DOCSLIB.ORG

Detection and Molecular Characterization of Herpes Simplex Virus from Tanzania and Norway

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Detection and Molecular Characterization of Herpes Simplex Virus from Tanzania and Norway DETECTION AND MOLECULAR CHARACTERIZATION OF HERPES SIMPLEX VIRUS FROM TANZANIA AND NORWAY Mabula Joseph Kasubi Doctoral thesis submitted to the Faculty of Medicine, University of Bergen, in partial fulfilment of the requirements for a Ph.D degree Centre for International Health and Department of Microbiology and Immunology, The Gade Institute University of Bergen, Norway 2006 Table of Contents Acknowledgements .................................................................................................................... 3 List of original papers ................................................................................................................ 5 Abbreviations ............................................................................................................................. 6 1.0 Herpes simplex virus – General aspects......................................................................... 8 1.1 Taxonomy................................................................................................................... 8 1.2 Structure ..................................................................................................................... 8 1.3 Regulation of gene expression ................................................................................. 10 1.4 Entry of HSV into host cells .................................................................................... 11 1.5 Life cycle of HSV .................................................................................................... 11 1.6 HSV infections......................................................................................................... 12 1.7 Human disease.......................................................................................................... 13 1.8 Epidemiology of HSV infection............................................................................... 14 1.9 Treatment ................................................................................................................. 14 2.0 Diagnosis of HSV infection ......................................................................................... 15 3.0 Rationale for the present study..................................................................................... 16 3.1 Establishment of a new peptide ELISA for detection of HSV-1 antibodies................... 16 3.2 Detection of HSV specific antibodies in sera from children and young persons ........... 17 3.3 Genetic diversity of clinical HSV-2 isolates from Tanzania and Norway...................... 17 3.4 Aetiology of genital ulcers among patients attending STD clinic in Tanzania .............. 17 4.0 Aims of the study ......................................................................................................... 18 5.0 Summary of results....................................................................................................... 19 Paper I ……………………………………………………………………………………...19 Paper 11 ................................................................................................................................ 19 Paper III ................................................................................................................................ 20 Paper IV ................................................................................................................................ 20 6.0 General discussion........................................................................................................21 Peptide ELISA for detection of HSV-1 antibodies............................................................... 21 Detection of HSV specific antibodies................................................................................... 22 Genetic diversity of gG-2, gE-2 and gI-2 ............................................................................. 23 Aetiology of genital ulcer diseases ....................................................................................... 24 7.0 Conclusions .................................................................................................................. 26 8.0 Future perspectives....................................................................................................... 27 9.0 References .................................................................................................................... 28 10.0 Papers I - IV ................................................................................................................. 44 2 Acknowledgements The work presented in this thesis was carried out at the Centre for Research in Virology, University of Bergen, Norway. The work was funded by the Norwegian Educational Loan Fund and the University of Bergen, Norway. I would like to express my gratitude to everyone who has made it possible for me to reach the final point of this work. I wish you all peace and success. I would also like to express my sincere and special appreciation to the following: Professor Lars Haarr, my main supervisor. I wish to express my sincere gratitude for his dedicated and generous support in all aspects of my work. I am grateful for his valuable scientific advice, constructive criticism, encouragement, deep commitment and guidance throughout the study. My family and I, we will never forget the good times at his place, the warmth and kindness of his family. Professor Nina Langeland and Assistant Professor Arvid Nilsen, my co-supervisors. I would like to express my deepest gratitude for your support, enthusiasm, optimistic encouragements, valuable discussions and active participation in all stages of the study. Professor Tomas Bergström and Howard Marsden, collaborators of this study. I would like to express my sincere gratitude for having accepted to be part of this work. Your constructive comments, valuable scientific advice and commitments have been very important and useful for this thesis. Sigve Landstein, PhD student, Department of Molecular Biology. Thank you very much for helping me with the staden computer program. I am indebted to all staff at the Centre for International Health and all members at the Centre for Research in Virology for their help, encouragement and providing a very good working environment throughout the study period. 