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New molecular tools for meningitis diagnostics in Ethiopia - a necessary step towards improving antimicrobial prescription
Meningitis remains a top cause of premature death and loss of disability-adjusted life years in low-income countries. In resource-limited settings, proper laboratory diagnostics are often scarce and knowledge about national and local epidemiology is limited. Misdiagnosis, incorrect treatment and ove...
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Published in: | BMC infectious diseases 2018-12, Vol.18 (1), p.684-684, Article 684 |
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creator | Bårnes, Guro K Gudina, Esayas Kebede Berhane, Melkamu Abdissa, Alemseged Tesfaw, Getnet Abebe, Gemeda Feruglio, Siri Laura Caugant, Dominique A Jørgensen, Hannah Joan |
description | Meningitis remains a top cause of premature death and loss of disability-adjusted life years in low-income countries. In resource-limited settings, proper laboratory diagnostics are often scarce and knowledge about national and local epidemiology is limited. Misdiagnosis, incorrect treatment and overuse of antibiotics are potential consequences, especially for viral meningitis.
A prospective study was conducted over three months in a teaching hospital in Ethiopia with limited laboratory resources. Cerebrospinal fluid (CSF) samples from patients with suspected meningitis were analysed using a multiplex PCR-based system (FilmArray, BioFire), in addition to basic routine testing with microscopy and culture. Clinical data, as well as information on treatment and outcome were collected.
Two hundred and eighteen patients were included; 117 (54%) neonates (0-29 days), 63 (29%) paediatrics (1 month-15 years) and 38 (17%) adults (≥16 years). Of 218 CSF samples, 21 (10%) were PCR positive; 4% in neonates, 14% in paediatrics and 18% in adults. Virus was detected in 57% of the PCR positive samples, bacteria in 33% and fungi in 10%. All CSF samples that were PCR positive for a bacterial agent had a white cell count ≥75 cells/mm
and/or turbid appearance. The majority (90%) of patients received more than one antibiotic for treatment of the meningitis episode. There was no difference in the mean number of different antibiotics received or in the cumulative number of days with antibiotic treatment between patients with a microorganism detected in CSF and those without.
A rapid molecular diagnostic system was successfully implemented in an Ethiopian setting without previous experience of molecular diagnostics. Viral meningitis was diagnosed for the first time in routine clinical practice in Ethiopia, and viral agents were the most commonly detected microorganisms in CSF. This study illustrates the potential of rapid diagnostic tests for reducing antibiotic usage in suspected meningitis cases. However, the cost of consumables for the molecular diagnostic system used in this study limits its use in low-income countries. |
doi_str_mv | 10.1186/s12879-018-3589-4 |
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A prospective study was conducted over three months in a teaching hospital in Ethiopia with limited laboratory resources. Cerebrospinal fluid (CSF) samples from patients with suspected meningitis were analysed using a multiplex PCR-based system (FilmArray, BioFire), in addition to basic routine testing with microscopy and culture. Clinical data, as well as information on treatment and outcome were collected.
Two hundred and eighteen patients were included; 117 (54%) neonates (0-29 days), 63 (29%) paediatrics (1 month-15 years) and 38 (17%) adults (≥16 years). Of 218 CSF samples, 21 (10%) were PCR positive; 4% in neonates, 14% in paediatrics and 18% in adults. Virus was detected in 57% of the PCR positive samples, bacteria in 33% and fungi in 10%. All CSF samples that were PCR positive for a bacterial agent had a white cell count ≥75 cells/mm
and/or turbid appearance. The majority (90%) of patients received more than one antibiotic for treatment of the meningitis episode. There was no difference in the mean number of different antibiotics received or in the cumulative number of days with antibiotic treatment between patients with a microorganism detected in CSF and those without.
