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A tale of two diseases
Trachoma is in a sense two diseases: the infection most apparent in children and the blinding sequelae found in adults. Ocular strains of Chlamydia trachomatis cause repeated episodes of conjunctivitis, with the peak prevalence of infection usually occurring in 3–5 year olds.1 Progressive scarring, entropion, and trichiasis lead to blinding corneal ulceration, typically some 40 years or more later.2 This long lag time between infection and blindness has always been somewhat of a puzzle. Several explanations have been offered. The normal, age related decrease in tears, goblet cells, and lid elasticity may make the elderly more prone to the effects of scarring.3 Existing scars may contract slowly over time. Further episodes of chlamydial infection may cause scarring to progress.4,5 If this last hypothesis is the case, then the frequent recurrence of trichiasis after surgical repair could in part be because of recurrent infection. This is a testable hypothesis. A single dose of oral azithromycin is effective in eliminating chlamydial infection in an individual,6 and treatment given to a community can offer a sustained reduction of infection even a year later.7 With some effort, infection can be prevented, at least for the year or so after surgery.
In this issue of the BJO (p 1282), Burton et al report a trial in which they randomised patients receiving trichiasis surgery into two groups. One group received topical tetracycline post-surgery as standard of care. The other received topical tetracycline and, in addition, they and their household members received a dose of oral azithromycin at the time of surgery and 6 months later. Recurrence of trichiasis 12 months after surgery proved to be a fairly common event, providing the study with some power to detect a difference. However, recurrence was equally frequent in the two arms. Also, chlamydial infection was not a risk factor for recurrence.
This trial makes us think about trachoma differently, even though azithromycia could not be shown to prevent recurrence of trichiasis after surgery
Although the authors could not implicate chlamydia in the failure of trichiasis surgery, secondary analyses suggest that other bacteria may have a role. Identification of a pathogenic species of bacteria colonising the conjunctiva was a twofold risk factor for recurrence of severe trichiasis. Bacterial colonisation may just be a surrogate marker for more severe scarring, which itself is a risk factor for recurrence. However, it is also possible that bacterial infections themselves cause progression of disease. This would not be the first time that non-chlamydial bacteria have been implicated in trachoma,8 but it might be the most convincing evidence so far. Colonisation of the conjunctiva has also been found in other cicatricial conjunctivitides, such as ocular cicatricial pemphigoid (OCP). In fact, corneal ulceration in OCP is often caused by the same species of bacteria that had colonised the conjunctiva on previous visits.9 In Western countries, prophylactic antibiotic drops are sometimes provided to patients at such a high risk for corneal ulcers. Burton et al’s results suggest that maybe we should consider such prophylaxis in trachoma patients after trichiasis surgery.
This was a well designed and well organised trial. Strengths include a large number of patients, a large number of surgeons, good follow up, and excellent microbiology. However, it may not be the last word on the importance of chlamydia in the progression of cicatricial trachoma. Azithromycin is already being distributed to everyone in endemic areas; some may argue that extra doses in older, post-surgical patients are hardly necessary since infection in adults is less common,1 of a shorter duration,10 and a lower load.11 On the other hand, estimates of this progression are higher in areas with more infection (Tanzania) than they are in areas with less infection (Gambia).12–14 Two other groups are examining this question with somewhat similar designs (Emily West, Sheila West, Wondu Alemayehu, and Deborah Dean, personal communications). One trial is being performed in an area of Ethiopia where trachoma is hyper-endemic and the opportunity for re-infection far greater. These studies may or may not produce similar results.
This trial makes us think about trachoma differently, even though azithromycin could not be shown to prevent recurrence of trichiasis after surgery. Currently, programs treat trachoma as two different diseases, reducing infection with antibiotics and eliminating trichiasis with surgery. Burton et al tested whether the link between the two was stronger than appreciated. Their bacteriological results may even suggest an entirely new front in trachoma control. The question of how cicatricial trachoma will progress in the absence of recurrent chlamydial infections is an important one. Even if mass antibiotic distributions and other measures are successful in dramatically reducing infection in entire populations, there will still remain a generation of individuals with scarred conjunctivae. In some areas, we may no longer have to contend with two trachomas, only the cicatricial form. It would have been comforting had this trial found that trichiasis would not recur in the absence of chlamydia. Hopefully, further research will optimise the management of cicatricial trachoma.
Note in Proof
A tale of two diseases