In an era marked by unprecedented global health challenges, measles virus (MeV) reemerges as a significant threat to public health, despite being one of the most preventable diseases through vaccination. Caused by an enveloped, single-stranded negative sense RNA virus of the genus Morbillivirus, measles is not only highly contagious but also present in various strains, with at least 20 different genotypes identified across the globe [1]. Despite this genetic diversity, there exists only one serotype of MeV, making its widespread impact particularly daunting [1].

Abstract Eosinophilic esophagitis (EoE) is a chronic Th2 mediated inflammatory disease of the esophagus driven by dietary or inhalant allergens which if left untreated, leads to fibrosis and poor esophageal function. Although the inflammation in the esophagus is dominated by eosinophils, there are also elevated levels of T and B cells.Blood samples from ten patients with EoE before and after treatment with orodispersible budesonide and ten healthy controls were compared using cytometry by time-of-flight (CyTOF). An antibody panel was designed that covers the major immunological cell populations with particular focus on eosinophils. The data was analyzed with multivariate methods and cluster analysis. Correlation analysis was done between immune markers and endoscopic, histological and symptomatologic assessments.Our analysis revealed that patients with EoE had lower levels of effector memory T cells after treatment with orodispersible budesonide to the same level as healthy subjects. In addition, more suppressive eosinophils were present in the circulation of EoE patients before treatment and more immature eosinophils were present after treatment. Furthermore, levels of galectin-10+ eosinophils correlated with histological findings in esophageal tissue from EoE patients. In all patients, the peak eosinophils were decreased after treatment with orodispersible budesonide. Intriguingly, 90% of the patients had remission in the histological assessment and 50% improved in the endoscopic assessment.This study reports a detailed immune profile in patients with EoE before and after treatment with orodispersible budesonide and it is a step toward finding blood-based immune parameters that could be useful to monitor response to treatment.

ObjectivesTo test whether inflammatory processes link the expression of childhood neurodivergent traits to chronic disabling fatigue in adolescence. DesignLongitudinal case–control study. SettingWe analysed data from The Avon Longitudinal Study of Parents and Children (ALSPAC). Participants8115 and 8036 children of the ALSPAC cohort at ages 7 and 9 years, respectively, 4563 of whom also completed self-report measures at age 18 years. Primary and secondary outcome measuresWe assessed if children scoring above screening threshold for autism/attention deficit hyperactivity disorder (ADHD) at ages 7 and 9 years had increased risk of chronic disabling fatigue at age 18 years, computing ORs and CIs for effects using binary logistic regression. Mediation analyses were conducted to test if an inflammatory marker (interleukin 6 (IL-6)) at age 9 years linked neurodivergent traits to chronic disabling fatigue at age 18 years. ResultsChildren with neurodivergent traits at ages 7 and 9 years were two times as likely to experience chronic disabling fatigue at age 18 years (likely ADHD OR=2.18 (95% CI=1.33 to 3.56); p=0.002; likely autism OR=1.78 (95% CI=1.17 to 2.72); p=0.004). Levels of IL-6 at age 9 were associated with chronic disabling fatigue at age 18 (OR=1.54 (95% CI=1.13 to 2.11); p=0.006). Inflammation at age 9 years mediated effects of neurodivergent traits on chronic disabling fatigue (indirect effect via IL-6: ADHD b=1.08 (95% CI=1.01 to 1.15); autism b=1.06; (95% CI=1.03 to 1.10)). All effects remained significant when controlling for the presence of depressive symptoms. ConclusionsOur results indicate higher risk of chronic disabling fatigue for children with neurodivergent traits, likely linked to higher levels of inflammation. The implementation of transdiagnostic screening criteria to inform support strategies to counteract risk early in life is recommended. …

IntroductionAcute undifferentiated febrile illnesses (AUFIs) impose a large burden in the tropics. Understanding of AUFI’s epidemiology is limited. Insufficient diagnostic capacity hinders the detection of outbreaks. The lack of interconnection in healthcare systems hinders timely response. We describe a protocol to study the epidemiology and aetiologies of AUFI and pathogen discovery in strategic areas of Latin America (LA). Methods and analysisGlobal Infectious Diseases Network investigators comprising institutions in Colombia, Dominican Republic, México, Perú and the USA, developed a common cohort study protocol. The primary objective is to determine the aetiologies of AUFI at healthcare facilities in high-risk areas. Data collection and laboratory testing for viral, bacterial and parasitic agents are performed in rural and urban healthcare facilities and partner laboratories. Centralised laboratory and data management cores deploy diagnostic tests and data management tools. Subjects >6 years with fever for

IntroductionMental health concerns globally impact millions of people, resulting in significant financial impact and adverse health outcomes. People living with mental health concerns are at higher risk of developing physical health issues, which can lead to a shortened life expectancy. Barriers to physical healthcare, such as limited service capacity, low help seeking and stigma, contribute to health disadvantage. Quality improvement (QI) interventions can address these challenges by addressing staff-level and service-level factors to improve the focus on physical healthcare in mental health settings. The aim of this scoping review is to describe studies of QI interventions to improve physical healthcare in mental health settings. Methods and analysisThe proposed scoping review will be conducted in accordance with guidance for scoping reviews from the Joanna Briggs Institute Manual and in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. A systematic review search for peer-reviewed and published articles will be conducted across eight databases: PubMed, MEDLINE (Ovid), Web of Science, CINAHL (EBSCOhost), ProQuest Central, PsycINFO (Ovid), Scopus and Embase (Elsevier). Two independent reviewers will screen the titles, abstracts and full text using Covidence. Any disagreement will be resolved through discussion or with a third reviewer. Data collection will be facilitated using Microsoft Excel. The details of included studies will be extracted by two authors independently. Ethics and disseminationNo ethical approval is required for the scoping review. The results of this review will be presented at conferences and published in a peer-reviewed scientific journal. This review will also inform the development of a QI strategy to influence mental health staff practices in the provision of physical healthcare in Australian mental health settings. …

