Chronic Infection Research Articles

Recommendations for Research to Develop a Patient‐Centered Clinical Follow‐Up Protocol for Oral Epithelial Dysplasia

ABSTRACTOral epithelial dysplasia (OED) is the primary histological marker for assessing the progression of oral potentially malignant disorders (OPMDs) to cancer. Despite challenges in grading and low inter‐pathologist reproducibility, OED severity remains the key predictor of malignant transformation. However, globally accepted guidelines for OED monitoring are lacking, despite calls for individualized management based on host and lesion characteristics. The proposed research protocol involves acquiring high‐quality intraoral images, assessing oral hygiene and periodontal status, eliminating chronic mechanical irritation and Candida infections, and applying adjunctive diagnostic methods like toluidine blue staining, optical evaluation, and brush cytology. Tailored follow‐up regimens based on individual risk assessments are emphasized, with frequent monitoring for high‐grade dysplasia or patients at higher risk of progression. Therefore, effective OED management should consider the patient's immune status, dietary habits, and oral microbiota, aiming to develop personalized treatment strategies that optimize patient‐centered care.

TET2 regulates early and late transitions in exhausted CD8+ T cell differentiation and limits CAR T cell function.

CD8+ T cell exhaustion hampers control of cancer and chronic infections and limits chimeric antigen receptor (CAR) T cell efficacy. Targeting TET2 in CAR T cells provides therapeutic benefit; however, TET2's role in exhausted T cell (TEX) development is unclear. In chronic lymphocytic choriomeningitis virus (LCMV) infection, TET2 drove conversion from stem cell-like TEX progenitors toward terminally differentiated and effector (TEFF)-like TEX. TET2 also enforced a terminally differentiated state in the early bifurcation between TEFF and TEX, indicating broad roles for TET2 in acquisition of effector biology. To exploit the therapeutic potential of TET2, we developed clinically actionable TET2-targeted CAR T cells by disrupting TET2 via knock-in of a safety switch alongside CAR knock-in at the TRAC locus. TET2-targeted CAR T cells exhibited restrained terminal exhaustion in vitro and enhanced antitumor responses in vivo. Thus, TET2 regulates fate transitions in TEX differentiation and can be targeted with a safety mechanism in CAR T cells for improved tumor control.

A case of penicillin-resistant group B Streptococcus isolated from a patient in the UK.

In England, group B streptococci (GBS; Streptococcus agalactiae) are considered universally susceptible to penicillin. Reports from Africa, Asia, North America and a few European countries have described GBS isolates with penicillin MICs above the epidemiological cut-off (0.125 mg/L). Our aim was to characterize a penicillin-resistant GBS (PRGBS) isolate recovered in 2016 from a patient treated with long-term antimicrobials in the UK. Antibiotic susceptibility of a referred isolate from a discharging sinus overlying a chronic prosthetic joint infection was determined using gradient strip testing for seven antibiotics. Illumina short read sequencing was carried out using a HiSeq 2500 platform to determine MLST, capsular type, to detect mutations in the pbp genes, and to compare the isolate with contemporaneous GBS isolates circulating in the UK. The GBS isolate belonged to capsular type Ia and MLST 144. We observed resistance to penicillin (MIC = 1 mg/L) and tetracycline (32 mg/L) with susceptibility to linezolid (1 mg/L), erythromycin (0.064 mg/L), clindamycin (0.064 mg/L), teicoplanin (0.064 mg/L) and vancomycin (0.25 mg/L). Deduced amino acid sequences revealed substitutions and non-synonymous changes in PBP2x and PBP2b. Genomic analysis of contemporaneous cases (n = 34) from across the UK identified single nucleotide polymorphism (SNP) variation ranged from 153-6596 SNPs. We confirm the first identification of a PRGBS isolate amongst referrals to the UK's national reference laboratory. Substitutions in pbp1a, pbp2a, pbp2x and pbp2b were identified that likely developed in the face of long-term beta-lactam antibiotic use.

Three modes of viral adaption by the heart.

