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PLoS Neglected Tropical Diseases May 2024Haemophilus ducreyi was historically known as the causative agent of chancroid, a sexually-transmitted disease causing painful genital ulcers endemic in many...
Haemophilus ducreyi was historically known as the causative agent of chancroid, a sexually-transmitted disease causing painful genital ulcers endemic in many low/middle-income nations. In recent years the species has been implicated as the causative agent of nongenital cutaneous ulcers affecting children of the South Pacific Islands and West African countries. Much is still unknown about the mechanism of H. ducreyi transmission in these areas, and recent studies have identified local insect species, namely flies, as potential transmission vectors. H. ducreyi DNA has been detected on the surface and in homogenates of fly species sampled from Lihir Island, Papua New Guinea. The current study develops a model system using Musca domestica, the common house fly, as a model organism to demonstrate proof of concept that flies are a potential vector for the transmission of viable H. ducreyi. Utilizing a green fluorescent protein (GFP)-tagged strain of H. ducreyi and three separate exposure methods, we detected the transmission of viable H. ducreyi by 86.11% ± 22.53% of flies sampled. Additionally, the duration of H. ducreyi viability was found to be directly related to the bacterial concentration, and transmission of H. ducreyi was largely undetectable within one hour of initial exposure. Push testing, Gram staining, and PCR were used to confirm the identity and presence of GFP colonies as H. ducreyi. This study confirms that flies are capable of mechanically transmitting viable H. ducreyi, illuminating the importance of investigating insects as vectors of cutaneous ulcerative diseases.
Topics: Animals; Houseflies; Haemophilus ducreyi; Chancroid; Papua New Guinea; Insect Vectors; Female; Male
PubMed: 38814945
DOI: 10.1371/journal.pntd.0012194 -
Research and Practice in Thrombosis and... May 2024Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired hematologic disease characterized by complement-mediated hemolysis and thrombosis. Complement component 5...
BACKGROUND
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired hematologic disease characterized by complement-mediated hemolysis and thrombosis. Complement component 5 (C5) inhibitors have decreased PNH-related thrombosis rates and reduced mortality compared with those of age-matched controls. A small but significantly increased risk of life-threatening infections, especially , represents a long-term safety risk of complement inhibition.
OBJECTIVES
To evaluate the rates of thrombosis and meningococcal infections in patients with PNH treated with the complement component 3-targeted therapy pegcetacoplan.
METHODS
Cumulative patient-year exposure to pegcetacoplan was calculated, and thrombotic events and meningococcal infections were reviewed in 7 clinical trials and in the postmarketing setting. The clinical trial protocols and pegcetacoplan labeling required vaccination against , , and before pegcetacoplan use; the label allowed for prophylactic antibiotic use if pegcetacoplan must be administered before vaccination.
RESULTS
As of November 13, 2022, 464 patients with PNH had 619.4 patient-years of pegcetacoplan exposure in completed/ongoing clinical trials and the postmarketing setting. Seven thrombotic events were reported: 5 in clinical trials (2 in the same patient) and 2 in the postmarketing setting. The overall thrombosis rate was 1.13 events per 100 patient-years (clinical trials: 1.22 events/100 patient-years in 409.4 years; postmarketing: 0.95 events/100 patient-years in 210.0 years). No infections with meningococcal bacteria were reported.
CONCLUSION
Event rates for thrombosis were comparable between pegcetacoplan and previously reported rates of C5 inhibitors in patients with PNH, and no cases of meningococcal infection were reported with pegcetacoplan. Continued follow-up is required.
PubMed: 38812989
DOI: 10.1016/j.rpth.2024.102416 -
Frontiers in Public Health 2024is one of the porcine pathogens that have recently emerged as a pathogen capable of causing zoonoses in some humans. Patients infected with can present with sepsis,...
INTRODUCTION
is one of the porcine pathogens that have recently emerged as a pathogen capable of causing zoonoses in some humans. Patients infected with can present with sepsis, meningitis, or arthritis. Compared to common pathogens, such as , , and , infections in humans have been reported only rarely.
