BOA1

29 Jul 2015

#Ebola: missed #opportunities for #Europe – #Africa #research (The Lancet Infect Dis., summary, edited)

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

Comment

Ebola: missed opportunities for Europe–Africa research [      ]

Giuseppe Ippolito, Simone Lanini, Philippe Brouqui, Antonino Di Caro, Francesco Vairo, Salim Abdulla, Francesco Maria Fusco, Sanjeev Krishna, Maria Rosaria Capobianchi, Henry Kyobe-Bosa, David J M Lewis, Vincenzo Puro, Roman Wolfel, Tatjana Avsic-Zupanc, Osman Dar, Peter Mwaba, Matthew Bates, David Heymann, Alimuddin Zumla

Published Online: 28 July 2015 / Publication stage: In Press Corrected Proof / DOI: http://dx.doi.org/10.1016/S1473-3099(15)00236-4

© 2015 Elsevier Ltd. All rights reserved.

 

Summary

The current unprecedented Ebola virus disease outbreak in parts of west Africa, which has caused more than 11 200 deaths, has emphasised how the medical and scientific communities lack specific pathways for tackling relevant logistical, design, and ethical issues for assessment of novel diagnostics, treatments, and vaccines through implementation of appropriate clinical trials.1,2 The phenomenal outbreak arose because of several weaknesses in local, regional, and international public health responses, which delayed provision and implementation of effective interventions.

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#Evaluation of candidate #vaccine approaches for #MERS-CoV (Nature Commun., abstract, edited)

[Source: Nature Communications, full page: (LINK). Abstract, edited.]

Nature Communications / Article / Open

Evaluation of candidate vaccine approaches for MERS-CoV [      ]

Lingshu Wang, Wei Shi, M. Gordon Joyce, Kayvon Modjarrad, Yi Zhang, Kwanyee Leung, Christopher R. Lees, Tongqing Zhou, Hadi M. Yassine, Masaru Kanekiyo, Zhi-yong Yang, Xuejun Chen, Michelle M. Becker, Megan Freeman, Leatrice Vogel, Joshua C. Johnson, Gene Olinger, John P. Todd, Ulas Bagci, Jeffrey Solomon, Daniel J. Mollura, Lisa Hensley, Peter Jahrling, Mark R. Denison, Srinivas S. Rao, Kanta Subbarao, Peter D. Kwong, John R. Mascola, Wing-Pui Kong & Barney S. Graham et al.

Journal name: Nature Communications - Volume: 6, Article number: 7712 - DOI: doi:10.1038/ncomms8712

Received 21 April 2015 - Accepted 03 June 2015 - Published 28 July 2015

 

Abstract

The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) as a cause of severe respiratory disease highlights the need for effective approaches to CoV vaccine development. Efforts focused solely on the receptor-binding domain (RBD) of the viral Spike (S) glycoprotein may not optimize neutralizing antibody (NAb) responses. Here we show that immunogens based on full-length S DNA and S1 subunit protein elicit robust serum-neutralizing activity against several MERS-CoV strains in mice and non-human primates. Serological analysis and isolation of murine monoclonal antibodies revealed that immunization elicits NAbs to RBD and, non-RBD portions of S1 and S2 subunit. Multiple neutralization mechanisms were demonstrated by solving the atomic structure of a NAb-RBD complex, through sequencing of neutralization escape viruses and by constructing MERS-CoV S variants for serological assays. Immunization of rhesus macaques confers protection against MERS-CoV-induced radiographic pneumonia, as assessed using computerized tomography, supporting this strategy as a promising approach for MERS-CoV vaccine development.

Subject terms: Biological sciences • Immunology • Virology

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The #Effect of #Oral #Polio #Vaccine at #Birth on #Infant #Mortality: A Randomized Trial (Clin Infect Dis., abstract, edited)

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

The Effect of Oral Polio Vaccine at Birth on Infant Mortality: A Randomized Trial [      ]

Najaaraq Lund 1,2, Andreas Andersen 1, Anna Sofie K. Hansen 3, Frida S Jepsen 3, Amarildo Barbosa 3, Sofie Biering-Sørensen 3, Amabelia Rodrigues 3, Henrik Ravn 1,4, Peter Aaby 1,3, and Christine Stabell Benn 1,4

Author Affiliations: 1Research Center for Vitamins and Vaccines (CVIVA), Statens Serum Institut, DK-2300 Copenhagen S DK-2300, Denmark 2Department of Pediatrics, Kolding Hospital/IRS University of Southern Denmark, Kolding, Denmark 3Bandim Health Project, Indepth Network, Bissau, Guinea-Bissau 4OPEN, Institute of Clinical Research, University of Southern Denmark/Odense University Hospital, Denmark

Correspondence to: Christine Stabell Benn, Research Center for Vitamins and Vaccines, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark, E-mail: cb@ssi.dk; Tel:+4532688354+4532688354.