Viruses elicit long-term adaptive responses in the tissues they infect. Understanding viral adaptions in humans is difficult in organs such as the heart, where primary infected material is not routinely collected. In search of asymptomatic infections with accompanying host adaptions, we mined for cardio-pathogenic viruses in the unaligned reads of nearly 1000 human hearts profiled by RNA sequencing. Among virus-positive cases (~20%), we identified three robust adaptions in the host transcriptome related to inflammatory nuclear factor κB (NF-κB) signaling and posttranscriptional regulation by the p38-MK2 pathway. The adaptions are not determined by the infecting virus, and they recur in infections of human or animal hearts and cultured cardiomyocytes. Adaptions switch states when NF-κB or p38-MK2 is perturbed in cells engineered for chronic infection by the cardio-pathogenic virus, coxsackievirus B3. Stratifying viral responses into reversible adaptions adds a targetable systems-level simplification for infections of the heart and perhaps other organs.

Factors Influencing the Success of Non Vascularized Iliac Bone Graft for Mandibular Reconstruction: A Retrospective Study of 26 Cases

Objective: This study aimed to identify the prognostic factors influencing the success of nonvascularized iliac bone grafts for mandibular reconstruction. Methods: This was a retrospective cohort study conducted at a single center, involving 26 patients who underwent segmental mandibulectomy followed by nonvascularized iliac bone grafts between 2012 and 2022 at the Oral and Maxillofacial Surgery Unit, Buddhachinaraj Phitsanulok Hospital. Data were collected by reviewing electronic medical records and radiographic images. Patients who had received vascularized bone grafts or had a history of head and neck irradiation therapy were excluded from the study. The patients were classified into two groups: successful and failed. Success was defined as clinical and radiographic evidence of bone continuity, a graft resorption rate not exceeding 30% of the initial height, and no evidence of chronic infection for at least 6 months. Results: Successful bone grafting was achieved in 19 patients (73.1%). Multivariable risk difference regression analysis identified that the factors influencing graft incorporation were jaw immobilization using reconstruction plates with maxillomandibular fixation for at least 21 days (RD 63.0; 95% CI 33.1, 93.0; p<0.001) and long segmental block graft design (51.3%; 95% CI 16.9, 85.7; p<0.003). A clinically significant factor, although statistically insignificant, was the duration of plate stabilization, which should ideally range from 172 to 232 days prior to plate removal. The sample size constituted a limitation of this study. Conclusions: Nonvascularized bone grafting remains a viable option for reconstructing mandibular segmental defects. The factors influencing graft stability can help improve clinical outcomes.

Epigenetics behind CD8+ T cell activation and exhaustion.

CD8+ T cells play a critical role in specific immunity. In recent years, cell therapy has been emerging rapidly. The specific cytotoxic capabilities of these cells enable them to precisely identify and kill cells presenting specific antigens. This has demonstrated promise in the treatment of autoimmune diseases and cancers, with wide-ranging applications and value. However, in some diseases, such as tumors and chronic infections, T cells may adopt an exhausted phenotype, resulting in a loss of cytotoxicity and limiting their further application. Epigenetics plays a significant role in the differentiation and regulation of gene expression in cells. There is extensive evidence indicating that epigenetic remodeling plays an important role in T cell exhaustion. Therefore, further understanding its role in CD8+ T cell function can provide insights into the programmatic regulation of CD8+ T cells from a genetic perspective and overcome these diseases. We attempted to describe the relationship between the activation, function, and exhaustion mechanisms of CD8+ T cells, as well as epigenetics. This understanding makes it possible for us to address the aforementioned issues.

A Systemic Review on Phytochemicals and Novel Approaches for the Management of Hepatic Cancer