ObjectivesTo investigate the association of diabetes with postoperative outcomes in patients undergoing primary total hip arthroplasty (THA). DesignRetrospective cohort study using data from the US National Inpatient Sample (NIS). SettingStudy cohort was hospitalisations for primary THA in the USA, identified from the 2016–2020 NIS. ParticipantsWe identified 2 467 215 adults in the 2016–2020 NIS who underwent primary THA using International Classification of Diseases, 10th Revision codes. Primary THA hospitlizations were analysed as the overall group and also stratified by the underlying primary diagnosis for THA. Outcome measuresOutcome measures of interest were the length of hospital stay>the median, total hospital charges>the median, inpatient mortality, non-routine discharge, need for blood transfusion, prosthetic fracture, prosthetic dislocation and postprocedural infection, including periprosthetic joint infection, deep surgical site infection and postprocedural sepsis. ResultsAmong 2 467 215 patients who underwent primary THA, the mean age was 68.7 years, 58.3% were female, 85.7% were white, 61.7% had Medicare payer and 20.4% had a Deyo-Charlson index (adjusted to exclude diabetes mellitus) of 2 or higher. 416 850 (17%) patients had diabetes. In multivariable-adjusted logistic regression in the overall cohort, diabetes was associated with higher odds of a longer hospital stay (adjusted OR (aOR) 1.38; 95% CI 1.35 to 1.41), higher total charges (aOR 1.11; 95% CI 1.09 to 1.13), non-routine discharge (aOR 1.18; 95% CI 1.15 to 1.20), the need for blood transfusion (aOR 1.19; 95% CI 1.15 to 1.23), postprocedural infection (aOR 1.62; 95% CI 1.10 to 2.40) and periprosthetic joint infection (aOR 1.91; 95% CI 1.12 to 3.24). We noted a lack of some associations in the avascular necrosis and inflammatory arthritis cohorts (p>0.05). ConclusionDiabetes was associated with increased healthcare utilisation, blood transfusion and postprocedural infection risk following primary THA. Optimisation of diabetes with preoperative medical management and/or institution of specific postoperative pathways may improve these outcomes. Larger studies are needed in avascular necrosis and inflammatory arthritis cohorts undergoing primary THA. …

Abstract Background Antiretroviral therapy (ART) has transformed HIV management, with various regimens available. Dolutegravir (DTG) plus lamivudine (3TC) dual therapy is now the one of the first line regimens. Methods A retrospective, observational study included treatment naïve people living with HIV (PLWH) with baseline HIV RNA viral load (VL) greater than 500,000 copies/mL from March 2020 to June 2022. PLWH on DTG + 3TC were included in the 2DR group, while others on INSTI-based three-drug regimens were divided in the 3DR group. Viral suppression, immunological recovery, and safety were assessed. Results The study included 52 PLWH, with no significant baseline differences. Virologic suppression rates at weeks 24 and 48 were similar in both groups, even with baseline HIV RNA VL greater than 1,000,000 copies/mL. CD4 + T cell counts improved rapidly. No serious adverse effects were reported. Conclusions DTG + 3TC dual therapy demonstrates effectiveness in treatment naïve PLWH with high baseline HIV RNA VL, suggesting its potential as a first line regimen for all treatment naïve PLWH. …

Abstract Background The global impact of the coronavirus disease 2019 (COVID-19) pandemic has resulted in significant morbidity and mortality. Immunocompromised patients, particularly those treated for B-cell lymphoma, have shown an increased risk of persistent infection with SARS-CoV-2 and severe outcomes and mortality. Multi-mutational SARS-CoV-2 variants can arise during the course of such persistent cases of COVID-19. No optimal, decisive strategy is currently available for patients with persistent infection that allows clinicians to sustain viral clearance, determine optimal timing to stop treatment, and prevent virus reactivation. We introduced a novel treatment combining antivirals, neutralizing antibodies, and genomic analysis with frequent monitoring of spike-specific antibody and viral load for immunocompromised patients with persistent COVID-19 infection. The aim of this retrospective study was to report and evaluate the efficacy of our novel treatment for immunocompromised B-cell lymphoma patients with persistent COVID-19 infection. Methods This retrospective descriptive analysis had no controls. Patients with B-cell lymphoma previously receiving immunotherapy including anti-CD20 antibodies, diagnosed as having COVID-19 infection, and treated in our hospital after January 2022 were included. We selected anti-SARS-CoV-2 monoclonal antibodies according to subvariants. Every 5 days, viral load was tested by RT-PCR, with antivirals continued until viral shedding was confirmed. Primary outcome was virus elimination. Independent predictors of prolonged viral shedding time were determined by multivariate Cox regression. Results Forty-four patients were included in this study. Thirty-five patients received rituximab, 19 obinutuzumab, and 26 bendamustine. Median treatment duration was 10 (IQR, 10–20) days; 22 patients received combination antiviral therapy. COVID-19 was severe in 16 patients, and critical in 2. All patients survived, with viral shedding confirmed at median 28 (IQR, 19–38) days. Bendamustine use or within 1 year of last treatment for B-cell lymphoma, and multiple treatment lines for B-cell lymphoma significantly prolonged time to viral shedding. Conclusions Among 44 consecutive patients treated, anti-SARS-CoV-2 monoclonal antibodies and long-term administration of antiviral drugs, switching, and combination therapy resulted in virus elimination and 100% survival. Bendamustine use, within 1 year of last treatment for B-cell lymphoma, and multiple treatment lines for B-cell lymphoma were the significant independent predictors of prolonged viral shedding time. …

