Chlamydia (Chlamydial Genitourinary Infections)

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Chlamydia (Chlamydial Genitourinary Infections)

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Chlamydial infection can cause disease in many organ systems, including the genitourinary tract. Chlamydiae are small gram-negative obligate intracellular microorganisms that preferentially infect squamocolumnar epithelial cells. They include the genera Chlamydia (of which the type species is Chlamydia trachomatis) and Chlamydophila (eg, Chlamydophila pneumoniae and Chlamydophila psittaci).

C trachomatis can be differentiated into 18 serovars (serologically variant strains) on the basis of monoclonal antibody–based typing assays. These serovars are associated with different medical conditions, as follows:

Serovars A, B, Ba, and C – Trachoma, a serious eye disease endemic in Africa and Asia that is characterized by chronic conjunctivitis and can lead to blindness

Serovars D-K – Genital tract infections

Serovars L1-L3 – Lymphogranuloma venereum (LGV), which is associated with genital ulcer disease in tropical countries

C trachomatis infection affects the cervix, urethra, salpinges, uterus, nasopharynx, and epididymis^{[1, 2, 3]}; it is the most commonly reported bacterial sexually transmitted disease (STD) in the United States and a leading cause of infertility in women. C trachomatis infection causes other diseases as well, including conjunctivitis, pneumonia or pneumonitis, afebrile pneumonia syndrome (in infants born vaginally to infected mothers), Fitz-Hugh-Curtis syndrome, and trachoma (the world’s leading cause of acquired blindness).^[4]

C pneumoniae infection is spread via respiratory droplets and causes pharyngitis, bronchitis, and pneumonia. C psittaci infection is spread by bird droppings and aerosols and causes psittacosis. These infections are not discussed in this article.

At present, fewer than 50% of sexually active young females in the United States are screened for the presence of chlamydiae. Nationally, the annual screening rate increased from 25.3% in 2000 to 43.6% in 2006, then decreased slightly to 41.6% in 2007.^[5]

The US Preventive Services Task Force recommends routine screening for chlamydial infections. The USPSTF recommends screening for chlamydia in sexually active females aged 24 years or younger and in older women who are at increased risk for infection. Routine Chlamydia screening of sexually active young women is recommended to prevent consequences of untreated chlamydial infection (eg, pelvic inflammatory disease (PID), infertility, ectopic pregnancy, and chronic pelvic pain).^{[6, 7]}A guideline synthesis is also available from the National Guideline Clearinghouse.^[8]

The pathophysiologic mechanisms of chlamydial infection are poorly understood at best. Chlamydia infects columnar epithelial cells, which places the adolescent female at particular risk because of the presence of the squamocolumnar junction on the ectocervix until early adulthood. The initial response of epithelial cells to infection is a neutrophilic infiltration, followed by lymphocytes, macrophages, plasma cells, and eosinophilic invasion. The release of cytokines and interferons by the infected epithelial cell initializes this inflammatory cascade.

Infection with chlamydial organisms invokes a humoral cell response, resulting in secretory immunoglobulin A (IgA) and circulatory immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies and a cellular immune response. A 40-kd major outer membrane protein (MOMP) and 10- and 60-kd chlamydial heat-shock proteins (cHSPs) have been implicated in the immunopathologic response, but further studies are needed to provide a better understanding of these cell-mediated immune responses.^[9]

Chlamydiae have a unique biphasic life cycle that is adaptable to both intracellular and extracellular environments. In the extracellular milieu, the so-called elementary body (EB) is found. EBs are metabolically inactive infectious particles; functionally, they are spore-type structures. Once inside a susceptible host cell, the EB prevents phagosome-lysozyme fusion and then undergoes reorganization to form a reticulate body (RB).

The RB synthesizes its own DNA, RNA, and proteins but requires energy in the form of adenosine triphosphate (ATP) from the host cell. After a sufficient amount of RBs have formed, some transform back into EBs, exiting the cell to infect others.

The bacterium is usually spread through sexual activity. An infected male has a 25% chance per sexual encounter of transmitting the infection to an uninfected female. Chlamydiae can be vertically spread as well. The transmission rate from infected mother to newborn is 50-60%, causing conjunctivitis (in most cases) or pneumonia (in 10-20% of cases; see Afebrile Pneumonia Syndrome).

Infection of the genital tract is the most common clinical presentation. The incubation period is 1-3 weeks. Approximately 50% of infected males and 80% of infected females are asymptomatic, but infection may cause a mucopurulent cervicitis in females and urethritis in males. Ascending infection can result in PID in women and is the most common cause of epididymitis in men younger than 35 years. Of women with PID, 5-10% develop perihepatitis (ie, Fitz-Hugh-Curtis syndrome).

