Chlamydia trachomatis genital infections and single-dose azithromycin therapy

The recognized species of Chlamydia are all prokaryotic obligate intracellu lar parasites. Chlamydia trachomatis has a developmental cycle which is com plex and dimorphic. The infective forms (elementary bodies) attach to and e nter columnar and pseudostratified columnar epithelial host cells where the y transform into noninfective forms (reticulate bodies) within endosomes wh ich do not undergo fusion with host cell lysosomes. Individual endosomes fu se into a single inclusion within which the reticulate bodies multiply Matu ration of the reticulate bodies into infective elementary bodies is followe d by the release of the latter from the host cell to infect neighbouring ce lls. Chlamydial infections constitute the most common class of bacterial se xually transmitted disease in western countries. Including asymptomatic ind ividuals, the annual worldwide incidence of new infections is estimated to be in the region of 50 million. Prevalence rates differ widely according to the population subgroup, being highest amongst young, sexually active indi viduals. The majority of infected women, and about half of all infected men , remain asymptomatic. The mechanisms responsible for the pathological chan ges seen during chlamydial infection have yet to be fully elucidated, but h ypersensitivity to repeated infections is probably an important element. Th e possibility of developing a vaccine continues to be explored. In men, sym ptomatic chlamydial infections of the urogenital tract present as nongonoco ccal urethritis, orchitis, epididymitis, prostatitis or proctitis. In women , the symptoms are mucopurulent cervicitis, with or without cervical bleedi ng, and/or pelvic inflammatory disease (endometritis and salpingitis). Stru ctural damage resulting from chlamydial infection, whether or not asymptoma tic, may lead to the serious sequelae of tubal infertility or ectopic pregn ancy. Chlamydial infection may impair ovarian function or increase the risk of cervical intraepithelial neoplasia. The extent to which chlamydial infe ction affects the outcome of pregnancy is a matter of debate. Neonates born to women with Chlamydia trachomatis infection may develop pneumonitis or c onjunctivitis. Azithromycin is administered as a single dose of Ig in the t reatment of Chlamydia trachomatis genital infections. The mechanism of acti on of azithromycin against Chlamydia trachomatis involves inhibition of pro tein synthesis, which results in damage to metabolically active chlamydiae in inclusions and significantly reduces cell entry results in an inability of chlamydiae to modify their endosomal vacuole; this results in diversion of the chlamydia-containing endosome to the lysosomal pathway and blocks th e normal developmental cycle. Azithromycin is concentrated within phagocyte s which carry it to sites of local infection, where it is retained within t issue cell lysosomes. Release from the tissues is slow, and this, in conjun ction with a store held in various cell types, but particularly in fibrobla sts, ensures sustained high tissue concentrations, in excess of the MIG, fo r periods longer than the chlamydial developmental cycle. Most clinical tri als with azithromycin have been open-label, and the majority of these have involved comparisons with doxycycline given at a dose of 100 mg twice daily for 7 days. Azithromycin was found to be at least as effective as doxycycl ine therapy and has also been compared favourably with various other altern ative therapies. Double-blind trials confirm the results of the open-label trials. Azithromycin is well tolerated, and possesses a favourable adverse event and safety profile. The availability of sensitive and specific nonculture test procedures makes possible the introduction of screening programmes for Chlamydia trachomati s; the use of a single oral dose of 1 g azithromycin enables treatment to b e delivered quickly, and with a minimum of noncompliance. The identificatio n of relevant risk factors permits screening and treatment to be targeted, and there has been a decline in the incidence of new infections where scree ning and treatment programmes have been put in place. Nonculture techniques for identifying Chlamydia trachomatis include direct fluorescent antibody tests, enzyme immunoassays, nucleic acid detection and amplification proced ures (polymerase and ligase chain reactions). A rapid, but nonspecific, leu kocyte esterase dipstick test is also available and might be useful in asso ciation with other, more specific, test procedures. The costs of chlamydial infections and their sequelae are substantial. Health economic analyses in dicate that a screening programme for chlamydial infection, coupled with ef fective treatment of patients and their partners, will be financially viabl e as a consequence of avoiding the acute and chronic morbidity effects of c hlamydial infection. Treatment of Chlamydia trachomatis infection using azi thromycin has considerable cost advantages over other available treatments (such as doxycycline) with which it has been compared, the high compliance rate with a single-dose regimen being largely responsible for this advantag e. There remains much work to be done in this area, and particularly in reg ard to the continued economic viability of screening and treatment programm es in the face of the rapidly falling prevalence and incidence of chlamydia l infections which such initiatives will undoubtedly produce.