3 I am grateful to all members of the herpes group, particularly Kjerstin Jakobsen, Reidun Haegland and Lindsey Moore. The generous help, support and different socio-cultural gatherings organized have been a very wonderful and unforgettable to my family and me. With all my love, I would like to thank my wife, Beatrice and my daughter Anna for all the love and support they have shown me. They truly gave me strength, and support that I needed through these tough years. Thank you so much for your tolerance all these years. Finally, I owe special and deepest gratitude to God for giving me strength, both physically and mentally throughout the study period. Mange takk! Bergen, September 2006 Mabula Joseph Kasubi 4 List of original papers The thesis is based on the following papers referred to in the text by their respective roman numerals. Paper 1: Kasubi, M.J., Nilsen, A., Marsden, H.S., Bergström, T., Langeland, N., and Haarr, L. A branched, synthetic peptide corresponding to a region of glycoprotein G of HSV-1 reacts sensitively and specifically with HSV-1 antibodies in an ELISA. J. Virol. Methods. 2005; 125:137-143. Paper 11: Kasubi, M.J., Nilsen, A., Bergström, T., Langeland, N., Marsden, H.S., and Haarr, L. Prevalence of antibodies against herpes simplex viruses type 1 and type 2 in children and young people in an urban region in Tanzania. J. Clin. Microbiol. 2006; 44:2801-2807. Paper III: Kasubi, M.J., Norberg, P., Nilsen, A., Liljeqvist, JA., Bergström, T., Langeland, N., and Haarr, L. Clinical herpes simplex virus type 2 isolates from Tanzania and Norway cluster in two different genogroups. In manuscript. Paper IV: Nilsen, A., Kasubi, M.J., Mohn S.C., Mwakagile, D., Langeland, N., and Haarr, L. Herpes simplex virus infection and genital ulcer disease from STD patients in Dar es Salaam, Tanzania. Accepted with some modifications, Acta Dermato-Venereologica. 5 Abbreviations HSV Herpes simplex virus HSV-1 Herpes simplex virus type 1 HSV-2 Herpes simplex virus type 2 VZV Varicella zoster virus HCMV Human cytomegalovirus HHV-6 Human herpes virus 6 HHV-7 Human herpes virus 7 EBV Epstein-Barr virus Nm Nanometers DNA Deoxyribonucleic acid mRNA Messenger ribonucleic acid g Before a capital letter, glycoprotein B – N (gB - gN) kbp kilo base pair UL Long unique sequence of HSV genome US Short unique sequence of HSV genome TRS / L Terminal repeat sequences flanking US or UL Vhs Virus-host shut-off protein VP16 Virion protein 16 HveA Herpes virus entry protein A TNF Tumor necrosis factor Prr1/2 Poliovirus receptor-related proteins-1 or 2 HveB Herpes virus entry protein B HveC Herpes virus entry protein C MtrI Morphological transforming region of HSV-1 mtrII / mtrIII Morphological transforming regions of HSV-2 RRI Ribonucleotide reductase HPV Human papillomavirus WB Western blot ELISA Enzyme linked-immunosorbent assay PCR Polymerase chain reaction HCV Hepatitis C virus 6 HIV Human immunodeficiency virus GUD Genital ulcer disease STD Sexually transmitted disease STI Sexually transmitted infection 7 1.0 Herpes simplex virus – General aspects 1.1 Taxonomy Herpes simplex viruses (HSV) are important human pathogens causing diseases in a variety of different tissues and animal species. There are two antigenic
Load more

Recommended publications
  • Evaluation of the Febrile Young Infant
    February 2013 Evaluation Of The Febrile Volume 10, Number 2 Young Infant: An Update Author Paul L. Aronson, MD Assistant Professor of Pediatrics, Department of Pediatrics, Abstract Section of Emergency Medicine, Yale School of Medicine, New Haven, CT Peer Reviewers The febrile young infant is commonly encountered in the emergency V. Matt Laurich, MD, FAAP department, and the incidence of serious bacterial infection in these Assistant Professor of Pediatrics, University of Connecticut patients is as high as 15%. Undiagnosed bacterial infections such School of Medicine, Connecticut Children’s Medical Center, as meningitis and bacteremia can lead to overwhelming sepsis and Hartford, CT Deborah A. Levine, MD, FAAP death or neurologic sequelae. Undetected urinary tract infection can Clinical Assistant Professor of Pediatrics and Emergency lead to pyelonephritis and renal scarring. These outcomes necessitate Medicine, New York University School of Medicine, New York, the evaluation for a bacterial source of fever; therefore, performance NY of a full sepsis workup is recommended to rule out bacteremia, CME Objectives urinary tract infection, and bacterial meningitis in addition to other Upon completion of this article, you should be able to: invasive bacterial diseases including pneumonia, bacterial enteritis, 1. Recognize and explain to parents the rationale for performance of the sepsis workup in the well-appearing cellulitis, and osteomyelitis. Parents and emergency clinicians often febrile young infant. question the necessity of this approach in the well-appearing febrile 2. Apply the low-risk criteria to the well-appearing febrile young infant with normal urine, serum, and cerebrospinal young infant, and it is important to understand and communicate studies to avoid unnecessary hospitalization.
