Journal of Medical Virology, Volume 96, Issue 3, March 2024.

Journal of Medical Virology, Volume 96, Issue 3, March 2024.

Journal of Medical Virology, Volume 96, Issue 3, March 2024.

Mycobacterium tuberculosis (Mtb) is a major human pathogen, responsible for an estimated 10.6 million cases of active tuberculosis (TB) and 1.3 million deaths worldwide in 2022.[1] Most adult cases of active TB arise from progression of asymptomatic Mtb infection, whose global prevalence has been estimated at 23%.[2] Risk of progression from infection to disease can be significantly reduced by administration of preventive antimicrobial therapy,[3] and global roll-out of this intervention will be needed to achieve the World Health Organization (WHO) target of TB elimination by 2050.

Tuberculosis, caused by the bacterium Mycobacterium tuberculosis, is responsible for an estimated 1.3 million deaths each year, despite effective treatment being available for the past six decades. Progress in the development and point of care rollout of improved vaccines, diagnostics and treatments has been very slow, and TB remains a neglected global health problem. Moreover, access to available WHO recommended TB diagnostics and treatment regimens for all forms of TB remains a major challenge, especially in low- and middle-income countries, where 80% of annual TB case load occurs [1].

The SARS-CoV-2 pandemic necessitated the implementation of specific measures to minimize its impact on global public health. Non-pharmaceutical precautions played a crucial role in preventing the massive spread of SARS-CoV-2.[1] However, it was widely recognized that only widespread and global vaccination could effectively bring the virus under control.[2] The rapid development of various types of vaccines, supported by numerous countries and international organizations, was successfully completed within less than a year, enabling the commencement of widespread vaccination of the world\'s population in December 2020.

In the four years since COVID-19 was declared a global pandemic on March 11, 2020, more than 760 million cases have been reported worldwide leading to a death toll of almost 7 million people [1]. During the first year of the pandemic, while high rates of SARS-CoV-2 infections were reported globally, initial reports suggested that infection rates were significantly lower in sub-Saharan Africa than in other parts of the world [2,3]. Subsequent studies revealed that although seroprevalence was rapidly increasing in sub-Saharan African countries during the start of the pandemic, it was estimated that less than 1% of infections were detected [4].

There is a need to identify biomarkers to predict progression and to diagnose TB disease at an early stage. Following infection with Mtb, only about 10% of individuals progress to TB disease, while the majority mount a protective immune response that clears the infection or controls it in the long term [1]. Those Individuals whose immune system exhibit measurable memory response to Mtb are termed Mtb-immunoreactive. The immune profile of Mtb-immunoreactive individuals, without TB disease, reflects a more protective pattern compared to individuals with TB disease, who have failed to control Mtb growth [2].

Tuberculosis (TB) is an airborne infectious disease caused by Mycobacterium tuberculosis (Mtb). The stages of Mtb infection exist on a continuum, ranging from an eliminated infection to contagious TB disease. Standard diagnostics for determining whether someone has latent, non-infectious TB include the tuberculin skin test (TST) and interferon-γ release assay (IGRA). However, due to the complexity of the Mtb infection and heterogeneity between individuals, there is currently a debate whether it is correct to use IGRA to determine the presence of truly “latent” TB infection (LTBI), i.e., which can reactivate to the contagious form of the disease, as a positive result can be due to memory T cell responses, which may not be indicative of current infection [1].

Tropical Medicine &International Health, EarlyView.

Abstract Background The duration of the protective effect of TB preventive therapy (TPT) is controversial. Some studies have found that the protective effect of TPT is lost after cessation of therapy among people living with HIV in settings with very high tuberculosis incidence, but others have found long-term protection in low incidence settings.Methods We estimated the incidence rate (IR) of new tuberculosis disease (TB) for up to 12 years after randomization to four months of rifampin or nine months of isoniazid, among 991 Brazilian participants in a TPT trial in the state of Rio de Janeiro, with incidence 68.6/100,000 population in 2022. Adjusted hazard ratios (aHR) of independent variables for incident TB were calculated.Results Overall TB incidence rate (IR) was 1.7 (1.01; 2.7)/1,000 person years (PY). The TB IR among those who did not complete TPT was higher than in those who completed [2.9/1000 PY (95% CI: 1.3; 5.6) versus 1.1/1000 PY (95% CI: 0.4; 2.3), IR ratio (IRR)= 2.7 (95% CI: 1.0; 7.2)]. TB IR was higher within 28 months after randomization [IR: 3.5/1000 PY (1.6; 6.6) PY, compared to 1.1/1000 PY (95% CI: 0.5; 2.1) between 28 and 143 months, IRR= 3.1, 95% CI: 1.2-8.2]. Treatment non-completion was the only variable associated with incident TB [aHR= 3.2 (1.1; 9.7)].Conclusion In a mostly HIV non-infected population, a complete course of TPT conferred long-term protection against tuberculosis.

