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Introduction to trachoma

Trachoma is a chronic conjunctivitis caused by intra-cellular infection of epithelial cells with Chlamydia trachomatis, usually chlamydial strains belonging to the so called ocular serovars A, B, Ba or C. Trachoma is one of the world's leading causes of preventable blindness [see: prevalence] and is currently the target of a WHO campaign to eradicate the disease by the year 2020 [see: prevention]. Active trachoma, associated with intermittent shedding of viable chlamydiae, ranges from a mild asymptomatic inflammation with collections of immune cells visible on the upper tarsal conjunctiva [follicular trachoma grade TF; see: trachoma in pictures for the clinical grading] to an intense inflammatory response [grade TI] in which most of the tarsal plate is obscured by capillary congestion. Repeated ocular infections cause scarring of the conjunctiva (scarring trachoma grade TS; often referred to as cicatricial trachoma). This leads to distortion of the eye-lids (entropion) and deviation of the eyelashes so that they beat the orb of the eye (trichiasis, grade TT), resulting ultimately in corneal abrasion. opacity and visual loss (grade CO). 

It is clear that some degree of protective immunity to trachoma occurs because the active disease is a disease of childhood. C. trachomatis-specific antibody responses can be found in the blood and in tears following natural infection. There is evidence from both field studies of trachoma and from experimental ocular infection in non-human primates that limited, short-term, serovar-specific immunity occurs.  Local secretory IgA (sIgA) antibody responses against chlamydiae are associated with limited protection from ocular infection [Bailey et al., 1993], perhaps by targeting neutralization sites on the surface exposed chlamydial major outer membrane protein.  However the bulk of recent evidence from gene knock-out animal models indicates, as for other intracellular bacterial infections, that cell mediated immunity, particularly  and CD4+ T-helper cells,  is critical for the eradication of established intracellular infection [Johansson et al., 1998] [see: interferon gamma].  A mathematical model for this has been developed [Wilson et al., 2003].

Although the incidence and duration of active trachoma episodes decrease with age [see: pathogenesis], repeated infection is more likely to be associated with intense inflammation [see: repeated infection]. Empirical attempts in the 1960s and 1970s to prevent trachoma by vaccination with crude whole organism vaccines were unsuccessful, as, although some subjects were protected, there was a suggestion that other vaccinated subjects developed enhanced disease [Sowa et al., 1969]. These adverse hypersensitivity responses were not serovar specific and they persisted longer than any protective immunity [Wang & Grayston, 1967]. Various chlamydial antigens have been implicated in these adverse hypersensitivity responses, most notably chlamydial heat shock protein [Morrison, 1991]. Convincing evidence for this hypothesis is lacking, although higher antibody levels to chlamydial heat shock protein 60 are found in subjects with trachomatous scarring compared with controls lacking the disease from endemic communities  [Peeling et al., 1997]. While the role of heat shock protein is uncertain, it seems likely that there are host genotype determined differences in susceptibility to severe scarring disease [see: pathogenesis; also host genotype]. In this respect it is interesting that the antibody response to chlamydial heat shock protein was found to be associated with specific HLA class II alleles which might also affect the protective T-helper 1 response [Peeling et al., 1997]. It has been suggested that individuals who mount a predominantly T-helper 2, antibody-dominated response might be more likely to develop severe scarring disease than those who mount an effective cytotoxic T lymphocyte  response [Conway et al., 1996]. For a review of trachoma see the following web pages and also Mabey et al., 2003.

[Note: The trachoma section first illustrates the clinical disease and its grading, then presents information on its prevalence, transmission, pathology and prevention].

[MEW] August 2003

NEXT: Clinical presentation and grading

References

Bailey, R. L., Kajbaf, M., Whittle, H. C., Ward, M. E. & Mabey, D. C. (1993). The influence of local antichlamydial antibody on the acquisition and persistence of human ocular chlamydial infection: IgG antibodies are not protective. Epidemiology and Infection 111, 315 – 324.

Conway, D. J ., Holland, M. J., Campbell, A. E., Bailey, R. L., Krausa, P., Peeling, R. W., Whittle, H. C. & Mabey, D. C. (1996). HLA class I and II polymorphisms and trachomatous scarring in a Chlamydia trachomatis-endemic population. Journal of  Infectious Diseases 174, 643 -646.

Johansson, M., Schon, K., Ward, M. E. & Lycke, N. (1997). Frontline: Studies in knockout mice reveal that anti-chlamydial protection requires TH1 cells producing IFN-gamma: is this true for humans? Scandinavian Journal of  Immunology 46, 546 - 552.

Mabey, D. C., Solomon, A. W. & Foster, A. (2003). Trachoma. Lancet 362, 223 - 229. Full article .

Morrison, R. P. 1991. Chlamydial hsp60 and the immunopathogenesis of chlamydial disease. Seminars in Immunology 3, 25 – 33.

Peeling, R. W., Bailey, R. L., Conway, D. J., Holland, M. J., Campbell, A. E., Jallow, O., Whittle, H. C. & Mabey, D. C. (1997). Antibody response to the 60-kDa chlamydial heat-shock protein is associated with scarring trachoma. Journal of Infectious Diseases. 177, 256 - 259.

Sowa, S., Sowa, J., Collier, L. H. &. Blyth, W. A.  (1969). Trachoma vaccine field trials in The Gambia. Journal of Hygiene (London) 67, 699 – 717.

Wang, S. P., and J. T. Grayston. 1967. Pannus with experimental trachoma and inclusion conjunctivitis agent infection of Taiwan monkeys. American Journal of  Ophthalmology 63 (Suppl.), 1133 – 1145.

Wilson, D. P., Timms, P. & McElwain, D. L. (2003). A mathematical model for the investigation of the Th1 immune response to Chlamydia trachomatis. Mathematical Bioscience 182, 27 - 44.

NEXT: Trachoma in pictures; clinical grading