Introduction: Hepatic cancer, an aggressive tumour that often develops along with cirrhosis and chronic liver disease like infections with the hepatitis B and hepatitis C viruses, while nonalcoholic steatohepatitis, is linked to metabolic syndrome or diabetes mellitus. It is the third most prevalent cause of cancer-related mortality globally and ranks fifth in cancer incidence. According to GLOBOCON, the prevalence is expected to rise by 55.0% and the fatalities by 56.4% in the near future. Objective: The present review offered natural plant-based substances and compounds having curative effects on liver cancer, along with novel drug delivery systems and nanocarrier-based therapies. Methods: The literature has been taken from PubMed, Google Scholar, SciFinder, Springer Nature, Bentham Science, PLOS one, or other internet sites. Result: Treatment for heterogeneous malignancy is multidimensional, and care guidelines differ depending on the specialty and location. Several nutritional herbal remedies and their active phytoconstituents may have an abundance of impacts on the management of liver cancer, including preventing the growth and spread of tumor cells, shielding the body from liver carcinogens, boosting the effects of chemotherapy and immunomodulating the body. Conclusion: The treatment of liver cancer involves multidisciplinary and multimodel therapy. The literature is a compilation of extract, compounds, and novel approaches like nanoparticles, microsphere, liposomes, niosomes, phytosomes and microparticles. These approaches not only manage cancer but also boost the immunity of the individuals.

Global vaccination against hepatitis E virus: position paper from the ESGVH-ESCMID.

Hepatitis E Virus (HEV) is a significant global health issue, impacting both low- and middle-income countries (LMICs) and industrialized nations. HEV genotypes 1 and 2, primarily transmitted through contaminated water, are endemic in LMICs, while genotypes 3 and 4 are zoonotically transmitted in industrialized regions. Acute HEV infection poses severe risks, particularly to pregnant women and immunocompromised individuals, while chronic HEV infection leads to serious complications in those with pre-existing liver disease and transplant recipients. The development of an HEV vaccine offers new prevention opportunities, though its availability and integration into global immunization programs remain limited. This position paper was developed by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Viral Hepatitis Study Group (ESGVH) through an extensive review of clinical data, safety profiles, efficacy, and immunogenicity of HEV vaccines. The study group focused particularly on high-risk and special populations, synthesizing global health insights and incorporating recommendations from the Strategic Advisory Group of Experts (SAGE) to formulate strategies for wider HEV vaccination use. The position paper evaluates the efficacy and safety of HEV vaccines in both general and special populations. It identifies key barriers to the integration of HEV vaccines into routine immunization programs, including infrastructure limitations, costs, and vaccine accessibility. The paper also proposes strategies to overcome these challenges and improve vaccine distribution. Furthermore, it addresses ways to enhance public awareness and international cooperation to promote HEV vaccination efforts globally. ESGVH-ESCMID recommends HEV vaccination for high-risk groups, including women of childbearing age, patients with chronic liver diseases, and immunosuppressed individuals. Prioritizing investments in vaccine logistics, integrating diagnostics, and educational outreach can enhance uptake.

Accuracy of International Guidelines in Identifying Normal Liver Histology in Chinese Patients With HBeAg-Positive Chronic HBV Infection.

We evaluated the diagnostic accuracy of various international guideline criteria for identifying HBeAg-positive chronic HBV infection patients with no significant liver disease. A total of 1108 HBeAg-positive CHB patients were retrospectively enrolled. The guidelines assessed included those from the European Association for the Study of the Liver (EASL) 2017, the American Association for the Study of the Liver Disease (AASLD) 2018, the Asian Pacific Association for the Study of the Liver (APASL) 2015 and the Chinese Society of Hepatology (CSH) 2022. The CSH criteria demonstrated a higher proportion of patients with G0-1 and S0-1 (82.9%) compared to the EASL (75.9%), AASLD (75.3%) and APASL groups (58.8%). Additionally, the CSH criteria exhibited a significantly higher predictive value (AUC 0.782, 95% CI 0.754-0.809) than the EASL (AUC 0.765, 95% CI 0.737-0.793), AASLD (AUC 0.749, 95% CI 0.720-0.778) and APASL (AUC 0.720, 95% CI 0.690-0.750) criteria for identifying G0-1 and S0-1. Adding quantitative HBsAg levels (> 104 IU/mL) to the EASL, AASLD and APASL criteria improved diagnostic performance. Consequently, the CSH guideline thresholds showed higher accuracy in identifying Chinese HBeAg-positive patients with no significant liver disease compared to EASL, AASLD and APASL criteria, emphasising the importance of considering quantitative HBsAg in the evaluation of HBeAg-positive chronic HBV infection.