Abstract Purpose This aimed to identify the factors associated with severe/critical coronavirus disease 2019 (COVID-19) infection in rheumatoid arthritis (RA) patients. Methods Two-hundred RA patients diagnosed according to the American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) classification criteria with proven COVID-19 infection were recruited and categorized according to the world health organization (WHO) COVID-19 severity grading into 2 groups: patients with mild/moderate COVID-19 (n = 164) and patients with severe/critical COVID-19 (n = 36). Comparison between both groups was done to identify the risk factors associated with severe/critical infection. Incidence of RA disease activity flare defined as increase in clinical disease activity index (CDAI) more than 10 points following infection was calculated. Results Multivariate analysis identified history of previous serious infection, age > 60 years, and diabetes as factors positively associated, whereas COVID-19 vaccination was negatively associated with severe/critical infection. Following COVID-19 infection, the number of patients with severe/critical COVID-19 who had high RA disease activity and the incidence of flares was significantly higher in comparison to patients with mild/moderate COVID-19 (P  60 years, diabetes, and history of previous serious infections are risk factors for severe/critical COVID-19, while vaccination has a protective role in RA patients. Infection particularly when severe is associated with risk of disease flare. …

Abstract Purpose This study examined the characteristics, incidence and prognostic factors of the first AIDS-defining condition developed after more than one year of continuous antiretroviral therapy (ART) among people living with HIV (PLHIV). Methods We used data from two multicentre observational cohorts of PLHIV in Germany between 1999 and 2018. Our outcome was the first AIDS-defining event that occurred during follow-up after more than one year of continuous ART. Descriptive analyses at ART initiation, at the time of the AIDS event and of the most frequently observed types of AIDS-defining illnesses were performed. We calculated the incidence rate (IR) per 1000 person-years (PY) and used a bootstrap stepwise selection procedure to identify predictors of the outcome. Results A total of 12,466 PLHIV were included in the analyses. 378 developed the outcome, constituting an overall IR of 5.6 (95% CI 5.1–6.2) AIDS events per 1000 PY. The majority of PLHIV was virally suppressed at the time of the event. Oesophageal candidiasis and wasting syndrome were the most frequently diagnosed AIDS-defining illnesses. We found a low CD4 count at ART initiation, a previous AIDS-defining condition and transmission through intravenous drug use to be meaningful prognostic factors of the outcome. Conclusion The overall rate of AIDS-defining events among PLHIV under long-term ART was low, highlighting the importance of continuous treatment. PLHIV who started ART with indicators of impaired immune functioning were more susceptible to disease progression, suggesting that the public health response should continue to focus on early and sustained treatment for all PLHIV. …

Abstract Purpose Sepsis suspicion by Emergency Medical Services (EMS) is associated with improved patient outcomes. This study assessed sepsis incidence and recognition by EMS and analyzed which of the screening tools recommended by the Surviving Sepsis Campaign best facilitates sepsis prediction. Methods Retrospective cohort study of claims data from health insurances (n = 221,429 EMS cases), and paramedics’ and emergency physicians’ EMS documentation (n = 110,419); analyzed outcomes were: sepsis incidence and case fatality compared to stroke and myocardial infarction, the extent of documentation for screening-relevant variables and sepsis suspicion, tools’ intersections for screening positive in identical EMS cases and their predictive ability for an inpatient sepsis diagnosis. Results Incidence of sepsis (1.6%) was similar to myocardial infarction (2.6%) and stroke (2.7%); however, 30-day case fatality rate was almost threefold higher (31.7% vs. 13.4%; 11.8%). Complete vital sign documentation was achieved in 8.2% of all cases. Paramedics never, emergency physicians rarely (0.1%) documented a sepsis suspicion, respectively septic shock. NEWS2 had the highest sensitivity (73.1%; Specificity:81.6%) compared to qSOFA (23.1%; Sp:96.6%), SIRS (28.2%; Sp:94.3%) and MEWS (48.7%; Sp:88.1%). Depending on the tool, 3.7% to 19.4% of all cases screened positive; only 0.8% in all tools simultaneously. Conclusion Incidence and mortality underline the need for better sepsis awareness, documentation of vital signs and use of screening tools. Guidelines may omit MEWS and SIRS as recommendations for prehospital providers since they were inferior in all accuracy measures. Though no tool performed ideally, NEWS2 qualifies as the best tool to predict the highest proportion of septic patients and to rule out cases that are likely non-septic. …

Abstract Background Infectious etiologies of lower respiratory tract infections (LRTIs) by the conventional microbiology tests (CMTs) can be challenging. Metagenomic next-generation sequencing (mNGS) has great potential in clinical use for its comprehensiveness in identifying pathogens, particularly those difficult-to-culture organisms. Methods We analyzed a total of 205 clinical samples from 201 patients with suspected LRTIs using mNGS in parallel with CMTs. mNGS results were used to guide treatment adjustments for patients who had negative CMT results. The efficacy of treatment was subsequently evaluated in these patients. Results mNGS-detected microorganisms in 91.7% (188/205) of the clinical samples, whereas CMTs demonstrated a lower detection rate, identifying microorganisms in only 37.6% (77/205) of samples. Compared to CMT results, mNGS exhibited a detection sensitivity of 93.5% and 95.4% in all 205 clinical samples and 180 bronchoalveolar lavage fluid (BALF) samples, respectively. A total of 114 patients (114/201; 56.7%) showed negative CMT results, among which 92 received treatment adjustments guided by their positive mNGS results. Notably, 67.4% (62/92) of patients demonstrated effective treatment, while 25% (23/92) experienced a stabilized condition. Subgroup analysis of cancer patients revealed that 41.9% (13/31) exhibited an effective response to treatment, and 35.5% (11/31) maintained a stable condition following medication adjustments guided by mNGS. Conclusion mNGS demonstrated great potential in identifying microorganisms of clinical significance in LRTIs. The rapid turnaround time and reduced susceptibility to the impact of antimicrobial administration make mNGS a valuable supplementary tool for diagnosis and treatment decision-making for suspected LRTIs in clinical practice. …