METHODS
This case report described a 57-year-old man who presented with impaired consciousness and fever following several days of backache. He was a butcher who worked in an abattoir and had wounded his hands 2 weeks prior. The patient was dependent on alcohol for almost 40 years. was detected in the cerebrospinal fluid by metagenomic next-generation sequencing. Although he received adequate meropenem and low-dose steroid therapy, the patient suffered from bilateral sudden deafness after 5 days of the infection. The final diagnosis was meningitis and sepsis.
RESULTS
The patient survived with hearing loss in both ears and dizziness at the 60-day follow-up.
DISCUSSION
We reported a case of infection manifested as purulent meningitis and sepsis. Based on literature published worldwide, human meningitis shows an acute onset and rapid progression in the nervous system. Similar to bacterial meningitis, effective antibiotics, and low-dose steroids play important roles in the treatment of human meningitis.
Topics: Humans; Streptococcus suis; Male; Middle Aged; Streptococcal Infections; China; Meningitis, Bacterial; Anti-Bacterial Agents; Sepsis; Hearing Loss, Sudden
PubMed: 38808002
DOI: 10.3389/fpubh.2024.1369703 -
PloS One 2024Yaws affects children in tropical regions, while syphilis primarily affects sexually active adults worldwide. Despite various campaigns towards the eradication of yaws...
Prevalence of yaws and syphilis in the Ashanti region of Ghana and occurrence of H. ducreyi, herpes simplex virus 1 and herpes simplex virus 2 in skin lesions associated with treponematoses.
Yaws affects children in tropical regions, while syphilis primarily affects sexually active adults worldwide. Despite various campaigns towards the eradication of yaws and elimination of syphilis, these two diseases are still present in Ghana. The aetiological agents of both diseases, two Treponema pallidum subspecies, are genetically similar. This study aimed to assess the prevalence of these treponematoses and the occurrence of pathogens causing similar skin lesions in the Ashanti region of Ghana. A point-of-care test was used to determine the seroprevalence of the treponematoses. Both yaws and syphilis were identified in the Ashanti region of Ghana. Multiplex PCR was used to identify treponemes and other pathogens that cause similar skin lesions. The results indicated that the seroprevalences of T. pallidum in individuals with yaws-like and syphilis-like lesions were 17.2% and 10.8%, respectively. Multiplex PCR results showed that 9.1%, 1.8% and 0.9% of yaws-like lesions were positive for Haemophilus ducreyi, herpes simplex virus-1 (HSV-1) and T. pallidum respectively. Among syphilis-like lesions, 28.3% were positive for herpes simplex virus -2 (HSV-2) by PCR. To our knowledge, this is the first time HSV-I and HSV-2 have been reported from yaws-like and syphilis-like lesions, respectively, in Ghana. The presence of other organisms apart from T. pallidum in yaws-like and syphilis-like lesions could impede the total healing of these lesions and the full recovery of patients. This may complicate efforts to achieve yaws eradication by 2030 and the elimination of syphilis and warrants updated empirical treatment guidelines for skin ulcer diseases.
Topics: Humans; Ghana; Yaws; Syphilis; Female; Adult; Male; Haemophilus ducreyi; Adolescent; Prevalence; Treponema pallidum; Child; Young Adult; Herpesvirus 1, Human; Middle Aged; Seroepidemiologic Studies; Skin; Child, Preschool; Treponemal Infections
PubMed: 38776332
DOI: 10.1371/journal.pone.0295088 -
BMC Microbiology May 2024We evaluated whether the sputum bacterial microbiome differs between nontuberculous mycobacteria pulmonary disease (NTM-PD) patients with stable disease not requiring... (Comparative Study)
Comparative Study
BACKGROUND
We evaluated whether the sputum bacterial microbiome differs between nontuberculous mycobacteria pulmonary disease (NTM-PD) patients with stable disease not requiring antibiotic treatment and those requiring antibiotics.
