Trachoma therapy with topical tetracycline and oral erythromycin: a comparative trial.

Because topical antibiotic treatment has had a limited effect in previous controlled trials against trachoma, treatment with oral erythromycin was compared with topical tetracycline in 6-8-year-old children in southern Tunisia who had potentially blinding active trachoma. A total of 169 children were divided into two groups that were carefully matched for age, sex, locality, and intensity of disease. Oral erythromycin ethyl succinate in a paediatric dosage form was administered to one group and topical 1% tetracycline ointment to the other group, twice daily, six days a week for three weeks. The two treatments were equivalent in effectiveness and resulted in a substantial decrease in disease intensity and a marked reduction in chlamydial infection detected in conjunctival smears. To maintain blood levels of antibiotics known to be effective in the treatment of chlamydial infections with a dosage schedule possible in a trachoma control programme, one of the long-acting tetracyclines (doxycycline or minocycline) might be considered. Such systemic chemotherapy should be limited to selective treatment of individuals who can be adequately monitored.

Intermittent trachoma chemotherapy: a controlled trial of topical tetracycline or erythromycin.

In communities with endemic blinding trachoma, mass (or "blanket") treatment with a topically applied tetracycline derivative is a standard control measure. The widely used "intermittent" treatment schedule consists of the twice daily application of antibiotic ointment for five consecutive days once a month for six months. In this study, the efficacy of "intermittent" treatment was evaluated for the treatment of severe and moderate intensity trachoma in children in southern Tunisia. Tetracycline or erythromycin ointments (specific antichlamydial drugs) were compared with 5% boric acid ointment (a simple antiseptic) given by the intermittent schedule during the winter and spring. There was a statistically significant degree of improvement at only one examination, four weeks after the full course of treatment had been completed. When re-examined five months later there were no differences in intensity in the three groups. The limited effect of topical chemotherapy might be attributable to several causes, among which could be inadequate drug levels, inadequate treatment periods, reinfection from non-treated children in the community, and auto-infection from extraocular sites (e.g., respiratory tract) in the same child. The possible value of short-term (two weeks) systemic antimicrobial therapy as an additional strategy to prevent blindness of children with potentially blinding active trachoma is discussed.

Isolation of Chlamydia trachomatis from different areas of conjunctiva in relation to intensity of hyperendemic trachoma in school children in Southern Tunisia.

The simplified one-passage technique of culture in irradiated McCoy cells, in conjunction with certain other developments in technique, was used to isolate Chlamydia trachomatis from specimens collected from 78 children with trachoma in Douz, Southern Tunisia. The results show that C. trachomatis is not confined to the upper tarsal area of the conjunctiva in hyperendemic trachoma. The higher isolation rate and corresponding increase in the number of inclusions obtained from swabbings of the upper fornix and lower lid in addition to the conventional collection from the upper tarsus show the superiority of collecting specimens for culture from the whole conjunctiva. Specimens could be collected from the whole conjunctiva by using 1 swab for each eye and pooled for subsequent inoculation, so that the laboratory incurred no additional work. A close correlation was observed between isolation rate, together with the number of inclusions, obtained in cell culture, and intensity of inflammatory disease in hyperendemic trachoma. The sensitivity and practicability of this cultural test should provide a valuable laboratory index for use in epidemiological and therapeutic studies of trachoma.

Antichlamydial antibody in tears and sera, and serotypes of Chlamydia trachomatis isolated from schoolchildren in Southern Tunisia.

A predominance of TRIC serotype A has been isolated from schoolchildren in a population in Southern Tunisia with severe hyperendemic trachoma. The serotyping results correspond precisely with the serological findings in patients' tears and sera. Geometric mean titres of serum or tear antibody in defined populations or areas can thus give a useful indication of the prevalent serotypes. Collection of tear fluids on sponges is a more practical method than collection by filter paper strips and gives higher levels of antibody. The presence of antibody to Chlamydia trachomatis in tears correlates well with the presence of infectious agent in the eye and with the intensity of conjunctival inflammatory disease. The measurement of antichlamydial tear antibody can thus provide a meaningful index of the prevalence and intensity of active trachoma in a population. The role these antibodies may play in resistance to re-infection is not yet clear.