Abstract Klebsiella pneumoniae is the leading cause of neonatal sepsis and is increasingly difficult to treat due to antibiotic resistance. Vaccination represents a tractable approach to combat this resistant bacterium; however, there is currently not a licensed vaccine. Surface polysaccharides, including O-antigens of lipopolysaccharide, have long been attractive candidates for vaccine inclusion. Herein we describe the generation of a bioconjugate vaccine targeting seven predominant O-antigen subtypes in K. pneumoniae. Each bioconjugate was immunogenic in isolation, with limited cross-reactivity among subtypes. Vaccine-induced antibodies demonstrated varying degrees of binding to a wide variety of K. pneumoniae strains. Further, sera from vaccinated mice induced complement-mediated killing of many of these strains. Finally, increased capsule interfered with O-antigen antibodies’ ability to bind and mediate killing of some K. pneumoniae strains. Taken together, these data indicate that this novel heptavalent O-antigen bioconjugate vaccine formulation exhibits limited efficacy against some, but not all, K. pneumoniae isolates.

Abstract Background Atypical/Nor98 scrapie (AS) is an idiopathic infectious prion disease affecting sheep and goats. Recent findings suggest that zoonotic prions from bovine spongiform encephalopathy (C-BSE) may co-propagate with atypical/Nor98 prions in AS sheep brains. Investigating the risk AS poses to humans is crucial.Methods To assess the risk of sheep/goat-to-human transmission of AS, we serially inoculated brain tissue from field and laboratory isolates into transgenic mice overexpressing human prion protein (Met129 allele). We studied clinical outcomes as well as presence of prions in brains and spleens.Results No transmission occurred on the primary passage, with no clinical disease or pathological prion protein in brains and spleens. On subsequent passages, one isolate gradually adapted, manifesting as prions with a phenotype resembling those causing MM1-type sporadic Creutzfeldt-Jakob disease in humans. However, further characterization using in vivo and in vitro techniques confirmed both prion agents as different strains, revealing a case of phenotypic convergence. Importantly, no C-BSE prions emerged in these mice, especially in the spleen, which is more permissive than the brain for C-BSE cross-species transmission.Conclusions The results obtained suggest a low the zoonotic for AS. Rare adaptation may allow the emergence of prions phenotypically resembling those spontaneously forming in humans.

HCVHIVdirect acting antiviralsnon-invasive liver fibrosis markerstransient elastometryTIMP-1…

Abstract Background Chlamydia trachomatis (CT) testing and treatment strategies have not decreased infection rates, justifying need for a CT vaccine. A murine study showed that a vaccine consisting of MOMP and 4 polymorphic membrane proteins (Pmps E, F, G, H) elicited protective immunity; studies on human cellular immune responses to Pmps are sparse.Methods Interferon gamma (IFN-γ) responses to these 5 CT proteins were measured by ELISPOT in PBMCs from women returning for treatment of a positive CT screening test. Responses were compared in those with spontaneous CT clearance vs. persisting infection at baseline and no reinfection vs. reinfection at a 3-month follow-up visit.Results IFN-γ response to one or more proteins was detected in 39% at baseline and 51.5% at follow-up; PmpE and MOMP most often elicited positive responses. IFN-γ responses to MOMP were detected less often at follow-up vs. baseline in women with reinfection, but were maintained in those without reinfection. Women with spontaneous clearance had a higher magnitude of IFN-γ response to PmpE and MOMP.Conclusions IFN-γ responses to these 5 CT vaccine candidate proteins were heterogenous and primarily directed against MOMP and PmpE. Spontaneous clearance of infection and absence of reinfection may be clinical correlates of protection.

Abstract Objective To evaluate the efficacy of urokinase (UK) treatment for tuberculous pleural effusion (TPE). Methods We searched Chinese biomedical literature database, WanFang data, CNKI, PubMed, EMbase, Web of Science and The Cochrane Library for the randomized controlled trials (RCTs) of urokinase treatment for tuberculous pleurisy from January 2000 to February 2023. Pleural tuberculosis, urokinase and randomized controlled trial were used as keywords. The eligible studies were meta-analyzed by using Revman 5.4.1: risk of bias was assessed, mean difference (MD) and 95% CI were used for continuous variables, pooled studies were conducted using random-effects or fixed-effects models, forest plots were drawn to analyze efficacy, and funnel plots were drawn to discuss publication bias. Results Twenty-nine RCTs were included. The meta-analyzed results showed that, on the basis of routine anti-tuberculosis, comparison between the treatment group treated with urokinase and the control group treated with antituberculosis alone, the time of pleural effusion absorption [MD-5.82, 95%CI (− 7.77, − 3.87); P

