Epidemiology of hepatitis C virus among hemodialysis patients in the Middle East and North Africa: systematic syntheses, meta-analyses, and meta-regressions.

We aimed to investigate hepatitis C virus (HCV) epidemiology among hemodialysis (HD) patients in the Middle East and North Africa (MENA). Our data source was an HCV biological measures database populated through systematic literature searches. Descriptive epidemiologic syntheses, effects meta-analyses and meta-regressions, and genotype analyses were conducted. We analyzed 289 studies, including 106 463 HD patients. HCV incidence ranged between 0 and 100% as seroconversion risk, and between 0 and 14·7 per 1000 person-years as incidence rate. The regional pooled mean estimate was 29·2% (95% CI: 25·6-32·8%) for HCV antibody positive prevalence and 63·0% (95% CI: 55·4-70·3%) for the viremic rate. Region within MENA, country income group, and year of data collection were associated with HCV prevalence; year of data collection adjusted odds ratio was 0·92 (95% CI: 0·90-0·95). Genotype diversity varied across countries with four genotypes documented regionally: genotype 1 (39·3%), genotype 2 (5·7%), genotype 3 (29·6%), and genotype 4 (25·4%). Our findings showed that one-third of HD patients are HCV antibody positive and one-fifth are chronic carriers and can transmit the infection. However, HCV prevalence is declining. In context of growing HD patient population and increasing HCV treatment availability, it is critical to improve standards of infection control in dialysis and expand treatment coverage

Hospital admission and risk assessment associated to exposure of fungal bioaerosols at a municipal landfill using statistical models

The object of this research to determine the statistical relationship and degree of association between variables: hospital admission days and diagnostic (disease) potentially associated to fungal bioaerosols exposure. Admissions included acute respiratory infections, atopic dermatitis, pharyngitis and otitis. Statistical analysis was done using Statgraphics Centurion XVI software. In addition, was estimated the occupational exposure to fungal aerosols in stages of a landfill using BIOGAVAL method and represented by Golden Surfer XVI program. Biological risk assessment with sentinel microorganism A. fumigatus and Penicillium sp, indicated that occupational exposure to fungal aerosols is Biological action level. Preventive measures should be taken to reduce the risk of acquiring acute respiratory infections, dermatitis or other skin infections

Echinocandin Treatment of Pneumocystis Pneumonia in Rodent Models Depletes Cysts Leaving Trophic Burdens That Cannot Transmit the Infection

Fungi in the genus Pneumocystis cause pneumonia (PCP) in hosts with debilitated immune systems and are emerging as co-morbidity factors associated with chronic diseases such as COPD. Limited therapeutic choices and poor understanding of the life cycle are a result of the inability of these fungi to grow outside the mammalian lung. Within the alveolar lumen, Pneumocystis spp., appear to have a bi-phasic life cycle consisting of an asexual phase characterized by binary fission of trophic forms and a sexual cycle resulting in formation of cysts, but the life cycle stage that transmits the infection is not known. The cysts, but not the trophic forms, express β -1,3-D-glucan synthetase and contain abundant β -1,3-D-glucan. Here we show that therapeutic and prophylactic treatment of PCP with echinocandins, compounds which inhibit the synthesis of β -1,3-D-glucan, depleted cysts in rodent models of PCP, while sparing the trophic forms which remained in significant numbers. Survival was enhanced in the echincandin treated mice, likely due to the decreased β -1,3-D-glucan content in the lungs of treated mice and rats which coincided with reductions of cyst numbers, and dramatic remodeling of organism morphology. Strong evidence for the cyst as the agent of transmission was provided by the failure of anidulafungin-treated mice to transmit the infection. We show for the first time that withdrawal of anidulafungin treatment with continued immunosuppression permitted the repopulation of cyst forms. Treatment of PCP with an echinocandin alone will not likely result in eradication of infection and cessation of echinocandin treatment while the patient remains immunosuppressed could result in relapse. Importantly, the echinocandins provide novel and powerful chemical tools to probe the still poorly understood bi-phasic life cycle of this genus of fungal pathogens

The intracellular dynamic of protein palmitoylation

S-palmitoylation describes the reversible attachment of fatty acids (predominantly palmitate) onto cysteine residues via a labile thioester bond. This posttranslational modification impacts protein functionality by regulating membrane interactions, intracellular sorting, stability, and membrane micropatterning. Several recent findings have provided a tantalizing insight into the regulation and spatiotemporal dynamics of protein palmitoylation. In mammalian cells, the Golgi has emerged as a possible super-reaction center for the palmitoylation of peripheral membrane proteins, whereas palmitoylation reactions on post-Golgi compartments contribute to the regulation of specific substrates. In addition to palmitoylating and depalmitoylating enzymes, intracellular palmitoylation dynamics may also be controlled through interplay with distinct posttranslational modifications, such as phosphorylation and nitrosylation

