#Epidemic #preparedness: why is there a need to accelerate the #development of #diagnostics? (Lancet Infect Dis., summary)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Epidemic preparedness: why is there a need to accelerate the development of diagnostics?

Prof Rosanna W Peeling, PhD, Maurine Murtagh, PhD, Piero L Olliaro, MD

Published: December 11, 2018 / DOI: https://doi.org/10.1016/S1473-3099(18)30594-2

 

Summary

Global epidemics of infectious diseases are increasing in frequency and severity. Diagnostics are needed for rapid identification of the cause of the epidemic to facilitate effective control and prevention. Lessons learned from the recent Ebola virus and Zika virus epidemics are that delay in developing the right diagnostic for the right population at the right time has been a costly barrier to disease control and prevention. We believe that it is possible to accelerate and optimise diagnostic development through a five-pronged strategy: by doing a global landscape analysis of diagnostic availability worldwide; through strategic partnerships for accelerating test development, in particular with vaccine companies to identify novel diagnostic targets; by creating and sharing repositories of data, reagents, and well characterised specimens for advancing the development process; by involving key public and private stakeholders, including appropriate regulatory bodies and policy makers, to ensure rapid access for researchers to diagnostics; and last, by fostering an enabling environment for research and access to diagnostics in the countries that need them. The need is great, but not insurmountable and innovative and faster development pathways are urgently required to address current shortfalls.

Keywords: Emerging Diseases; Infectious Diseases; Pandemic preparedness; Diagnostic tests.

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The #Cat’s #Meow: Using Novel #Serological Approaches to Identify Cat-to- #Human #Influenza A(#H7N2) Transmission (J Infect Dis., summary)

[Source: Journal of Infectious Diseases, full page: (LINK). Summary, edited.]

The Cat’s Meow: Using Novel Serological Approaches to Identify Cat-to-Human Influenza A(H7N2) Transmission

Seema Jain, Erin L Murray

The Journal of Infectious Diseases, jiy596, https://doi.org/10.1093/infdis/jiy596

Published: 03 November 2018

(See the major Article by Poirot et al on pages XX-XX)

“What greater gift than the love of a cat?”—Charles Dickens, Great Expectations

Avian influenza viruses have rarely been detected in cats and, until 2016, no cat had ever been documented to have an influenza A(H7N2) virus infection or to transmit the virus to a human. In December 2016, the New York City Department of Health and Mental Hygiene (NYC DOHMH) was alerted about a cat admitted to a Manhattan animal shelter on 12 November 2016 that subsequently died and was confirmed positive for influenza A(H7N2) virus, a low-pathogenic avian influenza virus [1, 2].

(…)

Keywords: Avian Influenza; H7N2; Cats; Human; USA; NYC.

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#Assessment of #blood #enterovirus #PCR testing in #paediatric populations with fever without source, #sepsis-like disease, or suspected #meningitis: a prospective, multicentre, observational cohort study (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Assessment of blood enterovirus PCR testing in paediatric populations with fever without source, sepsis-like disease, or suspected meningitis: a prospective, multicentre, observational cohort study

Jérémy Lafolie, PharmD, Prof André Labbé, PhD *, Anne Sophie L’Honneur, PharmD *, Fouad Madhi, MD, Bruno Pereira, PhD, Marion Decobert, MD, Marie Noelle Adam, PhD, François Gouraud, MD, Frédéric Faibis, PhD, Francois Arditty, MD, Stéphanie Marque-Juillet, PhD, Marie Aline Guitteny, PhD, Gisele Lagathu, PhD, Matthieu Verdan, MD, Prof Flore Rozenberg, PhD, Audrey Mirand, PhD, Prof Hélène Peigue-Lafeuille, PhD, Prof Cécile Henquell, PhD †, Jean-Luc Bailly, PhD †, Christine Archimbaud, PhD on behalf of theBlood Enterovirus Diagnosis Infection (BLEDI) in paediatric population study team ‡

Published: October 30, 2018 / DOI: https://doi.org/10.1016/S1473-3099(18)30479-1

 

Summary

Background

Enteroviruses are the most frequent cause of acute meningitis and are seen increasingly in sepsis-like disease and fever without source in the paediatric population. Detection of enterovirus in cerebrospinal fluid (CSF) specimens by PCR is the gold standard diagnostic test. Our aim was to assess a method of detecting enterovirus in blood specimens by PCR.

