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The article focuses on a case of a previously healthy, vaccinated 7-year-old experiencing occipital scalp and neck pain following a bicycle accident, later developing acute hearing loss and difficulty walking. Topics include the patient's clinical presentation, including neurological symptoms and abnormal laboratory findings, and diagnostic evaluations such as imaging and blood tests, leading to the diagnosis of a concussion and subsequent neurological complications.

The purpose of the study was to evaluate the clinical utility of multiplex PCR for detecting bacterial respiratory pathogens in nasopharyngeal samples. Acutely ill adults in the emergency department with respiratory infection symptoms, fever, chest pain or poor general condition were enrolled for this cohort study. Samples were stored at –70 °C until being analysed with multiplex PCR for seven respiratory bacteria. Of the 912 patients enrolled, those with positive bacterial samples (n = 130, 14%) were significantly younger than those with a negative finding (55.5 years vs 62.2 years, p < 0.001), and their mean C‐reactive protein (CRP) concentration was higher (110 mg/L vs 59 mg/L, p < 0.0001). Patients with a positive respiratory bacterial finding had a higher probability of pneumonia (35% vs 13%, p < 0.001) and a higher likelihood of receiving a prescription for antibiotics than those with a negative finding (79% vs 59%, p < 0.0001). Positive detection of Streptococcus pneumoniae was associated with a 4.5‐fold risk of pneumonia in a multivariate model and detection of an atypical respiratory pathogen with a 9‐fold risk. Bacterial PCR performed on nasopharyngeal samples appeared to offer a valuable addition to the diagnostics of infections in adults in acute care. [ABSTRACT FROM AUTHOR]

To understand the preferences of healthcare providers (HCPs) in Switzerland for pediatric hexavalent vaccine attributes. A discrete-choice experiment included a series of choices between 2 hypothetical pediatric hexavalent vaccines with varying attributes: device type (including preparation time and risk of dosage errors), proportion of infants seroprotected against Haemophilus influenzae type b (Hib) at 11–12 months (pre-booster), packaging size, years on the market, and the thermostability at room temperature. Odds ratios (ORs) and conditional relative attribute importance (CRAI) were calculated using random-parameters logit. HCPs (150 pediatricians and 40 nursing staff) in Switzerland were unlikely to choose a vaccine conferring 50% (OR 0.00; 95% CI 0.00–0.00) or 70% (OR 0.01; 95% CI 0.00–0.01) of infants with Hib seroprotection at 11-12 months (pre-booster) compared with a vaccine conferring 90% seroprotection. The odds of choosing a vaccine available on the market for more than 3 years were nearly 5 times the odds of choosing a vaccine available on the market for less than 1 year (OR 4.76; 95% CI 1.87–7.65). The odds of choosing a vaccine in a prefilled syringe were nearly 3 times the odds of choosing a reconstituted vaccine (OR 2.77; 95% CI 1.39–4.15), and the odds of choosing a vaccine with a smaller package size were nearly 2 times the odds of choosing a vaccine with larger package size (OR 1.89; 95% CI 1.23–2.55). HCPs were equally likely to choose vaccines that can stay at room temperature for 6 versus 3 days (OR 1.07; 95% CI 0.73–1.42). According to CRAI, the most important attribute was Hib seroprotection, followed by years on the market, device type, and packaging size. Hib seroprotection at 11–12 months was the most important hexavalent vaccine attribute to HCPs in this study. [ABSTRACT FROM AUTHOR]

Haemophilus influenzae (H. influenzae) has evolved as a prominent pathogen, with nontypeable strains (NTHi) emerging as a leading cause of invasive disease, particularly among the elderly. Since the introduction of Haemophilus influenzae B (Hib) vaccine, invasive infection has shifted from children with Hib to the elderly with NTHi. NTHi affects those primarily with predisposing factors such as an immunocompromised state, CSF leakage, or ENT infections. We present two cases that emphasize the shift of invasive infection, risk factors, and elevated intracranial pressure (ICP) as a complication. Case 1. A 75-year-old female with a sudden onset of weakness and respiratory symptoms deteriorated rapidly. Imaging revealed mastoid effusion and ventriculitis, likely originating from otomastoiditis. Lumber puncture confirmed NTHi. ICU course complicated by elevated ICP prompted repeat lumbar puncture. The patient recovered after 8 days but not near baseline. Case 2. A 50-year-old female with altered mental status, headache, and ear pain exhibited signs of pansinusitis and pseudotumor cerebri. Elevated ICP was evident upon lumbar puncture, and NTHi was isolated in CSF and blood cultures. MRI of the brain showed prominent optic nerve sheaths and transverse sinus arachnoid granulations' concern for underlying pseudotumor cerebri. Repeat lumbar puncture or ventricular drainage was deferred after discussion with neurosurgery. Diabetes was identified as a comorbidity. The patient's condition improved after 14 days of antibiotics and dexamethasone. These cases emphasize the shifting landscape of H. influenzae meningitis, primarily driven by NTHi, especially among the elderly. Although NTHi infections were considered less invasive, recent epidemiology review indicated it as the leading cause of H. influenzae meningitis. With the increasing prevalence of NTHi and its increase in invasive patterns, it is crucial to implement vaccination strategies and develop new vaccines targeting NTHi. [ABSTRACT FROM AUTHOR]

Membrane proteins constitute about 20% of the human proteome and play crucial roles in cellular functions. However, a complete understanding of their structure and function is limited by their hydrophobic nature, which poses significant challenges in purification and stabilization. Detergents, essential in the isolation process, risk destabilizing or altering the proteins' native conformations, thus affecting stability and functionality. This study leverages single-particle cryo-electron microscopy to elucidate the structural nuances of membrane proteins, focusing on the SLAC1 bacterial homolog from Haemophilus influenzae (HiTehA) purified with diverse detergents, including n-dodecyl β-D-maltopyranoside (DDM), glycodiosgenin (GDN), β-D-octyl-glucoside (OG), and lauryl maltose neopentyl glycol (LMNG). This research not only contributes to the understanding of membrane protein structures but also addresses detergent effects on protein purification. By showcasing that the overall structural integrity of the channel is preserved, our study underscores the intricate interplay between proteins and detergents, offering insightful implications for drug design and membrane biology. [ABSTRACT FROM AUTHOR]

AbstractThe objective of this study was to evaluate the efficacy of various dosing regimens of omadacycline against main drug-resistant pathogens in the treatment of acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP). Monte Carlo simulations were conducted using pharmacokinetic parameters and pharmacodynamic data to calculate cumulative fractions of response (CFRs) in terms of drug area under the concentration curve/minimum inhibition concentration targets.CFR ≥ 90% was considered optimal for a dosage regimen. CFR of any approved oral/intravenous regimen with loading-dose was ≥ 90% against methicillin-resistant Staphylococcus aureus (MRSA) for ABSSSI and penicillin-resistant Streptococcus pneumonia, tetracycline-resistant Streptococcus pneumonia, MRSA and β-lactamase positive Haemophilus influenzae for CABP. In conclusion, approved oral/intravenous loading and maintenance doses of omadacycline showed enough efficacy in the treatment of ABSSI and CABP caused by the main drug-resistant pathogens. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) is a global public health threat with significant impact on treatment outcomes. The World Health Organization's Global Action Plan on AMR recommended strengthening the evidence base through surveillance programs and research. Comprehensive, timely data on AMR for organisms isolated from ocular infections are needed to guide treatment decisions and inform researchers and microbiologists of emerging trends. This article aims to provide an update on the development of AMR in ocular organisms, AMR in bacterial ocular infections and on AMR stewardship programs globally. The most common ocular pathogens are Pseudomonas aeruginosa, Staphylococcus spp., Streptococcus pneumoniae, and Haemophilus influenzae in ocular infections. A variety of studies and a few surveillance programs worldwide have reported on AMR in these infections over time. Fluoroquinolone resistance has increased particularly in Asia and North America. For conjunctivitis, the ARMOR cumulative study in the USA reported a slight decrease in resistance to ciprofloxacin. For keratitis, resistance to methicillin has remained stable for S. aureus and CoNS, while resistance to ciprofloxacin has decreased for MRSA globally. Methicillin‐resistance and multidrug resistance are also emerging, requiring ongoing monitoring. Antimicrobial stewardship (AMS) programmes have a critical role in reducing the threat of AMR and improving treatment outcomes. To be successful AMS must be informed by up‐to‐date AMR surveillance data. As a profession it is timely for ophthalmology to act to prevent AMR leading to greater visual loss through supporting surveillance programmes and establishing AMS. [ABSTRACT FROM AUTHOR]

