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Medical Mycology Jun 2024This systematic review evaluates the current global impact of invasive infections caused by Pneumocystis jirovecii (principally pneumonia: PJP), and was carried out to...
Features and global impact of invasive fungal infections caused by Pneumocystis jirovecii: A systematic review to inform the World Health Organization fungal priority pathogens list.
This systematic review evaluates the current global impact of invasive infections caused by Pneumocystis jirovecii (principally pneumonia: PJP), and was carried out to inform the World Health Organization Fungal Priority Pathogens List. PubMed and Web of Science were used to find studies reporting mortality, inpatient care, complications/sequelae, antifungal susceptibility/resistance, preventability, annual incidence, global distribution, and emergence in the past 10 years, published from January 2011 to February 2021. Reported mortality is highly variable, depending on the patient population: In studies of persons with HIV, mortality was reported at 5%-30%, while in studies of persons without HIV, mortality ranged from 4% to 76%. Risk factors for disease principally include immunosuppression from HIV, but other types of immunosuppression are increasingly recognised, including solid organ and haematopoietic stem cell transplantation, autoimmune and inflammatory disease, and chemotherapy for cancer. Although prophylaxis is available and generally effective, burdensome side effects may lead to discontinuation. After a period of decline associated with improvement in access to HIV treatment, new risk groups of immunosuppressed patients with PJP are increasingly identified, including solid organ transplant patients.
Topics: Humans; Pneumocystis carinii; Invasive Fungal Infections; World Health Organization; Immunocompromised Host; Risk Factors; Global Health; Pneumonia, Pneumocystis; Antifungal Agents; Incidence
PubMed: 38935910
DOI: 10.1093/mmy/myae038 -
Medical Mycology Jun 2024Histoplasmosis, a significant mycosis primarily prevalent in Africa, North and South America, with emerging reports globally, poses notable health challenges,...
Histoplasmosis, a significant mycosis primarily prevalent in Africa, North and South America, with emerging reports globally, poses notable health challenges, particularly in immunocompromised individuals such as people living with HIV/AIDS and organ transplant recipients. This systematic review, aimed at informing the World Health Organization's Fungal Priority Pathogens List, critically examines literature from 2011 to 2021 using PubMed and Web of Science, focusing on the incidence, mortality, morbidity, antifungal resistance, preventability, and distribution of Histoplasma. We also found a high prevalence (22%-44%) in people living with HIV, with mortality rates ranging from 21% to 53%. Despite limited data, the prevalence of histoplasmosis seems stable, with lower estimates in Europe. Complications such as central nervous system disease, pulmonary issues, and lymphoedema due to granuloma or sclerosis are noted, though their burden remains uncertain. Antifungal susceptibility varies, particularly against fluconazole (MIC: ≥32 mg/l) and caspofungin (MICs: 4-32 mg/l), while resistance to amphotericin B (MIC: 0.125-0.16 mg/l), itraconazole (MICs: 0.004-0.125 mg/l), and voriconazole (MICs: 0.004-0.125 mg/l) remains low. This review identifies critical knowledge gaps, underlining the need for robust, globally representative surveillance systems to better understand and combat this fungal threat.
Topics: Humans; Histoplasmosis; Antifungal Agents; World Health Organization; Drug Resistance, Fungal; Histoplasma; Prevalence; Immunocompromised Host
PubMed: 38935903
DOI: 10.1093/mmy/myae039 -
PloS One 2024The Youth Risk Behavior Survey (YRBS) among high school students includes standard questions about sexual identity and sex of sexual contacts, but these questions are...
PURPOSE
The Youth Risk Behavior Survey (YRBS) among high school students includes standard questions about sexual identity and sex of sexual contacts, but these questions are not consistently included in every state that conducts the survey. This study aimed to develop and apply a method to predict state-level proportions of high school students identifying as lesbian, gay, or bisexual (LGB) or reporting any same-sex sexual contacts in those states that did not include these questions in their 2017 YRBS.
