Trachoma: there’s progress to report

2 Dec 2009

Paul Chinnock

Source: TropIKA.net

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A baby with flies on its face, which can transmit bacteria leading to trachoma. © CBM / Argum / Einberger.

There are 1.3 million people living with blindness caused by the bacterial infection trachoma. Some 1.8 million more have impaired vision and in addition 8 million other trachoma-infected people have trichiasis – painful ingrowing eyelashes.

Trachoma is classed as a neglected tropical disease (NTD) and is usually considered to be one of the “main seven” NTDs, all of them very common conditions for which effective methods of prevention and treatment already exist but fail to get through to most of the people who need them. For trachoma, the priority must be to scale up implementation of the “SAFE” strategy: surgery, antibiotics, facial cleanliness and environmental improvements. But further research is needed too, in order to learn more about the epidemiology of this disease and how best to go about implementing prevention and treatment programmes. And we need to evaluate and monitor the level of success being achieved with programmes already in operation. Gratifyingly, the last few months have seen the publication of several research studies focusing on trachoma and several of them have encouraging findings to report.

Surveys

Reliable population-based prevalence data are essential for understanding the scale of the trachoma problem and for planning, monitoring and evaluating control programmes. However, for many of the world’s 56 trachoma-endemic countries such data is not available. A number of surveys have been published in the journals recently and they add to the information that is available. Kur et al. (1) used a two-stage cluster random sampling method to assess trachoma prevalence in Sudan’s Western Equatoria State, which is adjacent to other areas of southern Sudan where surveys in recent years have found remarkably high prevalence levels. The survey team found that in most villages the prevalence of active trachoma was well below the 10% threshold recommended by WHO for introduction of large-scale SAFE programmes. This new finding indicates how prevalence rates can vary unpredictably within the same region.

Rapid assessments in the Pacific islands of Kiribati, Nauru, Vanuatu, Solomon Islands and Fiji (2) found active trachoma to be present in all the islands; rates of active trachoma in children were over 20% in Nauru. The authors recommend that the introduction of control measures should be considered. In contrast, a rapid assessment survey in a previously hyperendemic rural area in Haryana, India (3) found only 40 active cases in 1,000 children examined. The authors conclude that trachoma is no longer a public health problem in this part of India.

A sample of school children in Brazil’s Alagoas State (4) were checked for the presence of trachoma and signs of the disease were found in 4.5% of them. While not a full community survey, this finding does establish that the disease has not yet been eradicated from this part of Brazil. And a small survey in Australia (5) has again confirmed that this highly developed country has also failed to eradicate trachoma from its indigenous population.

But how should surveys for trachoma be conducted? As discussed in a review article (6), three methods have been advocated: cluster random sampling (CRS); trachoma rapid assessment (TRA); and acceptance sampling trachoma rapid assessment (ASTRA). The reviewers are in agreement with WHO that CRS is the survey design of choice for trachoma control programmes. However, as with some of the surveys mentioned above, many different techniques are currently in use, which it makes it hard to compare the results obtained from different surveys.

Antibiotics

Most recently published trachoma studies have focused on the impact of antibiotic treatment, in most cases with azithromycin. In Cameroon (7) a campaign was undertaken to treat the entire population of one district with azithromycin eye drops (1.5%). To measure the effectiveness of treatment on the prevalence of active trachoma, two epidemiological studies were conducted on a representative sample of children aged 1–10 years. The first study was performed just prior to the treatment campaign and the second a year later. The prevalence of active trachoma dropped from 31.5% before treatment to 6.3%, with no reports of serious side effects.

In severely infected children a single standard dose of azithromycin is often not enough to eliminate the infection. Might increasing the dose rate address this problem? Researchers in Tanzania (8) randomized 99 children with severe trachoma to receive a single azithromycin dose of either 20 mg/kg or 30 mg/kg. However, six weeks later, they found no significant difference between the two treatment groups in the infection rate

A community-based drug distribution programme will never reach every individual living in that community but is it possible that untreated individuals receive an indirect protective effect from living in repeatedly treated communities? The idea is equivalent to the concept of “herd protection” in vaccine programmes. US researchers working in Ethiopia (9) tested the hypothesis in a cluster randomised trial involving over 10,000 children, who received either four doses of azithromycin over one year, or had their treatment delayed until after the study was complete. After one year, 637 children aged 1-10 years and 561 adults and children aged 11 years and older were analysed in the children-treated group, and 618 and 550, respectively, in the control group. The mean prevalence of infection in children who had been treated decreased from 48.4% to 3.6%. But, in addition mean prevalence of infection in the untreated individuals over 11 was 47% less than baseline; it was also 35% less than that in untreated communities. These findings are very encouraging and suggest that frequent treatment of children could eventually eliminate infection from the entire community.

