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Identification and management of Guillain-Barré syndrome in the context of Zika virus Interim guidance 25 February 2016
1. Introduction critical care physicians and nurses. This guidance may also be used by those responsible for developing local and 1.1 Background
national health protocols and policies, and policy-makers in Guillain-Barré syndrome (GBS) is a disorder in which the regions affected by Zika virus transmission. body's own immune system attacks part of the peripheral nervous system. GBS can be triggered by a variety of infections, including dengue and chikungunya viruses. The 2. Interim recommendations syndrome can affect the peripheral nerves that control a. Health care providers should be trained in the muscle strength as well as those that transmit feelings of recognition, evaluation and management of patients pain, temperature and touch. This can result in muscle with GBS. Specifically, neurological examination skills weakness and loss of sensation in the legs and/or arms. and training in the acute management of GBS should be Approximately 25% of GBS patients require intensive care and 3-5% die even with appropriate supportive care, due to complications related to: paralysis of the muscles that b. The Brighton criteria (3) should be used for the case control breathing; cardiac arrest; or blood clots (1). definition of GBS (see below). Neurological examinations should be performed on all patients with Currently, health authorities in Brazil, Colombia, El suspected GBS, and ancillary testing with nerve Salvador, Suriname and Venezuela have reported increases conduction studies/electromyography and lumbar in cases of GBS in the context of widespread Zika virus puncture if available. transmission. In French Polynesia, all 42 GBS cases identified during an outbreak of Zika virus from 2013– c. The risk of death in patients with GBS is associated 2014 on retrospective analysis (seroneutralisation test) with complications including respiratory failure, cardiac tested positive for both dengue and Zika virus infection (2). arrhythmias, and blood clots. Optimal supportive care The cause of the increase in incidence of GBS observed in including frequent neurological assessments, vital sign Brazil, Colombia, El Salvador and Suriname remains and respiratory function monitoring should be provided unknown, especially as dengue, chikungunya and Zika to patients with GBS. viruses all circulate simultaneously in the Americas. d. Intravenous immunoglobulin therapy or therapeutic Investigations to establish the cause, risk factors, and plasma exchange should be provided to GBS patients consequences of these clusters of GBS cases and other who are unable to walk or who have rapidly progressive neurological complications are currently underway. symptoms. Access to these medications and training This document aims to provide interim guidance on the for their appropriate administration should be made case definition of GBS and strategies to manage the syndrome, in the context of Zika virus and its potential e. Hospital beds for patients with severe manifestations of association with GBS. This document is intended to inform GBS should be made available, so that patients can the development of local clinical protocols and health receive optimal supportive care. policies related to the care of patients with GBS. An expert meeting will be organized in March 2016 to develop additional guidance to identify and manage GBS and other 3. Case definition of Guillain-Barré syndrome possible neurological disorders in the context of Zika virus using the Brighton Criteria The Brighton criteria (3) should be used as the case 1.2 Target audience
definition of GBS. These are based on presenting clinical findings and ancillary testing including neurophysiology and The primary audience for this guidance are health care lumbar puncture findings. Patients are categorized as level professionals including family medicine physicians, general 1 (the highest level of diagnostic certainty) to level 3 (the practitioners, neurologists, emergency medicine physicians, lowest level of diagnostic certainty) These criteria were Identification and management of Guil ain-Barré syndrome in the context of Zika virus developed to standardize collection and assessment of although potentially applicable in a clinical setting, the level information on GBS, and are applicable in: study settings of diagnostic certainty is primarily intended for with different availability of resources; health care settings epidemiologic purposes and not as a criterion for treatment that differ by availability of and access to health care; and different geographic regions. It should be stressed that, Table 1. Brighton criteria for case definition of Guillain-Barré syndrome
Level 1 of diagnostic certainty
Level 2 of diagnostic certainty
Level 3 of diagnostic certainty
 Bilateral and flaccid weakness of the  Bilateral and flaccid weakness of the  Bilateral and flaccid weakness of the limbs; AND
limbs; AND
limbs; AND
 Decreased of absent deep tendon  Decreased or absent deep tendon  Decreased or absent deep tendon reflexes in weak limbs; AND
reflexes in weak limbs; AND
reflexes in weak limbs; AND
 Monophasic il ness pattern; and  Monophasic il ness pattern; and  Monophasic il ness pattern; and interval between onset and nadir of interval between onset and nadir of interval between onset and nadir of weakness between 12h and 28 days; weakness between 12h and 28 days; weakness between 12h and 28 days; and subsequent clinical plateau; AND
and subsequent clinical plateau; AND
and subsequent clinical plateau; AND
 Absence of identified alternative  Absence of identified alternative  Absence of identified alternative diagnosis for weakness; AND
diagnosis for weakness; AND
