DOCSLIB.ORG

Investigation of Host Genetic Factors in Infectious Disease

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Investigation of Host Genetic Factors in Infectious Disease Investigation of Priya Duggal, PhD, MPH Host Genetic Johns Hopkins Bloomberg School of Public Health Factors in Infectious Disease: Acute July 23, 2019 Centers for Disease Control and Prevention Flaccid Myelitis [email protected] @priya4genes Navigating the Human Genome WHY consider genetics in the study of infectious disease? HOW do we evaluate host genetic associations? WHAT are the implications of host genetic predispositions to infection? WHERE are the genes? 2 Traditional Infectious Path Infectious Pathogen Host Disease Do you Do you get get infected? disease? 3 Does it matter? Everyone gets infections. Heterogeneity Tuberculosis: Estimated that 1/3 of the worlds population is infected with mycobacteria, but among those infected only ~10% will develop clinical disease. Hepatitis B: 2 billion people (1 out of 3 people) have been infected with hepatitis B in the world, but ~10% will develop chronic disease. Lyme Disease: ~10-20% of people have continued symptoms and disease post antibiotic treatment HIV/AIDS: variability in time to AIDS (in the pre-HAART and controlled post-HAART era) 4 Other Factors What are you Age, Sex, exposed other Virulence to? covariates Infectious Pathogen Host Disease Do you Do you get get infected? Age, Sex, disease? other Genetics Genetics covariates 5 Why do we care? If we can understand why people have different outcomes---we will better understand the immune response and eventually exploit this understanding for therapeutics and vaccines. Our goals…are still to better understand disease so we can prevent and treat. 6 Infectious Disease: A complex trait? Infectious Disease is a perfect example of a complex trait Environmental Exposure: Exposure to a pathogen is critical. Redundancy and Complexity of the immune system suggest multiple genes may be involved in immune response. The pathogen (virus, bacteria, parasite) may also have genetic factors that are important. 7 Is there evidence of genetics influencing infectious disease? 8 Examples from the literature • Rare Mendelian Diseases • Natural Selection-Population Genetics • Vaccine controlled examples • Adoption studies 9 Rare Disorders of Immunity Mendelian susceptibility to mycobacterial disease (MSMD) Clinically described in 1951 Highly susceptible to weakly virulent mycobacteria but resistant to most other infectious diseases, except Salmonella. Multiple gene mutations in the IL-12/IL-23, IFN-γ mediated immunity pathway. This pathway is crucial for host defense of mycobacterium and Salmonella 10 Early Suggestions with ABO blood groups and infection Disease Blood Type Association Reference Cholera O Increased susceptibility Sircar, 1981 Clemens, 1989 Shigella O Increased susceptibility Robinson ,1971 Norovirus O Increased susceptibility Hutson, 2002 Hennessey, 2003 P. Falicparum O Protected Rowe, 2007 Cserti, 2007 Schistosomiasis A Increased Susceptibility Lima, 1979 Ndamba, 1997 Camus, 1977 11 Twin Studies Disease MZ DZ Country of Reference Concordance Concordance Study Leprosy* 52 22 India Chakravarti and Vogel 1973 HBV 35 4 Taiwan Lin, Anticancer Research, 1979 TB 65 25 Germany Diehl, 1936 32 14 UK Comstock, Am, Rev Respir Dis, 1978 * In cases where both twins had leprosy, the type of leprosy—tuberculoid or lepromataus was more likely to be concordant if the pair was monozygotic ** We expect MZ > DZ since they share the same alleles 12 Genetics or Environment or Pathogen? However, despite this noticeable heterogeneity in outcome (disease, response, etc) many consider that dose and environment likely explain many of these differences, NOT genetics. 