    [Show full text]
  • Fever Without Localizing Signs, 0-60 Days
    February 2021 TEXAS CHILDREN’S HOSPITAL EVIDENCE-BASED OUTCOMES CENTER Fever Without Localizing Signs (0-60 Days Old) Evidence-Based Guideline Definition: An acute febrile illness (temperature ≥100.4F Table 1. Signs and Symptoms of Shock (8,9) [38C]) with uncertain etiology after completion of a thorough Cold Warm Shock Non-specific history and physical examination. (1-3) Shock Etiology: The most common cause of fever without localizing Pulses Decreased Bounding signs (FWLS) is a viral infection. The challenge lies in the (central vs. or weak difficulty of distinguishing serious bacterial illness (SBI) from peripheral) viral illness in neonates and early infancy. (4,5) Capillary refill ≥3 sec Flash (<1 Inclusion Criteria: (central vs. sec) Age 0-60 days (Term infants ≥37 weeks gestation) peripheral) Neonates and infants without underlying conditions Mottled, Flushed, Petechiae Actual rectal temp ≥100.4F (38C) OR reported temp cool ruddy, below the (axillary or rectal) of ≥100.4F (38C) in home setting Skin erythroderma nipple, any (other than purpura Exclusion Criteria: face) History of prematurity Decreased, Underlying conditions that affect immunity or may otherwise irritability, increase risk of SBI confusion Toxic/Septic appearance inappropriate Receiving antibiotic treatment for FWLS crying or Routine vaccinations given within the previous 48 hours Mental drowsiness, Presenting with seizures status poor Requiring intensive care management interaction Identified focus of infection (e.g., cellulitis, acute otitis with parents, media in infants >28 days old) lethargy, diminished Differential Diagnosis: arousability, Meningitis obtunded Bone and joint infections *↑ HR followed by HR with BP changes will be noted as shock becomes Pneumonia uncompensated. Urinary tract infection (8,9) Sepsis/Bacteremia Table 2.
    [Show full text]
  • Genotypic and Phenotypic Diversity Within the Neonatal HSV-2
    bioRxiv preprint doi: https://doi.org/10.1101/262055; this version posted February 8, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Akhtar et al., biorxiv submission Feb.2018 Genotypic and phenotypic diversity within the neonatal HSV-2 population Lisa N. Akhtar1, Christopher D. Bowen2, Daniel W. Renner2, Utsav Pandey2, Ashley N. Della Fera3, David W. Kimberlin4, Mark N. Prichard4, Richard J. Whitley4, Matthew D. Weitzman3,5*, Moriah L. Szpara2* 1 Department of Pediatrics, Division of Infectious Diseases, Children’s Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine 2 Department of Biochemistry and Molecular Biology, Center for Infectious Disease Dynamics, and the Huck Institutes of the Life Sciences, Pennsylvania State University 3 Division of Protective Immunity and Division of Cancer Pathobiology, Children’s Hospital of Philadelphia 4 Department of Pediatrics, Division of Infectious Diseases, University of Alabama at Birmingham 5 Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine *Corresponding Authors Moriah L. Szpara Dept. of Biochemistry & Molecular Biology The Huck Institutes of the Life Sciences W-208 Millennium Science Complex (MSC) Pennsylvania State University University Park, PA 16802 USA Phone: 814-867-0008 Email: [email protected] Matthew D. Weitzman Division of Protective Immunity The Children’s Hospital of Philadelphia 4050 Colket Translational Research Building 3501 Civic Center Blvd Philadelphia, PA 19104-4318 Phone: 267-425-2068 Email: [email protected] 1 bioRxiv preprint doi: https://doi.org/10.1101/262055; this version posted February 8, 2018.
