Comparison of genovars and Chlamydia trachomatis infection loads in ocular samples from children in two distinct cohorts in Sudan and Morocco.

Trachoma is a blinding disease caused by repeated conjunctival infection with different Chlamydia trachomatis (Ct) genovars. Ct B genovars have been associated with more severe trachoma symptoms. Here, we investigated associations between Ct genovars and bacterial loads in ocular samples from two distinct geographical locations in Africa, which are currently unclear. We tested ocular swabs from 77 Moroccan children (28 with trachomatous inflammation-follicular (TF) and 49 healthy controls), and 96 Sudanese children (54 with TF and 42 healthy controls) with a Ct-specific real-time polymerase chain reaction (PCR) assay. To estimate bacterial loads, Ct-positive samples were further processed by multiplex real-time qPCR to amplify the chromosomal outer membrane complex B and plasmid open reading frame 2 of Ct. Genotyping was performed by PCR-based amplification of the outer membrane protein A gene (~1120 base pairs) of Ct and Sanger sequencing. Ct-positivities among the Moroccan and Sudanese patient groups were 60·7% and 31·5%, respectively. Significantly more Sudanese patients than Moroccan patients were genovar A-positive. In contrast, B genovars were significantly more prevalent in Moroccan patients than in Sudanese patients. Significantly higher Ct loads were found in samples positive for B genovars (598596) than A genovar (51005). Geographical differences contributed to the distributions of different ocular Ct genovars. B genovars may induce a higher bacterial load than A genovars in trachoma patients. Our findings emphasize the importance of conducting broader studies to elucidate if the noted difference in multiplication abilities are genovar and/or endemicity level dependent.

Haemolacria: a case of pseudomembranous conjunctivitis in a neonate.

We report an unusual case of an 11-day-old neonate presenting with haemolacria on a background of sticky conjunctival discharge. This was secondary to Chlamydia pseudomembranous conjunctivitis which responded well to systemic erythromycin. Early appropriate treatment is important to prevent progression of the ophthalmic infection, which could lead to blindness, and to prevent other manifestations of neonatal chlamydial infection, particularly pneumonia, which could be fatal. Management also includes treating the mother and educating about sexually transmitted infections.

Trachoma and ocular Chlamydia trachomatis were not eliminated three years after two rounds of mass treatment in a trachoma hyperendemic village.

PURPOSE: The World Health Organization recommends mass treatment of trachoma-hyperendemic communities, but there are scant empiric data on the number of rounds of treatment that are necessary for sustainable reductions. The rates of active trachoma and infection with C. trachomatis were determined in a community 3.5 years after two rounds of mass treatment with azithromycin. METHODS: Maindi village in Tanzania received a first round of mass treatment with azithromycin after a baseline survey for trachoma and infection. All residents aged 6 months and older were offered single-dose treatment with azithromycin (excluding pregnant women with no clinical trachoma, who were offered topical tetracycline). The residents were followed over an 18-month period, and, according to similar treatment criteria, were offered retreatment at 18 months. Five years after baseline (3.5 years after the second round of mass treatment), a new census and survey of current residents for trachoma and infection was conducted. Children are the sentinel markers of infection and trachoma in communities, so data are presented specifically for ages 0 to 7 years (preschool age) and 8 to 16 years. RESULTS: Treatment coverage was above 80% for all ages in the first round, and highest (90%) in preschool-aged children. Second-round coverage was lower, <70%, and 70% in preschool-aged children. At 5 years, trachoma rates were still lower than baseline, ranging from 45% in those aged 0 to 3 years to 8% in those aged 11 to 15 years (compared with 81% and 39% at baseline, respectively). Infection rates at baseline ranged from 71% to 57%, but were 27% to 17% at 5 years after two rounds of mass treatment. At 5 years, there were no differences in trachoma or infection rates, when comparing new residents who came after the second mass treatment with those who had been resident in the village during both rounds (P > 0.05). Infection rates were lower in those who had been treated twice or at 18 months than in those treated only at baseline or never treated. CONCLUSIONS: Although mass treatment appears to be associated with lower disease and infection rates in the long term, trachoma and C. trachomatis infection were not eliminated in this trachoma hyperendemic village 3.5 years after two rounds of mass treatment. Continued implementation of the SAFE strategy in this environment is needed.

[Persistent, therapy-resistant conjunctivitis: consider infection with Chlamydia trachomatis]. / Persisterende therapieresistente conjunctivitis.

