Bacteremia and septicemia in Qatar

Objectives: The aims of the study are to define the pattern of bacteremia and septicemia in Hamad Medical Corporation in relation to the susceptibility of the implicated microbes to various antimicrobial agents. Methods: During a period of 12 months of study, blood cultures were performed on 9074 patients in Hamad Medical Corporation, Qatar, with clinical signs of infection. Among these, 789 (9%) episodes of septicemia were diagnosed, which corresponds to 20/1000 hospital admissions. Results: About 59% of the episodes were due to Gram positive organisms, the most common of which were coagulase negative staphylococci (31%), Staphylococcus aureus (7%) and Candida spp (6%), and other Gram positive organisms. Gram negative organisms implicated in 40% of episodes were mainly Salmonella spp (8%), Escherichia coli (7%), Klebsiella spp (5%) and other Gram negative organisms. The antibiotic resistance pattern of the organisms showed that S.aureus had the highest incidence of drug resistance. The case fatality rate among 66 episodes of septicemia was 24%, which increased with age, but was not influenced by sex. Polymicrobial septicemia carried the highest mortality rate. The case fatality rate of Gram positive septicemia was higher than that of Gram negative. Patients with underlying conditions, such as malignancy, chronic liver diseases, diabetes mellitus, renal failure, heart failure and conditions requiring surgery had higher mortality rates. The chance of survival increased with the use of appropriate therapy and absence of underlying disease. None of the patients with underlying conditions survived after receiving inappropriate therapy as compared with 50% who were previously healthy. Conclusions: Factors such as patients age, type of microorganism involved, the presence of underlying disease and the appropriateness of antibiotic therapy all influence the outcome of septicemia. While some patients with an underlying condition die of the consequences of septicemia despite appropriate antimicrobial therapy, other patients without any underlying disease tolerate septicemia reasonably well

Reference ranges of lymphocyte subsets in healthy Qatari adults

Aim: Determine reference ranges of lymphocyte subsets in healthy Qatari adults. Patients & Methods: Blood samples (n = 150) were investigated using four colors flow cytometery. Results: The mean percentage and absolute values of the lymphocyte subsets were: CD3: 73.6 ± 6.1%; 2,072 ± 644 cells/μl; CD4: 41.1 ± 7.9%; 1,167 ± 396 cells/ μl; CD8: 33.8 ± 7.1%; 967 ± 364 cells/μl; B cells (CD19+): 11.3 ± 3.9%; 318 ± 144 cells/μl and natural killer (NK) cells (CD16/56+): 16.5 ± 6.3%, 440 ± 401 cells/μl, respectively. The CD4/CD8 ratio was 1.3 ± 0.5. The ratio, CD3+ and CD4+ percentage and CD4+ cell counts were significantly higher in females; CD8+ and NK cell count and CD8+ percentage were significantly higher in males. The impact of age was less certain. Conclusion: The reference values of lymphocyte subsets appear to be specific to this population, demonstrating the importance of establishing local reference ranges

Characterising the aetiology of severe acute gastroenteritis among patients visiting a hospital in Qatar using real-time polymerase chain reaction

Background: Acute gastroenteritis (AGE) remains a common cause of clinic visits and hospitalizations, though its aetiology has not been determined in Qatar. Methods: We performed a prospective, emergency department–based study of 288 children and adults with AGE. Stool specimens were collected at presentation from June to November 2009. Faecal specimens were tested, using real-time PCR, for a panel of four viral (norovirus, adenovirus, astrovirus and rotavirus) and bacterial pathogens. Results: Viral and bacterial pathogens were detected in 131 (45.5%) and 34 (12.2%) of the 288 patients recruited. The most commonly detected pathogens were norovirus (28.5%), rotavirus (10.4%), followed by adenovirus (6.25%) and astrovirus (0.30%). Norovirus was the most commonly detected viral pathogen amongst all the age groups with an almost even distribution in all age groups. Rotavirus and adenovirus were more common in children under 5 yr of age. Astrovirus was found in only one person. Conclusions: Viruses, especially noroviruses, are associated with severe diarrhoea in children and adults in Qatar. Further studies to confirm the findings and to explore the causes of illness among patients from whom a pathogen cannot be determined are needed

Antibiotic resistance and virulence patterns of pathogenic Escherichia coli strains associated with acute gastroenteritis among children in Qatar