Abstract Background The use of telemedicine has grown significantly since the COVID-19 pandemic and has the potential to improve access to specialized care for otherwise underserved populations. Incarcerated people living with HIV (PLWH) could potentially benefit from expanded access to HIV care through telemedicine. Methods All PLWH who were incarcerated within the Tennessee Department of Corrections and received care through the HIV telemedicine clinic at Regional One Hospital between 5/1/2019 through 2/28/2022 were identified from the electronic health records (EHR). Demographics, laboratory data, vaccine history, and treatment outcomes were abstracted from the EHR. Retention in care and viral suppression were defined using Centers for Disease Control and Prevention definitions. Results Of the 283 incarcerated PLWH receiving care from this telemedicine clinic, 78% remained retained in care and 94% achieved or maintaining viral suppression at 12 months. Many preventative care measures remained unperformed or undocumented, including vaccinations and testing for concurrent sexually transmitted infections. There were 56 patients (20%) found to have chronic hepatitis C in this population, with 71% either cured or still on treatment in this study period. Conclusions Retention in care and viral suppression rates were excellent among incarcerated PLWH receiving telemedicine care for their HIV. HIV related primary health care screenings and vaccinations, however, were less consistently documented and represent areas for improvement. …

by Benjamin A. Katz, Iftah Yovel …

by Atenea Vázquez-Sánchez, Dalia Rodríguez-Ríos, Dannia Colín-Castelán, Jorge Molina-Torres, Enrique Ramírez-Chávez, Gloria del Carmen Romo-Morales, Silvio Zaina, Gertrud Lund …

by Mauricio Tano, Juha Baek, Adriana Ordonez, Rita Bosetti, Terri Menser, George Naufal, Bita Kash …

by Ibrahim Ali Ibrahim Muhina, Abid M. Sadiq, Fuad H. Said, Faryal M. Raza, Sarah K. Gharib, Sophia S. Muhali, Andrea R. Costantine, Mulhati S. Abdalla, Laura J. Shirima, Nyasatu G. Chamba, Furaha S. Lyamuya, Elifuraha W. Mkwizu, Kajiru G. Kilonzo, Venance P. Maro, Elichilia R. Shao Background Africa has consistently had the highest prevalence (70.1%) of H. pylori, and this has led to significant cases of dyspepsia, gastric cancers, and upper gastrointestinal bleeding. However, most studies have used sero-prevalence, which might not give the current state of the infection. Among the tests, the stool antigen test is simple, quick, and effective. The study aimed to determine the feco-prevalence, endoscopic pattern, and associated factors of H. pylori infection among symptomatic adult patients in Northern Tanzania. Materials and methods A hospital-based, cross-sectional study was conducted from October 2022 to April 2023 among adults attending the gastroenterology clinic at Kilimanjaro Chistian Medical Centre. A systematic random sampling was used to select the participants with indications of undergoing esophagogastroduodenoscopy. Questionnaires, stool and blood samples, and endoscopy were used to collect variable data. Numerical and categorical variables were summarized into narrations and tables. Logistic regression was used to assess the factors associated with H. pylori. Results The feco-prevalence of H. pylori was 43.4%. Chronic gastritis (51.1%) was the most common endoscopic pattern, whereas duodenal ulcers and gastric ulcers were significantly associated with H. pylori infection. Increasing in age (p…

by Mireille Savoie, Aurora Mattison, Laurel Genge, Julie Nadeau, Sylwia Śliwińska-Wilczewska, Maximilian Berthold, Naaman M. Omar, Ondřej Prášil, Amanda M. Cockshutt, Douglas A. Campbell Prochlorococcus marinus, the smallest picocyanobacterium, comprises multiple clades occupying distinct niches, currently across tropical and sub-tropical oligotrophic ocean regions, including Oxygen Minimum Zones. Ocean warming may open growth-permissive temperatures in new, poleward photic regimes, along with expanded Oxygen Minimum Zones. We used ocean metaproteomic data on current Prochlorococcus marinus niches, to guide testing of Prochlorococcus marinus growth across a matrix of peak irradiances, photoperiods, spectral bands and dissolved oxygen. MED4 from Clade HLI requires greater than 4 h photoperiod, grows at 25 μmol O2 L-1 and above, and exploits high cumulative diel photon doses. MED4, however, relies upon an alternative oxidase to balance electron transport, which may exclude it from growth under our lowest, 2.5 μmol O2 L-1, condition. SS120 from clade LLII/III is restricted to low light under full 250 μmol O2 L-1, shows expanded light exploitation under 25 μmol O2 L-1, but is excluded from growth under 2.5 μmol O2 L-1. Intermediate oxygen suppresses the cost of PSII photoinactivation, and possibly the enzymatic production of H2O2 in SS120, which has limitations on genomic capacity for PSII and DNA repair. MIT9313 from Clade LLIV is restricted to low blue irradiance under 250 μmol O2 L-1, but exploits much higher irradiance under red light, or under lower O2 concentrations, conditions which slow photoinactivation of PSII and production of reactive oxygen species. In warming oceans, range expansions and competition among clades will be governed not only by light levels. Short photoperiods governed by latitude, temperate winters, and depth attenuation of light, will exclude clade HLI (including MED4) from some habitats. In contrast, clade LLII/III (including SS120), and particularly clade LLIV (including MIT9313), may exploit higher light niches nearer the surface, under expanding OMZ conditions, where low O2 relieves the stresses of oxidation stress and PSII photoinhibition.

by Xiaolan Huang, Zhihua Du RNA pseudoknots play a crucial role in various cellular functions. Established pseudoknots show significant variation in both size and structural complexity. Specifically, three-stemmed pseudoknots are characterized by an additional stem-loop embedded in their structure. Recent findings highlight these pseudoknots as bacterial riboswitches and potent stimulators for programmed ribosomal frameshifting in RNA viruses like SARS-CoV2. To investigate the possible presence of functional three-stemmed pseudoknots in human mRNAs, we employed in-house developed computational methods to detect such structures within a dataset comprising 21,780 full-length human mRNA sequences. Numerous three-stemmed pseudoknots were identified. A selected set of 14 potential instances are presented, in which the start codon of the mRNA is found in close proximity either upstream, downstream, or within the identified three-stemmed pseudoknot. These pseudoknots likely play a role in translational initiation regulation. The probability of their existence gains support from their ranking as the most stable pseudoknot identified in the entire mRNA sequence, structural conservation across homologous mRNAs, stereochemical feasibility as demonstrated by structural modeling, and classification as members of the CPK-1 pseudoknot family, which includes many well-established pseudoknots. Furthermore, in four of the mRNAs, two or three closely spaced or tandem three-stemmed pseudoknots were identified. These findings suggest the frequent occurrence of three-stemmed pseudoknots in human mRNAs. A stepwise co-transcriptional folding mechanism is proposed for the formation of a three-stemmed pseudoknot structure. Our results not only provide fresh insights into the structures and functions of pseudoknots but also unveil the potential to target pseudoknots for treating human diseases.

