PNEUMOCYSTIS IN PATIENTS LIVING WITH HIV: EXPERIENCE OF THE INFECTIOUS DISEASES DEPARTMENT OF CHU MOHAMED VI-MARRAKECH

Pneumocystis is the most serious and common respiratory opportunistic infection after tuberculosis during HIV infection. To describe the epidemiological, clinical, therapeutic and evolutionary aspects of HIV-infected patients who presented with pneumocystis. Retrospective study of the records of 45 HIV-infected patients followed at the Department of Infectious Diseases of the CHU Mohamed VI and hospitalized for Pneumocystis jirovecii infection between January 2007 and March 2021. Out of 1286 HIV-infected patients followed at the department during the study period, 45 patients (3.5%) had pneumocystis. Pneumocystis was inaugural to HIV infection in 36 cases (80%). The predominance was male in 63% of cases (28 males to 17 females), with an average age of 35.5 years [16-64 years]. The mean TCD4 cell count was 74 cells/mm3 [0- 656 cells/mm3]. The mean LDH level was 874.89 IU/L. The clinical picture was marked by cough in 84% of cases and dyspnea in 64% of cases. The most frequent radiological signs were a diffuse interstitial syndrome in 84.4% of cases on chest X-ray and ground glass appearance in 63% of cases on chest CT. The diagnosis of pneumocystis was confirmed in 16 patients by the detection of Pneumocystis jIrovecii in sputum and BAL. All our patients were treated with Trimethoprim-Sulfamethoxazole combination. Antiretroviral treatment was started in 32 patients, i.e. 71% of the patients, with a favorable evolution in 24 patients, i.e. 53%. Pneumocystis is a serious infection in immunocompromised patients especially PLHIV. In Morocco, it is still frequent during HIV infection and is one of the main causes of death.

The rationality behind performance of routine lumber puncture in simple febrile seizure in 6-18 months old children

Background: Pediatrics seizures can be either due to febrile seizure or underlying serious infection such as meningitis. It is important to rule out meningitis in children presenting with fever and seizure. The aim of the study was conducted to assess the necessity of routine lumber puncture and to determine the incidence of meningitis among children aged 6 to 18 months presenting with first episode of febrile seizure.Methods: This prospective observational study was conducted among 47 children with first episode of simple febrile seizure presenting to emergency in Medical College Kolkata, West Bengal from April 2018 to September 2019.Results: Total 47 children were studied among 32 (68%) children were between 6-12 months and 15 (32%) were between 12-18 months of age. Only 1 child (2.1%) diagnosed as meningitis. Clinically 7 children (14.9%) showed signs of sepsis and meningitis like picture and 6 children (12.8%) were in 6-12 months of age and only 1 child (2.1%) was in 12-18month of age. Only 1 child in 6-12 months of age showed CSF positive and all other CSF studies were within normal limit. A significant association was seen between age group and hyponatremia and family history of febrile seizure (p<0.05). There was no statically significant between clinical diagnosis and CSF results (p=0.15).Conclusions: The risk of meningitis in children presenting with simple febrile seizure between 6-18 months of age is very low, specially in 12-18 months of age. Therefore, current guidelines regarding lumber puncture in simple febrile seizure should be reconsidered.

Molecular Analysis of Pathogenic Genes (lasB and exoA) in Pseudomonas aeruginosa Strains Isolated from Animal and Human Samples and Determination of Their Resistance Pattern