We report for the first time in Portugal a serotype c Haemophilus influenzae isolated from an adult, with HIV-1 infection. Whole-genome sequencing characterized the isolate as clonal complex ST-7, albeit with a novel MLST (ST2754) due to a unique atpG profile. Integration of this genome with other available H. influenzae serotype c genomes from PubMLST revealed its overall genetic distinctiveness, with the closest related isolate being identified in France in 2020. This surveillance study, involving collaboration among hospitals and reference laboratory, successfully contributed to the identification and characterization of this rare serotype. [ABSTRACT FROM AUTHOR]

Severe acute respiratory tract infections (SARIs) has been well described in South Africa with seasonal patterns described for influenza and respiratory syncytial virus (RSV), while others occur year-round (rhinovirus and adenovirus). This prospective syndromic hospital-based surveillance study describes the prevalence and impact of public interventions on the seasonality of other respiratory pathogens during the coronavirus disease-19 (COVID-19) pandemic. This occurred from August 2018 to April 2022, with 2595 patients who met the SARS case definition and 442 controls, from three sentinel urban and rural hospital sites in South Africa. Naso/oro-pharyngeal (NP/OP) swabs were tested using the FastTrack Diagnostics® Respiratory pathogens 33 (RUO) kit. Descriptive statistics, odds ratios, and univariate/multivariate analyses were used. Rhinovirus (14.80%, 228/1540) and Streptococcus pneumoniae (28.50%, 439/1540) were most frequently detected in NP/OP swabs and in children <1 years old (35%, 648/1876). Among others, pathogens associated with SARI cases causing disease were influenza A&B, HRV, RSV, hCoV 229e, Haemophilus influenzae, Staphylococcus aureus, and Streptococcus pneumoniae. Pre-COVID-19, seasonal trends of these pathogens correlated with previous years, with RSV and influenza A seasons only resuming after the national lockdown (2021). It is evident that stringent lockdown conditions have severe impacts on the prevalence of respiratory tract infections. [ABSTRACT FROM AUTHOR]

Bacterial meningitis is a severe infection with a high fatality rate, and affects children in particular. Three vaccines against the most common bacterial causatives of meningitis, Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitides, exist. Monitoring the type and incidence of bacterial meningitis is important for making future prevention and control plans. In this study, we retrospectively analyzed data regarding bacterial meningitis recovered in the Italian Hospital of Desio from 2000 to 2019. Samples from a total of 128 patients were included. Streptococcus pneumoniae was the most common microorganism, isolated in 45 cases, followed by Neisseria meningitidis (14), Listeria monocytogenes (8), Streptococcus agalactiae (group B) (4), and Haemophilus influenzae type b (2). The implementation of vaccination schedules decreased the number of bacterial meningitis cases caused by H. influenzae type b, S. pneumoniae, and N. meningitidis. Considering the bacterial meningitis cases in subjects aged 0–12 years, no H. influenzae type b strain was isolated, five cases of N. meningitidis were identified before the introduction of vaccination, and seven S. pneumoniae strains were isolated before the introduction of the PCV13 vaccination. Surveillance studies allowed us to monitor changes in bacteria distribution and to guide vaccination strategies. [ABSTRACT FROM AUTHOR]

Wheezing is the cardinal symptom of asthma; its presence early in life, mostly caused by viral infections, is a major risk factor for the establishment of persistent or recurrent disease. Early‐life wheezing and asthma exacerbations are triggered by common respiratory viruses, mainly rhinoviruses (RV), and to a lesser extent, respiratory syncytial virus, parainfluenza, human metapneumovirus, coronaviruses, adenoviruses, influenza, and bocavirus. The excess presence of bacteria, several of which are part of the microbiome, has also been identified in association with wheezing and acute asthma exacerbations, including haemophilus influenza, streptococcus pneumoniae, moraxella catarrhalis, mycoplasma pneumoniae, and chlamydophila pneumonia. While it is not clear when asthma starts, its characteristics develop over time. Airway remodeling already appears between the ages of 1 and 3 years of age even prior to the presence of atopic inflammation or an asthma diagnosis. The role of genetic defect or variations hampering the airway epithelium in response to environmental stimuli and severe disease morbidity are now considered as major determinants for early structural changes. Repeated viral infections can induce and perpetuate airway hyperresponsiveness. Allergic sensitization, that often precedes infection‐induced wheezing, shifts inflammation toward type‐2, while common respiratory infections themselves promote type‐2 inflammation. Nevertheless, most children who wheeze with viral infections during infancy and during preschool years do not develop persistent asthma. Multiple factors, including illness severity, viral etiology, allergic sensitization, and the exposome, are associated with disease persistence. Here, we summarize current knowledge and developments in infection epidemiology of asthma in children, describing the known impact of each individual agent and mechanisms of transition from recurrent wheeze to asthma. [ABSTRACT FROM AUTHOR]

Community-acquired pneumonia (CAP) is a common disease in children, and its aetiological and clinical diagnosis are challenging for physicians in both private practice and hospitals. Over the past three decades, conjugate vaccines have successfully reduced the burden of the former main causes of CAP, Streptococcus pneumoniae and Haemophilus influenzae type b. Today, viruses are by far the most commonly detected pathogens in children with CAP. Conclusion: New insights into the aetiology and treatment of CAP in children in recent years have influenced management and are the focus of this review. In addition to reducing diagnostic uncertainty, there is an urgent need to reduce antibiotic overuse and antimicrobial resistance in children with CAP. What is Known: • Conjugate vaccines against Streptococcus pneumoniae and Haemophilus influenzae type b have shifted the epidemiology of childhood CAP to predominantly viral pathogens and Mycoplasma pneumoniae. • Clinical, laboratory, and radiological criteria cannot reliably distinguish between bacterial and viral aetiology in children with CAP. What is New: • Test results and epidemiological data must be carefully interpreted, as no single diagnostic method applied to non-pulmonary specimens has both high sensitivity and high specificity for determining pneumonia aetiology in childhood CAP. • This review provides a simple and pragmatic management algorithm for children with CAP to aid physicians in providing optimal and safe care and reducing antibiotic prescribing. [ABSTRACT FROM AUTHOR]

Objectives Haemophilus parainfluenzae is an opportunistic pathogen causing respiratory tract infection and sexually transmitted diseases. The emergence of multidrug resistance in this species is particularly worrisome, especially since the recent description of CTX-M-15 ESBL-producing isolates in Spain. The aim of this study was to characterize a CTX-M-15-producing H. parainfluenzae clinical isolate, HP01, obtained from a urethral swab. Methods MICs were determined with gradient strips for this isolate. Hydrolysis assays were performed with the β LACTA test. Genomic DNA from HP01 was subjected to Illumina and Oxford Nanopore sequencing to investigate the genetic environment of bla CTX-M-15. Phylogenetic analysis was performed with available H. parainfluenzae genomes from the NCBI database, including CTX-M-15 producers. Results HP01, an XDR isolate, was resistant to penicillin, third-generation cephalosporins, fluoroquinolones, macrolides, cyclines and co-trimoxazole and susceptible only to carbapenems and rifampicin. HP01 carried bla TEM-1, bla CTX-M-15, tet (M), catS and mef (E) /mel and harboured amino acid substitutions in PBP3, PBP5, GyrA, ParC and FolA implicated in resistance. Genomic analysis revealed that bla CTX-M-15 was carried by a Tn 3 -like transposon inserted into a novel integrative and conjugative element (ICE), ICE Hpa SLS, present on the chromosome and belonging to the ICE Hin1056 family described in Haemophilus influenzae. The tet (M)-MEGA element was also detected on the chromosome. No plasmid was found. The phylogenetic analysis showed that four H. parainfluenzae producing CTX-M-15 clustered in the same clade. Conclusions Here we report the description of an XDR H. parainfluenzae producing bla CTX-M-15 isolated from a urethral swab. The bla CTX-M-15 gene was inserted into an ICE structure similar to those recently described in CTX-M-15 producers in Spain. The emergence of XDR H. parainfluenzae producing bla CTX-M-15 is a matter of great concern. Careful surveillance is required to prevent its spread. [ABSTRACT FROM AUTHOR]

Tripartite ATP-independent periplasmic (TRAP) transporters are secondary-active transporters that receive their substrates via a soluble-binding protein to move bioorganic acids across bacterial or archaeal cell membranes. Recent cryo-electron microscopy (cryo-EM) structures of TRAP transporters provide a broad framework to understand how they work, but the mechanistic details of transport are not yet defined. Here we report the cryo-EM structure of the Haemophilus influenzae N-acetylneuraminate TRAP transporter (HiSiaQM) at 2.99 Å resolution (extending to 2.2 Å at the core), revealing new features. The improved resolution (the previous HiSiaQM structure is 4.7 Å resolution) permits accurate assignment of two Na+ sites and the architecture of the substrate-binding site, consistent with mutagenic and functional data. Moreover, rather than a monomer, the HiSiaQM structure is a homodimer. We observe lipids at the dimer interface, as well as a lipid trapped within the fusion that links the SiaQ and SiaM subunits. We show that the affinity (KD) for the complex between the soluble HiSiaP protein and HiSiaQM is in the micromolar range and that a related SiaP can bind HiSiaQM. This work provides key data that enhances our understanding of the 'elevator-with-an-operator' mechanism of TRAP transporters. [ABSTRACT FROM AUTHOR]

