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Dispatch
Eliminating Trachoma in Areas
with Limited Disease
Bruce D. Gaynor,* Yinghui Miao,* Vicky Cevallos,* Hem Jha,† JSP Chaudary,†
Ramesh Bhatta,† Susan Osaki-Holm,* Elizabeth Yi,* Julius Schachter,* John
P. Whitcher,* and Thomas Lietman*
*University of California, San Francisco, San Francisco, California, USA;
and †Geta Eye Hospital, Geta, Nepal
Suggested citation for this article: Gaynor BD, Miao
Y, Cevallos V, Jha H, Chaudary JSP, Bhatta R, et al. Eliminating trachoma
in areas with limited disease. Emerg Infect Dis [serial online] 2003
May [date cited]. Available from: URL: http://www.cdc.gov/ncidod/EID/vol9no5/02-0577.htm
The common wisdom
is that a trachoma program cannot eliminate ocular chlamydia from a
community, just reduce infection to a level where blindness would be
minimal. We describe the success of multiple mass antibiotic treatments,
demonstrating that complete elimination of infection may be an attainable
goal in an area with modest disease.
The World Health Organization (WHO) and a number of its partners have
initiated a program to eliminate blinding trachoma by the year 2020 (1).
Many healthcare workers feel that attempting to eradicate the ocular strains
of chlamydia that cause trachoma (serovars A, Ba, B, and C) would be unrealistic
and perhaps even unnecessary. A more attainable goal would be to reduce
clinically active trachoma to some threshold, below which scarring and
blindness would never occur or at least would become so rare that trachoma
would no longer be a major public health concern (2).
Although in common usage the terms eradication and elimination can be
synonymous, in the field of public health, they are not (3).
Both terms imply reduction of incidence to zero. However, eradication
applies to the whole world, whereas elimination applies to a defined geographic
area and would require further monitoring; in a sense, elimination can
be viewed as a local eradication (4). In practice, WHO
has allowed an even looser usage of the term elimination: for example,
leprosy elimination is defined as a prevalence of <1 case in 10,000
population, and tuberculosis elimination is an incidence of <1 case
in 100,000 persons per year (5,6). WHO is currently in
the process of defining such a level for trachoma.
Defining an appropriate target for trachoma elimination is particularly
difficult because infection itself is rarely monitored. Control programs
rely almost exclusively on the clinical examination because the most sensitive
chlamydial tests are expensive and not widely available in trachoma-endemic
areas. The clinical examination is certainly a reasonable tool to assess
whether ocular chlamydia is hyperendemic in a community. However, the
examination may not be an accurate indicator of infection when disease
prevalence is low, as is often seen after treatment (7-11).
The follicles so characteristic of clinically active trachoma may linger
even when chlamydia is no longer detectable by using the most sensitive
laboratory techniques (7,12). The few
studies that have tracked ocular chlamydial infection using DNA amplification
tests suggest that a single mass antibiotic distribution is very effective,
much more successful than a clinical survey would indicate (9,10).
Could ocular chlamydia be eliminated with multiple treatments? A mathematical
model has shown that periodic treatments could theoretically eliminate
infection even without a perfect antibiotic or perfect coverage of the
population (13). This same model predicts that annual
treatment in areas with moderate amounts of trachoma should progressively
reduce the prevalence of ocular chlamydia in a community. To date, however,
no reports of the efficacy of multiple annual treatments on infection
have been published.
The Study
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Figure
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![Figure.](images/02-0577t.gif) |
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Click to view
enlarged image
Figure. The prevalence of clinically
active trachoma (gray curve) and ocular chlamydial infection, as
determined by DNA amplification tests (black curve, with 95% confidence
intervals...
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We monitored trachoma prevalence in a village in Western Nepal for 3
years, using both a clinical grading system and nucleic acid amplification
tests. Three annual azithromycin (20 mg/kg) treatments were distributed
to all children ages 1–10 years in the village (Figure).
All children were examined biannually, and the conjunctivae of a stratified
random sample of children were swabbed and later tested for Chlamydia
trachomatis DNA. At the final visit, 6 months after the last treatment,
every child was examined, and their conjunctivae were swabbed. Before
the first treatment, 39% had active infection determined by the clinical
examination, and an estimated 26% (95% confidence interval [CI] 16% to
35%) were infected with chlamydia. At the final, May 2001 visit, 7 (4%)
of 187 pediatric cases were clinically active. Only 1 child of the 187
(0.5%) had evidence of chlamydia by polymerase chain reaction.
Conclusions
This study suggests that local elimination of the ocular chlamydia that
causes trachoma may be possible in a village with moderate baseline disease.
After three annual treatments, only one infected child could be identified.
Children are by far the most likely to harbor ocular chlamydia, and mathematical
models imply that they will be the most difficult group to clear from
infection (13,14). In fact, 1 year after mass azithromycin
treatment in a village in Egypt, more infection was identified in children
1–5 years old than in the rest of the community combined (9,15).
Thus, the nearly complete absence of infection in children after three
treatments implies that elimination is a possibility. Whether success
in this village was due solely to our treatment program or due in part
to a secular trend in the area, the results are encouraging.
Is elimination of ocular chlamydia necessary? It may not be for at least
three reasons. First, repeat infections are almost certainly required
to cause severe conjunctival scarring; occasional sporadic infections
probably do not lead to blindness. Second, some investigators hope that
if ocular chlamydia is reduced to a low enough level, the disease will
have difficulty repopulating the community (population biologists call
such a prevalence threshold an Allee effect [16]). While
we see no reason for such a phenomenon a priori, if present, it would
certainly establish a threshold target. Finally, bacterial, viral, and
allergic conjunctivitides can occasionally mimic ocular chlamydia, so
eradication of “clinically active” trachoma will never be possible.