A rapid molecular diagnostic system was successfully implemented in an Ethiopian setting without previous experience of molecular diagnostics. Viral meningitis was diagnosed for the first time in routine clinical practice in Ethiopia, and viral agents were the most commonly detected microorganisms in CSF. This study illustrates the potential of rapid diagnostic tests for reducing antibiotic usage in suspected meningitis cases. However, the cost of consumables for the molecular diagnostic system used in this study limits its use in low-income countries.</description><identifier>ISSN: 1471-2334</identifier><identifier>EISSN: 1471-2334</identifier><identifier>DOI: 10.1186/s12879-018-3589-4</identifier><identifier>PMID: 30572843</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Adolescent ; Adult ; Adults ; Aged ; Aged, 80 and over ; Anti-infective agents ; Anti-Infective Agents - classification ; Anti-Infective Agents - economics ; Anti-Infective Agents - therapeutic use ; Antibiotics ; Antimicrobial agents ; Aseptic meningitis ; Bacterial meningitis ; Cell culture ; Cerebrospinal fluid ; Child ; Child, Preschool ; Diagnosis ; Diagnosis, Differential ; Diagnostic systems ; Disease ; Drug resistance ; Economic aspects ; Encephalitis ; Epidemiology ; Ethiopia ; Female ; FilmArray ; Fungi ; Health care ; Health Resources ; Hospitals, Teaching - economics ; Humans ; Income ; Infant ; Infant, Newborn ; Infectious diseases ; Laboratories ; Low income groups ; Male ; Meningitis ; Meningitis - cerebrospinal fluid ; Meningitis - diagnosis ; Meningitis - drug therapy ; Meningitis - genetics ; Meningitis, Bacterial - cerebrospinal fluid ; Meningitis, Bacterial - diagnosis ; Meningitis, Bacterial - drug therapy ; Meningitis, Viral - cerebrospinal fluid ; Meningitis, Viral - diagnosis ; Meningitis, Viral - drug therapy ; Microorganisms ; Microscopy ; Middle Aged ; Molecular Diagnostic Techniques - economics ; Molecular Diagnostic Techniques - methods ; Molecular Diagnostic Techniques - trends ; Mortality ; Multiplex PCR ; Multiplex Polymerase Chain Reaction - economics ; Neonates ; Patient outcomes ; Patients ; Pediatrics ; Polymerase chain reaction ; Practice Patterns, Physicians' - economics ; Practice Patterns, Physicians' - standards ; Practice Patterns, Physicians' - trends ; Quality Improvement ; Teaching hospitals ; Viral meningitis ; Viruses ; Young Adult</subject><ispartof>BMC infectious diseases, 2018-12, Vol.18 (1), p.684-684, Article 684</ispartof><rights>COPYRIGHT 2018 BioMed Central Ltd.</rights><rights>Copyright © 2018. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The Author(s). 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c628t-a27374f3c56873a4709d6e4a6cacf6d197cefe6bea076d60cca7a48ae73e18eb3</citedby><cites>FETCH-LOGICAL-c628t-a27374f3c56873a4709d6e4a6cacf6d197cefe6bea076d60cca7a48ae73e18eb3</cites><orcidid>0000-0003-2765-9844</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6302510/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2168525096?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,882,25734,27905,27906,36993,36994,44571,53772,53774</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30572843$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bårnes, Guro K</creatorcontrib><creatorcontrib>Gudina, Esayas Kebede</creatorcontrib><creatorcontrib>Berhane, Melkamu</creatorcontrib><creatorcontrib>Abdissa, Alemseged</creatorcontrib><creatorcontrib>Tesfaw, Getnet</creatorcontrib><creatorcontrib>Abebe, Gemeda</creatorcontrib><creatorcontrib>Feruglio, Siri Laura</creatorcontrib><creatorcontrib>Caugant, Dominique A</creatorcontrib><creatorcontrib>Jørgensen, Hannah Joan</creatorcontrib><title>New molecular tools for meningitis diagnostics in Ethiopia - a necessary step towards improving antimicrobial prescription</title><title>BMC infectious diseases</title><addtitle>BMC Infect Dis</addtitle><description>Meningitis remains a top cause of premature death and loss of disability-adjusted life years in low-income countries. In resource-limited settings, proper laboratory diagnostics are often scarce and knowledge about national and local epidemiology is limited. Misdiagnosis, incorrect treatment and overuse of antibiotics are potential consequences, especially for viral meningitis.
A prospective study was conducted over three months in a teaching hospital in Ethiopia with limited laboratory resources. Cerebrospinal fluid (CSF) samples from patients with suspected meningitis were analysed using a multiplex PCR-based system (FilmArray, BioFire), in addition to basic routine testing with microscopy and culture. Clinical data, as well as information on treatment and outcome were collected.