Objectives Lefamulin (Xenleta™), a pleuromutilin antibiotic, was approved for the oral and IV treatment of community-acquired bacterial pneumonia (CABP) in adults in 2019/2020. This study evaluated the in vitro activity of lefamulin and comparators against 19 584 unique bacterial isolates collected from patients with community-acquired respiratory tract infections and hospitalized patients with pneumonia within the global SENTRY Antimicrobial Surveillance Program during 2015–21. Methods Isolates were susceptibility tested by the CLSI broth microdilution method, and resistance mechanisms were investigated in isolates with elevated lefamulin MICs. Results Lefamulin exhibited potent antibacterial activity against the most common and typical CABP pathogens tested, including Streptococcus pneumoniae [MIC50/90, 0.06/0.25 mg/L; 99.9% susceptible (S)], Staphylococcus aureus (MIC50/90, 0.06/0.12 mg/L; 99.6% S), Haemophilus influenzae (MIC50/90, 0.5/2 mg/L; 99.1% S) and Moraxella catarrhalis (MIC50/90, 0.06/0.12 mg/L; 100.0% S). Potent activity was also observed against the less common pneumonia pathogens: β-haemolytic (MIC50/90 of 0.03/0.06 mg/L) and viridans group Streptococcus spp. (MIC50/90 of 0.06/0.25 mg/L) and Haemophilus parainfluenzae (MIC50/90 of 1/4 mg/L). Lefamulin's activity was not adversely affected by resistance to macrolides, penicillin, tetracyclines, fluoroquinolones and other resistance phenotypes. Non-susceptibility/resistance to lefamulin was rare and primarily determined by ribosomal protection through vga (A) variants in S. aureus, overexpression of AcrAB-TolC efflux pump in H. influenzae or modifications in L3, L4 and 23SrRNA in Streptococcus spp. Conclusions Based on the coverage of the most important CABP pathogens and lacking cross-resistance, lefamulin may represent a valuable empirical treatment option for ambulatory and hospitalized patients with CABP, particularly in settings with high prevalence of resistance. [ABSTRACT FROM AUTHOR]

Objective: Rare disease Background: Catastrophic antiphospholipid syndrome (CAPS) is a rare, life-threatening form of antiphospholipid syndrome characterized by widespread thrombotic complications leading to multiorgan ischemia and failure. Although there are no standard treatment guidelines for CAPS, it often involves triple therapy with anticoagulation, corticosteroids, and plasma exchange. Recently, biologics such as rituximab and eculizumab have also shown promise as potential new therapies for CAPS, as observed in our case. Case Report: We describe a 59-year-old female patient who presented with altered mental status and diffuse weakness. Imaging studies revealed multiorgan thrombosis along with thrombocytopenia that markedly improved with plasma exchange therapy, steroids, and a heparin drip. While the exact etiology of CAPS remained unknown, it was likely precipitated by her warfarin discontinuation and confirmed Haemophilus influenzae infection. The patient's hospital course was complicated by hemorrhagic shock after a renal biopsy, followed by an acute drop in thrombocytopenia and new embolic infarcts in the brain that raised concern for CAPS re-emergence. To address the refractory nature of her condition, the patient underwent a trial of rituximab, which remarkably improved her clinical picture and platelet count by an 8-fold increase within 1 week. Conclusions: This case highlights the importance of early recognition and diagnosis of catastrophic antiphospholipid syndrome, a true rheumatological emergency that requires aggressive treatment to prevent irreversible complications. Our patient's presentation and response to treatment also underscores the complexity of managing CAPS and the use of newer biological therapies in refractory cases. [ABSTRACT FROM AUTHOR]

Background: After issuing the "Global action plan on antimicrobial resistance" in 2015, the World Health Organization (WHO) established a priority pathogens list for supporting research and development of novel antimicrobials. We conducted a comprehensive analysis of the WHO priority organisms in a Japanese tertiary hospital to apprehend the local AMR epidemiology. Methods: Data were obtained from electrical medical records in Osaka University Hospital between January 2010 and March 2021. The critical, high, and medium "priority pathogens list" categories of the WHO were used to compare results between the early (2010–2015) and late (2016–2021) phases. Results: Out of 52,130 culture-positive specimens, a total of 9,872 (18.9%) contained WHO priority isolates. In comparison to early phases, late phases were likely to have higher rates of carbapenem resistance in Pseudomonas aeruginosa (15.7% vs 25.0%, P<0.001), 3rd generation cephalosporin resistance in Escherichia coli (11.5% vs 17.8%, P<0.001) as well as Klebsiella pneumoniae (1.6% vs 4.4%, P<0.001), and ampicillin resistance in Haemophilus influenzae (2.4% vs 3.9%, P<0.001). After 2015, however, the proportion of methicillin-resistant and vancomycin-intermediate Staphylococcus aureus was low. In this study, in-hospital mortality was comparable among patients with resistance to the three WHO priority pathogen types: critical (5.9%), high (3.9%), and medium (3.8%), and no significant change was observed between two phases in each category. However, significant interactions for in-hospital mortality were observed in subgroup analyses between "critical priority" AMR and the presence of comorbid conditions, such as chronic kidney disease or diabetes mellitus. Conclusions: To implement better antimicrobial stewardship policies and practices, local priority pathogens and "high-risk" patients for in-hospital death need to be acknowledged and evaluated periodically. [ABSTRACT FROM AUTHOR]

Biologically active compounds in most spices possess antimicrobial and other important biomedical properties. There have been huge demands for natural immunity boosters (spices and herbs), considering the recent global pandemic and challenges relating to drug-resistant pathogens. This study was designed to compare the efficacy of ginger, garlic and turmeric spices against some pathogenic microorganisms. Aqueous extraction of spices, antimicrobial sensitivity and minimum inhibitory concentration tests were done using standard microbiological methods. Bioactive compounds were estimated using the gas chromatography--mass spectrometry (GC-MS) method. Aqueous extracts of ginger inhibited the growth of all test isolates except Streptococcus pneumoniae, with inhibition zones ranging between 0.9 mm and 13.5 mm. Escherichia coli, S. pneumoniae and Haemophilus influenzae were resistant to turmeric extracts, while the extract of garlic inhibited only four of the test pathogens. Inhibition zones for turmeric ranged between 4.4 mm and 10.9 mm, while those for garlic were between 4.7 mm and 11.5 mm. All the spice extracts did not inhibit microbial growth at 10-40%. An antibiotic spectrum indicated that Bacillus sp. was resistant to all but one, nitrofurantoin, which also inhibited the growth of almost all pathogens, except H. influenzae, with zones ranging between 10.5 mm and 11.6 mm. All test pathogens were resistant to cloxacillin except E. coli (10.6 mm). The major phyto-active compounds present in ginger are 2-Butanone,4-(4-hydroxy-3-methoxyphenyl), 1,3-Cyclohexadiene and 1-(4-Hydroxy-3-methoxyphenyl). Significance: Conclusively, ginger, turmeric and garlic have varied inhibitory activities against diverse organisms, indicating their antimicrobial properties; however, ginger showed a higher inhibitory effect and more diverse antimicrobial property amongst selected isolates. Furthermore, certain bioactive compounds of biomedical importance were present. We therefore recommend the use of these spices as alternative natural food preservatives against spoilage organisms, as well as potential natural sources for bioactive compounds in drug development against pathogens. [ABSTRACT FROM AUTHOR]

Outer membrane vesicles (OMVs) are spontaneously released by many gram-negative bacteria during their growth and constitute an important virulence factor for bacteria, helping them to survive through harsh environmental conditions. Native OMVs, naturally-released from bacteria, are produced at a level too low for vaccine manufacturing, requiring chemical treatment (detergent-extracted) or genetic manipulation, resulting in generalized modules for membrane antigens (GMMAs). Over the years, the nature and properties of OMVs have made them a viable platform for vaccine development. There are a few licensed OMV vaccines mainly for the prevention of meningitis caused by Neisseria meningitidis serogroup B (MenB) and Haemophilus influenzae type b (Hib). There are several candidates in clinical development against other gram-negative organisms from which the OMVs are derived, but also against heterologous targets in which the OMVs are used as carriers (e.g. coronavirus disease 2019 [COVID-19]). The use of OMVs for targets other than those from which they are derived is a major advancement in OMV technology, improving its versatility by being able to deliver protein or polysaccharide antigens. Other advances include the range of genetic modifications that can be made to improve their safety, reduce reactogenicity, and increase immunogenicity and protective efficacy. However, significant challenges remain, such as identification of general tools for high-content surface expression of heterologous proteins on the OMV surface. Here, we outline the progress of OMV vaccines to date, particularly discussing licensed OMV-based vaccines and candidates in clinical development. Recent trends in preclinical research are described, mainly focused on genetic manipulation and chemical conjugation for the use of OMVs as carriers for heterologous protein and polysaccharide antigens. Remaining challenges with the use of OMVs and directions for future research are also discussed. [ABSTRACT FROM AUTHOR]

