Reliability of Clinical Diagnosis in Identifying Infectious Trachoma in a Low-Prevalence Area of Nepal K
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Reliability of clinical diagnosis in identifying infectious trachoma in a low-prevalence area of Nepal K. Baral,1 S. Osaki,2 B. Shreshta,3 C.R. Panta,4 A. Boulter,5 F. Pang,6 V. Cevallos,7 J. Schachter,8 & T. Lietman9 The WHO Alliance for Global Elimination of Trachoma by 2020 has increased the need to identify ocular chlamydial infections by clinical examination in areas of both high and low prevalence. The relationship between clinically active trachoma (as defined by clinical examination) and chlamydial infection is known for areas with hyperendemic trachoma, but not for areas with a low prevalence of the clinical disease. In the present study, we examined, photographed, and DNA tested the conjunctivae of children in the Surkhet district of mid-western Nepal, an area known to have a low prevalence of clinically active trachoma. Although 6% of the children aged 10 years and under were found to have clinically active trachoma, none were found to have chlamydia infection by the most sensitive DNA amplification tests available. A very low prevalence of clinically active trachoma is not necessarily evidence of the presence of chlamydial infection. Therefore, the WHO policy of not recommending an intensive trachoma control effort when the prevalence of clinically active trachoma is less than 10% in children is appropriate for this area of Nepal. Voir page 464 le reÂsume en francËais. En la pa gina 465 figura un resumen en espanÄ ol. Introduction Alliance for Global Elimination of Trachoma by the year 2020 (2). This programme is dependent on Trachoma is the leading cause of preventable identification of communities where blinding tracho- infectious blindness worldwide and is endemic in ma is present and individuals within these commu- poor, dry regions of Africa, Australia, South America, nities in need of treatment. Although novel DNA and South-East Asia. Children in endemic areas are amplification techniques such as the polymerase repeatedly infected with ocular serovars of Chlamydia chain reaction (PCR) and the ligase chain reaction trachomatis, the causative agent of trachoma. Pro- (LCR) are the most sensitive tests for diagnosing gressive scarring from these infections causes a infection (3), they are relatively expensive to perform, cascade of effects: entropion, trichiasis, corneal do not give immediate results, and are not readily infections, corneal scarring and, ultimately, blindness available in areas of the world where trachoma is (1). WHO has recently launched the initiative prevalent (4). Thus, the need to accurately identify ocular chlamydial infection by clinical examination is very important. 1 Director of Community Programmes, Mid-Western Regional Eye Care Studies in the United Republic of Tanzania and Centre, Nepalgunj, Nepal. the Gambia have provided some data on the 2 Clinical Research Coordinator, Francis I. Proctor Foundation for relationship between clinically active trachoma, as Research in Ophthalmology, University of California, San Francisco, CA, identified by examination according to WHO criteria, USA. and chlamydial infection, as determined by DNA 3 Ophthalmic Officer, Birendranager Eye Care Centre, Birendranager, amplification tests. Infection without clinically active Nepal. disease, and clinically active disease without infection 4 Senior Ophthalmic Assistant, Bardia Eye Care Centre, Bardia, Nepal. are relatively common. In one area of the United 5 Programme Coordinator, Swiss Red Cross, Nepalgunj, Nepal. Republic of Tanzania where the prevalence of 6 Staff Research Associate, Department of Laboratory Medicine, clinically active trachoma among 1±7-year-olds was University of California, San Francisco, CA, USA. 48%, the sensitivity and specificity of clinical 7 Medical Technologist (ASCP), Francis I. Proctor Foundation for examination in identifying infection were 79% and Research in Ophthalmology, University of California, San Francisco, CA, 61%, respectively (5). In an area of the Gambia where USA. the prevalence of clinically active trachoma among 8 Professor of Laboratory Medicine, University of California, San children aged 410 years was 31%, clinical examina- Francisco, CA, USA. Director, WHO Collaborating Centre for Reference and Research on Chlamydia. tion was 77% sensitive and 89% specific in 9 Assistant Professor, Francis I. Proctor Foundation for Research in identifying infection (6, 7;R.Bailey,personal Ophthalmology, University of California, Box 0944, San Francisco, CA communication, 1998). Since both the sensitivity 94143-0944, USA. Requests for reprints should be sent to this author and the specificity of a given test can vary with the (e-mail: [email protected]). prevalence of the disease (8), this relationship Reprint No. 5798 Bulletin of the World Health Organization, 1999, 77 (6) # World Health Organization 1999 461 Research between clinically active trachoma and chlamydial inclusively from 000 to 999. If the number assigned infection may be different in areas with a significantly was less than 125, the child was further evaluated, lower prevalence of clinical disease. whether or not he or she had clinically active disease. WHO has declared Nepal to be a country of high priority for trachoma control (2). An extensive epidemiological survey carried out in 1981 revealed Procedures that trachoma was the second leading cause of blindness in Nepal and that 31% of the children aged Clinical examination. An ophthalmic assistant (B.S. 410 years in the Bheri zone had clinically active or C.R.P.), who had considerable experience using trachoma (9). Subsequently, the prevalence of active the WHO simplified trachoma grading scale (11), trachoma has been markedly reduced to 9.7% and examined each child using a 1.8±2.5 6 binocular 7.0%, respectively, in the Banke and Bardia districts loupe. The tarsal conjunctival area of the upper lid of the Bheri zone. This decrease is presumably due to was examined in both eyes, although only the results economic development and to the intensive com- of the examination of the right eye were used in this munity-based education and treatment programmes study. Conjunctival inflammation was graded as of the Nepal Netra Jhoti Sangh, the Nepalese Red follicular trachoma ((TF): the presence of five or Cross, and the Swiss Red Cross (10). The Surkhet more follicles in the lower two-thirds of the upper district of Bheri zone has not been surveyed recently, palpebral conjunctiva) or intense trachoma ((TI): but correction of trichiasis from trachoma is the most greater than one-half of the underlying upper frequent outpatient surgery performed at the regio- palpebral conjunctival blood vessels obscured by nal eye care centre in Birendranagar (B. Shreshta, pronounced inflammation) (11). personal communication, 1997); thus infectious Photography. Two photographs of the tarsal trachoma has previously been prevalent. Small-scale, conjunctiva of the right upper lid were taken for each rapid assessment surveys of the area have revealed child. These were later graded, masked, by an that clinically active trachoma is now present but at a ophthalmologist (T.L.), again using the WHO low prevalence. This article reports on a study simplified grading system for trachoma (11). undertaken to determine whether conjunctival exam- LCR testing. A swab was taken of the right ination predicts the presence of C. trachomatis in an conjunctiva and placed in LCR transport medium. area with a low prevalence of active clinical disease. Samples were immediately put in an ice-chest in the field, and kept on ice or refrigerated (4 oC) until being analysed at the University of California San Francisco Methods (UCSF). LCR was used to determine the presence of C. trachomatis DNA (LCx probe system, Abbott Population Laboratories, Abbott Park, IL, USA). Further analyses Six villages, chosen arbitrarily, but with consideration were undertaken on 12 LCR-negative specimens taken for their geographical diversity, were selected in the from children with clinically active disease; tests Surkhet district of Bheri zone. The inhabitants of five included repeat LCR, LCR of diluted samples, and of the villages were predominantly Tharu, an ethnic LCR for target DNA within the chlamydial major group found to have the highest prevalence of outer membrane protein gene (omp1) (performed by trachoma by the 1981 Nepal Blindness Survey (9). Abbott Laboratories, Abbott Park, IL, USA). The inhabitants from the sixth village were pre- Giemsa staining. Giemsa staining was per- dominantly from the ethnic group known as the ``hilly formed on an arbitrary subset (15) of the clinically people''. The chief of each village was contacted and active children. Conjunctival scrapings of the right the risks and benefits to children entering the study eye were collected using a Kimura spatula. Specimens were explained. were immediately fixed with ethanol, and later All children aged 1±10 years in each of the six analysed with Giemsa staining at UCSF (12±14). villages were traced and requested to undergo a Definitions of clinically active trachoma and clinical examination by at least one examiner. The chlamydial infection. Clinically active trachoma was parents or guardians of each child were contacted for defined by the initial examiner as either TF or TI in their consent, and examinations were performed the right eye. Chlamydial infection was defined as a between 17 November and 1 December 1997. All positive LCR test for C. trachomatis. children with clinically active trachoma (see definition It should be noted that clinical