Diagnostics to Pathogenomics of Sexually Transmitted Infections

Comprehensively explores sexually transmitted diseases, from epidemiology, causative pathogens, clinical impact, and immunology, to management strategies utilizing new strategies of genomics and next-generation diagnostic tools

Sexually transmitted infections (STI) are very common worldwide. More than 20 different STIs have been identified, and about 19 million men and women are infected each year in the United States alone. This book looks at the complete picture of common STIs? how they form, evolve, and transmit, as well as how they can be treated and managed with modern techniques, medicines, and tools.

Diagnostics to Pathogenomics of Sexually Transmitted Infections runs the spectrum of discussion ranging from introduction of causative pathogen, their pathogenesis to epidemiology, immunology, to anatomy and physiology of human genitalia and management strategies. The book offers in-depth chapter coverage on effect of probiotics on reproductive health; mucosal immunity in sexually transmitted infections; the role of circumcision in preventing STIs; Human Immunodeficiency Virus (HIV); genital herpes; molluscum contagiosum; genital warts; chlaymydia trachomatis; donovanosis; gonorrhoea; treponematoses; genital mycoplasms; bacterial vaginosis; vulvovaginal candidiasis; chlaymydia; scabies; chancroid, yeast infections; and more.

• Comprehensively compiles most of the major sexually transmitted infections
• Presents updated information on clinical aspects of sexually transmitted infections
• Examines the priorities in pathogenesis of human sexually transmitted infections and discusses new strategies of genomics and next-generation diagnostic tools used for detection of such pathogens
• Explores the future of rapid molecular diagnostic techniques and the challenges posed in the diagnosis of human STIs
• Includes bench to bedside content that will appeal to both basic and clinical researchers

By offering the latest knowledge about recent advances in sexually transmitted infections in an interdisciplinary fashion, Diagnostics to Pathogenomics of Sexually Transmitted Infections is the perfect book for virologists, microbiologists, infectious disease experts, vaccinologists, biomedical researchers, clinicians, pharmacologists, and public health specialists.

About the Editor xv

Contributors xvii

Preface xxi

1 Mucosal Immunity in Sexually Transmitted Infections 1
Jiri Mestecky and Michael W. Russell

1.1 Introduction 1

1.2 Innate Immunity in the Genital Tract 2

1.2.1 Humoral Defense Factors in Female Secretions 2

1.2.2 Innate Defense Factors in the Male Tract 4

1.3 Immunoglobulins in Secretions of the Genital Tract 4

1.3.1 Female Genital Tract Secretions 4

1.3.2 Origin of Igs in Human Genital Tract Secretions 7

1.3.3 Functions of Genital Tract Antibodies 8

1.4 Cells of the Mucosal Immune System of the Genital Tract 10

1.4.1 Epithelial Cells 10

1.4.2 Immunoglobulin‐Producing Cells 10

1.4.3 T Cells and Other Cell Types 11

1.5 Induction of Immune Responses in the Genital Tract 12

1.5.1 Induction of Humoral Immune Responses in Human Male Genital Tract Secretions 14

1.5.2 Immune Responses in the Genital Tract after Infections 15

1.5.2.1 Gonorrhea 15

1.5.2.2 Chlamydia 15

1.5.2.3 Human Immunodeficiency Virus (HIV) 16

1.5.2.4 Human Papilloma Virus 16

1.6 Concluding

Remarks 17

References 17

2 The Role of Circumcision in Preventing Sexually Transmitted Infections 27
Kourosh Afshar, Behnam Kazemi, and Andrew E. MacNeily

