Sarah Alsubaie

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

Summary 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.

Screening for Middle East respiratory syndrome coronavirus infection in hospital patients and their healthcare worker and family contacts: a prospective descriptive study

Abstract The Saudi Arabian Ministry of Health implemented a pro-active surveillance programme for Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV). We report MERS-CoV data from 5065 Kingdom of Saudi Arabia individuals who were screened for MERS-CoV over a 12-month period. From 1 October 2012 to 30 September 2013, demographic and clinical data were prospectively collected from all laboratory forms received at the Saudi Arabian Virology reference laboratory. Data were analysed by referral type, age, gender, and MERS-CoV real-time PCR test results. Five thousand and 65 individuals were screened for MER-CoV: hospitalized patients with suspected MERS-CoV infection (n = 2908, 57.4%), healthcare worker (HCW) contacts (n = 1695; 33.5%), and family contacts of laboratory-confirmed MERS cases (n = 462; 9.1%). Eleven per cent of persons tested were children (<17 years of age). There were 108 cases (99 adults and nine children) of MERS-CoV infection detected during the 12-month period (108/5065, 2% case detection rate). Of 108 cases, 45 were females (six children and 39 adults) and 63 were males (three children and 60 adults). Of the 99 adults with MERS-CoV infection, 70 were hospitalized patients, 19 were HCW contacts, and ten were family contacts. There were no significant increases in MERS-CoV detection rates over the 12-month period: 2.6% (19/731) in July 2013, 1.7% (19/1100) in August 2013, and 1.69% (21/1238) in September 2013. Male patients had a significantly higher MERS-CoV infection rate (63/2318, 2.7%) than females (45/2747, 1.6%) (p 0.013). MERS-CoV rates remain at low levels, with no significant increase over time. Pro-active surveillance for MERS-CoV in newly diagnosed patients and their contacts will continue.

Respiratory Tract Samples, Viral Load, and Genome Fraction Yield in Patients With Middle East Respiratory Syndrome

Abstract Background. Analysis of clinical samples from patients with new viral infections is critical to confirm the diagnosis, to specify the viral load, and to sequence data necessary for characterizing the viral kinetics, transmission, and evolution. We analyzed samples from 112 patients infected with the recently discovered Middle East respiratory syndrome coronavirus (MERS-CoV). Methods. Respiratory tract samples from cases of MERS-CoV infection confirmed by polymerase chain reaction (PCR) were investigated to determine the MERS-CoV load and fraction of the MERS-CoV genome. These values were analyzed to determine associations with clinical sample type. Results. Samples from 112 individuals in which MERS-CoV was detected by PCR were analyzed, of which 13 were sputum samples, 64 were nasopharyngeal swab specimens, 30 were tracheal aspirates, and 3 were bronchoalveolar lavage specimens; 2 samples were of unknown origin. Tracheal aspirates yielded significantly higher MERS-CoV loads, compared with nasopharyngeal swab specimens (P = .005) and sputum specimens (P = .0001). Tracheal aspirates had viral loads similar to those in bronchoalveolar lavage samples (P = .3079). Bronchoalveolar lavage samples and tracheal aspirates had significantly higher genome fraction than nasopharyngeal swab specimens (P = .0095 and P = .0002, respectively) and sputum samples (P = .0009 and P = .0001, respectively). The genome yield from tracheal aspirates and bronchoalveolar lavage samples were similar (P = .1174). Conclusions. Lower respiratory tract samples yield significantly higher MERS-CoV loads and genome fractions than upper respiratory tract samples.

Outbreak of Bacille Calmette-Guérin-related lymphadenitis in Saudi children at a university hospital after a change in the strain of vaccine.

BACKGROUND AND OBJECTIVES Bacille Calmette-Guérin (BCG) vaccination is part of the expanded program of vaccination in Saudi Arabia. Lymphadenitis is the most common complication of the BCG vaccine. We observed an increase in the rate of BCG lymphadenitis that coincided with the introduction of a new strain of BCG vaccine. The aim of this study was to determine the incidence and the possible causes of BCG lymphadenitis at a university hospital in Riyadh, Saudi Arabia. DESIGN AND SETTING Retrospective chart review and prospective follow up of infants who received BCG vaccine. METHODS We studied all infants presenting with suppurative or nonsuppurative adenopathy with nodes ≥2 cm seen at the infectious diseases clinic at KKUH. The study duration was divided into two periods. The first period reviewed infants who received different BCG vaccine strains between January 2002 and December 2007. The second study period was conducted after close evaluation of the BCG administration technique of the vaccinating staff and reviewed infants who received the BCG SSI Danish strain 1331 between January 2008 and December 2010. RESULTS During the study period from January 2002 to December 2007, 19 402 infants received four different BCG vaccine strains. Eight infants developed BCG lymphadenitis, and all were associated with the BCG SSI vaccine. The incidence rate in 2007 was 1.96 per 1000. In the second period, 66 of 9921 infants who received the BCG SSI vaccine developed BCG lymphadenitis between January 2008 and December 2010. The incidence rate was 10.14 per 1000 in 2010. CONCLUSION We conclude that receipt of the BCG SSI vaccine might have contributed to the increased incidence of lymphadenitis in these children. Hence, caution should be exercised in switching from one vaccine to another, as is often done in developing countries.