Two hundred and eighteen patients were included; 117 (54%) neonates (0-29 days), 63 (29%) paediatrics (1 month-15 years) and 38 (17%) adults (≥16 years). Of 218 CSF samples, 21 (10%) were PCR positive; 4% in neonates, 14% in paediatrics and 18% in adults. Virus was detected in 57% of the PCR positive samples, bacteria in 33% and fungi in 10%. All CSF samples that were PCR positive for a bacterial agent had a white cell count ≥75 cells/mm
and/or turbid appearance. The majority (90%) of patients received more than one antibiotic for treatment of the meningitis episode. There was no difference in the mean number of different antibiotics received or in the cumulative number of days with antibiotic treatment between patients with a microorganism detected in CSF and those without.
A rapid molecular diagnostic system was successfully implemented in an Ethiopian setting without previous experience of molecular diagnostics. Viral meningitis was diagnosed for the first time in routine clinical practice in Ethiopia, and viral agents were the most commonly detected microorganisms in CSF. This study illustrates the potential of rapid diagnostic tests for reducing antibiotic usage in suspected meningitis cases. However, the cost of consumables for the molecular diagnostic system used in this study limits its use in low-income countries.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Adults</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Anti-infective agents</subject><subject>Anti-Infective Agents - classification</subject><subject>Anti-Infective Agents - economics</subject><subject>Anti-Infective Agents - therapeutic use</subject><subject>Antibiotics</subject><subject>Antimicrobial agents</subject><subject>Aseptic meningitis</subject><subject>Bacterial meningitis</subject><subject>Cell culture</subject><subject>Cerebrospinal fluid</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Diagnosis</subject><subject>Diagnosis, Differential</subject><subject>Diagnostic systems</subject><subject>Disease</subject><subject>Drug resistance</subject><subject>Economic aspects</subject><subject>Encephalitis</subject><subject>Epidemiology</subject><subject>Ethiopia</subject><subject>Female</subject><subject>FilmArray</subject><subject>Fungi</subject><subject>Health care</subject><subject>Health Resources</subject><subject>Hospitals, Teaching - economics</subject><subject>Humans</subject><subject>Income</subject><subject>Infant</subject><subject>Infant, Newborn</subject><subject>Infectious diseases</subject><subject>Laboratories</subject><subject>Low income groups</subject><subject>Male</subject><subject>Meningitis</subject><subject>Meningitis - cerebrospinal fluid</subject><subject>Meningitis - diagnosis</subject><subject>Meningitis - drug therapy</subject><subject>Meningitis - genetics</subject><subject>Meningitis, Bacterial - cerebrospinal fluid</subject><subject>Meningitis, Bacterial - diagnosis</subject><subject>Meningitis, Bacterial - drug therapy</subject><subject>Meningitis, Viral - cerebrospinal fluid</subject><subject>Meningitis, Viral - diagnosis</subject><subject>Meningitis, Viral - drug therapy</subject><subject>Microorganisms</subject><subject>Microscopy</subject><subject>Middle Aged</subject><subject>Molecular Diagnostic Techniques - economics</subject><subject>Molecular Diagnostic Techniques - methods</subject><subject>Molecular Diagnostic Techniques - trends</subject><subject>Mortality</subject><subject>Multiplex PCR</subject><subject>Multiplex Polymerase Chain Reaction - economics</subject><subject>Neonates</subject><subject>Patient outcomes</subject><subject>Patients</subject><subject>Pediatrics</subject><subject>Polymerase chain reaction</subject><subject>Practice Patterns, Physicians' - economics</subject><subject>Practice Patterns, Physicians' - standards</subject><subject>Practice Patterns, Physicians' - trends</subject><subject>Quality Improvement</subject><subject>Teaching hospitals</subject><subject>Viral meningitis</subject><subject>Viruses</subject><subject>Young