Methods

We did a prospective, multicentre, observational study at 35 French paediatric and emergency departments in 16 hospitals. We recruited newborn babies (aged ≤28 days) and infants (aged >28 days to ≤2 years) with fever without source, sepsis-like disease, or suspected meningitis, and children (aged >2 years to ≤16 years) with suspected meningitis, who were admitted to a participating hospital. We used a standardised form to obtain demographic, clinical, and laboratory data, which were anonymised. Enterovirus PCR testing was done in blood and CSF specimens.

Findings

Between June 1, 2015, and Oct 31, 2015, and between June 1, 2016, and Oct 31, 2016, we enrolled 822 patients, of whom 672 had enterovirus PCR testing done in blood and CSF specimens. Enterovirus was detected in 317 (47%) patients in either blood or CSF, or both (71 newborn babies, 83 infants, and 163 children). Detection of enterovirus was more frequent in blood samples than in CSF specimens of newborn babies (70 [99%] of 71 vs 62 [87%] of 71; p=0·011) and infants (76 [92%] of 83 vs 62 [75%] of 83; p=0·008), and was less frequent in blood samples than in CSF specimens of children (90 [55%] of 163 vs 148 [91%] of 163; p<0·0001). Detection of enterovirus was more frequent in blood samples than in CSF specimens of infants aged 2 years or younger with fever without source (55 [100%] of 55 vs 41 [75%] of 55; p=0·0002) or with sepsis-like disease (16 [100%] of 16 vs nine [56%] of 16; p=0·008). Detection of enterovirus was less frequent in blood than in CSF of patients with suspected meningitis (165 [67%] of 246 vs 222 [90%] of 246; p<0·0001).

Interpretation

Testing for enterovirus in blood by PCR should be an integral part of clinical practice guidelines for infants aged 2 years or younger. This testing could decrease the length of hospital stay and reduce exposure to antibiotics for low-risk patients admitted to the emergency department with febrile illness.

Funding

University Hospital Clermont-Ferrand.

Keywords: Enterovirus; Diagnostic tests.

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#MERS #coronavirus #intermittent positive cases: Implications for #infection control (Am J Infect Control., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Am J Infect Control. 2018 Oct 20. pii: S0196-6553(18)30871-X. doi: 10.1016/j.ajic.2018.08.020. [Epub ahead of print]

Middle East respiratory syndrome coronavirus intermittent positive cases: Implications for infection control.

Alfaraj SH1, Al-Tawfiq JA2, Memish ZA3.

Author information: 1 Corona Center, Infectious Diseases Division, Department of Pediatrics, Prince Mohamed Bin Abdulaziz Hospital, Ministry of Health, Riyadh, Saudi Arabia; University of British Columbia, Vancouver, BC, Canada. 2 Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia; Indiana University School of Medicine, Indianapolis, IN; Johns Hopkins University School of Medicine, Baltimore, MD. 3 College of Medicine, Alfaisal University, Riyadh, Saudi Arabia; Infectious Diseases Division, Department of Medicine, Prince Mohamed Bin Abdulaziz Hospital, Ministry of Health, Riyadh, Saudi Arabia; Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA. Electronic address: zmemish@yahoo.com.

 

Abstract

BACKGROUND:

Middle East respiratory syndrome coronavirus (MERS-CoV) continues to be reported from the Kingdom of Saudi Arabia. Data on the phenomenon of intermittent positive results for MERS-CoV on reverse-transcription polymerase chain reaction (RT-PCR) with negative results in between are lacking. Here we describe cases with intermittent positive MERS-CoV test results and highlight the required number of tests to rule out or rule in MERS-CoV infection based on a large retrospective cohort of patients with confirmed MERS-CoV.

