The Possible Mechanisms of Cu and Zn in the Treatment and Prevention of HIV and COVID-19 Viral Infection.

Due to their unique properties and their potential therapeutic and prophylactic applications, heavy metals have attracted the interest of many researchers, especially during the outbreak of COVID-19. Indeed, zinc (Zn) and copper (Cu) have been widely used during viral infections. Zn has been reported to prevent excessive inflammatory response and cytokine storm, improve the response of the virus to Type I interferon (IFN-1), and enhance the production of IFN-a to counteract the antagonistic effect of SARS-CoV-2 virus protein on IFN. Additionally, Zn has been found to promote the proliferation and differentiation of T and B lymphocytes, thereby improving immune function, inhibiting RNA-dependent RNA polymerase (RdRp) in SARS- CoV-2 reducing the viral replication and stabilizing the cell membrane by preventing the proteolytic processing of viral polyprotein and proteases enzymes. Interestingly, Zn deficiency has been correlated with enhanced SARS-CoV-2 viral entry through interaction between the ACE2 receptor and viral spike protein. Along with zinc, Cu possesses strong virucidal capabilities and is known to be effective at neutralizing a variety of infectious viruses, including the poliovirus, influenza virus, HIV type 1, and other enveloped or nonenveloped, single- or double-stranded DNA and RNA viruses. Cu-related antiviral action has been linked to different pathways. First, it may result in permanent damage to the viral membrane, envelopes, and genetic material of viruses. Second, Cu produces reactive oxygen species to take advantage of the redox signaling mechanism to eradicate the virus. The present review focused on Zn and Cu in the treatment and prevention of viral infection. Moreover, the application of metals such as Cu and gold in nanotechnology for the development of antiviral therapies and vaccines has been also discussed.

Multilineage Differentiating Stress Enduring (Muse) Cells: A New Era of Stem Cell-Based Therapy.

Stem cell transplantation has recently demonstrated a significant therapeutic efficacy in various diseases. Multilineage-differentiating stress-enduring (Muse) cells are stress-tolerant endogenous pluripotent stem cells that were first reported in 2010. Muse cells can be found in the peripheral blood, bone marrow and connective tissue of nearly all body organs. Under basal conditions, they constantly move from the bone marrow to peripheral blood to supply various body organs. However, this rate greatly changes even within the same individual based on physical status and the presence of injury or illness. Muse cells can differentiate into all three-germ-layers, producing tissue-compatible cells with few errors, minimal immune rejection and without forming teratomas. They can also endure hostile environments, supporting their survival in damaged/injured tissues. Additionally, Muse cells express receptors for sphingosine-1-phosphate (S1P), which is a protein produced by damaged/injured tissues. Through the S1P-S1PR2 axis, circulating Muse cells can preferentially migrate to damaged sites following transplantation. In addition, Muse cells possess a unique immune privilege system, facilitating their use without the need for long-term immunosuppressant treatment or human leucocyte antigen matching. Moreover, they exhibit anti-inflammatory, anti-apoptotic and tissue-protective effects. These characteristics circumvent all challenges experienced with mesenchymal stem cells and induced pluripotent stem cells and encourage the wide application of Muse cells in clinical practice. Indeed, Muse cells have the potential to break through the limitations of current cell-based therapies, and many clinical trials have been conducted, applying intravenously administered Muse cells in stroke, myocardial infarction, neurological disorders and acute respiratory distress syndrome (ARDS) related to novel coronavirus (SARS-CoV-2) infection. Herein, we aim to highlight the unique biological properties of Muse cells and to elucidate the advantageous difference between Muse cells and other types of stem cells. Finally, we shed light on their current therapeutic applications and the major obstacles to their clinical implementation from laboratory to clinic.

Green polymer altered in-situ gel oral liquid sustainable release preparation of vildagliptin suitable for dysphagic diabetic patients: assessment in-vitro & in-vivo.

