Infection Research Articles

Efficacy of Calcium Sulfate Antibiotic Carriers in the Treatment of Severe Infections of the Temporal Bone

Objective: To study the additional use of topical antibiotic-loaded calcium sulfate pellets in difficult-to-treat cases of temporal bone infections. Patients: Four patients with advanced and pretreated temporal bone disease. Intervention: Application of topical antibiotic-loaded calcium sulfate pellets following surgical debridement in infections of the temporal bone. Main Outcome Measures: Reinfection- and revision-free follow-up analysis and assessment of audiometric data. Results: A total of 4 patients were included (3 females and 1 male, mean age of 29.5 years [SD 19.8]). All patients (4/4) had a revision-free follow-up during a mean of 24.5 (SD, 6.19) months. Reinfections (n = 3) were observed in 2 patients (2/4) occurring 1 and 15, as well as 8 months after surgery. Reinfections could be successfully treated using topically and/or orally applied antibiotic therapy. No change in air-conducted pure-tone average was observed after treatment (mean change 1.3 dB; P = 0.99). Conclusion: Local application of antibiotic-loaded calcium sulfate pellets in combination with surgical debridement represents an effective treatment for local infection control in difficult-to-treat cases of temporal bone infections.

Performance and safety of PowerPICC catheters and accessories: a prospective observational study

ObjectiveThis study aimed to evaluate the safety and performance of PowerPICC catheters in a real-world setting.DesignProspective, observational, multicentre study.SettingNine European countries, involving 14 centres.ParticipantsGeneral patient population.InterventionPowerPICC catheter inserted by the...

Trial to compare mixed-use (multi-use and single-use) intermittent catheter management with single-use management over 12 months (The MultICath Trial): protocol for a non-inferiority randomised controlled trial

IntroductionEvaluating the safety and acceptability of reusing catheters for intermittent catheterisation (IC) is one of the top 10 continence research priorities identified by the UK James Lind Alliance Priority Setting...

Protection of Omicron Bivalent Vaccine, Previous Infection, and Their Induced Neutralizing Antibodies Against Symptomatic Infection With Omicron XBB.1.16 and EG.5.1.

Data are limited on the protective role of the Omicron BA bivalent vaccine, previous infection, and their induced neutralizing antibodies against Omicron XBB.1.16 and EG.5.1 infection. We conducted a nested case-control analysis among tertiary hospital staff in Tokyo who had received ≥3 doses of COVID-19 vaccines and donated blood samples in June 2023 (1 month before the Omicron XBB.1.16 and EG.5.1 wave). We identified 206 symptomatic cases between June and September 2023 and selected their controls with 1:1 propensity score matching. We examined the association of vaccination, previous infection, and preinfection live virus neutralizing antibody titers against Omicron XBB.1.16 and EG.5.1 with the risk of COVID-19 infection. Previous infection during the Omicron BA- or XBB-dominant phase was associated with a significantly lower infection risk during the XBB.1.16 and EG.5.1-dominant phase than infection-naive status, with 70% and 100% protection, respectively, whereas Omicron BA bivalent vaccination showed no association. Preinfection neutralizing titers against XBB.1.16 and EG.5.1 were 39% (95% CI, 8%-60%) and 28% (95% CI, 8%-44%) lower in cases than matched controls. Neutralizing activity against XBB.1.16 and EG.5.1 was somewhat detectable in the sera of individuals with previous infection but barely detectable in those who were infection naive and received the Omicron bivalent vaccine. In the era when the Omicron XBB vaccine was unavailable, the Omicron BA bivalent vaccine did not confer the neutralizing activity and protection against Omicron XBB.1.16 and EG.5.1 symptomatic infection. The previous infection afforded neutralizing titers and protection against symptomatic infection with these variants.