13 Controlling Dose: We learn from our mistakes… 1926, Lubeck Germany 249 babies injected with the same live dose of virulent M. tuberculosis instead of BCG. Babies too young to have significant prior exposure to mycobacteria, and not previously vaccinated to BCG. All got the same strain, same dose. 76 babies died, 173 babies survived Dubos, The White Plague 1952 14 Adoption Studies Sorensen et al, NEJM 1988 . Followed 960 families that included children born between 1924-1926 who were placed with adoptive parents early in life. The adoptive parents were not related to them. Evaluated risk of dying between the ages of 16-58 years for adoptees with a biologic or adoptive parent who died of the same cause before age 50 and before age 70. This was compared to parents who were still alive at the ages of 50 and 70. 15 16 Is there a place for genetics? ✓ Rare Mendelian Diseases ✓ Natural Selection-Population Genetics ✓ Vaccine controlled examples ✓ Adoption studies 17 Navigating the Human Genome cont. WHY consider genetics in the study of infectious disease? HOW do we evaluate host genetic associations? WHAT are the implications of host genetic predispositions to infection? 18 How do we evaluate genetic associations? HBV ADMIXTURE FAMILY SEQUENCING BASED HIV DENGUE LINKAGE MALARIA GWAS Tuberculosis POPULATION BASED HCV Genetics and Infectious Disease: What do we already know? HIV: HLA, CCR5, Cullin 5 Pulmonary TB: MFN2, HLA, RPS4XP18 Malaria: HBB, ABO, ATP2B4 Dengue: MICB, PLCE1 HCV: Interferon Lambda, HLA, GPR158 Genetic links between symptomatic Entamoeba histolytica infection and inflammatory bowel disease Entamoeba Histolytica • Protozoan parasite • Fecal-oral transmission route • Causative agent of amebiasis • Colonic mucosal invasion and tissue destruction STUDY POPULATIONS • Birth cohort, with all infants recruited from small area of Mirpur in Dhaka, Bangladesh • All children received all EPI vaccinations and tOPV • Biweekly home visits with extensive characterization of symptomatic enteric and respiratory infections • Anthropometric measurements, including stunting and wasting status • Biomarkers of environmental enteropathy, including intestinal permeability 0 6 10 14 17 18 39 40 52 53 Week Week Week Week Week Week Week Week Week Week EPI Vaccines tOPV Anthropometry Serum Biomarkers )Enteric Co-Pathogens STUDY POPULATIONS cont. Both the NIH Birth Cohort (DBC) and PROVIDE are birth cohorts in Mirpur, Study EH No EH Total Dhaka, Bangladesh. Case definition: A symptomatic infection DBC (diarrheal episode) within the first year of 60 252 312 life, as detected by RT-PCR or ELISA Control definition: No diarrheal episodes PROVIDE 110 322 432 or monthly visits positive for E. histolytica within the first year of life Total 170 574 744 POTENTIAL COVARIATES DBC DBC DBC PROVIDE PROVIDE PROVIDE cases cases Covariate Mean Mean P Mean Mean P Phet Controls Controls HAZ12 months -2.02 -2.02 0.99 -1.45 -1.47 0.83 0.85 Number of days of exclusive 122.7 130.54 0.42 125.5 123.0 0.69 0.41 breastfeeding Sex 56.3% 56.7% 0.96 54.7% 52.7% 0.73 0.79 GENETIC ANALYSIS METHODS Test for association at 6.7 million sites genome-wide. Gen Wojcik GENOME-WIDE RESULTS FOR DIARRHEAL EPISODES POSITIVE FOR E. HISTOLYTICA 5 x 10-7 VALUE - LOG P - Gen Wojcik CHROMOSOME TOP ASSOCIATIONS NIH Birth Cohort 2.34 [1.46, 3.74] rs58000832 PROVIDE 2.53 [1.73, 3.69] -9 Pmeta=2.4x10 Meta-Analysis 2.45 [1.83, 3.29] NIH Birth Cohort 2.42 [1.51, 3.88] rs11599920 -8 PROVIDE 2.26 [1.55, 3.29] Pmeta=2.4x10 Meta-Analysis 2.32 [1.73, 3.11] GENETIC RECOMBINATION MAP CUL2 CREM CCNY ASSOCIATION RESULTS GENETIC RECOMBINATION MAP Gen Wojcik How do we disentangle which gene is responsible for the signal? We can look to databases of what is known about this genetic region. Specifically, are these SNPs known to OUR ASSOCIATION RESULTS influence the expression of a specific gene? VALUE - CREM seems more likely. LOG P cAMP responsive element modulator - This gene encodes a