    [Show full text]
  • Cytomegalovirus and Herpes Simplex Virus Infections in the Fetus And
    Thesis for doctoral degree (Ph.D.) 2010 Thesis for doctoral degree (Ph.D.) 2010 Cytomegalovirus and herpes simplex virus infections in the fetus and newborn infant, with regard to neurodevelopmental disabilities Cytomegalovirus and herpes simplex virus infections in the fetus and newborn and infant. in the virusfetus herpes infections and simplex Cytomegalovirus Mona-Lisa Engman Mona-Lisa Engman From Division of Pediatrics, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden Cytomegalovirus and herpes simplex virus infections in the fetus and newborn infant, with regard to neurodevelopmental disabilities Mona-Lisa Engman Stockholm 2010 All previously published papers were reproduced with permission from the publisher. Cover: Picture published with permission from Dr Hong Zhou, Deartment of Pathology, Texas University, Houston, USA. Published by Karolinska Institutet. Printed by Reproprint AB © Mona-Lisa Engman, 2010 ISBN 978-91-7409-922-5 Printed by 2010 Gårdsvägen 4, 169 70 Solna To my beloved son Andreas ABSTRACT The congenital cytomegalovirus infection (CMV) is the most common congenital infection causing childhood morbidity. The majority (85%) of infected infants have no signs of infection in the newborn period, and when sequelae such as a hearing deficit or neurological impairment manifest themselves, the possibility of a CMV infection is easily overlooked. Neonatal herpes simplex virus (HSV) infection is a rare but devastating infection. Improvements with regard to outcome have been achieved by antiviral treatment, but the morbidity remains unacceptably high in children following neonatal HSV encephalitis. The general aim of the thesis is to increase the knowledge of childhood morbidity related to CMV and HSV infections.
    [Show full text]
  • Neurological Complications of Herpes Simplex Virus Type 2 Infection
    CLINICAL IMPLICATIONS OF BASIC NEUROSCIENCE RESEARCH SECTION EDITOR: HASSAN M. FATHALLAH-SHAYKH, MD Neurological Complications of Herpes Simplex Virus Type 2 Infection Joseph R. Berger, MD; Sidney Houff, MD, PhD erpes simplex virus type 2 (HSV-2) infection is responsible for significant neurologi- cal morbidity, perhaps more than any other virus. Seroprevalence studies suggest that as many as 45 million people in the United States have been infected with HSV-2, and the estimated incidence of new infection is 1 million annually. Substantial num- Hbers of these persons will manifest neurological symptoms that are generally, although not always, mild and self-limited. Despite a 50% genetic homology between HSV-1 and HSV-2, there are sig- nificant differences in the clinical manifestations of these 2 viruses. We herein review the neuro- logical complications of HSV-2 infection. Arch Neurol. 2008;65(5):596-600 The herpes viruses are responsible for sig- ready been infected by HSV-1. Primary nificant neurological morbidity. Three of HSV-2 infection in immunocompetent ado- the 8 human herpes virus types—herpes lescents and adults is usually asymptom- simplex virus type 1 (HSV-1), HSV-2, and atic, with most patients being unaware of varicella zoster virus—establish latency in their HSV-2 exposure. the peripheral sensory ganglia and per- sist in the host for a lifetime. Primary in- LATENCY AND REACTIVATION fection occurs at a mucocutaneous sur- face with retrograde transportation of the Neurons in the sacral ganglia tradition- virus to the peripheral sensory ganglia, ally have been considered to be the site of maintenance of the viral genome within HSV-2 latency.
