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Re: Concerns

Posted by skwest on 12 Aug 2009 at 15:26 GMT

RE: Ray, et al. When can antibiotic treatments for trachoma be discontinued? PLoS Negl Trop Dis 3(6): e458. doi:10:1371/journal.pntd.0000458

Letter to the Editor

Dear Editor;

The article by Ray, et al, concerns the highly relevant topic of ceasing mass antibiotic administration in trachoma endemic areas, and my colleagues have undertaken considerable work. Perhaps they can clarify for me several issues that make it difficult to interpret what they have done, to wit:
1. The study purports to reflect three countries, yet the data for Tanzania is from one village. While the authors report that 15 balozis were enrolled, in fact balozis are scattered collections of households within a village and these data are from one village. It is hard to imagine how the authors can conclude “this area of Tanzania” is meso-endemic when referring to a single village. If I recall, one of the authors has gone on record as saying that data from a single village are not adequate, and in this case, I would heartily agree (1).To extrapolate to the whole of Tanzania, or even suggest these balozi represent communities, seems unwise.
2. The authors fail to mention that the village in Tanzania was not only treated with azithromycin, but had topical tetracycline given to each person who had TF at interim visits as well. This may explain the anomalous finding of higher mean prevalence if infection at baseline in the village in Tanzania compared to the Gambia, but the model finding that three treatments would decrease infection to 0% in Tanzania but only to 2% in The Gambia. Unfortunately, the authors did not include in their review another article from Tanzania with a far more typical village, where it is clear that multiple rounds will not eliminate infection (2). The statement that “trachoma transmission in many of the Tanzanian communities” is low is simply unsubstantiated and belied by a recent report from villages across Tanzania (3).
3. While the authors allowed variation in the threshold for 5% or less infection, there is not a clear presentation of the risk, based on empirical data (rather than a model) of re-emergence at any of the thresholds studied. This is a key concept, as the notion of graduating a community assumes any lingering infection will not lead to re-emergent trachoma necessitating re-institution of control programs. While the single village in Tanzania did not experience re-emergence with infection below 2%, nor the hypo-endemic villages of The Gambia, there are ample data from many villages in Tanzania and from the authors own work in Ethiopia to suggest this is a problem.
This paper, where the results report that three annual mass treatments would reduce infection in Tanzania to 0.03% and the conclusion suggests a 5% target, I fear should be questioned at best and at worse will continue to foster a misconception that has translated into the worst possible outcome for National Trachoma Control Programs like Tanzania-the “three annual mass treatments and you are done” approach.


Sheila West, Ph.D.
Johns Hopkins University


1. Lietman TM, Neuwelt MD, Gandhi NG, Dalmon CA, Benitah N. Trachoma research: it takes more than a village. Lancet. 2006 ;367:395
2. West, SK Munoz B, Mkocha H, Gaydos C, Quinn T. Trachoma and ocular Chlamydia trachomatis were not eliminated three years after two rounds of mass treatment in a trachoma hyperendemic village.Invest Ophthalmol Vis Sci. 2007 ;48:1492-7
3. Mkocha H, Munoz, B, West, SK. Trachoma and Ocular Chlamydia Trachomatis Rates in Children in Trachoma –endemic communities enrolled for at least three years in the Tanzania National Trachoma Control Program. Tanz J Health Res. 2009; 11:pp.

No competing interests declared.

RE: Concerns

tlietman replied to skwest on 27 Aug 2009 at 15:27 GMT

Dr. West,

Thank you for posting these comments. Specific responses to your 3 concerns:

1) We agree with you completely. A single community is not representative of an entire country. Any results from the Tanzanian community studied here cannot generalize to the entire country. We are surprised that you would have thought this, and we too hope that readers do not get that impression from this report—it takes more than a village. We attempted to specifically refer to the communities studied, but perhaps our wording was not clear enough in all locations. Let us attempt to be clearer now. One of the purposes of this project was to demonstrate that different results are expected in different locations. There is no reason that results as varied as, or more varied than these could not be observed in the same country.

The three sites in this study used completely different geographical units: state teams in Ethiopia, balozis in Tanzania, and villages in the Gambia. Although these each contained roughly the same number of children (24-50), they were found to have very different inter-unit variance and inter-unit transmission in the best fit models (Table 2). For example, there was little variation between the Tanzanian balozis studied and a great deal of inter-balozi transmission, which is completely consistent with your comment that these are really large households (or perhaps neighborhoods) in the same overall community.

2) Clinically active trachoma cases in the Tanzanian balozis modeled in this report were indeed treated with topical tetracycline, but only after the 6-month visit—thus this could not have affected the baseline, 2-month, and 6-month data used to fit the model. Note that in this area infection decreased from 2 to 6 months in the absence of tetracycline treatment. The other Tanzanian community that you referred to received only two mass antibiotic distributions 18 months apart, one of which had a coverage of 70%. Here, we modeled three annual distributions of 80% coverage—it is not surprising that the results are different. Also, infection was not found to fall below 5% in your Tanzanian community, so graduation would never have been triggered. Your other reference sounds quite interesting, but we have been unable to find it in the location cited.

3) This paper compared the prevalence of infection in children one year after three annual treatments to the same prevalence after a strategy which graduated communities when infection was reduced below 5% in children. There was little difference between the two strategies in terms of effectiveness in all 3 settings. This is because infection is gradually disappearing in the model of a hypo-endemic area such as the community we had data for in Tanzania. Infection is only rarely reduced below 5% in the model of the hyper-communities found in Ethiopia, so the graduation strategy is rarely adopted. In the Gambia, the communities with lower transmission were more likely to graduate. Note that there are significant cost differences in the different areas, and we did not recommend, nor would it be likely one would be able to justify using this graduation approach in severely affected areas similar to the Ethiopian communities studied here.

We would strongly disagree that these results suggest a “three and done approach” everywhere. However, in some settings we expect that not even three treatments are necessary.

The paper over all is meant for readers to consider alternatives to repeated mass oral azithromycin distributions without interim assessment. Distribution costs are high, and side effects and the potential for resistance are important issues. A plan like this would allow for more funds to be allocated to other areas. Keep in mind the graduation plan is not “country-wide”, it is based on the community infection level, so the villages with infection greater than 5% (in these cases more than 1-3 children) are still protected by this plan.

Please feel free to request any other clarifications.

Kathryn Ray
Tom Lietman
Matthew Burton
Robin Bailey
David Mabey

No competing interests declared.