PURPOSE: This work aimed to fabricate alginate based in-situ gelling matrix of vildagliptin improved by calcium and carboxy methyl cellulose (CMC) for appropriate adjustment of the onset and duration of action. This easy-to-swallow thickened liquid preparation aimed to improve compliance for dysphagic or elderly diabetic patients. METHODS: Vildagliptin dispersions containing alginate were fabricated in the presence or absence of calcium chloride to assess the effect of calcium ion, then a matrix containing 1.5% w/v of sodium alginate with calcium was further examined after the addition of CMC with different concentrations ranging from 0.1% to 0.3%. The viscosity, gelling forming property, Differential scanning calorimetry, and in-vitro drug release were assessed before monitoring the hypoglycemic effect of the selected formulation. RESULTS: In-situ gel matrixes were fabricated at gastric pH with and without calcium ions. The best formula concerning viscosity and the gel-forming property was achieved with higher CMC concentrations, which in turn decreased the rate of vildagliptin release in stimulated gastric pH. In-vivo results confirmed the extended hypoglycemic effect of the vildagliptin in-situ gelling matrix compared to the vildagliptin aqueous solution. CONCLUSION: This study represents a green polymeric-based in-situ gel as a liquid oral retarded release preparation intended for reducing dose frequency, easier administration of vildagliptin, and improving compliance in geriatric and dysphagic diabetic patients.

Exosomes in COVID-19 infection: Focus on role in diagnosis, pathogenesis, immunity, and clinical trials.

Since the end of 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread as a new strain of coronavirus disease (COVID-19) and progressed as a global pandemic. Exosomes are membrane-bound vesicles released from almost all cells and are crucially involved in cell-cell communication. Interestingly, COVID-19 viral particles produce exosomes that moderate communication between infected and uninfected cells. Hence, there is growing evidence highlighting the crucial implications of exosomes in COVID-19 infection, transmission, intercellular spread, and reinfection. On the other hand, clinical trials have demonstrated mesenchymal stem cell-derived exosomes as a promising therapeutic strategy for severely affected COVID-19 patients. Also, convalescent plasma-derived exosomes have been proposed for multiple efficacies in COVID-19 patients. Furthermore, messenger RNAs (mRNA)-loaded exosomes were superior to mRNA-loaded lipid nanoparticles as a delivery system. Hence, exosomes can be used to safely induce SARS-CoV-2 immunity via their loading with mRNAs encoding immunogenic forms of SARS-CoV-2 spike and nucleocapsid proteins. Moreover, exosomes can be used as a nano-delivery system for microRNA to alleviate cytokine storm and prevent the progression of organ failure in COVID-19 patients. The present review summarizes state of the art concerning the role of exosomes in COVID-19 infection and accompanying organ complications as well as the potential use of exosomes in COVID-19 diagnosis, treatment, drug delivery, and vaccination. The review also sheds the light on the common biogenic pathway between the SARS-CoV-2 virus and exosomes. Additionally, the latest and current clinical trials using exosomes for COVID-19 infection are summarized.

Histomorphological, histochemical and scanning electron microscopic investigation of the proventriculus (Ventriculus glandularis) of the hooded crow (Corvus cornix).

The current investigation aimed to clarify the histomorphological features, scanning electron microscopy (SEM) and histochemistry of the proventriculus in the adult hooded crow (Corvus cornix). Twenty-two adult birds of both sexes were collected from El-Fayoum and Beni-Suef governorates, Egypt; ten were used for anatomical investigation, two were scanned using SEM, and ten were subjected to routine histological technique. The obtained anatomical results revealed a small-sized spindle-shaped proventriculus obliquely located in the left ventral part of the body cavity with an average body weight, length and diameter of 1.689 ± 0.231 gm, 1.54 ± 0.383cm and 3.51 ± 0.416cm, respectively. The histological examination revealed a typical tubular organ. The mucosa exhibited several plicae and sulci that were lined with simple columnar cells. The lamina propria was composed of collagenous connective tissue infiltrated by lymphocytes, lymphatic aggregations and tubular glands. The submucosa consisted of collagenic fibres and compound tubuloalveolar glandular lobules lined with oxynticopeptic cells and enteroendocrine cells. The oxynticopeptic cells reacted negatively with PAS and Alcian Blue stains, whereas the ductal cells reacted positively with PAS only. Enteroendocrine cells were seen singly in the lamina epithelialis mucosae and were abundant in submucosal glands. The tunica musclaris was arranged in two layers covered by serosa. The proventricular glands' openings were noticed by SEM as raised tubes with regular circular outlines surrounded by anastomosed microscopic folds. The obtained histomorphological structure of the hooded crow's proventriculus revealed some shared morphological features with most species of birds and some variations that might be attributed to their diet and feeding behaviour.