Conjunctivitis is a frequently diagnosed disease, usually caused by a virus. A less well-known cause is a chlamydia infection. This may result in missed diagnoses, delay of treatment and several complications. We present two cases of a persistent, therapy-resistant conjunctivitis in patients who were over 70 years of age. One patient had conjunctival follicles, characteristic of chlamydia conjunctivitis. The polymerase chain reaction tests of conjunctival samples from both patients were positive for chlamydia. Both patients and their sexual partners were treated with oral azithromycin. There was a treatment delay in both cases due to late recognition which was partially due to the older age of the patients. These cases illustrate that when a patient presents with persistent, therapy-resistant conjunctivitis, particularly if conjunctival follicles are present, chlamydial conjunctivitis should be considered and conjunctival swabs should be taken, no matter what the age of the patient.

Ocular chlamydial infections: pathogenesis and emerging treatment strategies.

Chlamydiae cause a spectrum of diseases in multiple organ systems, and chlamydial infections of the eye lead to sequelae varying from mild conjunctivitis to blindness. This paper reviews current concepts in the pathogenesis and management of ocular chlamydial infections. Trachoma, the leading cause of preventable blindness in the world, is compared with other ocular chlamydial diseases to underscore key concepts in chlamydial pathogenesis. Emerging treatment strategies are discussed in the context of chlamydial pathogenesis and the World Health Organization initiative to eradicate trachoma by 2020.

Inclusion blennorrhea: a case report.

The case described here represents the first laboratory-confirmed case of inclusion blennorrhea at the Mayo Clinic since laboratory isolation of Chlamydia trachomatis was instituted in 1974. Treatment with a sulfonamide preparation proved effective. Further aspects of the diagnosis and treatment of inclusion blennorrhea are discussed.

Severe persistent inclusion conjunctivitis in a young child.

A 14-month-old girl had inclusion conjunctivitis although there had been no signs or symptoms that required medical attention in her first year. By 2 1/2 years of age, the child had extensive pannus and corneal scarring that severely reduced vision. The infection was caused by a genital strain of Chlamydia trachomatis, TRIC type E, that was probably acquired at birth. Although genitally transmitted chlamydial strains normally cause a self-limiting inclusion conjunctivitis in areas where trachoma is not endemic, this case illustrates that they may occasionally cause severe trachoma. Possibly local idoxuridine (IDU) treatment (administered to this patient before the correct diagnosis was made) contributed to the severity of this infection.

Azithromycin vs doxycycline in the treatment of inclusion conjunctivitis.

PURPOSE: The aim of the study was to compare the efficacy and safety of azithromycin and doxycycline in the treatment of chlamydial conjunctivitis in adults. DESIGN: An open, randomized clinical trial. METHODS: Seventy-eight adult patients with incluson conjunctivitis were enrolled in this multicenter clinical study. Patients with chlamydial conjunctivitis as indicated by a positive direct fluorescent antibody (DFA) test or cell culture were randomized to receive a single 1-g dose of azithromycin or doxycycline, 100 mg twice daily for 10 days. A conjuctival swab for cell culture was obtained from all patients immediately before the treatment for subsequent confirmation of the presence of chlamydial infection in the central laboratory. Control examinations were performed 10 to 12 days and 4 to 6 weeks after the treatment initiation. Clinical and bacteriological responses to the treatment were evaluated at the last visit. The occurrence and frequency of adverse events were analyzed as well. RESULTS: Of 78 patients enrolled, 51 completed the study and were evaluated for efficacy. The main reasons for withdrawal were lack of confirmation of the presence of chlamydial infection by the central laboratory and failure to attend the follow-up visit. Eradication of C. trachomatis was achieved in 23 of 25 (92%) patients treated with azithromycin and in 25 of 26 (96%) patients treated with doxycycline. Clinical cure was observed in 15 (60%) and 18 (69%) patients treated with azithromycin and doxycycline, respectively. Both drugs were equally well tolerated. CONCLUSIONS: A single 1-g azithromycin therapy was as effective as standard 10-day treatment with doxycycline (100 mg twice daily) in the treatment of adult inclusion conjunctivitis.

Rapid, reliable diagnosis of chlamydial ophthalmia by means of monoclonal antibodies.

The use of fluorescein-conjugated monoclonal antibody (Syva, UK) provided a rapid reliable diagnostic test for Chlamydia trachomatis in conjunctival samples from 100 adults with acute follicular conjunctivitis and seven babies with suspected chlamydial ophthalmia neonatorum. Elementary bodies (EBs) were seen in smears from 11 of the adults, and culture confirmed C. trachomatis infection in nine of them. Both tests were positive with specimens from four of the neonates. No specimens from either group of patients produced a negative result in the smear test but a positive result by culture. However, the two adult patients with chlamydial ophthalmia who had negative cultures but were EB-positive had both had prior topical tetracycline therapy.

