Characterization of greater middle eastern genetic variation for enhanced disease gene discovery

The Greater Middle East (GME) has been a central hub of human migration and population admixture. The tradition of consanguinity, variably practiced in the Persian Gulf region, North Africa, and Central Asia1-3, has resulted in an elevated burden of recessive disease4. Here we generated a whole-exome GME variome from 1,111 unrelated subjects. We detected substantial diversity and admixture in continental and subregional populations, corresponding to several ancient founder populations with little evidence of bottlenecks. Measured consanguinity rates were an order of magnitude above those in other sampled populations, and the GME population exhibited an increased burden of runs of homozygosity (ROHs) but showed no evidence for reduced burden of deleterious variation due to classically theorized ‘genetic purging’. Applying this database to unsolved recessive conditions in the GME population reduced the number of potential disease-causing variants by four- to sevenfold. These results show variegated genetic architecture in GME populations and support future human genetic discoveries in Mendelian and population genetics

Characterization of invasive Neisseria meningitidis isolates recovered from children in Turkey during a period of increased serogroup B disease, 2013-2017

Emiroglu, Melike/0000-0003-1307-0246WOS: 000525318100007PubMed: 32199701Diverse Neisseria meningitidis strains belonging to various serogroups and clonal complexes cause epidemic and endemic life-threatening disease worldwide. This study aimed to investigate the genetic diversity of recent invasive meningococci in Turkey with respect to multilocus sequence type (MLST) and also meningococcal serogroup B (MenB) vaccine antigens to enable assessment of potential MenB strain coverage using the genetic Meningococcal Antigen Typing System (gMATS). Fifty-four isolates, representing 37.5% of all pediatric (ages 0-18 years) invasive meningococcal disease cases in Turkey from January 2013 to December 2017, underwent genome sequence analysis. Thirty-six (66.7%) isolates were MenB, 10 (18.5%) were serogroup W (MenW), 4 (7.4%) were serogroup A (MenA), 3 (5.6%) were serogroup Y (MenY) and 1 (1.8%) was serogroup X (MenX). the MenB isolates were diverse with cc35 (19.4%), cc41/44 (19.4%) and cc32 (13.8%) as the most prevalent clonal complexes. the MenW isolates (n = 10) comprised cc11 (n = 5), ST-2754 (cc-unassigned; n = 4) and cc22 (n = 1). gMATS was indicative of high 4CMenB coverage (72.2-79.1%) of Turkish invasive MenB strains from pediatric patients. Strain coverage of several clonal complexes differed from that seen elsewhere in Europe highlighting the importance of performing local assessments and also the use of phenotypic methods, i.e. MATS, where possible. All of the isolates possessed in-frame fhbp alleles and so were potentially covered by MenB-fHbp. Continued surveillance is essential to guide recommendations for current and future vaccines as well as understanding changes in epidemiology. (C) 2020 Elsevier Ltd. All rights reserved.Wellcome TrustWellcome Trust; European UnionEuropean Union (EU)This publication made use of the Neisseria Multi Locus Sequence Typing website (https://pubmlst.org/neisseria/) sited at the University of Oxford [version 1; referees: 2 approved]) [45]. the development of this site has been funded by the Wellcome Trust and European Union

Multicenter Hospital-Based Prospective Surveillance Study of Bacterial Agents Causing Meningitis and Seroprevalence of Different Serogroups of Neisseria meningitidis, Haemophilus influenzae Type b, and Streptococcus pneumoniae during 2015 to 2018 in Turkey

Emiroglu, Melike/0000-0003-1307-0246; Basaranoglu, Sevgen Tanir/0000-0002-9416-1512; Sutcu, Murat/0000-0002-2078-9796; Duman, Murat/0000-0001-6767-5748WOS: 000551068100003PubMed: 32213620The etiology of bacterial meningitis in Turkey changed after the implementation of conjugated vaccines against Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) in the Turkish National Immunization Program (NIP). Administration of Hib vaccine and PCV-7 (7-valent pneumococcal conjugate vaccine) was implemented in NIP in 2006 and 2009, respectively. in 2011, PCV-7 was replaced with PCV-13. Meningococcal vaccines have not yet been included in Turkish NIP. This prospective study comprised 27 hospitals located in seven regions of Turkey and represented 45% of the population. Children aged between 1 month and 18 years who were hospitalized with suspected meningitis were included. Cerebrospinal fluid (CSF) samples were collected, and bacterial identification was made according to the multiplex PCR assay results. During the study period, 994 children were hospitalized for suspected meningitis, and Hib (n = 3, 2.4%), S. pneumoniae (n = 33, 26.4%), and Neisseria meningitidis (n = 89, 71%) were detected in 125 samples. the most common meningococcal serogroup was MenB. Serogroup W comprised 13.9% (n = 5) and 7.5% (n = 4) of the meningococci in 2015 to 2016 and 2017 to 2018, respectively. Serogroup C was not detected. There were four deaths in the study; one was a pneumococcus case, and the others were serogroup B meningococcus cases. the epidemiology of meningococcal diseases has varied over time in Turkey. Differing from the previous surveillance periods, MenB was the most common serogroup in the 2015-to-2018 period. Meningococcal epidemiology is so dynamic that, for vaccination policies, close monitoring is crucial. IMPORTANCE Acute bacterial meningitis (ABM) is one of the most common life-threatening infections in children. the incidence and prevalence of ABM vary both geographically and temporally; therefore, surveillance systems are necessary to determine the accurate burden of ABM. the Turkish Meningitis Surveillance Group has been performing a hospital-based meningitis surveillance study since 2005 across several regions in Turkey. Meningococcus was the major ABM-causing agent during the 2015-to-2018 period, during which MenB was the dominant serogroup.GlaxoSmithKlineGlaxoSmithKlineFunding for this study was provided by GlaxoSmithKline