Alternate corresponding author: Peter Aaby, Research Center for Vitamins and Vaccines, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark, E-mail: p.aaby@bandim.org

 

Abstract

Background.

Routine vaccines may have non-specific effects on mortality. An observational study found OPV-at-birth (OPV0) to be associated with increased male infant mortality. We investigated the effect of OPV0 on infant mortality in a randomized trial in Guinea-Bissau.

Methods.

7012 healthy normal-birth-weight neonates were randomized to BCG-only (intervention group) or OPV0 with BCG (usual practice). All children were to receive OPV with Pentavalent vaccine (diphtheria, tetanus, pertussis, H. Influenzae-type b, and hepatitis B) at 6, 10, and 14 weeks of age. Seven national OPV campaigns were also conducted during the trial period. Children were followed to age 12 months. We used Cox regression to calculate Hazard Ratios (HR) for mortality.

Results.

The trial contradicted the original hypothesis about OPV0 increasing male infant mortality. Within 12 months 73 died in the BCG+OPV group and 87 children in the BCG-only group, all from infectious diseases. Comparing BCG+OPV0 versus BCG-only the HR was 0.83 (95% confidence interval: 0.61-1.13); 0.72 (0.47-1.10) in males and 0.97 (0.61-1.54) in females. For children enrolled within the first 2 days of life, the HR for BCG+OPV0 versus BCG-only was 0.58 (0.38-0.90). From enrollment and until the time of OPV campaigns, the HR was 0.68 (0.43-1.00); the beneficial effect being separately significant for males (0.55 (0.32-0.95)).

Conclusion.

This is the only randomized trial of the effect of OPV0 on mortality. OPV0 may be associated with non-specific protection against infectious disease mortality, particularly when given early in life. There are reasons to monitor mortality when OPV is being phased out.

10.1093/cid/civ619

© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com.

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#HK, No new suspected #MERS #cases reported (CHP, July 29 2015)

[Source: Centre for Health Protection, Hong Kong PRC SAR, full page: (LINK).]

No new suspected MERS cases reported [      ]

The Centre for Health Protection (CHP) of the Department of Health (DH) today (July 29) reported that no suspected cases of Middle East Respiratory Syndrome (MERS) had been recorded from noon yesterday (July 28) to noon today.

"The public, in particular those with chronic illnesses, should avoid unnecessary travel to Korea. Travellers in Korea and the Middle East should avoid unnecessary visits to healthcare facilities," a spokesman for the CHP said.

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The public may visit the pages below for more information and health advice:

Tour leaders and tour guides operating overseas tours are advised to refer to the CHP's health advice on MERS (www.chp.gov.hk/en/view_content/26551.html).

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S. #Korea reported no new #MERS-CoV cases in the last 24 hours (MoH, July 29 2015, extract, edited)

[Source: South Korea Ministry of Health, full page: (LINK). Automatic translation, extract, edited.]

S. #Korea reported no new #MERS-CoV cases in the last 24 hours [      ]

(July 29 2015)

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Middle East respiratory Syndrome Daily Tracking Report

  • 12 patients are currently under treatment (6.4%), 138 patients recovered and discharged from hospital (74.2%), 36 patients died (19.4%), cumulative number of confirmed cases: 186.
  • In the last 24 hours: no new recoveries, no new deaths and no new confirmed cases have been reported.
  • Contact tracing: The last confirmed case was reported on July 4; no contacts are currently under surveillance.
  • Of the 12 patients currently under treatment: 9 are in stable condition, 3 are critical.

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28 Jul 2015

Essential roles of #methionine and S-adenosylmethionine in the autarkic lifestyle of #Mycobacterium #tuberculosis (Proc Natl Acad Sci USA, abstract, edited)

[Source: Proceedings of the National Academy of Sciences of the United States of America, full page: (LINK). Abstract, edited.]