2.1 Introduction 27

2.2 Biological Mechanisms 27

2.3 Methods of Circumcision 28

2.4 Complications 28

2.5 Role of MC in Transmission of HIV 29

2.5.1 Male‐to‐Female Transmission 29

2.5.2 Female‐to‐Male Transmission 29

2.5.3 Male‐to‐Male Transmission 30

2.6 Human Papilloma Virus (HPV) 30

2.7 Nonulcerative STIs 31

2.7.1 Gonorrhea 31

2.7.2 Trichomonas Vaginalis (Tv) 32

2.7.3 Chlamydia Trachomatis (Ct) 32

2.8 Ulcerative STIs/Genital Ulcer Disease (GUD) 32

2.8.1 Syphilis 33

2.8.2 Chancroid 34

2.9 Use of Male Circumcision as a Public Health Measure 34

2.10 Female Genital Mutilation (FGM) 35

References 36

3 Effect of Probiotics on Reproductive Health 41
Piotr Kochan, Magdalena Strus, and Piotr B. Heczko

3.1 Introduction 41

3.2 Definition of Probiotics 43

3.3 Vaginal Microflora (Microbiota) 46

3.4 Applications of Probiotics in Vaginal and Reproductive Health 49

3.4.1 Vaginitis (Aerobic Vaginitis (AV), Bacterial Vaginosis (BV), and Vulvovaginal Candidiasis (VVC)) 50

3.4.2 UTI 52

3.4.3 Pregnancy 52

3.4.4 Other Obstetrics and Gynecology (OB/GYN) Uses of Probiotics 53

3.5 Conclusions 53

References 54

4 Human Immunodeficiency Virus (HIV) Infection 61
Santosh Kumar Singh and Sunit K. Singh

4.1 Introduction 61

4.2 HIV Structure/Genome 62

4.3 Routes of Transmission 64

4.3.1 Sexual Transmission 64

4.3.1.1 STDs and Sexual Transmission of HIV 64

4.3.1.2 Vulnerability of Female Genital Tract for HIV Transmission 66

4.3.2 Transmission by Contaminated Blood/Blood Product Transfusion 68

4.3.3 Transmission by Sharing Syringe and Needles 68

4.3.4 Transmission from Mother to Fetus or Newborn Babies 68

4.3.5 Occupational Risk in Healthcare Workers 68

4.4 Host Factors Influencing HIV Infectivity in Sexual Transmission 69

4.4.1 Systemic Host Factors 69

4.4.2 Local Host Factors 69

4.5 Viral Factors Influencing HIV Infectivity in Sexual Transmission 70

4.6 Mechanism of Pathogenesis 71

4.7 Diagnosis of HIV Infections 72

4.8 Therapeutics 73

4.8.1 Antiretroviral Therapies (ARTs) 73

4.8.2 Combinational ARTs 74

4.9 Conclusion 74

References 75

5 Genital Herpes 83
Andreas Sauerbrei

5.1 Introduction 83

5.2 Pathogen 83

5.3 Epidemiology 84

5.4 Pathogenesis and Immunity 84

5.5 Clinical Features 86

5.6 Diagnosis 87

5.7 Treatment 90

5.8 Prevention and Control 93

5.9 Conclusion 94

References 95

6 Molluscum Contagiosum 101
Tugba Kevser Uzuncakmak and Ayse Serap Karadag

6.1 Introduction 101

6.2 Epidemiology 101

6.3 Molecular Pathogenesis 102

6.4 Diagnosis 103

6.5 Clinical Features 106

6.6 Mode of Spread of Infections 107

6.7 Treatment 107

6.7.1 Treatment Options 108

6.7.1.1 Watchful Waiting 108

6.7.1.2 Procedure‐Based Treatments 109

6.7.1.3 Chemical Agents 110

6.7.1.4 Immune Modulators 111

6.7.1.5 Antiviral Agents 112

6.7.1.6 Immunocompromised Patients 112

6.8 Conclusion 113

References 113

7 Genital Warts 119
Filip Rob

7.1 Introduction 119

7.2 Human Papillomavirus 119

7.2.1 Taxonomy 119

7.2.2 Life Cycle 120

7.2.3 Interaction with Immune System 120

7.2.4 Transmission 120

7.2.5 Clearance 120

7.3 Epidemiology 121

7.4 Risk and Protective Factors 121

7.4.1 Risk Factors 121

7.4.2 Protective Factors 122

7.5 Clinical Features 122

7.5.1 Physical Signs 122

7.5.2 Symptoms 123

7.6 Diagnostics 124

7.6.1 Clinical Investigation 124

7.6.2 3–5% Acetic Acid 124

7.6.3 Histopathology 124

7.6.4 HPV DNA Detection 125

7.6.5 HPV Antibodies 125

7.7 Differential Diagnosis 125

7.8 Treatment 126

7.8.1 Cryotherapy 126

7.8.2 Laser Therapy (CO2 laser, Er:YAG laser) 127

7.8.3 Electrocautery 127

7.8.4 Surgical Excision 127

7.8.5 Trichloracetic Acid (80–90% solution) 127

7.8.6 Podophyllotoxin (0.05% solution or 0.15% gel) 127

7.8.7 Imiquimod (3.75% or 5% cream) 127

7.8.8 Sinecatechins (10% or 15% ointment) 129

7.9 Specific Groups 129

7.9.1 Immunocompromised Patients 129

7.9.2 Pregnant Women 129

7.9.3 Children 129

7.10 HPV Vaccination 130

References 131

8 Chlamydia Trachomatis Urogenital Infections: Epidemiology, Clinical Presentations, and Pathogenesis 135
Charles W. Armitage, Alison J. Carey, Danica K. Hickey, and Kenneth W. Beagley