Although patients with any STD are at increased risk of coinfection with another STD, coinfection of chlamydia and gonorrhea is most common. Forty percent of women and 20% of men with chlamydial infection are co-infected with gonorrhea. Patients with chlamydia also have a higher frequency of Reiter syndrome (ie, urethritis, conjunctivitis, reactive arthritis) than the general population.

LGV is rare in the United States but is responsible for 10% of cases of genital ulcer disease in tropical countries. Localized inguinal adenopathy and ulceration develop 2-12 weeks after exposure. Proctitis, rectal strictures, and lymphatic obstruction with secondary elephantiasis can occur in untreated disease.

Chlamydial transmission usually is caused by sexual contact through oral, anal, or vaginal intercourse. Neonatal infection (eg, conjunctivitis or pneumonia) may occur secondary to passage through the birth canal of an infected mother. Specific risk factors for chlamydial infection include the following:

Nonwhite race

Multiple sexual partners or a new sexual partner

Age 15-24 years (especially < 19 years)

Poor socioeconomic conditions (eg, homelessness)

Exchange of sex for drugs or money

Single marital status

Intercourse without a barrier contraceptive

History of a previous STD or current coinfection with another STD

Certain cytokine polymorphisms – These have been associated with severe disease and risk of tubal factor infertility^[10]

Certain variants in Toll-like receptor 1 and 4 genes – These predispose to infection^[11]

Having been a foster child (males only)^[12]

Chlamydial infection is the most frequently reported infectious disease in the United States, and its prevalence is highest in persons aged 24 years or younger.^[13]The annual incidence of C trachomatis genital infections was estimated to be 2.86 million cases in the United States in 2008.^[14]

Sexually active female populations average chlamydial carriage rates of about 20%. Many patients are asymptomatic. The incidence is 2-3 times that of Neisseria gonorrhoeae.

The prevalence of chlamydia has been reported to be as high as 14% among African American females aged 18-26 years and 17% among females with a history of gonorrhea or chlamydia in the previous 12 months. In addition, approximately 100,000 neonates are exposed to chlamydiae annually. The 2007-2012 National Health and Nutrition Examination Survey (NHANES) indicates that an estimated 1.8 million persons aged 14-39 years in the United States have a genital chlamydial infection.^[15]

More than one million sexually transmitted infections (STIs) are acquired every day worldwide.^[16]C trachomatis genital tract infections are common, with an estimated 105.7 million new worldwide cases in 2008.^[17]Serosurveys have documented similar incidence figures in Australia,^[18]New Zealand,^[19]France,^[20]Germany,^[21]and the Netherlands.^[22]A report from the World Health Organization (WHO) Initiative for Vaccine Research (IVR) estimated that there were more than 140 million cases of C trachomatis infection worldwide.^[23]

Age factors in chlamydial genitourinary infection relate to the age of first sexual exposure and the frequency of exposure. Chlamydia is most prevalent in persons aged 15-24 years. Acquisition rates are comparable for the 2 sexes. Women are more likely to be asymptomatic than men (80% vs 50%); however, they are also more likely to develop long-term complications (eg, PID and infertility).

Data from 2011 demonstrate that the disease is most common in adolescents and young adults aged 15-24 years, with higher rates in women and African Americans than in Hispanics and non-Hispanic whites.^[24]

Antibiotic treatment is 95% effective for first-time therapy. The prognosis is excellent if treatment is initiated early and the entire course of antibiotics is completed. Although treatment failures with primary therapies are quite rare, relapse may occur with alternative therapies. Reinfection is very common and is related to nontreatment of infected sexual partners or acquisition from a new partner; thus all sexual partners should be treated.

Deaths are rare and are caused by progression to salpingitis and tuboovarian abscess with rupture and peritonitis. The most significant morbidity occurs when repeated episodes of chlamydia lead to obstruction and scarring of the fallopian tubes, resulting in partial or total sterility. Chlamydia is an indirect cause of mortality from ectopic pregnancies.^[25]Mortality due to ectopic pregnancy is probably more common than is death due to tuboovarian abscess.

Appropriate counseling of infected individuals must be performed. Inform patients of the possible long-term risks and complications of their infection, including the possibility of infertility. Educate them regarding the risk of other STDs. Counsel patients to take steps to prevent reinfection. They should avoid sexual contact until their treatment is completed and all partners also have been evaluated and treated. They should also consider using latex condoms to minimize the chances of reinfection.

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Shahab Qureshi, MD, FACP is a member of the following medical societies: American College of Physicians, College of Physicians and Surgeons of Ontario, Ontario Medical Association