In another study in Ethiopia (10), Orbis International researchers provided four biannual, community-wide azithromycin distributions to 16 randomly selected villages. The average prevalence of infection in 1–5-year-old children was reduced from 63.5% pre-treatment to 2.6% six months after the final treatment. In the next 18 months, infection returned to 25.2%, a significant increase but far lower than baseline. The researchers conclude that repeated mass oral azithromycin distributions progressively reduce infection in a community, as long as these distributions are given frequently enough and at a high enough coverage. However, infection returns into the communities after the last treatment.

So – in such highly-endemic areas – will regular drug treatment of communities be required indefinitely or is there a point at which it can be discontinued? On the basis of a modelling study (11), US researchers propose that communities can “graduate” from mass antibiotic treatment when infection rates fall below 5%. They use their model to compare the effects of implementing the standard WHO strategy with an alternative, in which communities are allowed to graduate when prevalence falls below 5%.

Finally, a large trial (12) already discussed on TropIKA.net has shown that azithromycin distribution for trachoma leads also to significant reductions in overall child mortality, most probably because the antibiotic also protects against respiratory and diarrhoeal infections. More research is needed to determine how the effectiveness of community drug administration can be maximised but there is already ample evidence to support the introduction of such programmes in all areas highly endemic for trachoma.

Sanitation

Flies play a major role in the transmission of trachoma from person to person and flies breed in insanitary conditions. It would therefore seem logical that families with adequate toilets would be at reduced risk of the disease. Nevertheless, the evidence to support this has been inconclusive. A case–control study (13) in nearly 1000 households in eight Tanzanian villages examined the association between use and quality of latrines and the risk of trachoma. Use of latrines was significantly associated with a decreased risk of trachoma. Surprisingly, this was regardless of the quality of the latrines, as – contrary to their expectations – the researchers did not find an inverse association between increasing latrine quality and decreasing odds of trachoma. This suggests that latrines need not be expensive or elaborate to provide health benefits. The authors conclude that their findings underscore the importance of achieving 100% latrine use in communities.

In a community-based study of 500 children in Ethiopia (14) lack of access to a latrine increased the risk of having active trachoma by over 4.36 fold. Prevalence of the active disease was very high in this study (53.9%). Other risk factors studied were lack of access to piped water (2.19 fold risk), absence of facial cleanliness (7.59), illiterate mother (5.88) and presence of “fly-eye” (fly contact with the eyelid margin during eye examination) (4.03).

The SAFE package

Programmes to control trachoma now seek to implement SAFE as a package and we need to know how effective this is proving to be. A study in Sudan (15) evaluated the impact of the A, F and E elements of SAFE in five trachoma hyperendemic districts of Amhara region. Sadly the published paper is not available with open access and cannot be obtained through any of the TropIKA.net team’s resources. The abstract indicates that the programme was successful in reducing disease prevalence, supporting the view that A, F and E interventions should be implemented simultaneously.

Vaccine hopes

More good news comes from a study with monkeys in the US (16) extending work already done with mice that could mark the beginnings of the development of a vaccine that would protect against trachoma. The authors argue that a vaccine is likely to provide “the best possible defence” against the pathogen. While a vaccine would be welcome, alleviation of the poverty that creates the environments in which the infection flourishes must surely be the ultimate goal.

References

1. Kur LW, Picon D, Adibo O, Robinson E, Sabasio A, et al. (2009) Trachoma in Western Equatoria State, Southern Sudan: Implications for National Control. PLoS Negl Trop Dis 3(7): e492. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19636366

2. Mathew AA, Keeffe JE, Le Mesurier RT, Taylor HR (2009). Trachoma in the Pacific Islands: evidence from Trachoma Rapid Assessment. Br J Ophthalmol; 93(7):866-870. Epub 2009 Jan 27. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19174394

3. Khanduja S, Jhanji V, Sharma N, Vashist P, Murthy GV, Gupta S, Satpathy G, Tandon R, Titiyal JS, Vajpayee RB (2009). Rapid assessment of trachoma among children living in rural northern India. Ophthalmic Epidemiol; 16(4):206-211. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19874140