Seizure is a rare but documented adverse event associated with ampicillin, which is one of the most commonly used antibiotics used in pediatrics. We report a case of a 4-month-old male infant with Haemophilus influenzae type A meningitis that experienced recurrent tonic-clonic seizures, possibly secondary to ampicillin treatment. After ampicillin administration was withdrawn and antiepileptic agents were administered, the seizures resolved, improving the patient's clinical status rapidly. This case report adds to the growing body of literature on ampicillin-induced seizures. [ABSTRACT FROM AUTHOR]

Most naturally competent bacteria tightly regulate the window of the competent state to maximize their ecological fitness under specific conditions. Development of competence by Haemophilus influenzae strain Rd KW20 is stimulated by cAMP and inhibited by purine nucleotides, respectively. In contrast, cAMP inhibits cell growth, but nucleotides are important for KW20 growth. However, the mechanisms underlying the abovementioned reciprocal effects are unclear. Here, we first identified a periplasmic acid phosphatase AphAEc of Escherichia coli as a new cAMP-binding protein. We show cAMP competitively inhibits the phosphatase activities of AphAEc and its homolog protein AphAHi in the KW20 strain. Furthermore, we found cAMP inhibits two other periplasmic nonspecific phosphatases, NadNHi (which provides the essential growth factor V, NAD) and HelHi (eP4, which converts NADP to NAD) in KW20. We demonstrate cAMP inhibits cell growth rate, especially via NadNHi. On the other hand, the inhibitory effect of purine nucleotide AMP on competence was abolished in the triple deletion mutant ΔhelHiΔnadNHiΔaphAHi, but not in the single, double deletion or complemented strains. Adenosine, however, still inhibited the competence of the triple deletion mutant, demonstrating the crucial role of the three phosphatases in converting nucleotides to nucleosides and thus inhibiting KW20 competence. Finally, cAMP restored the competence inhibited by GMP in a dose-dependent manner, but not competence inhibited by guanosine. Altogether, we uncovered these three periplasmic phosphatases as the key players underlying the antagonistic effects of cAMP and purine nucleotides on both cell growth and competence development of H. influenzae. [ABSTRACT FROM AUTHOR]

Pseudomonas sp. HIB_D has been observed to have nitrification activity that can oxidize ammonia/ammonium to nitrite and nitrate. This bacterium was isolated from the aquaculture environment with Ancol Indonesian marine water sources. Pseudomonas sp. HIB_D was applied in the rearing water of Litopenaeus vannamei to decrease nitrogen pollution levels and support a sustainable cultivation environment. This present study was set up using a completely randomized design with four treatments and three replications, i.e., control (without bacterial application) and bacterial application with a cell density of 107, 108, and 109 CFU mL−1 in a volume of 100 mL for 90 L seawater treatment. Thirty-six individuals of 15-day-old postlarvae L. vannamei (PL 15) (a density of 120 PL m-2) were used in this study for an 8-week rearing period. Based on the water quality analysis, the ammonia level under the bacterial applications was lower than in the control after 8-week cultivation. Nitrate levels increased at week 6 and decreased at week 8, specifically in 109 CFU mL−1 treatment. L. vannamei with 109 CFU mL−1 bacterial application had the best production performance with a survival rate of 94.33 ± 2.78%, an absolute length gain of 10.59 ± 0.22 cm, an absolute weight gain of 8.16 ± 0.33 g, a specific growth rate of 14.12% ± 0.01% day−1, and a feed conversion ratio of 1.26 ± 0.03. The blood glucose level and total hemocyte count of shrimp under the bacterial application with a density of 109 CFU mL−1 showed the highest level (30.71 ± 13.9 mg dL−1) and the lowest level (15 × 106 cells mL−1), respectively. The results showed that all treatments performed better than the control, in which the 109 CFU mL−1 bacterial application was the best treatment. [ABSTRACT FROM AUTHOR]

Objective: We aimed to investigate the difference between the bacterial profiles of the nasal cavities and adenoid surfaces of children with chronic rhinosinusitis (CRS). We also intended to determine and analyze the potential correlation between the pre- and post-adenoidectomy differences in the nasal bacterial profile and clinical prognosis. Methods: The clinical information of pediatric patients was collected. All the children underwent adenoidectomy (with or without tonsillectomy), and swab samples were collected during the operation. Visual analog scales (VAS) were used at 3, 6, and 12 months postoperatively. At the 12-month follow-up examination, swab samples were collected again. PCR amplification was performed of the v3-v4 variable regions of 16S rRNA of the collected specimens, as well as high-throughput sequencing using the Illumina platform. The species information was obtained by OTUs clustering, species annotation, and α-diversity analysis. Results: Twenty-two male and eight female pediatric patients were included in the investigation The most abundant genus level bacterial representatives on the nasal surface before adenoidectomy were Moraxella catarrh, Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus, whereas on the surface of adenoids, they were Streptococcus pneumonia, Haemophilus influenza, Nucleobacter, and Moraxella catarrhalis. One year postoperatively, the bacteria with the highest abundance on the nasal surface at the genus level were Moraxella catarrhalis, Streptococcus pneumonia, Staphylococcus aureus, and non-culturable Dolosigranulum. One year postoperatively, the bacterial richness in the nasal cavity was significantly higher than at baseline (P <.05). Furthermore, the subjective nasal score of all children significantly decreased at 3, 6, and 12 months postoperatively (P <.01). Conclusion: The preoperative bacterial abundance of the nasal cavity and the adenoid surfaces was similar, showing a clear correlation. No single specific bacterium was established to be a dominant species associated with the development of CRS in children. The post-adenoidectomy bacterial richness in the nasal cavity was significantly increased, which may be closely related to the relief of postoperative sinusitis symptoms. [ABSTRACT FROM AUTHOR]

Background: Rifampin is a potent chemoprophylactic antibiotic for Haemophilus influenzae infection, and the resistance rate in H. influenzae is low. In this study, we assessed rifampin resistance-related genetic variations in H. influenzae. Methods: Rifampin susceptibility testing and whole-genome sequencing were performed in 51 H. influenzae isolates. Variations associated with rifampin resistance were identified using Fisher's exact tests. Functional assays were performed to evaluate the effect of RpoB substitutions on rifampin susceptibility. Results: Using the genome of the Rd KW20 H. influenzae strain as the reference, we detected 40 genetic variations in rpoB, which resulted in 39 deduced amino acid substitutions among the isolates. Isolate A0586 was resistant to rifampin, with a minimum inhibitory concentration (MIC) = 8 μg/mL. Phylogenetic analyses revealed that the RpoB sequence of isolate A0586 was distinct from other isolates. Five substitutions, including H526N located in cluster I and L623F, R628C, L645F, and L672F in the region between clusters II and III, were unique to isolate A0586. In two rifampin-susceptible H. influenzae isolates, RpoB-H526N alone and in combination with RpoB-L672F increased the MICs of rifampin to 4 and 8 μg/mL, respectively. RpoB-L672F did not affect cell growth and transcription in H. influenzae isolates. No amino acid substitutions in the AcrAB-TolC efflux pump or outer membrane proteins were found to be associated with rifampin resistance in H. influenzae. Conclusions: Our findings indicate that L672F substitution in the region between RpoB clusters II and III has an aggravating effect on rifampin resistance in H. influenzae. [ABSTRACT FROM AUTHOR]

This document contains summaries of various articles related to asthma research. The first article discusses the bacterial species found in the sputum of patients with asthma, highlighting the presence of Haemophilus influenzae and Moraxella catarrhalis in severe asthma cases. The second article focuses on the long-term efficacy of dupilumab, a medication used to treat type 2 asthma. The third article categorizes Japanese patients with allergic bronchopulmonary aspergillosis (ABPA) into different groups based on their predisposing conditions. The fourth article explores the use of extracellular vesicle miRNA signatures to gain insights into the molecular mechanisms of obesity-associated low type-2 asthma. The fifth article investigates the frequency of circulating mast cell progenitors in birch-pollen sensitized asthma patients. The sixth article aims to create childhood risk scores for predicting adult asthma. The seventh article examines the role of the allopurinol metabolite, oxypurinol, in driving oligoclonal expansions of drug-reactive T cells. These summaries provide a brief overview of the topics covered in each article and can be useful for library patrons conducting research on asthma-related subjects. [Extracted from the article]