Background: The treatment of Enterobacteriaceae family including diarrheagenic E. coli (DEC) has been increasingly complicated due to the emergence of resistant strains. Here we report on the phenotypic resistance profiles and ESBL genotype and virulence profiles of Enteroaggregative E. coli (EAEC) and Enteropathogenic E. coli (EPEC) isolated from children hospitalized with acute gastroenteritis in Qatar (AGE). Results: E. coli were isolated and characterized from 76 diarrheagenic stool positive samples, collected from hospitalized children less than 10 years old. Isolates were tested for antibiotic susceptibility against eighteen clinically relevant antibiotics using E-test method. Conventional PCR was performed to detect genes encoding ESBL and virulence factors. Chi-square test was performed to compare the individual antibiotic resistance between EPEC and EAEC. A significant percentage (73.7%) of isolates were resistant to at least one antibiotic. Overall, high resistance (70%) was reported to the first-line antibiotics such as ampicillin, tetracycline (46.4%), and sulfamethoxazole-trimethoprim (42.9%). Further, 39.5% of the isolates were multidrug resistant (MDR), with 22.4% being ESBL producers. On the other hand, all isolates were susceptible to carbapenem, fosfomycin, amikacin and colistin. The incidences of resistance to the 18 antibiotics between EPEC and EAEC were not significantly different by Pearson chi -square test (P > 0.05). Genetic analysis revealed that 88.23% of ESBL production was bla CTX-M-G1 (bla CTX-M-15, bla CTX-M-3) - encoded. Several different combinations of virulence markers were observed, however, there was no specific trend among the isolates apart from absence of the bundle-forming pilus (bfpA) gene, which encodes the type IV fimbriae in EPEC adherence factor (EAF) plasmid (pEAF), among all EPEC (atypical). 15% of the EAEC strains were positive for a combination of astA, aap & capU, while 10% were positive for three different combinations. The aap, aatA, capU and aggR virulence genes showed the highest frequency of 65, 60, 55 and 55% respectively. Others genes, east, astA, and aai, showed frequencies of 35, 30 and 20% respectively. Conclusions: Atypical EPEC and EAEC were the primary etiological agents of diarrhea in children among DEC pathotypes. Our results indicated high rate of antimicrobial resistance pattern of DEC strains, which necessities the development of regulatory programs and reporting systems of antimicrobial resistance in DEC and other AGEassociated bacteria to insure effective control of diarrheal diseases. Results from this study demand a further research on identifying the phenotypic and genotypic profiles of more DEC pathotypes in various clinical samples

Molecular Mechanisms of Peritoneal Dialysis–Induced Microvascular Vasodilation

Peritoneal dialysis (PD) solutions dilate microvessels by undefined mechanisms. This vasodilation directly affects ultrafiltration and solute exchange during a PD dwell and is thought to account for the variable mass transfer area coefficient for small solutes during a glucose-based hypertonic dwell. We hypothesized that PD-mediated vasodilation occurs by endothelium-dependent mechanisms that involve endothelium energy-dependent K+ channels (KATP), adenosine A1 receptor activation, and NO release. We used intravital videomicroscopy to study 3 levels of microvessels (A1 inflow arterioles about 100 μm diameter to pre-capillary A3 arterioles 10 – 15 μm diameter) in the terminal ileum of anesthetized rats under control conditions in vivo in a tissue bath. Ileum was bathed with hypertonic mannitol or 2.5% glucose-based PD solution (Delflex: Fresenius Medical Care North America, Waltham, MA, U.S.A.) with or without topical application of individual or combined specific inhibitors of the endotheliumdependent dilation pathways: NO (L-NMMA), prostaglandin I2 (mefenamic acid), endothelium hyperpolarizing factor (glibenclamide), and adenosine A1 receptor antagonist (DPCPX). The mannitol and PD solutions induced rapid and sustained peritoneal vasodilation whose magnitude depended on microvascular level and osmotic solute. Combined inhibition of endothelium-dependent dilation pathways completely abolished the mannitolinduced hyperosmolality-mediated dilation at all microvascular levels, but selectively eliminated the PD solution–mediated A3 dilation. The KATP and adenosine receptor antagonists, individually or combined, remarkably attenuated dilation in the smaller pre-capillary arterioles; NO inhibition, alone or combined with KATP and adenosine receptor antagonists, eliminated the PD solution–induced dilation. The cyclooxygenase pathway is not involved in PD-induced dilation. Solutions for PD dilate the visceral peritoneal microvasculature by endothelium-dependent mechanisms, primarily the NO pathway. Adenosine receptor–activated NO release and KATP channelmediated endothelium hyperpolarization significantly contribute to vasodilation in the smaller peritoneal pre-capillary arterioles.Qatar National Research Fund NPRP 09-268-3-06