METHODS
We collected sputum samples from 21 clinically stable NTM-PD patients (stable group) and 14 NTM-PD patients needing antibiotic treatment (treatment group). We also obtained 13 follow-up samples from the stable group. We analyzed the 48 samples using 16S rRNA gene sequencing (V3-V4 region) and compared the groups.
RESULTS
In the linear discriminant analysis effect size (LEfSe) analysis, the species Porphyromonas pasteri, Haemophilus parahaemolyticus, Prevotella nanceiensis, and Gemella haemolysans were significantly more prevalent in the sputum of the stable group compared to the treatment group. No taxa showed significant differences in alpha-/beta-diversity or LEfSe between the 21 baseline and 13 follow-up sputum samples in the stable group. In the stable group, the genus Bergeyella and species Prevotella oris were less common in patients who achieved spontaneous culture conversion (n = 9) compared to those with persistent NTM positivity (n = 12) (effect size 3.04, p = 0.039 for Bergeyella; effect size 3.64, p = 0.033 for P. oris). In the treatment group, H. parainfluenzae was more common in patients with treatment success (n = 7) than in treatment-refractory patients (n = 7) (effect size 4.74, p = 0.013).
CONCLUSIONS
Our study identified distinct bacterial taxa in the sputum of NTM-PD patients based on disease status. These results suggest the presence of a microbial environment that helps maintain disease stability.
Topics: Humans; Sputum; Male; Female; Microbiota; Aged; Mycobacterium Infections, Nontuberculous; RNA, Ribosomal, 16S; Middle Aged; Anti-Bacterial Agents; Bacteria; Nontuberculous Mycobacteria; DNA, Bacterial; Lung Diseases
PubMed: 38760693
DOI: 10.1186/s12866-024-03308-2 -
Frontiers in Cellular and Infection... 2024Non-typeable (NTHi) and (Mcat) are two common respiratory tract pathogens often associated with acute exacerbations in Chronic Obstructive Pulmonary Disease (COPD) as...
Non-typeable (NTHi) and (Mcat) are two common respiratory tract pathogens often associated with acute exacerbations in Chronic Obstructive Pulmonary Disease (COPD) as well as with otitis media (OM) in children. Although there is evidence that these pathogens can adopt persistence mechanisms such as biofilm formation, the precise means through which they contribute to disease severity and chronicity remains incompletely understood, posing challenges for their effective eradication. The identification of potential vaccine candidates frequently entails the characterization of the host-pathogen interplay even though this approach is limited by the fact that conventional models do not permit long term bacterial infections. In the present work, by using air-liquid-interface (ALI) human airway models, we aimed to recreate COPD-related persistent bacterial infections. In particular, we explored an alternative use of the ALI system consisting in the assembly of an inverted epithelium grown on the basal part of a transwell membrane with the aim to enable the functionality of natural defense mechanisms such as mucociliary clearance and cellular extrusion that are usually hampered during conventional ALI infection experiments. The inversion of the epithelium did not affect tissue differentiation and considerably delayed NTHi or Mcat infection progression, allowing one to monitor host-pathogen interactions for up to three weeks. Notably, the use of these models, coupled with confocal and transmission electron microscopy, revealed unique features associated with NTHi and Mcat infection, highlighting persistence strategies including the formation of intracellular bacterial communities (IBCs) and surface-associated biofilm-like structures. Overall, this study demonstrates the possibility to perform long term host-pathogen investigations with the aim to define persistence mechanisms adopted by respiratory pathogens and individuate potential new vaccine targets.
Topics: Moraxella catarrhalis; Humans; Haemophilus influenzae; Biofilms; Moraxellaceae Infections; Persistent Infection; Host-Pathogen Interactions; Haemophilus Infections; Pulmonary Disease, Chronic Obstructive; Models, Biological; Respiratory Tract Infections; Epithelial Cells
PubMed: 38751999
DOI: 10.3389/fcimb.2024.1397940 -
Respiratory Medicine Jun 2024Antibiotic-resistant bacteria associated with LRTIs are frequently associated with inefficient treatment outcomes. Antibiotic-resistant Streptococcus pneumoniae,... (Review)
Review
Inhaled antibiotics: A promising drug delivery strategies for efficient treatment of lower respiratory tract infections (LRTIs) associated with antibiotic resistant biofilm-dwelling and intracellular bacterial pathogens.