Epidemiological, Clinical and Biological Aspects of Childhood HIV in Libreville

Introduction: Human immunodeficiency virus (HIV) infection is a chronic viral infection characterized by the progressive destruction of CD4 T lymphocytes. Its prevalence in Gabon is estimated 4.1% with approximately 2,500 affected children. This pathology remains a real public health problem on a global scale. The objective of our work was to describe the epidemiological, clinical and biological aspects of HIV-positive children in Libreville. Materials and Methods: This is a retrospective study which involved patients followed in the four major pediatric care centers in Libreville from January 2015 to December 2022. We included all complete medical records of children and adolescents aged 0 to 19 years with positive HIV serology or PCR. Results: The mean age was 10.6 ± 5.1 years. The 10-14 year old group represented 32.3%. The sex ratio was 1.13 male to female. In our study 46.9% were orphans and they were more affected by academic delay (51.9% versus 45.7%). The clinical signs were dominated by fever (40.6%). The main opportunistic infection found was digestive (7.3%) and tuberculosis represented the first co-infection (13.2%). We had 5.2% of patients with acute malnutrition. Conclusion: HIV-AIDS in children remains a public health problem given its socio-economic impact on the population. The cost of follow-up assessments and hospitalizations are among the problems that slow down the regular follow-up of our patients.

Chronic Strongyloides stercoralis infection in Fijian migrants to the UK.

Introduction. Strongyloides stercoralis, the human threadworm, is a parasitic nematode with global distribution, estimated to infect over 600 million people. Chronic infection is often asymptomatic, but hyperinfection and dissemination syndromes can occur in the immunosuppressed with high case fatality rates. Whilst strongyloidiasis is endemic in Fiji, its prevalence in Fijian migrant groups in the UK is unknown.Gap Statement. No previous studies have been conducted on the prevalence of Strongyloides and other gastrointestinal parasites (GIPs) in Fijian migrants to the UK.Aim. We conducted a cross-sectional study of the prevalence of GIPs in a Fijian migrant population.Methodology. Participants completed a questionnaire on residence, travel and clinical symptoms and were asked to provide a serum sample for S. stercoralis IgG ELISA, venous blood samples for eosinophil count and a faecal sample for charcoal culture, multiplex real-time PCR (rtPCR) and microscopy after formalin-ethyl acetate concentration. Sequencing was performed on pooled Strongyloides larvae for nuclear 18S rRNA hyper-variable regions (HVRs) I and IV.Results. A total of 250 participants (94% male) with median (range) age 37 (20-51) years entered the study, 15 (1-24) years since leaving Fiji. S. stercoralis IgG ELISA was positive in 87/248 (35.1 %) and 14/74 (18.9 %) had a GIP detected in faeces. This included 7/74 (9.5 %) with Strongyloides and 5/74 (6.8 %) with hookworms. Dermatological symptoms were more common in those with Strongyloides, and eosinophilia (>0.5×109 cells per litre) was present in 55.6% of those with positive S. stercoralis IgG. rtPCR was the most sensitive faecal diagnostic test for Strongyloides and hookworms in faeces. Sequences of nuclear 18S rRNA for HVRs I and IV confirmed the presence of S. stercoralis.Conclusion. This first cross-sectional study in Fijian migrants found a high rate of chronic infection with GIPs, particularly S. stercoralis. Faecal microscopy was insensitive compared to charcoal culture, rtPCR or serology, demonstrating the importance of specialist parasitological tests when investigating people with a suspected chronic infection. Our study highlights an overlooked burden of strongyloidiasis in the UK and has implications for screening and treatment programmes in Fiji and for migrants from Fiji.

Intracellular ATP concentration is a key regulator of bacterial cell fate.