Morphological characteristics of the forebrain in the donkey (Equus asinus): A compared atlas of magnetic resonance imaging and cross-sectional anatomy.

The brain is the most essential part of the central nervous system which regulates and coordinates all body activities. Based on its phylogenetic development from the neural tube, the brain is divided into rhombencephalon (hindbrain), mesencephalon (midbrain) and prosencephalon (forebrain). The present study is achieved to describe the morphological characteristics of the normal forebrain in the donkey using the matched magnetic resonance imaging (MRI) and cross-sectional anatomy. Ten cadaveric heads of healthy adult donkeys of both sexes were used. Two heads were examined using a 1.5 Tesla MRI scanner, and the brains of the other heads were gently extracted; six brains were sectioned into transverse, dorsal and sagittal slices, and two brains were grossly inspected. MR images were selected in correlation to their closely corresponding gross sections. Both cross-sectional anatomy and MRI scans showed extensive gyration of the neocortex. The forebrain structures appeared with variable intensities on three sequences, Flair, T1-weighted and T2-weighted MRI, enabling comprehensive evaluation of the relevant neuroanatomical structures. The present study provided a precise neuroanatomical atlas of the forebrain in the donkey which could help in the quick and efficient interpretation of clinical diseases of the forebrain, localization of the forebrain functions and evolutionary neurobiology.

Pattern of psychiatric in-patient admissions in Al Ain, United Arab Emirates.

An understanding of the current state of mental health services in the United Arab Emirates (UAE) from a clinical perspective is an important step in advising government and stakeholders on addressing the mental health needs of the fast-growing population. We conducted a retrospective study of data on all patients admitted to a regional psychiatric in-patient unit between June 2012 and May 2015. More Emiratis (UAE nationals) were admitted compared with expatriates. Emiratis were diagnosed more frequently with substance use disorders and expatriates with stress-related conditions. Psychotic and bipolar disorders were the most common causes for admission and had the longest in-patient stays; advancing age was associated with longer duration of in-patient stay.

Radiation-induced synthesis of copper sulfide nanotubes with improved catalytic and antibacterial activities.

In the current paper, copper sulfide nanotubes have been successfully synthesized via the green, simple, and effective gamma-radiolysis method without adding any capping or reducing agents. The structural and morphological characteristics of the as-prepared CuS nanotubes were investigated by X-ray diffraction (XRD), N2 adsorption-desorption measurements at 77 K, transmission electron microscopy (TEM), and ultraviolet-visible (UV-vis) spectroscopy, which all demonstrated the formation of pure CuS covellite phase with tubular morphology. The synthesized CuS nanotubes possessed not only high activity towards the reduction of both cationic (methylene blue) and anionic (Congo red) dyes in the presence of NaBH4 but also exhibited excellent reusability. In addition, the pseudo-first-order kinetic model represented the reduction of MB very well, and the value of the normalized rate constant (2.4 × 10-2 s-1 mg-1) was higher than those of other solid catalysts reported in the literature. Ultimately, CuS nanotubes were found to have a broad-spectrum microbicidal action against the common microbiota, such as Gram-positive (exemplified by Bacillus subtilis and Staphylococcus aureus), Gram-negative bacteria (exemplified by Pseudomonas aeruginosa and Escherichia coli), yeast (exemplified by Candida albicans), and plant pathogenic fungi (exemplified by Aspergillus niger).

Exosomes: Isolation, characterization, and biomedical applications.

Exosomes are nano-sized bioactive vesicles of 30-150 nm in diameter. They are secreted by exocytosis of nearly all type of cells in to the extracellular fluid. Thereby, they can be found in many biological fluids. Exosomes regulate intracellular communication between cells via delivery of their cargo which include lipids, proteins, and nucleic acid. Many desirable features of exosomes made them promising candidates in several therapeutic applications. In this review, we discuss the use of exosomes as diagnostic tools and their possible biomedical applications. Additionally, current techniques used for isolation, purification, and characterization of exosomes from both biological fluids and in vitro cell cultures were discussed.

Gross anatomical, computed tomographic and magnetic resonance imaging study of the metacarpo/metatarsophalangeal joint in Egyptian buffalo (Bubalus bubalis).