Abstract Background While there is a high burden of methicillin-resistant Staphylococcus aureus (MRSA) infections among pediatric patients, studies on the molecular epidemiology of MRSA infections in Korean children since the 2010s are lacking. This study aimed to investigate the molecular genotypes and clinical characteristics of MRSA isolates from children with MRSA bacteremia at Asan Medical Center Children’s Hospital from 2016 to 2021. Methods Clinical data were retrospectively reviewed, and the molecular types of MRSA were determined using multilocus sequence typing (MLST) and Staphylococcal cassette chromosome mec (SCCmec) typing. Results The overall methicillin resistance rate of S. aureus bacteremia was 44.8% (77/172); 49.5% in the period 2016–2018 (period 1) and 37.3% in the period 2019–2021 (period 2) (P = 0.116). Community-acquired infections accounted for only 3.9% of cases. The predominant ST group was ST72 group (67.6%), followed by ST5 group (18.9%) and ST1 group (5.4%). The proportion of ST5 was significantly lower in period 2 compared to period 1 (P = 0.02). Compared to the ST5 and ST1 groups, the ST72 group exhibited lower overall antibiotic resistance and multidrug-resistant (MDR) rates (12.0% [6/50] in ST72 group vs. 100.0% [14/14] in ST5 group vs. 50.0% [2/4] in ST1 group; P 

Abstract Background Gabon still bears significant malaria burden despite numerous efforts. To reduce this burden, policy-makers need strategies to design effective interventions. Besides, malaria distribution is well known to be related to the meteorological conditions. In Gabon, there is limited knowledge of the spatio-temporal effect or the environmental factors on this distribution. This study aimed to investigate on the spatio-temporal effects and environmental factors on the distribution of malaria prevalence among children 2–10 years of age in Gabon. Methods The study used cross-sectional data from the Demographic Health Survey (DHS) carried out in 2000, 2005, 2010, and 2015. The malaria prevalence was obtained by considering the weighting scheme and using the space–time smoothing model. Spatial autocorrelation was inferred using the Moran’s I index, and hotspots were identified with the local statistic Getis-Ord General Gi. For the effect of covariates on the prevalence, several spatial methods implemented in the Integrated Nested Laplace Approximation (INLA) approach using Stochastic Partial Differential Equations (SPDE) were compared. Results The study considered 336 clusters, with 153 (46%) in rural and 183 (54%) in urban areas. The prevalence was highest in the Estuaire province in 2000, reaching 46%. It decreased until 2010, exhibiting strong spatial correlation (P 

Publication date: Available online 23 February 2024 Source: Infectious Disease Modelling Author(s): Marta C. Nunes, Edward Thommes, Holger Fröhlich, Antoine Flahault, Julien Arino, Marc Baguelin, Matthew Biggerstaff, Gaston Bizel-Bizellot, Rebecca Borchering, Giacomo Cacciapaglia, Simon Cauchemez, Alex Barbier––Chebbah, Carsten Claussen, Christine Choirat, Monica Cojocaru, Catherine Commaille-Chapus, Chitin Hon, Jude Kong, Nicolas Lambert, Katharina B. Lauer …

Globally, the isolation of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) harbouring both the Panton–Valentine leucocidin (PVL) and toxic shock syndrome toxin 1 (TSST-1) genes is rare. However, we encountered an outbreak of the ST22-PT clone exhibiting this phenotype in Japan. Notably, the TSST-1 gene was duplicated in most of the strains. This study aimed to elucidate the mechanisms underlying this gene duplication.

Abstract Chronic immune activation from persistent malaria infections can induce immunophenotypic changes associated with T cell exhaustion. However, associations between T and B cells during chronic exposure remain undefined. We analyzed peripheral blood mononuclear cells from malaria-exposed pregnant women from Papua New Guinea and Spanish malaria-naïve individuals using flow cytometry to profile T cell exhaustion markers phenotypically. T cell lineage (CD3, CD4, CD8), inhibitory (PD1, TIM3, LAG3, CTLA4, 2B4) and senescence (CD28-) markers were assessed. Dimensionality reduction methods revealed increased PD1, TIM3, and LAG3 expression in malaria-exposed individuals. Manual gating confirmed significantly higher frequencies of PD1+CD4+ and CD4+, CD8+, and double-negative (DN) T cells expressing TIM3 in malaria-exposed individuals. Increased frequencies of T cells co-expressing multiple markers were also found in malaria-exposed individuals. T cell data were analyzed with B cell populations from a previous study where we reported an alteration of B cell subsets, including increased frequencies of atypical memory B cells (aMBC) and reduction in marginal zone-like (MZ-like) B cells during malaria exposure. Frequencies of aMBC subsets and MZ-like B cells expressing CD95+ had significant positive correlations with CD4+ and DN T cells expressing CD28+PD1+TIM3+ and CD28+TIM3+2B4+CD8+ T cells. Frequencies of aMBC, known to associate with malaria anemia, were inversely correlated with hemoglobin levels in malaria-exposed women. Similarly, inverse correlations with hemoglobin levels were found for TIM3+CD8+ and CD28+PD1+TIM3+CD4+ T cells. Our findings provide further insights into the effects of chronic malaria exposure on circulating B and T cell populations, which could impact immunity and responses to vaccination.