    [Show full text]
  • <I>Papio Hamadryas Anubis</I>
    Journal of the American Association for Laboratory Animal Science Vol 45, No 1 Copyright 2006 January 2006 by the American Association for Laboratory Animal Science Pages 64–68 A Naturally Occurring Fatal Case of Herpesvirus papio 2 Pneumonia in an Infant Baboon (Papio hamadryas anubis) Roman F. Wolf,1,* Kristin M. Rogers,3 Earl L. Blewett,4 Dirk P. Dittmer,2 Farnaz D. Fakhari,2 Corey A. Hill,3 Stanley D. Kosanke,1 Gary L. White,1 and Richard Eberle3 Here we describe the unusual finding of herpesvirus pneumonia in a 7-d-old infant baboon Papio( hamadryas anubis). This animal had been separated from its dam the morning of its birth and was being hand-reared for inclusion in a specific- pathogen-free colony. The baboon was presented for anorexia and depression of 2 d duration. Physical examination revealed a slightly decreased body temperature, lethargy, and dyspnea. The baboon was placed on a warm-water blanket and was given amoxicillin–clavulanate orally and fluids subcutaneously. The animal’s clinical condition continued to deteriorate despite tube feeding, subcutaneous fluid administration, and antibiotic therapy, and it died 2 d later. Gross necropsy revealed a thin carcass and severe bilateral diffuse pulmonary consolidation. Histopathology of the lung revealed severe diffuse necrotizing pneumonia. Numerous epithelial and endothelial cells contained prominent intranuclear herpetic inclusion bodies. Virus isolated from lung tissue in cell culture was suspected to be Herpesvirus papio 2 (HVP2) in light of the viral cytopathic effect. Real-time polymerase chain reaction (PCR) analysis and DNA sequencing of PCR products both confirmed that the virus was HVP2.
    [Show full text]
  • Herpes Simplex Virus (Last Updated June 27, 2018; Last Reviewed June 27, 2018)
    Herpes Simplex Virus (Last updated June 27, 2018; last reviewed June 27, 2018) Panel’s Recommendations I. Will condoms (compared with not using condoms) prevent herpes simplex virus (HSV) infection in sexually active adolescents and young adults with HIV? • Condoms should be used to prevent HSV infection (and other sexually transmitted diseases) in adolescents and young adults with HIV (strong; low). The data regarding the level of protection provided by condoms are very limited for individuals with HIV in general, and for youth specifically. II. Will adolescents and young adults with HIV who have recurrent, genital HSV infection benefit from suppressive anti-HSV antiviral therapy (compared with not using suppressive therapy)? • Adolescents and young adults with HIV who suffer severe, frequent, and/or troubling recurrent genital HSV infection will benefit from anti-HSV suppression therapy (strong; moderate). III. Should children and adolescents with HIV who have severe primary or recurrent HSV (genital or orolabial) infection receive intravenous (IV) acyclovir (compared with receiving oral antiviral therapy)? • Children and youth with HIV who have severe mucocutaneous HSV infections should be treated with IV acyclovir. When improvement is noted, they can be switched to oral therapy until healing is complete (strong; moderate). IV. Should children and adolescents with HIV be treated with oral acyclovir, valacyclovir, or famciclovir for non-severe primary episodes or recurrent episodes of orolabial or genital HSV (compared with no antiviral therapy)? • Oral anti-HSV drugs will shorten the duration and reduce the severity of non-severe HSV infections in children and adolescents with HIV. Oral valacyclovir and famciclovir have superior pharmacokinetic profiles compared with oral acyclovir (strong; moderate).
