Prevalence of Legionella among pneumonia patients and environmental water samples in an Egyptian University Hospital

AbstractObjectives: to diagnose Legionella infection in community- acquired pneumonia (CAP) cases admitted to chest department of Zagazig University Hospital and in hospital- acquired pneumonia (HAP) patients hospitalized in the emergency and surgery ICU, to determine incidence of these disease condition and to identify risk factors. Another objective was to determine the occurrence of Legionella genus in the water of these departments.Subjects and methods: one hundred pneumonic patients; 50 patients with CAP and 50 with HAP were the subject of this laboratory-based, comparative cross sectional study. Full clinical history and lower respiratory tract specimens were collected from each patient. Water samples were taken from 25 water outlets. DNA was extracted by QIAamp DNA Mini Kit, and real time PCR amplification of 16s r-RNA gene was used for diagnosis of Legionella genus. Risk factors were analyzed by logistic regression analysis.Results: Legionella genus was identified in eight out of 50 patients of CAP (16%), and ten out of 50 patients with HAP (20%). As regards CAP, Legionella was prevalent in old- age, smoker males, with diabetes mellitus (DM) and/or chronic obstructive pulmonary disease (COPD). Gastrointestinal tract (GIT) and neurological manifestations were the main presentations. Seventy-five percent needed ICU admission. Concerning HAP, hospitalization for more than ten days and having a stroke or head trauma were significant risk factors. Ten out of the 25 water samples tested were positive for Legionella genus; seven samples were from the chest department and three were from emergency ICU. No water-contamination with Legionella was found in the surgery ICU.Discussion: diagnosis of Legionella should be considered for both CAP and HAP in our locality. Periodic surveillance for detection of that genus with subsequent disinfection of water sources when indicated should be carried out

Spontaneous Bacterial Peritonitis in the Medical Intensive Care Unit of a University Hospital in Egypt: Frequency, Bacteriological Profile, Risk Factors and Outcomes

Objectives: This work was carried out to assess the frequency of spontaneous bacterial peritonitis (SBP) and its variants in the medical intensive care unit (ICU) of the Internal Medicine department, zagazig Faculty of Medicine, Egypt and to identify the causative organisms and their susceptibility to commonly used antimicrobials. Other objectives were to determine risk factors and clinical outcomes. Subjects and methods: One-hundred and eighty- nine patients having ascites due to liver cirrhosis were studied. Each patient was subjected to: history collection, physical examination, diagnostic paracentesis, radiological and laboratory investigations and assessment of disease severity. Organisms isolated were identified and their antibiotic susceptibility profiles were tested. MELD score was used for diseases assessment. Risk factors and clinical outcomes were concluded using statistical methods. Results: Frequency of SBP was 56.1%. Classic SBP accounted for 47.2% of cases, while the remaining 52.8% were culture negative neutrocytic ascites (CNNA). E-coli were the most frequently isolated bacteria. Piperacillin- tazobactam was the most effective antibiotic.  SBP cases were significantly associated with hepatocellular carcinoma and with use of beta blockers. Patients with SBP were more likely to present with fever and abdominal pain, whereas those with non- SBP were more likely to present with hypotension. Non- significant relationship was found between SBP and non-SBP cases regarding ICU stay. Meanwhile mortality was higher among SBP cases; age and MELD score were the independent risk factor

Role of Procalcitonin As an Inflammatory Marker in a Sample of Egyptian Children with Simple Obesity

BACKGROUND: Obesity is a multifactorial disease, associated with metabolic disorders and chronic low-grade inflammation. Procalcitonin (PCT) is well known as a biomarker of infection, and systemic inflammation. Recently, it has potential as a marker for chronic low-grade inflammation.AIM: This study aims to evaluate the role of serum PCT as an inflammatory biomarker in the diagnosis of obesity-related low-grade inflammation.METHOD: In this case-control study, 50 obese and 35 normal weight children and adolescents aged 5–15 years were enrolled. Anthropometric parameters were measured in all subjects. Blood samples were collected for measurement of lipid profile, blood glucose, insulin, high sensitivity-CRP (Hs-CRP) and serum procalcitonin. Serum (PCT) levels were assessed using enzyme-linked immunosorbent assay.RESULTS: Obese participants had higher concentrations of serum PCT, total cholesterol, triglycerides, LDL-c, glucose and Hs-CRP than control group. On correlation analysis, procalcitonin had significant positive correlation with (BMI) z-score (P = 0.02), insulin (P = 0.00), insulin resistance (HOMA-IR) (P = 0.006), Hs-CRP (P = 0.02), total cholesterol (P = 0.04) and triglycerides (P = 0.00) in obese group.CONCLUSION: The increased serum procalcitonin concentrations were closely related to measures of adiposity, Hs-CRP and insulin resistance, suggesting that PCT may be an excellent biomarker for obesity-related chronic low-grade inflammation in children and adolescents

Melatonin ameliorates serobiochemical alterations and restores the cardio-nephro diabetic vascular and cellular alterations in streptozotocin-induced diabetic rats