bZIP transcription factor that binds to the cAMP responsive element found in many viral and cellular promoters. KNOWN GENE EXPRESSION LOCI EH activates CRE-regulated gene expression in intestinal epithelial cells Silencing CREM decreases CRE reporter induction by EH CREM expression is induced in early infection in mice by EH Bill Petri and Chelsea Marie CREM-/- MICE ARE MORE SUSCEPTIBLE TO AMEBIC COLITIS CREM -/- more Apoptotic death of cecal susceptible to infection intestinal epithelial cells CREM -/- with increased apoptosis Mayuresh Abhyankar, Bill Petri, and Chelsea Marie KNOWN ASSOCIATIONS OF GENETIC LOCI Risk Allele P OR Risk Functional SNP Reference Disease (Previous (Previous (Previous Allele P (EH) OR (EH) Class GWAS) GWAS) GWAS) (EH) Downstream Liu JZ Crohn’s rs11010067 G 1x10-26 1.142 G 4.5x10-6 1.82 Gene Variant (2015) Disease Inflammatory Downstream Jostins L rs11010067 Bowel G 2x10-25 1.115 G 4.5x10-6 1.82 Gene Variant (2012) Disease Inflammatory Liu JZ rs34779708 Intron (CREM) Bowel 2x10-25 - G 1.2x10-6 1.88 (2015) Disease Anderson Ulcerative rs12261843 Intron (CCNY) G 7x10-7 1.07 G 8.2x10-5 1.69 CA (2011) Colitis Upstream Franke A Crohn’s rs12242110 G 1x10-9 1.15 G 8.4x10-5 1.70 (CREM) (2010) disease Barrett JC Crohn’s rs17582416 intergenic G 2x10-9 1.16 G 4.0x10-6 1.83 (2008) disease The same loci predispose both inflammatory bowel disease and amebiasis. Genome-wide association study (GWAS) shows association of CREM with symptomatic E. CONCLUSIONS histolytica infection. Risk alleles also predispose individuals for inflammatory bowel disease (IBD). Potential role for shared immune response between amebiasis and IBD. Amebiasis is one infectious disease, many other diarrheal outcomes in this population have resulted in other genome wide associations. How to we evaluate genetic associations? HBV ADMIXTURE FAM ILY SEQUENCING BASED HIV DENGUE LINKAGE MALARIA GWAS Tuberculosis AMEBIASIS POPULATION BASED HCV AFM Mystery paralysis in children in perplexing
Load more

Recommended publications
  • Acute Flaccid Myelitis a Rare Entity. Hina Yusuf Shifa International Hospital
    Pakistan Journal of Neurological Sciences (PJNS) Volume 14 | Issue 2 Article 3 6-2019 Is it really transverse myelitis? Acute flaccid Myelitis a rare entity. Hina Yusuf Shifa International Hospital. Islamabad, Pakistan Arsalan Ahmad Shifa International Hospital. Islamabad, Pakistan. Ejaz Ahmed Khan Shifa International Hospital, Islamabad Follow this and additional works at: https://ecommons.aku.edu/pjns Part of the Neurology Commons Recommended Citation Yusuf, Hina; Ahmad, Arsalan; and Khan, Ejaz Ahmed (2019) "Is it really transverse myelitis? Acute flaccid Myelitis a rare entity.," Pakistan Journal of Neurological Sciences (PJNS): Vol. 14 : Iss. 2 , Article 3. Available at: https://ecommons.aku.edu/pjns/vol14/iss2/3 CASE REPORT remained bed bound, fully dependant on her family for months to 15 years. The illness usually begins with a REFERENCES IS IT REALLY TRANSVERSE MYELITIS? ACUTE FLACCID all activities of daily life. As before there were no prodromal phase of febrile illness with flu like 4. Sejvar JJ, Lopez AS, Cortese MM, Leshem E, Pastula MYELITIS A RARE ENTITY bladder or bowel complaints. She continued to have symptoms, usually followed by headache, neck . Pastula DM, Aliabadi N, Haynes AK, Messacar K, DM, Miller L, Glaser C, Kambhampati A, Shioda K, flaccid paralysis with marked muscle wasting and stiffness and backache. The patients then develop Schreiner T, Maloney J, Dominguez SR, Davizon Aliabadi N, Fischer M. Acute flaccid myelitis in the occasional fasciculations. Power had improved to 2/5 rapidly progressive lower motor neuron type limb ES, Leshem E, Fischer M, Nix WA. Acute neurologic United States, August–December 2014: results of 1 2 3 Dr Hina Yusuf , Prof Arsalan Ahmad , Prof Ejaz Ahmed Khan in both upper limbs.
