Sexually Transmitted Diseases

Vaccines, Prevention, and Control

Lawrence R. Stanberry, Susan L Rosenthal, Lawrence R. Stanberry, Susan L Rosenthal

• Publisher: Academic Press
• Year: 2012
• ISBN:
  9780124157569
• Edition: 2
• Topic: Medicina
• Subtopic: AIDS e HIV

The last decade has seen a huge amount of change in the area of sexually transmitted infection control and prevention, including the development of high-profile vaccines for preventing the spread of cervical cancer-causing human papillomavirus (HPV), novel control methods for HIV and AIDS, and even the discussion of more widespread use of controversial abstinence-only sex education programs. Fully revised and updated to reflect the changes of the past ten years, Sexually Transmitted Diseases: Vaccines, Control and Prevention, Second Edition brings researchers, clinical investigators, clinicians, and students the most up-to-date research, findings and thought on sexual infection prevention, control and therapy available and serves as an essential reference for anyone working in the field.

• Provides comprehensive coverage of epidemiology, physiology and immunology, featuring general preventive strategies such as behavioural modification, barrier methods and topical microbicides
• Presents individual chapters on Herpes Simplex Virus, Papillomavirus, Hepatitis B, Chlamydia, Gonorrhea, Syphilis, and Bacterial Vaginosis
• Includes pathogenesis, microbiology and clinical manifestations of each STD, along with current advances in vaccine development

Part I

Epidemiology, Physiology, and Immunology

Chapter 1 Global Epidemiology of Sexually Transmitted Diseases

Chapter 2 The Genital Tract

Chapter 3 Mucosal Immunity in the Human Reproductive Tract

Chapter 1

Global Epidemiology of Sexually Transmitted Diseases

Adrian Mindel

Professor of Sexual Health Medicine, University of Sydney and Director of the Sexually Transmitted Infections Research Centre (STIRC), Marian Villa, Westmead Hospital, 170 Hawkesbury Road, Westmead, NSW 2145, Australia

Dominic Dwyer

Clinical Professor, Centre for Infectious Diseases & Microbiology, Westmead Hospital, Westmead, NSW 2145, Australia

Belinda Herring

Senior Lecturer, Sexually Transmitted Infections Research Centre (STIRC), Marian Villa, Westmead Hospital, 170 Hawkesbury Road, Westmead, NSW 2145, Australia

Anthony L. Cunningham

Professor of Research Medicine and Sub-Dean (Research), Western Clinical School, University of Sydney and Executive Director, Westmead Millennium Institute, Darcy Road, Westmead, NSW 2145, Australia

Chapter Outline

Introduction

Human Immunodeficiency Viruses

Virology of HIV

Transmission of HIV

HIV Epidemics

HIV-2

Molecular Epidemiology of HIV

HTLV

Genital Herpes

Cytomegalovirus

Epstein-Barr Virus

Human Herpesvirus 8 (HHV8)

Hepatitis B

Hepatitis Delta

Hepatitis C

Hepatitis A

Human Papillomavirus Infection

Chlamydia

Syphilis

Gonorrhea

The Tropical Sexually Transmitted Diseases

Trichomoniasis

References

Introduction

Many infections are sexually transmitted although some, including HIV and hepatitis B and C, are also transmitted by blood or blood products; others, like human papillomavirus (HPV) and herpes simplex virus (HSV) can also be transmitted by close bodily contact.

In 2005, the World Health Organization (WHO) estimated there were 448 million cases of the four major curable sexually transmitted infections (STIs) (trichomoniasis, chlamydia, gonorrhea and syphilis) among people aged 15–49 worldwide (Schmid et al., 2009). The viral STIs are also extremely common, with an estimated 33 million people infected with HIV in the world, 24 million new HSV type 2 infections annually and 10% of women in the world harbouring genital HPV at any time (70% of cervical cancers are attributable to HPV types 16 and 18). The vast majority of cases occur in developing countries (Gerbase, Rowley, Heymann, Berkley & Piot, 1998). One of the major reasons why STIs are more common in developing nations is that a large proportion of these populations is aged 18–35 years, the age group considered to be at greatest risk for STI acquisition. Gender inequalities, limited services and poor education opportunities in many of these communities also contribute to the ongoing spread of these infections.

STIs are a major cause of morbidity and mortality, with HIV causing over one million deaths per year worldwide. In addition, chlamydia and gonorrhea are the leading causes of tubal infertility; oncogenic HPV infections are associated with cervical, anal, and other genital tract tumours; many of the STIs (including HIV, syphilis, hepatitis B, gonorrhea, chlamydia, and HSV) can be transmitted from mother to baby, resulting in neonatal death, severe disability, or chronic infection. STIs may enhance HIV transmission and acquisition, and this appears to be particularly important in parts of the world where STIs are very common, including parts of sub-Saharan Africa and South East Asia.

The rate of STI spread within a community depends on several factors, including the size of the susceptible population, exposure to an infected individual, efficiency of transmission, and duration of infectiousness. Epidemiological patterns of individual infections depend on the interplay between these factors and the social, economic, and political environment. At an individual level, risk factors for STI acquisition include early coitarche, multiple sexual partners, partners from high-risk groups, poor condom usage, and drug use. A major limitation to any STI control initiative is that most individuals with an STI do not have symptoms or, even if they do, they may not recognize these to be due to an infection. This means that, unless sexual contacts are found and treated and that screening for asymptomatic infections occurs on a regular basis in ‘at-risk’ populations, the majority of people with STIs will remain undetected and untreated.

Societal factors may also have a profound effect on STI transmission. An example of the effect of social, economic, and political changes on STIs is the epidemic growth of these infections in the former USSR. Profound social and economic changes, and a partial collapse of the health system, have been contributory. The epidemic has been fuelled by growth in the commercial sex industry, unsafe intravenous drug use (IDU), and exchange of sex for drugs.

