Chandler R. Dawson

Azithromycin in control of trachoma

The new Global Initiative by the World Health Organization has an ambitious goal of eliminating blinding trachoma by 2020, twenty years into the next millennium. GET 2020 consists of a four-pronged strategy to reduce active trachoma through community-based antibiotic distribution and health education on face washing and environmental sanitation, and to reduce vision loss from trichiasis through provision of appropriate surgical services. The SAFE strategy – Surgery, Antibiotics, Face-washing, Environmental change – is currently being implemented or planned for five pilot countries where the antibiotic component will be based on the drug azithromycin under a donation programme by Pfizer, Inc. Azithromycin represents a breakthrough for the community-based, antibiotic treatment of ocular Chlamydia trachomatis infection. Trachoma is a community disease, which clusters in neighbourhoods and within families, children having the highest rates of disease.1 Treatment of a few cases in such a setting guarantees re-infection from familial or neighbourhood sources, unless the treatment is more widespread. Moreover, re-infection from extra-ocular sites can occur if only topical treatment is used,2 and re-infection from other people can occur if treatment of members of the community is not carried out at the same time. Previously, topical agents, such as tetracycline, have been the agents of choice. This was done due to the absence of systemic side effects in children (seen with oral tetracycline) and the high cost and lack of availability of oral erythromycin in many of these remote communities. However, topical tetracycline must be used every day for four to six weeks to be effective. It also stings, is messy to use, and results in blurred vision because of its oily base. Compliance (regular use of the prescribed medicine) with topical agents is typically quite poor.

Acyclovir for the Prevention of Recurrent Herpes Simplex Virus Eye Disease

BACKGROUND Long-term treatment with antiviral agents has been shown to prevent recurrences of genital and orofacial herpes simplex virus (HSV) disease, but it is uncertain whether prophylactic treatment can prevent recurrences of ocular HSV disease. METHODS We randomly assigned 703 immunocompetent patients who had had ocular HSV disease within the preceding year to receive 400 mg of acyclovir or placebo orally twice daily. The study outcomes were the rates of development of ocular or nonocular HSV disease during a 12-month treatment period and a 6-month observation period. RESULTS The cumulative probability of a recurrence of any type of ocular HSV disease during the 12-month treatment period was 19 percent in the acyclovir group and 32 percent in the placebo group (P<0.001). Among the 337 patients with a history of stromal keratitis, the most common serious form of ocular HSV disease, the cumulative probability of recurrent stromal keratitis was 14 percent in the acyclovir group and 28 percent in the placebo group (P=0.005). The cumulative probability of a recurrence of nonocular (primarily orofacial) HSV disease was also lower in the acyclovir group than in the placebo group (19 percent vs. 36 percent, P<0.001). There was no rebound in the rate of HSV disease in the six months after treatment with acyclovir was stopped. CONCLUSIONS After the resolution of ocular HSV disease, 12 months of treatment with acyclovir reduces the rate of recurrent ocular HSV disease and orofacial HSV disease. Long-term antiviral prophylaxis is most important for patients with a history of HSV stromal keratitis, since it can prevent additional episodes and potential loss of vision.

Herpes simplex eye infections: Clinical manifestations, pathogenesis and management☆

Herpes infection of the eye may be acquired as the patients first exposure to the virus (primary infection) or as involvement of a new anatomical site (the eye) in a patient with previous HSV infection. In either case, patients with herpetic eye infection risk recurrent eye disease throughout their lives. The infective lesions of the corneal epithelium (dendritic and geographic ulcers) occasionally develop into noninfective indolent or trophic ulcers, particularly under the influence of cauterizing chemicals or corticosteroids. Inflammation of the corneal stroma may accompany herpetic epithelial lesions or occur independently. Stromal keratitis probably represents the hosts immune response to viral antigens filtering down from epithelial lesions or from viral replication in stromal cells. The clinical manifestations of ocular HSV infection are reviewed, pathogenesis and possible pathways of the infection are analyzed, and some practical guidelines for management and prevention are presented.

Herpetic Eye Disease Study: A Controlled Trial of Topical Corticosteroids for Herpes Simplex Stromal Keratitis

PURPOSE To evaluate the efficacy of topical corticosteroids in treating herpes simplex stromal keratitis. METHODS The authors performed a randomized, double-masked, placebo-controlled, multicenter clinical trial of 106 patients with active herpes simplex stromal keratitis who had not received any corticosteroids for at least 10 days before study enrollment. Patients were assigned to the placebo group (n = 49) or the steroid group (topical prednisolone phosphate; n = 57); both regimens were tapered over 10 weeks. Both groups received topical trifluridine. Visual acuity assessment and slit-lamp biomicroscopy were performed weekly for 10 weeks, every other week for an additional 6 weeks or until removal from the trial, and at 6 months after randomization. RESULTS The time to treatment failure (defined by specific criteria as persistent or progressive stromal keratouveitis or an adverse event) was significantly longer in the steroid group compared with the placebo group. Compared with placebo, corticosteroid therapy reduced the risk of persistent or progressive stromal keratouveitis by 68%. The time from randomization to resolution of stromal keratitis and uveitis was significantly shorter in the steroid group compared with the placebo group even though both groups included patients who were removed from the study and treated with topical corticosteroids according to best medical judgment. Nineteen (33%) of the steroid-treated patients and 11 (22%) of the placebo-treated patients completed the 10 weeks of protocol therapy and had stable, noninflamed corneas after 16 weeks. At 6 months after randomization, no clinically or statistically significant differences in visual outcome or recurrent herpetic eye disease were identified between the steroid and placebo groups. CONCLUSIONS The topical corticosteroid regimen used in this study was significantly better than placebo in reducing persistence or progression of stromal inflammation and in shortening the duration of herpes simplex stromal keratitis. Postponing steroids during careful observation for a few weeks delayed resolution of stromal keratitis but had no detrimental effect as assessed by visual outcome at 6 months.