Causal relationships between gut microbiota, plasma metabolites, and HIV infection: insights from Mendelian randomization and mediation analysis

ObjectiveGut dysbiosis and metabolic abnormalities have been implicated in HIV infection. However, the exact causal relationships among the gut microbiota, metabolites, and HIV infection remain poorly understood. Our study involving Mendelian randomization (MR) and mediation analysis aims to unveil these causalities.MethodsGenetic instrumental variables for the gut microbiota were retrieved from MiBioGen consortium (n = 18,340). Metabolism-related genetic variants were sourced from the CLSA cohort (n = 8299). GWAS summary statistics for symptomatic HIV infection were derived from the FinnGen study (n = 309,154), and the UK Biobank (n = 208,808). We performed the bidirectional two-sample MR to assess causalities with the inverse-variance weighted (IVW) method as the primary analysis. Moreover, we executed a mediation analysis using two-step MR methods.ResultsCompared to the causal effects of HIV infection on gut microbiota (or metabolites), those of gut microbiota (or plasma metabolites) on the risk of HIV infection were more substantial. Phylum Proteobacteria (OR: 2.114, 95% CI 1.042–4.288, P = 0.038), and genus Ruminococcaceae UCG013 (OR: 2.127, 95% CI 1.080–4.191, P = 0.029) exhibited an adverse causal effect on HIV infection, whereas genus Clostridium sensu stricto 1(OR: 0.491, 95% CI 0.252–0.956, P = 0.036) and family Erysipelotrichaceae (OR: 0.399, 95% CI 0.193–0.827, P = 0.013) acted as significant protective factors for HIV. The salicyluric glucuronide level (OR = 2.233, 95% CI 1.120–4.453, P = 0.023) exhibited a considerably adverse causal effect on HIV infection. Conversely, the salicylate-to-citrate ratio (OR: 0.417, 95% CI 0.253–0.688, P = 0.001) was identified as a protective factor for HIV. We identified only one bidirectional causality between 1-palmitoyl-GPI and HIV infection. Mechanistically, genus Haemophilus mediated the causal effects of three phospholipids on HIV infection risk: 1-palmitoyl-GPI (mediation proportion = 33.7%, P = 0.018), 1-palmitoyl-2-arachidonoyl-GPI (mediation proportion = 18.3%, P = 0.019), and 1-linoleoyl-2-linolenoyl-GPC (mediation proportion = 20.3%, P = 0.0216). Additionally, 5-Dodecenoylcarnitine (C12:1) mediated the causal effect of genus Sellimonas on the risk of HIV infection (mediation proportion = 13.7%, P = 0.0348).ConclusionOur study revealed that gut microbiota and metabolites causally influence HIV infection risk more substantially than the reverse. We identified the bidirectional causality between 1-palmitoyl-GPI (16:0) and HIV infection, and elucidated four mediation relationships. These findings provide genetic insights into prediction, prevention, and personalized medicine of HIV infection.

Acute Chikungunya Virus Infection Triggers a Diverse Range of T Helper Lymphocyte Profiles.

Chikungunya virus (CHIKV) is an arbovirus causing acute febrile illness with severe joint pain, often leading to chronic arthralgia. This study investigated the adaptive immune responses during the early stages of symptomatic acute CHIKV infection, focusing on the transcription factors and cytokines linked to Th1, Th2, Th17, and Treg cells. Thirty-six individuals were enrolled: nine healthy controls and 27 CHIKV-positive patients confirmed by qRT-PCR. Blood samples were analyzed for the mRNA expression of transcription factors (Tbet, GATA3, FoxP3, STAT3, RORγt) and cytokines (IFN-γ, IL-4, IL-17, IL-22, TGF-β, IL-10). The results showed the significant upregulation of Tbet, GATA3, FoxP3, STAT3, and RORγt in CHIKV-positive patients, with RORγt displaying the highest increase. Correspondingly, cytokines IFN-γ, IL-4, IL-17, and IL-22 were upregulated, while TGF-β was downregulated. Principal component analysis (PCA) confirmed the distinct immune profiles between CHIKV-positive and healthy individuals. A correlation analysis indicated that higher Tbet expression correlated with a lower viral load, whereas FoxP3 and TGF-β were associated with higher viral loads. Our study sheds light on the intricate immune responses during acute CHIKV infection, characterized by a mixed Th1, Th2, Th17, and Treg response profile. These results emphasize the complex interplay between different adaptive immune responses and how they may contribute to the pathogenesis of Chikungunya fever.