    [Show full text]
  • NMPRA-Perspective-Spring-2021.Pdf
    Spring 2021 The Perspective A quarterly newsletter published by the National Med- Peds Residents’ Association in collaboration with the Med-Peds Program Directors Association & the AAP Section on Med-Peds What’s Inside 1 // 2020-2021 Executive Board 7 // Spotlight On 2 // President’s Welcome 8 // Topics in Med-Peds 3 // NMPRA Elections 10 // Essays 4 // AAP Section on Med-Peds 16 // Cases 5 // Match Day 2021 24 // NMPRA Notes 6 // Classifieds The Perspective 2020-2021’Executive Board Jonathan Phillips Phillips Jonathan Maximillian Cruz Maximillian Urban Sophia Colby Dendy ColbyDendy President President-Elect Past President Treasurer Alexis Tchaconas AlexisTchaconas DeSalvo Jen Adrianna Stanley Stanley Adrianna Leyens Kathryn Secretary PR Secretary Webmaster MPAC Liaison Sasha Kapil Kapil Sasha Lao-Tzu Allan-Blitz Allan-Blitz Lao-Tzu Sophie Sun SophieSun Nick Lee NickLee Dir Community Dir Recruitment/ Dir Health Dir Professional Service/Outreach Med Students Policy/Advocacy Advancement 1 NMPRA medpeds.org The Perspective President’s Welcome Hey Med-Peds family! As I hang up my cleats and transition out of the Presidency role, I just want to thank everyone in our Med-Peds community for all the inspiration you have provided me over the past years. This last year especially highlighted all the reasons that I was initially drawn to this specialty; the advocacy, the stick- to-itiveness, the collaboration, and the growth-mindset that seems to be ever prevalent in this community. I saw applicants come together and help each other out amidst
    [Show full text]
  • Neonatal Herpes: What Lessons to Learn
    CASE REPORT Neonatal herpes: what lessons to learn KL Hon 韓錦倫 TF Leung 梁廷勳 Vesicular rashes in neonates are challenging in terms of diagnosis and management. Herpes 張漢明 HM Cheung infection is an important diagnostic consideration. We report two illustrative neonatal cases 陳基湘 Paul KS Chan of herpesvirus infections with vesicular rashes. Such babies may be remarkably asymptomatic. A high index of suspicion leading to a prompt diagnosis, timely quarantine measures, and institution of antiviral treatment are pivotal for desirable outcomes. Case reports Case 1 An afebrile and asymptomatic neonate with 39 weeks and 6 days of gestation received a 5-day course of intravenous penicillin and gentamicin, because of prolonged rupture of maternal membranes and a slightly elevated plasma C-reactive protein level (14.6 mg/L; reference level, <10 mg/L). He developed a vesicular rash on day 12 of life, initially involving the face and forehead that subsequently spread to the entire body. Spontaneous rupture of the vesicles yielded yellow non-purulent fluid. He was admitted to a newborn unit (Fig 1), and cared for in a cubicle. The mother had childhood chickenpox, and developed some vesicles (which became crusted) on the dorsum of her right hand and arm 2 days before delivery. As chickenpox is an air-borne infection, the neonate was immediately transferred to an isolation room. He was treated as having herpes or a bacterial skin infection with acyclovir plus intravenous ampicillin and cloxacillin, and remained asymptomatic. Immunofluorescence staining of vesicular fluid confirmed the presence of varicella-zoster virus (VZV). Consequently, one cubicle of the newborn unit (involving 12 babies and their parents) was quarantined.
    [Show full text]
  • A Puzzling Diagnosis of Neonatal Herpes Simplex Virus Infection
    Case report BMJ Case Rep: first published as 10.1136/bcr-2020-241405 on 10 March 2021. Downloaded from Prolonged fever and hyperferritinaemia: a puzzling diagnosis of neonatal herpes simplex virus infection during COVID-19 pandemic Mohammed Kamal Badawy ,1 Sophie Hurrell ,1 Catherine Baldwin ,2 Heba Hassan1 1Paediatrics, Southend University SUMMARY lymphohistiocytosis (HLH) that could be induced Hospital NHS Foundation Trust, Neonatal herpes simplex virus (HSV) infection is rare, by infection with HSV. Disseminated infection or Westcliff- on- Sea, UK severe organ dysfunction may also be associated 2 with an estimated incidence of 3.58 per 100 000 Paediatrics, East and North live births in the UK and should be suspected in any with hyperferritinaemia.5 Hertfordshire NHS Trust, newborn with fever and bacterial culture-negative We report the case of disseminated HSV infec- Stevenage, UK sepsis. We describe a case of a previously well full- term tion in a clinically well-term neonate who presented with a persistent unexplained fever that could not Correspondence to male neonate who presented with persistent fever Dr Mohammed Kamal Badawy; and elevated ferritin level that was carried out during be attributed to neonatal sepsis because of the mohammed. badawy@ doctors. the era of the COVID-19 pandemic as part of SARS- absence of other manifestations of sepsis and nega- net. uk CoV-2 panel investigations. Despite the initial negative tive cultures. Extensive screening of SARS-CoV -2 HSV serology, HSV-1 PCR from a scalp lesion returned inflammatory biomarkers was carried out during Accepted 3 March 2021 positive. He made a full recovery after acyclovir therapy.