The use of cycloheximide-treated cells for isolating trachoma agents under field conditions.

Standard procedures for the isolation of Chlamydia trachomatis require pretreatment of the tissue culture cells. We evaluated the use of cycloheximide, an antimetabolite that can be added to the cells with the inoculum. Cycloheximide-treated cells provided a sensitive system for isolating trachoma agents. This system was applicable to field studies as requirements for equipment were minimal and the cells were 2 weeks old when inoculated.

Severe endemic trachoma in Tunisia.

In two villages in southern Tunisia where trachoma was endemic 7 per cent and 14 per cent of adults respectively had visual acuity of 20/400 or less. In both villages active trachoma affected most children under the age of two, reached a peak in two- to five-year-olds, then declined to age 15. The chronic inflammatory disease in childhood appeared to produce irreversible scarring of the eyelids, and loss of vision occurred in adult life due to corneal scarring caused by inturned eye lashes and loss of tears (dry-eyed syndrome). Economic development in one village was associated with a decline in active, infectious disease. In the second village, whose traditional economy was unchanged, there was the same prevalence of active disease over a three-year period. Unless economic development or public health control programmes reduce the prevalence of severe and moderate trachoma children now affected will develop the same blinding lesions as their parents. With the increasing numbers of children who survive there will probably be a dramatic increase in the numbers of the blind from trachoma in 10 to 20 years. Since active inflammatory trachoma in childhood responds to tetracyclines, erythromycin, and sulphonamides the disease should be attacked in those undeveloped rural areas where it continues to lead to blindness.

Herpes simplex keratitis in a developing country. Natural history and treatment of epithelial ulcers in Tunisia.

Herpes simplex keratitis was found to be a common ophthalmic problem in Tunisia. Dendritic and geographic ulcers were complicated by deep stromal keratitis in 31% of patients, two thirds of whom were known to have been treated previously with corticosteroids. Herpes simplex virus was isolated from 41% of patients from whom corneal material was cultured. To develop an effective program for management of epithelial herpes in developing countries, treatment with idoxuridine was compared with debridement and patching. Average healing time for 31 ulcers treated with idoxuridine was 13 days, with three treatment failures; average healing time for 20 ulcers treated with debridement and patching was five days, with one failure. Debridement and patching of herpetic ulcers was an efficient way to treat herpes simplex keratitis within the context of overall medical care in Tunisia.

Acute hemorrhagic conjunctivitis in Tunisia. Report of viral isolations.

Acute hemorrhagic conjunctivitis (AHC), a new disease entity first reported in 1969, has since become pandemic throughout the world. In Tunisia during an epidemic in 1972 to 1973 we studied 25 cases of AHC, which were characterized by explosive onset of lid edema, chemosis, conjunctival hemorrhages, follicular hypertrophy, and epithelial keratitis. Clinical signs peaked in 48 hours and cleared without sequelae in five to seven days. Paired acute- and convalescent-phase sera from six of the patients showed a rising titer of neutralizing antibody to the prototype strain of AHC virus (J6 70/71), which was isolated in Japan. Two viral isolates from Tunisian patients were also antigenically related to the Japanese strain, indicating that a single etiologic agent (a new member of the picornavirus group) is probably responsible for the current pandemic of AHC.

Topical tetracycline and rifampicin therapy of endemic trachoma in Tunisia.