Understanding antibody magnitude and durability following vaccination against SARS-CoV-2

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) results in transient antibody response against the spike protein. The individual immune status at the time of vaccination influences the response. Using mathematical models of antibody decay, we determined the dynamics of serum immunoglobulin G (IgG) and serum immunoglobulin A (IgA) over time. Data fitting to longitudinal IgG and IgA titers was used to quantify differences in antibody magnitude and antibody duration among infection-naïve and infection-positive vaccinees. We found that prior infections result in more durable serum IgG and serum IgA responses, with prior symptomatic infections resulting in the most durable serum IgG response and prior asymptomatic infections resulting in the most durable serum IgA response. These findings can guide vaccine boosting schedules.

Elliptical excision and primary closure of nasal defect to achieve best esthetic outcome: A case series of 50 patients.

To evaluate the cosmetic result of nasal of an elliptical excision and primary closure on small nasal defect by using Scar assessment using the Stony Brook Scar Evaluation Scale (SBSES) score. This retrospective interventional study was conducted in a private clinic over a 2-year duration. Patients aged 18-60 years with nasal defects <1.5 cm were enrolled after obtaining informed consent. Exclusion criteria included immunocompromised status, keloidal tendency, local site infection, bleeding disorder, age <18 years, and lack of consent. Scar assessment using the SBSES was performed at the end of 6 months. Statistical analysis included summary statistics, analysis of variance tests, and a significance level of P < 0.05. The study included 50 patients, with 54% males and 46% females. The most common age group was 21-40 years, and melanocytic nevi was the most common cause for excision. Lesions were excised mainly from the lateral wall and dorsum of the nose. The mean SBSES score was 3.79 ± 0.467. The best cosmetic outcome was observed in lesions involving the dorsum followed by the root of the nose. No significant difference was found among the SBSES scores for various subunits. Elliptical excision with primary closure is a simple and effective technique for small nasal defects, providing good cosmetic results. The location of the nasal defect influences the cosmetic outcome, with better results observed in areas with thinner skin and increased skin laxity.

Climate, demography, immunology, and virology combine to drive two decades of dengue virus dynamics in Cambodia

The incidence of dengue virus disease has increased globally across the past half-century, with highest number of cases ever reported in 2019 and again in 2023. We analyzed climatological, epidemiological, and phylogenomic data to investigate drivers of two decades of dengue in Cambodia, an understudied endemic setting. Using epidemiological models fit to a 19-y dataset, we first demonstrate that climate-driven transmission alone is insufficient to explain three epidemics across the time series. We then use wavelet decomposition to highlight enhanced annual and multiannual synchronicity in dengue cycles between provinces in epidemic years, suggesting a role for climate in homogenizing dynamics across space and time. Assuming reported cases correspond to symptomatic secondary infections, we next use an age-structured catalytic model to estimate a declining force of infection for dengue through time, which elevates the mean age of reported cases in Cambodia. Reported cases in >70-y-old individuals in the 2019 epidemic are best explained when also allowing for waning multitypic immunity and repeat symptomatic infections in older patients. We support this work with phylogenetic analysis of 192 dengue virus (DENV) genomes that we sequenced between 2019 and 2022, which document emergence of DENV-2 Cosmopolitan Genotype-II into Cambodia. This lineage demonstrates phylogenetic homogeneity across wide geographic areas, consistent with invasion behavior and in contrast to high phylogenetic diversity exhibited by endemic DENV-1. Finally, we simulate an age-structured, mechanistic model of dengue dynamics to demonstrate how expansion of an antigenically distinct lineage that evades preexisting multitypic immunity effectively reproduces the older-age infections witnessed in our data.

Association of pathogenic determinants of Fusobacterium necrophorum with bacteremia, and Lemierre’s syndrome

Fusobacterium necrophorum is a Gram-negative anaerobic bacterium responsible for localized infections of the oropharynx that can evolve into bacteremia and/or septic thrombophlebitis of the jugular vein or peritonsillar vein, called Lemierre’s syndrome. To identify microbial genetic determinants associated with the severity of this life-threatening disease, 70 F. necrophorum strains were collected and grouped into two categories according to the clinical presentation: (i) localized infection, (ii) bacteremia with/without Lemierre’s syndrome. Comparative genomic analyses revealed two clades with distinct genetic content, one clade being significantly enriched with isolates from subjects with bacteremia. To identify genetic determinants contributing to F. necrophorum pathogenicity, genomic islands and virulence factor orthogroups (OVFs) were predicted. The presence/absence profiles of OVFs did not group isolates according to their clinical category, but rather according to their phylogeny. However, a variant of lktA, a key virulence factor, with a frameshift deletion that results in two open reading frames, was associated with bacteremia. Moreover, a genome-wide association study identified three orthogroups associated with bacteremic strains: (i) cas8a1, (ii) a sodium/solute symporter, and (iii) a POP1 domain-containing protein. Further studies must be performed to assess the functional impact of lktA mutation and of these orthogroups on the physiopathological mechanisms of F. necrophorum infections.