4. Damasceno RW, Santos RR, Cavalcanti TR, Hida RY, Santos MJ, Santos AM, Dantas PE (2009). [Trachoma: epidemiologic study in students in Alagoas State - Brazil] Arq Bras Oftalmol; 72(3):355-359. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19668966

5. Wright HR, Keeffe JE, Taylor HR (2009). Trachoma, cataracts and uncorrected refractive error are still important contributors to visual morbidity in two remote indigenous communities of the Northern Territory, Australia. Clin Experiment Ophthalmol; 37(6):550-557. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19702703

6. Ngondi J, Reacher M, Matthews F, Brayne C, Emerson P (2009). Trachoma survey methods: a literature review. Bull World Health Organ; 87(2):143-151. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2636192/

7. Huguet P, Bella L, Einterz E, Goldschmidt P, Bensaid P (2009).Trachoma mass treatment with azithromycin 1.5% eye drops in Cameroon: feasibility, tolerance and effectiveness. Br J Ophthalmol. Aug 26. [Epub ahead of print] Available from: http://www.ncbi.nlm.nih.gov/pubmed/19692356

8. Campbell JP, Mkocha H, Munoz B, West SK (2009). Randomized trial of high dose azithromycin compared to standard dosing for children with severe trachoma in Tanzania. Ophthalmic Epidemiol; 16(3):175-180. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19437312

9. House JI, Ayele B, Porco TC, Zhou Z, Hong KC, Gebre T, Ray KJ, Keenan JD, Stoller NE, Whitcher JP, Gaynor BD, Emerson PM, Lietman TM (2009). Assessment of herd protection against trachoma due to repeated mass antibiotic distributions: a cluster-randomised trial. Lancet; 373(9669):1111-1118. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19329003

10. Lakew T, House J, Hong KC, Yi E, Alemayehu W, Melese M, Zhou Z, Ray K, Chin S, Romero E, Keenan J, Whitcher JP, Gaynor BD, Lietman TM (2009). Reduction and return of infectious trachoma in severely affected communities in Ethiopia. PLoS Negl Trop Dis; 3(2):e376. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19190781

11. Ray KJ, Lietman TM, Porco TC, Keenan JD, Bailey RL, Solomon AW, Burton MJ, Harding-Esch E, Holland MJ, Mabey D (2009). When can antibiotic treatments for trachoma be discontinued? Graduating communities in three African countries. PLoS Negl Trop Dis; 3(6):e458. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19529761

12. Porco TC, Gebre T, Ayele B, House J, Keenan J, Zhou Z, Hong KC, Stoller N, Ray KJ, Emerson P, Gaynor BD, Lietman TM (2009). Effect of mass distribution of azithromycin for trachoma control on overall mortality in Ethiopian children: a randomized trial. JAMA; 302(9):962-968. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19724043

13. Montgomery MA, Desai MM, Elimelech M (2009). Assessment of latrine use and quality and association with risk of trachoma in rural Tanzania. Trans R Soc Trop Med Hyg; 17 Nov. [Epub ahead of print] Available from: http://www.ncbi.nlm.nih.gov/pubmed/19926106

14. Golovaty I, Jones L, Gelaye B, Tilahun M, Belete H, Kumie A, Berhane Y, Williams MA (2009). Access to water source, latrine facilities and other risk factors of active trachoma in Ankober, Ethiopia. PLoS One; 4(8):e6702. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19693271

15. Ngondi JM, Gebre T, Shargie EB, Adamu L, Teferi T, Zerihun M, Ayele B, King JD, Cromwell EA, Emerson PM (2009). Estimation of effects of community intervention with Antibiotics, Facial cleanliness, and Environmental improvement (A,F,E) in five districts of Ethiopia hyper-endemic for trachoma. Br J Ophthalmol; Nov 5. [Epub ahead of print] Available from: http://www.ncbi.nlm.nih.gov/pubmed/19897474

16. Kari L, Whitmire WM, Crane DD, Reveneau N, Carlson JH, Goheen MM, Peterson EM, Pal S, de la Maza LM, Caldwell HD (2009). Chlamydia trachomatis native major outer membrane protein induces partial protection in nonhuman primates: implication for a trachoma transmission-blocking vaccine. J Immunol; 182(12):8063-8070. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19494332