Comparative Phylogenetic and Residue Analysis of Hepatitis C Virus E1 Protein from the Middle East and North Africa Region

Hepatitis C virus (HCV) is a major public health problem in the Middle East and North Africa (MENA) region with an estimate of over 15 million chronically infected patients. However, molecular characterization of circulating genotypes in the MENA region remains elusive. Here, we performed a comparative phylogenomic analysis of so-far available E1 gene sequences (937), originating from eight countries in the MENA region. All HCV E1 protein sequences present in NCBI from the MENA region were retrieved and cataloged per year and country of origin. Phylogenetic analysis revealed a maximum diversity of genotypes and subtypes in South Arabia [G-1 (1a, 1b, 1g), G-2 (2a, 2c), G-3 (3a) and G-4 (4a, 4d, 4n, 4o, 4r, 4s)] followed by Egypt [G-1 (1b, 1g) and G-4 (4a, 4l, 4n, 4m, 4u)], Iran [G-1 (1b) and G-3 (3a) G-6 (6a)], Tunisia [G-1 (1b) and G-2 (2a, 2b, 2c)], Algeria [G-1 (1i), 4(4f), Pakistan [G-1 (1a), G-3(3a, 3b)], Afghanistan [G-1 (1a), GT-3 (3a)], and 5(5a), and Yemen [G-4 (4r)]. The calculated evolution rate of retrieved sequences was 1.601 × 10−3 substitutions/site/year and the mean nucleotide diversity rate was 0.2684 (P < 0.001). The ratio of synonymous to non-synonymous (mean dN/dS) substitutions was higher in genotypes 2 and 4 compared to the genotypes 1 and 3. A higher degree of nucleotide identity in E1 gene was found between subtypes 1a and 1b, between 2c and 2g, and between 4a, 4d, and 4o. Comparative residue analysis of E1 protein epitope sequences of previously reported H111, A4, and A6 monoclonal antibodies showed relatively poor and genotype-specific conservancy. Perhaps, none of the reported epitope sequences had immunogenicity score higher than 0.4 (A minimum threshold for vaccine sequence prediction). Furthermore, these epitope sequences were heavily glycosylated at amino acid 196, 209, and 234 sites in all GTs. In conclusion, a high genetic variability in E1 protein coupled with increased glycosylation may deduce heterogeneity and subsequent escape from vaccine-generated immune response, thereby ascertaining necessary interventions for disease management and control.The work was performed at BRC internal resource

Polymerase chain reaction ribotyping of Clostridium difficile isolates in Qatar: a hospital-based study

Background Clostridium difficile infection (CDI) is not generally reported to public health authorities in the Middle East and its true prevalence remains largely unknown. The aims of this study were to determine the prevalence of CDI and its associated ribotypes among C. difficile isolates in Qatar. Influence of age and correlation with other risk factors e.g. proton pump inhibitor use, antibiotic use, existence of chronic conditions, etc was also investigated for CDI positive patients. Methods A total of 1,532 patients with suspected CDI were recruited from two hospitals between 2011 and 2012. C. difficile was identified using glutamate dehydrogenase (GDH) lateral flow assay and toxins A and B Enzyme Immunoassay (EIA). The C. difficile positive samples were then cultured for PCR-ribotyping. Results 122 of the 1,532 (7.9%) samples from individual patients were identified as C.difficile positive; and 79 of these were viably cultured (~65%). From these, 36 different PCR ribotypes were isolated, of which strains 258 (6 [7.6%]), 01/014/046 (5 [6.3%]), and 011/053/056/107 (4 [5%]) were the most prevalent. The prevalence of PCR-ribotype 027 was 1.3% (n = 1). An age of ≥65 years and treatment with proton pump inhibitors correlated with higher frequency of CDI. Treatment with third generation cephalosporins (50 [41%]) and piperacillin/tazobactam antibiotics (55 [45.1%]) was most frequently associated with CDI. Conclusion The most common C. difficile ribotype identified in Qatar was 258, which is different from those found in North America, Europe and Asia. The prevalence of CDI was higher in Qatar than Europe; though comparable to other Middle Eastern countries. These findings underscore the importance of local surveillance to detect and control C. difficile infection

