Endoftalmitis de inicio tardío asociada a ampolla de filtración por Moraxella nonliquefaciens / Delayed-onset bleb-related endophthalmitis caused by Moraxella nonliquefaciens

Las endoftalmitis asociadas a la ampolla de filtración tras cirugía filtrante de glaucoma son poco frecuentes, de inicio tardío y la mayoría están asociadas a una blebitis. Los agentes causales suelen ser estreptococos o bacterias gramnegativas. Existen pocos casos descritos en la literatura de endoftalmitis causada por Moraxella nonliquefaciens y la mayoría están asociados a una blebitis tras cirugía filtrante de glaucoma. Presentamos el caso de una paciente de 90 años con endoftalmitis en ojo derecho por Moraxella nonliquefaciens asociada a blebitis 10 años después de la cirugía de glaucoma. Tras el tratamiento, se observó la desaparición de la blebitis 2 semanas después y resolución de la vitritis 29 días después, con recuperación de la visión a valores previos (20/200). La endoftalmitis por Moraxella nonliquefaciens es rara y está asociada a blebitis de inicio tardío tras una cirugía filtrante de glaucoma. A pesar de la virulencia del cuadro, el pronóstico visual suele ser favorable

Bleb-related endophthalmitis is rare and appears months or years after surgery. The causative agents are usually streptococci or gram-negative bacteria. There are few cases in the literature of endophthalmitis caused by Moraxella nonliquefaciens, and most are delayed-onset associated with blebitis after glaucoma filtration surgery. The case is presented of a 90-year-old patient with endophthalmitis in the right eye due to Moraxella nonliquefaciens associated with blebitis 10 years after glaucoma surgery. After treatment, disappearance of blebitis is observed 2 weeks later and resolution of vitritis 29 days later, with recovery of vision to previous values (20/200). Endophthalmitis due to Moraxella nonliquefaciens is rare, and is associated with late onset blebitis after glaucoma filtration surgery. Despite the virulence of the clinical symptoms, the visual prognosis is usually favourable

Lymphocyte predominant cells of nodular lymphocyte predominant Hodgkin lymphoma interact with rosetting T cells in an immunological synapse.

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a subtype of Hodgkin lymphoma with a preserved B-cell phenotype and follicular T helper (TFH ) cells rosetting around the tumor cells, the lymphocyte-predominant (LP) cells. As we recently described reactivity of the B-cell receptors of LP cells of some NLPHL cases with Moraxella spp. proteins, we hypothesized that LP cells could present peptides to rosetting T cells in a major histocompatibility complex class II (MHCII)-bound manner. Rosetting PD1+ T cells were present in the majority of NLPHL cases, both in typical (17/20) and variant patterns (16/19). In most cases, T-cell rosettes were CD69+ (typical NLPHL, 17/20; NLPHL variant, 14/19). Furthermore, both MHCII alpha and beta chains were expressed in the LP cells in 23/39 NLPHL. Proximity ligation assay and confocal laser imaging demonstrated interaction of the MHCII beta chain expressed by the LP cells and the T-cell receptor alpha chain expressed by rosetting T cells. We thus conclude that rosetting T cells in NLPHL express markers that are encountered after antigenic exposure, that MHCII is expressed by the LP cells, and that LP cells interact with rosetting T cells in an immunological synapse in a subset of cases. As they likely receive growth stimulatory signals in this way, blockade of this interaction, for example, by PD1-directed checkpoint inhibitors, could be a treatment option in a subset of cases in the future.

TLR4 Polymorphism, Nasopharyngeal Bacterial Colonization, and the Development of Childhood Asthma: A Prospective Birth-Cohort Study in Finnish Children.