8.1 Introduction 135

8.2 Epidemiology 135

8.3 Chlamydial Biology 136

8.3.1 The Attachment and Entry of Chlamydial EBs 136

8.3.2 The Chlamydial Inclusion 137

8.3.3 Chlamydial Replication and Persistence 137

8.4 Clinical Features 138

8.4.1 Urogenital Tract Infections 139

8.4.2 Female Urogenital Tract 139

8.4.3 Infection and Pregnancy 141

8.4.4 Male Urogenital Tract 142

8.4.5 Anorectal Tract Infections 143

8.4.6 Gastrointestinal Chlamydial Infections and Persistence 144

8.4.7 Lymphogranuloma Venereum 144

8.5 Pathogenesis of Chlamydial Infections 145

8.5.1 Pathogenesis of Female Genital Tract Chlamydial Infections 145

8.5.2 Lower FRT Pathogenesis 146

8.5.3 Upper FRT Pathogenesis 146

8.5.4 Pathogenesis of Male Urogenital Tract 148

8.5.5 Chlamydial Urethritis and Prostatitis 148

8.5.6 Chlamydial Infections of the Upper MRT 148

8.5.7 Chlamydial Epididymitis 149

8.5.8 Chlamydial Orchitis 149

8.6 Diagnosis and Treatment 150

8.7 Prevention and Control 151

8.8 Conclusion 152

References 153

9 Donovanosis 167
Sarita Martins De Carvalho Bezerra, Marcio Martins Lobo Jardim, and Juliana Uchiyama

9.1 Introduction 167

9.2 Epidemiology 168

9.3 Pathology 168

9.4 Incubation Period 169

9.5 Clinical Pictures 170

9.6 Sites of Involvement 174

9.7 Complications and Sequelae 175

9.8 Diagnosis 175

9.9 Differential Diagnosis 176

9.10 Treatment 176

9.11 Prevention and Control 177

9.12 Disease Control and Prevention 178

References 178

10 Gonorrhea 181
María Teresa Pérez‐Gracia and Beatriz Suay‐García

10.1 Introduction 181

10.2 Pathogen 182

10.2.1 Morphology 182

10.2.2 Virulence Factors 183

10.2.2.1 Type IV Pili (Tfp) 183

10.2.2.2 Por Proteins 183

10.2.2.3 Opacity Proteins (Opa) 184

10.2.2.4 Rmp Proteins 184

10.2.2.5 Lipooligosaccharide (LOS) 184

10.2.2.6 IgA Protease 185

10.2.3 Physiology 185

10.2.4 Genome 185

10.3 Pathogenesis and Immunity 185

10.4 Epidemiology 186

10.5 Clinical Features 188

10.5.1 Gonococcal Infection in Men 188

10.5.2 Gonococcal Infection in Women 188

10.5.3 Extragenital Locations 188

10.6 Diagnosis 189

10.6.1 Samples 189

10.6.2 Staining 191

10.6.3 Culture 191

10.6.4 Identification 193

10.6.5 Neisseria gonorrhoeae Genotyping 193

10.6.6 Nucleic Acid Amplification Tests (NAATs) 197

10.7 Treatment 198

10.8 Prevention and Control 200

10.9 Conclusion 202

References 202

11 Sexually Transmitted Treponematoses 211
Lenka Mikalová and David Šmajs

11.1 Introduction 211

11.2 Genetics of TPA and TEN Strains 212

11.3 Virulence Factors of Syphilis and Bejel 214

11.4 Diagnostics of Syphilis and Bejel 215

11.5 Treatment of Syphilis and Bejel 217

11.6 Molecular Typing of Syphilis and Bejel Treponemes 220

11.7 Vaccine Development for Syphilis and Bejel 222

References 223

12 Genital Mycoplasmas 233
Suncanica Ljubin‐Sternak

12.1 Introduction 233

12.2 Biology 234

12.3 Pathogenesis 235

12.3.1 Adhesion Proteins 236

12.3.2 Antigenic Variation 236

12.3.3 Production of Enzymes 236

12.3.4 Facultative Intracellular Localization 237