    [Show full text]
  • Rational Design of Live-Attenuated Vaccines Against Herpes Simplex Viruses
    viruses Review Rational Design of Live-Attenuated Vaccines against Herpes Simplex Viruses Brent A. Stanfield 1, Konstantin G. Kousoulas 2,3,*, Agustin Fernandez 3 and Edward Gershburg 3,* 1 Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA; [email protected] 2 Division of Biotechnology and Molecular Medicine, Louisiana State University, Baton Rouge, LA 70803, USA 3 Rational Vaccines Inc., Woburn, MA 01801, USA; [email protected] * Correspondence: [email protected] (K.G.K.); [email protected] (E.G.) Abstract: Diseases caused by human herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) affect millions of people worldwide and range from fatal encephalitis in neonates and herpes keratitis to orofacial and genital herpes, among other manifestations. The viruses can be shed efficiently by asymptomatic carriers, causing increased rates of infection. Viral transmission occurs through direct contact of mucosal surfaces followed by initial replication of the incoming virus in skin tissues. Subsequently, the viruses infect sensory neurons in the trigeminal and lumbosacral dorsal root ganglia, where they are primarily maintained in a transcriptionally repressed state termed “latency”, which persists for the lifetime of the host. HSV DNA has also been detected in other sympathetic ganglia. Periodically, latent viruses can reactivate, causing ulcerative and often painful lesions primarily at the site of primary infection and proximal sites. In the United States, recurrent genital herpes alone accounts for more than a billion dollars in direct medical costs per year, while there are much higher costs associated with the socio-economic aspects of diseased patients, such as loss of productivity due to mental anguish.
    [Show full text]
  • Management of Genital Herpes in Pregnancy
    Management of Genital Herpes in Pregnancy October 2014 Management of Genital Herpes in Pregnancy Foley E, Clarke E, Beckett VA, Harrison S, Pillai A, FitzGerald M, Owen P, Low-Beer N, Patel R. Guideline date: October 2014 Date of review: by 2018 Guideline development group: Elizabeth Foley MB BS BSc FRCP FRCOG (lead author), Consultant in Genitourinary and HIV Medicine, Solent NHS Trust Emily Clarke BSc BM MSc MRCP (UK), ST3 Genitourinary Medicine, Solent NHS Trust Virginia Beckett MB BS BSc FRCOG (lead author on behalf of RCOG), Consultant Obstetrician and Gynaecologist, Bradford Teaching Hospitals NHS Foundation Trust, Honorary Senior Lecturer, University of Bradford Sam Harrison MRCOG, ST6 Obstetrics and Gynaecology, Bradford Teaching Hospitals NHS Foundation Trust Anil Pillai MRCP, Consultant Neonatologist, Bradford Teaching Hospitals NHS Foundation Trust Mark FitzGerald FRCP, Lead Editor, BASHH guideline on Management of Genital Herpes (2014), BASHH Clinical Effectiveness Group, Consultant Physician in Genitourinary Medicine, Musgrove Park Hospital, Taunton Philip Owen MD FRCOG, Chair (to May 2014), RCOG Guidelines Committee, Consultant Obstetrician and Gynaecologist, Princess Royal Maternity, Glasgow Naomi Low-Beer MBBS MD MRCOG MEd, Consultant Gynaecologist, Chelsea and Westminster Hospital NHS Foundation Trust, Honorary Senior Clinical Lecturer, Imperial College London Rajul Patel FRCP, Senior Lecturer, University of Southampton, Consultant in Genitourinary and HIV Medicine, Solent NHS Trust 2 Contents 1. Objective and scope 4 2. Search strategy 5 3. Background 6 4. Management of pregnant women with first episode genital herpes 8 5. Management of pregnant women with recurrent genital herpes 10 6. Management of women with primary or recurrent genital lesions at the onset of labour 11 7.
    [Show full text]