METHODS:

This analysis included cases admitted between January 2014 and December 2017. The included patients had a minimum of 3 nasopharyngeal MERS-CoV RT-PCR tests for confirmation and needed 2 negative samples for MERS-CoV evaluated 48 hours apart with clinical improvement or stabilization apart to ensure clearance.

RESULTS:

A total of 408 patients with positive MERS-CoV test results were treated at the referring hospital. We excluded 72 patients who had only 1 swab result available in the system and were treated in the initial years of the disease. Of the remaining 336 patients, 300 (89%) had a positive result after 1 swab, 324 (96.5%) had a positive result after 2 consecutive swabs, and 328 (97.6%) had a positive result after 3 consecutive swabs. Of the total cases, 46 (13.7%) had a positive MERS-CoV test then a negative test, followed by positive test results.

CONCLUSIONS:

Our data indicate that 2 to 3 nasopharyngeal samples are needed to produce the highest yield of positive results for MERS-CoV. In addition, 2 negative results 48 hours apart with clinical improvement or stabilization are needed to clear patients from MERS-CoV. Evaluation of the yield of sputum samples is needed to assess the effectiveness against nasopharyngeal swabs.

Copyright © 2018 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

KEYWORDS: MERS-CoV; Middle East respiratory syndrome coronavirus; Outbreak Saudi Arabia

PMID: 30352694 DOI: 10.1016/j.ajic.2018.08.020

Keywords: MERS-CoV; Diagnostic Tests.

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Rapid #detection and discrimination of chromosome- and #MCR-plasmid-mediated #resistance to #polymyxins by MALDI-TOF MS in #Escherichia coli: the MALDIxin test (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

Rapid detection and discrimination of chromosome- and MCR-plasmid-mediated resistance to polymyxins by MALDI-TOF MS in Escherichia coli: the MALDIxin test

Laurent Dortet, Remy A Bonnin, Ivana Pennisi, Lauraine Gauthier, Agnès B Jousset, Laura Dabos, R Christopher, D Furniss, Despoina A I Mavridou, Pierre Bogaerts, Youri Glupczynski, Anais Potron, Patrick Plesiat, Racha Beyrouthy, Frédéric Robin, Richard Bonnet, Thierry Naas, Alain Filloux, Gerald Larrouy-Maumus

Journal of Antimicrobial Chemotherapy, dky330, https://doi.org/10.1093/jac/dky330

Published: 01 September 2018

 

Abstract

Background

Polymyxins are currently considered a last-resort treatment for infections caused by MDR Gram-negative bacteria. Recently, the emergence of carbapenemase-producing Enterobacteriaceae has accelerated the use of polymyxins in the clinic, resulting in an increase in polymyxin-resistant bacteria. Polymyxin resistance arises through modification of lipid A, such as the addition of phosphoethanolamine (pETN). The underlying mechanisms involve numerous chromosome-encoded genes or, more worryingly, a plasmid-encoded pETN transferase named MCR. Currently, detection of polymyxin resistance is difficult and time consuming.

Objectives

To develop a rapid diagnostic test that can identify polymyxin resistance and at the same time differentiate between chromosome- and plasmid-encoded resistances.

Methods

We developed a MALDI-TOF MS-based method, named the MALDIxin test, which allows the detection of polymyxin resistance-related modifications to lipid A (i.e. pETN addition), on intact bacteria, in <15 min.

Results

Using a characterized collection of polymyxin-susceptible and -resistant Escherichia coli, we demonstrated that our method is able to identify polymyxin-resistant isolates in 15 min whilst simultaneously discriminating between chromosome- and plasmid-encoded resistance. We validated the MALDIxin test on different media, using fresh and aged colonies and show that it successfully detects all MCR-1 producers in a blindly analysed set of carbapenemase-producing E. coli strains.

Conclusions

The MALDIxin test is an accurate, rapid, cost-effective and scalable method that represents a major advance in the diagnosis of polymyxin resistance by directly assessing lipid A modifications in intact bacteria.