We aimed to explore the role of TLR4 (rs4986790) polymorphism in the nasopharyngeal (NP) bacterial colonization and its consequent impact on the development of childhood asthma. A semi-quantitative culture of NP swabs was performed on 473 children at 2 months of age and on 213 children at 13 months of age. TLR4 polymorphism was analyzed for 396 children. Children were followed from birth to the age of 7.5 years and the final outcome was physician-diagnosed asthma. The associations between TLR4 genotype, bacterial colonization, and asthma were analyzed. Children with TLR4 AG or GG genotype were more often colonized with Moraxella catarrhalis at 2 months of age (p = 0.009) and Haemophilus influenzae at 13 months of age (p = 0.018). Children who were colonized with H. influenzae at 13 months of age had a significantly higher risk of later development of asthma (p = 0.004). M. catarrhalis or H. Influenzae colonization at 2 months of age or TLR4 genotype Asp299Gly were not associated with the development of childhood asthma. TLR4 Asp299Gly polymorphism was associated with an increased risk of colonization of M. catarrhalis and H. influenzae in children. The colonization with H. influenzae at 13 months of age was associated with a higher risk of later development of childhood asthma.

Complement evasion by the human respiratory tract pathogens Haemophilus influenzae and Moraxella catarrhalis.

All infective bacterial species need to conquer the innate immune system in order to colonize and survive in their hosts. The human respiratory pathogens Haemophilus influenzae and Moraxella catarrhalis are no exceptions and have developed sophisticated mechanisms to evade complement-mediated killing. Both bacterial species carry lipooligosaccharides preventing complement attacks and attract and utilize host complement regulators C4b binding protein and factor H to inhibit the classical and alternative pathways of complement activation, respectively. In addition, the regulator of the terminal pathway of complement activation, vitronectin, is hijacked by both bacteria. An array of different outer membrane proteins (OMP) in H. influenzae and M. catarrhalis simultaneously binds complement regulators, but also plasminogen. Several of the bacterial complement-binding proteins are important adhesins and contain highly conserved regions for interactions with the host. Thus, some of the OMP are viable targets for new therapeutics, including vaccines aimed at preventing respiratory tract diseases such as otitis media in children and exacerbations in patients suffering from chronic obstructive pulmonary disease.

Antimicrobial susceptibility and impact of macrolide antibiotics on Moraxella catarrhalis in the upper and lower airways of children with chronic endobronchial suppuration.

INTRODUCTION: Moraxella catarrhalis is an important but insufficiently studied respiratory pathogen. AIM: To determine antibiotic susceptibility and impact of recent antibiotics on M. catarrhalis from children with chronic endobronchial suppuration. METHODOLOGY: We cultured nasopharyngeal (NP) swabs and bronchoalveolar lavage (BAL) fluids collected from children who were prospectively enrolled in studies of chronic cough and had flexible bronchoscopy performed. Recent ß-lactam or macrolide antibiotic use was recorded. M. catarrhalis isolates stored at -80 °C were re-cultured and susceptibility determined to a range of antibiotics including the macrolide antibiotic erythromycin. RESULTS: Data from concurrently collected NP and BAL specimens were available from 547 children (median age 2.4 years) enrolled from 2007 to 2016. M. catarrhalis NP carriage was detected in 149 (27  %) children and lower airway infection (≥104 c.f.u. ml-1 BAL) in 67 (12  %) children. In total, 91  % of 222 M. catarrhalis isolates were ß-lactamase producers, and non-susceptibility was high to benzylpenicillin (98 %), cefaclor (39 %) and cotrimoxazole (38 %). Overall, >97  % isolates were susceptible to cefuroxime, chloramphenicol, erythromycin and tetracycline; three isolates were erythromycin-resistant (MIC >0.5 mg l-1). Recent macrolide antibiotics (n=152 children, 28 %) were associated with significantly reduced M. catarrhalis carriage and lower airway infection episodes compared to children who did not receive macrolides; odds ratios 0.19 (95  % CI 0.10-0.35) and 0.15 (0.04-0.41), respectively. CONCLUSION: Despite the frequent use of macrolides, few macrolide-resistant isolates were detected. This suggests a fitness cost associated with macrolide resistance in M. catarrhalis. Macrolide antibiotics remain an effective choice for treating M. catarrhalis lower airway infection in children with chronic endobronchial suppuration.

Identification of Moraxella lacunata from pulmonary abscesses in three zoo herbivores.