Enzymatic Degradation of PrPSc by a Protease Secreted from Aeropyrum pernix K1

BACKGROUND: An R30 fraction from the growth medium of Aeropyrum pernix was analyzed for the protease that can digest the pathological prion protein isoform (PrP(Sc)) from different species (human, bovine, deer and mouse). METHODOLOGY/PRINCIPAL FINDINGS: Degradation of the PrP(Sc) isoform by the R30 fraction and the purified protease was evaluated using the 6H4 anti-PrP monoclonal antibody. Fragments from the N-terminal and C-terminal of PrP(Sc) were also monitored by Western blotting using the EB8 anti-PrP monoclonal antibody, and by dot blotting using the C7/5 anti-PrP monoclonal antibody, respectively. For detection of smaller peptides from incomplete digestion of PrP(Sc), the EB8 monoclonal antibody was used after precipitation with sodium phosphotungstate. Characterization of the purified active protease from the R30 fraction was achieved, through purification by fast protein liquid chromatography, and identification by tandem mass spectrometry the serine metalloprotease pernisine. SDS-PAGE and zymography show the purified pernisine plus its proregion with a molecular weight of ca. 45 kDa, and the mature purified pernisine as ca. 23 kDa. The purified pernisine was active between 58 °C and 99 °C, and between pH 3.5 and 8.0. The temperature and pH optima of the enzymatic activity of the purified pernisine in the presence of 1 mM CaCl(2) were 105 °C ± 0.5 °C and pH 6.5 ± 0.2, respectively. CONCLUSIONS/SIGNIFICANCE: Our study has identified and characterized pernisine as a thermostable serine metalloprotease that is secreted from A. pernix and that can digest the pathological prion protein PrP(Sc)

SARS-CoV-2 infection hospitalization, severity, criticality, and fatality rates in Qatar.

The SARS-CoV-2 pandemic resulted in considerable morbidity and mortality as well as severe economic and societal disruptions. Despite scientific progress, true infection severity, factoring both diagnosed and undiagnosed infections, remains poorly understood. This study aimed to estimate SARS-CoV-2 age-stratified and overall morbidity and mortality rates based on analysis of extensive epidemiological data for the pervasive epidemic in Qatar, a country where < 9% of the population are ≥ 50 years. We show that SARS-CoV-2 severity and fatality demonstrate a striking age dependence with low values for those aged < 50 years, but rapidly growing rates for those ≥ 50 years. Age dependence was particularly pronounced for infection criticality rate and infection fatality rate. With Qatar's young population, overall SARS-CoV-2 severity and fatality were not high with < 4 infections in every 1000 being severe or critical and < 2 in every 10,000 being fatal. Only 13 infections in every 1000 received any hospitalization in acute-care-unit beds and < 2 in every 1000 were hospitalized in intensive-care-unit beds. However, we show that these rates would have been much higher if Qatar's population had the demographic structure of Europe or the United States. Epidemic expansion in nations with young populations may lead to considerably lower disease burden than currently believed

Epidemiological impact of prioritizing SARS-CoV-2 vaccination by antibody status: Mathematical modeling analyses

AbstractBackgroundVaccines against SARS-CoV-2 have been developed, but their availability falls far short of global needs. This study aimed to investigate the impact of prioritizing available doses on the basis of recipient antibody status, that is by exposure status, using Qatar as an example.MethodsVaccination impact was assessed under different scale-up scenarios using a deterministic meta-population mathematical model describing SARS-CoV-2 transmission and disease progression in the presence of vaccination.ResultsFor a vaccine that protects against infection with an efficacy of 95%, half as many vaccinations were needed to avert one infection, disease outcome, or death by prioritizing antibody-negative individuals for vaccination. Prioritization by antibody status reduced incidence at a faster rate and led to faster elimination of infection and return to normalcy. Further prioritization by age group amplified the gains of prioritization by antibody status. Gains from prioritization by antibody status were largest in settings where the proportion of the population already infected at the commencement of vaccination was 30-60%, which is perhaps where most countries will be by the time vaccination programs are up and running. For a vaccine that only protects against disease and not infection, vaccine impact was reduced by half, whether this impact was measured in terms of averted infections or disease outcomes, but the relative gains from using antibody status to prioritize vaccination recipients were similar.ConclusionsMajor health, societal, and economic gains can be achieved more quickly by prioritizing those who are antibody-negative while doses of the vaccine remain in short supply.</jats:sec

Immune Imprinting and Protection against Repeat Reinfection with SARS-CoV-2

More than 2 years into the coronavirus disease 2019 (Covid-19) pandemic, the global population carries heterogeneous immune histories derived from various exposures to infection, viral variants, and vaccination.1 Evidence at the level of binding and neutralizing antibodies and B-cell and T-cell immunity suggests that a history of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can have a negative effect on subsequent protective immunity.1 In particular, the immune response to B.1.1.529 (omicron) subvariants could be compromised by differential immune imprinting in persons who have had a previous infection with the original virus or the B.1.1.7 (alpha) variant.