    [Show full text]
  • Acute Flaccid Myelitis (AFM) Surveillance Guidance for County Health Departments (Chds) Th Version 6 | August 5 , 2020
    Acute Flaccid Myelitis (AFM) Surveillance Guidance for County Health Departments (CHDs) Version 6 | August 5th, 2020 Surveillance and Investigation When counties receive a report of possible AFM, we ask that you do the following: 1. Ask the provider to complete the FL-specific patient summary form and submit medical records (including infectious disease and neurology consult notes and MRI report), and MRI images (MRI images can come on a CD or flash drive). Ask the provider to mail MRI images on a CD/flash drive to the AFM Epidemiologist: Jenna Webb, 4052 Bald Cypress Way, Bin A-12 Tallahassee, FL 32399–1720 2. Create a case in Merlin using the Acute Flaccid Myelitis disease code (04910). Attach the MRI report, medical records, and patient summary form (select “report form” document type), then submit. The state will complete the rest of the data entry. 3. Notify your regional epidemiologist and laboratory liaison and the AFM Epidemiologist, Jenna Webb, of the AFM Person Under Investigation (PUI). 4. Ask the provider to work with their laboratory to submit available specimens to the Bureau of Public Health Laboratories (BPHL) along with a completed BPHL lab submission form with “AFM PUI” in the comments section. No specific test orders are necessary. Although shipping frozen specimens is ideal, refrigerated specimens are acceptable if shipped to BPHL overnight in a cooler box with frozen gel ice. Find the here: CDC Specimen Collection Instructions 5. BPHL will conduct enterovirus (including Enterovirus-D68), influenza, and respiratory virus panel PCR testing and West Nile virus IgM testing. 6. Providers should be made aware that laboratory results via BPHL or CDC are not intended for clinical diagnosis or clinical decision making and may not get reported back to Bureau of Epidemiology (BOE) or the submitting provider.
    [Show full text]
  • Acute Flaccid Myelitis (AFM) Fact Sheet
    Acute Flaccid Myelitis (AFM) Fact Sheet What is acute flaccid myelitis? Acute flaccid myelitis (AFM) is a condition that affects the nervous system, specifically the spinal cord. Most patients have sudden onset of limb (arm and leg) weakness. AFM is thought to be caused by infections with different types of viruses. The infections most commonly mentioned with AFM include polio or West Nile virus and related infections. Most patients with AFM have a respiratory illness or fever before their limbs are affected. Other causes of AFM are still being explored and may include environmental toxins or genetic disorders. Who gets AFM? Anyone of any age can get AFM, but it is more commonly reported in children. How is AFM spread? AFM is not spread from person to person. The viruses that are believed to cause AFM may be contagious from one person to another or may be spread by a mosquito or other vector depending on which virus causes the AFM. What are the symptoms of AFM? Most patients will have sudden onset of limb weakness and loss of muscle tone and reflexes. In addition, some patients will experience: facial droop/weakness, difficulty moving the eyes, drooping eyelids, or difficulty with swallowing or slurred speech. Numbness or tingling is rare in patients with AFM, though some people have pain in their arms or legs. Some patients with AFM may be unable to urinate. The most severe symptom of AFM is respiratory failure, which happens when the muscles involved with breathing become weak. This can require urgent ventilator (breathing machine) support.