: Pseudomonas aeruginosa (P. aeruginosa) has a wide range of virulence factors. These factors have the potential to increase bacterial pathogenicity and serious infection. The purpose of this study was to evaluate the virulence profiles and antibiotic susceptibility of isolates of P. aeruginosa originated from animal and human samples. The samples were cultured on selective media before being extracted for DNA and subjected to a PCR technique to detect virulence genes. There was a significant difference in the isolation of P. areuginosa isolated from human and animal sources. Where, in humans, the percentage of P. areuginosa was 52 (68.42%) while in animals the percentage of P.aeruginosa was 24 (31.57%). In humans, the percentage of P. aeruginosa in blood was 26.92% (14 isolates), in urine it was 25% (13 isolates), in wound it was 40.38%21 isolates), and in sputum it was 7.69% (4 isolates). We used a PCR technique that produced highly specific and accurate results for detecting virulence factor genes in P. aeruginosa isolates that cause disease in humans and animals. The percentage of exoA genes was (83.33%) and (81.66%) in the animal and human, and that of lasB was (58.33%) and (92.30%) in animal and human samples respectively. Furthermore, both the exoA and lasB genes are found in 26.31% of animal strains and 17.10% of human strains. The disc diffusion method was used to determine antimicrobial susceptibility. In both animal and human isolates, P. aeruginosa showed the highest resistance to amikacin and the lowest resistance to ciprofloxacin. These findings could aid in the understanding of pathogenicity processes, treatment direction, and the development of strategies to control the spread of epidemic P. aeruginosa strains.

Investigation of hub gene associated with the infection of Staphylococcus aureus via weighted gene co-expression network analysis

Introduction Staphylococcus aureus is a gram-positive bacterium that causes serious infection. With the increasing resistance of bacteria to current antibiotics, it is necessary to learn more about the molecular mechanism and cellular pathways involved in the Staphylococcus aureus infection. Methods We downloaded the GSE33341 dataset from the GEO database and applied the weighted gene co-expression network analysis (WGCNA), from which we obtained some critical modules. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) were applied to illustrate the biological functions of genes in these modules. We constructed the protein-protein interaction (PPI) network by Cytoscape and selected five candidate hub genes. Five potential hub genes were validated in GSE30119 by GraphPad Prism 8.0. The diagnostic values of these genes were calculated and present in the ROC curve based on the GSE13670 dataset. Their gene functions were analyzed by Gene Set Enrichment Analysis (GSEA). Results A co-expression network was built with 5000 genes divided into 11 modules. The genes in green and turquoise modules demonstrated a high correlation. According to the KEGG and GO analyses, genes in the green module were closely related to ubiquitination and autophagy. Subsequently, we picked out the top five hub genes in the green module. And UBB was determined as the hub gene in the GSE30119 dataset. The expression level of UBB, ASB, and MKRN1 could significantly differentiate between Staphylococcus aureus infection and healthy controls based on the ROC curve. The GSEA analysis indicated that lower expression levels of UBB were associated with the P53 signal pathway. Conclusions We identified some hub genes and significant signal enrichment pathways in Staphylococcus aureus infection via bioinformatics analysis, which may facilitate the development of potential clinical therapeutic strategies.

A diagnostically challenging case of pyelonephritis caused by Lactobacillus

Lactobacillus can lead to serious infection in individuals with multiple predisposing factors. Therefore, individuals with risk factors, including steroid use, and those harboring immunocompromised conditions such as hypothyroidism and cancer, should be promptly evaluated and appropriate treatment should be initiated without delay if the culture test is positive for Lactobacillus.

Integrated safety analysis of filgotinib in patients with moderately to severely active rheumatoid arthritis receiving treatment over a median of 1.6 years