METHODS
We used state-level high school YRBS data from 2013, 2015, and 2017. We defined two primary outcomes relating to self-reported LGB identity and reported same-sex sexual contacts. We developed machine learning models to predict the two outcomes based on other YRBS variables, and comparing different modeling approaches. We used a leave-one-out cross-validation approach and report results from best-performing models.
RESULTS
Modern ensemble models outperformed traditional linear models at predicting state-level proportions for the two outcomes, and we identified prediction methods that performed well across different years and prediction tasks. Predicted proportions of respondents reporting LGB identity in states that did not include direct measurement ranged between 9.4% and 12.9%. Predicted proportions of respondents reporting any same-sex contacts, where not directly observed, ranged between 7.0% and 10.4%.
CONCLUSION
Comparable population estimates of sexual minority adolescents can raise awareness among state policy makers and the public about what proportion of youth may be exposed to disparate health risks and outcomes associated with sexual minority status. This information can help decision makers in public health and education agencies design, implement and evaluate community and school interventions to improve the health of LGB youth.
Topics: Humans; Adolescent; Sexual and Gender Minorities; Male; Female; United States; Sexual Behavior; Surveys and Questionnaires; Machine Learning; Risk-Taking; Students
PubMed: 38935807
DOI: 10.1371/journal.pone.0304175 -
PloS One 2024Several hepatitis A outbreaks have recently been reported in Kerala state, India. To inform coverage decision of hepatitis A vaccine in Kerala, this study aimed to...
Several hepatitis A outbreaks have recently been reported in Kerala state, India. To inform coverage decision of hepatitis A vaccine in Kerala, this study aimed to examine the cost-effectiveness of 1) hepatitis A vaccination among children aged 1 year and individuals aged 15 years, and 2) serological screening of individuals aged 15 years and vaccination of susceptible as compared to no vaccination or vaccination without serological screening. Both live attenuated hepatitis A vaccine and inactivated hepatitis A vaccine were considered in the analysis. A combination of decision tree and Markov models with a cycle length of one year was employed to estimate costs and benefits of different vaccination strategies. Analysis were based on both societal and payer perspectives. The lifetime costs and outcomes were discounted by 3%. Our findings indicated that all strategies were cost-saving for both societal and payer perspectives. Moreover, budget impact analysis revealed that vaccination without screening among individuals aged 15 years could save the government's budget by reducing treatment cost of hepatitis A. Our cost-effectiveness evidence supports the inclusion of hepatitis A vaccination into the vaccination program for children aged 1 year and individuals aged 15 years in Kerala state, India.
Topics: Humans; India; Cost-Benefit Analysis; Hepatitis A; Adolescent; Hepatitis A Vaccines; Vaccination; Infant; Child; Female; Male; Child, Preschool; Adult; Markov Chains; Young Adult
PubMed: 38935781
DOI: 10.1371/journal.pone.0306293 -
PloS One 2024Chronic liver diseases are caused by hepatic viral infection, chemicals, and metabolic stress. The protein Grb2-associated binder 1 (Gab1) binds to various growth factor...
Chronic liver diseases are caused by hepatic viral infection, chemicals, and metabolic stress. The protein Grb2-associated binder 1 (Gab1) binds to various growth factor receptors, and triggers cell differentiation/survival signaling pathways. To identify signaling molecules involved in the progression of liver diseases, we performed reverse-phase protein microarray (RPMA)-based screening of hepatocytes isolated from humanized mice after acute HCV infection. Acute viral infection in humanized liver mice significantly decreased the level of hepatocyte p-Gab1. Moreover, hepatoma cells upon HCV infection decreased Gab1 mRNA at later times of infection (D3 to D5) and p-Gab1 level was inversely related to the production of TGF-β. In contrast, the level of p-Gab1 was increased in CCL4-induced fibrotic liver. Hepatoma cells showed elevation of p-Gab1, along with an increase in STAT3 and ERK activation, upon treatment with HGF (ligand of HGF receptor/c-Met) and CCL4. In Gab1 knockdown hepatoma cells, cell proliferative signaling activity was reduced but the level of activated caspase-3 was increased. These findings suggest that hepatocyte Gab1 expression may play a role in promoting liver fibrosis progression by triggering ERK activation and inhibiting apoptosis. It implies that the Gab1-mediated signaling pathway would be a promising therapeutic target to treat chronic liver diseases.
