Middle East Respiratory Syndrome Coronavirus Transmission among Healthcare Workers: Implication for Infection Control

Background Many outbreaks of Middle East respiratory syndrome coronavirus (MERS-CoV) have occurred in health care settings and involved health care workers (HCWs). We describe the occurrence of an outbreak among HCWs and attempt to characterize at-risk exposures to improve future infection control interventions. Methods This study included an index case and all HCW contacts. All contacts were screened for MERS-CoV using polymerase chain reaction. Results During the study period in 2015, the index case was a 30-year-old Filipino nurse who had a history of unprotected exposure to a MERS-CoV–positive case on May 15, 2015, and had multiple negative tests for MERS-CoV. Weeks later, she was diagnosed with pulmonary tuberculosis and MERS-CoV infection. A total of 73 staff were quarantined for 14 days, and nasopharyngeal swabs were taken on days 2, 5, and 12 postexposure. Of those contacts, 3 (4%) were confirmed positive for MERS-CoV. An additional 18 staff were quarantined and had MERS-CoV swabs. A fourth case was confirmed positive on day 12. Subsequent contact investigations revealed a fourth-generation transmission. Only 7 (4.5%) of the total 153 contacts were positive for MERS-CoV. Conclusions The role of HCWs in MERS-CoV transmission is complex. Although most MERS-CoV–infected HCWs are asymptomatic or have mild disease, fatal infections can occur and HCWs can play a major role in propagating health care facility outbreaks. This investigation highlights the need to continuously review infection control guidance relating to the role of HCWs in MERS-CoV transmission in health care outbreaks, especially as it relates to the complex questions on definition of risky exposures, who to test, and the frequency of MERS-CoV testing; criteria for who to quarantine and for how long; and clearance and return to active duty criteria

Emergence of Klebsiella pneumoniae Carbapenemase (blaKPC-2) in members of the Enterobacteriaceae family in Palestine

Abstract Background: The global spread of carbapenem resistant Enterobacteriaceae (CRE) has limited the physicians’ antimicrobial treatment options of infected patients. CRE’s which carry the Klebsiella pneumonia Carbapenemase (blaKPC) resistance mechanism have been rapidly spreading in many parts of the world, and have been responsible for high patients’ morbidity and mortality. Methods: Two protocols recommended by the Center for Disease Control and Prevention (CDC) were followed to detect CRE’s in Palestine. In addition, the antimicrobial sensitivity patterns for several antibiotic classes were determined for the isolated CRE’s by the disc diffusion method according to the clinical and laboratory standard institute (CLSI) M100-S22 guidelines. The Minimal Inhibitory Concentrations (MICs) of the carbapenem, ertapenem, imipenem and meropenem were determined for all the CRE’s by E-test. The isolates β-lactam resistance mechanisms were further investigated by analyzing 31 different types of β–lactamase genes by polymerase chain reaction (PCR). Results: Four bacterial isolates, 3 Enterobacter cloacae and 1 Klebsiella pneumoniae, were determined to be non-susceptible to one or all of the carbapenems (ertapenem, imipenem and meropenem) tested. All isolates which carried the blaKPC-2 gene showed an extreme drug resistance profile. These isolates were resistant to all β-lactam antibiotics, co-trimoxazole and gentamicin, while susceptible to only amikacin and colistin sulfate. Different combination of plasmid encoded b–lactamase genes (blaTEM, blaSHV, blaOXA-1, blaMIR-1, blaGES-23 and blaKPC-2) were present in these isolates. Of interest, was the isolation of the first E. cloacae strains co-producing the blaKPC-2 and a novel blaGES-23 β-lactamase. Conclusions: The presence of all these plasmid encoded b-lactamase in Palestine is alarming and mandates actions to be taken to control antibiotics usage and the activation of hospital infection control programs in order to prevent the spread of these extremely drug resistant bacteria

Evaluation of Meropenem, Imipenem and Ertapenem Impregnated MacConkey Agar Plates for the Detection of Carbapenem Resistant Enterobacteriaceae