12.3.5 Capacity to Induce Host Immune Response 237

12.4 Epidemiology 237

12.5 Clinical Presentation 238

12.5.1 Urogenital Infections in Women 238

12.5.1.1 Bacterial Vaginosis 238

12.5.1.2 Cervicitis 239

12.5.1.3 Pelvic Inflammatory Disease (PID) and Its Sequalae 239

12.5.1.4 Infections in Pregnancy 240

12.5.2 Urogenital Infections in Men 241

12.5.2.1 Nongonococcal Urethritis (NGU) 241

12.5.2.2 Epididymitis and Prostatitis 241

12.5.2.3 Infertility 241

12.5.3 Rare Manifestations and Clinical Features in Immunocompromised Persons 242

12.5.3.1 Urinary Calculi 242

12.5.3.2 Systemic Infection and Arthritis 242

12.5.3.3 Infection in Immunocompromised Patients 242

12.6 Laboratory Diagnosis 243

12.6.1 Specimen Collection 243

12.6.2 Culture Methods 243

12.6.3 Molecular Methods 245

12.6.4 Serology 246

12.7 Treatment 247

12.8 Prevention and Control 248

References 249

13 Bacterial Vaginosis 257
Aliona Rosca and Nuno Cerca

13.1 Introduction 257

13.2 Implication of G. vaginalis in Bacterial Vaginosis 258

13.3 Epidemiology and Risk Factors 260

13.4 Pathogenesis and Immunity 261

13.5 Clinical Features 263

13.6 Diagnosis 263

13.7 Treatment 266

13.8 Conclusions 268

References 268

14 Chancroid 277
Margaret E. Bauer and Diane M. Janowicz

14.1 Introduction 277

14.2 Epidemiology of Chancroid and H. ducreyi 277

14.3 Clinical Features 278

14.4 The Pathogen 279

14.5 Pathogenesis and Immunity 280

14.5.1 Overview of Pathogenesis 280

14.5.2 Virulence Mechanisms 280

14.5.3 Regulation of Virulence 282

14.5.4 Immune Response 283

14.6 Diagnosis, Treatment, and Prevention 284

14.7 Chronic Limb Ulcers Caused by H. ducreyi 285

14.8 Conclusions 286

References 287

15 Vulvovaginal Candidosis 293
Gilbert G.G. Donders, Katerina S. Ruban, Gert Bellen, and Sivtrigaile Grinceviciene

15.1 Introduction 293

15.2 Etiology 293

15.2.1 Pathogens 293

15.2.2 Morphology 294

15.3 Epidemiology 294

15.3.1 Prevalence 294

15.3.1.1 Asymptomatic Colonization 294

15.3.1.2 Symptomatic Infection 295

15.3.2 Risk Factors 298

15.3.3 Sexual Transmission 298

15.3.4 Young and Elderly Women 298

15.4 Pathogenesis and Immunity 300

15.4.1 Hormones 300

15.4.2 Pregnancy 300

15.4.3 Impaired Glucose Tolerance 301

15.4.4 Genetic Predisposition 301

15.4.4.1 STAT1 Gain of Function Mutations 302

15.4.4.2 CARD9 302

15.4.4.3 AIRE Mutation 302

15.4.4.4 NALP3/CIAS1 304

15.4.4.5 Interleukin-4 304

15.4.4.6 Dectin-1 304

15.4.4.7 Mannose‐Binding Lectin (MBL) 304

15.4.5 Other Factors Affecting Pathogenesis 305

15.5 Symptoms and Signs 305

15.5.1 Acute/Episodic Infection 305

15.5.2 Recurrent Vulvovaginal Candidosis 306

15.6 Diagnosis and Differential Diagnosis 306

15.6.1 Clinical Signs 306

15.6.2 Clinical Examination 306

15.6.3 Wet Mount Microscopy 307

15.6.4 Vaginal pH 309

15.6.5 Vaginal Mycological Culture 310

15.6.6 Molecular Biology 310

15.6.7 Histology 310

15.6.8 Differential Diagnosis 310

15.7 Treatment 311

15.7.1 General Principles of Treatment 311

15.7.2 Treatment of Uncomplicated Acute Infection 311