In addition to the personal health consequences, many STIs have important social, economic, and public health consequences, including family disharmony and breakdown, maternal and child ill-health, loss of income and productivity, and an enormous burden on social and health services. The global importance of STIs was acknowledged in 2000 when the United Nations drew up the Millennium Development Goals (MDG), aimed at reducing the global burden of disease and extreme poverty. One of the eight goals, MDG 6, ‘combat HIV/AIDS, malaria and other diseases’, relates directly to the most important STI worldwide. In addition, STIs are important in relation to several other MDGs, including MDG 3 ‘promoting gender equality and empowering women’, MDG 4 ‘reduce child mortality’ and MDG 5 ‘improving maternal health’ (United Nations, 2000).

As expected from the diverse cultures and sexual mores throughout the world, the epidemiology of sexually transmitted diseases (STDs) is highly variable in distribution and changing in different ways in different regions. The factors that influence these differences in prevalence and incidence are the nature of the STD itself, whether curable or incurable by antimicrobials, or preventable or non-preventable by vaccines. The availability of the highly developed healthcare network in western industrialized countries in contrast to developing countries influences the epidemiology, through ease of transmission, availability of diagnostic facilities and drugs, transmissibility of behavior modification messages, and levels of education allowing receptiveness to these messages. New diagnostic tests allow the definition of large reservoirs of asymptomatic infection, leading to marked changes in our understanding of the epidemiology of these infections. However, within the western industrialized countries there are also marked differences according to race, socioeconomic status, sexual preference, and the influence of drugs and prostitution. The data available to measure the epidemiology of STIs is limited, even in many western industrialized countries, and is often only available in developing countries through infrequent sampling studies. The importance of global comparisons of epidemiology is that it allows cross-comparison of the factors influencing spread and of optimal strategies for control, allowing adaption of the latter to the unique cultural characteristics and healthcare system of individual countries.

Human Immunodeficiency Viruses

Infection with the human immunodeficiency virus type 1 (HIV) and development of the acquired immunodeficiency syndrome (AIDS) was one of the major epidemics of the latter part of the twentieth century. The epidemic has spread to over 150 countries on the six populated continents with significant differences in the epidemiology both between and within countries. The first clinical description of AIDS was made in the USA in 1981, with the recognition of unusual clusters of Kaposi’s sarcoma and Pneumocystis carinii pneumonia, found in homosexual men. However, the deaths of a family in Norway (1976) were attributed retrospectively to HIV infection, and the isolation of HIV from a plasma sample collected in 1959 confirms the presence of HIV in the human population long before the 1980s (Jonassen, et al., 1997; Zhu, et al., 1998).

Following this initial observation in homosexual men in the USA, AIDS was reported in other populations, including IDUs, hemophiliacs, blood transfusion recipients, heterosexual adults from Central Africa, and infants born to mothers with HIV, showing that HIV was transmitted by homosexual and heterosexual sex, contaminated blood, and vertically from mother to baby. HIV has now reached virtually all demographic groups globally, irrespective of age, race, and income level.

Virology of HIV

HIV was first isolated at the Institut Pasteur Paris in 1983 (Barre-Sinoussi, et al., 1983) from the lymph node of a patient with lymphadenopathy. Further analysis by electron microscopy and DNA sequencing confirmed the virus to be a member of the lentivirus genus of the Retroviridae family.

The lentivirus genus is further divided into five groups, based on the vertebrate hosts they infect: bovine, equine, feline, ovine, and primate. The primate lentivirus group is divided into 14 separate lineages based on phylogenetic analysis of pol sequences. This group contains HIV-1, HIV-2 and 12 primate species-specific simian immunodeficiency viruses (SIVs), which do not infect humans. Lentiviruses are primarily characterized by long incubation periods before the onset of disease and cause a persistent, lifelong infection. Additionally, lentiviruses have the ability to infect lineages of hemopoietic cells, in particular non-dividing cells such as CD4+ lymphocytes and differentiated macrophages. Consequently, disease manifests as an immunodeficiency.

Transmission of HIV

HIV is transmitted in three major ways: through sexual contact, in blood, and from mother to child. The majority of HIV-1 infections are acquired through heterosexual contact, which accounts for approximately 85% of all infections globally; however, increasing numbers of infections are being reported in other ‘at risk’ groups such as men having sex with men (MSM), IDUs, and sex workers. At the start of the HIV epidemic, homosexual or bisexual male-to-male (sometimes combined with IDU) transmission was the main risk behavior identified in developed countries, and this remains one of the main modes of transmission in these countries. In contrast, heterosexual spread in the general population is the main mode of transmission in sub-Saharan Africa, which remains the most heavily affected region, with 68% of the global burden. Currently, HIV affects both men and women worldwide in approximately equal numbers, although more women than men are living with HIV in sub-Saharan Africa. The presence of other diseases, in particular STIs such as genital herpes, chancroid (ulcerative diseases), gonorrhea, and chlamydia (non-ulcerative), enhances the risk of sexual transmission of HIV.

Mother-to-child transmission (MTCT) of HIV can occur in utero, during labor, and postpartum via breastfeeding. The risk of transmission from mother to child in utero and during labor is increased if the maternal CD4+ T lymphocyte count is low, the maternal plasma HIV viral load is high, there are concurrent STIs, maternal tuberculosis, prolonged rupture of membranes, and if the baby is delivered vaginally. Breastfeeding transmission is dependent on duration of breastfeeding, high breastmilk viral HIV RNA levels, and maternal mastitis (Mepham, Bland, & Newell, 2011). Globally, the number of children born with...