Chlamydiae have long been important causes of ocular infections and are still the second leading cause of blindness in Africa (1,2). Trachoma is one of the oldest recorded diseases of mankind, documented in the Egyptian Eber’s papyrus in 1900 BC (2,3). It is still endemic in sub-Saharan Africa, including Ghana, Mali, and Tanzania, as well as eastern Mediterranean countries such as Iraq, Saudi Arabia, United Arab Emirates, Qatar, and Oman (1,2,4,5). According to the World Health Organization (WHO) there are 146 million people worldwide with active trachoma (2). It is one of the greatest single causes of preventable blindness and impaired vision in the world today (6). Western Europe and the United States have been trachoma free in the last century, correlating with economic development, and in Southeast Asia progress is being made for the same reason (4). Transmission of the chlamydial agent causing trachoma is by eye-to-eye or hand-to-eye contact. The disease is usually acquired in early childhood. Chronic inflammation from recurrent infections leads to conjunctival scarring and blinding complications in adults. A number of environmental factors such as low living standard and poor hygiene, influence prevalence and severity of trachoma.

The second ocular disease caused by Chlamydia trachomatis is adult inclusion conjunctivitis, also called paratrachoma. Reported prevalences range from zero to 28% (7, 8, 9, 10), but population selection biases, the absence of controls, and differing diagnostic assays used in these studies explain the wide range of results. Adult inclusion conjunctivitis typically occurs in sexually active young adults following transfer of bacteria from the genitalia to the eye. There is a high incidence of cervical or urethral chlamydia in these individuals (9, 10, 11).

With the advent of widespread neonatal ocular prophylaxis, gonococcal infections have decreased and C. trachomatis is now the most common cause of ophthalmia neonatorum in industrialized countries as well as in several developing countries (12, 13, 14, 15). It may be responsible for 20% to 73% of all cases of neonatal conjunctivitis (16, 17, 18). In developing countries the prevalence of genital chlamydial infection in pregnant women ranges from 7% to 29%. One third of infants exposed at birth will develop chlamydial disease (2,14). In North America and Europe, 2% to 6% of all newborns are infected with neonatal chlamydiae (19). However, the incidence of C. trachomatis conjunctivitis is declining, as shown in Argentina with 4.39/1,000 live births in 1995 down to 0.78/1000 live births in 1998 (2).

Chlamydia are unique among bacteria in that they are obligate intracellular gram-negative organisms with a complex intracellular development cycle that consists of an infectious metabolically inactive elementary body and a noninfectious, metabolically active reticulate body. They are unable to produce adenosine triphosphate and thus are energy parasites
(55). Because of their singular biologic character, the chlamydiae are assigned their own order, the Chlamydiales, consisting in turn of one family, the Chlamydiaceae, two genera, the Chlamydia and the Chlamydophila, and nine species. Human chlamydial infection is often caused by Chlamydia trachomatis, less frequently by Chlamydophila pneumoniae, and rarely by Chlamydophila psittaci, Chlamydophila abortus, or Chlamydophila felis (56). C. trachomatis isolates are commonly classified into 15 distinct serovars, designated A-K, L1-L3, and MoPn, which is a mouse adapted strain. Serovars A-C cause trachoma, serovars D-K (and occasionally, variants of B or Ba) are primarily associated with sexually transmitted infections, and serovars L1-L3 cause lymphogranuloma venereum (57,58). C. trachomatis is essentially a pathogen of mucosal surfaces, infecting and replicating within epithelial cells. The infected cell ruptures, releasing thousands of elementary bodies.

The pathophysiology of chronic chlamydial disease is still unknown in detail, but most likely depends on both parasite and host factors. Recent data provide compelling evidence for a chlamydial cytotoxin for epithelial cells present in the elementary body and delivered to host cells very early during infection. This cytotoxin may also provide a mechanism for immune evasion compatible with the clinical characteristics of persistent oculogenital infections (57). Infection with C. trachomatis leads to the upregulation of several functionally important genes in the host cell such as IL-11, LIF, chemokine gene MIP2a, transcription factor genes, apoptosis-related genes, and adhesion molecule genes such as ICAM-1 (59). Chlamydia seems to reprogram the host cells at various key positions that act as intra- or intercellular switches (59).

Ocular infections are characterized by distinct immunologic and pathologic responses to the different chlamydial strains causing either trachoma or inclusion conjunctivitis. The immune response seems to confer partial protection against subsequent infection, yet appears also to be responsible for much of the observed pathology and tissue destruction seen in trachoma. In trachoma, repeated infection with the causative organism, perhaps exacerbated by superinfection with other organisms, is necessary to cause severe conjunctival scarring and blinding complications. The stimulus for continual inflammation may not be from repeated exposure to chlamydial surface antigens but may rather be due to a labile product released by the living organisms (60). Cellular responses elicited in nonimmune cells (i.e., mucosal epithelial cells) infected by chlamydiae may be necessary and sufficient to account for chronic and intense inflammation and the promotion of cellular proliferation, tissue remodeling, and scarring (61). Inflammatory cells become activated in both an antigen-nonspecific and, for reinfection, an antigen-specific manner to produce their own repertoire of cytokines and growth factors (61).

Both humoral and cell-mediated immune responses are involved. Target antigens are the major outer membrane protein (MOMP) and heat shock proteins (HSP60) (62,63). Antichlamydial antibodies can neutralize chlamydiae and block attachment and internalization of the organism (62). Experimental studies in monkeys and human indicate that tear immunoglobulins, especially immunoglobulin A (IgA), may play a vital role in mediating protective immunity (64,65). But antibodies may limit the extent of chlamydial multiplication and prevent more invasive disease rather than to effect a cure (66). Moreover, antichlamydial antibodies do not protect against reinfection (67,68). Serum IgG antichlamydia antibody was detected in 42% of patients with trachoma and in 37% of patients with acute inclusion conjunctivitis by Numazaki et al. (69). Antichlamydial IgM was present in 13% of patients with trachoma and in 33% of patients with acute inclusion conjunctivitis. Forty percent of the trachoma patients and 34% of patients with inclusion conjunctivitis were IgA-positive. However, antichlamydial IgG and IgA was also present in 25% and 22% of healthy controls, respectively, compared to IgM, which was positive in only 2% of the healthy population (69). IgA antibodies in tears were detected as early as 5 days after onset of clinical symptoms in patients with inclusion conjunctivitis. The IgA response in tears was not significantly correlated with the severity of the ocular infection, whereas serum IgA titers increased with the severity of clinical findings (70, 71, 72). In neonatal inclusion blennorrhea, passively transferred maternal antibodies supposedly do not confer any protection against the transmitted chlamydiae. The detection of IgA antibodies in tears and serum among chlamydia-positive neonates without corresponding maternal antibodies may suggest a production of antichlamydial IgA antibodies in the newborn. The antibody response in serum of newborns with chlamydial conjunctivitis is poor, as would be expected (70, 71, 72).