by Ning Xie, Haixin Fan, Xiaochun Liu, Feng Ye, Zhenlin Weng Using weekly data from January 2020 to December 2021 on the prices of various links in the Chinese broiler industry chain and the COVID-19 epidemic, we employed a time-varying parametric vector auto-regressive (TVP-VAR) model to investigate the dynamic effects of public health events on price fluctuations of upstream, midstream, and downstream products in the Chinese broiler industry chain. Our findings showed that the COVID-19 epidemic had different effects on the prices of various broiler products, both in direction and magnitude, at different lags and time intervals. Chicken and live chicken prices were impacted the most, followed by broiler chick prices, while broiler feed prices were impacted the least. The epidemic constantly impacted broiler chick and chicken prices, while its effect on live chicken prices was initially negative but turned positive afterwards. Additionally, the impact of the COVID-19 epidemic on broiler product prices consistently increased with more extended lag periods. The impulse responses at different epidemic time points were heterogeneous. With the results of this study, policy recommendations can be suggested to relevant government departments to optimize the prevention and control measures for public health emergencies and ensure price stability in the broiler industry.

by Burcu Ünlütabak, Graciela Trujillo Hernandez, İlayda Velioğlu, David Menendez, Karl S. Rosengren Question-asking is a crucial tool for acquiring information about unseen entities, such as viruses; thus, examining children’s questions within the context of COVID-19 is particularly important for understanding children’s learning about the coronavirus. The study examined 3-12-year-old children’s questions and teachers’ responses about the COVID-19 pandemic in Türkiye, a non-Western developing context, and the United States, a Western cultural context. A total of 119 teachers from Türkiye and 95 teachers from the US participated in the study. Teachers completed an online survey consisting of a demographic form and a questionnaire asking them to report three questions about COVID-19 asked by children in their classrooms and their responses to these questions. We analyzed children’s questions and teachers’ responses for their type and content and examined demographic factors associated with children’s questions and teachers’ responses. Consistent with the literature, children from Türkiye asked fewer explanation-seeking (i.e., why/how) questions than children from the United States. Children asked questions about viruses and precautions. Teachers responded to children’s questions realistically in both countries. The findings have important implications for how children gain knowledge from teachers when discussing health, disease, and virus topics in two countries.

by Kosuke Oyama, Tadashi Ueda Antigen-presenting cells (APCs) play a crucial role in the immune system by breaking down antigens into peptide fragments that subsequently bind to major histocompatibility complex (MHC) molecules. Previous studies indicate that stable proteins can impede CD4+ T cell stimulation by hindering antigen processing and presentation. Conversely, certain proteins require stabilization in order to activate the immune response. Several factors, including the characteristics of the protein and the utilization of different adjuvants in animal experiments, may contribute to this disparity. In this study, we investigated the impact of adjuvants on antigen administration in mice, specifically focusing on the stability of the CH2 domain. Consequently, the CH2 domain induced a stronger IgG response in comparison to the stabilized one when using Alum and PBS (without adjuvant). On the other hand, animal experiment using Freund’s adjuvant showed the opposite results. These findings indicate the significance of considering the intrinsic conformational stability of a protein when eliciting its immunogenicity, particularly within the context of vaccine development.

Abstract Purpose This study assessed the frequency, clinical significance, and risk factors for Herpes simplex virus (HSV) reactivation in immunocompetent patients with community-acquired pneumonia (CAP). Methods The study included adult CAP-patients who were enrolled in the CAPNETZ study between 2007 and 2017 and had a residual sputum sample available for analysis. In addition to routine diagnostics, sputum and blood samples were tested for HSV-1/2 using PCR. Demographics, comorbidities, and CRB-65 score were compared between HSV-positive and negative patients using Fisher exact or Mann Whitney test. Logistic regression analyses investigated the influence of HSV reactivation on a modified hospital recovery scale (HRS) until day 7, divided into 3 categories (no oxygen therapy, oxygen therapy, ICU admission or death). Results Among 245 patients, HSV-1 and HSV-2 were detected in 30 patients (12.2%, 95%CI 8.7–16.9) and 0 patients, respectively. All HSV-positive patients were hospitalized, had a CRB-65 severity score of 0–2 and survived the first 28 day. In the HSV-positive group, patients had a non-significantly higher median age (70.5 versus 66 years) and a higher rate of oncological comorbidities (16.7% versus 8.8%) compared to the HSV-negative group. Distribution of co-pathogens and outcome parameters did not significantly differ between both groups. In a multivariate logistic regression model, age (AOR 1.029, p = 0.012) and CRB-65 score (AOR 1.709, p = 0.048), but not HSV-1 as single or co-pathogen were independently associated with higher HRS. Conclusion Our study suggests that HSV-1 reactivation is common in CAP but might not be associated with specific risk factors or a complicated disease course. …

Abstract Background Loiasis is one of the significant filarial diseases for people living in West and Central Africa with wide endemic area but is not seen in China. As economy booms and international traveling increase, China faces more and more imported parasitic diseases that are not endemic locally. Loiasis is one of the parasitic diseases that enter China by travelers infected in Africa. The better understanding of the clinical and laboratory features of loa loa infection will facilitate the diagnosis and treatment of loiasis in China. Methods The study targeted travelers who were infected with L. loa in endemic Africa regions and returned to Beijing between 2014 and 2023. Epidemiological, clinical, and biological data as well as treatment of these patients were collected. Results Total 21 cases were identified as L. loa infection based on their typical clinical manifestations and parasite finding. All cases had a history of travel to Africa for more than 6 months, most of them are the construction workers dispatched to West Africa with outdoor activities. Calabar swelling (n = 19; 90.5%) and pruritus (n = 11; 52.4%) were among the most common clinical symptoms followed by muscle pain (n = 7; 33.3%) and skin rash (n = 2; 9.5%). The adult worms were observed in the eyelid or subconjunctiva (n = 2; 9.5%) and subcutaneous tissues (n = 2; 9.5%). Although all patients presented with a high eosinophil count (> 0.52 × 109/L), only two cases displayed microfilariae in fresh venous blood and positive for filarial antigen. A cut section of adult worm was observed through biopsy on a skin nodule surrounded by lymphocytes, plasma cells and eosinophils. All subjects were positive in PCR targeting L. loa ITS-1. The constructed phylogenetic tree based on the amplified ITS-1 sequences identified their genetical relation to the L. Loa from Africa. All patients treated with albendazole and diethylcarbamazine were recovered without relapse. Conclusion This study provides useful information and guideline for physicians and researchers in non-endemic countries to diagnose and treat loiasis and L. loa infections acquired from endemic regions. …