Adult</subject><issn>1471-2334</issn><issn>1471-2334</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNqNks1u1DAUhSMEoqXwAGyQJTawSPFfbGeDVFUFRqqoxN_WcpybqUeJHWynBZ4eD1NKB7FAWSRyvvM5vjlV9ZTgY0KUeJUIVbKtMVE1a1Rb83vVIeGS1JQxfv_O80H1KKUNxkQq2j6sDhhuJFWcHVY_3sM1msIIdhlNRDmEMaEhRDSBd37tskuod2btQ8rOJuQ8OsuXLszOoBoZ5MFCSiZ-RynDXPLXJvYFm-YYrooAGZ_d5GwMnTMjmiMkG92cXfCPqweDGRM8ubkfVZ_fnH06fVefX7xdnZ6c11ZQlWtDJZN8YLYRSjLDJW57AdwIa-wgetJKCwOIDgyWohfYWiMNVwYkA6KgY0fVauftg9noObqpfK4OxulfCyGutYnlcCNoUBI6DmIQvONdmRXvetUJyou0xYoW1-uda166CXoLPkcz7kn333h3qdfhSguGaUNwEby4EcTwdYGU9eSShXE0HsKSNCVN2ypGCSno87_QTViiL6MqlFANbXAr_lBrUw7g_BDKvnYr1SeNaLGUnG-p439Q5eqh_JzgYXBlfS_wci9QmAzf8tosKenVxw__z1582WfJji2NSCnCcDs7gvW21HpXal1Krbel1rxknt0d-m3id4vZT-Xx8uc</recordid><startdate>20181220</startdate><enddate>20181220</enddate><creator>Bårnes, Guro K</creator><creator>Gudina, Esayas Kebede</creator><creator>Berhane, Melkamu</creator><creator>Abdissa, Alemseged</creator><creator>Tesfaw, Getnet</creator><creator>Abebe, Gemeda</creator><creator>Feruglio, Siri Laura</creator><creator>Caugant, Dominique A</creator><creator>Jørgensen, Hannah Joan</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><general>BMC</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QL</scope><scope>7T2</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-2765-9844</orcidid></search><sort><creationdate>20181220</creationdate><title>New molecular tools for meningitis diagnostics in Ethiopia - a necessary step towards improving antimicrobial prescription</title><author>Bårnes, Guro K ; Gudina, Esayas Kebede ; Berhane, Melkamu ; Abdissa, Alemseged ; Tesfaw, Getnet ; Abebe, Gemeda ; Feruglio, Siri Laura ; Caugant, Dominique A ; Jørgensen, Hannah Joan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c628t-a27374f3c56873a4709d6e4a6cacf6d197cefe6bea076d60cca7a48ae73e18eb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Adults</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Anti-infective agents</topic><topic>Anti-Infective Agents - classification</topic><topic>Anti-Infective Agents - economics</topic><topic>Anti-Infective Agents - therapeutic use</topic><topic>Antibiotics</topic><topic>Antimicrobial agents</topic><topic>Aseptic meningitis</topic><topic>Bacterial meningitis</topic><topic>Cell culture</topic><topic>Cerebrospinal fluid</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Diagnosis</topic><topic>Diagnosis, Differential</topic><topic>Diagnostic systems</topic><topic>Disease</topic><topic>Drug resistance</topic><topic>Economic aspects</topic><topic>Encephalitis</topic><topic>Epidemiology</topic><topic>Ethiopia</topic><topic>Female</topic><topic>FilmArray</topic><topic>Fungi</topic><topic>Health care</topic><topic>Health Resources</topic><topic>Hospitals, Teaching - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>BMC infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bårnes, Guro K</au><au>Gudina, Esayas Kebede</au><au>Berhane, Melkamu</au><au>Abdissa, Alemseged</au><au>Tesfaw, Getnet</au><au>Abebe, Gemeda</au><au>Feruglio, Siri Laura</au><au>Caugant, Dominique A</au><au>Jørgensen, Hannah Joan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>New molecular tools for meningitis diagnostics in Ethiopia - a necessary step towards improving antimicrobial prescription</atitle><jtitle>BMC infectious diseases</jtitle><addtitle>BMC Infect Dis</addtitle><date>2018-12-20</date><risdate>2018</risdate><volume>18</volume><issue>1</issue><spage>684</spage><epage>684</epage><pages>684-684</pages><artnum>684</artnum><issn>1471-2334</issn><eissn>1471-2334</eissn><abstract>Meningitis remains a top cause of premature death and loss of disability-adjusted life years in low-income countries. In resource-limited settings, proper laboratory diagnostics are often scarce and knowledge about national and local epidemiology is limited. Misdiagnosis, incorrect treatment and overuse of antibiotics are potential consequences, especially for viral meningitis.
A prospective study was conducted over three months in a teaching hospital in Ethiopia with limited laboratory resources. Cerebrospinal fluid (CSF) samples from patients with suspected meningitis were analysed using a multiplex PCR-based system (FilmArray, BioFire), in addition to basic routine testing with microscopy and culture. Clinical data, as well as information on treatment and outcome were collected.