Although Moraxella lacunata causes conjunctivitis, keratitis, endocarditis, and otolaryngitis in humans, its infection is rare in animals. We report three cases of asymptomatic pulmonary abscesses caused by M. lacunata in zoo herbivores, including two elks (Cervus canadensis) and a common eland (Taurotragus oryx). In all cases, macroscopic findings included coalescence of lung lobes and severe pulmonary abscesses filled with cheese-like materials in cysts. Microscopic findings included pneumonia characterized by marked fibrin exudates in alveolar spaces and infiltration of inflammatory cells. M. lacunata was identified in bacterial cultures from pulmonary abscesses using biochemical API 20NE system. M. lacunata is rarely isolated from zoo animals; however, herein, we describe the first report of pulmonary abscesses caused by M. lacunata infection.

Infectious keratoconjunctivitis in free-ranging mule deer in Wyoming: a retrospective study and identification of a novel alphaherpesvirus.

We describe the clinicopathologic findings, relative prevalence, and pathogens associated with infectious keratoconjunctivitis in mule deer ( Odocoileus hemionus) in Wyoming. Seventeen cases with ocular lesions were identified among 1,036 mule deer postmortem submissions (1.6%) in an ~16 y period. Sixteen cases were observed in winter and most were in male (15 cases) and juvenile (13 cases) deer. Blindness was the most commonly reported clinical sign (10 cases). A herpesvirus was detected only in the 4 cases of bilateral necrotizing bulbar conjunctivitis. Phylogenetic analysis of glycoprotein amino acid sequences consistently identified this virus as a novel alphaherpesvirus. In 2 of these herpesvirus-positive cases, Actinomyces sp. and Moraxella ovis were also identified. Trueperella pyogenes was identified in 4 cases of unilateral ulcerative keratitis, keratoconjunctivitis, and panophthalmitis. M. ovis was cultured from 3 cases of bilateral conjunctivitis and keratoconjunctivitis. In the remaining cases, isolates included Moraxella bovis (1 case), Staphylococcus sp. and Streptococcus sp. (2), Flavobacterium sp. and Pseudomonas sp. (2), Escherichia coli and Enterobacter sp. (1), and bovine viral diarrhea virus 1 (1). No pathogens were identified in 2 cases. The relative prevalence of keratoconjunctivitis in mule deer in Wyoming appears to be low, and this disease is most commonly associated with infection by a novel alphaherpesvirus, T. pyogenes, and M. ovis.

Fibrinous pericarditis secondary to bacterial infection in a cat.

A three-year-old spayed domestic short-haired cat presented for evaluation of weight loss, cardiomegaly and pleural effusion. Echocardiographic examination demonstrated a thickened pericardium with mild pericardial effusion and a large volume of pleural effusion characterized by exudate. Although the cat was treated with antibiotics, the clinical symptoms did not improve. The cat developed dyspnea and died on day 7. Necropsy revealed a large amount of modified transudates ascites, pleural effusion and markedly dilated pericardium. Histopathological examination revealed severe exudation of fibrin and granulation tissue in a thick layer of the epicardium. The cat was diagnosed with fibrinous pericarditis secondary to bacterial infection.

The Respiratory Pathogen Moraxella catarrhalis Targets Collagen for Maximal Adherence to Host Tissues.