ATP, most widely known as the primary energy source for numerous cellular processes, also exhibits the characteristics of a biological hydrotrope. The viable but nonculturable (VBNC) and persister states are two prevalent dormant phenotypes employed by bacteria to survive challenging environments, both of which are associated with low metabolic activity. Here, we investigate the intracellular ATP concentration of individual VBNC and persister cells using a sensitive ATP biosensor QUEEN-7μ and reveal that both types of cells possess a lower intracellular ATP concentration than culturable and sensitive cells, although there is a certain overlap in the intracellular ATP concentrations between antibiotic-sensitive cells and persisters. Moreover, we successfully separated VBNC cells from culturable cells using fluorescence-activated cell sorting based on the intracellular ATP concentration threshold of 12.5 µM. Using an enriched VBNC cell population, we confirm that the precipitation of proteins involved in key biological processes promotes VBNC cell formation. Notably, using green light-illuminated proteorhodopsin (PR), we demonstrate that VBNC cells can be effectively resuscitated by elevating their intracellular ATP concentration. These findings highlight the crucial role of intracellular ATP concentration in the regulation of bacterial cell fate and provide new insights into the formation of VBNC and persister cells.IMPORTANCEThe viable but nonculturable (VBNC) and persister states are two dormant phenotypes employed by bacteria to counter stressful conditions and play a crucial role in chronic and recurrent bacterial infections. However, the lack of precise detection methods poses significant threats to public health. Our study reveals lower intracellular ATP concentrations in these states and establishes an ATP threshold for distinguishing VBNC from culturable cells. Remarkably, we revive VBNC cells by elevating their intracellular ATP levels. This echoes recent eukaryotic studies where modulating metabolism impacts outcomes like osteoarthritis treatment and lifespan extension in Caenorhabditis elegans. Our findings underscore the crucial role of intracellular ATP levels in governing bacterial fate, emphasizing ATP manipulation as a potential strategy to steer bacterial behavior.

Abstract 4138350: Candidemia in Patients with Left Ventricular Assist Device-A Case Series

Introduction: Candidemia is rare but associated, have significant morbidity and mortality. Outcomes are not well-characterized in patients with left ventricular assist devices (LVADs). With an increasing number of patients living with LVADs, we sought to characterize risk factors to help optimize outcomes for this high-risk population. Methods: We retrospectively reviewed records of 97 patients who underwent LVAD implant between January 2012 to May 2024 at Indiana University Health, Indianapolis Indiana. Demographic and clinical data were extracted. Candidemia was defined as a positive blood culture with candida species. Result: We identified three patients with candidemia, with an overall attack rate of 3.09%. All patients had a HeartMate III (HM3) at the time of infection. The mean age of patients was 40.3 years (Range 29.0 – 58.0 years) and mean BMI was 35.7 kg/m 2 (Range, 30.0 – 42.0 kg/m 2 ). One patient grew Candida auris and Candida tropicana, the other patient grew Candida auris and the third patient grew Candida globrata. All patients had an automatic implantable cardiac defibrillation, a peripherally inserted central catheter line, and right heart failure. Two patients had driveline infections (one fungal, one bacterial) while one patient developed LVAD endocarditis with a right ventricular outflow tract vegetation. Two patients had persistently positive blood cultures despite treatment with a multi-drug anti-fungal regimen (Flucytosine, Amphotericin B and micafungin) and expired. The third patient initially cleared her blood cultures after treatment with IV micafungin only but was re-admitted with muti-organ failure and expired. Summarily, all patients with candidemia died with a mortality rate of 100%. None of the patients were candidates for heart transplantation. Average survival from the time of diagnosis of candidemia was 5 months (Range 1.0 – 11.0 months). RHF, chronic DL infection and high BMI were associated with candidemia in our series. Conclusion: Candidemia in LVAD patients, while less common than bacterial infections, carry high mortality without cardiac transplantation (100% mortality in our cohort). Its rare occurrence makes it challenging to identify reversible risk factors, leading to poor survival. Multicenter registries are needed to fully elucidate these risk factors and determine effective treatment strategies.

Gender specific differences in urethral swabs: a retrospective single-center analysis.

Sexually transmitted infections (STIs) are globally on the rise yet accurate data regarding infection rates remains scarce. There is the assumption that STIs among women with chronic urinary tract infections (UTIs) have been underestimated. This may arise from the reliance on specialised cultivation or Nucleic Acid Amplification Techniques (NAT) for detection, which are more costly than standard urine culture and are typically only conducted by specialists like urologists. A retrospective, observational, single-centre study using medicals records of patients who received a urethral swab in a German urological practice in the past five years has been conducted. 55% had a STI requiring treatment. People with recurrent UTI had a STI in 35% of the casees. Younger age is associated with the detection of STI. The female gender is significantly associated with a positive swab result. Distinguishing between cystitis and urethritis, particularly in women with recurrent UTIs experiencing dysuria, presents a clinical challenge. The prevalence of asymptomatic infections suggests that the true burden of urethritis, particularly STIs, may be substantially higher in the general population. This underscores the urgency of establishing guidelines for referral and diagnostic evaluation, as delayed or inadequate treatment may contribute to escalating infection rates and antibiotic resistance.