Essential roles of methionine and S-adenosylmethionine in the autarkic lifestyle of Mycobacterium tuberculosis [      ]

Michael Berney a,1, Linda Berney-Meyer a, Ka-Wing Wong a,b, Bing Chen c, Mei Chen a, John Kim a, Jingxin Wang d, David Harris e, Julian Parkhill e, John Chan a, Feng Wang f, and William R. Jacobs, Jr. a,c,1

Author Affiliations: aDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461; bShanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology at Shanghai Medical College, Fudan University, Shanghai 201508, China; cHoward Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, NY 10461; dDepartment of Chemistry, Scripps Research Institute, La Jolla, CA 92037; eWellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, United Kingdom; fCalifornia Institute for Biomedical Research, La Jolla, CA 92037

Contributed by William R. Jacobs Jr., July 8, 2015 (sent for review April 28, 2015; reviewed by Luiz Pedro de Carvalho)

 

Significance

Mycobacterium tuberculosis (Mtb) is the most deadly bacterial pathogen in the world, killing 1.5 million people in 2013. Very little is known about the way this pathogen interacts metabolically with its host to achieve long-term persistence and antibiotic tolerance. We uncovered a previously unknown metabolic vulnerability of Mtb, the absolute requirement for methionine and S-adenosylmethionine for successful host infection and virulence. Inactivation of methionine biosynthesis in Mtb leads to unusually rapid cell death, a highly desired feature for chemotherapy. Bactericidal auxotrophies are rare in Mtb, and so far their killing mechanisms have not been characterized systematically. Our study unravels a killing mechanism induced by amino acid starvation that leads to multitarget inhibition, opening new avenues for antimycobacterial interventions.

 

Abstract

Multidrug resistance, strong side effects, and compliance problems in TB chemotherapy mandate new ways to kill Mycobacterium tuberculosis (Mtb). Here we show that deletion of the gene encoding homoserine transacetylase (metA) inactivates methionine and S-adenosylmethionine (SAM) biosynthesis in Mtb and renders this pathogen exquisitely sensitive to killing in immunocompetent or immunocompromised mice, leading to rapid clearance from host tissues. Mtb ΔmetA is unable to proliferate in primary human macrophages, and in vitro starvation leads to extraordinarily rapid killing with no appearance of suppressor mutants. Cell death of Mtb ΔmetA is faster than that of other auxotrophic mutants (i.e., tryptophan, pantothenate, leucine, biotin), suggesting a particularly potent mechanism of killing. Time-course metabolomics showed complete depletion of intracellular methionine and SAM. SAM depletion was consistent with a significant decrease in methylation at the DNA level (measured by single-molecule real-time sequencing) and with the induction of several essential methyltransferases involved in biotin and menaquinone biosynthesis, both of which are vital biological processes and validated targets of antimycobacterial drugs. Mtb ΔmetA could be partially rescued by biotin supplementation, confirming a multitarget cell death mechanism. The work presented here uncovers a previously unidentified vulnerability of Mtb—the incapacity to scavenge intermediates of SAM and methionine biosynthesis from the host. This vulnerability unveils an entirely new drug target space with the promise of rapid killing of the tubercle bacillus by a new mechanism of action.

host–pathogen interaction - bactericidal auxotrophy - amino acid biosynthesis – metabolism


Footnotes

1To whom correspondence may be addressed. Email: michael.berney@einstein.yu.edu or jacobsw@hhmi.org.

Author contributions: M.B., L.B.-M., K.-W.W., B.C., M.C., J.K., J.W., D.H., J.P., F.W., and W.R.J. designed research; M.B., L.B.-M., K.-W.W., B.C., M.C., J.K., J.W., and D.H. performed research; M.B., L.B.-M., K.-W.W., B.C., M.C., J.K., J.W., D.H., J.P., J.C., F.W., and W.R.J. analyzed data; and M.B., L.B.-M., J.W., J.P., J.C., F.W., and W.R.J. wrote the paper.

Reviewers included: L.P.d.C., Francis Crick Institute.

The authors declare no conflict of interest.

Data deposition: The microarray raw data have been deposited in the Gene Expression Omnibus database (access code: GSE67843). Sequencing data have been deposited in the European Nucleotide Archive (accession nos. ERS684465 and ERS684467ERS684474; study accession: ERP009820; submission accession: ERA442842).