Background: Because of altered airway microbiome in asthma, we analysed the bacterial species in sputum of patients with severe asthma. Methods: Whole genome sequencing was performed on induced sputum from non‐smoking (SAn) and current or ex‐smoker (SAs/ex) severe asthma patients, mild/moderate asthma (MMA) and healthy controls (HC). Data were analysed by asthma severity, inflammatory status and transcriptome‐associated clusters (TACs). Results: α‐diversity at the species level was lower in SAn and SAs/ex, with an increase in Haemophilus influenzae and Moraxella catarrhalis, and Haemophilus influenzae and Tropheryma whipplei, respectively, compared to HC. In neutrophilic asthma, there was greater abundance of Haemophilus influenzae and Moraxella catarrhalis and in eosinophilic asthma, Tropheryma whipplei was increased. There was a reduction in α‐diversity in TAC1 and TAC2 that expressed high levels of Haemophilus influenzae and Tropheryma whipplei, and Haemophilus influenzae and Moraxella catarrhalis, respectively, compared to HC. Sputum neutrophils correlated positively with Moraxella catarrhalis and negatively with Prevotella, Neisseria and Veillonella species and Haemophilus parainfluenzae. Sputum eosinophils correlated positively with Tropheryma whipplei which correlated with pack‐years of smoking. α‐ and β‐diversities were stable at one year. Conclusions: Haemophilus influenzae and Moraxella catarrhalis were more abundant in severe neutrophilic asthma and TAC2 linked to inflammasome and neutrophil activation, while Haemophilus influenzae and Tropheryma whipplei were highest in SAs/ex and in TAC1 associated with highest expression of IL‐13 type 2 and ILC2 signatures with the abundance of Tropheryma whipplei correlating positively with sputum eosinophils. Whether these bacterial species drive the inflammatory response in asthma needs evaluation. [ABSTRACT FROM AUTHOR]

Enolase proteins play a significant role as moonlighting proteins. In their role as surface-associated enolase, they have multiple functions as they interact with extracellular matrix proteins. Type I and III collagens are the major constituents of this extracellular matrix, and collagen is one of the targets of interaction with the enolase of many pathogens, thereby helping the colonization process and promoting the subsequent invasion of the host. This work aimed to determine the participation of non-typeable H. influenzae enolase as a collagen-binding protein. In this study, through the use of in vitro tests it was demonstrated that recombinant enolase of non-typeable H. influenzae (rNTHiENO) strongly binds to type I collagen. Using molecular docking, the residues that could take part in the interaction of non-typeable H. influenzae enolase-type I collagen (NTHiENO-Cln I) and non-typeable H. influenzae enolase-type III collagen (NTHiENO-Cln III) were identified. However, in vitro assays show that NTHiENO has a better affinity to interact with Cln I, concerning type Cln III. The interaction of NTHiENO with collagen could play a significant role in the colonization process; this would allow H. influenzae to increase its virulence factors and strengthen its pathogenesis. [ABSTRACT FROM AUTHOR]

Acyl-CoA-thioesterases, which hydrolyze acyl-CoA-esters and thereby release the respective acid, have essential functions in cellular metabolism and have also been used to produce valuable compounds in biotechnological processes. Thioesterase YciA originating from Haemophilus influenzae has been previously used to produce specific dicarboxylic acids from CoA-bound intermediates of the ethylmalonyl CoA pathway (EMCP) in Methylorubrum extorquens. In order to identify variants of the YciA enzyme with the capability to hydrolyze so far inaccessible CoA-esters of the EMCP or with improved productivity, we engineered the substrate-binding region of the enzyme. Screening a small semi-rational mutant library directly in M.extorquens yielded the F35L variant which showed a drastic product level increase for mesaconic acid (6.4-fold) and 2-methylsuccinic acid (4.4-fold) compared to the unaltered YciA enzyme. Unexpectedly, in vitro enzyme assays using respective M.extorquens cell extracts or recombinantly produced thioesterases could not deliver congruent data, as the F35L variant showed strongly reduced activity in these experiments. However, applied in an Escherichia coli production strain, the protein variant again outperformed the wild-type enzyme by allowing threefold increased 3-hydroxybutyric acid product titers. Saturation mutagenesis of the codon for position 35 led to the identification of another highly efficient YciA variant and enabled structure-function interpretations. Our work describes an important module for dicarboxylic acid production with M. extorquens and can guide future thioesterase improvement approaches. Key points: • Substitutions at position F35 of YciAHI changed the productivity of YciA-based release of carboxylic acid products in M. extorquens AM1 and E. coli. • YciAHI F35N and F35L are improved variants for dicarboxylic production of 2-methylsuccinic acid and mesaconic acid with M. extorquens AM1. • In vitro enzyme assays did not reveal superior properties of the optimized protein variants. [ABSTRACT FROM AUTHOR]

Introduction: Immunization plays a pivotal role in public health. It is one of the most cost-effective inventions that have helped bring down a significant amount of burden of diseases among under-five children, some of which are now on the verge of extinction. Objective: To assess the diverse benefits of routine childhood immunization. Methodology: A literature review was conducted using electronic database to understand the broader benefits of immunization. Results: Studies have shown that routine childhood immunization have been able to reduce the incidence of influenza and other targeted diseases (diphtheria, Haemophilus influenzae type b, measles, mumps, polio, and rubella) by 17% and 100% respectively. Conclusion: Vaccines are known to have protective and positive health benefit which extends beyond infancy and childhood. It is therefore one of the best strategies in public health to reduce morbidity and mortality and enable child survival. [ABSTRACT FROM AUTHOR]

In patients early post–autologous stem cell transplant, seroprotection rates were high for Hemophilus influenzae type B and tetanus toxoid (70%–90%) but lower for Streptococcus pneumoniae (30%–50%) including after revaccination. There were high rates of seropositivity (67%–86%) to measles, mumps, and rubella and varicella zoster virus. Durability of protection requires assessment. [ABSTRACT FROM AUTHOR]

Background Rapidly instituted antimicrobial therapy is important in severe infections, and reduced time to the antimicrobial susceptibility testing (AST) report is thus of importance. Disc diffusion (DD) is a cheap, rapidly adaptable, flexible and comprehensive method for phenotypic AST. Previous studies have shown that early reading of inhibition zones for non-fastidious species is possible. Objectives To evaluate zone reading after short incubation of DD in Haemophilus influenzae (n  = 73) and Streptococcus pneumoniae (n  = 112). Methods The readability was evaluated and susceptibility interpretation (SIR) was performed, using the EUCAST 18 ± 2 h incubation breakpoint table (version 12.0), after 6 and 8 h of incubation. Categorical agreement (CA) and error rates were calculated using standard DD and broth microdilution as reference. Results The proportion of readable zones in H. influenzae was 19% (6 h) and 89% (8 h). The CA was 98% after 8 h. The corresponding readability in S. pneumoniae was 63%/98% and CA was 95%/97% after 6 and 8 h, respectively. Early reading of the screening discs (benzylpenicillin 1 unit in H. influenzae and oxacillin 1 µg in S. pneumoniae) correctly identified 18/22 of the H. influenzae isolates and all the readable S. pneumoniae isolates with reduced β-lactam susceptibility. For non-β-lactam agents, very major errors were most common for quinolones in S. pneumoniae. Introduction of areas of technical uncertainty (ATUs) reduced the error rate to ≤1.1%. Conclusions We conclude that shortened incubation is feasible for H. influenzae and S. pneumoniae. To reduce the risk of false categorization a buffer zone (i.e. ATU) near the breakpoints must be used. [ABSTRACT FROM AUTHOR]

