Background

Causative agents. Three Chlamydia species are currently recognized as human pathogens: Chlamydia trachomatis, Chlamydia pneumoniae and Chlamydia psittaci. C. trachomatis infections are the most common bacterial cause of sexually transmitted disease (STD) in humans1. Most infected patients are asymptomatic and do not seek medical treatment. Untreated infection in both sexes increases the risk of HIV infection2. In the absence of treatment, the infection can cause pelvic inflammatory disease in up to one-third of infected women, which can lead to infertility and potentially fatal ectopic pregnancies. Chlamydial infection is also common among young men, who rarely seek screening. Once diagnosed, the infection can be treated with doxycycline, azithromycin, ofloxacin or erythromycin. The species C. trachomatis also includes the trachoma serovars A, B, Ba and C. Trachoma is the leading cause of preventable infectious blindness, accounting for at least 15% of blindness worldwide3. The chlamydiae are transmitted from eye to eye, and eye-seeking (synanthropic) flies are an important factor in spreading disease4. Active trachoma ranges from a mild asymptomatic inflammation to an intense inflammatory response. Neonatal conjunctivitis can also be caused by the genital serovars of C. trachomatis and is acquired during birth5. Untreated, between 10 and 20% of infected children develop neonatal pneumonia. C. trachomatis is a significant cause of childhood pneumonia (20–30%) in hospitalized patients less than 6 months old. C. pneumoniae is transmitted by aerosols and is a common cause of human respiratory disease, causing approximately 10% of community-acquired pneumonia and 5% of pharyngitis, bronchitis and sinusitis6. Recent seroepidemiological evidence has associated C. pneumoniae infection with an enhanced risk of developing atherosclerotic and cerebrovascular disease7.

Distribution. Chlamydial STD and C. pneumoniae infections are found worldwide. Blinding trachoma is found predominantly in the poorest countries of Africa, Asia, the western Pacific and parts of Oceania (Fig. 1).

Figure 1: The distribution of blinding trachoma.
figure 1

The numbers indicate WHO estimates of the prevalence of sexually transmitted Chlamydia infections among adults in 1999.

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Current global status. An estimated 89 million new cases of sexually transmitted chlamydial infections occur worldwide each year1 (Fig. 1), and this is probably an underestimate of the actual number of cases5. In the United States, young adults aged 18 to 26 years have a prevalence of 4.19%, with women more likely to be infected than men8. Six million people are irreversibly blinded by trachoma3, and 146 million cases of active disease require treatment. More than 500 million people live in trachoma-endemic areas9. C. pneumoniae is a common cause of community-acquired pneumonia worldwide6. Half of the global adult population (>20 years of age) shows serological evidence of past infection with C. pneumoniae, with infection being more common in the elderly.

Recent developments

New basic knowledge. There is no useful gene-transfer system for chlamydiae. However, their small genome (∼1 Mb) has allowed complete genome sequencing of several human isolates. Comparative genomics has begun to yield new insights into the pathogenic potential of these organisms10. The presence or absence of a functional tryptophan synthase is a reliable marker for distinguishing ocular and genital biovars of C. trachomatis11, and might reflect the importance of the polymicrobial environment in the female lower genital tract for successful chlamydial transmission. Genomic data also indicate that chlamydiae possess a type III secretion system that coordinately translocates chlamydial effector proteins into the cytoplasm of the host cell10,12. This results in several important alterations, including initiation of signal-transduction pathways, modulation of apoptotic responses and alteration of membrane trafficking. Genome sequencing has also provided the means for identifying the complete chlamydial transcriptome and proteome patterns under several different growth conditions.

New tools and interventions. The most effective strategy for preventing chlamydial STDs is education about the consequences of unprotected sexual intercourse. As treatment with a single dose of oral antibiotics is effective, early detection is an important strategy to contain transmission. But as the infection is frequently asymptomatic, infected people are often not diagnosed. Alternatively, active screening for chlamydial STDs in high-risk populations could decrease the incidence of infection. The prevalence of infection was found to be 9.2% in US female military recruits, but it was estimated that 98.2% of these infections could have been prevented had a screening programme been in place13.

New strategies, policies and partnerships. Spread of the trachoma biovars is facilitated by poverty and lack of access to healthcare and clean water. The WHO is leading an international alliance — the Alliance for the Global Elimination of Blinding Trachoma by 2020 (GET 2020) — to work towards the worldwide elimination of trachoma14. These efforts will seek community involvement and will focus on a combination of interventions known as SAFE — surgery for trichiasis, antibiotics, facial cleanliness and environmental improvement. An important component of the strategy is the use of a single oral-dose antibiotic (azithromycin), an improvement on the previous regime of daily applications of tetracycline eye ointments over a six-week period. Pfizer has provided azithromycin free of charge for use in pilot trachoma-prevention studies. The development of a protective vaccine has involved the cooperation of government agencies (NIH, MRC), private foundations (Edna McConnell Clark Foundation) and corporate interests (GlaxoSmithKline).

Conclusion and future outlook

Eliminating trachoma will be possible if new intervention strategies are combined with improved hygiene standards and economic advancements in the developing world, where trachoma remains endemic. The problems associated with chlamydial STDs are more difficult to deal with due to the combination of a high rate of asymptomatic, acute infections and chronic upper genital tract sequelae in women. Better diagnostics and earlier intervention are crucial. Infections due to C. pneumoniae remain problematic as they can be related to chronic conditions such as asthma, cardiovascular disease and neurological disorders.