UNLABELLED: Moraxella catarrhalis is a human respiratory pathogen that causes acute otitis media in children and is associated with exacerbations in patients suffering from chronic obstructive pulmonary disease (COPD). The first step in M. catarrhalis colonization is adherence to the mucosa, epithelial cells, and extracellular matrix (ECM). The objective of this study was to evaluate the role of M. catarrhalis interactions with collagens from various angles. Clinical isolates (n= 43) were tested for collagen binding, followed by a detailed analysis of protein-protein interactions using recombinantly expressed proteins.M. catarrhalis-dependent interactions with collagen produced by human lung fibroblasts and tracheal tissues were studied by utilizing confocal immunohistochemistry and high-resolution scanning electron microscopy. A mouse smoke-induced chronic obstructive pulmonary disease (COPD) model was used to estimate the adherence of M. catarrhalis in vivo. We found that all M. catarrhalis clinical isolates tested adhered to fibrillar collagen types I, II, and III and network-forming collagens IV and VI. The trimeric autotransporter adhesins ubiquitous surface protein A2(UspA2) and UspA2H were identified as major collagen-binding receptors.M. catarrhalis wild type adhered to human tracheal tissue and collagen-producing lung fibroblasts, whereas UspA2 and UspA2H deletion mutants did not. Moreover, in the COPD mouse model, bacteria devoid of UspA2 and UspA2H had a reduced level of adherence to the respiratory tract compared to the adherence of wild-type bacteria. Our data therefore suggest that theM. catarrhalisUspA2 and UspA2H-dependent interaction with collagens is highly critical for adherence in the host and, furthermore, may play an important role in the establishment of disease. IMPORTANCE: The respiratory tract pathogen Moraxella catarrhalis adheres to the host by interacting with several components, including the ECM. Collagen accounts for 30% of total body proteins, and therefore, bacterial adherence to abundant host collagens mediates bacterial persistence and colonization. In this study, we characterized previously unknown M. catarrhalis-dependent interactions with host collagens and found that the trimeric autotransporter adhesins ubiquitous surface protein A2(UspA2) and UspA2H are highly important. Our observations also suggested that collagen-mediated adherence ofM. catarrhalis is indispensable for bacterial survival in the host, as exemplified by a mouse COPD model.

Pacemaker lead perforation of the right ventricle associated with Moraxella phenylpyruvica infection in a dog.

CASE DESCRIPTION: A 13-year-old neutered male Border Collie was presented with acute onset syncope, weakness and anorexia 10 months after transvenous pacemaker implantation. The patient was laterally recumbent, bradycardic (36 beats/min) and febrile (40.7°C) on presentation. An electrocardiogram (ECG) revealed recurrence of third-degree atrioventricular block with a ventricular escape rhythm. Fluoroscopy identified migration of the pacemaker tip through the apex of the right ventricle. Echocardiography failed to reveal any evidence of pericardial effusion or cardiac tamponade. Full postmortem was performed after euthanasia. The pacemaker lead had perforated the apex of the right ventricle and lodged in the right pleural space. Culture of blood (taken antemortem), pericardial sac, right ventricular wall (surrounding pacemaker lead), pacemaker lead tip and pericardial fluid revealed a pure growth of Moraxella phenylpyruvica. CONCLUSION: Bacteraemia associated with M. phenylpyruvica has never been reported in the dog, but sporadic cases are reported in humans. Infection could have resulted from either pre-existing myocarditis or opportunistic infection and bacteraemia post pacemaker implantation. Evaluation of the pacemaker function at regular intervals would allow early detection of poor pacemaker-to-myocardium contact, which would prompt further investigation of pacemaker lead abnormalities such as perforation.

A Pediatric Case of Bacteremia and Possible Cholecystitis Due to Moraxella osloensis.

We encountered a pediatric case of bacteremia and possible cholecystitis due to Moraxella osloensis that was treated successfully. We confirmed the diagnosis with the presence of a high serum titer of the antibody to the organism. Furthermore, 16S rRNA sequencing was performed to identify the bacteria.

[THE PATHOGENIC POTENTIAL OF MORAXELLA CATARRHALIS AND STAPHYLOCOCCUS EPIDERMIDIS UNDER INFLAMMATORY PROCESSES OF UPPER RESPIRATORY TRACTS].

The frequent isolation from biological material of Moraxella catarrhalis under bronchitis and pneumonia and Staphilococcus epidermidis under rhinitis and sinusitis requires profound investigation offactors ofpathogenicity ofthe mentioned microorganisms. The genetic and phenotypic markers of virulence of strains M. catarrhalis and S. epidermidis are examined. Their etiologic role in development of infection processes of respiratory tract and middle ear is determined The most of M catarrhalis strains isolated under bronchitis and pneumonia have gene mcaP responsiblefor production ofprotein McaP that provides adhesion to epithelium cell of host and lipolitic activity of bacteria. The strains isolated from patients with pneumonia had the most adhesive activity. The cluster of genes ICA with leading role of gene icaA is responsible for for availability offactors of intercellular adhesion in Staphilococci strains. In the clinical samples from patients with sinusitis this gene is detected 5 times more frequently than from healthy individuals. In phenotypic tests, expression of gene icaA in S. epidermidis isolated from patients is three times higher than in strains isolated from healthy individuals. To establish etiologic role of M. catarrhalis and S. epidermidis and to develop tactic of therapy of patients with bronchitis, pneumonia and sinusitis complex approach is needed, including detection of genetic and phenotypic markers of virulence in isolated microorganisms.