Invasive Haemophilus influenzae serotype a (Hia) disease is rare, with most cases reported among Indigenous populations in North America. In England, national surveillance was enhanced following an increase in laboratory-confirmed invasive Hia disease since the 2016–17 epidemiological year. This study aimed to describe the epidemiological trends, clinical characteristics of cases, and assess potential genomic drivers. Hospital laboratories in England routinely submit invasive H influenzae isolates to the UK Health Security Agency for confirmation and serotyping. In this prospective national surveillance study we contacted the general practitioners and clinicians of all patients with laboratory-confirmed invasive Hia from the 2008–09 to the 2021–22 epidemiological year to complete a clinical questionnaire on demographics, underlying conditions, clinical presentation, complications, outcomes, and travel history of the patient. All Hia invasive isolates from residents in England were included in the study; non-invasive isolates were excluded. Multilocus sequence typing (MLST), whole genome single-nucleotide polymorphism, and k-mer-based analysis of bacterial isolates were performed following Illumina whole-genome sequencing (WGS). Outcomes included epidemiological trends, clinical characteristics of confirmed Hia cases, and genomic analyses. From the 2008–09 to the 2021–22 epidemiological years, there were 52 cases of invasive infection with H influenzae serotype a in England (25 [48%] in female patients and 27 [52%] in male patients). There were zero to two annual Hia cases (accounting for <0·5% of serotyped H influenzae isolates) until 2015–16, after which cases increased across England to 19 cases in 2021–22 (incidence 0·03 cases per 100 000), when Hia accounted for 19 (4%) of 484 serotyped H influenzae isolates, 19 (19%) of 100 capsulated cases, and 37% (19 of 52) of all H influenzae cases between 2008–09 and 2021–22. Most of the recent increase in cases occurred among individuals aged 65 years and older (17 [33%] of 52), who typically presented with bacteraemic pneumonia (13 [76%] of 17), and infants younger than 1 year, who had the highest incidence and were more likely to present with meningitis (five [50%] of ten). Overall case fatality rate was 7·7% (95% CI 2·1–19·7; four of 52 patients). WGS found that closely related MLST sequence types ST1511 (20 [39%] of 51), ST23 (13 [25%] of 51), and ST56 (seven [14%] of 51) accounted for most cases, with no evidence of serotype b strains switching capsule to Hia. Duplication of the capsule operon, associated with more severe disease, was present in 32 (80%) of 40 of these sequence types. Analysis of the core and accessory genome content grouped most isolates into a single strain. The persistent increase in invasive Hia cases across England and across all age groups suggests widespread transmission, consistent with reports from other European countries, and will require close monitoring. UK Health Security Agency. [ABSTRACT FROM AUTHOR]

This paper focuses on the development of a novel electrode based on boron-doped diamond nanosheet full-volume-enriched screen-printed carbon electrodes (BDDPE) for use as an impedimetric biosensor. Impedimetric biosensors offer high sensitivity and selectivity for virus detection, but their use as point-of-care devices is limited by the complexity of nanomaterials' architecture and the receptor immobilisation procedures. The study presents a two-step modification process involving the electroreduction of diazonium salt at the BDDPE and the immobilisation of antibodies using zero-length cross-linkers for a selective impedimetric biosensor of Haemophilus influenzae (Hi). The incorporation of diamond nanosheets into BDDPE leads to enhanced charge transfer and electrochemical behaviour, demonstrating greatly improved electrochemically active surface area compared with unmodified screen-printed electrodes (by 44% and 10% on average for [Ru(NH3)6]Cl2 and K3[Fe(CN)6], respectively). The presented sensing system shows high specificity towards protein D in Hi bacteria, as confirmed by negative controls against potential interference from other pathogens, with an estimated tolerance limit for interference under 12%. The Hi limit of detection by electrochemical impedance spectroscopy was 1 CFU/mL (measured at − 0.13 V vs BDDPE pseudo-reference), which was achieved in under 10 min, including 5 min sample incubation in the presence of the analyte. [ABSTRACT FROM AUTHOR]

Objective: Otitis media (OM) is among the most frequently diagnosed pediatric diseases in the US. Despite the significant public health burden of OM and the contribution research in culture models has made to understanding its pathobiology, a singular immortalized human middle ear epithelial (MEE) cell line exists (HMEEC‐1, adult‐derived). We previously developed MEE cultures from pediatric patients with non‐inflamed MEE (PCI), recurrent OM (ROM), or OM with effusion (OME) and demonstrated differences in their baseline inflammatory cytokine expression and response to stimulation with an OM‐relevant pathogen lysate and cytokines. Herein, we sought to immortalize these cultures and assess retention of their phenotypes. Methods: MEE cultures were immortalized via lentivirus encoding temperature‐sensitive SV40 T antigen. Immortalized MEE lines and HMEEC‐1 grown in monolayer were stimulated with non‐typeable Haemophilus influenzae (NTHi) lysate. Gene expression (TNFA, IL1B, IL6, IL8, MUC5AC, and MUC5B) was assessed by qPCR. Results: Similar to parental cultures, baseline cytokine expressions were higher in pediatric OM lines than in HMEEC‐1 and PCI, and HMEEC‐1 cells were less responsive to stimulation than pediatric lines. Conclusion: Immortalized MEE lines retained the inflammatory expression and responsiveness of their tissues of origin and differences between non‐OM versus OM and pediatric versus adult cultures, supporting their value as novel in vitro culture models for OM. [ABSTRACT FROM AUTHOR]

Background: Diagnosis of bacterial meningitis remains a challenge in most developing countries due to low yield from bacterial culture, widespread use of non-prescription antibiotics, and weak microbiology laboratories. The objective of this study was to compare the yield from standard bacterial culture with the multiplex nested PCR platform, the BioFire® FilmArray® Meningitis/Encephalitis Panel (BioFire ME Panel), for cases with suspected acute bacterial meningitis. Methods: Following Gram stain and bacterial culture on cerebrospinal fluid (CSF) collected from children aged less than 5 years with a clinical suspicion of acute bacterial meningitis (ABM) as defined by the WHO guidelines, residual CSF specimens were frozen and later tested by BioFire ME Panel. Results: A total of 400 samples were analyzed. Thirty-two [32/400 (8%)] of the specimens were culture positive, consisting of; three Salmonella spp. (2 Typhi and 1 non-typhi), three alpha hemolytic Streptococcus, one Staphylococcus aureus, six Neisseria meningitidis, seven Hemophilus influenzae, 11 Streptococcus pneumoniae and 368 were culture negative. Of the 368 culture-negative specimens, the BioFire ME Panel detected at least one bacterial pathogen in 90 (24.5%) samples, consisting of S. pneumoniae, N. meningitidis and H. influenzae, predominantly. All culture positive specimens for H. influenzae, N. meningitidis and S. pneumoniae also tested positive with the BioFire ME Panel. In addition, 12 specimens had mixed bacterial pathogens identified. For the first time in this setting, we have data on the viral agents associated with meningitis. Single viral agents were detected in 11 (2.8%) samples while co-detections with bacterial agents or other viruses occurred in 23 (5.8%) of the samples. Conclusions: The BioFire® ME Panel was more sensitive and rapid than culture for detecting bacterial pathogens in CSF. The BioFire® ME Panel also provided for the first time, the diagnosis of viral etiologic agents that are associated with meningoencephalitis in this setting. Institution of PCR diagnostics is recommended as a routine test for suspected cases of ABM to enhance early diagnosis and optimal treatment. [ABSTRACT FROM AUTHOR]

Nearly 45% of under 5 mortality is directly or indirectly linked to malnutrition. Infection adds to the increased mortality and morbidity in these groups. Vaccination is very important in these undernourished children protecting against life-threatening infections. The goal of vaccination is to produce long-term protection by generating memory cells and the generation of antibodies. Since malnutrition is a state of immunodeficiency, the immune response to vaccines in these children is a matter of concern. We did an exhaustive search to gather more recent studies and corroborated previous findings. Oral Polio Vaccine (OPV), Pneumococcal Polysaccharide Vaccine, Haemophilus influenza vaccine, rabies, and cholera vaccine showed normal response to immunization. Measles and rotavirus vaccines were found to elicit lower seroprotection and lower efficacy in undernourished children. Data regarding response to vaccination against BCG, DPwT, Hepatitis B, pneumococcal conjugate vaccine, and meningococcal vaccine was inconclusive. Although most of the studies show a normal immune response to different vaccines, excluding other confounding factors and effect modifiers had not been easy to interpret. However, with the advances in the understanding of vaccine physiology with newer immunological techniques, good-quality studies might explore the gray areas that remain untouched. [ABSTRACT FROM AUTHOR]

