Cross-sectional seroprevalence study of antibody to Bordetella pertussis toxin in western Saudi Arabia: is there a need for a vaccine booster dose for adolescents and young adults?

Objectives The present study was conducted to estimate the seroprevalence of antibody to pertussis toxin among adult populations in western Saudi Arabia.Design A cross-sectional study.Setting King Abdulaziz Medical City, Jeddah, western Saudi Arabia. A tertiary care teaching hospital.Participants A total of 1200 participants (400 healthcare workers, 400 military recruits and 400 blood donors) were included. The majority were male (79.3%), and the mean (±SD) age was 27.2 (±6.7) years old.Interventions The study included the analysis of serum blood samples using commercial ELISA. A consecutive sampling technique was applied.Primary outcome measures Seropositivity of antipertussis toxin immunoglobulin G (anti-PT IgG) ≥62.5 IU/mL.Results Antibody titres ≥62.5 IU/mL, indicating exposure to Bordetella pertussis infection within the last year, were identified in 12.0% (95% CI 10.2% to 14.0%) of the participants. Titres ≥125 IU/mL, suggesting recent infection, were detected in 3.5% (95% CI 2.5% to 4.7%). Seroprevalence of positive IgG antibody titres (≥62.5 IU/mL) was highest among the healthcare workers (HCWs) (14%), then the military recruits (13.5%) and blood donors (8.5%; p=0.03). The multivariate regression analysis showed association between participants group (HCWs and military), male gender and younger age (<25 years old) and higher antibody to pertussis toxin.Conclusions High pertussis seropositivity was associated with participants’ occupation (ie, healthcare workers and military recruits), and anti-PT IgG titre was negatively correlated with age. A substantial deficiency in pertussis reporting in Saudi Arabia has been suggested, with potential increased risk to the most vulnerable populations (ie, infants and elderly). Enhancing the booster dose of pertussis vaccine for adolescents and adults is crucial to minimise the burden of pertussis

First report of Klebsiella quasipneumoniae harboring bla(KPC-2) in Saudi Arabia

Background Nosocomial infections caused by multi-drug resistant Enterobacteriaceae are a global public health threat that ought to be promptly identified, reported, and addressed accurately. Many carbapenem-resistant Enterobacteriaceae-associated genes have been identified in Saudi Arabia but not the endemic Klebsiella pneumoniae carbapenemases (KPCs), which are encoded by bla(KPC-type) genes. KPCs are known for their exceptional spreading potential. Methods We collected n = 286 multi-drug resistant (MDR) Klebsiella spp. isolates as part of screening for resistant patterns from a tertiary hospital in Saudi Arabia between 2014 and 2018. Antimicrobial susceptibility testing was carried out using both VITEK II and the broth microdilution of all collected isolates. Detection of resistance-conferring genes was carried out using Illumina whole-genome shotgun sequencing and PacBio SMRT sequencing protocols. Results A Carbapenem-resistant Enterobacteriaceae (CRE) Klebsiella quasipneumoniae subsp. similipneumoniae strain was identified as a novel ST-3510 carrying a bla(KPC-2) carbapenemase encoding gene. The isolate, designated as NGKPC-421, was obtained from shotgun Whole Genome Sequencing (WGS) surveillance of 286 MDR Klebsiella spp. clinical isolates. The NGKPC-421 isolate was collected from a septic patient in late 2017 and was initially misidentified as K. pneumoniae. The sequencing and assembly of the NGKPC-421 genome resulted in the identification of a putative similar to 39.4 kb IncX6 plasmid harboring a bla(KPC-2) gene, flanked by transposable elements (ISKpn6-bla(KPC-2)-ISKpn27). Conclusion This is the first identification of a KPC-2-producing CRE in the Gulf region. The impact on this finding is of major concern to the public health in Saudi Arabia, considering that it is the religious epicenter with a continuous mass influx of pilgrims from across the world. Our study strongly highlights the importance of implementing rapid sequencing-based technologies in clinical microbiology for precise taxonomic classification and monitoring of antimicrobial resistance patterns