Background: Rapid detection of carbapenem resistant bacteria, in particular, members of the Enterobacteriaceae family (CRE), is of utmost importance for the management of infected or colonized patients. Methods: Three carbapenems; meropenem, imipenem and ertapenem, with two different concentrations (0.5 mg/ml and 1.0 mg/ml), were impregnated in MacConkey agar. The carbapenem impregnated MacConkey agar plates; ([Mac-Mem], [Mac-Imp] and [Mac-Ert]), were then evaluated for the detection of carbapenem resistant Gram-negative bacteria in particular the blaKPC producing Enterobacteriaceae. The Limit of Detection (LOD) of the plates was determined after counting the colonies that grew on the plates after serial logarithmic dilutions of ten. Carbapenem resistant Gram-negative bacteria were prepared in normal saline, inoculated on the different plates and incubated at 35oC for 18-24 hours. The specificity and the shelf-life of the plates were determined by challenging the plates with six ESBL positive members of the Enterobacteriaceae family (K. pneumoniae, Salmonella species, Shigella species, E. coli, Proteus species and Citrobacter species) and one Enterobacter species with the blaAmpC phenotype. Finally, the MacConkey agar plates impregnated with 0.5 mg/ml meropenem were further challenged by incorporating them in the routine Caritas Baby Hospital active surveillance program for the detection of carbapenem resistant bacteria. Results: Of the three carbapenems impregnated plates, Mac-Ert plates gave the lowest number of colony forming units (CFU’s) detected regardless of the concentration of the antibiotic used. This was followed by the Mac-Mem plates which showed an LOD of less than 200 CFU’s for most of the blaKPC positive bacteria tested at both antibiotic concentrations. The worst performance was noted for the Mac-Imp plate regardless of the antibiotic concentration used as a number of carbapenem resistant bacterial strains failed to grow on the plate. The Mac-Mem plates showed the best specificity as none of the ESBL and blaAmpC positive isolates grew on the plates at either antibiotic concentration tested after 18-24hours incubation in ambient air at 35oC. On the other hand, the Mac-Ert plates failed to inhibit the growth of the Citrobacter species tested at both antibiotic concentrations and the Proteus species tested at the 0.5µg/ml antibiotic concentration. The Mac-Imp plates showed poor specificity as both concentrations failed to inhibit the growth of the Proteus, Enterobacter and Citrobacter species evaluated after 18-24 hours incubation in ambient air at 35oC. Of all the plates tested, the 0.5 µg/ml Mac-Mem agar had the best shelf-life of up to one month at 4-8oC. Conclusions: The high specificity and the good selectivity, in addition to the long shelf-life allowed the 0.5µg/ml Mac-Mem agar to be used as a cost effective selective medium for the isolation of carbapenem resistant Gram-negative bacteria, in particular the blaKPC producing members of the Enterobacteriaceae family

Serotype Distribution and Drug Resistance in Streptococcus pneumoniae, Palestinian Territories

To determine antimicrobial drug resistance of Streptococcus pneumoniae serotypes, we analyzed isolates from blood cultures of sick children residing in the West Bank before initiation of pneumococcal vaccination. Of 120 serotypes isolated, 50.8%, 73.3%, and 80.8% of the bacteremia cases could have been prevented by pneumococcal conjugate vaccines. Serotype 14 was the most drug-resistant serotype isolated

Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy

AbstractDevelopmental epileptic encephalopathies are devastating disorders characterized by intractable epileptic seizures and developmental delay. Here, we report an allelic series of germline recessive mutations in UGDH in 36 cases from 25 families presenting with epileptic encephalopathy with developmental delay and hypotonia. UGDH encodes an oxidoreductase that converts UDP-glucose to UDP-glucuronic acid, a key component of specific proteoglycans and glycolipids. Consistent with being loss-of-function alleles, we show using patients’ primary fibroblasts and biochemical assays, that these mutations either impair UGDH stability, oligomerization, or enzymatic activity. In vitro, patient-derived cerebral organoids are smaller with a reduced number of proliferating neuronal progenitors while mutant ugdh zebrafish do not phenocopy the human disease. Our study defines UGDH as a key player for the production of extracellular matrix components that are essential for human brain development. Based on the incidence of variants observed, UGDH mutations are likely to be a frequent cause of recessive epileptic encephalopathy.</jats:p

Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy

Developmental epileptic encephalopathies are devastating disorders characterized by intractable epileptic seizures and developmental delay. Here, we report an allelic series of germline recessive mutations in UGDH in 36 cases from 25 families presenting with epileptic encephalopathy with developmental delay and hypotonia. UGDH encodes an oxidoreductase that converts UDP-glucose to UDP-glucuronic acid, a key component of specific proteoglycans and glycolipids. Consistent with being loss-of-function alleles, we show using patients’ primary fibroblasts and biochemical assays, that these mutations either impair UGDH stability, oligomerization, or enzymatic activity. In vitro, patient-derived cerebral organoids are smaller with a reduced number of proliferating neuronal progenitors while mutant ugdh zebrafish do not phenocopy the human disease. Our study defines UGDH as a key player for the production of extracellular matrix components that are essential for human brain development. Based on the incidence of variants observed, UGDH mutations are likely to be a frequent cause of recessive epileptic encephalopathy

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p&lt;0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p&lt;0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Reduction of pediatric emergency hospital admissions by a change in pediatric emergency department policy

