Multidomain Convergence of Argonaute during RISC Assembly Correlates with the Formation of Internal Water Clusters.

Despite the relevance of Argonaute proteins in RNA silencing, little is known about the structural steps of small RNA loading to form RNA-induced silencing complexes (RISCs). We report the 1.9 Å crystal structure of human Argonaute4 with guide RNA. Comparison with the previously determined apo structure of Neurospora crassa QDE2 revealed that the PIWI domain has two subdomains. Binding of guide RNA fastens the subdomains, thereby rearranging the active-site residues and increasing the affinity for TNRC6 proteins. We also identified two water pockets beneath the nucleic acid-binding channel that appeared to stabilize the mature RISC. Indeed, mutating the water-pocket residues of Argonaute2 and Argonaute4 compromised RISC assembly. Simulations predict that internal water molecules are exchangeable with the bulk solvent but always occupy specific positions at the domain interfaces. These results suggest that after guide RNA-driven conformational changes, water-mediated hydrogen-bonding networks tie together the converged domains to complete the functional RISC structure.

Manganese-dependent microRNA trimming by 3'→5' exonucleases generates 14-nucleotide or shorter tiny RNAs.

MicroRNAs (miRNAs) are about 22-nucleotide (nt) noncoding RNAs forming the effector complexes with Argonaute (AGO) proteins to repress gene expression. Although tiny RNAs (tyRNAs) shorter than 19 nt have been found to bind to plant and vertebrate AGOs, their biogenesis remains a long-standing question. Here, our in vivo and in vitro studies show several 3'→5' exonucleases, such as interferon-stimulated gene 20 kDa (ISG20), three prime repair exonuclease 1 (TREX1), and ERI1 (enhanced RNAi, also known as 3'hExo), capable of trimming AGO-associated full-length miRNAs to 14-nt or shorter tyRNAs. Their guide trimming occurs in a manganese-dependent manner but independently of the guide sequence and the loaded four human AGO paralogs. We also show that ISG20-mediated guide trimming makes Argonaute3 (AGO3) a slicer. Given the high Mn2+ concentrations in stressed cells, virus-infected cells, and neurodegeneration, our study sheds light on the roles of the Mn2+-dependent exonucleases in remodeling gene silencing.

Oxidative stress and adverse cardiovascular effects among professional divers in Egypt.

Professional divers are exposed to unique multifactorial hazards in their working environment and adverse cardiovascular effects such as ischemia, arrhythmia, stroke, and death are associated with professional diving. Cardiovascular events are aggravated by diving-induced oxidative stress and account for one-fourth of diving fatalities. This study aimed to measure oxidative and cardiovascular stress in a group of professional divers in Alexandria, Egypt using a panel of biomarkers. A comparative cross-sectional study was conducted between June 2017 and May 2018 at the General Naval Hospital in Alexandria. A total of 50 professional divers and a comparison group of 50 marine seafarers sharing similar maritime environments were enrolled in the study. Participants were clinically evaluated by electrocardiography (ECG) and plasma measurement of trace metals (Fe+, Cu+, and Zn+), electrolytes (Na+, K+, Ca+), and oxidative stress biomarkers (OSBMs; MDA, TAS, GST, GSH, GR, GPx, SOD, and CAT). Significant ECG abnormalities including short corrected QT interval, sinus bradycardia, left ventricular hypertrophy, early repolarization, first-degree heart block, and intraventricular conduction defect were identified among divers. Biochemical analyses revealed high mean levels of FBG [89.0 ± 12.46 vs. 100.5 ± 29.03 mg/dl], LDH-C [41.46 ± 4.01 vs. 39.34 ± 4.34 mg/dl], electrolyte imbalance [higher Na+ (9.44 ± 0.52 vs. 9.19 ± 0.60 mmol/L), and lower Ca+ (141.72 ± 3.53 and 143.26 ± 3.99 mmol/L)], disturbed trace metals [Fe+ and Zn+ (101.1 ± 38.17 vs. 147.6 ± 38.08 and 85.52 ± 27.37 vs. 116.6 ± 21.95 µm/dl, respectively), higher Cu+ (271.3 ± 75.01 vs. 100.8 ± 30.20 µm/dl)], and higher OSBMs (high MDA and reduced CAT, GPx, GSH, GR, and GST enzyme levels) among professional divers compared to the marine seafarers (t-test p < 0.05). Oxidative stress and trace metal imbalance are associated with the pathophysiology of cardiovascular disease; this association, together with electrophysiological changes of ECG may serve as biomarkers for cardiovascular risk assessment in diver periodic medical examinations.