The current study aimed to describe the normal gross anatomy, computed tomography (CT) and magnetic resonance imaging (MRI) of the metacarpo/metatarsophalangeal (MCP/MTP) joint in Egyptian buffalo, and to determine the site of intra-articular injection of this joint. This study was conducted on eighteen fresh cadaveric distal limbs of healthy Egyptian buffaloes. Six cadaveric MCP/MTP joints were freshly dissected for studying their normal morphological features and determination of the suitable site for intra-articular injection. Another twelve MCP/MTP joints were imaged using a 16-slice CT scanner and a 1.5 Tesla MRI scanner, injected with coloured latex and then sectioned into dorsal, sagittal and transverse slices. The articular surface, joint cavity, ligaments and surrounding tendons of the MCP/MTP joint were identified and briefly described. CT and MRI provided identification of the bony and soft tissue structures of the MCP/MTP joint with variable signal intensities. The present study provided a brief description of the normal gross anatomy of MCP/MTP joint in buffalo to serve as a reference for the evaluation of CT and MRI images, which in turn could enable the veterinary clinicians in interpretation of the clinical diseases in this joint.

Measures of gluten-related reactivity in children with autism spectrum disorders in the absence of overt gastrointestinal symptoms: a pilot study from the United Arab Emirates.

OBJECTIVES: The aetiology of autism spectrum disorder (ASD) is multifactorial, sometimes genetic, and may be associated with abnormal immunological responses to peptides from proteins such as gluten. These peptides may cross the blood-brain barrier and affect neurotransmission, resulting in behavioural symptoms consistent with ASD. The aim of this study was to screen for markers of gluten-related immune reactivity in the absence of overt gastrointestinal symptoms in patients with ASD in the United Arab Emirates, a country associated with a high prevalence of ASD but lacking this type of research. METHODS: Patients diagnosed with ASD (using Diagnostic and Statistical Manual of Mental Disorders-IV-based criteria and Autism Diagnostic Observational Schedules) were compared with controls, regarding anti-tissue transglutaminase (tTG) immunoglobulin (Ig) A and anti-deamidated gliadin peptide (DGP) IgA levels. RESULTS: Sixty-six patients with ASD and 101 controls were included. Patients with ASD showed statistically significant lower anti-DGP IgA levels, but no significant difference in anti-tTG IgA levels, versus healthy controls. Correlations between immunological data and clinical symptoms were synergistic, but not statistically significant. CONCLUSION: ASD may be associated with reduced levels of anti-DGP IgA.

Umbilical cord stem cells: Background, processing and applications.

Stem cells have currently gained attention in the field of medicine not only due to their ability to repair dysfunctional or damaged cells, but also they could be used as drug delivery system after being engineered to do so. Human umbilical cord is attractive source for autologous and allogenic stem cells that are currently amenable to treatment of various diseases. Human umbilical cord stem cells are -in contrast to embryonic and fetal stem cells- ethically noncontroversial, inexpensive and readily available source of cells. Umbilical cord, umbilical cord vein, amnion/placenta and Wharton's jelly are all rich of many types of multipotent stem cell populations capable of forming many different cell types. This review will focus on umbilical cord stem cells processing and current application in medicine.

Normal anatomic reference of pastern and coffin joints in Egyptian buffalo (Bubalus bubalis): A compared atlas of cross-sectional anatomy, magnetic resonance imaging and computed tomography.

The purpose of this study was to describe normal magnetic resonance imaging and computed tomographic anatomy of pastern and coffin joints in Egyptian buffalo using cadaveric distal limbs. This study was achieved using twelve fresh cadaveric distal limbs from adult healthy buffaloes of both sexes. These cadaveric limbs were scanned using a 1 Tesla MRI scanner and CT scanner, injected with red latex, frozen at -20°C for 1 week, and then sectioned into sagittal, dorsal and transverse slices. The obtained MR and CT images were selected to be matched with their corresponding anatomical cross-sections for identification and evaluation of the clinically correlated anatomical structures of the pastern and coffin joints. The difference in signal intensities on CT and MRI scans amongst the tissues allowed clear differentiation of major bone and soft tissue structures of the pastern and coffin joints. CT provided a high spatial resolution of bone and soft tissue structures, however, MRI allowed a better and higher resolution and definition between soft tissues. The current study provided a normal CT and MRI anatomic reference which could help veterinary clinicians for interpretation and diagnosis of the clinically affected pastern and coffin joints in buffalo.