ObjectiveTo characterise safety of the Janus kinase-1 preferential inhibitor filgotinib in patients with moderately to severely active rheumatoid arthritis.MethodsData were integrated from seven trials (NCT01668641, NCT01894516, NCT02889796, NCT02873936, NCT02886728, NCT02065700, NCT03025308). Results are from placebo (PBO)-controlled (through week (W)12) and long-term, as-treated (all available data for patients receiving ≥1 dose filgotinib 200 (FIL200) or 100 mg (FIL100) daily) datasets. We calculated exposure-adjusted incidence rates (EAIRs)/100 patient-years filgotinib exposure (100PYE) for treatment-emergent adverse events (TEAEs).Results3691 patients received filgotinib for 6080.7 PYE (median 1.6, maximum 5.6 years). During the PBO-controlled period, TEAEs, including those of grade ≥3, occurred at comparable rates with filgotinib or PBO; long-term EAIRs of TEAEs grade ≥3 were 6.4 and 7.6/100PYE for FIL200 and FIL100. EAIRs for deaths were 0.6/100PYE for FIL200, FIL100 and PBO; long-term EAIRs were 0.5 and 0.3/100PYE for FIL200 and FIL100. EAIRs for serious infection were 3.9, 3.3 and 2.4/100PYE for FIL200, FIL100 and PBO; long-term EAIRs were 1.6 and 3.1/100PYE for FIL200 and FIL100. EAIRs for herpes zoster were 0.6, 1.1, and 1.1/100PYE for FIL200, FIL100 and PBO; long-term EAIRs were 1.8 and 1.1/100PYE for FIL200 and FIL100. EAIRs for major adverse cardiovascular events were 0, 1.7 and 1.1/100PYE for FIL200, FIL100 and PBO; long-term EAIRs were 0.4 and 0.6/100PYE for FIL200 and FIL100. No venous thromboembolism occurred during the PBO-controlled period; long-term EAIRs were 0.2 and 0/100PYE for FIL200 and FIL100.ConclusionsOver a median of 1.6 and maximum of 5.6 years of exposure, safety/tolerability of FIL200 and FIL100 were similar, with a lower incidence of infections with FIL200 among the long-term, as-treated dataset.

Limited Utility of SIRS Criteria for Identifying Serious Infections in Febrile Young Infants

(1) Background: Young infants have a high risk of serious infection. The Systematic Inflammatory Response Syndrome (SIRS) criteria can be useful to identify both serious bacterial and viral infections. The aims of this study were to evaluate the diagnostic performance of the SIRS criteria for identifying serious infections in febrile young infants and to identify potential clinical predictors of such infections. (2) Methods: We conducted this prospective cohort study including febrile young infants (aged < 90 days) seen at the emergency department with a body temperature of 38.0 °C or higher. We calculated the diagnostic performance parameters and conducted the logistic regression analysis to identify the predictors of serious infection. (3) Results: Of 311 enrolled patients, 36.7% (n = 114) met the SIRS criteria and 28.6% (n = 89) had a serious infection. The sensitivity, specificity, positive predictive value, and positive likelihood ratio of the SIRS criteria for serious infection was 45.9%, 69.4%, 43.5%, 71.4%, 1.5, and 0.8, respectively. Logistic regression showed that male gender, body temperature ≥ 38.5 °C, heart rate ≥ 178 bpm, and age ≤ 50 days were significant predictors. (4) Conclusions: The performance of the SIRS criteria for predicting serious infections among febrile young infants was poor.

937. A Clinical Prediction Tool to Determine Risk of Infection in the First Year Following Heart Transplant

Background Invasive infection is a dangerous complication of heart transplant (HT). No objectively-defined set of risk factors has been established which can reliably predict infection in this population. The aim of this study was to develop a clinical prediction model for use at one month post-HT with the ability to predict serious infection in the first year. Methods A retrospective cohort study of all HT recipients at a single center between 2000 and 2018 was performed, excluding dual-organ recipients, those who died within one month of HT, and those with insufficient data. The composite endpoint included cytomegalovirus infection (CMV), herpes simplex (HSV) or varicella zoster virus infection (VZV), blood stream infection (BSI), and invasive fungal infection (IFI). The follow-up period extended from 1 month to 1 year post-HT. A least absolute shrinkage and selection operator (LASSO) regression model was fit using 13 candidate variables. A C-statistic, calibration curve, and Brier score were used to assess model performance. Results 375 patients were analyzed; 93 outcomes occurred (65 CMV, 3 HSV, 2 VZV, 28 BSI, and 15 IFI). 12 of 13 variables remained in the final model: year of transplant, age at transplant, ischemic cardiomyopathy, diabetes, immune-mediating disease, need for renal replacement therapy in first month, CMV risk status (high, intermediate, low) derived from donor-recipient serology, use of basiliximab induction, use of cytolytic agent in first month, use of ritixumab in first month, rejection treated with high-dose steroids in first month, lymphocyte count under 0.75 x103cells/µL at 1 month, and inpatient status at 1 month. The C-statistic was 0.82 and Brier score 0.142. The calibration curve is shown in Figure 1. Figure 1. Calibration plot Actual versus predicted probability of infection by 1 year. Gray line = ideal Dotted line = smoothed non-parametric calibration curve Conclusion This model synthesizes multiple highly-relevant clinical and laboratory parameters, available at 1 month post-HT, into a unified, objective, and clinically-useful prediction tool for the occurrence of serious infection in the first post-transplant year. Good discrimination and calibration are demonstrated. External validation is required before generalized use. Disclosures Jennifer Chow, M.D., M.S., Merck (Grant/Research Support)Takeda (Grant/Research Support) David R. Snydman, MD, Merck (Consultant, Advisor or Review Panel member, Research Grant or Support)Takeda (Shire) (Advisor or Review Panel member)