Exploring the Role of Tertiary Lymphoid Structures Using a Mouse Model of Bacteria-Infected Lungs.

Animal models can be helpful tools for deciphering the generation, maintenance, and role of tertiary lymphoid structures (TLS) during infections or tumor development. We describe here the establishment of a persistent lung infection in immune-competent mice by intratracheal instillation of agarose beads containing Pseudomonas aeruginosa or Staphylococcus aureus bacteria. After instillation, animals develop a chronic pulmonary infection, marked by the presence of TLS. This experimental setting allows the study of the function of TLS induced by bacteria encountered in patients with cystic fibrosis (CF) as P. aeruginosa and S. aureus are the two main bacterial strains that infect the bronchi of adult CF patients. Additionally, we describe also how to manipulate the immune response in these infected animals by targeting immune cells involved in TLS function. Overall, this approach makes it possible to explore the role of chronic inflammation in the induction and maintenance of TLS in infected tissues.

Antimicrobial Peptides: A Promising Alternative to Conventional Antimicrobials for Combating Polymicrobial Biofilms.

Polymicrobial biofilms adhere to surfaces and enhance pathogen resistance to conventional treatments, significantly contributing to chronic infections in the respiratory tract, oral cavity, chronic wounds, and on medical devices. This review examines antimicrobial peptides (AMPs) as a promising alternative to traditional antibiotics for treating biofilm-associated infections. AMPs, which can be produced as part of the innate immune response or synthesized therapeutically, have broad-spectrum antimicrobial activity, often disrupting microbial cell membranes and causing cell death. Many specifically target negatively charged bacterial membranes, unlike host cell membranes. Research shows AMPs effectively inhibit and disrupt polymicrobial biofilms and can enhance conventional antibiotics' efficacy. Preclinical and clinical research is advancing, with animal studies and clinical trials showing promise against multidrug-resistant bacteria and fungi. Numerous patents indicate increasing interest in AMPs. However, challenges such as peptide stability, potential cytotoxicity, and high production costs must be addressed. Ongoing research focuses on optimizing AMP structures, enhancing stability, and developing cost-effective production methods. In summary, AMPs offer a novel approach to combating biofilm-associated infections, with their unique mechanisms and synergistic potential with existing antibiotics positioning them as promising candidates for future treatments.

More powerful dysregulation of Helicobacter pylori East Asian-type CagA on intracellular signalings.

Chronic infection by Helicobacter pylori strains expressing cytotoxin-associated gene A (CagA) are the strongest risk factor for gastric cancer. CagA can be classified into East Asian-type and Western-type (CagAE and CagAW), with CagAE being more closely associated with gastric cancer. This study aimed to investigate the impact of CagAE on intracellular signaling pathways to explain its high oncogenicity. Mutant H. pylori strains expressing either CagAE or CagAW were generated by transforming CagAE/W-expression plasmid into CagA-deleted G27 strain (G27ΔCagA). In human gastric epithelial cells (GES-1) infection, CagAE induced more severe cytopathic changes, including higher interleukin-8 (IL-8) secretion, reduced cell viability, more pronounced "hummingbird phenotype" alterations, and increased cell migration and invasion compared to CagAW. Transcriptome analysis revealed that CagAE had a stronger effect on the up-regulation of key intracellular processes, including tumor necrosis factor-ɑ (TNF-ɑ) signal pathway via nuclear factor kappa-B (NF-κB), inflammatory response, interferon-γ (IFN-γ) response, hypoxia, ultraviolet (UV) response, and Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) signaling. A significant upregulation of hypoxia-related genes was a notable feature of CagAE. GES-1 cells infected with CagAE exhibited more severe intracellular hypoxia and higher levels of reactive oxygen species (ROS) than those infected with CagAW. Inhibition of hypoxia-inducible factor-1α (HIF-1α), which blocks hypoxia signaling, mitigated CagAE-induced cell migration, emphasizing the role of hypoxia in mediating CagAE effects. The study provides transcriptome evidence of CagA-associated intracellular regulation during H. pylori infection, demonstrating that CagAE exerts stronger effects on intracellular signaling than CagAW. These findings offer insights into the heightened carcinogenic potential of CagAE in H. pylori-induced gastric cancer.