Surgical anatomy of the nasal and paranasal sinuses in Egyptian native sheep (Ovis aries) using computed tomography and cross sectioning.

The present work aimed to describe the normal computed tomography (CT) and cross-sectional anatomy of the nasal and paranasal sinuses in sheep and to correlate these features with the relevant clinical practices. Twenty apparent healthy heads of Egyptian native breed of sheep (Baladi sheep) of both sexes were used for studying these sinuses. CT images and their closely identical cross sections of the same head were selected and serially labelled in a progression from the rostral nasal region to the caudal aspect of the head using cheek teeth as landmarks. The current investigation reported seven sinuses in sheep, including maxillary, frontal, lacrimal and sphenoidal as paranasal, as well as dorsal and middle conchal and ethmoidal as nasal with unnoticeable palatine and ventral nasal conchal sinuses. The boundaries, extension, structure and communications of these sinuses were fully described. The current study provided anatomical guidelines for surgical interference in the frontal and maxillary sinuses during trephination, dehorning and sinuscopy. Also, an acceptable anatomical explanation was reported in this study for the high incidence of maxillary sinusitis than other sinuses. CT and cross-sectional anatomy could be used as helpful database for diagnosis and clinical interference of the nasal and paranasal sinuses in sheep.

Methicillin-Resistant Staphylococcus aureus Recovered from Healthcare- and Community-Associated Infections in Egypt.

Background. Methicillin-resistant Staphylococcus aureus (MRSA) has created significant epidemiological, infection-control, and therapeutic management challenges during the past three decades. Aim. To analyze the pattern of resistance of healthcare- and community-associated MRSA in Egypt and the trend of resistance of HA-MRSA over time (2005-2013). Methods. MRSA isolates were recovered from healthcare-associated (HA) and community-associated (CA) Staphylococcus aureus (S. aureus) infections. They were tested against 11 antimicrobial discs and the minimal inhibitory concentration (MIC) of vancomycin was determined. Inducible clindamycin resistance (iMLSB) was also screened using D-test. Findings. Of 631 S. aureus, MRSA was identified in 343 (76.6%) and 21 (11.5%) of HA and CA S. aureus isolates, respectively. The proportion of HA-MRSA increased significantly from 48.6% in 2005 to 86.8% in 2013 (p value < 0.001). Multidrug resistance (MDR) was observed in 85.8% of HA-MRSA and 48.6% of CA-MRSA. Vancomycin intermediate resistant S. aureus (VISA) was detected in 1.2% of HA-MRSA and none was detected in CA-MRSA. Among HA-MRSA strains, 5.3% showed iMLSB compared to 9.5% among CA-MRSA. Conclusion. The upsurge of the prevalence rates of HA-MRSA over time is alarming and urges for an effective infection control strategy and continuous monitoring of antimicrobial use.

Molecular characterization of multidrug resistant hospital isolates using the antimicrobial resistance determinant microarray.

Molecular methods that enable the detection of antimicrobial resistance determinants are critical surveillance tools that are necessary to aid in curbing the spread of antibiotic resistance. In this study, we describe the use of the Antimicrobial Resistance Determinant Microarray (ARDM) that targets 239 unique genes that confer resistance to 12 classes of antimicrobial compounds, quaternary amines and streptothricin for the determination of multidrug resistance (MDR) gene profiles. Fourteen reference MDR strains, which either were genome, sequenced or possessed well characterized drug resistance profiles were used to optimize detection algorithms and threshold criteria to ensure the microarray's effectiveness for unbiased characterization of antimicrobial resistance determinants in MDR strains. The subsequent testing of Acinetobacter baumannii, Escherichia coli and Klebsiella pneumoniae hospital isolates revealed the presence of several antibiotic resistance genes [e.g. belonging to TEM, SHV, OXA and CTX-M classes (and OXA and CTX-M subfamilies) of ß-lactamases] and their assemblages which were confirmed by PCR and DNA sequence analysis. When combined with results from the reference strains, ~25% of the ARDM content was confirmed as effective for representing allelic content from both Gram-positive and -negative species. Taken together, the ARDM identified MDR assemblages containing six to 18 unique resistance genes in each strain tested, demonstrating its utility as a powerful tool for molecular epidemiological investigations of antimicrobial resistance in clinically relevant bacterial pathogens.