    [Show full text]
  • Acute Flaccid Myelitis and Enterovirus D68: Lessons from the Past and Present
    European Journal of Pediatrics (2019) 178:1305–1315 https://doi.org/10.1007/s00431-019-03435-3 REVIEW Acute flaccid myelitis and enterovirus D68: lessons from the past and present Jelte Helfferich1 & Marjolein Knoester2 & Coretta C. Van Leer-Buter2 & Rinze F. Neuteboom3 & Linda C. Meiners4 & Hubert G. Niesters2 & Oebele F. Brouwer1 Received: 19 April 2019 /Revised: 11 July 2019 /Accepted: 16 July 2019 /Published online: 23 July 2019 # The Author(s) 2019 Abstract Acute flaccid myelitis is characterized by the combination of acute flaccid paralysis and a spinal cord lesion largely restricted to the gray matter on magnetic resonance imaging. The term acute flaccid myelitis was introduced in 2014 after the upsurge of pediatric cases in the USA with enterovirus D68 infection. Since then, an increasing number of cases have been reported worldwide. Whereas the terminology is new, the clinical syndrome has been recognized in the past in association with several other neurotropic viruses such as poliovirus. Conclusion: This review presents the current knowledge on acute flaccid myelitis with respect to the clinical presentation and its differential diagnosis with Guillain-Barré syndrome and acute transverse myelitis. We also discuss the association with enterovirus D68 and the presumed pathophysiological mechanism of this infection causing anterior horn cell damage. Sharing clinical knowledge and insights from basic research is needed to make progress in diagnosis, treatment, and prevention of this new polio-like disease. What is Known: • Acute flaccid myelitis (AFM) is a polio-like condition characterized by rapid progressive asymmetric weakness, together with specific findings on MRI • AFM has been related to different viral agents, but recent outbreaks are predominantly associated with enterovirus D68.
    [Show full text]
  • Acute Flaccid Myelitis Provider Guidance
    Acute Flaccid Myelitis August 2020 Provider Guidance Acute Flaccid Myelitis (AFM) is a rare syndrome characterized by rapid onset of flaccid weakness in one or more limbs with abnormalities of the spinal cord or brain grey matter on magnetic resonance imaging (MRI). Timing is Key for AFM Recognize AFM Collect specimens & Report to the department Diagnosis & medical get a MRI management Recognizing AFM Collect specimens & get a MRI • AFM tends occur in late summer or early fall • Specimens should be collected as early as possible in the course • Respiratory symptoms or fever consistent with a viral infec- of illness, preferably on the day of limb weakness onset tion occurs less than a week before onset of limb weakness • Specimens need to be sent to a State Public Health Laboratory, • Hospitalize patient immediately upon suspicion of AFM contact your county health department (CHD) to coordinate • Don’t wait for CDC’s case classification to diagnosis or • Order an MRI of the entire spine and brain with and without treat contrast 3 Tesla scanners are preferred and axial/sagittal images are the most helpful Symptoms • Arm or leg weakness • Loss of muscle tone • Difficulty moving the eyes • Loss of reflexes • Difficulty with swallowing • Facial droop or weakness • Pain in arms, legs, neck or • Slurred speech Additional information concerning specimen collection can be found in the back Job Aid for Clinicians Report to health department Diagnosis & medical management Please contact your CHD to report a suspected case of AFM at There are no proven ways to treat or prevent AFM FloridaHealth.gov/CHDEpiContact Providers should expedite neurology and infectious disease consults to discuss If the CHD cannot be reached, contact the state health department management and treatment at 850-245-4401 Long-term follow-up Items that need to be submitted The state health department is conducting long-term follow-ups on cases to • Admission and discharge notes better understand AFM outcomes.