ObjectivesEnsuring that children receive timely vaccinations is paramount for preventing infectious diseases, and parental attitude plays a pivotal role in this process. This study addresses this gap in the existing literature by examining parental attitudes towards vaccinating their children. DesignA cross-sectional study. MethodsAn online survey including parents’ sociodemographic characteristics, risk perception and attitudes towards child vaccination towards COVID-19 was conducted. The modified large-scale group decision-making approach for practicality and binary logistic regression was used to identify the predictors influencing parents’ decision-making. ResultsOf the 1292 parents participated, 957 (74.1%) were willing to vaccinate their children, while 335 (25.9%) refused the vaccination. The study indicated that age, parental anxiety regarding child vaccination, concerns about the child’s susceptibility to the disease, opinions towards vaccination benefits versus disadvantages, place of residence, average family income and children’s health were significant predictors (p

IntroductionPsoriasis, atopic dermatitis and contact dermatitis are common chronic inflammatory skin diseases that have a significant impact on individuals and society. Methods and analysisThe Copenhagen Translational Skin Immunology Biobank and Research Programme (BIOSKIN) is a translational biobank and research study that aims to prospectively collect high-quality biological samples and clinical data from 3000 patients with psoriasis, atopic dermatitis and contact dermatitis over a minimum period of 5 years. The longitudinal open design allows participants to enter and leave the study at different time points depending on their disease and treatment course. At every visit, the investigator collects biological samples, conducts interviews and assembles self-reported questionnaires on disease-specific and general health-related information. Clinical examination and biological sampling will be conducted at enrolment, during and after disease flare, before and after initiation of new treatment and at least once per year. The clinical examination includes dermatological verification of diagnosis, evaluation of disease severity and detailed information on phenotype. The biological samples include blood and when accessible and relevant, skin biopsies, tape strips and skin swabs. The data collected will undergo rigorous statistical analysis using appropriate analytical methods. As of December 2023, 825 patients have been enrolled in the study. Ethics and disseminationThe study is approved by the Scientific Ethical Committee of the Capital Region (H-21032986) and the Danish Data Protection Agency. Results will be published in peer-reviewed scientific journals and presented at national and international conferences. …

ObjectivesTo evaluate the diagnostic performance of urine HIV antibody rapid test kits in screening diverse populations and to analyse subjects’ willingness regarding reagent types, purchase channels, acceptable prices, and self-testing. DesignsDiagnostic accuracy studies ParticipantsA total of 2606 valid and eligible samples were collected in the study, including 202 samples from female sex workers (FSWs), 304 persons with injection drug use (IDU), 1000 pregnant women (PW), 100 subjects undergoing voluntary HIV counselling and testing (VCT) and 1000 students in higher education schools or colleges (STUs). Subjects should simultaneously meet the following inclusion criteria: (1) being at least 18 years old and in full civil capacity, (2) signing an informed consent form and (3) providing truthful identifying information to ensure that the subjects and their samples are unique. ResultsThe sensitivity, specificity and area under the curve (AUC) of the urine HIV-1 antibody rapid test kits were 92.16%, 99.92% and 0.960 (95% CI: 0.952 to 0.968, p

PurposeThe Canadian Addiction Treatment Centre (CATC) cohort was established during a period of increased provision of opioid agonist treatment (OAT), to study patient outcomes and trends related to the treatment of opioid use disorder (OUD) in Canada. The CATC cohort’s strengths lie in its unique physician network, shared care model and event-level data, making it valuable for validation and integration studies. The CATC cohort is a valuable resource for examining OAT outcomes, providing insights into substance use trends and the impact of service-level factors. ParticipantsThe CATC cohort comprises 32 246 people who received OAT prescriptions between April 2014 and February 2021, with ongoing tri-annual updates planned until 2027. The cohort includes data from all CATC clinics’ electronic medical records and includes demographic information and OAT clinical indicators. Findings to dateThis cohort profile describes the demographic and clinical characteristics of patients being treated in a large OAT physician network. As well, we report the longitudinal OAT retention by treatment type during a time of increasing exposure to a contaminated dangerous drug supply. Notable findings also include retention differences between methadone (32% of patients at 1 year) and buprenorphine (20% at 1 year). Previously published research from this cohort indicated that patient-level factors associated with retention include geographic location, concurrent substance use and prior treatment attempts. Service-level factors such as telemedicine delivery and frequency of urine drug screenings also influence retention. Additionally, the cohort identified rising OAT participation and a substantial increase in fentanyl use during the COVID-19 pandemic. Future plansFuture research objectives are the longitudinal evaluation of retention and flexible modelling techniques that account for the changes as patients are treated with OAT. Furthermore, future research aims are the use of conditional models, and linkage with provincial-level administrative datasets. …

Volume 13, Issue 1, December 2024 .

Volume 13, Issue 1, December 2024 .

Tuberculosis infection (TBI) comprises a spectrum of asymptomatic Mycobacterium tuberculosis (Mtb) infection states, with varying risk of developing to active tuberculosis disease (TB) [1] that reflects underlying heterogeneity of the dynamic balance between pathogen and host. Reliable identification of subgroups at greatest risk for targeted TB preventive treatment (TPT) is a critical component of the global TB prevention strategy [2].