Assessment of 35 children with abdominal tuberculosis

Background/Aims: To contribute to the diagnosis and treatment of pediatric abdominal tuberculosis cases by assessing the clinical, laboratory, and radiological features of patients who presented at our clinic and were diagnosed with abdominal tuberculosis

Evaluation of pneumococcal PCR and urinary antigen detection in children

Background: The rapid detection of Streptococcus pneumoniae could assist in the management of pneumococcal infections. The Binax NOW S. pneumoniae test is a rapid immunochromatographic test for this purpose. Methods: Multiplex PCR in parapneumonic pleural effusion fluid (PPEF) and cerebrospinal fluid (CSF) with Binax NOW urinary pneumococcal antigen test (PAT) from 80 children was compared in this study. Results: PAT had a sensitivity of 36.4%, specificity of 97.3%, in CSF. PAT had a sensitivity of 50%, specificity of 81% for parapneumonic pleural effusion fluid. Conclusions: When rapid management of a serious infection is needed the Binax NOW test could be a reliable method for the exclusion of S. pneumoniae infection

Serotype distribution of Streptococcus pneumoniae in children with invasive diseases in Turkey: 2008-2014

WOS: 000371745700019PubMed ID: 26325175Successful vaccination policies for protection from invasive pneumococcal diseases (IPD) dependent on determination of the exact serotype distribution in each country. We aimed to identify serotypes of pneumococcal strains causing IPD in children in Turkey and emphasize the change in the serotypes before and after vaccination with 7-valent pneumococcal conjugate vaccine (PCV-7) was included and PCV-13 was newly changed in Turkish National Immunization Program. Streptococcus pneumoniae strains were isolated at 22 different hospitals of Turkey, which provide healthcare services to approximately 65% of the Turkish population. Of the 335 diagnosed cases with S. pneumoniae over the whole period of 2008-2014, the most common vaccine serotypes were 19F (15.8%), 6B (5.9%), 14 (5.9%), and 3 (5.9%). During the first 5y of age, which is the target population for vaccination, the potential serotype coverage ranged from 57.5 % to 36.8%, from 65.0% to 44.7%, and from 77.4% to 60.5% for PCV-7, PCV-10, and PCV-13 in 2008-2014, respectively. The ratio of non-vaccine serotypes was 27.2% in 2008-2010 whereas was 37.6% in 2011-2014 (p=0.045). S. penumoniae serotypes was less non-susceptible to penicillin as compared to our previous results (33.7vs 16.5 %, p=0.001). The reduction of those serotype coverage in years may be attributed to increasing vaccinated children in Turkey and the increasing non-vaccine serotype may be explained by serotype replacement. Our ongoing IPD surveillance is a significant source of information for the decision-making processes on pneumococcal vaccination.PfizerPfizerThis study was supported by Pfizer

Bacterial Agents Causing Meningitis During 2013-2014 in Turkey: A Multi-Center Hospital-Based Prospective Surveillance Study

This is an observational epidemiological study to describe causes of bacterial meningitis among persons between 1 month and 18 y of age who are hospitalized with suspected bacterial meningitis in 7 Turkish regions. covering 32% of the entire population of Turkey. We present here the results from 2013 and 2014. A clinical case with meningitis was defined according to followings: any sign of meningitis including fever, vomiting, headache, and meningeal irritation in children above one year of age and fever without any documented source, impaired consciousness, prostration and seizures in those < 1 y of age. Single tube multiplex PCR assay was performed for the simultaneous identification of bacterial agents. The specific gene targets were ctrA, bex, and ply for N. meningitidis, Hib, and S. pneumoniae, respectively. PCR positive samples were recorded as laboratory-confirmed acute bacterial meningitis. A total of 665 children were hospitalized for suspected acute meningitis. The annual incidences of acute laboratory-confirmed bacterial meningitis were 0.3 cases / 100,000 population in 2013 and 0.9 cases/100,000 in 2014. Of the 94 diagnosed cases of bacterial meningitis by PCR, 85 (90.4%) were meningococcal and 9 (9.6%) were pneumococcal. Hib was not detected in any of the patients. Among meningococcal meningitis, cases of serogroup Y, A, B and W-135 were 2.4% (n = 2), 3.5% (n = 3), 32.9% (n = 28), and 42.4% (n = 36). No serogroup C was detected among meningococcal cases. Successful vaccination policies for protection from bacterial meningitis are dependent on accurate determination of the etiology of bacterial meningitis. Additionally, the epidemiology of meningococcal disease is dynamic and close monitoring of serogroup distribution is comprehensively needed to assess the benefit of adding meningococcal vaccines to the routine immunization program.Wo