Temporoparietal Fascial Flap Combined With Vascularized Outer Table Calvarial Bone Graft and Entire Temporalis Muscle: A Stable Pedicled Flap for Orbital Floor Reconstruction After Total Maxillectomy.

Orbital reconstruction after total maxillectomy is essential to maintain ocular function and facial contour. Free flap transfer with simultaneous orbital bone reconstruction is a straightforward approach; however, it is challenging in medically unstable patients with multimorbidity. The authors developed an easily harvested temporoparietal fascial flap combined with vascularized outer table calvarial bone and entire temporalis muscle. The authors applied this technique in an 81-year-old patient with multiple comorbidities who required orbital floor reconstruction following total maxillectomy. Intraoperative indocyanine green fluorescence imaging confirmed excellent perfusion of the temporoparietal fascia, entire temporalis muscle, and calvarial bone. Although the patient developed postoperative local wound infection, the vascularized bone graft resisted infection and preserved the orbital structure without bone exposure. Our technique is minimally invasive and results in a well-vascularized flap for orbital reconstruction after total maxillectomy involving the orbital bone, and particularly beneficial in patients with multimorbidity or at high risk of local infection.

ESR Essentials: imaging of middle ear cholesteatoma-practice recommendations by the European Society of Head and Neck Radiology.

Although non-malignant,middle ear cholesteatoma can result in significant complications due to local bone erosion and infection. The treatment of cholesteatoma is surgical, but residual disease is common and may be clinically occult, particularly when the canal wall is preserved or reconstructive techniques are employed. Imaging plays a pivotal role in the management of patients with middle ear cholesteatoma-aiding clinical diagnosis, identifying complications, planning surgery, and detecting residual disease at follow-up. Computed tomography is the primary imaging tool in the preoperative setting since it canprovide botha surgical roadmap and detect erosive complications of cholesteatoma. The ability of magnetic resonance imaging with non-echoplanar diffusion-weighted sequences to accurately detect residual disease has led to a shift in the diagnostic paradigm for post-surgical follow-up of cholesteatoma, such that routine "second-look" surgery is no longer required. The following practice recommendations are aimed athelping the radiologist choose appropriate imaging approaches and understand the key diagnostic considerations for the evaluation of pre- and post-surgical middle ear cholesteatoma. KEY POINTS: In the preoperative setting, CT is the first-line imaging modality and MRI is reserved for rare clinical scenarios (low evidence). Non-echoplanar imaging (EPI) DWI is the optimal MRI sequence for the detection of residual cholesteatoma (moderate evidence). Non-EPI DWI plays an important role in the postoperative surveillance of cholesteatoma (moderate evidence).

Pfizer-BioNTech (BNT162b2) Vaccine Effectiveness against Symptomatic Laboratory-Confirmed COVID-19 Infection among Outpatients in Sentinel Sites, Lebanon, July-December 2021.

On 14 February 2021, Lebanon implemented nationwide vaccination, offering the Pfizer-BioNTech (BNT162b2) vaccine to adults over 50 years of age. We estimated the effectiveness of the Pfizer-BioNTech vaccine in preventing symptomatic laboratory-confirmed COVID-19. We conducted a test-negative case-control (TND) study among symptomatic adults aged 50 years and older who presented with influenza-like illness (ILI) or COVID-19-like illness (CLI) in surveillance sentinel sites between 1 July and 31 December 2021. Unvaccinated participants did not receive any vaccine dose before symptom onset. Vaccinated participants received at least one dose within 14 days before onset of symptoms. We estimated vaccine effectiveness against symptomatic laboratory-confirmed COVID-19, adjusted for demographic and behavioral factors, using multivariable logistic regression. Out of 457 participants with symptoms, 150 (33%) were positive and 307 (67%) were negative for SARS-CoV-2. Adjusted vaccine effectiveness was 22% (95% CI: -70-65%) for those partially vaccinated and 44% (95% CI: 6-67%) for those fully vaccinated. Vaccination with two doses of the Pfizer-BioNTech vaccine was effective in preventing COVID-19 symptomatic illness in the older population. Vaccine effectiveness was lower for those partially vaccinated. We recommend enhancing vaccine uptake with at least one dose among risk groups for COVID-19 and keeping general recommendations on contact and droplet precautions in the general population.