Abstract Background The incidence of Antimicrobial Resistance (AMR) in uropathogens varies between countries and over time. We aim to study the patterns and potential predictors of AMR among patients with UTIs admitted to the Urology Department at Alexandria University Hospital. Methods An observational retrospective record-based study was conducted on all patients admitted to the Urology department from October 2018 to October 2020. Data collected from patients’ records included: demographic data, diagnosis on admission, history of chronic diseases, duration of hospital stay, insertion of a urinary catheter, duration of the catheter in days, history of the use of antibiotics in the previous three months, and history of urinary tract operations. If UTI was documented, we abstracted data about urine culture, use of antibiotics, results of urine cultures, type of organism isolated, and sensitivity to antibiotics. We conducted a multivariable logistic regression model. We performed Classification and Regression Tree Analysis (CART) for predicting risk factors associated with drug resistance among patients with UTI. Data were analyzed using SPSS statistical package, Version 28.0, and R software (2022). Results This study encompassed 469 patients with UTIs. The most commonly isolated bacterium was Escherichia coli, followed by Klebsiella pneumoniae. Multidrug resistance (MDR) was found in 67.7% (149/220) of patients with hospital-acquired UTIs and in 49.4% (83/168) of patients with community-acquired UTIs. Risk factors independently associated with antimicrobial resistance according to logistic regression analysis were the use of antibiotics within three months (AOR = 5.2, 95% CI 2.19–12.31), hospital-acquired UTI (AOR = 5.7, 95% CI 3.06–10.76), diabetes mellitus (AOR = 3.8, 95% CI 1.24–11.84), age over 60 years (AOR = 2.9, 95% CI 1.27–6.72), and recurrent UTI (AOR = 2.6, 95% CI 1.08–6.20). Classification and regression tree (CART) analysis revealed that antibiotic use in the previous three months was the most significant predictor for developing drug resistance. Conclusion The study concluded a high level of antimicrobial resistance as well as significant MDR predictors among hospitalized patients with UTIs. It is vital to assess resistance patterns in our hospitals frequently to improve rational antibiotic treatment as well as to sustain antimicrobial stewardship programs and a rational strategy in the use of antibiotics. Empirical therapy for UTI treatment should be tailored to the potential pathogens’ susceptibility to ensure optimal treatment. Strategic antibiotic use is essential to prevent further AMR increases. Further research should focus on suggesting new biological systems or designed drugs to combat the resistance of UTI pathogens. …

Abstract Background The incidence of Antimicrobial Resistance (AMR) in uropathogens varies between countries and over time. We aim to study the patterns and potential predictors of AMR among patients with UTIs admitted to the Urology Department at Alexandria University Hospital. Methods An observational retrospective record-based study was conducted on all patients admitted to the Urology department from October 2018 to October 2020. Data collected from patients’ records included: demographic data, diagnosis on admission, history of chronic diseases, duration of hospital stay, insertion of a urinary catheter, duration of the catheter in days, history of the use of antibiotics in the previous three months, and history of urinary tract operations. If UTI was documented, we abstracted data about urine culture, use of antibiotics, results of urine cultures, type of organism isolated, and sensitivity to antibiotics. We conducted a multivariable logistic regression model. We performed Classification and Regression Tree Analysis (CART) for predicting risk factors associated with drug resistance among patients with UTI. Data were analyzed using SPSS statistical package, Version 28.0, and R software (2022). Results This study encompassed 469 patients with UTIs. The most commonly isolated bacterium was Escherichia coli, followed by Klebsiella pneumoniae. Multidrug resistance (MDR) was found in 67.7% (149/220) of patients with hospital-acquired UTIs and in 49.4% (83/168) of patients with community-acquired UTIs. Risk factors independently associated with antimicrobial resistance according to logistic regression analysis were the use of antibiotics within three months (AOR = 5.2, 95% CI 2.19–12.31), hospital-acquired UTI (AOR = 5.7, 95% CI 3.06–10.76), diabetes mellitus (AOR = 3.8, 95% CI 1.24–11.84), age over 60 years (AOR = 2.9, 95% CI 1.27–6.72), and recurrent UTI (AOR = 2.6, 95% CI 1.08–6.20). Classification and regression tree (CART) analysis revealed that antibiotic use in the previous three months was the most significant predictor for developing drug resistance. Conclusion The study concluded a high level of antimicrobial resistance as well as significant MDR predictors among hospitalized patients with UTIs. It is vital to assess resistance patterns in our hospitals frequently to improve rational antibiotic treatment as well as to sustain antimicrobial stewardship programs and a rational strategy in the use of antibiotics. Empirical therapy for UTI treatment should be tailored to the potential pathogens’ susceptibility to ensure optimal treatment. Strategic antibiotic use is essential to prevent further AMR increases. Further research should focus on suggesting new biological systems or designed drugs to combat the resistance of UTI pathogens. …

Abstract Background BK polyomavirus (BKPyV) infection after kidney transplantation can lead to serious complications such as BKPyV-associated nephropathy (BKPyVAN) and graft loss. The aim of this study was to investigate the incidence of BKPyVAN after implementing a BKPyV screening program, to map the distribution of BKPyV genotypes and subtypes in the Uppsala-Örebro region and to identify host and viral risk factors for clinically significant events. Methods This single-center prospective cohort study included kidney transplant patients aged ≥ 18 years at the Uppsala University Hospital in Sweden between 2016 and 2018. BKPyV DNA was analyzed in plasma and urine every 3 months until 18 months after transplantation. Also genotype and subtype were determined. A logistic regression model was used to analyze selected risk factors including recipient sex and age, AB0 incompatibility and rejection treatment prior to BKPyVAN or high-level BKPyV DNAemia. Results In total, 205 patients were included. Of these, 151 (73.7%) followed the screening protocol with 6 plasma samples, while184 (89.8%) were sampled at least 5 times. Ten (4.9%) patients developed biopsy confirmed BKPyVAN and 33 (16.1%) patients met criteria for high-level BKPyV DNAemia. Male sex (OR 2.85, p = 0.025) and age (OR 1.03 per year, p = 0.020) were identified as significant risk factors for developing BKPyVAN or high-level BKPyV DNAemia. BKPyVAN was associated with increased viral load at 3 months post transplantation (82,000 vs. 

