Laboratory diagnosis of sexually transmitted infections, including human immunodeficiency virus human immunodeficiency including Laboratory transmitted infections, diagnosis of sexually Laboratory diagnosis of sexually transmitted infections, including human immunodeficiency virus Editor-in-Chief Magnus Unemo Editors Ronald Ballard, Catherine Ison, David Lewis, Francis Ndowa, Rosanna Peeling For more information, please contact: Department of Reproductive Health and Research World Health Organization Avenue Appia 20, CH-1211 Geneva 27, Switzerland ISBN 978 92 4 150584 0 Fax: +41 22 791 4171 E-mail: [email protected] www.who.int/reproductivehealth 7892419 505840 WHO_STI-HIV_lab_manual_cover_final_spread_revised.indd 1 02/07/2013 14:45 Laboratory diagnosis of sexually transmitted infections, including human immunodeficiency virus Editor-in-Chief Magnus Unemo Editors Ronald Ballard Catherine Ison David Lewis Francis Ndowa Rosanna Peeling WHO Library Cataloguing-in-Publication Data Laboratory diagnosis of sexually transmitted infections, including human immunodeficiency virus / edited by Magnus Unemo … [et al]. 1.Sexually transmitted diseases – diagnosis. 2.HIV infections – diagnosis. 3.Diagnostic techniques and procedures. 4.Laboratories. I.Unemo, Magnus. II.Ballard, Ronald. III.Ison, Catherine. IV.Lewis, David. V.Ndowa, Francis. VI.Peeling, Rosanna. VII.World Health Organization. ISBN 978 92 4 150584 0 (NLM classification: WC 503.1) © World Health Organization 2013 All rights reserved. Publications of the World Health Organization are available on the WHO web site (www.who.int) 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 web site (www.who.int/about/licensing/copyright_form/en/index.html). 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Printed by the WHO Document Production Services, Geneva, Switzerland Laboratory diagnosis of sexually transmitted infections, including human immunodeficiency virus 2013 Editor-in-Chief Magnus Unemo WHO Collaborating Centre for Gonorrhoea and other STIs Örebro University Hospital, Örebro, Sweden Editors Ronald Ballard Centers for Disease Control and Prevention Atlanta, Georgia, United States of America Catherine Ison Public Health England (formerly Health Protection Agency) London, United Kingdom David Lewis National Institute for Communicable Diseases Johannesburg, South Africa Francis Ndowa World Health Organization Geneva, Switzerland Rosanna Peeling London School of Hygiene and Tropical Medicine London, United Kingdom Contents Acronyms and abbreviations vii Preface ix Acknowledgements xi 1 Choosing tests for sexually transmitted infections Edward W. Hook III, Francis Ndowa, David Mabey, Manju Bala, and Ye Tun 1 2 Quality management in the laboratory Catherine Ison and Ronald Ballard 9 3 Genital mycoplasmas Jørgen Skov Jensen and Magnus Unemo 15 4 Gonorrhoea Magnus Unemo and Catherine Ison 21 5 Chlamydial infections Barbara Van Der Pol and Magnus Unemo 55 6 Trichomoniasis Yaw Adu-Sarkodie, Magnus Unemo, and Barbara Van Der Pol 73 7 Bacterial vaginosis Yaw Adu-Sarkodie and Catherine Ison 83 8 Candidiasis Yaw Adu-Sarkodie and Catherine Ison 89 9 Herpes simplex virus (HSV) infections Laurent Bélec 93 10 Syphilis Ronald Ballard and Edward W. Hook III 107 11 Lymphogranuloma venereum (LGV) Ronald Ballard 131 12 Chancroid David Lewis 133 13 Donovanosis (granuloma inguinale) David Lewis 139 14 Human papillomavirus (HPV) infections Suzanne Garland 143 15 Human immunodeficiency virus (HIV) infections Bharat S. Parekh, Dennis Ellenberger, Larry Westerman, Chunfu Yang, and John N. Nkengasong 155 Contents v Annexes Annex 1. Microscopy and principles of staining Catherine Ison 167 Annex 2. Rapid point-of-care test principles Rosanna Peeling 175 Annex 3. Principles of molecular tests for the diagnosis of sexually transmitted infections Cheng Y. Chen and Magnus Unemo 183 Annex 4. Media, reagents, diagnostic tests, and stains (recipes) Stefania Starnino and Jo-Anne R. Dillon 199 Annex 5. Laboratory supplies Stefania Starnino and Jo-Anne R. Dillon 219 vi Laboratory