Evolving molecular HIV clusters revealed genotype-specific dynamics in Guangzhou, China (2008-2020)

ObjectivesThis study investigated the genotype-specific dynamics of molecular HIV clusters (MHCs) in Guangzhou, China, aiming to enhance HIV control. MethodsHIV pol sequences from people with HIV (PWH) in Guangzhou (2008-2020) were obtained for genotyping and molecular network creation. MHCs were identified and categorized into three types: emerging, growing, or stable. Clustering rates, proportions of cluster types, and members within each type were calculated and their trends were assessed using joinpoint regression. ResultsAmong 8395 PWH, the most prevalent HIV-1 genotypes were CRF07_BC (39.7%) and CRF01_AE (32.6%). The genotype composition has been stable since 2012 (Ps > 0.05). The overall clustering rate was 43.3%, with significant variations across genotypes (P < 0.001), indicating genotype-specific transmission fitness. Significant declines in overall and genotype-specific clustering rates toward the end of 2020 (Ps < 0.05), potentially offer support for HIV control efforts in reducing local infections. The continuously increasing proportions of stable clusters and the gradually decreasing proportions of emerging and growing clusters (either Ps < 0.05 or Ps > 0.05) suggest a trend toward stable molecular network structure. However, growing clusters exhibited CRF55_01B, CRF07_BC, and CRF59_01B dominance that indicate their priority for interventions. ConclusionThe evolving MHCs highlight the genotype-specific cluster dynamics, providing fresh insights for enhanced prevention and control strategies.

Suppression of the host antiviral response by non-infectious varicella zoster virus extracellular vesicles.

Varicella zoster virus (VZV) is a ubiquitous human virus that predominantly spreads by direct cell-cell contact and requires efficient and immediate host immune evasion strategies to spread. The mechanisms of immune evasion prior to virion entry have not been fully elucidated and represent a critical gap in our complete understanding of VZV pathogenesis. This study describes a previously unreported antiviral evasion strategy employed by VZV through the exploitation of the infected host cell's small extracellular vesicle (sEV) machinery. These findings suggest that non-infectious VZV sEVs could travel throughout the body, affecting cells remote from the site of infection and challenging the current understanding of VZV clinical disease, which has focused on local effects and direct infection. The significance of these sEVs in early VZV pathogenesis highlights the importance of further investigating their role in viral spread and secondary disease development to reduce systemic complications following VZV infections.

Potential Biases in Test-Negative Design Studies of COVID-19 Vaccine Effectiveness Arising from the Inclusion of Asymptomatic Individuals.

The test-negative design (TND) is a popular method for evaluating vaccine effectiveness (VE). A "classical" TND study includes symptomatic individuals tested for the disease targeted by the vaccine to estimate VE against symptomatic infection. However, recent applications of the TND have attempted to estimate VE against infection by including all tested individuals, regardless of their symptoms. In this article, we use directed acyclic graphs and simulations to investigate potential biases in TND studies of COVID-19 VE arising from the use of this "alternative" approach, particularly when applied during periods of widespread testing. We show that the inclusion of asymptomatic individuals can potentially lead to collider stratification bias, uncontrolled confounding by health and healthcare-seeking behaviors (HSBs), and differential outcome misclassification. While our focus is on the COVID-19 setting, the issues discussed here may also be relevant in the context of other infectious diseases. This may be particularly true in scenarios where there is either a high baseline prevalence of infection, a strong correlation between HSBs and vaccination, different testing practices for vaccinated and unvaccinated individuals, or settings where both the vaccine under study attenuates symptoms of infection and diagnostic accuracy is modified by the presence of symptoms.

Melanin as a Photothermal Agent in Antimicrobial Systems.