First report of Klebsiella quasipneumoniae harboring bla KPC-2 in Saudi Arabia

Background: Nosocomial infections caused by multi-drug resistant Enterobacteriaceae are a global public health threat that ought to be promptly identified, reported, and addressed accurately. Many carbapenem-resistant Enterobacteriaceae-associated genes have been identified in Saudi Arabia but not the endemic Klebsiella pneumoniae carbapenemases (KPCs), which are encoded by bla genes. KPCs are known for their exceptional spreading potential. Methods: We collected n = 286 multi-drug resistant (MDR) Klebsiella spp. isolates as part of screening for resistant patterns from a tertiary hospital in Saudi Arabia between 2014 and 2018. Antimicrobial susceptibility testing was carried out using both VITEK II and the broth microdilution of all collected isolates. Detection of resistance-conferring genes was carried out using Illumina whole-genome shotgun sequencing and PacBio SMRT sequencing protocols. Results: A Carbapenem-resistant Enterobacteriaceae (CRE) Klebsiella quasipneumoniae subsp. similipneumoniae strain was identified as a novel ST-3510 carrying a bla carbapenemase encoding gene. The isolate, designated as NGKPC-421, was obtained from shotgun Whole Genome Sequencing (WGS) surveillance of 286 MDR Klebsiella spp. clinical isolates. The NGKPC-421 isolate was collected from a septic patient in late 2017 and was initially misidentified as K. pneumoniae. The sequencing and assembly of the NGKPC-421 genome resulted in the identification of a putative ~ 39.4 kb IncX6 plasmid harboring a bla gene, flanked by transposable elements (ISKpn6-bla -ISKpn27). Conclusion: This is the first identification of a KPC-2-producing CRE in the Gulf region. The impact on this finding is of major concern to the public health in Saudi Arabia, considering that it is the religious epicenter with a continuous mass influx of pilgrims from across the world. Our study strongly highlights the importance of implementing rapid sequencing-based technologies in clinical microbiology for precise taxonomic classification and monitoring of antimicrobial resistance patterns

Treatment of Middle East Respiratory Syndrome with a combination of lopinavir-ritonavir and interferon-β1b (MIRACLE trial): study protocol for a randomized controlled trial

Abstract Background It had been more than 5 years since the first case of Middle East Respiratory Syndrome coronavirus infection (MERS-CoV) was recorded, but no specific treatment has been investigated in randomized clinical trials. Results from in vitro and animal studies suggest that a combination of lopinavir/ritonavir and interferon-β1b (IFN-β1b) may be effective against MERS-CoV. The aim of this study is to investigate the efficacy of treatment with a combination of lopinavir/ritonavir and recombinant IFN-β1b provided with standard supportive care, compared to treatment with placebo provided with standard supportive care in patients with laboratory-confirmed MERS requiring hospital admission. Methods The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. Hospitalized adult patients with laboratory-confirmed MERS will be enrolled in this recursive, two-stage, group sequential, multicenter, placebo-controlled, double-blind randomized controlled trial. The trial is initially designed to include 2 two-stage components. The first two-stage component is designed to adjust sample size and determine futility stopping, but not efficacy stopping. The second two-stage component is designed to determine efficacy stopping and possibly readjustment of sample size. The primary outcome is 90-day mortality. Discussion This will be the first randomized controlled trial of a potential treatment for MERS. The study is sponsored by King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. Enrollment for this study began in November 2016, and has enrolled thirteen patients as of Jan 24-2018. Trial registration ClinicalTrials.gov, ID: NCT02845843. Registered on 27 July 2016

Treatment of Middle East respiratory syndrome with a combination of lopinavir/ritonavir and interferon-β1b (MIRACLE trial): statistical analysis plan for a recursive two-stage group sequential randomized controlled trial

Abstract The MIRACLE trial (MERS-CoV Infection tReated with A Combination of Lopinavir/ritonavir and intErferon-β1b) investigates the efficacy of a combination therapy of lopinavir/ritonavir and recombinant interferon-β1b provided with standard supportive care, compared to placebo provided with standard supportive care, in hospitalized patients with laboratory-confirmed MERS. The MIRACLE trial is designed as a recursive, two-stage, group sequential, multicenter, placebo-controlled, double-blind randomized controlled trial. The aim of this article is to describe the statistical analysis plan for the MIRACLE trial. The primary outcome is 90-day mortality. The primary analysis will follow the intention-to-treat principle. The MIRACLE trial is the first randomized controlled trial for MERS treatment. Trial registration ClinicalTrials.gov, NCT02845843. Registered on 27 July 2016

Additional file 1: of Treatment of Middle East Respiratory Syndrome with a combination of lopinavir-ritonavir and interferon-β1b (MIRACLE trial): study protocol for a randomized controlled trial

SPIRIT 2013 Checklist: recommended items to address in a clinical trial protocol and related documents*. (DOC 120 kb