Topics: Animals; Hepatocytes; Liver Cirrhosis; Adaptor Proteins, Signal Transducing; Apoptosis; Signal Transduction; Cell Proliferation; Humans; Mice; Proto-Oncogene Proteins c-met; Hepatocyte Growth Factor; Cell Line, Tumor; Hepatitis C
PubMed: 38935609
DOI: 10.1371/journal.pone.0306345 -
Clinical and Translational Medicine Jul 2024Hepatitis B virus (HBV) infection playsa significant role in the etiology and progression of liver-relatedpathologies, encompassing chronic hepatitis, fibrosis,... (Review)
Review
Hepatitis B virus (HBV) infection playsa significant role in the etiology and progression of liver-relatedpathologies, encompassing chronic hepatitis, fibrosis, cirrhosis, and eventual hepatocellularcarcinoma (HCC). Notably, HBV infection stands as the primary etiologicalfactor driving the development of HCC. Given the significant contribution ofHBV infection to liver diseases, a comprehensive understanding of immunedynamics in the liver microenvironment, spanning chronic HBV infection,fibrosis, cirrhosis, and HCC, is essential. In this review, we focused on thefunctional alterations of CD8 T cells within the pathogenic livermicroenvironment from HBV infection to HCC. We thoroughly reviewed the roles ofhypoxia, acidic pH, metabolic reprogramming, amino acid deficiency, inhibitory checkpointmolecules, immunosuppressive cytokines, and the gut-liver communication in shapingthe dysfunction of CD8 T cells in the liver microenvironment. Thesefactors significantly impact the clinical prognosis. Furthermore, we comprehensivelyreviewed CD8 T cell-based therapy strategies for liver diseases,encompassing HBV infection, fibrosis, cirrhosis, and HCC. Strategies includeimmune checkpoint blockades, metabolic T-cell targeting therapy, therapeuticT-cell vaccination, and adoptive transfer of genetically engineered CD8 T cells, along with the combined usage of programmed cell death protein-1/programmeddeath ligand-1 (PD-1/PD-L1) inhibitors with mitochondria-targeted antioxidants.Given that targeting CD8 T cells at various stages of hepatitis Bvirus-induced hepatocellular carcinoma (HBV + HCC) shows promise, we reviewedthe ongoing need for research to elucidate the complex interplay between CD8 T cells and the liver microenvironment in the progression of HBV infection toHCC. We also discussed personalized treatment regimens, combining therapeuticstrategies and harnessing gut microbiota modulation, which holds potential forenhanced clinical benefits. In conclusion, this review delves into the immunedynamics of CD8 T cells, microenvironment changes, and therapeuticstrategies within the liver during chronic HBV infection, HCC progression, andrelated liver diseases.
Topics: Humans; CD8-Positive T-Lymphocytes; Hepatitis B virus; Hepatitis B, Chronic; Carcinoma, Hepatocellular; Liver Neoplasms; Liver Diseases
PubMed: 38935536
DOI: 10.1002/ctm2.1731 -
Veterinary Research Communications Jun 2024Hepatitis E virus (HEV), species Paslahepevirus balayani, poses a global public health threat, especially in developing countries, by causing acute enterically...