Abstract Purpose The emerging zoonotic Borna disease virus 1 (BoDV-1) and the variegated squirrel bornavirus 1 (VSBV-1) cause severe and fatal human encephalitis in Germany. We conducted the first systematic clinical analysis of acute, molecularly confirmed fatal bornavirus encephalitis cases comprising 21 BoDV-1 and four VSBV-1 patients to identify options for better diagnosis and timely treatment. Methods Analyses were based on medical records and, for BoDV-1, on additional medical interviews with patients’ relatives. Results Disease onset was unspecific, often with fever and headache, inconsistently mixed with early fluctuating neurological symptoms, all rapidly leading to severe encephalopathy and progressive vigilance decline. Very shortly after seeking the first medical advice (median time interval 2 and 0 days for BoDV-1 and VSBV-1, respectively), all except one patient were hospitalised upon manifest neurological symptoms (median 10 and 16 days respectively after general symptom onset). Neurological symptoms varied, always progressing to coma and death. BoDV-1 and VSBV-1 patients required ventilation a median of three and five days, and died a median of 32 and 72 days, after hospitalisation. Death occurred mostly after supportive treatment cessation at different points in time based on poor prognosis. Disease duration therefore showed a wide, incomparable range. Conclusion The extremely rapid progression is the most obvious clinical characteristic of bornavirus encephalitis and the timeframe for diagnosis and targeted therapy is very short. Therefore, our results demand an early clinical suspicion based on symptomatology, epidemiology, imaging, and laboratory findings, followed by prompt virological testing as a prerequisite for any potentially effective treatment. …

Abstract Purpose Daptomycin-induced eosinophilic pneumonia (DIEP) is a rare yet severe adverse event that requires rapid recognition and management. Diagnosing a definite case is challenging and involves meeting the American Thoracic Society (ATS) criteria, although alternative criteria have been suggested. This study aims to conduct a systematic review of literature and includes a case series. Methods Six cases of DIEP identified at Perugia Hospital, Perugia, Italy have been described. A systematic review was carried out adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement guidelines. Results a total of 74 cases of DIEP were analysed. Using ATS clinical criteria, 15 were classified as definite (20.3%), 54 as probable (73.0%), and 5 as possible (6.8%). Phillips criteria and the Lyon Algorithm identified 43/74 (58.2%) and 64/67 (95.5%) cases as definite, respectively. Bronchoalveolar lavage (BAL) was performed in 43 cases, revealing an average eosinophil count of 28.6% (SD 24.4). Radiological findings highlighted recurring features like bilateral opacities (68.1%), ground-glass opacities (41.7%), patchy infiltrates (30.6%), and peripheral predominance (19.4%). Upon suspicion, daptomycin was discontinued; 20 cases required no additional treatment, 38 received corticosteroids, and 12 received both corticosteroids and antibiotics. Recovery rates were high across all treatment types (≥ 73.7%). Most reports described rapid improvement post-withdrawal (within 96 h). Conclusions DIEP is a rare, fast-progressing condition where early diagnosis and prompt treatment are vital. Diagnosis relies on clinical, laboratory, and radiological evaluations. Stopping daptomycin is essential, with corticosteroids often necessary. Further research is needed to enhance diagnostic accuracy for this disease. …

Journal of Medical Virology, Volume 96, Issue 7, July 2024.

Abstract Background To address the need for novel COVID-19 therapies, we evaluated the fully-human polyclonal antibody product SAB-185 in a phase 3 clinical trial.Methods Non-hospitalized high-risk adults within 7 days of COVID-19 symptom onset were randomized 1:1 to open-label SAB-185 3,840 units/kg or casirivimab/imdevimab 1200 mg. Non-inferiority comparison was undertaken for the pre-Omicron population (casirivimab/imdevimab expected to be fully active) and superiority comparison for the Omicron population (casirivimab/imdevimab not expected to be active). Primary outcomes were the composite of all-cause hospitalizations/deaths and grade ≥3 treatment-emergent adverse events (TEAEs) through day 28. Secondary outcomes included time to sustained symptom improvement and resolution.Results Enrollment was terminated early due to low hospitalization/death rates upon Omicron emergence. 733 adults were randomized, 255 included in pre-Omicron and 392 in Omicron analysis populations. Hospitalizations/deaths occurred in 6 (5.0%) and 3 (2.2%) of pre-Omicron SAB-185 and casirivimab/imdevimab arms, respectively (absolute difference [95% CI] 2.7% [-2.3%, 8.6%]), inconclusive for non-inferiority; and 5 (2.5%) versus 3 (1.5%) (absolute difference 1.0% [-2.3%, 4.5%]) for Omicron. Risk ratios for grade ≥3 TEAEs were 0.94 [0.52, 1.71] (pre-Omicron) and 1.71 [0.96, 3.07] (Omicron). Time to symptom improvement and resolution were shorter for SAB-185, median 11 vs 14 (pre-Omicron) and 11 vs 13 days (Omicron) (symptom improvement), and 16 vs 24 days and 18 vs >25 days (symptom resolution), p

Abstract Youth experiencing homelessness (YEH) and sexual and gender minority (SGM) YEH may be at increased risk for infectious diseases due to living arrangements, risk behaviors, and barriers to healthcare access that are dissimilar to those of housed youth and older adults experiencing homelessness. To better understand infectious diseases among YEH populations, we synthesized findings from 12 peer-reviewed articles published between 2012 to 2020 which enumerated YEH or SGM YEH infectious disease burden in locations across the U.S. or Canada. Pathogens presented in the studies were limited to sexually transmitted infections (STIs) and bloodborne infections (BBI). Only three studies enumerated infectious diseases among SGM YEH. There was a dearth of comparison data by housing status (ex., sheltered versus unsheltered youth), SGM identity, or other relevant counterfactual groups in the identified studies. We also introduce three publicly available, national-level surveillance datasets from the U.S. or Canada that quantify certain STIs, BBIs, and tuberculosis among YEH, which may be used for future disease burden assessments. Our review calls for more comprehensive YEH-centered research that includes multimodal data collection and timely disease surveillance to improve estimates of infectious diseases among this vulnerable population.