Abstract Background BK polyomavirus (BKPyV) infection after kidney transplantation can lead to serious complications such as BKPyV-associated nephropathy (BKPyVAN) and graft loss. The aim of this study was to investigate the incidence of BKPyVAN after implementing a BKPyV screening program, to map the distribution of BKPyV genotypes and subtypes in the Uppsala-Örebro region and to identify host and viral risk factors for clinically significant events. Methods This single-center prospective cohort study included kidney transplant patients aged ≥ 18 years at the Uppsala University Hospital in Sweden between 2016 and 2018. BKPyV DNA was analyzed in plasma and urine every 3 months until 18 months after transplantation. Also genotype and subtype were determined. A logistic regression model was used to analyze selected risk factors including recipient sex and age, AB0 incompatibility and rejection treatment prior to BKPyVAN or high-level BKPyV DNAemia. Results In total, 205 patients were included. Of these, 151 (73.7%) followed the screening protocol with 6 plasma samples, while184 (89.8%) were sampled at least 5 times. Ten (4.9%) patients developed biopsy confirmed BKPyVAN and 33 (16.1%) patients met criteria for high-level BKPyV DNAemia. Male sex (OR 2.85, p = 0.025) and age (OR 1.03 per year, p = 0.020) were identified as significant risk factors for developing BKPyVAN or high-level BKPyV DNAemia. BKPyVAN was associated with increased viral load at 3 months post transplantation (82,000 vs. 

Abstract Background BK polyomavirus (BKPyV) infection after kidney transplantation can lead to serious complications such as BKPyV-associated nephropathy (BKPyVAN) and graft loss. The aim of this study was to investigate the incidence of BKPyVAN after implementing a BKPyV screening program, to map the distribution of BKPyV genotypes and subtypes in the Uppsala-Örebro region and to identify host and viral risk factors for clinically significant events. Methods This single-center prospective cohort study included kidney transplant patients aged ≥ 18 years at the Uppsala University Hospital in Sweden between 2016 and 2018. BKPyV DNA was analyzed in plasma and urine every 3 months until 18 months after transplantation. Also genotype and subtype were determined. A logistic regression model was used to analyze selected risk factors including recipient sex and age, AB0 incompatibility and rejection treatment prior to BKPyVAN or high-level BKPyV DNAemia. Results In total, 205 patients were included. Of these, 151 (73.7%) followed the screening protocol with 6 plasma samples, while184 (89.8%) were sampled at least 5 times. Ten (4.9%) patients developed biopsy confirmed BKPyVAN and 33 (16.1%) patients met criteria for high-level BKPyV DNAemia. Male sex (OR 2.85, p = 0.025) and age (OR 1.03 per year, p = 0.020) were identified as significant risk factors for developing BKPyVAN or high-level BKPyV DNAemia. BKPyVAN was associated with increased viral load at 3 months post transplantation (82,000 vs. 

Abstract Background Hospital admission outcomes for people living with HIV (PLHIV) in resource-limited settings are understudied. We describe in-hospital mortality and associated clinical-demographic factors among PLHIV admitted at a tertiary-level public hospital in Uganda. Methods We performed a cross-sectional analysis of routinely collected data for PLHIV admitted at Kiruddu National Referral Hospital between March 2020 and March 2023. We estimated the proportion of PLHIV who had died during hospitalization and performed logistic regression modelling to identify predictors of mortality. Results Of the 5,827 hospitalized PLHIV, the median age was 39 years (interquartile range [IQR] 31–49) and 3,293 (56.51%) were female. The median CD4 + cell count was 109 cells/µL (IQR 25–343). At admission, 3,710 (63.67%) were active on antiretroviral therapy (ART); 1,144 (19.63%) had interrupted ART > 3 months and 973 (16.70%) were ART naïve. In-hospital mortality was 26% (1,524) with a median time-to-death of 3 days (IQR 1–7). Factors associated with mortality (with adjusted odds ratios) included ART interruption, 1.33, 95% confidence intervals (CI) 1.13–1.57, p 0.001; CD4 + counts ≤ 200 cells/µL 1.59, 95%CI 1.33–1.91, p 

Abstract Background Hospital admission outcomes for people living with HIV (PLHIV) in resource-limited settings are understudied. We describe in-hospital mortality and associated clinical-demographic factors among PLHIV admitted at a tertiary-level public hospital in Uganda. Methods We performed a cross-sectional analysis of routinely collected data for PLHIV admitted at Kiruddu National Referral Hospital between March 2020 and March 2023. We estimated the proportion of PLHIV who had died during hospitalization and performed logistic regression modelling to identify predictors of mortality. Results Of the 5,827 hospitalized PLHIV, the median age was 39 years (interquartile range [IQR] 31–49) and 3,293 (56.51%) were female. The median CD4 + cell count was 109 cells/µL (IQR 25–343). At admission, 3,710 (63.67%) were active on antiretroviral therapy (ART); 1,144 (19.63%) had interrupted ART > 3 months and 973 (16.70%) were ART naïve. In-hospital mortality was 26% (1,524) with a median time-to-death of 3 days (IQR 1–7). Factors associated with mortality (with adjusted odds ratios) included ART interruption, 1.33, 95% confidence intervals (CI) 1.13–1.57, p 0.001; CD4 + counts ≤ 200 cells/µL 1.59, 95%CI 1.33–1.91, p 

