We previously demonstrated that chlamydial infection at the time of TT surgery and at follow up was a significant risk factor for recurrence in a trachoma endemic district in Nepal.13
In the current community intervention study, we found a significant reduction in the incidence of TT recurrence for the azithromycin group compared with the placebo group at 6 months for those who had major TT at baseline. While the cumulative incidence at 6 months did not quite reach statistical significance, the p value of 0.057 (table 5) is supportive of the incidence data. For those individuals with minor TT at baseline, there was a greater number of TT recurrences in the azithromycin treatment group compared with placebo, although the numbers did not reach statistical significance. Importantly, the placebo group at 6 months and 12 months had a significantly higher number of recurrences for patients with major TT and severe scarring at baseline compared to those who had minor TT at baseline (tables 4 and 5; p
0.003). This would be expected given that severe scarring has been associated with TT recurrence.12
The cumulative incidence at 12 months showed a significant reduction in recurrence for those with major TT at baseline in the azithromycin group, which would be expected based on the 6 month findings. Thus, our data collectively support the notion that azithromycin treatment appears to be effective in preventing postoperative TT recurrence up to 12 months for patients with major TT at baseline.
Variation in surgical outcome for TT has been reported in previous studies where recurrence rates were 8–12.1% at 3 months,26,27
6.2–11.1% at 6 months,13,27
and 9–25% at approximately 1 year.11,13
Only one surgeon operated during the present study to eliminate inter‐surgeon variation as a confounding factor. Yet, we noted seven cases of surgical failure at 3 months. These cases were excluded from the data analyses since they would confound the effect of treatment.
We also found a high rate of active trachoma at the time of surgery. Patients were consistently graded by two ophthalmic assistants who had worked on previous trachoma studies where the concordance of active trachoma and infection was high.13
However, conjunctival inflammation might be due to infection with bacteria other than C trachomatis
. In many trachoma endemic countries including Nepal, there can be seasonal or non‐seasonal outbreaks of conjunctivitis from multiple bacterial species, including Haemophilus influenzae, Haemophilus aegyptius
, and Streptococcus pneumoniae
Consequently, co‐infection may promote inflammation,1
which may have contributed to the higher number of individuals who were graded with active trachoma at baseline in our study.
Chlamydial infection was 9.0% at baseline while the infection rate in our previous study in Nepal was
Chlamydial infection was determined by the same commercial test in both studies. The current study was conducted near the East‐West highway while the previous study was conducted in a more remote district with difficult access. Proximity to roads often correlates with environmental and sanitation improvement and higher socioeconomic status (SES), which has historically been linked to a substantial reduction or elimination of trachoma in countries undergoing some industrial development.10
This effect likely contributed to the lower rates of infection in the current study. The true rates of chlamydial infection may also be underestimated as there is recent evidence that the organism may persist in the conjunctiva of trachoma patients20
as well as the cervix.19
Persistent chlamydiae may evade detection by residing in subepithelial tissues that would not be accessible to current swabbing techniques.
We also evaluated whether topical tetracycline may have contributed to the low infection rates. At baseline, 56.9% and 61.8% of the azithromycin and placebo groups, respectively, received topical tetracycline for active trachoma. This should not affect the outcome because there was no significant difference between the azithromycin and placebo groups for tetracycline treatment. Furthermore, there were no significant differences at subsequent follow up time points where numbers of active trachoma cases were very small and thus few patients received tetracycline (table 2). While topical tetracycline would be expected to decrease infection rates after the baseline treatment, this response would be unlikely to be sustained for 6 months16
and, thus, unlikely to impact TT recurrence at 6 or 12 months. In fact, if it did, we would expect fewer recurrences in both azithromycin and placebo groups, which was not the case.
In conclusion, azithromycin treatment significantly improved the rate of TT recurrence compared with placebo up to 12 months for patients with major TT at the time of surgery, although there was a trend for increased TT recurrence in the azithromycin treatment group among those with minor TT at baseline. Larger studies, including randomised clinical trials, would help to elucidate whether azithromycin treatment will decrease the risk of TT recurrence among those with minor TT and in other endemic populations. Research in trachoma areas with higher chlamydial infection rates will also be important to determine the duration of treatment efficacy.