This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1513033112/-/DCSupplemental.

Freely available online through the PNAS open access option.

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The Individualised versus the #Public #Health #Approach to #Treating #Ebola (PLoS Med., abstract, edited)

[Source: PLoS Medicine, full page: (LINK). Abstract, edited.]

Open Access / Perspective

The Individualised versus the Public Health Approach to Treating Ebola [      ]

Tom H. Boyles

Published: July 28, 2015 / DOI: 10.1371/journal.pmed.1001858

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[Extract]

The mortality rate for patients with Ebola virus disease (EVD) in West Africa is approximately 65% [1]. There are no published figures for high-resource settings, but media sources and individual case reports suggest it is much lower and approaches 0% for those who receive this level of care from the beginning of their illness. In their article “Ebola Viral Disease: Experience and Decision Making for the First Cases outside of Africa,” David Stephens and colleagues give insight into the care that can be provided when available resources are not the limiting factor [2]. They describe the decision to open the Serious Communicable Diseases Unit (SCDU) of Emory University Hospital (EUH) when two United States patients contracted EVD while working in West Africa. Using a large specialist team, they provided high-quality care in a safe working environment and disseminated their knowledge and experience widely. In particular, they were able to respond to the huge increase in requests from health care facilities in the US for help in excluding the diagnosis of EVD. Caring for patients using an individualised approach under ideal circumstances contrasts with, but can also inform, the public health approach to care under resource-limited conditions in West Africa. The models of care employed in each environment show some similarities and also have a number of key differences.

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Citation: Boyles TH (2015) The Individualised versus the Public Health Approach to Treating Ebola. PLoS Med 12(7): e1001858. doi:10.1371/journal.pmed.1001858

Published: July 28, 2015

Copyright: © 2015 Tom H. Boyles. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Funding: No funding was received for this work.

Competing interests: The author has declared that no competing interests exist.

Abbreviations: EHU, Ebola holding unit; ETU, Ebola treatment unit; EUH, Emory University Hospital; EVD, Ebola virus disease; IPC, infection prevention and control; PPE, personal protective equipment; RDT, rapid diagnostic test; RT-PCR, real-time polymerase chain reaction; SCDU, Serious Communicable Diseases Unit

Provenance: Commissioned; not externally peer reviewed

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#Ebola #Virus #Disease: #Experience and #Decision #Making for the First #Patients outside of #Africa (PLoS Med., abstract, edited)

[Source: PLoS Medicine, full page: (LINK). Summary, edited.]

Open Access / Essay

Ebola Virus Disease: Experience and Decision Making for the First Patients outside of Africa [      ]

David S. Stephens,  Bruce S. Ribner,  Bryce D. Gartland,  Nancye R. Feistritzer,  Monica M. Farley,  Christian P. Larsen,  John T. Fox

Published: July 28, 2015 / DOI: 10.1371/journal.pmed.1001857

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Summary Points

  • Ebola hemorrhagic fever, or Ebola virus disease (EVD), has emerged in the last year as a global threat and humanitarian disaster for the affected countries of West Africa and has also come to the United States (US) and Europe.
  • The treatment of the first and three subsequent US patients outside of Africa at Emory University provided a number of challenges, as well as strategic and tactical lessons that included detailed planning and team work across multiple academic and health care units, emphasizing biosafety, the importance of institutional communications, addressing unanticipated challenges such as waste management, and the logistics of working closely with governmental agencies and outside collaborators.
  • In providing effective care for individuals, the value of mobilizing a diverse health and academic community to work collaboratively to addressing a global threat is emphasized. This includes dissemination of best practice information; providing education and training about EVD; expansion of new knowledge about the clinical course, complications, and pathogenesis of EVD; the creation of new institutional forums, and engagement in the broader policy and equity issues of contagious health threats.

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Citation: Stephens DS, Ribner BS, Gartland BD, Feistritzer NR, Farley MM, Larsen CP, et al. (2015) Ebola Virus Disease: Experience and Decision Making for the First Patients outside of Africa. PLoS Med 12(7): e1001857. doi:10.1371/journal.pmed.1001857

Published: July 28, 2015

Copyright: © 2015 Stephens et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Funding: No funding was received for this work.

Competing interests: The authors have declared that no competing interests exist.

