These case–control studies investigated the association between conjunctival bacterial infection and trachomatous trichiasis and scarring. Eyes with established trichiasis were significantly more likely to have conjunctival bacterial infection than normal control subjects. This association strengthened with increasing disease severity, indicated by the number of lashes touching the eye. It is likely that trichiasis facilitates the introduction of bacteria into the conjunctival sac. Moreover, trichiasis may also compromise the resolution of a conjunctival bacterial infection by providing a “foreign body” surface for attachment. Eyes with tarsal conjunctival scarring without trichiasis tended to have more bacterial infection than control subjects; however, this difference was not statistically significant, possibly because of a limited sample size. It is possible that we were not able to culture all bacteria in these subjects, given the environmental and logistic constraints of working in rural Africa. However, these factors would have affected both groups equally, so would not bias any inferences that are drawn.
The central event in progressive trachomatous scarring, in common with other cicatricial conditions, is probably chronic inflammation. Conjunctival inflammation could be triggered or maintained by several factors including chlamydial and bacterial infection, ocular surface dryness, a smoldering, poorly regulated immune response and mechanical irritation from trichiasis. In this study
C. trachomatis infection was very rarely detected. Therefore, it is unlikely to play a major role in driving disease progression in this environment at present. In contrast, bacterial infection was detected more frequently, particularly when trichiasis was present. Bacterial infection has previously been associated with conjunctival inflammation in eyes with trichiasis.
7 9 However, a prospective study with frequent sampling for bacterial culture over several years is needed to determine the contribution of bacterial infection to disease progression.
Earlier studies have explored the relationship between bacterial infection and clinically active trachoma in children.
12 13 14 15 16 17 It was thought that in regions where seasonal epidemics of bacterial conjunctivitis occurred bacterial infection may exacerbate the pathogenesis and transmission of trachoma.
14 It was suggested that the severity of conjunctival inflammation from
C. trachomatis infection may be increased by a coinfection with other bacteria. In addition, it was thought that person to person transmission of
C. trachomatis may be enhanced by the presence of more copious ocular secretions. However, it is difficult to draw definite conclusions from these studies as most did not have normal control groups for comparison. In addition, direct comparison with more recent studies is complicated by the use of the older MacCallan trachoma grading system. The range of organisms cultured from these children appears to be quite similar to that found in adults with scarring complication of trachoma. The lower level of
Haemophilus influenzae found in this study (compared with earlier studies in children) may be due the very effective Hib vaccination program, which was introduced into The Gambia in 1997.
18
Several animal models have been used to investigate the effect of coinfection with
Chlamydia and other bacteria.
19 20 21 These studies have given varied results. In a feline model of active trachoma using
Chlamydia psittaci, coinfection with streptococci exacerbated the inflammatory disease.
19 However, in a guinea pig model also using
C. psittaci, additional infection with
Staphylococcus aureus did not alter the course of the inclusion conjunctivitis.
20 The effect of secondary bacterial infection was also investigated in a monkey model of active trachoma, generated by repeated conjunctival inoculation with
C. trachomatis. Monkeys infected with
Chlamydia were no more susceptible to bacterial infection than were control monkeys, and the disease severity caused by a combined infection was similar to animals only inoculated with
Chlamydia.
21 In a separate series of experiments conducted on monkeys with conjunctival scarring produced by repeated exposure to
C. trachomatis, a more severe and sustained inflammatory reaction was produced by bacterial infection, compared with control animals.
21
Corneal opacification, the cause of blindness in trachoma, may result from various insults. Trichiasis is probably the single most important factor.
7 9 However, new corneal opacification has been found to develop after the successful surgical treatment of trichiasis.
9 This outcome suggests that other factors such as infection (bacterial and possibly chlamydial), ocular dryness, and chronic conjunctival inflammation may also contribute. Trichiasis traumatizes the corneal epithelium increasing vulnerability to secondary bacterial infection. Moreover, the increased prevalence of bacterial pathogens infecting the conjunctiva of eyes with trichiasis probably makes infection a frequent event.
6 9 In the present study although severe trichiasis (10+ lashes touching the eye) was found to be the strongest risk factor for corneal disease, bacterial infection was also associated with increased risk of corneal opacification.
Overall, these data suggest that bacterial infection may be more important in the pathogenesis of late-stage trachoma than previously recognized. Eyes with increasing severity of disease appear to be more susceptible to bacteria. It is likely, although not proven, that the bacterial infection promotes conjunctival inflammation, contributing to progressive scarring. In addition, bacterial infection is probably an important factor in the development of blinding corneal opacification in trachoma.
The authors thank the ophthalmic nurses of the Gambian NECP and the field staff from the Medical Research Council Laboratories for their hard work, often under challenging conditions.