Extended-spectrum β-lactamase-producing Klebsiella pneumoniae in the neonatal intensive care unit: Does vancomycin play a role?

BACKGROUND Extended-spectrum β-lactamase (ESBL)-producing Klebsiella species cause worldwide problems in neonatal intensive care units (NICUs). This study aimed to determine possible risk factors for infection or colonization with ESBL-producing Klebsiella pneumoniae (ESBLKp) during an outbreak in the NICU. METHODS A retrospective cohort study was conducted among neonates admitted to the NICU of a teaching hospital in Riyadh, Saudi Arabia, during an outbreak of ESBLKp from April to July 2008. The incidence density ratio was calculated to determine possible predictors of ESBLKp colonization or infection. RESULTS During 2,265 person-days of follow-up of 118 neonates, 4 became infected, and 8 were colonized with ESBLKp. Univariate analyzes revealed that, among 14 neonates who were treated with vancomycin, 9 (64.3%) developed infection or colonization with ESBLKp, whereas, among 104 neonates who were not treated with vancomycin, 3 (2.9%) were affected, with an incidence density ratio of 4.22 (95% confidence interval: 1.47-5.15). Parenteral feeding and mechanical ventilation were found to be marginally significant risk factors. CONCLUSION Treatment with vancomycin appears to be a risk factor for infection or colonization with ESBLKp in the NICU setting.

Nosocomial transmission of community-acquired methicillin-resistant Staphylococcus aureus in a well-infant nursery of a teaching hospital

Background:  Infection due to community‐acquired strains of methicillin‐resistant Staphylococcus aureus (CA‐MRSA) has been reported with increasing frequency. Herein is described the nosocomial transmission of CA‐MRSA involving 13 neonates and two mothers in a well‐infant nursery in a teaching hospital in Saudi Arabia.

Pediatric acute kidney injury induced by concomitant vancomycin and piperacillin-tazobactam

Vancomycin is very commonly used in combination with piperacillin–tazobactam (PTZ) as the initial empiric treatment for moderate–severe infection, whenever coverage for both methicillin‐resistant Staphylococcus aureus and Pseudomonas aeruginosa is required. The combination of vancomycin and PTZ in adults has recently been reported to significantly increase the risk of acute kidney injury (AKI) relative to vancomycin monotherapy; such reports in pediatrics, however, are sparse.

Neonatal brucellosis: A case report

Although brucellosis is not uncommon in Saudi Arabia, neonatal brucellosis has been infrequently reported. In this case of neonatal brucellosis, Brucella abortus was isolated by blood culture from both the mother and the neonate. Serology was positive only in the mother.

Knowledge, attitude and practice of secondary schools and university students toward Middle East Respiratory Syndrome epidemic in Saudi Arabia: A cross-sectional study

Abstract This study was aiming to investigate the knowledge, practice and attitudes of secondary school and university students toward MERS-CoV infection. This is a cross-sectional study conducted in Riyadh, Saudi Arabia. Study participants were recruited from several constituent colleges of King Saud University and secondary schools in Riyadh. Data were collected using self-administered, closed-ended questionnaires. Frequencies and proportions were computed for descriptive purposes. Chi square test was utilized to depict statistical difference between groups. Among the 1109 students who answered the questionnaires, 53.1% were male, and 46.9% were female. Level of knowledge about clinical presentation of MERS is generally similar among university and school students. The most frequently reported source of transmission is entering crowded spaces and being exposed to coughing and sneezing. Additionally, hand washing was the most commonly reported method of protection against the infection. The localized spread of MERS in Saudi Arabia and the number of fatalities associated with it might have increased public interest in understanding how to maintain proper precautionary measures both on a community and on an individual level. More emphasis should be placed on educating the student participants about preventive measures such as using tissues when sneezing and coughing and proper tissue disposal.

Clostridium tertium meningitis in neonate: An elusive diagnosis

Clostridium tertium is an uncommon human pathogen. The organism has been implicated in bacteremia, enterocolitis, posttraumatic brain abscesses, pneumonia and necrotizing fasciitis especially in neutropenic and immunocompromised patients. Unlike other clostridial species, it has not previously been reported to cause disease in neonates. This case report describes a neonate who has meningitis caused by C. tertium with no underlying risk factors.