15.7.3 Treatment of Complicated Acute Infection 312

15.7.3.1 Severe Symptoms, C. albicans Vulvovaginitis 314

15.7.3.2 Non‐Albicans Candida Infection 314

15.7.3.3 Poorly Controlled Diabetes, Immune Suppression 315

15.7.3.4 Pregnancy and Breastfeeding 315

15.7.4 Recurrent Vulvovaginal Candidiasis (RVVC) 316

15.7.4.1 Azole‐Resistant C. albicans 317

15.7.4.2 Elimination of Risk Factors of Recurrence in RVVC Patients 317

15.7.4.3 Underlying Reasons for Failing Maintenance Therapy 318

References 319

16 Tinea Cruris 329
Anuradha Bishnoi and Rahul Mahajan

16.1 Introduction 329

16.2 Etiology and Epidemiology 330

16.3 Tinea Cruris as a Sexually Transmitted Infection (STI) 331

16.4 Transmission 331

16.5 Pathogenesis 332

16.5.1 Environmental Factors 332

16.5.2 Agent Factors 332

16.5.3 Host Factors 332

16.5.4 Host Immune Response 333

16.5.5 Clinical Features 333

16.5.6 Variants 335

16.5.6.1 Tinea incognito 335

16.5.6.2 Vesico‐Bullous Tinea Cruris 335

16.5.6.3 White Paint Dots and Pseudomembranous Tinea 335

16.6 Differential Diagnoses 336

16.6.1 Candidiasis 336

16.6.2 Erythrasma 336

16.6.3 Hyperpigmented Pityriasis Versicolor 336

16.7 Laboratory Diagnosis 336

16.7.1 Direct Examination 336

16.7.2 Culture 337

16.7.3 Nucleic Acid Amplification Tests 337

16.8 Treatment of Tinea Cruris and Genitalis 337

16.8.1 Topicals 337

16.8.2 Systemic 337

16.8.3 Recalcitrant/Resistant Tinea: Pathomechanisms and Treatment 338

16.8.4 General Measures to Prevent Tinea Cruris 338

16.9 Conclusion 338

Acknowledgments 339

References 339

17 Trichomonas Vaginalis 341
Barbara Van Der Pol

17.1 Introduction 341

17.2 Epidemiology of T. vaginalis 342

17.3 HIV and Trichomonas 344

17.4 Biology and Pathogenesis of T. vaginalis 345

17.5 Clinical Features of T. vaginalis Infection 346

17.6 Diagnosis of T. vaginalis 348

17.6.1 Laboratory Diagnosis 349

17.7 Treatment of T. vaginalis 350

17.8 Conclusion 351

References 351

18 Scabies 357
Giuseppe Micali, Giorgia Giuffrida, and Francesco Lacarrubba

18.1 Introduction 357

18.2 Epidemiology 357

18.3 Etiopathogenesis 358

18.4 Clinical Features 359

18.5 Diagnosis 363

18.5.1 Microscopy 363

18.5.2 Dermatoscopy/Videodermatoscopy 363

18.5.3 Histopathology 365

18.5.4 Other Diagnostic Procedures 366

18.6 Treatment 366

18.6.1 Topical Agents 366

18.6.2 Oral Agents 367

18.6.3 Treatment for Crusted Scabies 367

18.7 Prevention and Control 368

18.8 Conclusion 368

References 368

Index 373

By offering the latest knowledge about recent advances in sexually transmitted infections in an interdisciplinary fashion, Diagnostics to Pathogenomics of Sexually Transmitted Infections is the perfect book for virologists, microbiologists, infectious disease experts, vaccinologists, biomedical researchers, clinicians, pharmacologists, and public health specialists.

About the Editor

Dr. Sunit K. Singh is Professor of Molecular Immunology and Head of the Molecular Biology Unit at the Faculty of Medicine, Institute of Medical Sciences (IMS), Banaras Hindu University (BHU), Varanasi, India.