Background: Reduction in admissions is an important aim of emergency department working policy to overcome the problems of a shortage of inpatient beds, rising costs and exhausted resources. A new policy was instituted in the pediatric emergency department (PED) of a hospital in Kuwait with the following components: (1) assigning senior doctor staff (2) implementation of new disease management guidelines; and (3) maximizing the use of the pediatric emergency department observation unit. Objective: to evaluate the effect of change in our policy on the admission rate. Materials and Methods: The effects of this policy on reduction of admission rates for total pediatric admissions and for some selected common pediatric conditions were prospectively studied over a period of 3 years from institution of the policy and compared with the 3-year period before the policy was instituted. Results: There was a significant reduction in admission rates after institution of the new policy. The proportion of hospital admissions to PED observation unit cases was significantly reduced as a whole from 64.9% ± 5.1% to 33.2 ± 0.6% and also for the common pediatric problems studied. Conclusion: A multidisciplinary pediatric emergency department policy, using as much available evidence as possible, was successful in significantly reducing pediatric hospital admissions

Survey on infant hearing loss at Caritas Baby Hospital in Bethlehem-Palestine

This study describes the epidemiology of infants hearing loss (IHL) among patients under 3 months of age at Caritas Baby Hospital, the only pediatric hospital in Palestine. It was aimed to demonstrate that IHL is a major health problem in Palestine and to assess the first available data of the newborn hearing screening program conducted between September 25, 2006 and December 31, 2011. Data was uploaded and analyzed using Microsoft Excel and the Statistical Package for the Social Sciences software (SPSS version 21). A total of 8144 infants were tested, 4812 (59%) were males and 3332 (41%) were females. As to their origin, 72% (5886) came from the Bethlehem district, 25% (2044) from the Hebron district, while 3% (214) from the other Palestinian districts (Jericho, Ramallah, Nablus, Jenin and Jerusalem). The transient evoked otoacoustic emissions (TEOAEs) and the automated auditory brainstem response were used according to the manufacturer guidelines. The results were interpreted according to the indications of the American Academy of Pediatrics, the National Institutes of Health, and the European Consensus Development Conference on Neonatal Hearing Screening. Out of the 8144 infants tested, 1507 (14.6%) did not pass the 1st test, 477 (32.8%) of these 1507 infants failed retesting, while 498 (33%) patients were lost to follow-up. Only 152 (31.9%) patients that failed retesting went to an audiologist. The audiologist evaluation revealed that 101 (66.4%) patients presented with a mild-moderate or profound hearing loss according to the Bureau International of Audiophonologie standards, 44 (28.9%) patients had otitis media, whereas 7 cases (4.7%) had no hearing disorders. The overall unadjusted percentage of hearing loss was 1.24%, and the adjusted overall percentage was 1.85%. The chart review showed that jaundice, sepsis, prematurity, lung disease were more common among the affected patients. The high prevalence of childhood deafness in Palestine is of utmost importance and deserves immediate attention on the part of the Palestinian government. Meanwhile, Caritas Baby Hospital undertook to set up a newborn hearing screening unit utilizing the TEOAE method

Distribution of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Mutations in a Cohort of Patients Residing in Palestine.

Cystic fibrosis (CF) is an autosomal recessive inherited life-threatening disorder that causes severe damage to the lungs and the digestive system. In Palestine, mutations in the Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR) that contributes to the clinical presentation of CF are ill defined. A cohort of thirty three clinically diagnosed CF patients from twenty one different Palestinian families residing in the central and southern part of Palestine were incorporated in this study. Sweat chloride testing was performed using the Sweat Chek Conductivity Analyzer (ELITECH Group, France) to confirm the clinical diagnosis of CF. In addition, nucleic acid from the patients' blood samples was extracted and the CFTR mutation profiles were assessed by direct sequencing of the CFTR 27 exons and the intron-exon boundaries. For patient's DNA samples where no homozygous or two heterozygous CFTR mutations were identified by exon sequencing, DNA samples were tested for deletions or duplications using SALSA MLPA probemix P091-D1 CFTR assay. Sweat chloride testing confirmed the clinical diagnosis of CF in those patients. All patients had NaCl conductivity >60 mmol/l. In addition, nine different CFTR mutations were identified in all 21 different families evaluated. These mutations were c.1393-1G>A, F508del, W1282X, G85E, c.313delA, N1303K, deletion exons 17a-17b-18, deletion exons 17a-17b and Q1100P. c.1393-1G>A was shown to be the most frequent occurring mutation among tested families. We have profiled the underling mutations in the CFTR gene of a cohort of 21 different families affected by CF. Unlike other studies from the Arab countries where F508del was reported to be the most common mutation, in southern/central Palestine, the c.1393-1G>A appeared to be the most common. Further studies are needed per sample size and geographic distribution to account for other possible CFTR genetic alterations and their frequencies. Genotype/phenotype assessments are also recommended and finally carrier frequency should be ascertained