Spread, circulation, and evolution of the Middle East respiratory syndrome coronavirus

The Middle East respiratory syndrome coronavirus (MERS-CoV) was first documented in the Kingdom of Saudi Arabia (KSA) in 2012 and, to date, has been identified in 180 cases with 43% mortality. In this study, we have determined the MERS-CoV evolutionary rate, documented genetic variants of the virus and their distribution throughout the Arabian peninsula, and identified the genome positions under positive selection, important features for monitoring adaptation of MERS-CoV to human transmission and for identifying the source of infections. Respiratory samples from confirmed KSA MERS cases from May to September 2013 were subjected to whole-genome deep sequencing, and 32 complete or partial sequences (20 were ≥99% complete, 7 were 50 to 94% complete, and 5 were 27 to 50% complete) were obtained, bringing the total available MERS-CoV genomic sequences to 65. An evolutionary rate of 1.12 × 10−3 substitutions per site per year (95% credible interval [95% CI], 8.76 × 10−4; 1.37 × 10−3) was estimated, bringing the time to most recent common ancestor to March 2012 (95% CI, December 2011; June 2012). Only one MERS-CoV codon, spike 1020, located in a domain required for cell entry, is under strong positive selection. Four KSA MERS-CoV phylogenetic clades were found, with 3 clades apparently no longer contributing to current cases. The size of the population infected with MERS-CoV showed a gradual increase to June 2013, followed by a decline, possibly due to increased surveillance and infection control measures combined with a basic reproduction number (R0) for the virus that is less than 1

Transmission and evolution of the Middle East respiratory syndrome coronavirus in Saudi Arabia:a descriptive genomic study

BACKGROUND: Since June, 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) has, worldwide, caused 104 infections in people including 49 deaths, with 82 cases and 41 deaths reported from Saudi Arabia. In addition to confirming diagnosis, we generated the MERS-CoV genomic sequences obtained directly from patient samples to provide important information on MERS-CoV transmission, evolution, and origin. METHODS: Full genome deep sequencing was done on nucleic acid extracted directly from PCR-confirmed clinical samples. Viral genomes were obtained from 21 MERS cases of which 13 had 100%, four 85-95%, and four 30-50% genome coverage. Phylogenetic analysis of the 21 sequences, combined with nine published MERS-CoV genomes, was done. FINDINGS: Three distinct MERS-CoV genotypes were identified in Riyadh. Phylogeographic analyses suggest the MERS-CoV zoonotic reservoir is geographically disperse. Selection analysis of the MERS-CoV genomes reveals the expected accumulation of genetic diversity including changes in the S protein. The genetic diversity in the Al-Hasa cluster suggests that the hospital outbreak might have had more than one virus introduction. INTERPRETATION: We present the largest number of MERS-CoV genomes (21) described so far. MERS-CoV full genome sequences provide greater detail in tracking transmission. Multiple introductions of MERS-CoV are identified and suggest lower R0 values. Transmission within Saudi Arabia is consistent with either movement of an animal reservoir, animal products, or movement of infected people. Further definition of the exposures responsible for the sporadic introductions of MERS-CoV into human populations is urgently needed. FUNDING: Saudi Arabian Ministry of Health, Wellcome Trust, European Community, and National Institute of Health Research University College London Hospitals Biomedical Research Centre

Biophysical and In Silico Studies of the Interaction between the Anti-Viral Agents Acyclovir and Penciclovir, and Human Serum Albumin

Acyclovir (ACV) and penciclovir (PNV) have been commonly used during the last few decades as potent antiviral agents, especially for the treatment of herpes virus infections. In the present research their binding properties with human serum albumin (HSA) were studied using different advanced spectroscopic and in-silico methods. The interactions between ACV/PNV and HSA at the three investigated temperatures revealed a static type of binding. Extraction of the thermodynamic parameters of the ACV-HSA and PNV-HSA systems from the measured spectrofluorimetric data demonstrated spontaneous interactions with an enthalpy change (∆H0) of −1.79 ± 0.29 and −4.47 ± 0.51 kJ·mol−1 for ACV and PNV, respectively. The entropy change (∆S0) of 79.40 ± 0.95 and 69.95 ± 1.69 J·mol−1·K−1 for ACV and PNV, respectively, hence supported a potential contribution of electrostatic binding forces to the ACV-HSA and PNV-HSA systems. Putative binding of ACV/PNV to HSA, using previously reported site markers, showed that ACV/PNV were bound to HSA within subdomains IIA and IIIA (Sudlow sites I and II). Further confirmation was obtained through molecular docking studies of ACV-HSA and PNV-HSA binding, which confirmed the binding site of ACV/PNV with the most stable configurations of ACV/PNV within the HSA. These ACV/PNV conformers were shown to have free energies of −25.61 and −22.01 kJ·mol−1 for ACV within the HSA sites I and II and −22.97 and −26.53 kJ·mol−1 for PNV in HSA sites I and II, with hydrogen bonding and electrostatic forces being the main binding forces in such conformers