Clinical significance of serum S100A12 in acute otitis media in young children.

BACKGROUND: S100A12 is a calcium-binding protein predominantly expressed in neutrophil granulocytes in response to infections or inflammation. Acute otitis media (AOM) is a local infection mainly caused by Streptococcus pneumoniae (Spn), nontypeable Haemophilus influenzae (NTHi), and/or Moraxella catarrhalis (Mcat). METHODS: To study if S100A12 values could serve as a diagnostic marker, serum S100A12 concentrations were tested in young children before, at onset, and after recovery from AOM. RESULTS: Among 116 children with AOM, we found that serum S100A12 concentrations were significantly increased at onset of AOM compared with before infection (P = 0.0001), and returned to normal levels when the children recovered from the infection (P = 0.01). Elevation of S100A12 correlated with the presence of Spn (P = 0.004) or NTHi (P = 0.04) in the middle ear, but not with Mcat or upper respiratory viral infection. Change in serum value of S100A12 at onset of AOM was not related to the frequency of occurrence of AOM or the age of the child. CONCLUSION: S100A12 may be a useful biomarker for onset of AOM due to Spn and NTHi, and for following children with AOM.

Immune evasion of Moraxella catarrhalis involves ubiquitous surface protein A-dependent C3d binding.

The complement system plays an important role in eliminating invading pathogens. Activation of complement results in C3b deposition (opsonization), phagocytosis, anaphylatoxin (C3a, C5a) release, and consequently cell lysis. Moraxella catarrhalis is a human respiratory pathogen commonly found in children with otitis media and in adults with chronic obstructive pulmonary disease. The species has evolved multiple complement evasion strategies, which among others involves the ubiquitous surface protein (Usp) family consisting of UspA1, A2, and A2 hybrid. In the present study, we found that the ability of M. catarrhalis to bind C3 correlated with UspA expression and that C3 binding contributed to serum resistance in a large number of clinical isolates. Recombinantly expressed UspA1 and A2 inhibit both the alternative and classical pathways, C3b deposition, and C3a generation when bound to the C3 molecule. We also revealed that the M. catarrhalis UspA-binding domain on C3b was located to C3d and that the major bacterial C3d-binding domains were within UspA1(299-452) and UspA2(165-318). The interaction with C3 was not species specific since UspA-expressing M. catarrhalis also bound mouse C3 that resulted in inhibition of the alternative pathway of mouse complement. Taken together, the binding of C3 to UspAs is an efficient strategy of Moraxella to block the activation of complement and to inhibit C3a-mediated inflammation.

Sepsis with prolonged hypotension due to Moraxella osloensis in a non-immunocompromised child.

We report a case of septicaemia with prolonged, refractory hypotension related to Moraxella osloensis isolated in a non-immunocompromised paediatric patient.

Pulmonary thin-section CT findings in acute Moraxella catarrhalis pulmonary infection.

OBJECTIVE: Moraxella catarrhalis is an important pathogen in the exacerbation of chronic obstructive pulmonary disease. The aim of this study was to assess the clinical and pulmonary thin-section CT findings in patients with acute M. catarrhalis pulmonary infection. METHODS: Thin-section CT scans obtained between January 2004 and March 2009 from 292 patients with acute M. catarrhalis pulmonary infection were retrospectively evaluated. Clinical and pulmonary CT findings in the patients were assessed. Patients with concurrent infection including Streptococcus pneumoniae (n = 72), Haemophilus influenzae (n = 61) or multiple pathogens were excluded from this study. RESULTS: The study group comprised 109 patients (66 male, 43 female; age range 28-102 years; mean age 74.9 years). Among the 109 patients, 34 had community-acquired and 75 had nosocomial infections. Underlying diseases included pulmonary emphysema (n = 74), cardiovascular disease (n = 44) or malignant disease (n = 41). Abnormal findings were seen on CT scans in all patients and included ground-glass opacity (n = 99), bronchial wall thickening (n = 85) and centrilobular nodules (n = 79). These abnormalities were predominantly seen in the peripheral lung parenchyma (n = 99). Pleural effusion was found in eight patients. No patients had mediastinal and/or hilar lymph node enlargement. CONCLUSIONS: M. catarrhalis pulmonary infection was observed in elderly patients, often in combination with pulmonary emphysema. CT manifestations of infection were mainly ground-glass opacity, bronchial wall thickening and centilobular nodules.