Abstract Within a multi-state viral genomic surveillance program, we evaluated whether proportions of SARS-CoV-2 infections attributed to the JN.1 variant and to XBB-lineage variants (including HV.1 and EG.5) differed between inpatient and outpatient care settings during periods of cocirculation. Both JN.1 and HV.1 were less likely than EG.5 to account for infections among inpatients versus outpatients (aOR=0.60 [95% CI: 0.43-0.84; p=0.003] and aOR=0.35 [95% CI: 0.21-0.58; p

Abstract Background The progression from Mycobacterium tuberculosis infection to active tuberculosis (TB) disease varies among individuals, and identifying biomarkers to predict progression is crucial for guiding interventions. In this study, we aimed to determine plasma immune biomarker profiles in healthy household contacts of index pulmonary TB (PTB) patients who either progressed to TB or remained as non-progressors.Methods A cohort of household contacts of adults with PTB was enrolled, consisting of 15 contacts who progressed to TB disease and 15 non-progressors. Plasma samples were collected at baseline, 4 months, and 12 months to identify predictive TB progression markers.Results Our findings revealed that individuals in the progressor group exhibited significantly decreased levels of IFNγ, IL-2, TNFα, IL1α, IL1β, IL-17A, and IL-1Ra at baseline, months 4 and 12. In contrast, the progressor group displayed significantly elevated levels of IFNα, IFNβ, IL-6, IL-12, GM-CSF, IL-10, IL-33, CCL2, CCL11, CXCL8, CXCL10, CX3CL1, VEGF, Granzyme-B and PDL-1 compared to the non-progressor group at baseline, months 4 and 12. ROC analysis identified IFNγ, GM-CSF, IL-1Ra, CCL2 and CXCL10 as the most promising predictive markers, with an AUC of ≥90. Furthermore, combinatorial analysis demonstrated that GM-CSF, CXCL10 and IL-1Ra, when used in combination, exhibited high accuracy in predicting progression to active TB disease.Conclusions Our study suggests that a specific set of plasma biomarkers GM-CSF, CXCL10 and IL-1Ra, can effectively identify household contacts at significant risk of developing TB disease. These findings have important implications for early intervention and preventive strategies in TB-endemic regions.

The bacterium Salmonella Typhi can cause a potentially life-threatening infection, typhoid. Spread through contaminated food and water, typhoid affects an estimated 27 million people each year causing 129,000-223,000 deaths globally.[1] Pakistan has an estimated typhoid incidence of 493·5 per 100,000 people per year, [2-4] with unsafe water supply and poor sanitary conditions leading to large epidemics of this disease.[5]…

Influenza is a highly contagious airborne disease caused by Influenza type A and type B viruses [1]. Influenza is one of the most common infectious diseases and occurs in seasonal epidemics [2] causing an acute febrile illness with variable degrees of systemic symptoms, ranging from mild fatigue to respiratory failure and death [3]. Although it is a preventable disease, Influenza is one of the main public health concerns worldwide, and during the last decade, awareness towards influenza virus diagnosis and monitoring increased [4].

IntroductionA substantial proportion of patients with inflammatory bowel disease (IBD) on intravenous infliximab require dose intensification. Accessing additional intravenous infliximab is labour-intensive and expensive, depending on insurance and pharmaceutical reimbursement. Observational data suggest that subcutaneous infliximab may offer a convenient and safe alternative to maintain disease remission in patients requiring dose-intensified infliximab. A prospective, controlled trial is required to confirm that subcutaneous infliximab is as effective as dose-intensified intravenous infliximab, to identify predictors of disease flare and to establish the role of subcutaneous infliximab therapeutic drug monitoring. Methods and analysisThe DISCUS-IBD trial is an investigator-initiated, prospective, multicentre, randomised, open-label non-inferiority study comparing the rate of disease flares in participants randomised to continue dose-intensified intravenous infliximab to those switched to subcutaneous infliximab after 48 weeks. Participants are adult patients with IBD in sustained corticosteroid-free remission on any regimen of dose-intensified infliximab up to a maximum of 10 mg/kg 4-weekly intravenously. Participants allocated to intravenous infliximab will continue infliximab at the same dose-intensified regimen they were receiving at study enrolment. Subcutaneous infliximab dosing will be stratified by prior intravenous infliximab dosing. Clinical (Harvey-Bradshaw Index, partial Mayo score), biochemical (C reactive protein, faecal calprotectin), pharmacokinetic (drug-level±antidrug antibodies) and qualitative data are collected 12-weekly until study conclusion at week 48. 13 sites across Australia will participate in recruitment to reach a calculated sample size of 120 participants. Ethics and disseminationMultisite ethics approval was obtained from the Health District Human Research Ethics Committee (HREC) at The Alfred Hospital under a National Mutual Acceptance (NMA) agreement (HREC/90559/Alfred-2022; Local Reference: Project 618/22, version 1.6, 2 March 2023). Findings will be reported at national and international gastroenterology meetings and published in peer-reviewed journals. DISCUS-IBD was prospectively registered with the Australian and New Zealand Clinical Trials Registry (ANZCTR) prior to commencing recruitment. Trial registration numberACTRN12622001458729. …

Abstract Background HIV remains a critical global public health challenge. In 2022, it was estimated that approximately 39.0 million people worldwide were living with HIV, and of these, around 29.8 million were receiving antiretroviral therapy (ART). The objective was to evaluate the clinical and epidemiological profile and factors associated with viral load (VL) non-suppression in people living with HIV/AIDS at the Maputo Military Hospital (CITRA/MMH). Methods A retrospective cross-sectional analytical study was conducted on 9105 people aged 15 years and over. We use secondary data from participants on ART for at least 2 years being followed up between the years 2019–2020 at CITRA/MMH. Those recently enrolled (on ART 