diagnosis for weakness  Cytoalbuminologic dissociation (i.e.  CSF total white cell count <50 cel s/μl elevation of CSF* protein level above (with or without CSF protein elevation laboratory normal value and CSF total above laboratory normal value); OR
white cel count <50 cells/µl; AND
electrophysiologic studies consistent  Electrophysiologic findings consistent with GBS if CSF not collected or results not available. * Cerebrospinal fluid (CSF) 4. Guidance development Professor, Department of Neurology, Columbia University College of Physicians and Surgeons, New York, USA); 4.1 Acknowledgements
Professor Joseph Zunt (Neurology and Global Health, The following individuals contributed to the development University of Washington, Seattle, USA). of this interim guidance: Professor Gretchen Birbeck Staff from the Department of Mental Health and Substance (Neurology and Epidemiology, University of Rochester Abuse, WHO Geneva (Tarun Dua, Shekhar Saxena and School of Medicine, Rochester, USA); Dr Francisco Javier Marius Vollberg) and WHO Regional Office for the Carod-Artal (Consultant Neurologist, Raigmore Hospital Americas (Armando Vasquez) contributed to this guidance. UK, Inverness UK; Professor Igor Koralnik (Neurology, Beth Israel Deaconess Medical Center, Boston, USA); Dr 4.2 Guidance development methods
Constantine Malama (Virologist, Ministry of Health Global experts in the areas of neurological infections, Zambia, Lusaka, Zambia); Dr Farrah Mateen (Assistant neuroimmunology and GBS were identified through Professor, Harvard Medical School, Boston, USA): existing networks of neurologists. This included experts Professor Avindra Nath (Senior Investigator, National from Africa, the Americas, south-east Asia, Europe and the Institute of Health, Bethesda, USA); Dr Erwan Oehler Pacific. Due to limited time, it was not possible to identify (Hospital Physician in General Medicine, Tahiti, French and include experts from other areas. Polynesia); Professor Lyda Osorio (Epidemiology, University of Valle, Cali, Valle del Cauca, Colombia); Dr A conference call was convened by the WHO Geneva Carlos Pardo (Director of the Johns Hopkins Transverse Department of Mental Health and Substance Abuse on 9 Myelitis Center, Johns Hopkins University, Baltimore, February 2016. Notes for the record were documented. USA); Professor Laura Rodrigues (Infectious Disease Based on these, an interim guidance was prepared. The Epidemiology, London School of Hygiene and Tropical notes for the record and draft interim guidance were Medicine, London, UK); Dr James Sejvar (Neurologist and circulated to the experts. Comments and references Epidemiologist, Center for Disease Control and Prevention, proposed by the experts were included in the revised Atlanta, USA); Professor Tom Solomon (Director of the Institute of Infection and Global Health, University of Liverpool, Liverpool, UK); Dr Kiran Thakur (Assistant Identification and management of Guil ain-Barré syndrome in the context of Zika virus 4.3 Declaration of interests
F Mateen declared that she is the recipient of an American 1. Yuki N, Hartung HP. Guillain–Barré syndrome. N Engl J Brain Foundation in 2010–2012 to study GBS in India Med. 2012 Jun; 366(24):2294-304. using polio surveillance data. This interest was deemed 2. World Health Organization [Internet]. Zika situation report non-conflicting, and the individual participated fully in the 12 February 2016; 2016 [cited 2016 Feb 22]. Available from: guidance development process. No other competing interests were identified. No specific funds were used to 3. Sejvar JJ, Kohl KS, Gidudu J, Amato A, Bakshi N, Baxter R, develop this interim guidance. Burwen DR, Cornblath DR, Cleerbout J, Edwards KM, Heininger U. Guillain–Barré syndrome and Fisher syndrome: 4.4 Review date
case definitions and guidelines for collection, analysis, and presentation of immunization safety data. Vaccine. 2011 Jan These recommendations have been produced under 10; 29(3):599–612. emergency procedures and will remain valid until August 2016. The Departments of Mental Health and Substance Abuse at WHO Geneva will be responsible for reviewing this guideline before or at that time, and updating it as World Health Organization 2016 Al rights reserved. Publications of the World Health Organization are available on the WHO website ( or can be purchased from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; e-mail: [email protected]). Requests for permission to reproduce or translate WHO publications –whether for sale or for non-commercial distribution– should be addressed to WHO Press through the WHO website ( The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted and dashed lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers' products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. Al reasonable precautions have been taken by the World Health Organization to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either expressed or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shal the World Health Organization be liable for damages arising from its use.


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STATE OF CONNECTICUT Connecticut Behavioral Health Partnership Department of Children and Families ADDENDUM # 1 Department of Social Services Request for Applications The State of Connecticut Behavioral Health Partnership, through the Departments of Children and Families and Social Services is issuing the following addendum to the Enhanced Care Clinics Request for Applications. The Department's responses to the three (3) questions that were submitted by applicants in accordance with the terms of the ECC RFA are set forth herein as an addendum to this RFA.


Drosophila and Antioxidant Therapy F. Missirlis1, J.P. Phillips2, H. Jäckle3 and T.A. Rouault1 1Cell biology and Metabolism Branch, National Institute of Child Health and Human Development, Bethesda, Maryland, U.S.A. 2Molecular Biology and Genetics, University of Guelph, Ontario, Canada. 3Max-Planck-Institut für biophysikalische Chemie, Göttingen, Germany