A controlled chemotherapy trial of trachoma was carried out in a Tunisian oasis among schoolchildren with active disease. We compared 1% tetracycline ointment (79 patients) or 1% rifampicin ointment (76 patients) with 5% boric acid ointment (79 patients). Medications were administered twice daily, six days a week, for ten weeks. Slit-lamp examinations by three ophthalmologists were made independently before treatment as well as five, 19, and 39 weeks after treatment. Bacteriologic cultures were taken during treatment as were smears to detect trachoma agent at each clinical examination. Five weeks after treatment, the intensity of conjunctival disease in the tetracycline and rifampicin groups was reduced significantly when compared with boric acid, but at 19 weeks this suppression was found only in the tetracycline group. Ocular bacterial pathogens were eliminated almost entirely in the two antibiotic groups during treatment. The initial prevalence of trachoma (29to 31%) was significantly reduced in the two antibiotic-treated groups at five weeks and 19 weeks after treatment. The prevalence of trachoma was equally low (7%) in all three groups following retreatment with tetracycline. Although both antibiotics were effective, rifampicin offered no advantage over tetracycline in this trial. Recurrent disease in this school-based treatment study probably was due to reinfection from younger siblings at home. While systematic, community-wide, antibiotic treatment programs are not always possible in countries where trachoma is endemic, limited antibiotic therapy programs should be continued in these areas to reduce the intensity and prevalence of trachoma, even though the disease cannot be eradicated.

PIP: In this study, the authors compared topically applied tetracycline or rifampicin ointment with boric acid ointment administered for 10 weeks for its effect on endemic trachoma. 234 children with active disease were included in the treatment study. Those with the active disease were divided into 2 groups containing equal numbers each of the 3 intensity categories. Then each group was assigned to 1 of 3 treatment categories. Medication was administered twice daily over a single 3-hour class period and a 70-day course of follow-up therapy with 1% tetracycline was provided once daily for all the children 25 weeks after completion of the initial treatment. 62 (26.5%) had severe trachoma and 133 (56.8%) had trachoma of moderate intensity. In March 1972, 5 weeks after treatment completion, the trachoma in the 2 groups treated with antibiotics was less severe compared with the boric acid group. However, by June 1972, only the tetracycline group had less active trachoma than the boric acid treated group. By this time, also, the 3 groups were equally improved. Following the 2nd course of tetracycline treatment 25-35 weeks after the initial trial, there were no differences in any of the groups. 2 courses of therapy, therefore, were no more advantageous than 1. In Giemsa-stained smears prior to treatment, the prevalence of positive smears for Chlamydia agent were similar in the 3 groups; following treatment, prevalence had dropped to 7% overall and then after retreatment, there were rarely any cases in any of the treated groups. While the 2 antibodies were significantly better than boric acid, rifampicin did not seem to offer any significant advantages over tetracycline. The prevalence of trachoma agent appeared to change more readily than the clinical disease. Clearly the pattern of disease intensity and microbial infection displayed a seasonal cycle thatmust be considered when evaluating antibiotic treatment efficacy. The prevalence of trachoma decreases with age and that, along with the seasonality, contribute to the disease intensity. In this study, treatment did alter the disease temporarily but did not affect its course in the long run since environmental factors which originally produced the disease had not changed. Only communitywide chemotherapy would have a significant effect. However, antibiotic treatment is necessary to reduce the occurrence of later complications.

Cytology as a guide to the presence of chlamydial inclusions in Giemsa-stained conjunctival smears in severe endemic trachoma.

Microscopical examination of 927 Giemsa-stained conjunctival smears from children with chronic trachoma in southern Tunisia showed 93 (10 per cent.) with typical trachoma (chlamydial) inclusions in epithelial cells. The accompanying cytological features were a useful indicator for inclusions. Inclusions were found only in slides with numerous polymorphonuclear neutrophils (PMNs) and separation of the epithelial cells. When these two features alone were present, 3 per cent. of the smears were inclusion-positive; when many lymphocytes were present also, 25 per cent. were inclusion positive; when other cytological features (plasma cells, macrophages, blastoid, and stem cells) were present as well, 70 per cent. of the smears were inclusion-positive. The occurrence of these sets of cytological features can be a useful guide for selecting smears for intensive examination for chlamydial inclusions. Immunofluorescent (FA) staining and Giemsa staining of 527 pairs of matched smears detected trachoma agent in 67 (13 per cent.); in thirty by both methods, in thirteen by Giemsa staining alone, and in 24 by FA alone. The examination of Giemsa-stained smears for chlamydial inclusions is a useful technique for the diagnosis of trachoma or inclusion conjunctivitis by laboratories that do not have the specialized facilities for the identification of these chlamydial infections by the technically more complex procedures of immunofluorescent staining or isolation in embryonated eggs or tissue cultures.