Vector-Borne diseases in Egypt: Present status and accelerating toward elimination.

Vector borne diseases (VBDs) remain one of the greatest dangers to global health. At least seven VBDs of public health concern are prevalent in Egypt, including schistosomiasis, fascioliasis, lymphatic filariasis, leishmaniasis, malaria, dengue, and Rift Valley fever. Although many of these diseases are preventable by using evidence-based protective measures, VBD expansion patterns over the past few decades pose a significant challenge for modern parasitology and tropical medicine. In their action plan, Egypt did not identify populations at risk of VBDs. Egypt intends to improve its regional and international communication to identify pathogens and infections and develop "One Health"- compliant preparedness and prevention strategies. However, cross-border collaborations are required for the control of VBDs. In this context, we provide a situational analysis and comprehensive review of the epidemiological data on Egypt's most prevalent VBDs based on an exhaustive search of the major electronic databases and literature from 1950 to 2019. We identified the gaps in Egypt's preparedness for vector-borne disease threats, including adaptation documents, surveillance and monitoring, environmental management, and preparations for the health system. There is a lack of implementation of an integrated vector management strategy that integrates chemical, environmental, and biological control as well as health education. This necessitates cross-sectoral coordination and community involvement to improve vector control activities and the use, storage, and disposal of pesticides.

Effectiveness of hepatitis B vaccination in chronic HCV patients after successful generic direct acting antiviral therapy: significance of isolated hepatitis B core antibodies.

OBJECTIVE: Previous reports show conflicting results regarding hepatitis B virus (HBV) vaccine efficacy in Hepatitis C virus (HCV) infected individuals and in those with isolated hepatitis B core antibodies (HBcAb). We aimed to evaluate the effectiveness of HBV vaccine and identify possible factors that may contribute to hyporesponsivness in HCV-treated patients, including those with isolated HBcAb. METHODS: We conducted a prospective study with 118 enrolled chronic HCV patients who followed a 12-week regimen of direct acting antivirals (DAAs) and were evaluated for HBV serological markers. Eventually, 98 received appropriate HBV vaccination and were assessed for response. RESULTS: A total of 57.1% were vaccine responders although only 5.1% achieved a seroprotective level of HBsAb titre. The response rate was significantly lower among treated HCV patients with isolated HBcAb [2 (5.6%) vs. 40 (64.5%) respectively]. On multivariate analysis, advanced age [OR (95% CI) = 1.09 (1.02-1.17)] and presence of isolated HbcAb [OR (95% CI) = 39.59 (7.98-196.63)] were predictors of vaccine non-response. In our cost-effectiveness models, the cost of HBV serological screening was less than the nationally adopted non-screening approach. A model ratifying reinforced vaccination in non-responder HBcAb seropositive HCV patients would incur extra cost. CONCLUSION: Hyporesponsiveness to the HBV vaccination is frequent in chronic HCV patients even after achieving SVR following DAAs. Although there is no consensus on the clinical management of patients with isolated HBcAb, our cost-effectiveness options may support decision-making for better clinical benefit and proper health investments.

HIV-1 Pr55Gag binds genomic and spliced RNAs with different affinity and stoichiometry.