Global elimination of trachoma: how frequently should we administer mass chemotherapy?

The World Health Organization has recommended repeat mass drug administration as part of their global initiative to eliminate blinding trachoma by the year 2020. The efficacy of repeat treatment will be tested empirically, but the results will not be available for many years, and recommendations for the necessary frequency of treatment are needed immediately. We have developed a mathematical model that uses available epidemiological data from a variety of countries. We recommend, based on our analysis, that in areas where trachoma is moderately prevalent (<35% in children), it should be treated annually, but hyperendemic areas (>50% in children), it should be treated biannually.

Herpetic Eye Disease Study: A Controlled Trial of Oral Acyclovir for Herpes Simplex Stromal Keratitis

PURPOSE To evaluate the efficacy of oral acyclovir in treating stromal keratitis caused by herpes simplex virus (HSV) in patients receiving concomitant topical corticosteroids and trifluridine. METHODS The authors performed a randomized, double-masked, placebo-controlled, multicenter trial in 104 patients with HSV stromal keratitis without accompanying HSV epithelial keratitis. Sample size was chosen so that a 5%, one-tailed test would have an 80% chance of detecting a doubling of the median time to treatment failure. Patients were randomized to receive a 10-week course of either oral acyclovir (400 mg 5 times daily, n = 51) or placebo (n = 53). All patients also received a standard regimen of topical prednisolone phosphate and trifluridine. Ophthalmologic examinations were performed weekly during the 10-week treatment period, every 2 weeks for an additional 6 weeks, and at 6 months after entry into the trial. RESULTS The median time to treatment failure (defined as worsening or no improvement of stromal keratitis or an adverse event) was 84 days (95% confidence interval, 69-93 days) for the acyclovir group and 62 days (95% confidence interval, 57-90 days) for the placebo group. By 16 weeks, 38 patients (75%) in the acyclovir group and 39 patients (74%) in the placebo group had failed treatment. Also by that time, the keratitis had resolved with trial medications, and there was no subsequent worsening in nine patients (18%) in the acyclovir group and ten (19%) in the placebo group. None of these results were significantly different between the two groups. However, visual acuity improved over 6 months in significantly more patients in the acyclovir group than in the placebo group. CONCLUSION There was no statistically or clinically significant beneficial effect of oral acyclovir in treating HSV stromal keratitis in patients receiving concomitant topical corticosteroids and trifluridine with regard to time to treatment failure, proportion of patients who failed treatment, proportion of patients whose keratitis resolved, time to resolution, or 6-month best-corrected visual acuity. Visual acuity improved over 6 months in more patients in the acyclovir group than in the placebo group.

Latrine ownership as a protective factor in inflammatory trachoma in Egypt.

We investigated the association between inflammatory trachoma in children aged 1-5 and environmental and sociodemographic risk factors in a rural Nile Delta hamlet. Inflammatory trachoma clustered in households, emphasising the child-to-child nature of transmission in the hamlet. Multiple logistic regression analysis revealed three factors predicting inflammatory trachoma in children: the absence of a latrine in the household, school-age siblings with inflammatory trachoma, and additional same-age siblings (with or without disease) in the household. In the Egyptian setting the presence of pit latrines in all houses, even when full and unscreened, might result in a reduction in trachoma prevalence in this population from the current 49% to 35%. The construction of pit latrines may offer the simplest and most acceptable environmental method for reducing trachoma in this trachoma endemic area.

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.

Chronic Follicular Conjunctivitis Associated with Chlamydia psittaci or Chlamydia pneumoniae

We determined whether patients with chronic conjunctivitis in whom direct fluorescent antibody (DFA) tests revealed genus-specific chlamydial antigens (but not species-specific Chlamydia trachomatis antigens) were infected with Chlamydia psittaci or Chlamydia pneumoniae. Patients were divided into a case group of possible non-trachomatis chlamydial conjunctivitis and a control group of nonchlamydial conjunctivitis on the basis of examination and DFA testing. Species-specific primers were used to amplify C. trachomatis, C. psittaci, and C. pneumoniae DNA with polymerase chain reaction (PCR). Four (27%) of 15 samples from the case group were positive for C. psittaci or C. pneumoniae DNA, whereas none of 24 control samples were positive. Sequencing revealed a C. pneumoniae, an avian C. psittaci, and two mammalian C. psittaci strains. A short course of oral antibiotic treatment appears to be inadequate for patients with non-trachomatis chlamydial conjunctivitis. Ocular infections due to C. pneumoniae and C. psittaci may be more common than previously recognized and can be identified by DFA and PCR.

Trachoma and blindness in the Nile Delta: current patterns and projections for the future in the rural Egyptian population.

A population based survey of trachoma and blindness was conducted in a rural Nile Delta hamlet. Trachoma remains hyperendemic in this region. Active trachoma was common among preschool children; over half had moderate to severe disease. Of residents 25 years old 90% had substantial conjunctival scarring. Severe conjunctival scarring was commoner among women (84%) than men (58%), and three-quarters of older women had trichiasis/entropion compared with 57% of older men. Males and females had equivalent age specific rates of inflammatory disease. Blindness was associated with old age; 17% of residents aged 50 and over were blind. Estimates of blindness based on this survey and other surveys in Egypt indicate that blindness is still a serious public health problem in rural Egypt. The number of blind persons in Egypt will increase from an estimated 420,000 in 1980 to 868,000 by the year 2020. The current crude blindness rate of 1.8% is expected to increase to 2.3% in the year 2000 and to 3.2% in 2020.