The Contribution of Lumbar Puncture in Neonatal Infections - About 206 cases

Background: Neonatal meningitis is a serious infection, no clinico-biological score has been established to accurately identify neonates at high risk of developing neonatal meningitis.Objective: The aim of this work is to clarify the place of lumbar puncture in neonatal infections and to identify the predictive factors of meningeal localization in case of neonatal infection.Materials and methods: This is a prospective study of 861 observations of newborns hospitalized in the pediatric department of Mohammed V Hospital, CHU of Tangier, during a 14-month period from 1January 2019 to 29 February 2020. Among these patients the diagnosis of neonatal infection (NNI) was retained in 473 cases. Initial lumbar puncture was performed in 206 cases (43%). We included neonates aged 0 to 28 days, suspected of NNI, who had a lumbar puncture. Neonates treated as carriers of neonatal infection without sufficient anamnestic and clinical evidence and with an inconclusive or unperformed biological workup were excluded from the study.Results: During the study period, 861 newborns were hospitalized and the diagnosis of neonatal infection was retained in 473 cases, a rate of 55%, and the initial lumbar puncture was performed in 206 cases (43%). 61 newborns were diagnosed with neonatal meningitis, with fever in 76% of cases, 85% with convulsions, hypotonia and/or refusal to suckle in 63% of cases, and CRP >25mg/l in 67% of newborns.Conclusion: Lumbar puncture is the only diagnostic means of meningitis. Indeed, the indication of this procedure should not be systematic, but it should be dictated by the careful and simultaneous analysis of the anamnestic, clinical and biological criteria evocative of the infection and its meningeal localization in order to diagnose meningitis early and treat it correctly. The need to establish scores combining these different parameters, in order to accurately identify newborns at high risk of developing neonatal meningitis

Design and Development of Advanced Glucose Biosensors via Tuned Interactions between Marine Polysaccharides and Diagnostic Elements – A Survey

Extensive scientific analysis on the susceptibility of different populations to COVID-19 highlights that compared to populations with no co-morbidities, people with co-morbidities such as diabetes mellitus (DM) are at a significantly higher risk of serious infection, hospitalization, or even death. This underscores the importance of controlling DM through self-monitoring of blood glucose (SMBG) or continuous glucose monitoring (CGM) using biosensors. These biosensors, which can be either enzymatic or non-enzymatic, have undergone several rounds of development in terms of the materials used for device construction. In terms of the immobilization agent needed to anchor enzymatic or non-enzymatic detection elements to the electrode surface, marine polysaccharides, such as chitosan and alginate, hold a distinct advantage. This, in turn, can be ascribed to their biocompatibility, chemical stability, film-forming ability, capacity to bind with enzymes/diagnostic elements, and easy availability. In this review, we focus extensively on the use of cationic chitosan and anionic alginate in the past decade for designing advanced glucose biosensors. Their role in enhancing sensor response via physical/chemical interactions with the conducting and diagnostic elements is analyzed in detail from a structural point of view. In addition, the possibility of using these polysaccharides in non-invasive CGM sensors is discussed and several potential future research avenues are presented.