Diseases Caused by Chlamydiae

The Pathogen

Chlamydiae have a gram-negative cell wall structure consisting of an outer membrane that contains lipopolysaccharide and an inner cytoplasmic membrane. The outer membrane contains a single 40-kD major protein (OmpA, also known as MOMP) and two cysteine-rich, minor outer membrane–associated proteins (OmcA and OmcB). Through intermolecular and intramolecular disulfide bonding, these proteins form a complex that provides structural rigidity.

Chlamydiae have small genomes ( C. trachomatis contains 894 protein-coding genes, and C. pneumoniae contains 1052 genes). Most strains of C. trachomatis and some strains of C. psittaci contain a 7-kilobase cryptic plasmid.

Chlamydiae grow only within intracellular membrane-bound vacuoles, termed inclusions, which seclude the organism from extracellular and cytoplasmic environments. All chlamydiae share a distinct biphasic developmental cycle ( Fig. 294-1 ) that includes an extracellular, metabolically inactive, infectious form (an elementary body) and an intracellular replicative form (a reticulate body). In vitro studies have shown that chlamydiae may enter a persistent state under certain conditions (e.g., penicillin treatment, challenge with certain cytokines, restriction of select nutrients) in which they have reduced metabolic activity and may be more refractory to antibiotic treatment. Chlamydiae are unable to synthesize adenosine triphosphate and therefore depend on the host cell for nutrients to meet their energy requirements.

Trachoma

Epidemiology

Trachoma is a chronic follicular conjunctivitis. The overall incidence is unknown, but the World Health Organization (WHO) estimates that 21.4 million people have active trachoma. Trachoma is endemic in more than 44 countries, and an estimated 137 million people are living in trachoma-endemic areas. Trachoma is especially common in poor areas of sub-Saharan Africa, where its prevalence in children may exceed 40%.

Trachoma is the most common preventable cause of blindness worldwide, affecting 1.9 million people by WHO estimates. Active trachoma often occurs in the first few years of life. The inflammation from recurrent or persistent trachoma can lead to conjunctival scarring, which can ultimately cause corneal damage and blindness later in life. The C. trachomatis serovars that produce trachoma are spread by direct contact with fingers or fomites (e.g., washcloths, handkerchiefs) that are contaminated with eye discharge from an infected person or by eye-seeking flies. Because of this mode of transmission, trachoma often clusters in households. Risk factors for trachoma include poor facial hygiene, limited access to water, poor sanitation, and proximity to other infected persons or to a heavy density of eye-seeking flies.

Clinical Manifestations

The two stages of trachoma disease can overlap. Initially, trachoma begins as an inflammatory follicular conjunctivitis (i.e., active trachoma). On eversion of the upper eyelid, white to pale yellow lymphoid follicles can be visualized on the superior tarsal conjunctival surface, and papillae may be noted between follicles. Minimal watery or mucoid ocular discharge also may be seen. In more severe active trachoma, the conjunctiva can be thickened and edematous. Subsequently, conjunctival inflammation can progress to cause scarring of the upper tarsal conjunctiva (the cicatricial stage of disease). Scarring deforms the eyelid and can lead to an inward turning of the eyelashes, which can result in corneal abrasion (trichiasis). Over time, trichiasis causes corneal edema, ulceration, vascularization (pannus), scarring, and opacification. The corneal damage leads to decreased vision or blindness, mostly in young adults and middle-aged persons. Viral conjunctivitis (e.g., adenovirus; Chapter 333 ) presents similarly to active trachoma, but it is self-limited and usually resolves within a week. Trachoma can be complicated by superinfection with other bacterial pathogens (e.g., Haemophilus influenzae ), which should be considered when purulent ocular discharge or significant inflammation of the bulbar conjunctiva is present.

Diagnosis

Because the majority of trachoma cases occur in developing countries without access to laboratory testing or the necessary resources, trachoma is often diagnosed clinically on the basis of findings of active trachoma (follicles on the upper tarsal conjunctiva or pronounced inflammatory thickening of the tarsal conjunctiva) or cicatricial disease. When laboratories are available, detection of C. trachomatis by nucleic acid amplification is the most sensitive diagnostic test, provides definitive evidence of active trachoma, and may identify infection in subjects with minimal clinical evidence of active trachoma. For adults with late scarring, C. trachomatis usually is not detected by any of these assays.

Treatment

Prevention

The WHO is committed to eliminating blinding trachoma by 2030 and recommends that all countries with endemic trachoma adopt the SAFE strategy: surgery (for trichiasis), antimicrobials (periodic community-wide treatment), facial cleanliness, and environmental improvement. Mass treatment of a community with single-dose oral azithromycin is safe, can dramatically reduce the prevalence of infection for up to 1 year after treatment, and reduces mortality in children. Annual azithromycin treatment is recommended for trachoma-endemic areas. However, trachoma can recur after mass treatment, due in part to decreased herd immunity. Repeated mass treatment (every few months) provides herd protection to the entire community.

Mass antibiotic treatment is unlikely to be successful as the sole intervention for eliminating trachoma if other factors that facilitate transmission are not addressed. Face washing and good hygiene help reduce the risk for transmission through contact with fingers and flies. Better environmental conditions through measures that reduce the density of flies in households and the community, improved waste management, and access to clean water can also limit transmission. Improvement in socioeconomic conditions in a community correlates with a decline in the prevalence of trachoma.

Sexually Transmitted Chlamydial Infections

Epidemiology

Chlamydia is the most prevalent bacterial sexually transmitted infection in the United States. About 1.6 million infections were reported to the Centers for Disease Control and Prevention (CDC) in 2020. The number of reported cases has increased since a chlamydia screening program was implemented, but data also support a true increase in the number of cases. Taking into account underreporting and underscreening, the CDC estimates that more than 2.8 million new chlamydial infections occur annually in the United States.

Higher prevalence rates of chlamydia have been associated with younger age sexually active adolescents and young adults, as well as with new or multiple sexual partners. The prevalence is highest in the Southeastern United States. The prevalence of chlamydia is higher in women than in men, but it is unclear whether this higher prevalence is due to higher screening rates in women or whether women may be more susceptible to acquisition or persistence of infection. The estimated total cost attributable to chlamydial disease in the United States exceeds $691 million annually. From a global perspective, WHO estimates that approximately 127 million new cases of chlamydia occur annually. In addition to the adverse effects on the reproductive health of women, chlamydia has a substantial impact on prenatal and perinatal outcomes, and it facilitates the transmission of human immunodeficiency virus (HIV).