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.

[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.

Evaluation of single-dose azithromycin versus standard azithromycin/doxycycline treatment and clinical assessment of regression course in patients with adult inclusion conjunctivitis.

BACKGROUND: Single-dose azithromycin (AZT) has been proved efficient in treating various human Chlamydia infections. However, it has not been thoroughly tested in patients with adult inclusion conjunctivitis (AIC). It is the aim of this study to perform a comparative evaluation of efficacy and safety of one-day AZT with long-term AZT and doxycycline (DOX) regimens in AIC and to present a clinical profile of regression course of the disease. MATERIALS: Eighty-three consecutive adults, with symptoms and signs of chronic conjunctivitis and positive Polymerase Chain Reaction (PCR) for chlamydia, were randomly assigned in four treatment groups; AZT 1-day 1000 mg orally, AZT 500 mg daily 9 and 14 days and DOX 200 mg 21 days orally. Follow-up visits were scheduled 1 and 2 weeks, 1, 3 and 6 months after treatment completion. PCR was repeated at the 2nd post-treatment week to confirm elimination of infectious agent. Detailed record of subjective symptoms and objective signs was performed at all visits. Retreatment rate among groups was evaluated as primary outcome. Regression rate of symptoms/signs among groups was recorded as secondary outcomes. RESULTS: All treatment groups provided statistically equivalent results of retreatment rate. Statistically significant regression of symptoms/signs was documented, initially from the 1st post-treatment week in general, but 1 month was required for complete patients' relief. Follicles were the most common clinical sign with the earliest regression after successful treatment. CONCLUSION: Single-dose azithromycin should be considered as equally reliable treatment option, comparing to long-term alternative regimens for AIC. Patients should wait for one week, until first signs of significant regression become obvious and should consider approximately one month to total relief. Follicles could be reasonably used as a key sign for clinical assessment of treatment success.

Effect of oral azithromycin in the treatment of chlamydial conjunctivitis.

PURPOSE: To assess the efficacy of oral azithromycin in the treatment of chlamydial conjunctivitis. METHODS: We performed a retrospective study in patients with clinically suspected chlamydial conjunctivitis who underwent conjunctival swab sampling for Chlamydia direct fluorescent antibody (DFA) tests between 1 January 2006 and 31 December 2006. Patients with positive DFA results were orally administered azithromycin once a week for 2 consecutive weeks. If DFA examinations still showed positive results after 4 weeks, additional azithromycin was orally administered once. The DFA tests were repeated 4 weeks later, and this was continued until the DFA tests showed negative results. RESULTS: Among the 67 suspected patients, 45 (67.2%) showed positive results from the DFA tests, of whom 42 received treatment. After the first 2 weeks, only 27 patients returned to the clinic and completed the treatment. The test results of 19 (70.4%) patients became negative after the treatment with two weekly doses of oral azithromycin. Among the remaining eight patients, four (14.8%) needed an additional dose of oral azithromycin, and the other four (14.8%) required two additional doses. All 27 patients tolerated the treatment well, with an adverse event of mild gastritis in only one patient. CONCLUSIONS: Two weekly doses of oral azithromycin were effective and well tolerated in the treatment of chlamydial conjunctivitis. However, more than one course of treatment was necessary in some patients.

Chlamydia trachomatis ompA variants in trachoma: what do they tell us?

BACKGROUND: Trachoma, caused by Chlamydia trachomatis (Ct), is the leading infectious cause of blindness. Sequence-based analysis of the multiple strains typically present in endemic communities may be informative for epidemiology, transmission, response to treatment, and understanding the host response. METHODS: Conjunctival and nasal samples from a Gambian community were evaluated before and 2 months after mass azithromycin treatment. Samples were tested for Ct by Amplicor, with infection load determined by quantitative PCR (qPCR). ompA sequences were determined and their diversity analysed using frequency-based tests of neutrality. RESULTS: Ninety-five of 1,319 (7.2%) individuals from 14 villages were infected with Ct at baseline. Two genovars (A and B) and 10 distinct ompA genotypes were detected. Two genovar A variants (A1 and A2) accounted for most infections. There was an excess of rare ompA mutations, not sustained in the population. Post-treatment, 76 (5.7%) individuals had Ct infection with only three ompA genotypes present. In 12 of 14 villages, infection had cleared, while in two it increased, probably due to mass migration. Infection qPCR loads associated with infection were significantly greater for A1 than for A2. Seven individuals had concurrent ocular and nasal infection, with divergent genotypes in five. CONCLUSIONS: The number of strains was substantially reduced after mass treatment. One common strain was associated with higher infection loads. Discordant genotypes in concurrent infection may indicate distinct infections at ocular and nasal sites. Population genetic analysis suggests the fleeting appearance of rare multiple ompA variants represents purifying selection rather than escape variants from immune pressure. Genotyping systems accessing extra-ompA variation may be more informative.

