Suppose that you are a new family practice physician and that you spend one weekend each month working in a mobile clinic that goes to underserved neighborhoods in a nearby large city. This weekend, the clinic is serving a neighborhood that is populated primarily by immigrants from North Africa and the Middle East. Most of the residents are quite poor and cannot afford regular medical care. They can call 911 for life-threatening situations (such as a heart attack), but they often have to wait for weeks or even months-until a clinic like yours shows up-to get help for other problems.

Your first patient this weekend is a 34-year-old man who presents with a bad eye infection. The conjunctivae of his right eye are badly inflamed and scarred. The eyelids have become distorted, apparently from the scarring, and have turned inward, so that the eyelashes now constantly abrade the surface of the eyeball. The cornea also appears to be badly damaged, with inflammatory leukocytic infiltrations and superficial vascularization (i.e., pannus formation). Parts of the corneal epithelium are badly abraded an ulcerated, and there is scarring in some of these areas. Not surprisingly, the vision in this eye is very much reduced.

In taking the patient's history, you learn that he grew up in a small village in rural Egypt, where there was no running water. He moved to the U.S. about 12 years ago. When asked about previous eye problems, he remembers that the same eye was infected when he was 13 years old (and still living in the remote village). The symptoms he remembers indicate that he probably had a relatively severe form of conjunctivitis.

Question 2.1: What is your diagnosis?

The patient's symptoms are characteristic of trachoma, a dangerous form of chronic conjunctivitis that, if left untreated, often leads to extensive damage of the cornea and permanent blindness. The clinical diagnosis of classic trachoma can be made if any two of the following signs are present: (1) lymphoid follicles on the upper tarsal conjunctiva; (2) conjunctival scarring that is typical of trachoma; (3) vascular pannus; and (4) limbal follicles or their sequelae, which are known as Herbert's pits. Definitive diagnosis of trachoma requires demonstration of the causative agent by Giemsa- or immunofluorescent-stained smears, by isolation in cell cultures, or by newer non-culture-based methods such as PCR.

Question 2.2: What is the causative agent?

The causative agent of trachoma is Chlamydia trachomatis, an important member of the Chlamydiaceae family of bacteria. The Chlamydiaceae are Gram-negative, but they lack the peptidoglycan layer that is found in nearly all other Gram-negative cell walls. In addition, they are obligate intracellular parasites that are able to reproduce only inside of suitable eukaryotic host cells. The Chlamydiaceae exist in two morphologically distinct forms: the small (300-400-nm), infectious elementary body (EB) and the larger (800-1000-nm), noninfectious reticulate body (RB). The EB is metabolically inactive (somewhat like a spore) and can survive outside of a host cell. EBs attach to receptors on the surfaces of host cells, thereby stimulating their uptake into those cells. Inside of the host cells, EBs differentiate into metabolically active RBs and then reproduce via binary fission for 18-24 hours. The newly produced RBs soon differentiate into infectious EBs, which are released when the host cell dies and ruptures. The released elementary bodies are then free to infect and kill additional host cells, thereby prolonging the infection process. To date, 19 serotypes (commonly called serologic variants or serovars) of C. trachomatis have been defined, based on antigenic differences in their major outer membrane proteins. Serovars A, B, Ba, and C are the principal causative agents of classic trachoma.

Question 2.3: What other eye diseases does this agent cause?

Chlamydia trachomatis biovars D through K can cause adult inclusion conjunctivitis, an acute follicular conjunctivitis that is associated with genital infections. It presents as the acute onset of unilateral follicular conjunctivitis and preauricular lymphadenopathy similar to that seen in acute adenovirus or herpesvirus conjunctivitis. If left untreated, the disease may persist for 6 weeks to 2 years. It is often associated with corneal inflammation in the form of discrete opacities ("infiltrates"), punctuate epithelial erosions, and minor degrees of superficial corneal vascularization. Conjunctival scarring and eyelid distortion occur only rarely (in contrast to trachoma). Neonatal conjunctivitis develops in infants exposed to C. trachomatis at birth. The infant's eyelids swell, hyperemia occurs, and a copious purulent discharge is produced. If left untreated, the infection may continue for months and lead to conjunctival scarring and corneal vascularization, with concurrent loss of visual acuity.

Question 2.4: What non-eye diseases does this agent cause?

Chlamydia trachomatis is best known for causing nongonococcal urethritis (NGU), currently the most frequently occurring STD in the U.S. The symptoms are similar to those of gonorrhea. C. trachomatis is also associated with Reiter's syndrome (most likely initiated by genital infections) and lymphogranuloma venereum (LGV).

Question 2.5: How is this disease transmitted?

Transmission is usually from eye to eye, primarily on hands, towels or contaminated clothing, or other fomites. However, the disease is also transmitted by eye-seeking flies that carry ocular discharges from the eyes of infected children to those of uninfected children in endemic areas (i.e., they function as mechanical vectors). Because a high percentage of children in endemic regions carry C. trachomatis in their respiratory and gastrointestinal tracts, trachoma may be transmitted by droplet infection or through fecal contamination. The patient in this case might have been infected by contact (or possibly repeated contact) with an infected individual in his neighborhood. It is more likely, however, that he was infected when he was a child living in an endemic region (i.e., the serious conjunctivitis that he had when he was 13 years old-most likely follicular conjunctivitis). Childhood infections sometimes appear to clear up spontaneously, but actually just become subclinical (and more or less latent). Conjunctival scars may continue to shrink over the years, eventually resulting in distortion of the eyelids and subsequent corneal scarring. This may lead to recurrence of an acute infection, or an acute infection may occur (spontaneously) at some other time after the childhood years (for reasons that are not yet well understood).

Question 2.6: Where is this disease endemic?

Trachoma tends to be endemic in communities where the living conditions are crowded and sanitation is poor. The principal endemic regions now are northern Africa, sub-Saharan Africa, the Middle East, and parts of Asia. In the U.S., endemic disease occurs in some Mexican-American communities, and sporadic acute cases of trachoma are seen in immigrants from endemic area.

Question 2.7: How important is this disease?

The worldwide incidence and severity of trachoma has decreased dramatically during the past 35 years, primarily as a result of improving hygienic and economic conditions in some parts of the world. Nevertheless, trachoma is still the principal cause of preventable blindness in those areas where it is still endemic (see above).

Question 2.8: How should you treat this case?

Early trachoma can be treated with an antibiotic ointment (typically containing erythromycin and tetracycline) and, if necessary, surgical correction of inturned eyelids. However, there is nothing that can be done to reverse the loss of vision or total blindness associated with an advanced case such as the one seen in this patient. The man should be treated with antibiotics to prevent spread of the disease to his other eye, but the damage to his diseased eye is permanent.