The HIV-1 Pr55Gag precursor specifically selects genomic RNA (gRNA) from a large variety of cellular and spliced viral RNAs (svRNAs), however the molecular mechanisms of this selective recognition remains poorly understood. To gain better understanding of this process, we analyzed the interactions between Pr55Gag and a large panel of viral RNA (vRNA) fragments encompassing the main packaging signal (Psi) and its flanking regions by fluorescence spectroscopy. We showed that the gRNA harbors a high affinity binding site which is absent from svRNA species, suggesting that this site might be crucial for selecting the HIV-1 genome. Our stoichiometry analysis of protein/RNA complexes revealed that few copies of Pr55Gag specifically associate with the 5' region of the gRNA. Besides, we found that gRNA dimerization significantly impacts Pr55Gag binding, and we confirmed that the internal loop of stem-loop 1 (SL1) in Psi is crucial for specific interaction with Pr55Gag. Our analysis of gRNA fragments of different length supports the existence of a long-range tertiary interaction involving sequences upstream and downstream of the Psi region. This long-range interaction might promote optimal exposure of SL1 for efficient Pr55Gag recognition. Altogether, our results shed light on the molecular mechanisms allowing the specific selection of gRNA by Pr55Gag among a variety of svRNAs, all harboring SL1 in their first common exon.

Fibrocytes Differ from Macrophages but Can Be Infected with HIV-1.

Fibrocytes (fibroblastic leukocytes) are recently identified as unique hematopoietic cells with features of both macrophages and fibroblasts. Fibrocytes are known to contribute to the remodeling or fibrosis of various injured tissues. However, their role in viral infection is not fully understood. In this study, we show that differentiated fibrocytes are phenotypically distinguishable from macrophages but can be infected with HIV-1. Importantly, fibrocytes exhibited persistently infected cell-like phenotypes, the degree of which was more apparent than macrophages. The infected fibrocytes produced replication-competent HIV-1, but expressed HIV-1 mRNA at low levels and strongly resisted HIV-1-induced cell death, which enabled them to support an extremely long-term HIV-1 production at low but steady levels. More importantly, our results suggested that fibrocytes were susceptible to HIV-1 regardless of their differentiation state, in contrast to the fact that monocytes become susceptible to HIV-1 after the differentiation into macrophages. Our findings indicate that fibrocytes are the previously unreported HIV-1 host cells, and they suggest the importance of considering fibrocytes as one of the long-lived persistently infected cells for curing HIV-1.

Toward a simple risk assessment screening tool for HCV infection in Egypt.

Asymptomatic patients with HCV infection identified through screening program could benefit not only from treatment but also from other interventions such as counseling to maintain health and avoid risk behaviors. This might prevent the spread of infection and result in significant public health benefits. However, mass screening would quickly deplete resources. This work aims to develop a brief HCV risk assessment questionnaire that inquires initially about a wide range of risk factors found to be potentially associated with HCV infection in order to identify the few most significant questions that could be quickly used to facilitate cost-effective HCV case-finding in the general population in Egypt. An exhaustive literature search was done to include all reported HCV risk factors that were pooled in a 65 item questionnaire. After an initial pilot study, a case-control study was performed that included 1,024 cases and 1,046 controls. In a multivariable model, a list of independent risk factors were found to be significant predictors for being HCV seropositive among two age strata (<45 and >45 years) for each gender. A simplified model that assigned values of the odds ratio as a weight for each factor present predicted HCV infection with high diagnostic accuracy. Attaining the defined cut-off value of the total risk score enhances the effectiveness of screening. HCV risk factors in the Egyptian population vary by age and gender. An accurate prediction screening tool can be used to identify those at high risk who may benefit most from HCV serologic testing. These results are to be further validated in a large scale cross-sectional study to assess the wider use of this tool. J. Med. Virol. 88:1767-1775, 2016. © 2016 Wiley Periodicals, Inc.

Insulin resistance as a predictor of early virologic response to HCV therapy among chronic HCV Egyptian patients.

