNA sequencing of 16S rRNA gene revealed that our isolate is closely related to Chlamydia pneumoniae TW183 strain. It is concluded that Chlamydia pneumoniae is found in fresh lung tissues of patients, suggesting past infection, reinfection, or persistent form, which may play a role in the development or exacerbation of lung tumors. Our results confirm the high prevalence of this type of bacteria in Iraqi patients.

Chlamydia pneumoniae-associated pleuropericarditis: a case report and systematic review of the literature

Background Chlamydia pneumoniae is a common cause of atypical community acquired pneumonia (CAP). The diagnostic approach of chlamydial infections remains a challenge. Diagnosis of delayed chlamydial-associated complications, involving complex autoimmune pathophysiological mechanisms, is still more challenging. C. pneumoniae-related cardiac complications have been rarely reported, including cases of endocarditis, myocarditis and pericarditis. Case presentation A 40-year old female was hospitalized for pleuropericarditis following lower respiratory tract infection. The patient had been hospitalized for CAP (fever, dyspnea, chest X-ray positive for consolidation on the left upper lobe) 5 weeks ago and had received ceftriaxone and moxifloxacin. Four weeks after her discharge, the patient presented with fever, shortness of breath and pleuritic chest pain and was readmitted because of pericardial and bilateral pleural effusions (mainly left). The patient did not improve on antibiotics and sequential introduction of colchicine and methylprednisolone was performed. The patient presented impressive clinical and laboratory response. Several laboratory and clinical assessments failed to demonstrate any etiological factor for serositis. Chlamydial IgM and IgG antibodies were positive and serial measurements showed increasing kinetics for IgG. Gold standard polymerase chain reaction of respiratory tract samples was not feasible but possibly would not have provided any additional information since CAP occurred 5 weeks ago. The patient was discharged under colchicine and tapered methylprednisolone course. During regular clinic visits, she remained in good clinical condition without pericardial and pleural effusions relapse. Conclusions C. pneumoniae should be considered as possible pathogen in case of pleuritis and/or pericarditis during or after a lower respiratory tract infection. In a systematic review of the literature only five cases of C. pneumoniae associated pericarditis were identified. Exact mechanisms of cardiovascular damage have not yet been defined, yet autoimmune pathways might be implicated.

Chlamydia pneumoniae-Induced Neuroinflammation Cell Model Using Lyophilized Cell-Free Supernatant v1

Chlamydia pneumoniae (Cpn) is a gram-negative intracellular pathogen that causes a variety of pulmonary diseases, and there is growing evidence that it may play a role in Alzheimer's disease (AD) pathogenesis. Cpn can interact functionally with host histones, altering the host's epigenetic regulatory system by introducing bacterial products into the host tissue and inducing a persistent inflammatory response. Because Cpn is difficult to propagate, isolate, and detect, a modified LPS-like neuroinflammation model was established using lyophilized cell free supernatant (CFS) obtained from infected cell cultures, and the effects of CFS were compared to LPS.

Identification of Coinfections by Viral and Bacterial Pathogens in COVID-19 Hospitalized Patients in Peru: Molecular Diagnosis and Clinical Characteristics

The impact of respiratory coinfections in COVID-19 is still not well understood despite the growing evidence that consider coinfections greater than expected. A total of 295 patients older than 18 years of age, hospitalized with a confirmed diagnosis of moderate/severe pneumonia due to SARS-CoV-2 infection (according to definitions established by the Ministry of Health of Peru) were enrolled during the study period. A coinfection with one or more respiratory pathogens was detected in 154 (52.2%) patients at hospital admission. The most common coinfections were Mycoplasma pneumoniae (28.1%), Chlamydia pneumoniae (8.8%) and with both bacteria (11.5%); followed by Adenovirus (1.7%), Mycoplasma pneumoniae/Adenovirus (0.7%), Chlamydia pneumoniae/Adenovirus (0.7%), RSV-B/Chlamydia pneumoniae (0.3%) and Mycoplasma pneumoniae/Chlamydia pneumoniae/Adenovirus (0.3%). Expectoration was less frequent in coinfected individuals compared to non-coinfected (5.8% vs. 12.8%). Sepsis was more frequent among coinfected patients than non-coinfected individuals (33.1% vs. 20.6%) and 41% of the patients who received macrolides empirically were PCR-positive for Mycoplasma pneumoniae and Chlamydia pneumoniae.