Melatonin possesses a wide range of pharmacological activities, including antidiabetic properties. Diabetes mellitus (DM) induces several physiopathological changes in body organs, which could be observed lately after systemic failure. In the current study, we aimed to investigate the serobiochemical changes and the histopathological picture in the diabetic heart and the kidney early before chronic complications and highlight the association between hyperglycemia, glomerular alterations, and cardiovascular changes. In addition, the role of melatonin in the treatment of cardio-nephro diabetic vascular and cellular adverse changes in streptozotocin-induced diabetic rats was also studied. A total of 40 mature Wistar albino rats were distributed into five groups; (1) control untreated rats, (2) diabetic mellitus untreated (DM) rats, in which DM was induced by the injection of streptozotocin (STZ), (3) control melatonin-treated (MLT), (4) melatonin-treated diabetic (DM + MLT) rats, in which melatonin was injected (10 mg/kg/day, i.p.) for 4 weeks, and (5) insulin-treated diabetic (DM + INS) rats. The serum biochemical analysis of diabetic STZ rats showed a significant (P < 0.05) increase in the concentrations of blood glucose, total oxidative capacity (TOC), CK-MB, endothelin-1, myoglobin, H-FABP, ALT, AST, urea, and creatinine as compared to control rats. In contrast, there was a significant (P < 0.05) decrease in serum concentration of insulin, total antioxidative capacity (TAC), total nitric oxide (TNO), and total protein level in DM rats vs. the control rats. Significant improvement in the serobiochemical parameters was noticed in both (DM + MLT) and (DM + INS) groups as compared with (DM) rats. The histological examination of the DM group revealed a disorder of myofibers, cardiomyocyte nuclei, and an increase in connective tissue deposits in between cardiac tissues. Severe congestion and dilation of blood capillaries between cardiac muscle fibers were also observed. The nephropathic changes in DM rats revealed various deteriorations in glomeruli and renal tubular cells of the same group. In addition, vascular alterations in the arcuate artery at the corticomedullary junction and interstitial congestion take place. Melatonin administration repaired all these histopathological alterations to near-control levels. The study concluded that melatonin could be an effective therapeutic molecule for restoring serobiochemical and tissue histopathological alterations during diabetes mellitus

Melatonin downregulates the increased hepatic alpha-fetoprotein expression and restores pancreatic beta cells in a streptozotocin-induced diabetic rat model: a clinical, biochemical, immunohistochemical, and descriptive histopathological study

BackgroundDiabetes mellitus (DM) is a chronic metabolic disorder. Hepatopathy is one of the serious effects of DM Melatonin (MT) is a potent endogenous antioxidant that can control insulin output. However, little information is available about the potential association between melatonin and hepatic alpha-fetoprotein expression in diabetes.ObjectiveThis study was conducted to assess the influence of MT on diabetes-related hepatic injuries and to determine how β-cells of the pancreas in diabetic rats respond to MT administration.Materials and methodsForty rats were assigned to four groups at random (ten animals per group). Group I served as a normal control group. Group II was induced with DM, and a single dose of freshly prepared streptozotocin (45 mg/kg body weight) was intraperitoneally injected. In Group III, rats received 10 mg/kg/day of intraperitoneal melatonin (IP MT) intraperitoneally over a period of 4 weeks. In Group IV (DM + MT), following the induction of diabetes, rats received MT (the same as in Group III). Fasting blood sugar, glycosylated hemoglobin (HbA1c), and serum insulin levels were assessed at the end of the experimental period. Serum liver function tests were performed. The pancreas and liver were examined histopathologically and immunohistochemically for insulin and alpha-fetoprotein (AFP) antibodies, respectively.ResultsMT was found to significantly modulate the raised blood glucose, HbA1c, and insulin levels induced by diabetes, as well as the decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Furthermore, MT attenuated diabetic degenerative changes in the pancreas and the hepatic histological structure, increased the β-cell percentage area, and decreased AFP expression in the liver tissue. It attenuated diabetes-induced hepatic injury by restoring pancreatic β-cells; its antioxidant effect also reduced hepatocyte injury.ConclusionCollectively, the present study confirmed the potential benefits of MT in downregulating the increased hepatic alpha-fetoprotein expression and in restoring pancreatic β-cells in a streptozotocin-induced diabetic rat model, suggesting its promising role in the treatment of diabetes

Zero by 2030 and OneHealth: The multidisciplinary challenges of rabies control and elimination

"Rabies, caused by a negative strand RNA-virus belonging to the genus Lyssavirus (family Rhabdoviridae of the order Mononegavirales), remains of global concern [1]. This vaccine-preventable viral zoonotic disease is present in more than 150 countries and territories [2]. Ac- cording to the World Health Organization (WHO), rabies is estimated to cause ~59,000 human deaths annually, with 95% of cases occurring in Africa and Asia [3,4]. However, rabies still occurs in other regions, such as Latin America and the Caribbean [5–8], Central Asia and the Middle East [9,10]. Whilst a number of animals can host the rabies virus, dogs are the main source of human rabies deaths, contributing up to 99% of all rabies transmissions to humans. Dog-mediated rabies has been eliminated from Western Europe, Canada, the United States of America (USA), Japan and some Latin American countries [11]. Nevertheless, the risk of reintroduction and disease among travellers to risk areas is a matter of concern [12–15]. As occurred with many other communicable and non-communicable diseases, the 2020–2022 COVID-19 pandemic negatively impacted the efforts of control and reemergence of rabies in certain countries [7,16,17]. Post-pandemic challenges to enhance con- trol and prevention are multiple and need urgent actions to achieve the goal in eight years by 2030 [16].

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival