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Feasibility of Eliminating Ocular Chlamydia Trachomatis with Repeat Mass Antibiotic Treatments

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Feasibility of Eliminating Ocular Chlamydia Trachomatis with Repeat Mass Antibiotic Treatments BRIEF REPORT Feasibility of Eliminating Ocular Chlamydia trachomatis With Repeat Mass Antibiotic Treatments Muluken Melese, MD, MPH Context Mass antibiotic administrations for ocular chlamydial infection play a key Jaya Devi Chidambaram, MBBS role in the World Health Organization’s trachoma control program. Mathematical mod- Wondu Alemayehu, MD, MPH els suggest that it is possible to eliminate trachoma locally with repeat mass treat- ment, depending on the coverage level of the population, frequency of mass treat- David Chung Lee, BSc ments, and rate that infection returns into a community after each mass treatment. Elizabeth H. Yi Precise estimates of this latter parameter have never been reported. Vicky Cevallos, BSc Objective To determine the rate at which chlamydial infection returns to a popula- tion after mass treatment and to estimate the treatment frequency required for elimi- Zhaoxia Zhou nation of ocular chlamydia from a community. Cathy Donnellan Design, Setting, and Participants Longitudinal cohort study of 24 randomly se- Michael Saidel, MD lected villages from the Gurage Zone in Ethiopia conducted February 2003 to Octo- ber 2003. A total of 1332 children aged 1 to 5 years were monitored for prevalence of John P. Whitcher, MD, MPH ocular chlamydial infection pretreatment and 2 and 6 months posttreatment. Bruce D. Gaynor, MD Interventions All individuals older than 1 year were eligible for single-dose oral azithro- Thomas M. Lietman, MD mycin treatment. Pregnant women were offered tetracycline eye ointment. Main Outcome Measures Prevalence of ocular chlamydial infection, measured by ASS ANTIMICROBIAL AD- polymerase chain reaction, in children aged 1 to 5 years, in each of 24 villages at each ministrations have been time point was used to estimate the rate of return of infection and the treatment fre- used in several control quency necessary for elimination. programs and have been Results The prevalence of infection was 56.3% pretreatment (95% confidence Mcontemplated for many others. They interval [CI], 47.5%-65.1%), 6.7% 2 months posttreatment (95% CI, have proven to be effective against some 4.2%-9.2%), and 11.0% 6 months posttreatment (95% CI, 7.3%-14.7%). Infec- parasitic diseases (eg, onchocerciasis and tion returned after treatment at an exponential rate of 12.3% per month (95% CI, 4.6%-19.9% per month). The minimum treatment frequency necessary for elimina- filariasis), but at times have not lived up 1-3 tion was calculated to be once every 11.6 months (95% CI, 7.2-30.9 months), to expectations (eg, malaria). Vari- given a coverage level of 80%. Thus, biannual treatment, already being performed ous forms of mass treatment have been in some areas, was estimated to be more than frequent enough to eventually elimi- used for bacterial diseases, including nate infection. sexually transmitted chlamydia and Conclusion The rate at which ocular chlamydial infection returns to a community 4,5 syphilis. The World Health Organiza- after mass treatment suggests that elimination of infection in a hyperendemic area 6 tion (WHO) and its partners are now is feasible with biannual mass antibiotic administrations and attainable coverage using repeated mass azithromycin ad- levels. ministrations to control the ocular JAMA. 2004;292:721-725 www.jama.com strains of chlamydia that cause tra- choma, the world’s leading cause of in- Author Affiliations: ORBIS International, Addis and Lietman), Institute for Global Health (Drs fectious blindness.7 Trachoma meets the Ababa, Ethiopia (Drs Melese and Alemayehu); WHO Whitcher and Lietman), University of California, San Collaborating Center, F.I. Proctor Foundation Francisco. critical criteria for eradicability: there is (Drs Chidambaram, Saidel, Whitcher, Gaynor, and Corresponding Author: Thomas M. Lietman, MD, an effective treatment for the ocular Lietman, Mr Lee, and Mss Yi, Cevallos, Zhou, and WHO Collaborating Center, F.I. Proctor Foundation, Donnellan), Department of Ophthalmology Room 307, 95 Kirkham St, University of California, strains of Chlamydia trachomatis, and (Drs Gaynor, Whitcher, and Lietman), Department San Francisco, San Francisco, CA 94143-0944 there is no known animal reservoir. Cur- of Epidemiology and Biostatistics (Drs Whitcher ([email protected]). ©2004 American Medical Association. All rights reserved. (Reprinted) JAMA, August 11, 2004—Vol 292, No. 6 721 Downloaded From: https://jamanetwork.com/ on 09/28/2021 OCULAR CHLAMYDIA TRACHOMATIS AND REPEAT MASS ANTIBIOTIC TREATMENTS all members of the community except Figure 1. Map of Gurage Zone of Ethiopia Displaying Villages Randomly Selected for the Study children younger than 1 year. Chil- dren younger than 1 year were ex- ERITREA cluded because azithromycin was ap- SUDAN YEMEN proved for use in Ethiopia only for Zone Borders DJIBOUTI children 1 year and older. Adherence ETHIOPIA Woreda Borders Selected Villages (24) to therapy was essentially 100% of those WEST SHEWA ZONE Note: Distances Are Approximate treated, since administration of the Gurage Zone single-dose antibiotic was directly ob- SOMALIA served. Pregnant women were offered KENYA topical tetracycline ointment. Guard- Sodo Kebena ians were asked to bring all children Abeshge Kokir Gedabano aged 1 to 5 years, the ages most likely Muher Aklil to harbor infection, to a central loca- tion in their village for examinations at JIMMA Cheha GURAGE ZONE baseline and 2 and 6 months after treat- ZONE Meskan Eja ment (±1 week, from March 2003 to N October 2003). Verbal consent was ob- Enemor tained from the parent or guardian of Mareko Gumer each child. The right upper tarsal con- junctiva of each child was everted and YEM Endegagne SILTI ZONE ZONE swabbed. Swabs were placed immedi- HADIYA ZONE EAST SHEWA ately at 4°C and at −20°C within 6 ZONE hours, and transported at 4° C to the University of California, San Fran- cisco for processing with the Ampli- rently, there is little evidence of emerg- fection returns to a community after cor polymerase chain reaction (PCR) ing chlamydial resistance to macro- mass treatment,11 but precise esti- test (Roche Molecular Systems, Branch- lides;8 however, susceptibility testing in mates of the important latter param- burg, NJ) according to protocol. chlamydia is difficult to measure and eter have never been reported. Here we Posttreatment samples from the same rarely performed, and further surveil- determine the rate at which chla- village were pooled by random selec- lance may be needed.9 Trachoma has al- mydial infection returns to a hyperen- tion into groups of 5, and 200 µL of ready disappeared from most devel- demic population in Ethiopia, and from each of the 5 samples was pooled into oped countries—the last documented this we estimate the treatment cover- a single tube for processing.12-14 The case of indigenous active trachoma in the age and frequency (ie, biannual, an- prevalence in each village was then es- United States appears to have been in the nual) required to eliminate infection. timated from the proportion of posi- 1970s.10 Nevertheless, the general con- That is, we determine whether elimi- tive pools, using maximum likelihood sensus among public health workers is nation of ocular chlamydia from se- estimation as previously described.15 that the incidence of ocular chlamydial verely affected areas is a feasible goal. Laboratory controls were included ac- infection cannot be reduced to zero in cording to the Roche Amplicor proto- the most hyperendemic areas with an- METHODS col. In addition, negative field controls tibiotics alone. A geographical area was selected from were obtained from at least 5 random Can trachoma infection be elimi- the Gurage Zone of Ethiopia that in- children from each village. Immedi- nated from the most hyperendemic cluded 3 subdistricts and about 112000 ately after the study swab and before areas with repeated mass antibiotic ad- people (FIGURE 1). A stratified sample changing gloves for the next patient, a ministrations? Mathematical models re- of 24 villages was randomly chosen second swab was passed within 1 inch veal that it is theoretically possible to from a complete list of all villages (8 of the conjunctiva without touching. eliminate infection locally even with- from each of the 3 subdistricts). A cen- These control swabs were processed in out complete antibiotic coverage by sus was conducted (February and a manner identical to the study swabs; progressively reducing the prevalence March 2003), and all village residents if a pooled control was found to be posi- of infection with each treatment.11 aged 1 year and older were eligible to tive, then all samples in that pool were Elimination is dependent on the effi- participate in the study. A single oral individually retested. All specimens were cacy of the antibiotic in an individual, dose of azithromycin (1 g to adults, 20 processed in a masked manner. the coverage and frequency of treat- mg/kg to children) was offered within The rate of return of infection after ment, and the initial rate at which in- 2 weeks of the baseline examination to treatment was determined from the ob- 722 JAMA, August 11, 2004—Vol 292, No. 6 (Reprinted) ©2004 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/28/2021 OCULAR CHLAMYDIA TRACHOMATIS AND REPEAT MASS ANTIBIOTIC TREATMENTS served increase in prevalence from 2 to Table. Antibiotic Coverage, Study Participation, and Prevalence of Ocular Chlamydia by 6 months after treatment. Using this rate, Village in Gurage Zone, Ethiopia the treatment frequency necessary to Baseline 2mo 6mo achieve elimination was obtained from Pretreatment Posttreatment Posttreatment the following inequality11: No. of villages sampled* 24 24 24 Total No. of children aged 1 to 5 y examined 1332 1316 1321 1 Estimates, mean % (95% CI)† Ͼe(rate ϫ period) 1−(coverage ϫ efficacy) Village treatment coverage 91.9 (89.3-94.5) Monitor only Monitor only Village PCR participation 91.1 (88.7-93.5) 91.5 (88.7-94.3) 90.1 (87.6-92.6) where efficacy is the efficacy of the an- Village prevalence by PCR 56.3 (47.5-65.1) 6.7 (4.2-9.2) 11.0 (7.3-14.7) tibiotic in an individual, and period is the Prevalence, No.
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