    [Show full text]
  • Update on Acute Flaccid Myelitis: Recognition, Reporting, Aetiology and Outcomes Duriel Hardy, Sarah Hopkins
    Review Arch Dis Child: first published as 10.1136/archdischild-2019-316817 on 10 February 2020. Downloaded from Update on acute flaccid myelitis: recognition, reporting, aetiology and outcomes Duriel Hardy, Sarah Hopkins Division of Neurology, Children’s ABStract What is already known? Hospital of Philadelphia, Acute flaccid myelitis, defined by acute flaccid limb Philadelphia, Pennsylvania, USA weakness in the setting of grey matter lesions of Acute flaccid myelitis (AFM) presents with the spinal cord, became increasingly recognised in ► Correspondence to sudden paralysis and grey matter abnormality 2014 following outbreaks in Colorado and California, Dr Sarah Hopkins, Neurology, of the spinal cord, related to enteroviruses. Children’s Hospital of temporally associated with an outbreak of enterovirus Philadelphia, Philadelphia, PA Patients have residual disability, and optimal D68 respiratory disease. Since then, there have been management is unclear. 19104, USA; biennial increases in late summer/early fall. A viral hopkinss1@ email. chop. edu infectious aetiology, most likely enteroviral, is strongly Received 8 October 2019 suspected, but a definitive connection has yet to be Revised 8 January 2020 established. Patients typically present with asymmetric What this study adds? Accepted 17 January 2020 weakness, maximal proximally, in the setting of a febrile Published Online First illness. MRI demonstrates T2/FLAIR abnormalities in the 10 February 2020 ► Concise review of current knowledge, including Seguridad Social - BINASSS. Protected by copyright. central grey matter of the spinal cord, and cerebrospinal defining clinical characteristics, need for close fluid typically shows a lymphocytic pleocytosis with monitoring in the acute period, outcomes and variable elevation in protein. The weakness may be questions for further study.
    [Show full text]
  • Acute Flaccid Myelitis: Current Status and Diagnostic Challenges
    JCN Open Access REVIEW pISSN 1738-6586 / eISSN 2005-5013 / J Clin Neurol 2020 Acute Flaccid Myelitis: Current Status and Diagnostic Challenges Xiang Fanga Acute flaccid myelitis (AFM) is a sudden-onset polio-like neuromuscular disability found Ruksana Hudab commonly in young children. There is an increasing incidence of confirmed AFM cases in aDepartments of Neurology and the USA and other countries in recent years, and in association with nonpolio enterovirus b Microbiology and Immunology, infection. This represents a significant challenge to clinicians and causes significant concern University of Texas Medical Branch, to the general public. Acute flaccid paralysis (AFP) is the long-known limb paralytic syn- Galveston, TX, USA drome caused by a viral pathogen. AFM is a subset of AFP that is also characterized by a limb paralytic condition, but it has certain distinct features such as lesions in magnetic resonance imaging of the spinal cord gray matter. AFM leads to spinal cord, brainstem, or motor neu- ron dysfunction. The clinical phenotypes, pathology, and patient presentation of AFM closely mimic AFP. This article provides a concise overview of our current understanding of AFM and the clinical features that distinguish AFM from AFP and similar other neurological in- fectious and autoimmune diseases or disorders. We also discuss the diagnosis, clinical pa- thology, possible pathogenetic mechanisms, and currently available therapies. Key Words ‌acute disease, myelitis, paralysis, enterovirus. INTRODUCTION Acute flaccid myelitis (AFM) is a subset of acute flaccid paralysis (AFP) that encompasses long-known cases of limb paralytic syndromes.1,2 AFM refers to the potentially fatal acute onset of flaccid weakness and muscle immobility in children at a median age of 1 to 7 years.