Chlamydia trachomatis as a cause of neonatal conjunctivitis in Dutch infants.

BACKGROUND: Chlamydia trachomatis is the most common sexually transmitted pathogen in adults, which at delivery may be transmitted from mother to child and cause conjunctivitis and pneumonia. In The Netherlands, prenatal chlamydial screening and treatment of pregnant women is not routine practice. The contribution of C. trachomatis to neonatal ophthalmic disease has not been studied in The Netherlands and remains unclear. METHODS: At the Sophia Children's Hospital and Rotterdam Eye Hospital, 2 cohorts of infants <3 months of age presenting with conjunctivitis were studied, 1 retrospectively (July 1996 to July 2001) and 1 prospectively (September 2001 to September 2002). Laboratory diagnosis was based on bacterial culture and polymerase chain reaction for C. trachomatis. RESULTS: C. trachomatis was detected in 27 (64%) of 42 retrospectively studied infants and 14 (61%) of 23 prospectively studied infants. Mucopurulent discharge was present in 35 (95%) of 37, swelling of the eyes in 27 (73%) of 37, conjunctival erythema in 24 (65%) of 37, respiratory symptoms in 14 (38%) of 37, and feeding problems in 5 (14%) of 37 infants respectively. Before microbiological diagnosis, general practitioners prescribed antichlamydial antibiotics locally to 5 (12%) of 41 and systemically to 4 (10%) of 41 infants who tested positive for chlamydia, and ophthalmologists prescribed to 21 (51%) of 41 and 7 (17%) of 41, respectively. CONCLUSIONS: C. trachomatis was the major cause of bacterial conjunctivitis in this population. Clinically, differentiation from other pathogens was not possible. Many infants who tested positive for chlamydia did not receive appropriate antibiotic treatment.

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.

Therapeutic approaches to Chlamydia infections.

Chlamydia trachomatis ocular and urogenital infections represent major public health problems, whereas Chlamydophila pneumoniae is a common aetiological agent of community-acquired pneumonia. The obligate intracellular lifestyle of these established pathogens poses challenges to both their diagnosis and treatment. Tetracyclines, macrolides and quinolones remain the antimicrobials of choice for the treatment of infections due to Chlamydiaceae.

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.

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.

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.

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.

Prevalencia de chlamdia trachomatis en conjuntivitis neonatal determinada mediante las técnicas de inmuno-fluorescencia y amplificación génica / Indirect fluorescence and genic amplification for the determination of chlamydia trachomatis prevalence in neonatal conjunctivitis

Backgrund: Chlamydia trachomatis is one of the most common identifiable infectious agents in neonatal conjunctivitis. It also causes pneumonitis, that is preceded by conjunctivitis in one third of cases. Aim: To asses the prevalence of Chlamydia trachomatis in newborns with conjunctivitis. Patients and methods: In 162 newborns, coming from 14 Primary Health Centers from Santiago de Chile, C. trachomatis was detected by indirect fluorescence and two polymerase chain reaction (PCR 1 and 2), wich amplified different sequences from the common endogenous plasmid. Those patients with positive indirect fluorescence and PCR 2 were definedas infected: Results: The prevalence of C. trachomatis was 8 percent, and the distribution of the positive cases was similar in the different Health Centers. Other isolates were: S. aureus (9.8 percent), S. pneumoniae (8 percent), S. viridans (6.2 percent) y H. influenzae (5.5 percent). Conclusions: The prevalence of C. trachomatis in neonatal conjunctivitis in Chile is similar to that of developed countries. Therefore, C. trachomatis should be considered in the election of antimicrobials for the treatment of neonatal conjunctivitis, to avoid ocular and respiratory complications

[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.