Prior assessment of insulin resistance by HOMA-IR is emerging as an important milestone in the treatment of patients with chronic hepatitis C. This cost-effective tool is recommended to individualize treatment duration, or to exclude those with low insulin sensitivity from being treated until ameliorating their state of insulin resistance (IR). The present work aims to elucidate further the effect IR state on early viral kinetic response to Chronic hepatitis C virus (HCV) therapy and the impact of HCV treatment and viral eradication on insulin sensitivity. Insulin sensitivity was assessed using the HOMA-IR method. All enrolled patients were treated with a dual therapy (pegylated interferon-alpha plus ribavirin) for 48 weeks and evaluated using qRT-PCR for early virologic response as well as the impact of treatment on insulin sensitivity throughout the early period of therapy. Of a total 392 chronic HCV cases, early virologic response was achieved by 318 (81.1%). IR was detected in 241 (61.5%) chronic HCV patient of which 73.4% responded to treatment. Early virologic response among patients with > 2.18 HOMA-IR value were significantly lower than those with HOMA-IR values ≤2.18 (P < 0.0001). IR was significantly associated with high baseline BMI. Steatosis and fibrosis correlated with IR but neither independently predicted early virologic response. Pretreatment IR < 2.18, low fasting blood glucose, low and intermediate HCV viral load, normal BMI, and non-smoking were independent factors associated with early virologic response. IR interferes with early virologic response to the antiviral care. Clinical application of pretreatment HOMA-IR assessment could help in predicting early treatment outcome and thus enable treatment regimens to be optimized and individually tailored.

A comprehensive hepatitis C virus risk factors meta-analysis (1989-2013): do they differ in Egypt?

BACKGROUND & AIMS: The prevention and control of HCV infection is complex and challenging in terms of describing risk factors and modes of transmission. This meta-analysis was conducted to summarize the best available data on HCV risk factors worldwide and in Egypt. METHODS: Through exhaustive literature searches (1989-2013) of HCV risk factors, 357 original eligible articles were included in this study. RESULTS: The highest detected risk was intravenous drug users (IDUs) (OR = 9.6) followed by HIV infection (OR = 4.9), having an IDU partner (OR = 4.1), HBV infection (OR = 3.5), Caesarean section (CS) (OR = 3.35), blood transfusion (OR = 3.2) and having an HCV+ partner (OR = 3). Organ transplantation, hospital admission, haemodialysis and having a sexually transmitted infection carry 2.96, 2.4, 2.18 and 2 risks of having HCV respectively. Other significant risk factors included poor education, older age, sharing sharp or blunt objects, MSM, tattooing, hijama, body piercing, minor operations and medical procedures. Some risks showed a decrease over the previous decade, including blood transfusion, organ transplantation, IDUs, IDU partner and CS. Others showed rising risks, including having an HCV+ partner, MSM and suffering from STI. In Egypt, male gender, rural residence, acupuncture and receiving parenteral antischistosomal treatment were significant risks, while neither HIV nor HBV were found to carry a risk of HCV infection. CONCLUSION: Blood transfusion, organ transplantation, CS, IDUs, haemodialysis, minor operations and medical procedures are established risk factors. Attention and urgent intervention should be given to the sexual route of transmission, as well as that through minor operations and medical procedures.

Helicobacter pylori infection in patients with inflammatory bowel diseases: a single-centre, prospective, observational study in Egypt.

OBJECTIVE: Conflicting results have been reported by numerous epidemiological studies investigating the association between Helicobacter pylori (H. pylori) infection and inflammatory bowel disease (IBD). We aimed in this study to assess the possible association between H. pylori infection and IBD and its effects on disease progression. DESIGN: Prospective observational study. SETTING: Specialised IBD care clinics at Alexandria University Student Hospital in northern Egypt, between March and June 2019. PARTICIPANTS: 182 patients with IBD. ANALYSIS AND OUTCOME MEASURES: Participants with IBD were screened for H. pylori infection and clinically evaluated at the initial visit and bimonthly for 3 months to record any potential improvement/flare of the IBD condition. RESULTS: Overall, 90 (49.5%) patients with IBD had evidence of H. pylori infection. The course of IBD did not significantly differ in association with H. pylori infection or IBD treatment strategy. Cox regression analysis revealed that patients aged 20-35 years (HR=6.20 (95% CI: 1.74 to 22.12)) and 35-55 years (557.9 (17.4-17 922.8)), high socioeconomic status (2.9 (1.11-7.8)), daily consumption of fibre-rich food (5.1 (1.32-19.5)), occasional consumption of snacks between meals (2.8 (2.5-70.5)) and eating four meals per day (13.3 (1.0-7.7)) were predictive of IBD flare. By contrast, eating fruits and vegetables showed a strongly protective association (HR=0.001 (95% CI: 0.0002 to 0.02)). The probabilities of improvement of IBD symptoms after 12 weeks of follow-up were comparable in assessments based on H. pylori infection status (0.793 for H. pylori negative vs 0.778 for H. pylori positive) and IBD treatment option (0.811 for conventional therapy vs 0.750 for biological therapy). CONCLUSION: The association between IBD and H. pylori infection is unresolved and should be further investigated in the context of specific environmental exposures that can influence the development or relapse of IBD.

