Abstract:Major outer membrane protein sequences, determined from Chlamydia-positive eye swab samples collected in 2 Egyptian villages, were used to analyze the epidemiology of trachoma in an endemic setting. Samples were collected during the 1999 Azithromycin in Control of Trachoma trial, in which residents of villages were mass treated with either oral azithromycin or topical tetracycline and were followed up for nearly 2 years. Three genovar families (A, Ba, and C) and 12 genovars were detected, with 2 genovars (A1 a… Show more
“…Six of the minority genovar A strains had SNPs resulting in amino acid changes within variable segment domains. A similar pattern of a few dominant strains with several other strains present at low frequency has been described previously [7],[10],[14]. The variety of strains in this limited geographical area might suggest that new strains are regularly introduced through mixing with other populations or alternatively that the emergence of new variants is promoted by pressure from the human immune response.…”
Section: Discussionsupporting
confidence: 81%
“…Excepting B2, these differed from strains previously sequenced from The Gambia and elsewhere [7]–[11],[13]. Before treatment most (87%) infections were one of two strains (A1 and A2).…”
Section: Discussionmentioning
confidence: 69%
“…OmpA genotyping has been used previously to investigate C.trachomatis infections in trachoma endemic populations [7]–[14], usually with the goal of better understanding C.trachomatis transmission. However the analysis of o mpA sequence variation is also relevant to the utility of MOMP as a target for chlamydial vaccine development.…”
BackgroundTrachoma, 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.MethodsConjunctival 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.ResultsNinety-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.ConclusionsThe 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.
“…Six of the minority genovar A strains had SNPs resulting in amino acid changes within variable segment domains. A similar pattern of a few dominant strains with several other strains present at low frequency has been described previously [7],[10],[14]. The variety of strains in this limited geographical area might suggest that new strains are regularly introduced through mixing with other populations or alternatively that the emergence of new variants is promoted by pressure from the human immune response.…”
Section: Discussionsupporting
confidence: 81%
“…Excepting B2, these differed from strains previously sequenced from The Gambia and elsewhere [7]–[11],[13]. Before treatment most (87%) infections were one of two strains (A1 and A2).…”
Section: Discussionmentioning
confidence: 69%
“…OmpA genotyping has been used previously to investigate C.trachomatis infections in trachoma endemic populations [7]–[14], usually with the goal of better understanding C.trachomatis transmission. However the analysis of o mpA sequence variation is also relevant to the utility of MOMP as a target for chlamydial vaccine development.…”
BackgroundTrachoma, 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.MethodsConjunctival 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.ResultsNinety-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.ConclusionsThe 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.
“…C. trachomatis isolation was carried out in cycloheximide-treated McCoy cells in 1-dram shell vials by using a modification of the procedure of Ripa and Mardh ( 8 ). We sequenced the ompA gene from all conjunctival isolates ( 9 ). The protocol for determining antimicrobial drug sensitivity ( 10 ) was used with minor modifications.…”
We investigated antimicrobial drug resistance in ocular Chlamydia trachomatis 18 months after 4 biannual communitywide distributions of antimicrobial drugs in a region of Ethiopia where ocular strains of C. trachomatis are highly endemic. We found no significant differences in susceptibilities to azithromycin and doxycycline in 6 posttreatment and 4 pretreatment samples.
“…17 In a community wide antibiotic treatment trial for trachoma, both reinfection and persistent infection in humans were documented indicating loss of antibiotic efficacy. 18 Reactivation of persistent Chlamydia is also a problem that prevents inhibition of Chlamydia replication and weakens the effectiveness of antibiotics. 20,21 Therefore, it is necessary to explore alternative treatment strategies to reduce the excessive production of inflammatory mediators.…”
Abstract:Chlamydia trachomatis is a very common sexually transmissible infection in both developing and developed countries. A hallmark of C. trachomatis infection is the induction of severe inflammatory responses which play critical roles in its pathogenesis. Antibiotics are the only treatment option currently available for controlling C. trachomatis infection; however, they are efficacious only when administered early after an infection. The objectives of this study are to explore alternative strategies in the control and regulation of inflammatory responses triggered by a C. trachomatis infection. We employed silver-polyvinyl pyrrolidone (Ag-PVP) nanoparticles, which have been shown to possess anti-inflammatory properties, as our target and the in vitro mouse J774 macrophage model of C. trachomatis infection. Our hypothesis is that small sizes of Ag-PVP nanoparticles will control inflammatory mediators triggered by a C. trachomatis infection. Cytotoxicity studies using Ag-PVP nanoparticles of 10, 20, and 80 nm sizes revealed .80% macrophage viability up to a concentration of 6.25 µg/mL, with the 10 nm size being the least toxic. All sizes of Ag-PVP nanoparticles, especially the 10 nm size, reduced the levels of the prototypic cytokines, tumor necrosis factor (TNF) and interleukin (IL)-6, as elicited from C. trachomatis infected macrophages. Additionally, Ag-PVP nanoparticles (10 nm) selectively inhibited a broad spectrum of other cytokines and chemokines produced by infected macrophages. Of significance, Ag-PVP nanoparticles (10 nm
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