682. The Changing Epidemiology Of Bacterial Meningitis During 2015–2017 In Turkey: A Hospital-Based Prospective Surveillance Study

Background The etiology of bacterial meningitis in Turkey has been changed after the implementation of conjugated vaccines against Streptococcus pneumonia and Haemophilus influenzae type b (Hib) in Turkish national immunization schedule. Methods. This prospective study was conducted in 25 hospitals located seven regions of Turkey (representing 30% of Turkey population) and children aged between 1 month and 18 years with suspected meningitis and hospitalized were included. Cerebrospinal fluid samples were collected and bacterial identification was made according to the multiplex PCR assay results. Results. During the study period, 927 children were hospitalized for suspected meningitis and Hib (n:1), S. pneumonia (n:17) and Neisseria meningitidis (n:59) were detected in 77 samples (Figure 1, Table 1). During 2015–2016, N. meningitidis serogroup W, B, A, Y, X frequencies were as 5 (13.9%), 16 (44.4%), 1 (2.8%), 1 (2.8%), 1 (2.8%), respectively. There were 12 nongroupable N. meningitidis samples and serogroup C was not detected. In 2017, of meningococcal meningitis serogroup B, W, A, Y and X were identified in two (8.7%), 15 (65.2%), two (8.7%), 1 (4.3%) and 1 (4.3%) cases, respectively (Figure 2). There were four deaths in this study period, all of them were caused by N. meningitidis serogroup B and three of them were under 1 year old. Conclusion. The epidemiology of meningococcal diseases has been varied in time with or without any apparent reasons. Hajj is a well-known cause for serogroup W epidemics and serogorup W was the most common cause of meningitis in Turkey during 2009–2014 as in other Middle East countries. After the impact of serogroup W epidemics related to Hajj seen in 2010’s was diminished, serogroup B has been leading cause of childhood meningitis since 2015. In countries affected from Hajj like Turkey, vaccination of children with serogroup B meningococcal vaccine as well as quadrivalentconjugated vaccine seems to be very important. It should be kept in mind that meningococcal epidemiology is dynamic and needed to be closely monitored to detect changes in years Disclosures All authors: No reported disclosures.PubMe

Multicenter Hospital-Based Prospective Surveillance Study of Bacterial Agents Causing Meningitis and Seroprevalence of Different Serogroups of Neisseria meningitidis, Haemophilus influenzae Type b, and Streptococcus pneumoniae during 2015 to 2018 in Turkey

The etiology of bacterial meningitis in Turkey changed after the implementation of conjugated vaccines against Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) in the Turkish National Immunization Program (NIP). Administration of Hib vaccine and PCV-7 (7-valent pneumococcal conjugate vaccine) was implemented in NIP in 2006 and 2009, respectively. In 2011, PCV-7 was replaced with PCV-13. Meningococcal vaccines have not yet been included in Turkish NIP. This prospective study comprised 27 hospitals located in seven regions of Turkey and represented 45\% of the population. Children aged between 1 month and 18 years who were hospitalized with suspected meningitis were included. Cerebrospinal fluid (CSF) samples were collected, and bacterial identification was made according to the multiplex PCR assay results. During the study period, 994 children were hospitalized for suspected meningitis, and Hib (n = 3, 2.4\%), S. pneumoniae (n = 33, 26.4\%), and Neisseria meningitidis (n = 89, 71\%) were detected in 125 samples. The most common meningococcal serogroup was MenB. Serogroup W comprised 13.9\% (n = 5) and 7.5\% (n = 4) of the meningococci in 2015 to 2016 and 2017 to 2018, respectively. Serogroup C was not detected. There were four deaths in the study; one was a pneumococcus case, and the others were serogroup B meningococcus cases. The epidemiology of meningococcal diseases has varied over time in Turkey. Differing from the previous surveillance periods, MenB was the most common serogroup in the 2015-to-2018 period. Meningococcal epidemiology is so dynamic that, for vaccination policies, close monitoring is crucial. IMPORTANCE Acute bacterial meningitis (ABM) is one of the most common life-threatening infections in children. The incidence and prevalence of ABM vary both geographically and temporally; therefore, surveillance systems are necessary to determine the accurate burden of ABM. The Turkish Meningitis Surveillance Group has been performing a hospital-based meningitis surveillance study since 2005 across several regions in Turkey. Meningococcus was the major ABM-causing agent during the 2015-to-2018 period, during which MenB was the dominant serogroup