Bacterial infection is one of the most problematic issues for human health and the resistance of bacteria to traditional antibiotics is a matter of huge concern. Therefore, research is focusing on the development of new strategies to efficiently kill these microorganisms. Recently, melanin is starting to be investigated for this purpose. Indeed, this very versatile material presents outstanding photothermal properties, already studied for photothermal therapy, which can be very useful for the light-induced eradication of bacteria. In this review, we present antibacterial melanin applications based on the photothermal effect, focusing both on the single action of melanin and on its combination with other antibacterial systems. Melanin, also thanks to its biocompatibility and ease of functionalization, has been demonstrated to be easily applicable as an antimicrobial agent, especially for the treatment of local infections.

Surgical resection of a bilateral temporomandibular joint ankylosis and interposition gap arthroplasty using bilateral temporo-parietal fascial flap in a 5 years old child: treatment challenges and literature review

Temporomandibular joint (TMJ) ankylosis is a debilitating state that involves fusion of glenoid fossa and condyle of mandible. This can lead to restriction in mouth opening and mandibular movements. Subsequently, patient develops difficulty in chewing, speech, breathing as well as poor dental hygiene. All of these have detrimental effects on patient’s wellbeing and their quality of life. TMJ ankylosis can also have secondary effects on facial growth like asymmetry of face, retro or micrognathia, malocclusion, anterior or posterior open bite and overcrowding of teeth specially if it presents at early age. Main event that leads to TMJ ankylosis is trauma but this can occur as a secondary insult to surgery, local and systemic infections or diseases like chronic otitis media, tuberculosis, juvenile rheumatoid arthritis and septic arthritis. The management of TMJ ankylosis poses a significant challenge because of technical difficulties and a high incidence of recurrence. It is mainly managed by surgery with different options like gap and interpositional arthroplasty, reconstruction arthroplasty or distraction osteogenesis and aggressive post op physiotherapy. Here, we present a case five years old girl child with post traumatic TMJ ankylosis who was managed with excision of ankylotic mass and interpositional arthroplasty by using bilateral temporo-parietal fascial flap. She was followed for a 1 year and had adequate mouth opening and no recurrence.

Pneumonia due to Mycoplasma hominis in a Full-Term Newborn - A Case Report with Literature Review

Mycoplasma ssp can colonize various human tissues and can cause infections. Their lack of a cell wall makes them difficult to cultivate and to treat as they are resistant to beta-lactam antibiotics. Mycoplasma hominis and ureaplasma urealyticum can colonize the genital tract. While colonization in healthy adults is usually asymptomatic, they can cause neonatal infections during pregnancy through transmission to the fetus or during birth and lead to increased morbidity and mortality, especially in premature infants. However, in full-term neonates with high colonization rates, the pathogenic role and its treatment is controversial. In the following, we present a case of neonatal pneumonia caused by M. hominis in a full-term neonate, which was successfully treated with clindamycin. Mycoplasma spp. can cause symptomatic infections in neonates in individual cases and should be considered as potential pathogens, especially in the case of a protracted course.

Science-based exit from stringent countermeasures against COVID-19: Mortality prediction using immune landscape between 2021 and 2022 in Japan

BackgroundStringent public health and social measures against COVID-19 infection were implemented to avoid an overwhelming hospital caseload and excessive number of deaths, especially among elderly people. We analyzed population-level immunity and predicted mortality, calculated as the potential number of deaths on a given calendar date in Japan, to develop a science-based exit strategy from stringent control measures. MethodsImmune proportions were inferred by age group using vaccination coverage data and the estimated number of naturally infected individuals. Immunity against symptomatic illness and death were estimated separately, allowing for inference of the immune fraction that was protected against either COVID-19-related symptomatic infection or death. By multiplying the infection fatality risk by age group for the immune fraction, the potential number of deaths was obtained. ResultsAccounting for a second and third dose of messenger RNA vaccine in the present-day population, approximately 155,000 potential deaths would be expected among people aged ≥ 60 years if all individuals were infected at the very end of 2022. A fourth dose (i.e., second booster) with a coverage identical to that of the third dose could reduce mortality by 60%. In all examined settings, the largest number of deaths occurred among people aged 80 years and older. ConclusionsOur estimates can help policymakers understand the mortality impact of the COVID-19 epidemic in a quantitative manner and the critical importance of timely immunization so as to assist in decision making.