    [Show full text]
  • Acute Transverse Myelitis and Acute Disseminated Encephalomyelitis
    Acute Transverse Myelitis and Acute Disseminated Encephalomyelitis Ilana Kahn, MD* *Children’s National Health System, George Washington University Medical School, Washington, DC Education Gap Most pediatricians report lack of knowledge related to the understanding of the diagnosis and treatment of both acute disseminating encephalomyelitis and acute transvers myelitis. Pediatric providers should understand presenting symptoms, initial diagnostic testing, and acute treatment. Clinicians should know when to refer to a neurologist for evaluation of long-term treatment. Objectives After completing this article, readers should be able to: 1. Define and characterize acquired demyelinating syndromes. 2. Identify the prevalence, etiology, and clinical presentations of acute disseminating encephalomyelitis (ADEM) and acute transverse myelitis (ATM). 3. Initiate a diagnostic evaluation, including an evaluation for medical emergencies. 4. Make treatment decisions for acute management. 5. Counsel patients on long-term outcomes after ADEM and ATM. AUTHOR DISCLOSURE Dr Kahn has disclosed 6. Counsel patients on recurrence risks for multiphasic or chronic no financial relationships relevant to this article. This commentary does not contain a demyelinating diseases. discussion of an unapproved/investigative use of a commercial product/device. ABBREVIATIONS INTRODUCTION ADEM acute disseminated encephalomyelitis ADS acquired demyelinating syndrome Acquired demyelinating syndromes (ADSs) encompass a group of immune- AQP4 aquaporin-4 mediated disorders in which there is breakdown of the myelin sheath, the lipid- ATM acute transverse myelitis CNS central nervous system rich covering around the axon that increases conduction speed and metabolic CSF cerebrospinal fluid efficiency of the neuron. ADSs are characterized by a sudden onset of new IgG immunoglobulin G neurologic symptoms in concurrence with neuroimaging evidence of demyelin- IVIg intravenous immunoglobulin MOG myelin oligodendrocyte glycoprotein ation.
    [Show full text]
  • Acute Flaccid Myelitis: What to Darkness Before Dawn
    Fall 2020 • Vol. 16, No. 3 NEWS IN NEUROVIROLOGY Official newsletter of the International Society for NeuroVirology Editor: Tory Johnson, PhD | Associate Editor: Fred Krebs, PhD In this issue: A Message from the President By Bruce Brew A Message from the President Page 1 The Board and I wish to express our ongoing support for our members during this extremely difficult time. As a society we want to Navigating Unknowns help each other. Please let us know if there are issues with which we Page 1 can assist. The road ahead is difficult to see but hopefully that is the Acute Flaccid Myelitis: what to darkness before dawn. watch for in 2020 and beyond Page 3 Congratulations Dr. Kennedy ISNV 2021 Meeting Update Page 5 Details regarding the 2021 ISNV virtual meeting will be coming soon. COVID-19 Virtual Biobank Page 6 On Our Desks Page 7 HIV-1 Tat and amyloidogenesis Navigating Unknowns Page 8 By Fergan Imbert Doctoral Candidate, Temple University, Langford Lab We often hear so much about how grad school makes you feel overwhelmed, sad, depressed or it “breaks your spirit”; that struggling in graduate school is normal and is some rite of passage. The COVID- Journal of 19 pandemic has unfortunately reinforced some of these feelings. Well NeuroVirology before the pandemic, there was mounting evidence that mental health among graduate students was a significant problem, with many Impact Factor 2.3 experiencing higher rates of depression and anxiety, and fewer actually seeking out professional help. As a new student myself, the movement of classes and lab meetings to an online platform to allow for social distancing provoked a destabilizing environment in which I struggled to stay focused.
    [Show full text]
  • Increase in Guillain-Barre Syndrome and Acute Flaccid Myelitis Cases
    TO: Neurologists, Pediatricians, Radiologists and Infectious Disease Physicians FROM: Thomas J. Safranek, M.D. Thomas Williams, M.D. State Epidemiologist Chief Medical Officer 402-471-2937 PHONE Director, Division of Public Health 402-471-3601 FAX Department of Health and Human Services RE: Increase in Guillain-Barre Syndrome and Acute Flaccid Myelitis Cases DATE: November 18, 2016 Guillain-Barre Syndrome (GBS) In October 2015, Nebraska Department of Health and Human Services (NDHHS) was notified of an apparent increase in Guillain-Barre Syndrome (GBS) in Lancaster County. Guillain-Barre is a potentially life-threatening, paralytic illness with an annual incidence of 1-2 per 100,000. The disease results in a loss of myelin on peripheral nerves and is believed to be autoimmune in nature. Past studies have implicated Campylobacter gastroenteritis, the influenza vaccine and Zika virus, but in most cases the etiology is unknown. GBS patients frequently require intensive care and ventilator support, with a 5-15% mortality rate, and approximately 20% experience continued disability after one year. As a result of this concern, NDHHS further in vestigated cases of Guillain-Barre in the state. Analysis of Nebraska’s hospital discharge data from 2007-2013 revealed an average of 39 GBS cases per year, or approximately 2.0 per 100,000. A follow-up chart review by public health medical staff identified 33, 41, and 58 cases in 2013, 2014 and 2015, respectively, for rates of 1.8 per 100,000, 2.3 per 100,000 and 3.2 per 100,000, respectively. These values reflect an overall increase of 75% from 2013 (N=33) to 2015 (N=58).