Abbreviations: BSL, biosafety level; CDC, US Centers for Disease Control and Prevention; CTSA, NIH Clinical and Translational Science Awards; DHCPP, Division of High-Consequence Pathogens and Pathology; ED, Emergency Department; EHC, Emory Healthcare; EHSO, Environmental Health and Safety Office; ELWA, Eternal Love Winning Africa; EPA, US Environmental Protection Agency; EUH, Emory University Hospital; EVD, Ebola virus disease; FDA, US Food and Drug Administration; HEPA, high-efficiency particulate air; ICU, intensive care unit; HHS, US Department of Health and Human Services; ID, infectious diseases; IND, investigational new drug; IRB, Institutional Review Board; IV, intravenous; mAbs, monoclonal antibodies; MICU, medical intensive care unit; MOOC, Massive Open Online Course; NIH, National Institutes of Health; PAPR, powered air-purifying respirator; PPE, personal protective equipment; RCE, Research Centers of Excellence; SARS, severe acute respiratory syndrome; SCDU, Serious Communicable Disease Unit; SERCEB, Southeast Regional Center of Excellence for Emerging Infections and Biodefence; SIM USA, Serving in Mission USA; SOP, standard operating procedure; UHC, University Healthsystem Consortium; WHO, World Health Organization

Provenance: Not commissioned; externally peer reviewed

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#Estimations of #worldwide #prevalence of chronic #hepatitis B virus #infection: a systematic review of data published between 1965 and 2013 (The Lancet, abstract, edited)

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

Articles

Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013 [      ]

Aparna Schweitzer, Johannes Horn, Rafael T Mikolajczyk, Gérard Krause, Jördis J Ott

Published Online: 28 July 2015 / Publication stage: In Press Corrected Proof / DOI: http://dx.doi.org/10.1016/S0140-6736(15)61412-X

© 2015 Elsevier Ltd. All rights reserved.

 

Summary

Background

The quantification of the burden of disease attributable to hepatitis B virus (HBV) infection and the adaptation of prevention and control measures requires knowledge on its prevalence in the general population. For most countries such data are not routinely available. We estimated the national, regional, and global prevalence of chronic HBV infection.

Methods

For this systematic review and pooled analysis, we searched for data on prevalence of chronic HBV infection published between Jan 1, 1965, and Oct 23, 2013, in the databases Medline, Embase, CAB Abstracts (Global health), Popline, and Web of Science. We included studies reporting the hepatitis B surface antigen (HBsAg) serological marker of chronic HBV infection in non-high-risk groups and extracted data into a customised database. For each country, we calculated HBsAg prevalence estimates and 95% CIs weighted by study size. We extrapolated prevalence estimates to population sizes in 2010 to obtain the number of individuals with chronic HBV infection.

Findings

Of the 17 029 records screened, 1800 report on the prevalence of HBsAg covering 161 countries were included. HBsAg seroprevalence was 3·61% (95% CI 3·61–3·61) worldwide with highest endemicity in countries of the African region (total 8·83%, 8·82–8·83) and Western Pacific region (total 5·26%, 5·26–5·26). Within WHO regions, prevalence ranged from 0·20% (0·19–0·21; Mexico) to 13·55% (9·00–19·89; Haiti) in the Americas, to 0·48% (0·12–1·90; the Seychelles) to 22·38% (20·10–24·83; South Sudan) in the African region. We estimated that in 2010, globally, about 248 million individuals were HBsAg positive.

Interpretation

This first global assessment of country-level population prevalence of chronic HBV infection found a wide variation between countries and highlights the need for continued prevention and control strategies and the collection of reliable epidemiologic data using standardised methodology.

Funding

World Health Organization.

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#Influenza A(#H6N1) #Virus in #Dogs, #Taiwan (@CDC_EIDjournal, abstract, edited)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 21, Number 12—December 2015 / Dispatch

Influenza A(H6N1) Virus in Dogs, Taiwan [      ]

Hui-Ting Lin, Ching-Ho Wang, Ling-Ling Chueh, Bi-Ling Su, and Lih-Chiann Wang

Author affiliations: National Taiwan University, Taipei, Taiwan

 

Abstract

We determined the prevalence of influenza A virus in dogs in Taiwan and isolated A/canine/Taiwan/E01/2014. Molecular analysis indicated that this isolate was closely related to influenza A(H6N1) viruses circulating in Taiwan and harbored the E627K substitution in the polymerase basic 2 protein, which indicated its ability to replicate in mammalian species.

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