• 65.5% of 2-year-old pwCF had ≥ one lung infection, and 27.9% chronically colonized. • 57.9% of 10-year-olds were infected by three distinct pathogens. • 10.6% of 10-year-olds were chronically colonised by more than three pathogens. • Risk of P. aeruginosa infection increases in pwCF with prior CF infection. • Risk of P. aeruginosa infection increases with increased CF pathogen infections. Pseudomonas aeruginosa (Pa) infection is detrimental to people with cystic fibrosis (pwCF). Several clinical and genetic factors predispose to early Pa infections. However, the role of earlier infections with other pathogens on the risk of Pa infection in paediatric pwCF remains unknown. Using Kaplan–Meier method, we computed the cumulative incidences of bacterial and fungal initial acquisition (IA) and chronic colonisation (CC) in 1,231 French pwCF under 18 years of age for methicillin-susceptible and resistant Staphylococcus aureus (MSSA and MRSA), Stenotrophomonas maltophilia, Haemophilus influenzae, Achromobacter xylosoxidans, and Aspergillus species. Previous infections were analysed as Pa- IA and Pa- CC risk factors using Cox regression models. By 2 years of age, 65.5% pwCF had experienced at least one bacterial or fungal IA, and 27.9% had experienced at least one CC. The median age of Pa- IA was 5.1 years, and Pa- CC was present in 25% pwCF by 14.7 years. While 50% acquired MSSA at 2.1 years, 50% progressed to chronic MSSA colonisation at 8.4 years. At 7.9 and 9.7 years, 25% pwCF were infected by S. maltophilia and Aspergillus spp., respectively. The risk of Pa- IA and Pa- CC increased with IAs of all other species, with hazard ratios (HR) up to 2.19 (95% Confidence interval (CI) 1.18–4.07). The risk of Pa- IA increased with the number of previous bacterial/fungal IAs (HR=1.89, 95% CI 1.57–2.28), with a 16% increase per additional pathogen; same trend was noted for Pa- CC. This study establishes that the microbial community in CF airways can modulate Pa occurrence. At the dawn of targeted therapies, it paves the way for characterizing future trends and evolution of infections. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is a chronic metabolic disease that is considered a major worldwide healthcare problem. Multiple studies have revealed that people with DM are more likely to acquire oral problems, such as periodontal diseases, because the oral microbiota plays a major role in oral health and may affect the saliva composition. This study aimed to characterize the oral microbiota of a sample of DM patients and its association with some demographic factors, such as smoking habits and gender. A total of 91 specimens, including 51 DM patients and 40 apparently healthy individuals, were enrolled in this study, which was carried out from November 2021 to February 2022. Whole saliva was collected in a sterile tube, and oral swabs were obtained from both patients and the control groups. The results of the present study show there was no significant difference between both genders in DM hits. As well, a smoking habit is considered a predisposing habit that may increase the risk of oral diseases in DM patients. The acidic pH of saliva recorded higher values between patients and control subjects than other pH items. On the other hand, the most prevalent bacterial isolates found in oral DM patients were Staphylococcus spp. (37.12%), E.coli (12.9%), Klebsiella spp. (10.60%), Pseudomonas spp. (9.84%), Enterobacter (8.33%), both Streptococcus spp. and Acinetobacter spp. (5.30%), Corynebacterium spp. and Proteus spp. (3.8%), Neisseria spp. and Haemophilus Influenza was 1.51%. These percentages were significantly different from those in the control group, which were Staphylococcus spp. (43.4%), Klebsiella spp. (25.0%), Enterobacter (7.89%), E.coli (6.58%), Bacillus spp. (5.2%), Acinetobacter spp. (3.9%), Pseudomonas spp., Streptococcus spp., and Proteus spp. (2.7%). [ABSTRACT FROM AUTHOR]

Pasteurella multocida , an encapsulated gram-negative bacterium, is a significant veterinary pathogen. The P. multocida is classified into 5 serogroups (A, B, D, E, and F) based on the bacterial capsular polysaccharide (CPS), which is important for virulence. Serogroups B and E are the primary causative agents of bovine hemorrhagic septicemia that is associated with significant yearly losses of livestock worldwide, primarily in low- and middle-income countries. The P. multocida disease is currently managed by whole-cell vaccination, albeit with limited efficacy. CPS is an attractive antigen target for an improved vaccine: CPS-based vaccines have proven highly effective against human bacterial diseases and could provide longer-term protection against P. multocida. The recently elucidated CPS repeat units of serogroups B and E both comprise a N-acetyl-β-D-mannosaminuronic acid/N-acetyl-β-D-glucosamine disaccharide backbone with β-D-fructofuranose (Fru f) side chain, but differ in their glycosidic linkages, and a glycine (Gly) side chain in serogroup B. Interestingly, the Haemophilus influenzae types e and d CPS have the same backbone residues. Here, comparative modeling of P. multocida serogroups B and E and H. influenzae types e and d CPS identifies a significant impact of small structural differences on both the chain conformation and the exposed potential antibody-binding epitopes (Ep). Further, Fru f and/or Gly side chains shield the immunogenic amino-sugar CPS backbone—a possible common strategy for immune evasion in both P. multocida and H. influenzae. As the lack of common epitopes suggests limited potential for cross-reactivity, a bivalent CPS-based vaccine may be necessary to provide adequate protection against P. multocida types B and E. [ABSTRACT FROM AUTHOR]

The SARS-CoV-2 pandemic has affected social patterns and consequently the prevalence of infections, such as seasonal influenza. It has been reported that invasive pneumococcal infection has markedly decreased worldwide. Method: We retrospectively investigated the bacteria cultured and isolated from 23,052 respiratory sputum samples obtained at our hospital from April 2015 to March 2022. The average patient age was 71.8 years old, with a standard deviation of 16.0 years old. There was no significant difference in the age of the patients or the female-to-male ratio between each year. The detection ratio of bacteria was analyzed in accordance with sputum quality based on the Geckler classification. Results: The detection ratio of community-acquired pneumonia pathogens such as Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae increased in parallel with the quality of the sputum, while that of hospital-acquired pneumonia pathogens such as Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus was not significantly affected by the quality of the sputum. The detection ratio of former pathogens in the good-quality respiratory sputum had decreased significantly since April 2020 by 60–80%, while that of P. aeruginosa and S. aureus had increased by 40–50%. Conclusions: The SARS-CoV-2 pandemic reduced the detection ratio of H. influenzae, M. catarrhalis, and S. pneumoniae but increased that of P. aeruginosa and S. aureus in the good-quality respiratory sputum from elderly patients. The influence of this selective change in isolated bacteria on the health and comorbidity of elderly patients remains to be investigated. [ABSTRACT FROM AUTHOR]

Introduction: Microbial infections are a major cause of morbidity and mortality among people living with HIV (PLWH). Respiratory tract infections (RTIs) are responsible for approximately 70% of illnesses among PLWH. Drug resistant bacteria are highly prevalent among PLWH and this is a public health concern. Methods: This is a retrospective analysis of data collected during the COSTOP trial between 2011 and 2013. Sputum collected on spot from participants presenting with a productive cough was examined using Gram, Ziehl-Neelsen stains and cultured on suitable bacteriological media. Antimicrobial sensitivity testing was done on isolated pathogens, by disc diffusion technique. Results: We included 687 participants with mean age 41.3 (SD 8.2) years of whom 76.4% were female. Two hundred one sputum samples grew bacteria; Moraxella species (27.4%), Streptococcus pneumoniae(25.4%), Haemophilus influenza(22.4%), Mycobacterium species(4.5%), Pseudomonas species(4.0%), Staphylococcus aureus(4.0%), Escherichia coli (1.0%), Klebsiella species (1.0%), other bacteria (10.4%). A higher monthly income greater than or equal to 30$ (aOR = 0.63, 95%CI: 0.40–0.99) and longer duration since HIV diagnosis (aOR = 1.06, 95%CI: 1.0–1.11) were found to be independently associated with a positive bacterial culture. Moraxella sp, H. influenza and Pseudomonas had zero sensitivity towards cotrimoxazole. Sensitivity to erythromycin was low among Moraxella sp (28.6%), H. influenza (31.6%) and S. aureus(42.9%) and other bacteria (42.9%). Most isolates were sensitive to Amoxicillin + Clavulanic acid and ceftriaxone. Conclusion: There is a very low sensitivity of isolated bacteria to commonly prescribed antibiotics that are more available through the national supply chain, which is of public health concern. Urgent steps to tackle the high antimicrobial resistance among PLWH is required. [ABSTRACT FROM AUTHOR]

Background: Pentavalent vaccines (DTP-HepB-Hib) have been introduced in many countries in their routine public immunization programmes to protect against diphtheria (D), tetanus (T), pertussis (P), hepatitis B (Hep B) and Hemophilus influenzae type b (Hib) diseases. This study compared the safety and immunogenicity of a new formulation of a whole-cell Bordetella pertussis (wP) based pentavalent vaccine (DTwP-HepB-Hib). The new formulation was developed using well-characterized hepatitis B and pertussis whole cell vaccine components. Methods: This was a phase III, observer-blind, randomized, non-inferiority, multi-center study conducted in India among 460 infants who were followed up for safety and immunogenicity for 28 days after administration of three doses of either investigational or licensed comparator formulations at 6–8, 10–12 and 14–16 weeks of age. Results: The investigational formulation of DTwP-HepB-Hib vaccine was non-inferior to the licensed formulation in terms of hepatitis B seroprotection rate (% of subjects with HepB antibodies ≥10mIU/mL were 99.1% versus 99.0%, respectively, corresponding to a difference of 0.1% (95% CI, -2.47 to 2.68)) and pertussis immune responses (adjusted geometric mean concentrations of antibodies for anti-PT were 76.7 EU/mL versus 63.3 EU/mL, with a ratio of aGMTs of 1.21 (95% CI, 0.89–1.64), and for anti-FIM were 1079 EU/mL versus 1129 EU/mL, with a ratio of aGMTs of 0.95 (95% CI, 0.73–1.24), respectively). The immune responses to other valences (D, T, and Hib) in the two formulations were also similar. The safety profile of both formulations was found to be similar and were well tolerated. Conclusions: The investigational DTwP-HepB-Hib vaccine formulation was immunogenic and well-tolerated when administered as three dose primary series in infants. Clinical trial registration: Clinical Trials Registry India number: CTRI/2018/12/016692. [ABSTRACT FROM AUTHOR]