Antibiotic-resistant bacteria associated with LRTIs are frequently associated with inefficient treatment outcomes. Antibiotic-resistant Streptococcus pneumoniae, Haemophilus influenzae, Pseudomonas aeruginosa, and Staphylococcus aureus, infections are strongly associated with pulmonary exacerbations and require frequent hospital admissions, usually following failed management in the community. These bacteria are difficult to treat as they demonstrate multiple adaptational mechanisms including biofilm formation to resist antibiotic threats. Currently, many patients with the genetic disease cystic fibrosis (CF), non-CF bronchiectasis (NCFB) and chronic obstructive pulmonary disease (COPD) experience exacerbations of their lung disease and require high doses of systemically administered antibiotics to achieve meaningful clinical effects, but even with high systemic doses penetration of antibiotic into the site of infection within the lung is suboptimal. Pulmonary drug delivery technology that reliably deliver antibacterials directly into the infected cells of the lungs and penetrate bacterial biofilms to provide therapeutic doses with a greatly reduced risk of systemic adverse effects. Inhaled liposomal-packaged antibiotic with biofilm-dissolving drugs offer the opportunity for targeted, and highly effective antibacterial therapeutics in the lungs. Although the challenges with development of some inhaled antibiotics and their clinicals trials have been studied; however, only few inhaled products are available on market. This review addresses the current treatment challenges of antibiotic-resistant bacteria in the lung with some clinical outcomes and provides future directions with innovative ideas on new inhaled formulations and delivery technology that promise enhanced killing of antibiotic-resistant biofilm-dwelling bacteria.
Topics: Humans; Biofilms; Administration, Inhalation; Anti-Bacterial Agents; Respiratory Tract Infections; Drug Delivery Systems; Drug Resistance, Bacterial; Streptococcus pneumoniae; Liposomes; Bronchiectasis; Haemophilus influenzae; Pulmonary Disease, Chronic Obstructive; Pseudomonas aeruginosa; Staphylococcus aureus; Cystic Fibrosis
PubMed: 38729529
DOI: 10.1016/j.rmed.2024.107661 -
RSC Advances May 2024Layered double hydroxides (LDH) are promising 2D nanomaterials being investigated for several engineering and biomedical applications. In this work, quinary Zr Al Fe Co...
Layered double hydroxides (LDH) are promising 2D nanomaterials being investigated for several engineering and biomedical applications. In this work, quinary Zr Al Fe Co Ni LDH and its Al Fe Co Ni LDH quaternary and Fe Co Ni LDH tertiary roots were prepared and characterized. All samples showed an aggregated, layered morphology with zero surface charge and approximately 300 nm of hydrodynamic size. BET surface area of Al Fe Co Ni LDH showed a remarkable value of 143.25 m g as opposed to 26.2 m g and 45.4 m g for Fe Co Ni LDH and Zr Al Fe Co Ni LDH, respectively. The antimicrobial activity of the prepared samples was assessed against the many pathogenic bacteria; () , () , () , () , () , and () , and six fungal species. Furthermore, anti-biofilm activity, growth curve assay, and effect of UV illumination were examined against various pathogenic microbes. Zr Al Fe Co Ni displayed remarkable antibacterial activity, as indicated by the lowest values of the minimum inhibitory concentrations (MIC) of 4-166.7 μg mL. Results for fungal strains varied in terms of their susceptibilities for the different samples tested. Zn Al Fe Co Ni was able to inhibit the biofilm formation of (96.09%), (98.32%), and () (95.93%). This study shown that certain LDH categories, particularly Zr Al Fe Co Ni, may be promising antibacterial agents against variety of pathogenic microorganisms that cause serious infections.