Abstract Background The ambitious goal to eliminate new pediatric HIV infections by 2030 requires accelerated prevention strategies in high-risk settings such as South Africa. One approach could be pre-exposure prophylaxis (PrEP) with broadly neutralizing anti-HIV-1 monoclonal antibodies (bNAbs). The aim of our study is to define the optimal dose(s), the ideal combination(s) of bNAbs in terms of potency and breadth, and timing of subcutaneous (SC) administration(s) to prevent breast milk transmission of HIV. Methods Two bNAbs, CAP256V2LS and VRC07-523LS, will be assessed in a sequential and randomized phase I, single-site, single-blind, dose-finding trial. We aim to investigate the 28-day safety and pharmacokinetics (PK) profile of incrementally higher doses of these bNAbs in breastfeeding HIV-1 exposed born without HIV neonates alongside standard of care antiretroviral (ARV) medication to prevent (infants) or treat (mothers) HIV infection. The trial design includes 3 steps and 7 arms (1, 2, 3, 4, 5, 6 and 6b) with 8 infants in each arm. The first step will evaluate the safety and PK profile of the bNAbs when given alone as a single subcutaneous (SC) administration at increasing mg/kg body weight doses within 96 h of birth: arms 1, 2 and 3 at doses of 5, 10, and 20 mg/kg of CAP256V2LS, respectively; arms 4 and 5 at doses of 20 and 30 mg/kg of VRC07-523LS, respectively. Step two will evaluate the safety and PK profile of a combination of the two bNAbs administered SC at fixed doses within 96 h of birth. Step three will evaluate the safety and PK profile of the two bNAbs administered SC in combination at fixed doses, after 3 months. Arms 1 and 6 will follow sequential recruitment, whereas randomization will occur sequentially between arms (a) 2 & 4 and (b) 3 & 5. Before each randomization, a safety pause will allow review of safety data of the preceding arms. Discussion The results of this trial will guide further studies on bNAbs to prevent breast milk transmission of HIV. Protocol version Version 4.0 dated 15 March 2024. Trial registration Pan African Clinical Trial Registry (PACTR): PACTR202205715278722, 21 April 2022; South African National Clinical Trial Registry (SANCTR): DOH-27–062022-6058. …

The journey from phenotypic observation to causal genetic mechanism is a long and challenging road. For pathogens like Mycobacterium tuberculosis (Mtb), which causes tuberculosis (TB), host–pathogen coevolution has spanned millennia, costing millions of human lives. Mammalian models can systematically recapitulate host genetic variation, producing a spectrum of disease outcomes. Leveraging genome sequences and deep phenotyping data from infected mouse genetic reference populations (GRPs), quantitative trait locus (QTL) mapping approaches have successfully identified host genomic regions associated with TB phenotypes. Here, we review the ongoing optimization of QTL mapping study design alongside advances in mouse GRPs. These next-generation resources and approaches have enabled identification of novel host–pathogen interactions governing one of the most prevalent infectious diseases in the world today.

Tropical Medicine &International Health, EarlyView.

Publication date: Available online 20 July 2024 Source: Infectious Disease Modelling Author(s): Vasiliki Bitsouni, Nikolaos Gialelis, Vasilis Tsilidis …

Abstract Background Malaria contributes substantially to the persistent burden of child deaths in sub-Saharan Africa. Accurate and comprehensive malaria mortality data are crucial to monitor the progress in reducing malaria incidence and mortality. Verbal Autopsy (VA) ascertains the cause of death despite its limitations leading to misclassification errors. Minimally Invasive Tissue Sampling (MITS) is being conducted in some settings as an alternative to Complete Diagnostic Autopsy (CDA). The present study examines the validity of malaria-related deaths comparing VA diagnoses with those obtained through MITS and/or CDA. Methods A comprehensive literature search for original studies in English language using Ovid MEDLINE, Ovid Embase, CINAHL via EBSCO, Scopus, The Cochrane Library via Wiley, Google Scholar and searching the MITS Surveillance Alliance papers was carried out. The reference period was January 1, 1990–March 31, 2024. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were adopted. Results Among 71 articles identified in the databases, 21 matched the eligibility criteria. Qualitative syntheses showed that malaria Cause Specific Mortality Fractions (CSMFs) across various studies ranged from 2 to 31%. Plasmodium falciparum was mostly responsible for these deaths and the most common complications were anaemia and cerebral malaria. The sensitivity and specificity of the VA validation studies ranged from 18.4% to 33% and from 86.6% to 97%, respectively, and there was a high level of misclassification for both InSilico and Expert Algorithm VA for malaria compared to MITS. The overall concordance rates between MITS and CDA diagnoses ranged from 68 to 90%, with the highest concordance seen in deaths due to infectious diseases and malignant tumours. Clinical data increased diagnostic coincidence between MITS blind to clinical data and the gold standard CDA by 11%. Conclusions The comprehensive review finds that MITS demonstrated better accuracy compared to VA in diagnosing malaria-attributed deaths, particularly in hospital settings. The high specificity of malaria in VA diagnosis suggests population-based estimates of the proportion of deaths due to malaria are broadly plausible. …