Assessment of dengue virus threat to blood safety and community health: A single center study in northern Egypt.

Background: The risk of transfusion transmitted dengue (DENV) is increasingly recognized and poses a risk to blood safety as well as spreading into non-immune communities. Objectives: To determine dengue serological profile, environmental risk, knowledge, and preventive measures among blood donors in a national blood bank in northern Egypt. Methods: A total of 500 blood donors were enrolled into this study between June and September 2018. Socio-demographic and medical data were collected using a predesigned questionnaire. Blood samples were screened for anti-DENV IgM, anti-DENV IgG and non-structural protein 1 antigen (DENV-NS1 antigen). Results: History of past dengue exposure was identified in 10.2% of blood donors. No samples (0.0%) tested positive for anti-DENV IgG, IgM or NS1 antigen. At the time of blood donation, no individuals had any symptoms suggestive of a dengue-related illness. Dengue exposure strongly correlated with travel to the Kingdom of Saudi Arabia (KSA), Sudan and the El-Quseir outbreak area in Egypt. Knowledge of dengue and prevention methods was found to be substantially deficient, and the relatively higher level of knowledge among exposed donors did not translate into appropriate preventative measures. Conclusions: Our risk assessment shows the impact of travel on DENV exposure and highlights its potential threat to disease spread in Egypt. Dengue awareness programs are urgently needed for effective prevention of transmission.

Validation of a COVID-19 self-assessment tool for the prediction of COVID-19 in a primary health care setting in Egypt.

BACKGROUND: As SARS-CoV-2 infection is sweeping the globe, early identification and timely management of infected patients will alleviate unmet health care demands and ultimately control of the disease. Remote COVID-19 self-assessment tools will offer a potential strategy for patient guidance on medical consultation versus home care without requiring direct attention from healthcare professionals. OBJECTIVE(S): This study aimed to assess the validity and interrater reliability of the initial and modified versions of a COVID-19 self-assessment prediction tool introduced by the Egyptian Ministry of Health and Population (MoHP) early in the epidemic. The scoring tool was released for the public through media outlets for remote self-assessment of SARS-CoV-2 infection connecting patients with the appropriate level of care. METHODS: We evaluated the initial score in the analysis of 818 consecutive cases presenting with symptoms suggesting COVID-19 in a single-primary health care clinic in Alexandria during the epidemic in Egypt (mid-February through July). Validity parameters, interrater agreement and accuracy of the score as a triage tool were calculated versus the COVID-19 polymerase chain reaction (PCR) test. RESULTS: A total of 818 patients reporting symptoms potentially attributable to COVID-19 were enrolled. The initial tool correctly identified 296 of 390 COVID-19 PCR +ve cases (sensitivity = 75.9%, specificity = 42.3%, positive predictive value = 54.5%, negative predictive value = 65.8%). The modified versions of the MoHP triage score yielded comparable results albeit with a better accuracy during the late epidemic phase. Recent history of travel [OR (95% CI) = 12.1 (5.0-29.4)] and being a health care worker [OR (95% CI) = 5.8 (2.8-11.9)] were major predictors of SARS-CoV-2 infection in early and late epidemic phases, respectively. On the other hand, direct contact with a respiratory infection case increased the risk of infection by three folds throughout the epidemic period. CONCLUSION: The tested score has a sufficient predictive value and potential as a triage tool in primary health care settings. Updated implementation of this home-grown tool will improve COVID-19 response at the primary health care level.

Identifying factors increasing the risk of acquiring HIV among Egyptians to construct a consensus web-based tool for HIV risk assessment.