Emergence of clinically relevant Non-Tuberculous Mycobacterial infections in Saudi Arabia.

BACKGROUND: Non-Tuberculous Mycobacteria (NTM) are emerging around the world due to a higher prevalence of immunosuppressive illness and therapy. Saudi Arabia is not an exception as there have been novel mycobacterial species also identified. In addition, several published case reports from different parts of the country suggest a growing pathogenic potential of NTM. As the first nationwide study, we sought to gain an insight into the species diversity of NTM clinical isolates. METHODOLOGY/PRINCIPAL FINDINGS: During June 2009-July 2010, 95 clinical isolates were collected from tuberculosis reference laboratories in major provinces within Saudi Arabia and subjected to standard line probe assay techniques to identify their species. Diagnostic guidelines of the American Thoracic Society were applied to determine the clinical relevance of respiratory isolates. Species diversity (13 species) was very high and dominated (61.0%) by rapid growing NTM. The major species obtained were Mycobacterium abscessus, M. fortuitum, M. intracellulare followed by M. kansassi, M. gordanae and M. avium. Interestingly this study reports for the first time the clinical relevance of M. celatum, M. xenopi, M. scrofulceum, M. lentiflavum, M. asiaticum and M. simiae in Saudi Arabia. Of the total, 67.1% were clinically relevant respiratory cases, 23.2% were non-respiratory cases and 9.7% were respiratory colonizers. Coexisting illness was reported in 53.7% of the studied cases. The major risk factors observed among the patients were previous history of tuberculosis, chronic obstructive pulmonary disorder and human immunodeficiency virus infection. CONCLUSION/SIGNIFICANCE: The high rates of clinically confirmed respiratory cases suggest that NTM infections are indeed a new challenge to health authorities. The current findings show an opposite picture of the Western world where M. avium complex and particularly slow growing NTM are the most predominant respiratory pathogens. The complexity of species demands an immediate strengthening of the current diagnostic facilities

Al-Hajoj, “Emergence of clinically relevant non-tuberculous mycobacterial infections

Background: Non-Tuberculous Mycobacteria (NTM) are emerging around the world due to a higher prevalence of immunosuppressive illness and therapy. Saudi Arabia is not an exception as there have been novel mycobacterial species also identified. In addition, several published case reports from different parts of the country suggest a growing pathogenic potential of NTM. As the first nationwide study, we sought to gain an insight into the species diversity of NTM clinical isolates. Methodology/Principal findings: During June 2009–July 2010, 95 clinical isolates were collected from tuberculosis reference laboratories in major provinces within Saudi Arabia and subjected to standard line probe assay techniques to identify their species. Diagnostic guidelines of the American Thoracic Society were applied to determine the clinical relevance of respiratory isolates. Species diversity (13 species) was very high and dominated (61.0%) by rapid growing NTM. The major species obtained were Mycobacterium abscessus, M. fortuitum, M. intracellulare followed by M. kansassi, M. gordanae and M. avium. Interestingly this study reports for the first time the clinical relevance of M. celatum, M. xenopi, M. scrofulceum, M. lentiflavum, M. asiaticum and M. simiae in Saudi Arabia. Of the total, 67.1 % were clinically relevant respiratory cases, 23.2 % were non-respiratory cases and 9.7 % were respiratory colonizers. Coexisting illness was reported in 53.7 % of the studied cases. The major risk factors observed among the patients were previous history of tuberculosis, chroni

Prevalence and Self-Medication for Acne among Students of Health-Related Science Colleges at King Saud University in Riyadh Region Saudi Arabia