Hepatitis E virus (HEV), species Paslahepevirus balayani, poses a global public health threat, especially in developing countries, by causing acute enterically transmitted hepatitis. HEV infects various mammalian hosts and belongs to the genus Paslahepevirus in the family Hepeviridae. While swine are recognized as the main hosts of HEV, rabbits, which can also be affected by swine HEV-3 related strains, serve as the primary reservoir for the distinct emerging and zoonotic HEV-3ra subtype. In Portugal, where the European wild rabbit is abundant, their role in HEV epidemiology remains unclear. The primary aim of the present research was to evaluate the circulation and the potential for HEV infection within these species. This study employed a molecular and longitudinal serological approach to investigate HEV in Portuguese rabbits. Among the 205 wild rabbits tested, a seroprevalence of 2.44% (95% CI: 0.80-5.60) was found, with no significant associations with age, sex, localization, or sampling dates. Seropositive animals were found in the south and center regions of the country. HEV RNA was not detected in 120 fecal samples, suggesting a natural, low level, and widespread viral circulation. The study underscores the need for further research to comprehend HEV dynamics in these species, which is crucial for assessing potential transmission risks to humans.
PubMed: 38935173
DOI: 10.1007/s11259-024-10452-7 -
Intervirology Jun 2024This study aimed to investigate the differences between pregnant women with chronic hepatitis B virus (HBV) infection and intrafamilial infection and those without...
INTRODUCTION
This study aimed to investigate the differences between pregnant women with chronic hepatitis B virus (HBV) infection and intrafamilial infection and those without intrafamilial infection.
METHODS
HBV DNA was extracted from the sera of 16 pregnant women with chronic hepatitis B (CHB) and their family members for gene sequencing and phylogenetic analyses. A total of 74 pregnant women with CHB were followed up from the second trimester to three months postpartum. Viral markers and other laboratory indicators were compared between pregnant women with CHB with and without intrafamilial infection.
RESULTS
The phylogenetic tree showed that HBV lines in the mother-spread pedigree shared a node, whereas there was an unrelated genetic background for HBV lines in individuals without intrafamilial infection. From delivery to three months postpartum, compared with those without intrafamilial infection, pregnant women with intrafamilial infection were related negatively to HBV DNA (β=-0.43, 95% Confidence Interval [CI]: -0.76 to -0.12, p=0.009), HBeAg (β=-195.15, 95% CI: -366.35 to -23.96, p=0.027), and hemoglobin changes (β=-8.09, 95%CI: -15.54 to -0.64, p=0.035) and positively to changes in the levels of alanine aminotransferase (β=73.9, 95%CI:38.92-108.95, p<0.001) and albumin (β=2.73, 95% CI:0.23-5.23, p=0.033).
CONCLUSION
The mother-spread pedigree spread model differs from that of non-intrafamilial infections. Pregnant women with intra-familial HBV infection have less hepatitis flares and liver damage, but their HBV DNA and HBeAg levels rebound faster after delivery, than those without intra-familial infection by the virus.
PubMed: 38934174
DOI: 10.1159/000539994 -
Open Forum Infectious Diseases Jun 2024We enrolled 21 patients with laboratory-confirmed yellow fever (YF), hospitalized at Eduardo de Menezes Hospital, Brazil, to be treated with sofosbuvir, a drug approved...
We enrolled 21 patients with laboratory-confirmed yellow fever (YF), hospitalized at Eduardo de Menezes Hospital, Brazil, to be treated with sofosbuvir, a drug approved for hepatitis C. Given the absence of specific YF antiviral treatments, the off-label nonrandomized sofosbuvir treatment aimed to address high disease severity and the risk of fatal outcomes. Patients received a daily dose of 400 mg sofosbuvir from 4 to 10 days post-symptom onset. YF viral load (VL) comparisons were made between treated and nontreated patients who either survived or died. The genomic VL for the treated group steadily decreased after day 7 post-symptom onset, suggesting that sofosbuvir might reduce YF VL. This study underscores the urgent need for YF antiviral therapies, advocating for randomized clinical trials to further explore sofosbuvir's role in YF treatment.
PubMed: 38933737
DOI: 10.1093/ofid/ofae312 -
Frontiers in Cellular and Infection... 2024
Topics: Inflammasomes; Humans; Virus Diseases; Animals; Host-Pathogen Interactions
PubMed: 38933692
DOI: 10.3389/fcimb.2024.1438310