In vitro antibiotic susceptibility testing of Brucella isolates from Egypt between 1999 and 2007 and evidence of probable rifampin resistance.

BACKGROUND: Brucellosis poses a significant public health problem in Mediterranean countries, including Egypt. Treatment of this disease is often empirical due to limited information on the antibiotic susceptibility profiles of Brucella spp. in this region of the world. The aim of this study was to determine the antibiotic susceptibility profiles of Brucella blood isolates in Egypt, a country endemic for brucellosis. METHODS: Brucella spp. isolates were identified from the blood cultures of acute febrile illness (AFI) patients presenting to a network of infectious disease hospitals from 1999-2007. Minimum inhibitory concentrations were determined for tetracycline, gentamicin, doxycycline, trimethoprim-sulfamethoxazole, streptomycin, ceftriaxone, ciprofloxacin and rifampin using the E-test. Interpretations were made according to Clinical and Laboratory Standards Institute (CLSI) guidelines. RESULTS: A total of 355 Brucella spp. isolates were analyzed. All were susceptible to tetracycline, doxycycline, trimethoprim-sulfamethoxazole, streptomycin and ciprofloxacin; probable resistance to rifampin and ceftriaxone was observed among 277 (64%) and 7 (2%) of the isolates, respectively. Percentages of isolates showing probable resistance to rifampin were significantly lower before 2001 than in the following years (7% vs. >81%, p < 0.01). CONCLUSIONS: Despite the high burden of brucellosis in Egypt and frequent empirical treatment, isolates have remained susceptible to the majority of tested antibiotics. However, this is the first report of high rates of probable resistance to rifampin among Brucella isolates from Egypt. Patients should be closely monitored while following standard treatment regimens. Continued surveillance, drug susceptibility studies and updated CLSI interpretive criteria are needed to monitor and update antibiotic prescribing policies for brucellosis.

Zoonotic cutaneous leishmaniasis: reservoir host and insect vector in north Sinai, Egypt.

Cutaneous leishmaniasis (ZCL) is a protozoan disease well documented not only in Egypt, but in nearly all the East Mediterranean Countries. Sinai Peninsula was a sparsely populated area where sporadic cases of ZCL were reported with the reconstruction of Sinai and people coming in and out, it was indicated to study the status of ZCL in North Sinai Governorate, the reservoir host(s) and insect vector(s) in Sinai. In the present study, the six species of rodents were trapped from areas or nearby areas where human ZCL cases were detected. Rodents (50) were Mus musculus (10), Rattus r. alexandrinus (18), R. norvegicus (2), Gerbillus gerbillus (4), G. pyramidum (12) and Jaculus jaculus (4). The rodents were examined clinically for any skin lesion or even nodule, particularly in head and tail. One G. pyramidumn had natural infection with L. major as indicated by smears and culture, but typing was not done. The spot light surveys for Phlebotomus were carried out by the sticky paper traps and the CDC light traps in four main centers; Al Hassanah, Nakhil, Al Arish, and Bir Al-Abd. A total of 1320 sandflies were identified. They were P. papatasi (1150) and P. sergenti (170) in a ratio of 7:1. A total of three isolates of zymodeme London 70 undistinguished from the formerly obtained human and rodent isolates were enzymatically identified in P. papatasi.

Retrospective serosurvey of leptospirosis among patients with acute febrile illness and hepatitis in Egypt.

The epidemiologic status of leptospirosis in Egypt has not been well defined because of difficulties in disease diagnosis. A retrospective study was conducted to detect leptospiral antibodies among undiagnosed acute febrile illness (AFI) and hepatitis cases. Approximately 16% of both AFI (141/886) and acute hepatitis (63/392) cases showed seroreactivity to Leptospira IgM by ELISA and microscopic agglutination test (MAT). Canicola, Djasiman, Grippotyphosa, Pyrogenes, Icterohemorrhagiae, and Pomona were the most commonly reactive serovars among patients with AFI. Djasiman, Grippotyphosa and Icterohemorrhagiae were the most reactive among patients with acute hepatitis. This study represents the first systematic report of Leptospira associated with patients with AFI and hepatitis in Egypt. Physicians need to have increased awareness about the importance of leptospirosis in the differential diagnosis of AFI and acute hepatitis in Egypt. In addition, laboratory capacity should be developed at fever hospitals to diagnose leptospirosis.