Abstract Background Hospital admission outcomes for people living with HIV (PLHIV) in resource-limited settings are understudied. We describe in-hospital mortality and associated clinical-demographic factors among PLHIV admitted at a tertiary-level public hospital in Uganda. Methods We performed a cross-sectional analysis of routinely collected data for PLHIV admitted at Kiruddu National Referral Hospital between March 2020 and March 2023. We estimated the proportion of PLHIV who had died during hospitalization and performed logistic regression modelling to identify predictors of mortality. Results Of the 5,827 hospitalized PLHIV, the median age was 39 years (interquartile range [IQR] 31–49) and 3,293 (56.51%) were female. The median CD4 + cell count was 109 cells/µL (IQR 25–343). At admission, 3,710 (63.67%) were active on antiretroviral therapy (ART); 1,144 (19.63%) had interrupted ART > 3 months and 973 (16.70%) were ART naïve. In-hospital mortality was 26% (1,524) with a median time-to-death of 3 days (IQR 1–7). Factors associated with mortality (with adjusted odds ratios) included ART interruption, 1.33, 95% confidence intervals (CI) 1.13–1.57, p 0.001; CD4 + counts ≤ 200 cells/µL 1.59, 95%CI 1.33–1.91, p 

Abstract Objective This study aimed to investigate the clinical characteristics of severe fever with thrombocytopenia syndrome complicated by viral myocarditis (SFTS-VM) and analyze relevant influencing factors. Methods Retrospective analysis was conducted on clinical data from 79 SFTS-VM patients, categorized into common (SFTS-CVM, n = 40) and severe groups (SFTS-SVM, n = 39). Clinical manifestations, laboratory results, cardiac ultrasonography, and electrocardiogram features were analyzed. Univariate and multivariate analyses identified significant indicators, which were further assessed using ROC curves to predict SFTS-SVM. Results SFTS-SVM group exhibited higher rates of hypotension, shock, abdominal pain, cough with sputum, and consciousness disorders compared to SFTS-CVM group. Laboratory findings showed elevated platelet count, ALT, AST, amylase, lipase, LDH, D-dimer, procalcitonin, TNI, and NT-proBNP in SFTS-SVM. Abnormal electrocardiograms, especially atrial fibrillation, were more prevalent in SFTS-SVM (P  978.5U/L) and NT-proBNP (> 857.5pg/ml)) indicated increased likelihood of SFTS progression into SVM. Conclusion Elevated LDH, NT-proBNP, and consciousness disorders independently correlate with SFTS-SVM. LDH and NT-proBNP can aid in early identification of SFTS-SVM development when above specified thresholds. …

Abstract Objective This study aimed to investigate the clinical characteristics of severe fever with thrombocytopenia syndrome complicated by viral myocarditis (SFTS-VM) and analyze relevant influencing factors. Methods Retrospective analysis was conducted on clinical data from 79 SFTS-VM patients, categorized into common (SFTS-CVM, n = 40) and severe groups (SFTS-SVM, n = 39). Clinical manifestations, laboratory results, cardiac ultrasonography, and electrocardiogram features were analyzed. Univariate and multivariate analyses identified significant indicators, which were further assessed using ROC curves to predict SFTS-SVM. Results SFTS-SVM group exhibited higher rates of hypotension, shock, abdominal pain, cough with sputum, and consciousness disorders compared to SFTS-CVM group. Laboratory findings showed elevated platelet count, ALT, AST, amylase, lipase, LDH, D-dimer, procalcitonin, TNI, and NT-proBNP in SFTS-SVM. Abnormal electrocardiograms, especially atrial fibrillation, were more prevalent in SFTS-SVM (P  978.5U/L) and NT-proBNP (> 857.5pg/ml)) indicated increased likelihood of SFTS progression into SVM. Conclusion Elevated LDH, NT-proBNP, and consciousness disorders independently correlate with SFTS-SVM. LDH and NT-proBNP can aid in early identification of SFTS-SVM development when above specified thresholds. …

Abstract Objective This study aimed to investigate the clinical characteristics of severe fever with thrombocytopenia syndrome complicated by viral myocarditis (SFTS-VM) and analyze relevant influencing factors. Methods Retrospective analysis was conducted on clinical data from 79 SFTS-VM patients, categorized into common (SFTS-CVM, n = 40) and severe groups (SFTS-SVM, n = 39). Clinical manifestations, laboratory results, cardiac ultrasonography, and electrocardiogram features were analyzed. Univariate and multivariate analyses identified significant indicators, which were further assessed using ROC curves to predict SFTS-SVM. Results SFTS-SVM group exhibited higher rates of hypotension, shock, abdominal pain, cough with sputum, and consciousness disorders compared to SFTS-CVM group. Laboratory findings showed elevated platelet count, ALT, AST, amylase, lipase, LDH, D-dimer, procalcitonin, TNI, and NT-proBNP in SFTS-SVM. Abnormal electrocardiograms, especially atrial fibrillation, were more prevalent in SFTS-SVM (P  978.5U/L) and NT-proBNP (> 857.5pg/ml)) indicated increased likelihood of SFTS progression into SVM. Conclusion Elevated LDH, NT-proBNP, and consciousness disorders independently correlate with SFTS-SVM. LDH and NT-proBNP can aid in early identification of SFTS-SVM development when above specified thresholds. …