BACKGROUND: Accurate information on HIV transmission risk is required to construct evidence-based risk reduction practices for individuals and to direct the provision of prevention strategies at the population level. HIV transmission risk assessment will help in identifying individuals at high risk of HIV infection and directing the provision of post exposure prophylaxis (PEP). OBJECTIVE: To identify the common risk factors for HIV transmission in the Egyptian community in order to construct a web-based HIV risk assessment tool. METHODS: Following a systematic review and meta-analysis of published literature on HIV transmission and risk factors, we retrieved the key determinants of HIV exposure risk. In parallel, we conducted a case control study to identify the common risk factors for HIV transmission in the Egyptian community. The identified risk factors were incorporated in weighted risk scoring models to allow the quantification of the risk of HIV acquisition. RESULTS: There were 38 determinants associated with HIV seropositivity [people living with HIV (PLWH)] among Egyptians compared to 34 risk factors identified in our meta-analysis. All the derived scores showed high accuracy for predicting HIV infection status [sensitivity, specificity, PPV and NPV of greater than 90.0%, (AUC = 0.998-1.000; p < .001)]. CONCLUSION: Key drivers of HIV transmissions can be incorporated into a risk scoring model in order to quantify the risks of HIV acquisition. Such tools can facilitate the screening of PLWH and at-risk-individuals and direct interventions to halt HIV transmission.

A clinical rule for the prediction of meningitis in HIV patients in the era of combination antiretroviral therapy.

BACKGROUND: The diagnosis of meningitis in HIV patients is challenging due to altered immune responses. Diagnostic scoring systems were recently proposed for use in research settings to help prompt and easy differential diagnosis. The objective of this study was to create a clinical prediction rule (CPR) for meningitis in HIV-infected patients and to address the enigma of differentiating bacterial (BM), TB (TBM) and cryptococcal (CCM) meningitis based on clinical features alone, which may be enhanced by easy-to-obtain laboratory testing. METHODS: We retrospectively enrolled 352 HIV patients presenting with neurological manifestations suggesting meningitis over the last 18 y (2000-2018). Relevant clinical and laboratory information were retrieved from inpatient records. The features independently predicting meningitis or its different types in microbiologically proven meningitis cases were modelled by multivariate logistic regression to create a CPR in an exploratory data set. The performance of the meningitis diagnostic score was assessed and validated in a subset of retrospective data. RESULTS: AIDS clinical stage, injecting drug use, jaundice and cryptococcal antigen seropositivity were equally important as classic meningitic symptoms in predicting meningitis. Arthralgia and elevated cerebrospinal fluid Lactate dehydrogenase (LDH) were strong predictors of BM. Patients with cryptococcal antigenemia had 25 times the probability of having CCM, whereas neurological deficits were highly suggestive of TBM. CONCLUSION: The proposed CPRs have good diagnostic potential and would support decision-making in resource-poor settings.

Sofosbuvir-/Daclatasvir-based therapy for chronic HCV and HCV/hepatitis B virus coinfected patients in Egypt.

BACKGROUND: Dramatic advances in hepatitis C virus (HCV) treatment were witnessed with the introduction of direct-acting antivirals (DAAs). Generic DAAs with remarkable efficacy and good safety profiles are currently manufactured by local pharmaceutical companies in Egypt. METHODS: In the real-world setting, of a total of 367 patients chronically infected with HCV, 289 (277 treatment-naïve and 12 treatment-experienced) patients were enrolled. Approximately 15% of the patients were coinfected with hepatitis B virus (HBV). Patients were treated with sofosbuvir+daclatasvir with or without ribavirin for 12 or 24 wk as the standard of care. HBV DNA levels were monitored throughout the study. RESULTS: A sustained virologic response at 12 wk (SVR12) was achieved in 98.3% of the patients. All non-responders were treatment-naïve and the response rate among treatment-experienced patients was 100.0%. Elevated α-fetoprotein and treatment with sofosbuvir+daclatasvir+ribavirin for 6 mo were predictors of non-response (OR [95% CI] = 1.06 [1.02 to 1.1] and 15.9 [1.8 to 136.2]; p<0.05, respectively). No HBV reactivation was noticed throughout the treatment and follow-up periods in HCV/HBV coinfected patients. CONCLUSION: The present real-world findings add to the evidence for the efficacy of generic DAAs for the treatment of patients infected with HCV. HBV reactivation is unlikely to occur in those coinfected with HBV. Although liver cirrhosis affected the outcome, pretreatment liver chemistry did not seem to correlate with the results of treatment.