Background and Objectives: In Saudi Arabia, Acne vulgaris is a very predominant ailment among adolescents, especially female university students, and self-medication has become a trend to manage this condition. To determine the prevalence of Acne vulgaris among health care students and to access the scenario of its self-medication in light of students’ knowledge, attitude, and practice towards it. Materials and Methods: This was an observational study conducted at King Saud University, Riyadh, Kingdom of Saudi Arabia, from January 2022 to March 2022. The study was undertaken using a pre-structured questionnaire. Results: A total of 550 university students were recruited and the incidence of acne was observed to be 78.5% (432 out of 550) with a female predominance. A total of 56.0% (244 of 432) students used self-medications for acne without a prescription and the most used prescription drugs were topical and oral antibiotics (38.1%), followed by Isotretinoin (22.55), and topical adaplene (20.9%). Female students (n = 181, 63.5%) were significantly more likely to self-medicate compared to male students (n = 63, 42.9%, p ≤ 0.001). Almost 60% of medical students had proper knowledge of medication for acne. Conclusion: Acne vulgaris is a highly prevalent condition among university students of Saudi Arabia and use of self-medication among acne sufferers is high. Education programs should be made to raise awareness about acne and its treatment

Proportions of EPTB site diversity based on demographical data.

<p>¹ Gastro Intestinal Tract</p><p>² Central Nervous System</p><p>³ Osteoarticular</p><p>⁴ Urogenital</p><p>⁵ Pericardial, Kidney, Skin, Miliary, Disseminated, abscesses other than classified sites.</p><p>⁶ SAS-South Asian, SEA-South East Asian, AFR-African, ARB-Arab</p><p>Proportions of EPTB site diversity based on demographical data.</p

Demographical and clinical summary of 381 EPTB cases.

<p>¹ Indian sub-continent-India, Pakistan, Bangladesh, Myanmar, Nepal, Sri Lanka.</p><p>² South East Asia-Philippines and Indonesia</p><p>³ Africa-Chad, Cameroon, Djibouti, Eritrea, Nigeria, Ethiopia, Somalia, Sudan</p><p>⁴ Arab countries-Egypt, Syria, Yemen, Lebanon</p><p>⁵ Multi-drug resistant tuberculosis</p><p>Demographical and clinical summary of 381 EPTB cases.</p

Major extra-pulmonary infection sites among local and immigrant populations of Saudi Arabia.

<p>Distribution of various extrapulmonary sites among Saudi Arabian and Non-Saudi Arabian population.</p

Tuberculosis transmission among immigrants and autochthonous populations of the eastern province of Saudi Arabia.

BACKGROUND:Eastern province of Saudi Arabia is an industrial zone with large immigrant population and high level of tuberculosis case notification among immigrants. The impact of immigration and current trends of tuberculosis transmission among immigrants and autochthonous population in the region had not been investigated so far using molecular tools. METHODOLOGY:During 2009- 2011, a total of 524 Mycobacterium tuberculosis isolates were collected from the central tuberculosis reference laboratory, representing an estimated 79.2% of the culture-positive tuberculosis cases over the study period in the province. These isolates were genotyped by using 24 locus-based MIRU-VNTR typing and spoligotyping followed by first line drug susceptibility testing. The molecular clustering profiles and phylogenetic diversity of isolates were determined and compared to the geographical origins of the patients. PRINCIPLE FINDINGS:Genotyping showed an overall predominance of Delhi/CAS (29.4%), EAI (23.8%) and Ghana (13.3%) lineages, with slightly higher proportions of Delhi/CAS among autochthonous population (33.3 %) and EAI (30.9%) among immigrants. Rate of any drug resistance was 20.2% with 2.5% of multi-drug resistance. Strain cluster analysis indicated 42 clusters comprising 210 isolates, resulting in a calculated recent transmission index of 32.1%. Overall shared cluster ratio was 78.6% while 75.8% were shared between autochthonous population and immigrant population with a predominance of immigrants from South east Asia (40.7%). In contrast, cross national transmission within the immigrant population was limited (24.2%). Younger age (15-30- p value-0.043, 16-45, p value 0.030), Saudi nationality (p value-0.004) and South East Asian origin (p value-0.011) were identified as significant predisposing factors for molecular strain clustering. CONCLUSIONS:The high proportion of molecular clusters shared among the autochthonous and immigrant populations suggests a high permeability of tuberculosis transmission between both populations in the province. These results prompt for the need to strengthen the current tuberculosis control strategies and surveillance programs