    [Show full text]
  • Acute Flaccid Myelitis Patient Summary Form
    Acute Flaccid Myelitis: Patient Summary Form FOR LOCAL USE ONLY Name of person completing form: ______________________________________________________ State assigned patient ID: ____________________________ Affiliation__________________________________________ Phone: ____________________________Email: __________________________________________ Name of physician who can provide additional clinical/lab information, if needed ___________________________________________________________________ Affiliation_____________________________________________ Phone: ___________________________ Email: ________________________________________ Name of main hospital that provided patient’s care: ________________________________________________ State: _____ County: ______________________ -------------------------------------------------------------DETACH and transmit only lower portion to [email protected] if sending to CDC------------------------------------------------------------- Form Approved Acute Flaccid Myelitis: Patient Summary Form OMB No. 0920-0009 Exp Date: 08/31/2022 Please send the following information along with the patient summary form: MRI report MRI images 1. Today’s date__ __/__ __/__ __ __ __ (mm/dd/yyyy) 2. State assigned patient ID: ______________________________ 3. Sex: M F 4. Date of birth __ __/ __ __/ __ __ __ __ Residence: 5. State_______ 6. County______________________ 7. Race: American Indian or Alaska Native Asian Black or African American 8. Ethnicity: Hispanic or Latino Native Hawaiian or Other Pacific Islander White (check all that apply) Not Hispanic or Latino 9. Date of onset of limb weakness __ __/__ __/__ __ __ __ (mm/dd/yyyy) 10. Was patient admitted to a hospital? yes no unknown 11.Date of admission to first hospital__ __/__ __/__ __ __ __ 12.Date of discharge from last hospital__ __/__ __/__ __ __ __(or still hospitalized at time of form submission) 13. Did the patient die from this illness? yes no unknown 14. If yes, date of death__ __/__ __/__ __ __ SIGNS/SYMPTOMS/CONDITION: Right Arm Left Arm Right Leg Left Leg 15.
    [Show full text]
  • Standardized Case Definition for Acute Flaccid Myelitis I. Statement Of
    15-ID-01 Committee: Infectious Disease Title: Standardized Case Definition for Acute Flaccid Myelitis I. Statement of the Problem Acute flaccid myelitis (AFM) is a syndrome characterized by rapid onset of weakness in one or more limbs and distinct abnormalities of the spinal cord gray matter on magnetic resonance imaging (MRI). During the summer and fall of 2014, an apparent increase in reports of AFM occurring in the United States was identified. Interpreting the increase in reports of AFM in 2014 has been challenging in the absence of baseline incidence of AFM. This position statement proposes a standardized case definition for AFM. II. Background and Justification AFM is a subset of acute flaccid paralysis (AFP). AFP is the acute onset of weakness absent signs of spasticity or other signs indicating a central nervous system disorder, and includes AFM, Guillain-Barré syndrome (GBS), toxic neuropathy, and muscle disorders. The annual rate of AFP among children under 15 years of age is expected to occur at approximately 1 per 100,000 children. Although AFP is the global surveillance gold standard method of monitoring for poliomyelitis due to poliovirus, and is routinely performed in many countries, AFP is not a reportable condition in any U.S. state and routine surveillance and assessment for AFP is not performed. Therefore, understanding of the incidence and epidemiology of AFM and its public health impact in the United States is significantly limited. While AFM is most commonly attributable to poliovirus or West Nile virus and other flaviviruses; other viruses, including non-polio enteroviruses, may rarely cause AFM.
    [Show full text]