How accurate is the diagnosis of rheumatic fever in Egypt? Data from the national rheumatic heart disease prevention and control program (2006-2018).

Rheumatic heart disease (RHD) as a chronic sequela of repeated episodes of acute rheumatic fever (ARF), remains a cause of cardiac morbidity in Egypt although it is given full attention through a national RHD prevention and control program. The present report reviews our experience with subjects presenting with ARF or its sequelae in a single RHD centre and describes the disease pattern over the last decade. A cross-sectional study was conducted in El-Mahalla RHD centre between 2006 and 2018. A total of 17014 individual were enrolled and evaluated. Diagnosis ARF was based on the 2015 revised Jones criteria and RHD was ruled in by echocardiography. The majority of the screened subjects were female (63.2%), in the age group 5-15 years (64.6%), rural residents (61.2%), had primary education (43.0%), and of low socioeconomic standard (50.2%). The total percentage of cases presenting with ARF sequelae was 29.3% [carditis/RHD (10.8%), rheumatic arthritis (Rh.A) (14.9%), and Sydenham's chorea (0.05%)]. Noticeably, 72% were free of any cardiac insult, of which 37.7% were victims of misdiagnoses made elsewhere by untrained practitioners who prescribed for them long term injectable long-acting penicillin [Benzathine Penicillin G (BPG)] without need. About 54% of the study cohort reported the occurrence of recurrent attacks of tonsillitis of which 65.2% underwent tonsillectomy. Among those who experienced tonsillectomy and/or received BPG in the past, 14.5% and 22.3% respectively had eventually developed RHD. Screening of family members of some RHD cases who needed cardiac surgery revealed 20.7% with undiagnosed ARF sequalae [RHD (56.0%) and Rh.A (52.2%)]. Upon the follow-up of RHD cases, 1.2% had improved, 98.4% were stable and 0.4% had their heart condition deteriorated. Misdiagnosis of ARF or its sequelae and poor compliance with BPG use may affect efforts being exerted to curtail the disease. Updating national guidelines, capacity building, and reliance on appropriate investigations should be emphasized. Since the genetic basis of RHD is literally confirmed, a family history of RHD warrants screening of all family members for early detection of the disease.

Attributes of HIV infection over decades (1982-2018): A systematic review and meta-analysis.

Understanding the risk factors for HIV infection is the foundation of successful preventive strategies, which must bundle sociocultural, behavioural and biomedical interventions to halt disease transmission. We aimed in this study to provide a pooled estimation of HIV risk factors and trace changes across decades in order to drive consensus and accurate assessment of disease transmission risk. We comprehensively searched PubMed, ISI Web of Knowledge, Medline, EMBASE, ScienceDirect, Ovid, EBSCO, Google Scholar and the Egyptian Universities Library Consortium from October to December 2018. Two independent reviewers extracted data from eligible studies. Funnel plots were inspected to identify publication bias. Heterogeneity across studies was checked using the Q and I2 statistics. The results were reported based on the pooled odds ratio (pOR) with 95% CI using a random-effects model. Meta-analysis of HIV risk factors revealed a superior role for risky sexual practices (unprotected vaginal/anal sex), injecting drug use (IDU), sharing needles, sexually transmitted infections (STIs), child sexual abuse and vertical transmissions. Trends across decades (1982-1999 and 2000-2018, respectively) showed rising evidence for prostitution [pOR (95% CI)= 2.3 (1.12-4.68) versus 2.69 (1.67-4.32)] and men who have sex with men (MSM) [pOR (95% CI)= 2.28 (1.64-3.17) versus 3.67 (1.88-7.17)], while transmission through IDU [pOR (95% CI)= 3.42 (2.28-5.12) versus 2.16 (1.74-2.70)], alcoholism [pOR (95% CI)= 2.35 (0.73-7.59) versus 1.71(1.08-2.72)], and sharing syringes [pOR (95% CI)= 6.10 (2.57-14.5) versus 2.70 (2.01-6.35)] showed notable decline. Harm reduction programs and condom use have been recognized as chief HIV prevention strategies, while male circumcision contributed a partial role. Collectively, sexual risk factors continue to be a key driver of the global HIV epidemic. Persistent and emerging risk factors identified in our analysis should constitute the forefront targets of HIV prevention programmes to accelerate efforts towards HIV elimination.