Trachoma programs have already distributed more than 1 million doses
of oral azithromycin, and some villages have received three annual treatments.
How will we know when to stop? Now is the time to discuss the most appropriate
target for trachoma programs and the most appropriate definition for trachoma
elimination. The common wisdom is that complete local elimination of ocular
chlamydia to zero in a defined geographic area is an unattainable goal,
and that programs should settle for reducing the prevalence of ocular
chlamydia to a level where little if any subsequent blindness would exist.
These results from Nepal imply that the strict definition of elimination
of ocular chlamydia in children may be an attainable goal, at least in
areas with modest to moderate disease. Whether or not elimination is necessary
is a separate question.
Acknowledgments
We thank the following people for their invaluable
help with the project: members of Geta Eye Hospital, including R.R.
Bhatta, B.K. Jamuna, R.B. Chaudhary, G.B. Chaudhary, B.R. Chaudhary,
B.S. Dhami, B. Gurung, M. Gurung, L.R. Panta, K.S. Khuna, and T.B. Deupa;
the staff from Helen Keller International, in particular B. Bahadur
and G. Rana; D. Rijal; H.S. Bista; S. Costanza; and University of California
at San Francisco Chlamydia Laboratory staff members F. Pang, J. Moncada,
and E. Schneider.
This project was generously supported by the Edna McConnell
Clark Foundation, Geta Eye Hospital, Helen Keller International, Nepal
Netra Jyoti Sangh (Nepal National Society for Comprehensive Eye Care),
Pfizer Inc. (which donated azithromycin), the National Institute of
Allergy and Infectious Diseases (Grants R01 AI48789 and K08 AI 01441),
the South Asia Research Fund, Research to Prevent Blindness, and the
F.I. Proctor Foundation.
Dr. Gaynor is an ophthalmologist with subspecialty training
in the cornea, external diseases, and uveitis. He is assistant clinical
professor of ophthalmology at the F.I. Proctor Foundation and the Department
of Ophthalmology at the University of California, San Francisco, USA.
His recent research is on chlamydia infections of the eye in developing
countries.
References
- Negrel AD, Mariotti SP. WHO alliance for the global
elimination of blinding trachoma and the potential use of azithromycin.
Int J Antimicrob Agents 1998;10:259–62.
- Gaynor BD, Yi E, Lietman T. Rationale
for mass antibiotic distribution for trachoma elimination. Int Ophthalmol
Clin 2002;43:85–92.
- Post-conference small group report. Bull World Health Organ 1998;76(Suppl
2):113.
- Dowdle WR. The
principles of disease elimination and eradication. Bull World Health
Organ 1998;76(Suppl 2):22–5.
- Hinman AR. Report
of the Workgroup on Bacterial Diseases. Bull World Health Organ
1998;76:85–8.
- Foege W. Conference
synthesis and vision for the future. Bull World Health Organ 1988;74(Suppl2):109-12.
- Lietman T, Dawson C, Osaki S, Zegans M. Clinically
active trachoma versus Chlamydia infection. Med J Aust 2000;172:93–4.
- Baral K, Osaki S, Shreshta B, Panta CR, Boulter A, Pang F, et al.
Reliability
of clinical diagnosis in identifying infectious trachoma in a low-prevalence
area of Nepal. Bull World Health Organ 1999;77:461–6.
- Schachter J, West SK, Mabey D, Dawson CR, Bobo L, Bailey R, et al.
Azithromycin
in control of trachoma. Lancet 1999;354:630–5.
- Holm SO, Jha HC, Bhatta RC, Chaudhary JS, Thapa BB, Davis D, et al.
Comparison
of two azithromycin distribution strategies for controlling trachoma
in Nepal. Bull World Health Organ 2001;79:194–200.
- Thein J, Zhao P, Liu H, Xu J, Jha H, Miao Y, et al.
Does
clinical activity indicate ocular chlamydial infection in areas with
low prevalences of trachoma? Ophthalmic Epidemiol 2002;9:263–9.
- Bailey RL, Arullendran P, Whittle HC, Mabey DC. Randomised
controlled trial of single-dose azithromycin in treatment of trachoma.
Lancet 1993;342:453–6.
- Lietman T, Porco T, Dawson C, Blower S. Global
elimination of trachoma: how frequently should we administer mass chemotherapy?
Nat Med 1999;5:572–6.
- Lietman T, Porco T, Dawson C, Blower S. Mass antibiotics in trachoma
control: Whom shall we treat and how often? In: Stephens R, Byrne GI,
Christiansen G, Clarke IN, Grayson JT, Rank RG, et al., editors. Chlamydial
infections: proceedings of the Ninth International Symposium on Human
Chlamydial Infection, San Francisco, California; 1998. Napa (CA): International
Chlamydia Symposium; 1998. p. 259–62.
- Schachter J, West S, Mabey D, Vitale S, Group A. Azithromycin in control
of trachoma 3. effect of treatment on Chlamydia trachomatis infection
in trachoma. In: Stephens R, Byrne GI, Christiansen G, Clarke IN, Grayson
JT, Rank RG, et al., editors. Chlamydial infections: proceedings of
the Ninth International Symposium on Human Chlamydial Infection, San
Francisco, California; 1998. Napa (CA): International Chlamydia Symposium;
1998. p. 347–50.
- Allee WC. Principles of animal ecology. Philadelphia: W.B. Saunders
Co.; 1949.
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