Sexually Transmitted Diseases
Chlamydia trachomatis
- Disease Burden
- Bacteriology
- Vaccines
- Global prevalance and incidence of selected curably sexually transmitted infections [opens in new window]
Disease Burden
More cases of STD are caused by Chlamydia trachomatis than by any other bacterial pathogen, making C. trachomatis infections an enormous public health problem throughout the world. In both men and women, silent, asymptomatic infection is common. The bacterium is transmitted from one partner to another by sexual intercourse. In men, C. trachomatis is the commonest cause of non-gonococcal (non-specific) urethritis. Conjunctivitis (that does not progress to blindness) and joint inflammation may occur. Men with asymptomatic infection serve as carriers of the disease, spreading the infection while only rarely suffering long-term health problems. Women, in contrast, are at high risk of severe complications of infection. Acute infection with Chlamydia can result in acute salpingitis and PID, whose long-term consequences include chronic pain, ectopic pregnancy and infertility. Contamination of the hands with genital discharge may lead to a conjunctival infection following contact with the eyes. Babies born to mothers with infection of their genital tract frequently present with chlamydial eye infection within a week of birth (chlamydial “ophthalmia neonatorum”), and may subsequently develop pneumonia. Various studies have estimated that there are four to five million new cases of chlamydial infection each year in the USA alone. Among urban adolescent females, the incidence rate can be as high as 30%. The annual costs of treating and caring for patients with PID might be as high as US$10 billion.
Worldwide, the most important disease caused by C. trachomatis is trachoma that affects the inner upper eyelid and cornea and is one of the commonest infectious causes of blindness. The disease starts as an inflammatory infection of the eyelid and evolves to trachomatous trichiasis (at least one eyelash rubbing on the eyeball, or loss of interned eyelashes) and blindness due to corneal opacity. In some parts of the developing world, over 90% of the population is infected. Despite long-standing control efforts, it is estimated that more than 500 million people still are at high risk of infection, over 140 million persons are infected and about 6 million are blind in Africa, the Middle East, Central and South-East Asia, and countries in Latin America. The disease is particularly prevalent and severe in rural populations living in poor and arid areas of the world where people have limited access to water and personal hygiene is difficult. Visual loss from trachoma often starts in middle life and is 2–3 times more common in women. It is therefore a major cause of disability in affected communities, attacking the economically important middle-aged female population. Trachoma is a communicable disease of families, with repeated reinfection occurring among family members.
Bacteriology
C. trachomatis is a small obligate intracellular bacterium found in two forms: the elementary body (EB) and the reticulate body (RB). The infectious form is the EB which lies outside cells. After attachment, EBs penetrate into their host cells where they reorganize into metabolically active and replicative RBs that accumulate by division in a large cytoplasmic inclusion. RBs then reorganize into infectious and spore-like EBs, which are released by host cell lysis or extrusion. The genus Chlamydia includes three species: C. trachomatis, an exclusively human pathogen; C. psittaci, which infects a variety of animals and can cause pneumonia or psittacosis in humans; and C. pneumoniae, a relatively common cause of LRIs in humans. Based on the type of disease produced, C. trachomatis has been divided into biovars, including: the lymphogranuloma (LGV) biovar, associated with lymphogranuloma venereum, an inguinal lymphadenopathy; and the trachoma biovar, associated with human conjunctival or urogenital columnar epithelium infections. C. trachomatis is further divided into serotypes (or serovars), some of which produce almost exclusively ocular trachoma in endemic countries, whereas others are associated with both ocular trachoma and genital-tract infections. The whole nucleotide sequence of the genome of C. trachomatis (serovar D) has been determined. Chlamydiae are sensitive to a number of antibiotics including erythromycin and tetracyclins. Chemotherapeutic intervention thus consists of topical (tetracyclin) or systemic (azithromycin) treatment with antibiotics. Other interventions consist of surgery of the eyelid. Global elimination of trachoma as a disease of public health importance has been targeted by WHO for 2020.
Vaccines
A safe vaccine administered prior to adolescence that is effective through childbearing age would have a significant impact on the spread of the disease. The lack of a suitable animal model and the difficulties in genetic manipulation of the bacterium have hampered progress in the field. Antex Biologics has developed a subunit vaccine candidate (TRACVAX) which has been tested in a randomized Phase I trial designed to assess the safety and immunogenicity of the candidate vaccine. NIAID (USA) is focusing on a conserved surface-exposed antigen termed polymorphic membrane protein D (PmpD) which induces neutralizing antibodies in vitro in animal models.
Identification of potential vaccine antigens is today an active area of research which is greatly helped by the availability of the complete C. trachomatis genome sequence, allowing for the identification and testing of candidate proteins based on their similarity to proteins important in protective immunity against other bacterial pathogens.