Spatio-temporal Distribution of Meningitis in HIV Patients in Northern Egypt (2000-2018).

BACKGROUND: Meningitis is a leading cause of death among patients living with HIV. There is no adequate tracking of the disease occurrence, distribution and etiologic agents among this risk group in Egypt, although the pattern could differ from that of the general population. OBJECTIVES: We aimed to describe the spatio-temporal distribution of meningitis in HIV patients in a region of Northern Egypt over 18 years (2000-2018). METHODS: We conducted a retrospective study of 352 adult HIV patients admitted to a tertiary care fever hospital with neurological manifestations suggesting meningitis. We retrieved from inpatient records all data relevant to patient demographics, clinical presentation, diagnostic work-up, results of laboratory investigations (CSF, blood, imaging), definitive diagnosis, and in-hospital mortality. RESULTS: The overall trend of over 2 decades showed fluctuating incidence of meningitis in HIV infected patients and increasing spread into rural areas, with a uniform circulation among adult males. Cryptococcal meningitis was the most common etiologic agent (26.9%) and was associated with worse outcomes. Focal neurological deficit (38.5%), cranial nerve involvement (48.1%) were common features in TB Meningitis. The mortality was high (56.8%) and was significantly associated with low CD4+ count, advanced AIDs clinical stage and the presence of co-morbidities. CONCLUSION: Despite the availability of cART, meningitis, particularly cryptococcal, is common in HIV/AIDS population in Egypt. Continued efforts are desperately needed to improve the outcomes of HIV-infected patients.

Assessment of oxidative stress among refueling workers in an Egyptian setting.

BACKGROUND: Unlike developing countries, in Egypt, gasoline is dispensed at dedicated stations by gasoline filling workers. This leads to high levels of exposure to the aromatic compounds in gasoline [principally benzene, toluene, ethyl benzene, and xylene (BTEX)] with the consequences of adverse health effects including oxidative stress. OBJECTIVE(S): To assess oxidative stress and trace metal levels among Egyptian gas filling workers. METHODS: A cross-sectional study was conducted among 50 gasoline filling station workers (exposed group) and a matched group of 50 clerical workers (non-exposed group). Trace metal levels (Cu, Zn, Fe, and Mn) and the activities of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) were measured in sera of all enrolled participants using atomic absorption spectroscopy. BTEX levels were assessed in the environment of the studied gas filling stations using the MIRAN IR system. RESULTS: All the measured trace metal levels and antioxidant enzyme activities were significantly lower among the exposed workers than among the non-exposed workers. All trace metals decreased significantly in relation to SOD activity among the exposed workers, whereas only Zn and Cu decreased in relation to SOD and GPx activity among the non-exposed workers. The exposed workers did not comply with the use of the required personal protective equipment (PPE) to avoid the dangerous effects of BTEX exposure. Among BTEX components, benzene exceeded the allowable Egyptian TLV in the studied gasoline stations (110.4 mg/m3 versus 1.6 mg/m3, respectively). The hygienic effect (HE) of the BTEX pollutant mixture exceeded the allowed borderline HE in Egypt although it did not show a significant correlation with different oxidative stress biomarkers and trace metals. CONCLUSION: Exposure to BTEX at gasoline filling stations lowers the levels of antioxidant enzyme activities and trace metals due to the strong hygienic effect of BTEX. Individual protection using the proper PPE should therefore be enforced. Research assessing the need of providing refueling workers with supplements of necessary trace metals and antioxidants is warranted.