Oral doxycycline in the treatment of adult chlamydial ophthalmia.

Ninety-three consecutive patients with adult chlamydial ophthalmia were treated with four different regimens of oral doxycycline. In patients treated with a single dose of 5 mg/kg of body weight (300 mg) of doxycycline the severity of clinical signs was reduced, and in half of the patients shedding of the infective agent was stopped. Treatment with a weekly dose of 300 mg of doxycycline for three weeks or a daily dose of 1.5 mg/kg of body weight (100 mg) for one week produced a clinical and microbiological cure in 100% of patients. However, in some of these patients mild to moderate papillary responses were present up to six months from completion of the treatment. The best results were obtained with a daily dose of 100 mg for two weeks, which produced rapid clinical and microbiological cure in all patients.

A double-blind comparison of topical therapy of chlamydial ocular infection (TRIC infection) with rifampicin or chlortetracycline.

A double-blind stratified trial was carried out on 85 patients to assess the efficacy of topical therapy with 1% chlortetracycline eye ointment in comparison with 1% rifampicin eye ointment in the treatment of chlamydial ocular infection of sexually transmitted origin (paratrachoma). Patients included were selected on the basis of positive culture for Chlamydia trachomatis. A 6-week course of treatment with chlortetracycline or rifampicin 3 times daily gave a clinical cure rate of 80% and 75% and a microbiological cure rate of 93% and 86% respectively. In patients who were not cured the intensity of inflammatory responses was considerably reduced.

The treatment and follow up of adult chlamydial ophthalmia.

Sixty two patients diagnosed as having adult chlamydial ophthalmia were treated with oral doxycycline and roxithromycin in association and tetracycline eye wash for 2 weeks. Chlamydial ophthalmia was diagnosed by laboratory detection of the micro-organism in ocular specimens using direct immunofluorescent monoclonal antibody staining for Chlamydia trachomatis, chlamydial culture in cycloheximide treated McCoy cells, and Giemsa staining. An immunoenzymatic method for detection of specific IgG and IgA in patients' serum was used as an additional test to confirm the diagnosis. All patients were reexamined 3 weeks after completing their course of antibiotics and in the case of persistent infection a further course of treatment was given. With this treatment regimen 48 out of 62 patients (77.4%) were cured after three courses. Because of the risks of an inadequate response to therapy, we recommend a proper post-treatment follow up in all patients with chlamydial eye infections.

Prevalence of chlamydial eye infection in patients attending an eye clinic, a VD clinic, and in healthy persons.

Chlamydial eye infection was detected in 28 of 983 ophthalmological patients with conjunctivitis or keratoconjunctivitis, with a peak frequency of over 9% in patients aged 16-20 years and with decreasing frequency thereafter. In patients aged 1 to 15 years chlamydial conjunctivitis was not observed. Chlamydial eye infection could not be detected in patients at a venereal diseases clinic, though chlamydial genital infection was rather frequent in these patients. Nor was Chlamydia trachomatis found in the eyes of healthy young adults. In patients with proved chlamydial conjunctivitis unilateral symptoms were the rule. Pseudoptosis was the most conspicuous presentation in two cases. A prolonged course can be expected in chlamydial eye infection if the condition is unrecognised and effective treatment delayed. The venereal background of the condition must also influence the management.

The effect of antibiotic treatment on active trachoma and ocular Chlamydia trachomatis infection.

Antibiotics are one of four arms of the SAFE strategy for the control of trachoma, an eye infection that is responsible for more cases of blindness than any condition other than cataract. The evidence for the use of topical tetracycline and oral tetracycline, doxycycline, erythromycin, cotrimoxazole and azithromycin in trachoma are reviewed here and a number of issues are nominated as research and policy priorities.

Diagnostic methods for Chlamydia trachomatis disease in neonates.

Chlamydia trachomatis is an obligate intracellular parasite responsible for many clinical syndromes, including neonatal conjunctivitis and pneumonia. The gold standard of diagnosis has been isolation in cell culture. However, this requires days of processing. Several rapid diagnostic tests are available. Giemsa staining of conjunctival smears, enzyme immunoassay, and the fluorescein-conjugated monoclonal antibody test. Both the EIA and the FA tests show promise as ideal rapid diagnostic tests. Treatment of chlamydial conjunctivitis must focus upon the eradication of nasopharyngeal carriage as well as cure of ophthalmic symptoms. The need for nasopharyngeal eradication is underscored by the fact that it is the source for chlamydial pneumonia as well as for conjunctival re-infection. Clinical studies have shown that oral erythromycin estolate or ethylsuccinate suspension 50 mg/kg/day twice-daily or four times a day for 14 to 21 days are the therapeutic regimens of choice. Neonatal ocular prophylaxis is currently under study. One per cent silver nitrate does not prevent chlamydial conjunctivitis but preliminary studies do show favorable results with topical erythromycin. Nevertheless, neither 1 per cent silver nitrate nor topical erythromycin eradicate nasopharyngeal carriage, elimination of which is necessary for the prevention of neonatal chlamydial pneumonia.