diagnosis of sexually transmitted infections, including human immunodeficiency virus Acronyms and abbreviations AE Acridinium ester FRET Fluorescence resonance energy transfer AIDS Acquired immunodeficiency syndrome FTA-Abs Fluorescent treponemal antibody ART Antiretroviral therapy absorption ARV Antiretroviral g Acceleration due to gravity BD Becton, Dickinson and Company GASP Gonococcal Antimicrobial Susceptibility bDNA Branched chain DNA Surveillance Programme BV Bacterial vaginosis GCMB GC medium agar base C2CA Circle-to-circle amplification gG Glycoprotein G CCUG Culture Collection University of Gothenburg GKNP Glucose-potassium-sodium-phosphate (Gothenburg, Sweden) solution CDC Centers for Disease Control and Prevention GUD Genital ulcer disease (Atlanta, Georgia, United States of HBV Hepatitis B virus America) HC/HC2 Hybrid Capture/Hybrid Capture 2 CDS Calibrated dichotomous sensitivity HCV Hepatitis C virus CFU Colony-forming units HIV Human immunodeficiency virus CIA Chemiluminescence assay HIVDR HIV drug resistance CIN Cervical intraepithelial neoplasia HPA Hybridization protection assay CLSI Clinical and Laboratory Standards Institute HPV Human papillomavirus CMT Cytosine DNA methyltransferase HR High-risk types CO2 Carbon dioxide HSIL High-grade intraepithelial lesion COSHH Control of substances hazardous to health HSV Herpes simplex virus CSF Cerebrospinal fluid ICT Immunochromatographic test Ct Cycle threshold IF Immunofluorescence CTA Cysteine trypticase agar IFA Immunofluorescence assay CV Coefficient of variation IgA/IgG/IgM Immunoglobulin A, G, M CVA Cofactors-vitamins-amino acids IMDM-VGA Iscove’s modified Dulbecco medium DALY Disability-adjusted life year IP Immunoperoxidase DBS Dried blood spot IQA Internal quality assessment DFA Direct immunofluorescence assay IQC Internal quality control DGI Disseminated gonococcal infection ISO International Organization for DKA Dual kinetic assay Standardization DNA Deoxyribonucleic acid KOH Potassium hydroxide dsDNA Double-stranded DNA LDA Laboratory-developed assays EIA Enzyme immunoassay LGV Lymphogranuloma venereum EID Early infant diagnosis LIA Line immunoassay ELISA Enzyme-linked immunosorbent assay LJ Levey–Jennings plots EQA External quality assessment LPS Lipopolysaccharide EU European Union LR Low-risk types EUCAST European Committee on Antimicrobial LSIL Low-grade intraepithelial lesion Susceptibility Testing MALDI-TOF Matrix-assisted laser desorption FDA United States of America Food and Drug ionization–time of flight Administration MH Mueller–Hinton FITC Fluorescein isothiocyanate MIC Minimal inhibitory concentration Acronyms vii MIF Microimmunofluorescence RNA Ribonucleic acid MOMP Major outer membrane protein RPR Rapid plasma reagin MS Mass spectrometry RRP Recurrent respiratory papillomatosis MSM Men who have sex with men RT Reverse transcriptase MTM Modified Thayer–Martin medium SARA Sexually acquired reactive arthritis NAAT Nucleic acid amplification test SD Standard deviations NAH Non-amplified nucleic acid hybridization SDA Strand displacement amplification assays SNP Single nucleotide polymorphism NASBA Nucleic acid sequence-based amplification SOP Standard operating procedure NCNGU Non-chlamydial NGU SPG Sucrose-phosphate-glutamate NCTC National Collection of Type Cultures spp. Species NGU Non-gonococcal urethritis STI Sexually transmitted infection NIBSC National Institute for Biological Standards TC Target capture and Control TMA Transcription-mediated amplification NPV Negative predictive value TOC Test-of-cure nvCT New variant of Chlamydia trachomatis TPHA Treponema pallidum haemagglutination NYC New York City agar assay OF Oral fluid TPPA Treponema pallidum passive particle Pap Papanicolaou agglutination assay PBS Phosphate-buffered saline solution TRUST Toluidine red unheated serum test PCR Polymerase chain reaction TSB Trypticase soy broth PET Preformed Enzyme Test UK NEQAS United Kingdom National External Quality PID Pelvic inflammatory disease Assessment Service PIP Prolyliminopeptidase UNAIDS Joint United Nations