Abstract Background Recommended since 2012 by the World Health Organization (WHO), seasonal malaria chemoprevention (SMC) is a community-based intervention to prevent malaria in children in African regions where malaria transmission follows a seasonal pattern. Following the publication of consolidated WHO guidelines for malaria, SMC is expected to reach more children in new geographies in future years. Though SMC has been shown to reduce malaria-related morbidity and mortality, there is potential for quality improvement of the intervention implementation. Assisted by ten quality standards from a framework developed by Malaria Consortium, this paper aims to better understand the quality of SMC implementation and identify potential barriers to quality delivery of SMC. Methods A qualitative thematic analysis on data collected after the annual SMC rounds implemented in Burkina Faso and Chad in 2019 was conducted. Sixteen focus group discussions conducted with caregivers and community distributors were analysed. Three selected quality standards for SMC delivery; planning and enumeration; community engagement; and administration of SMC medicines provided overarching quality themes under which subthemes were identified. Results Eight subthemes relating to the three quality standards were identified. Although SMC was well accepted by communities in both settings, common barriers to the quality delivery of SMC were identified including difficulty ensuring adherence to the SMC administration protocol; difficulties reaching mobile populations; concerns around adverse drug reactions; rumours, and concerns about SMC safety; and community distributors’ working conditions. Context-specific barriers included: the suboptimal timeliness of the SMC round in Burkina Faso, and the lack of involvement of female caregivers in mobilization activities in Chad. Conclusion In the context of increased adoption of SMC, this paper provides relevant insights and recommendations for the improved implementation of SMC programmes. These include the integration of strategies addressing communities’ concerns around adverse drug reactions, gender-specific mobilization strategies, and attention to community distributors’ working conditions. It also highlights the importance and utility of further, robust research on the quality of SMC delivery. …

Abstract Background Pfhrp2 and pfhrp3 deletions are threatening Plasmodium falciparum malaria diagnosis by rapid diagnostic tests (RDT) due to false negatives. This study assesses the changes in the frequencies of pfhrp2 and pfhrp3 deletions (pfhrp2Del and pfhrp3Del, respectively) and the genes in their flaking regions, before and after RDT introduction in Equatorial Guinea. Methods A total of 566 P. falciparum samples were genotyped to assess the presence of pfhrp2 and pfhrp3 deletions and their flanking genes. The specimens were collected 18 years apart from two provinces of Equatorial Guinea, North Bioko (Insular Region) and Litoral Province (Continental Region). Orthologs of pfhrp2 and pfhrp3 genes from other closely related species were used to compare sequencing data to assess pfhrp2 and pfhrp3 evolution. Additionally, population structure was studied using seven neutral microsatellites. Results This study found that pfhrp2Del and pfhrp3Del were present before the introduction of RDT; however, they increased in frequency after their use, reaching more than 15%. Haplotype networks suggested that pfhrp2Del and pfhrp3Del emerged multiple times. Exon 2 of pfhrp2 and pfhrp3 genes had high variability, but there were no significant changes in amino acid sequences. Conclusions Baseline sampling before deploying interventions provides a valuable context to interpret changes in genetic markers linked to their efficacy, such as the dynamic of deletions affecting RDT efficacy. …

Abstract Objectives Advancements in Artificial Intelligence(AI) have made platforms like ChatGPT increasingly relevant in medicine. This study assesses ChatGPT’s utility in addressing bacterial infection-related questions and antibiogram-based clinical cases. Methods This study involved a collaborative effort involving infectious disease (ID) specialists and residents. A group of experts formulated six true/false, six open-ended questions, and six clinical cases with antibiograms for four types of infections (endocarditis, pneumonia, intra-abdominal infections, and bloodstream infection) for a total of 96 questions. The questions were submitted to four senior residents and four specialists in ID and inputted into ChatGPT-4 and a trained version of ChatGPT-4. A total of 720 responses were obtained and reviewed by a blinded panel of experts in antibiotic treatments. They evaluated the responses for accuracy and completeness, the ability to identify correct resistance mechanisms from antibiograms, and the appropriateness of antibiotics prescriptions. Results No significant difference was noted among the four groups for true/false questions, with approximately 70% correct answers. The trained ChatGPT-4 and ChatGPT-4 offered more accurate and complete answers to the open-ended questions than both the residents and specialists. Regarding the clinical case, we observed a lower accuracy from ChatGPT-4 to recognize the correct resistance mechanism. ChatGPT-4 tended not to prescribe newer antibiotics like cefiderocol or imipenem/cilastatin/relebactam, favoring less recommended options like colistin. Both trained- ChatGPT-4 and ChatGPT-4 recommended longer than necessary treatment periods (p-value = 0.022). Conclusions This study highlights ChatGPT’s capabilities and limitations in medical decision-making, specifically regarding bacterial infections and antibiogram analysis. While ChatGPT demonstrated proficiency in answering theoretical questions, it did not consistently align with expert decisions in clinical case management. Despite these limitations, the potential of ChatGPT as a supportive tool in ID education and preliminary analysis is evident. However, it should not replace expert consultation, especially in complex clinical decision-making. …

Abstract Introduction Non-fermenting Gram-negative bacilli (NFGNB) other than Pseudomonas aeruginosa and Acinetobacter baumannii complex are pathogens of interest due to their ability to cause health-care associated infections and display complex drug resistance phenotypes. However, their clinical and microbiological landscape is still poorly characterized. Methods Observational retrospective study including all hospitalized patients presenting with a positive positive blood culture (BC) episode caused by less common NFGNB over a four-year period (January 2020–December 2023). Clinical-microbiological features and factors associated with mortality were investigated. Results Sixty-six less common NFGNB isolates other than Pseudomonas and Acinetobacter species causing 63 positive BC episodes were recovered from 60 patients. Positive BC episodes were predominantly sustained by Stenotrophomonas maltophilia (49.2%) followed by Achromobacter species (15.9%) that exhibited the most complex resistance phenotype. Positive BC episodes had bloodstream infection criteria in 95.2% of cases (60 out 63), being intravascular device (30.2%) and respiratory tract (19.1%) the main sources of infection. Fourteen-day, 30-day, and in-hospital mortality rates were 6.4%, 9.5%, and 15.9%, respectively. The longer time from admission to the positive BC episode, older age, diabetes, admission due to sepsis, and higher Charlson Comorbidity Index were identified as the main predictors of in-hospital mortality. Conclusions Positive BC episodes sustained by NFGNB other than Pseudomonas and Acinetobacter species were predominantly sustained by Stenotrophomonas maltophilia and Achromobacter species, having bloodstream infection criteria in the vast majority of cases. Factors that have emerged to be associated with mortality highlighted how these species may have more room in prolonged hospitalisation and at the end of life for patients with chronic organ diseases. …

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Antimicrobial Agents and Chemotherapy, Ahead of Print.