PubMed: 38716105
DOI: 10.1039/d4ra00508b -
Scientific Reports May 2024Respiratory infections are common causes of acute exacerbation of chronic obstructive lung disease (AECOPD). We explored whether the pathogens causing AECOPD and...
Respiratory infections are common causes of acute exacerbation of chronic obstructive lung disease (AECOPD). We explored whether the pathogens causing AECOPD and clinical features changed from before to after the coronavirus disease 2019 (COVID-19) outbreak. We reviewed the medical records of patients hospitalized with AECOPD at four university hospitals between January 2017 and December 2018 and between January 2021 and December. We evaluated 1180 patients with AECOPD for whom medication histories were available. After the outbreak, the number of patients hospitalized with AECOPD was almost 44% lower compared with before the outbreak. Patients hospitalized with AECOPD after the outbreak were younger (75 vs. 77 years, p = 0.003) and more often stayed at home (96.6% vs. 88.6%, p < 0.001) than patients of AECOPD before the outbreak. Hospital stay was longer after the outbreak than before the outbreak (10 vs. 8 days. p < 0.001). After the COVID-19 outbreak, the identification rates of S. pneumoniae (15.3 vs. 6.2%, p < 0.001) and Hemophilus influenzae (6.4 vs. 2.4%, p = 0.002) decreased, whereas the identification rates of P. aeruginosa (9.4 vs. 13.7%, p = 0.023), Klebsiella pneumoniae (5.3 vs. 9.8%, p = 0.004), and methicillin-resistant Staphylococcus aureus (1.0 vs. 2.8%, p = 0.023) increased. After the outbreak, the identification rate of influenza A decreased (10.4 vs. 1.0%, p = 0.023). After the outbreak, the number of patients hospitalized with AECOPD was lower and the identification rates of community-transmitted pathogens tended to decrease, whereas the rates of pathogens capable of chronic colonization tended to increase. During the period of large-scale viral outbreaks that require quarantine, patients with AECOPD might be given more consideration for treatment against strains that can colonize chronic respiratory disease rather than community acquired pathogens.
Topics: Humans; COVID-19; Pulmonary Disease, Chronic Obstructive; Aged; Male; Female; Hospitalization; Aged, 80 and over; SARS-CoV-2; Middle Aged; Pandemics; Respiratory Tract Infections; Disease Progression; Retrospective Studies; Streptococcus pneumoniae; Haemophilus influenzae
PubMed: 38714885
DOI: 10.1038/s41598-024-61360-4 -
Journal of Clinical Tuberculosis and... Aug 2024Workup of bronchiectasis patients mandates microbiological characterization often being sought via Bronchoscopy. However, whether to perform bronchial or lung biopsies,...
BACKGROUND
Workup of bronchiectasis patients mandates microbiological characterization often being sought via Bronchoscopy. However, whether to perform bronchial or lung biopsies, is unknown, especially for the diagnosis of NTM pulmonary disease. We aimed to assess the current practice and yield of the different bronchoscopic procedures in this setting.
METHODS
Data from an adult cohort with bronchiectasis referred for bronchoscopy for microbiologic sampling was reviewed, including demographics, etiology, imaging and results of the different bronchoscopic procedures performed.
RESULTS
127 subjects were analyzed (mean age 61, 56% female). BAL culture was positive in 44%. Frequent pathogens were Hemophilus Influenza (20%), pseudomonas aeruginosa (8%) and Staphylococcus aureus (7%). NTM and tuberculosis were found in 6% and 1.5% respectively. BAL cytology was sent in 125 procedures, EBB was performed in 51 patients (40%) and TBLB in 38 patients (30%). BAL cytology and both EBB and TBB (including tissue cultures) had no benefit over BAL with respect to microbiological diagnosis, including identification of mycobacterial disease.
CONCLUSIONS
In adult subjects with Non-CF bronchiectasis requiring bronchoscopy for microbiological characterization, BAL cytology and lung tissue biopsies were frequently performed but were of minimal additional benefit over BAL culture (including for mycobacterial pulmonary disease), and are most likely futile.
PubMed: 38708038
DOI: 10.1016/j.jctube.2024.100447