Epidemiologic and microbiologic characteristics of culture-positive spontaneous otorrhea in children with acute otitis media.

OBJECTIVES: We aimed to describe the epidemiologic and microbiologic characteristics of acute otitis media (AOM) with spontaneous otorrhea in children and compare it with AOM with intact tympanic membrane in children who underwent tympanocentesis. PATIENTS AND METHODS: All infants and young children aged <3 years with culture-positive AOM of < or =7 days duration diagnosed during 1999 to 2006 and in whom epidemiologic and microbiologic data were available, were analyzed. Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pyogenes were considered true AOM pathogens. Multivariable regression analysis models adjusting for age, gender, ethnicity, seasonality, previous antibiotics, AOM history, tympanocentesis history, and pathogens isolated, were used. RESULTS: Of 12,617 AOM patients from whom a middle ear fluid was obtained, 5247 (42%) culture-positive patients were enrolled; spontaneous otorrhea was observed in 822 (15%) patients. Patients with spontaneous otorrhea were older than patients with AOM who underwent tympanocentesis (15.8 +/- 8.2 vs. 9.7 +/- 6.7 months, respectively, P < 0.01; 36.9% vs. 69.1%, respectively, were <12 months, P < 0.01). S. pyogenes was found in a higher proportion (47/822, 5.7% vs. 44/4425, 1%, P < 0.01) and H. influenzae in a lower proportion (264/822, 32.1% vs. 1805/4425, 40.8%, P < 0.01) among patients with spontaneous otorrhea than in patients with AOM and tympanocentesis. In the multivariate model, Bedouin ethnicity (OR: 1.5, 95% CI: 1.2-1.7, P < 0.001), age (OR: 1.1, 95% CI: 1.0-1.11, P < 0.001) for each consecutive month, lack of antibiotic treatment for the 48 hours preceding diagnosis (OR: 2.1, 95% CI: 1.7-2.6, P < 0.001), > or =1 previous AOM episode (OR: 3.2, 95% CI: 2.6-4.0, P < 0.001), >1 previous tympanocentesis (OR: 1.4, 95% CI: 1.4-1.7, P = 0.001), and infection with S. pyogenes (OR: 8.2, 95% CI: 5.4-12.3, P < 0.001) were independent risk factors for AOM presenting as spontaneous otorrhea. CONCLUSIONS: AOM presenting as spontaneous otorrhea in patients less than 3 years of age is characterized by older age, previous repeated tympanocenteses, > or =1 previous AOM episodes, lack of recent antibiotic treatment, and infection with S. pyogene.

Moraxella catarrhalis-specific Th1 cells in BAL fluids of chronic obstructive pulmonary disease patients.

In chronic obstructive pulmonary disease (COPD) patients airway mucosa is infiltrated by macrophages and T lymphocytes, potentially reactive to pathogens. We studied the antigen-specificity and the effector functions of in vivo activated T lymphocytes isolated from BAL (Bronchoalveolar lavage) of 5 Moraxella catarrhalis (Mc)-infected and 5 Mc-non-infected COPD patients. Mc-specific T cells were detected only in BAL or peripheral blood of Moraxella catarrhalis-infected patients. The majority of BAL Mc-specific T cells expressed the T helper type 1 (Th1) cytokine profile with high cytotoxic and pro-apoptotic activity. Upon antigen stimulation, all Mc-specific T clones were able to help the immunoglobulin production by autologous B cells and the MMP (Matrix MetalloProteinase)-12 activity by monocytes. Our results suggest a role for Th1-driven response to Moraxella catarrhalis in the genesis of COPD.