Two hundred and eighteen patients were included; 117 (54%) neonates (0-29 days), 63 (29%) paediatrics (1 month-15 years) and 38 (17%) adults (≥16 years). Of 218 CSF samples, 21 (10%) were PCR positive; 4% in neonates, 14% in paediatrics and 18% in adults. Virus was detected in 57% of the PCR positive samples, bacteria in 33% and fungi in 10%. All CSF samples that were PCR positive for a bacterial agent had a white cell count ≥75 cells/mm
and/or turbid appearance. The majority (90%) of patients received more than one antibiotic for treatment of the meningitis episode. There was no difference in the mean number of different antibiotics received or in the cumulative number of days with antibiotic treatment between patients with a microorganism detected in CSF and those without.
A rapid molecular diagnostic system was successfully implemented in an Ethiopian setting without previous experience of molecular diagnostics. Viral meningitis was diagnosed for the first time in routine clinical practice in Ethiopia, and viral agents were the most commonly detected microorganisms in CSF. This study illustrates the potential of rapid diagnostic tests for reducing antibiotic usage in suspected meningitis cases. However, the cost of consumables for the molecular diagnostic system used in this study limits its use in low-income countries.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>30572843</pmid><doi>10.1186/s12879-018-3589-4</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0003-2765-9844</orcidid><oa>free_for_read</oa></addata></record> |
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recordid | cdi_doaj_primary_oai_doaj_org_article_e87eb4e6f64b4b8294bd8b624cca9082 |
source | Publicly Available Content Database; PubMed Central |
subjects | Adolescent Adult Adults Aged Aged, 80 and over Anti-infective agents Anti-Infective Agents - classification Anti-Infective Agents - economics Anti-Infective Agents - therapeutic use Antibiotics Antimicrobial agents Aseptic meningitis Bacterial meningitis Cell culture Cerebrospinal fluid Child Child, Preschool Diagnosis Diagnosis, Differential Diagnostic systems Disease Drug resistance Economic aspects Encephalitis Epidemiology Ethiopia Female FilmArray Fungi Health care Health Resources Hospitals, Teaching - economics Humans Income Infant Infant, Newborn Infectious diseases Laboratories Low income groups Male Meningitis Meningitis - cerebrospinal fluid Meningitis - diagnosis Meningitis - drug therapy Meningitis - genetics Meningitis, Bacterial - cerebrospinal fluid Meningitis, Bacterial - diagnosis Meningitis, Bacterial - drug therapy Meningitis, Viral - cerebrospinal fluid Meningitis, Viral - diagnosis Meningitis, Viral - drug therapy Microorganisms Microscopy Middle Aged Molecular Diagnostic Techniques - economics Molecular Diagnostic Techniques - methods Molecular Diagnostic Techniques - trends Mortality Multiplex PCR Multiplex Polymerase Chain Reaction - economics Neonates Patient outcomes Patients Pediatrics Polymerase chain reaction Practice Patterns, Physicians' - economics Practice Patterns, Physicians' - standards Practice Patterns, Physicians' - trends Quality Improvement Teaching hospitals Viral meningitis Viruses Young Adult |
title | New molecular tools for meningitis diagnostics in Ethiopia - a necessary step towards improving antimicrobial prescription |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-19T21%3A45%3A45IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_doaj_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=New%20molecular%20tools%20for%20meningitis%20diagnostics%20in%20Ethiopia%20-%20a%20necessary%20step%20towards%20improving%20antimicrobial%20prescription&rft.jtitle=BMC%20infectious%20diseases&rft.au=B%C3%A5rnes,%20Guro%20K&rft.date=2018-12-20&rft.volume=18&rft.issue=1&rft.spage=684&rft.epage=684&rft.pages=684-684&rft.artnum=684&rft.issn=1471-2334&rft.eissn=1471-2334&rft_id=info:doi/10.1186/s12879-018-3589-4&rft_dat=%3Cgale_doaj_%3EA569077446%3C/gale_doaj_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c628t-a27374f3c56873a4709d6e4a6cacf6d197cefe6bea076d60cca7a48ae73e18eb3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2168525096&rft_id=info:pmid/30572843&rft_galeid=A569077446&rfr_iscdi=true |