Advances in the restoration of CFTR in children and pwCF with "mild disease".

Cystic fibrosis (CF) is a progressive genetic disorder, with lung disease being the main cause of morbidity and mortality. While advances in treatment have extended life expectancy, lung function still declines over time. Early inflammation and chronic infection, particularly with pseudomonas, worsen outcomes. Current management focuses on nutrition, airway clearance and infection control, but CFTR modulators directly target the genetic defect, improving lung function and reducing pulmonary exacerbations. Early use of CFTR modulators can alter the course of the disease.

Active tuberculosis disease among people living with HIV on ART who completed tuberculosis preventive therapy at three public hospitals in Uganda.

Tuberculosis (TB) preventive therapy (TPT) reduces the incidence of TB among people living with the human immunodeficiency virus (PLHIV). However, despite an increase in TPT uptake, TB/HIV coinfection remains stagnant in Uganda especially in areas of increasing HIV incidence such as the Bunyoro sub-region. This study was a retrospective review records (antiretroviral therapy [ART] files) of PLHIV who were active on ART and completed TPT in 2019/2020 at three major hospitals in the Bunyoro sub-region, Uganda: Masindi General Hospital, Hoima Regional Referral Hospital, and Kiryandongo General Hospital. The sample size (987) for each facility was determined using a proportionate sampling method to ensure the study's power and precision. Factors independently associated with acquiring TB disease post TPT were determined using modified Poisson regression analysis. An adjusted prevalence risk ratio (aPRR) with corresponding 95% confidence intervals were reported. The participants' mean age was 38.23 (±11.70) and the majority were female (64.94%). Overall, 9.63% developed active TB disease post TPT completion. In the adjusted analysis, factors associated with active TB disease were a history of an unsuppressed viral load after TPT (aPRR 4.64 (2.85-7.56), p<0.001), opportunistic infections after TPT completion (aPRR 4.31 (aPRR 2.58-7.2), p<0.001), a history of TB active TB disease (aPRR 1.60 (1.06-2.41), p = 0.026), and chronic illness during or after TPT (aPRR 1.68 (1.03-2.73), p = 0.038). To reduce the development of TB disease post TPT thereby improving the effectiveness of TPT, ART adherence should be emphasized to resolve viral suppression and active management of chronic and opportunistic infections. Further clinical management consideration and research is needed for PLHIV who receive TPT but have a previous history of TB disease.

Changes in lipid abundance are associated with disease progression and treatment response in chronic Trypanosoma cruzi infection

BackgroundChagas disease, caused by the parasite Trypanosoma cruzi, is a zoonosis that affects more than seven million people. Current limitations on the diagnosis of the disease hinder the prognosis of patients and the evaluation of treatment efficacy, slowing the development of new therapeutic options. The infection is known to disrupt several host metabolic pathways, providing an opportunity for the identification of biomarkers.MethodsThe metabolomic and lipidomic profiles of a cohort of symptomatic and asymptomatic patients with T. cruzi infection and a group of uninfected controls were analysed using liquid chromatography/mass spectrometry. Differences among all groups and changes before and after receiving anti-parasitic treatment across those with T. cruzi infection were explored.ResultsThree lipids were found to differentiate between symptomatic and asymptomatic participants: 10-hydroxydecanoic acid and phosphatidylethanolamines PE(18:0/20:4) and PE(18:1/20:4). Additionally, sphinganine, 4-hydroxysphinganine, hexadecasphinganine, and other sphingolipids showed post-treatment abundance similar to that in non-infected controls.ConclusionsThese molecules hold promise as potentially useful biomarkers for monitoring disease progression and treatment response in patients with chronic T. cruzi infection.Graphical