Erythromycin.

Even with the continuing emergence of new antibiotics, erythromycin continues to be used extensively in obstetrics and gynecology. It is inexpensive, with a long history of usage and proven safety. When oral erythromycin preparations are given in the correct dose and with proper timing in relation to meals, no individual preparation offers a significant therapeutic advantage. Its uses include the treatment of respiratory tract infections, chlamydial and other genital tract infections in pregnancy, puerperal mastitis, and acute conjunctivitis of the newborn.

Feasibility of eliminating ocular Chlamydia trachomatis with repeat mass antibiotic treatments.

CONTEXT: Mass antibiotic administrations for ocular chlamydial infection play a key role in the World Health Organization's trachoma control program. Mathematical models suggest that it is possible to eliminate trachoma locally with repeat mass treatment, depending on the coverage level of the population, frequency of mass treatments, and rate that infection returns into a community after each mass treatment. Precise estimates of this latter parameter have never been reported. OBJECTIVE: To determine the rate at which chlamydial infection returns to a population after mass treatment and to estimate the treatment frequency required for elimination of ocular chlamydia from a community. DESIGN, SETTING, AND PARTICIPANTS: Longitudinal cohort study of 24 randomly selected villages from the Gurage Zone in Ethiopia conducted February 2003 to October 2003. A total of 1332 children aged 1 to 5 years were monitored for prevalence of ocular chlamydial infection pretreatment and 2 and 6 months posttreatment. INTERVENTIONS: All individuals older than 1 year were eligible for single-dose oral azithromycin treatment. Pregnant women were offered tetracycline eye ointment. MAIN OUTCOME MEASURES: Prevalence of ocular chlamydial infection, measured by polymerase chain reaction, in children aged 1 to 5 years, in each of 24 villages at each time point was used to estimate the rate of return of infection and the treatment frequency necessary for elimination. RESULTS: The prevalence of infection was 56.3% pretreatment (95% confidence interval [CI], 47.5%-65.1%), 6.7% 2 months posttreatment (95% CI, 4.2%-9.2%), and 11.0% 6 months posttreatment (95% CI, 7.3%-14.7%). Infection 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 elimination was calculated to be once every 11.6 months (95% CI, 7.2-30.9 months), given a coverage level of 80%. Thus, biannual treatment, already being performed in some areas, was estimated to be more than frequent enough to eventually eliminate infection. CONCLUSION: The rate at which ocular chlamydial infection returns to a community after mass treatment suggests that elimination of infection in a hyperendemic area is feasible with biannual mass antibiotic administrations and attainable coverage levels.

[Chlamydia trachomatis conjunctivitis in the newborn]. / La conjonctivite à Chlamydia trachomatis du nouveau-né.

Infections of the conjunctiva are frequent in the neonatal period. While Neisseria gonorrhoea and chemical agents were considered as the main etiologies of ophtalmiae neonatorum in the past, Chlamydia trachomatis is today a major cause of neonatal conjunctivitis. Thus in a study of 180 uni-or bilateral neonatal conjunctivitis the authors found a prevalence of Chlamydia trachomatis infection of 41%. The importance of the etiological diagnosis of neonatal conjunctivitis is emphasized, in order to define a specific treatment. Etiological diagnosis of Chlamydia trachomatis infection is based upon immunofluorescence and molecular diagnosis techniques (PCR, LCR). Prevention of neonatal Chlamydia trachomatis conjunctivitis relies upon screening and treatment of Chlamydia trachomatis infections in pregnant women and their partners. Treatment requires oral macrolides, the topical treatment being ineffective.

[Rifadin activity in trachoma and paratrachoma]. / Aktivnost' rifadina pri trakhome i paratrakhome

Rifadin after a single inoculation in a dose of 100 microng/ml completely inhibited the development of the causative agent of trachoma in cell culture. In patients with trachoma (18) and paratrachoma (4) cure was achieved by topical application of 5% ointment. Additional administration of the drug per os did not produce any considerable improvement. The cure was confirmed by the results of clinical, biomicroscopic, cytological and histological examinations of the tarsoconjunctival tissue (biopsy according to indications). Repeated examinations of the patients were carried out for 4 years and no cases of relapse were observed.