Issue Section: ORIGINAL RESEARCH

© The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Antibiotics; Drugs Resistance; Polymyxin; MCRx; Diagnostic Tests; E. Coli.

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#Colistin susceptibility #test evaluation of multiple-resistance-level #Pseudomonas aeruginosa isolates generated in a morbidostat device (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

Colistin susceptibility test evaluation of multiple-resistance-level Pseudomonas aeruginosa isolates generated in a morbidostat device

Mumina Javed, Viola Ueltzhoeffer, Maximilian Heinrich Hans, Justus Siegrist, Ronja Wildermuth, Freia-Raphaella Lorenz, Richard A Neher, Matthias Willmann

Journal of Antimicrobial Chemotherapy, dky337, https://doi.org/10.1093/jac/dky337

Published: 22 August 2018

 

Abstract

Objectives

Colistin is a last-resort antibiotic against the critical-status pathogen Pseudomonas aeruginosa. There is still uncertainty regarding how to accurately measure colistin susceptibility in P. aeruginosa. Evaluation of antimicrobial susceptibility testing (AST) methods is largely hampered by the lack of resistant isolates and those around the susceptibility breakpoint. The aim of this study was to generate such strains in a morbidostat device for use in AST method evaluation.

Methods

A morbidostat device was used to cultivate susceptible clinical strains into isolates with a wide range of colistin MICs. Subsequently, five commercial AST methods were compared against the gold standard broth microdilution (BMD) method: MICRONAUT-S, SensiTest, Sensititre, Rapid Polymyxin Pseudomonas and Etest.

Results

A total of 131 P. aeruginosa isolates were used for colistin susceptibility test evaluation (100 colistin susceptible and 31 colistin resistant). The 31 colistin-resistant isolates evolved resistance in the morbidostat to different MIC ranges (4–512 mg/L, 100% resistance generation efficacy). The categorical agreement (CA) rates for MICRONAUT-S, SensiTest and Rapid Polymyxin Pseudomonas were 94.7%, 93.9% and 92.4%, respectively. The Sensititre achieved the highest CA score (96.9%), whereas the Etests had the lowest CA score (84%). The very major discrepancy (VMD) rates for all tests were between 3.2% and 67.7%.

Conclusions

The morbidostat device can efficiently provide laboratories with colistin-resistant strains for test evaluation. Although CA rates were high for commercial AST methods except for Etests, none met the ≤1.5% CLSI limit for VMD rates. Performance was generally inferior when using isolates with low-level resistance.

Issue Section: ORIGINAL RESEARCH

© The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

Keywords: Antibiotics; Drugs Resistance; Diagnostic tests; Colistin; Pseudomonas aeruginosa.

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Long-Range #PCR Method for #Sequencing the #Ebola Virus Genome From #Ecological and #Clinical Samples (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Long-Range Polymerase Chain Reaction Method for Sequencing the Ebola Virus Genome From Ecological and Clinical Samples

Stephanie N Seifert, Jonathan E Schulz, M Jeremiah Matson, Trenton Bushmaker, Andrea Marzi, Vincent J Munster

The Journal of Infectious Diseases, jiy290, https://doi.org/10.1093/infdis/jiy290

Published: 02 August 2018

 

Abstract

Sequencing viral genomes during an outbreak can facilitate response and containment efforts. In this study, we describe a reverse transcription long-range polymerase chain reaction for efficient amplification and sequencing of the Ebola virus (EBOV) genome in 2 seminested reactions. We demonstrate that our method remains robust with complex biological samples by amplifying and sequencing the EBOV genome from EBOV-infected nonhuman primates (NHPs). We further demonstrate that we are able to recover viral genomes from starting concentrations as low as 103 50% tissue culture infective dose (TCID50)/mL, suggesting that this method can be employed to sequence EBOV genomes from ecologically or clinically derived samples.

Issue Section: Supplement Article

Published by Oxford University Press for the Infectious Diseases Society of America 2018. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Keywords: Ebola; Diagnostic Tests.

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