Sexually transmitted diseases

Sexually transmitted diseases are bacterial or viral infections. They cause untold misery. Prevention is essential. The pharmaceutical industry has developed many medicines, and research continues in various directions. AIDS and Hepatitis B are not discussed here, because these diseases were covered in separate chapters and cards of the 'Medicines for Mankind' publications.

What are sexually transmitted diseases? Top

Sexually transmitted diseases (STDs), also commonly referred to as venereal diseases, are passed from one person to another through sexual contact. STDs probably are as old as human history, with the earliest records dating back nearly 5,000 years. STDs remain a major global cause of acute illness, infertility, long term disability and mortality. Today, syphilis, gonorrhoea, chlamydial infection and genital herpes are considered to constitute a secret world epidemic.

Syphilis (the word is derived from Latin meaning pestilence) is caused by the bacterium Treponema pallidum which enters the human body through mucous membranes. The primary stage is characterised by genital ulceration. Sores also can occur on the lips and in the mouth. In pregnant women, syphilis causes congenital infection, spontaneous abortion and stillbirth. If left untreated, 30 per cent of all cases result in late stage complications which include neuro-syphilis, granulomatous lesions in the skin, liver, bones and cardiovascular involvement. In 1530 Hieronymus Fracastor gave the disease its name in a poem. It relates the tale of the shepherd Syphilis, who for an act of impiety, was struck with the disease. The poem became so famous that the noun syphilis became the universal term for the infection.

Gonorrhoea is caused by Neisseria gonorrhoeae, a bacterium that grows in the warm, moist areas of the reproductive tract, including the cervix, uterus, and fallopian tubes in women, and in the urethra in women and men. Two to five days after infection, some men experience a painful sensation when urinating, or a white or yellow discharge from the penis. In the second century BC, Galen, a Greek physician, coined the noun gonorrhoea, which means “flow of seed.“ He mistakenly believed the urethral discharge was an involuntary loss of semen. Sometimes men with gonorrhoea develop swollen testicles. In most infected women, symptoms are mild or go unnoticed. They include a burning sensation when urinating, increased vaginal discharge, or vaginal bleeding between periods.

Chlamydial infection is caused by the bacterium Chlamydia trachomatis. Often, women are infected without knowing. They are frequently re-infected if their partners are not treated. Untreated, Chlamydia can lead to an infection of the womb and fallopian tubes called pelvic inflammatory disease, which may end in infertility.

Genital herpes is caused by herpes simplex virus (HSV). There are two types of the virus, type 1 (HSV-1) and type 2 (HSV-2); both can cause the disease, although the latter is more likely to produce frequent recurrences of genital lesions. The blisters break, leaving tender ulcers that may take some weeks to heal. Because of the ulceration, HSV-2 infection may act as cofactor for transmission of other STDs, including AIDS, a factor that has long been underestimated.

Who do sexually transmitted diseases affect? Top

Syphilis remains prevalent in developing countries and areas of the USA, Asia, and Europe, especially Eastern Europe, with up to 250 cases per 100,000 population. Its incidence has been increasing again since 2000, peaking at the age group 15-34 years. The increase is primarily noted in homosexual men. The cases reported in women decreased, as did congenital syphilis cases.

Microscopic picture of Treponema pallidum

During the 1980s, Western Europe saw a decline of the incidence of gonorrhoea to below 20 per 100,000, but since 1990, an increase in cases has been reported. A major rebound has been noted in Eastern Europe, with up to 125 cases per 100 000 population. The male to female ratio remained unchanged at 4:1. The 2003 rate for gonorrhoea in the USA was 117 per 100,000 people.

Microscopic picture of Neisseria gonorrhoeae

Infection with Chlamydia trachomatisis the most commonly diagnosed bacterial sexually transmitted infection in the developed world. Under-reporting is substantial because most people are not aware of their infection. An estimated four million Europeans are infected with chlamydia each year.

Microscopic picture of Chlamydia trachomatis

Genital HSV-2 infection is more common in women (approximately 25 per cent) than in men (20 per cent); due to male-to-female transmissions being more likely than female-to-male transmission. With a prevalence of one in four to five adults, the number of people with genital herpes in the EU is estimated to be around 60 million. Recent epidemiological studies have shown that infection with HSV-2 is highly prevalent in sub-Saharan Africa, and that the finding of antibodies against HSV-2 is a marker of high-risk sexual behaviour.

Electron-microscopic picture of the Herpes simplex virus

Present treatments Top

Treating patients without treating their sexual partners results in a high rate of reinfection, so that notification of partners and contact treatment are essential. For all stages of syphilis, the treatment of choice is intramuscularly injected penicillin, either as a single dose or long-term therapy. The need for alternative medicines is reserved for documented penicillin-allergic patients. Alternative regimens include tetracycline or macrolide antibiotics.

Treatment of gonorrhoea must be initiated as soon as possible after diagnosis. Therapeutic options include a single dose of a macrolide antibiotic or a multiple dosing regime with a tetracycline antibiotic, a gyrase inhibitor or a different macrolide antibiotic.

Chlamydia infection is treated with a single dose of a macrolide antibiotic. This simplifies treatment compliance. The other option is a seven-day course of a tetracycline antibiotic.

HSV-2 infection can nowadays be targeted by anti-herpetic specific medicines, either as a continuous prophylactic treatment during its asymptomatic shedding phase, or as an episodic treatment during clinically-apparent genital ulcerations. There is no cure for herpes, but antiviral medication shortens and prevents outbreaks.

What’s in the development pipeline? Top

In a phase 3 study, researchers are investigating the equivalence of the effectiveness of a macrolide antibiotic administered orally as a single dose for treatment of untreated primary, secondary or early latent syphilis compared to the recommended treatment, penicillin given intramuscularly.

A phase 1 trial evaluating the safety, tolerability and immune response of a newly developed vaccine against HSV-2 is underway in patients suffering from genital lesions. A special emphasis of vaccine development includes preventing primary infection, preventing the establishment of latency, and preventing transmission to neonates.

Stemming the spread of STDs is a major issue. In 2005, investigators showed that providing fast and direct access to antibiotics for partners of newly infected patients reduces the spread of STDs, compared to standard practice. Some 1,800 patients and their sexual partners were randomly assigned and offered either a standard referral or expedited treatment. The latter resulted in significantly fewer re-infections with Neisseria gonorrhoeae and Chlamydia trachomatis.

The longer-term future Top

The sequencing of the genome of Treponema pallidum containing some 1.2 million base pairs has been completed. The genome of Neisseria gonorrhoeae has been shown to consist of 2.2 million base pairs, while the genome of Chlamydia trachomatis contains around one million base pairs. The catalogue of genes will give a direction to new options for the treatment of the infections.

Sexual transmission of bacteria and viruses involves a breach of the natural mucous defence mechanism. Women currently have no way to protect themselves from STDs that does not require male cooperation. While the male condom is effective in preventing transmission of STDs, its use is hampered by deeply rooted cultural and social barriers. Alternative prevention tools, such as locally applied microbiocides, would be an interesting tool to prevent STD-causing organisms from entering their target cells in the vagina or the cervix. Several candidate microbiocides are set to enter advanced safety and efficacy testing.