Bacterial biofilms contribute significantly to pathogenesis, recurrence and/or chronicity of the majority of bacterial diseases due to their notable recalcitrance to clearance. Herein, we examined kinetics of the enhanced sensitivity of nontypeable Haemophilus influenzae (NTHI) newly released (NRel) from biofilm residence by a monoclonal antibody against a bacterial DNABII protein (α-DNABII) to preferential killing by a β-lactam antibiotic. This phenotype was detected within 5 min and lasted for ~ 6 h. Relative expression of genes selected due to their known involvement in sensitivity to a β-lactam showed transient up-regulated expression of penicillin binding proteins by α-DNABII NTHI NRel, whereas there was limited expression of the β-lactamase precursor. Transient down-regulated expression of mediators of oxidative stress supported similarly timed vulnerability to NADPH-oxidase sensitive intracellular killing by activated human PMNs. Further, transient up-regulated expression of the major NTHI porin aligned well with observed increased membrane permeability of α-DNABII NTHI NRel, a characteristic also shown by NRel of three additional pathogens. These data provide mechanistic insights as to the transient, yet highly vulnerable, α-DNABII NRel phenotype. This heightened understanding supports continued validation of this novel therapeutic approach designed to leverage knowledge of the α-DNABII NRel phenotype for more effective eradication of recalcitrant biofilm-related diseases. [ABSTRACT FROM AUTHOR]

Synthesis of spacer-armed pseudodi-, pseudotetra-, and pseudohexasaccharides related to the capsular phosphoglycan of Haemophilus influenzae type a, the second most virulent serotype of H. influenzae (after type b), was performed for the first time via iterative chain elongation using H-phosphonate chemistry for the formation of inter-unit phosphodiester bridges. These compounds were prepared for the design of neoglycoconjugates, as exemplified by the transformation of the obtained pseudohexasaccharide derivative into a biotinylated glycoconjugate suitable for use in immunological studies, particularly in diagnostic screening systems as a coating antigen for streptavidin-coated plates and chip slides. [ABSTRACT FROM AUTHOR]

Haemophilus influenzae serotype b has been the main cause of invasive infections in children, during the prevaccination period. More than 20 years after the introduction of the conjugate vaccine against Hib, HiNT has emerged as the cause of localized infections in children and adults. The main objective of this work is to evaluate the susceptibility and resistance mechanisms of H. influenzae strains from carriers and describe the molecular epidemiology and their clonal relationships by multilocus sequence typing (MLST). Sixty-nine strains from clinical cases and asymptomatic carriers from 2009 to 2019 were analyzed, confirmed as H. influenzae, and serotyped by polymerase chain reaction. The susceptibility to antibiotics was evaluated by E-test strips. Genotyping was performed by MLST. HiNT was the most frequent in all age groups. Resistance to ampicillin, sulfamethoxazole+trimethoprim, and amoxicillin+clavulanic acid was detected, with the production of β-lactamase being the main resistance mechanism. Among 21 HiNT strains with complete allelic MLST profiles, 19 new sequence types were described, reinforcing the already reported heterogeneity of nontypeable strains, and only one clonal complex (cc-1355) was observed. Our results show a high percentage of colonization regardless of age, increased antimicrobial resistance, and high genetic diversity, along with an increased number of cases caused by HiNT strains. These findings reinforce the need for continuous surveillance for HiNT strains as it has been reported worldwide after the introduction of the Hib conjugate vaccine. [ABSTRACT FROM AUTHOR]

Bacterial lipoproteins are structurally divided into two groups, based on their lipid moieties: diacylated (present in Gram-positive bacteria) and triacylated (present in some Grampositive and most Gram-negative bacteria). Diacylated and triacylated lipid moieties differ by a single amide-linked fatty acid chain. Lipoproteins induce host innate immune responses by the mammalian Toll-like receptor 2 (TLR2). In this study, we added a lipid moiety to recombinant OMP26, a native nonlipidated (NL) membrane protein of Haemophilus influenzae, and characterized it extensively under different expression conditions using flow cytometry, LC/MS, and MALDITOF. We also investigated the ability of NL and lipidated (L) OMP26 to induce in vitro stimulation of HEK Blue-hTLR2- TR1 and hTLR-TLR6 cells. Our L-OMP26 was predominantly expressed in diacylated form, so we employed an additional gene copy of apolipoprotein N-acetyltransferase enzyme (Lnt)-rich Escherichia coli strain that further acylates the diacyl lipoproteins to enhance the production of triacylated L-OMP26. The diacyl and triacyl versions of L-OMP26, intended as a vaccine for use in humans, were characterized and evaluated as protein vaccine components in a mouse model. We found that the diacyl and triacyl L-OMP26 protein formulations differed markedly in their immune-stimulatory activity, with diacylated L-OMP26 stimulating higher adaptive immune responses compared with triacylated L-OMP26 and both stimulating higher adaptive immune response compared to NL-OMP26. We also constructed and characterized an L-OMP26ΦNL-P6 fusion protein, where NL-P6 protein (a commonly studied H. influenzae vaccine candidate) was recombinantly fused to L-OMP26. We observed a similar pattern of lipidation (predominantly diacylated) in the L-OMP26ΦNL-P6 fusion protein. [ABSTRACT FROM AUTHOR]

Non-cystic fibrosis bronchiectasis (NCFB) is a chronic respiratory disease resulting in chronic cough, thick sputum, and lower airway microbial colonization, akin to patients with cystic fibrosis (CF). NCFB is a common, yet under recognized entity which inflicts significant morbidity and mortality particularly to older individuals, with a rising prevalence in the developed world. Given that sputum cultures are a non-invasive method to characterize the lower airway microbiota in NCFB patients, for which pathogenic organisms are associated with worsened outcomes, we sought to characterize the microbiological pattern and clinical outcomes associated with sputum culture in a cohort of NCFB patients from Western Canada. A total of 20 subjects were prospectively recruited from various bronchiectasis clinics across the Greater Edmonton area. A retrospective chart review and a symptoms questionnaire was performed, gathering information not limited to symptoms, comorbidities, exacerbations, hospitalizations, sputum production, and sputum culture results over the prior 5 years. Subjects reported frequent hospitalization alongside a significant burden of symptoms. A large majority of sputum cultures grew pathogenic organisms such as Haemophilus influenzae and Pseudomonas aeruginosa. We also note the considerable waste and inefficiency associated with sputum cultures, outlining areas for which this important diagnostic modality can be improved. Accurate characterization of the airway microbiota alongside efficient delivery of health services are key to ensuring the proper treatment of individuals with NCFB, given their high disease burden and frequent hospitalization. [ABSTRACT FROM AUTHOR]

Background: Non-typeable Haemophilus influenzae (NTHi) has become the major cause of invasive H. influenzae diseases in the post-H. influenzae type b vaccine era. The emergence of multidrug-resistant (MDR) NTHi is a growing public health problem. Herein, we investigated the molecular basis of MDR in NTHi. The isolated NTHi were subjected to antimicrobial susceptibility testing for 12 agents. Whole genome and plasmid sequencing were conducted and analyzed to identify significant genetic variations and plasmid-encoded genes conferred antibiotic resistance. Results: Thirteen (50%) MDR NTHi isolates were obtained; of these, 92.3% were non-susceptible to ampicillin, 30.8% to amoxicillin-clavulanate, 61.5% to cefuroxime, 61.5% to ciprofloxacin/levofloxacin, 92.3% to trimethoprim-sulfamethoxazole, 30.8% to tetracycline, and 7.7% to azithromycin. Eight ampicillin-resistant isolates were β-lactamase positive; of these, 6 carried blaTEM-1 and 2 carried blaROB-1, whereas 4 were β-lactamase negative. Genetic variations in mrdA, mepA, and pbpG were correlated with amoxicillin-clavulanate non-susceptibility, whereas variations in ftsI and lpoA conferred cefuroxime resistance. Five variations in gyrA, 2 in gyrB, 3 in parC, 1 in parE, and 1 in the parC-parE intergenic region were associated with levofloxacin/ciprofloxacin non-susceptibility. Among these genes, 8 variations were linked to high-level levofloxacin resistance. Six variations in folA were associated with trimethoprim-sulfamethoxazole resistance. Plasmid-bearing tet(B) and mef(A) genes were responsible for tetracycline and azithromycin resistance in 4 and 1 MDR isolates, respectively. Conclusions: This study clarified the molecular epidemiology of MDR in NTHi. This can benefit the monitoring of drug resistance trends in NTHi and the adequate medical management of patients with NTHi infection. [ABSTRACT FROM AUTHOR]