Urine Tests for Diagnosis of Infectious Diseases and Antibiotic-Resistant Pathogens

The relation between disease and urine was recognized by physicians since the earliest civilization BC. Urine is considered an ideal diagnostic specimen for its noninvasive and easy method of collection. Urinalysis encompasses a wide range of tests, which includes a variety of chemical tests, urine microscopy, bacterial cultures, and molecular tests. Importantly, urine tests can diagnose patients with antibiotic-resistant urinary tract infections (UTI), directly from urine and/or bacterial culture. This chapter summarizes the most common urine tests in the infectious disease field, with a special focus on diagnosing UTI and characterizing their antibiotic resistant. In addition to describing the advantages and limitation of these tests, the chapter explores the promising emerging technologies and methods in this field. This chapter is beneficial for scientists and healthcare workers in the field

Helminth infections among long-term residents and settled immigrants in Qatar in the decade from 2005 to 2014: temporal trends and varying prevalence among subjects from different regional origins

Background: Travel and migration from developing regions, where tropical diseases are common, to more developed industrialised nations can contribute to the introduction and subsequent spread of infections. With its rapidly expanding economy, Qatar has attracted vast numbers of immigrant workers in the last two decades, often from countries with poor socio-economic levels. Many used to arrive with patent intestinal parasitic infections. Methods: We analysed the prevalence of helminth infections in a dataset of 29,286 records of subjects referred for stool examination at the Hamad Medical Corporation over the course of a decade (2005 to 2014, inclusive). Results: Overall prevalence of combined helminth infections was low (1.86 %) but there were significant temporal trends, age and sex effects and those arising from the region of origin of the subjects. The most common helminths were hookworms (overall prevalence 1.22 %), which accounted for 70.1 % of cases, and therefore patterns for combined helminth infections were largely driven by hookworms. In both cases, and also in Trichuris trichiura and Ascaris lumbricoides, prevalence peaked in 2008, since when prevalence has been steadily falling. Helminth infections were largely concentrated among subjects from five Asian countries (Nepal, Bangladesh, Sri Lanka, India and Pakistan), and there was a highly biased prevalence in favour of male subjects in all cases. Prevalence of all three nematodes peaked in age class 7 (mean age 25.5 years, range = 20–29) and there were significant interactions between region of origin, sex of subjects and prevalence of hookworms. Conclusion: These results offer optimism that prevalence will continue to decline in the years ahead, especially if control is targeted at those most at risk of carrying infections.Qatar National Research Fund (QRNF) at Qatar Foundation for supporting this study through the National Priorities Research Program (NPRP) (Project No. NPRP 4-1283-3-327)

Qatar Biobank: COVID-19 biorepository project

Background: The rapid spread of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its resulting disease (COVID-19) is one of the greatest global public health crisis of the recent decades 1 . The COVID-19 Biorepository is a national project aimed to support the high demand of biomedical research by multiple groups and the need to have access to high quality, curated clinical data, and specimens contributing to the understanding of, and response to, the COVID-19 pandemic and its impacts in Qatar 2, 3 . Methods/Case presentation: Patients with a laboratory diagnosis of COVID-19, who were Qatar residents that could communicate in Arabic, English, Hindi, and Urdu were eligible to participate in the study. COVID-19 diagnosed patients were recruited at the time of their disease period from the main three public hospitals (Communicable Disease Center, Cuban, and Hazm Mebaireek Hospitals) serving as isolation facilities of symptomatic patients in Qatar, during a 7-month period from March 2020 until September 2020. Consented participants were followed up on a weekly basis until recovery, and then monthly for a year. Sociodemographic and clinical data were collected in electronic questionnaires via a face-to-face interview by trained Qatar Biobank (QBB) staff. Results: A total of 2097 consented participants were recruited up to September 2020, males (N = 1050) and females (N = 1047), with a mean age of 41 years (SD: 15.5). 61.0% of the participants had at least one follow up while 27% adhered to monthly follow up visits. Data was collected for 99.7% of the participants, while the follow up process is still ongoing. In total there are 107,171 high quality specimens in the biorepository including plasma, erythrocytes, buffy coat, serum, PAXgene whole blood, nasopharyngeal secretions, and DNA. Conclusion: The COVID-19 Biorepository is a national asset to illuminate the pathophysiological and identify markers of disease prognosis as well as to describe the clinical features and epidemiology of COVID-19 in Qatar and worldwide.qscienc