Ribosomal RNA evidence of ocular Chlamydia trachomatis infection following 3 annual mass azithromycin distributions in communities with highly prevalent trachoma.
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ABSTRACT:
SUBMITTER: Keenan JD
PROVIDER: S-EPMC3245728 | biostudies-literature | 2012 Jan
REPOSITORIES: biostudies-literature
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Ribosomal RNA evidence of ocular Chlamydia trachomatis infection following 3 annual mass azithromycin distributions in communities with highly prevalent trachoma.
Keenan Jeremy D JD Ayele Berhan B Gebre Teshome T Moncada Jeanne J Stoller Nicole E NE Zhou Zhaoxia Z Porco Travis C TC McCulloch Charles E CE Gaynor Bruce D BD Emerson Paul M PM Schachter Julius J Lietman Thomas M TM
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20111117 2
Twelve trachoma-hyperendemic communities were treated with 3 annual mass azithromycin distributions. Children aged 0-9 years were monitored 1 year following the third treatment. An RNA-based test detected ocular chlamydial infection in more children than did a DNA-based test (6.9% vs 4.2%), and in a larger number of communities (8 vs 7). ...[more]
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Project description:Prior studies have theorized that low chlamydial genetic diversity following mass azithromycin treatments for trachoma may create a population bottleneck that prevents the return of infection, but little empirical evidence exists to support this hypothesis. In this study, a single mass azithromycin distribution was administered to 21 communities in the Gurage Zone of Ethiopia in 2003. All children aged 1-5 years had conjunctival swabs performed before treatment and 2 and 6 months after treatment. All swabs positive for Chlamydia trachomatis at 2 months underwent typing of the gene encoding the major outer membrane protein (ompA) of C. trachomatis, as did the same number of swabs per community from the pretreatment and 6-month visits. Diversity of ompA types, expressed as the reciprocal of Simpson's index, was calculated for each community. In total, 15 ompA types belonging to the A and B genovars were identified. The mean diversity was 2.11 (95% confidence interval: 1.79, 2.43) before treatment and 2.16 (95% confidence interval: 1.76, 2.55) 2 months after treatment (P = 0.78, paired t test). Diversity of ompA was not associated with the prevalence of ocular chlamydia (P = 0.76) and did not predict subsequent changes in the prevalence of ocular chlamydia (P = 0.32). This study found no evidence to support the theory that ompA diversity is associated with transmission of ocular chlamydia.
| S-EPMC6118063 | biostudies-literature
Project description:BackgroundThe chlamydial major outer membrane protein, encoded by the ompA gene, is a primary target for chlamydial vaccine research. However, human studies of ompA-specific immunity are limited, and prior studies have been limited in differentiating re-infection from persistent infection. The purpose of this study was to assess whether children living in trachoma-endemic communities with re-infections of ocular chlamydia were more likely to be infected with a different or similar genovar.Methodology and findingsThe study included 21 communities from a trachoma-hyperendemic area of Ethiopia that had been treated with a mass azithromycin distribution for trachoma. Conjunctival swabbing was offered to all children younger than 5 years of age at baseline (i.e., pre-treatment), and then at follow-up visits 2 and 6 months later. Swabs were subjected to polymerase chain reaction (PCR) to detect C. trachomatis. A random sample of 359 PCR-positive swabs, stratified by study visit and study community, was chosen for ompA sequencing. In addition, ompA sequencing was performed on all swabs of 24 children who experienced chlamydial re-infection (i.e., positive chlamydial test before treatment, negative test 2 months following mass distribution of azithromycin, and again a positive test 6 months post-treatment). ompA sequencing was successful for 351 of 359 swabs of the random sample and 44 of 48 swabs of the re-infection sample. In the random sample, ompA types clustered within households more than would be expected by chance. Among the 21 re-infected children with complete ompA data, 14 had the same ompA type before and after treatment.ConclusionThe high frequency of ompA concordance suggests incomplete genovar-specific protective immunity and the need for multiple antigens as vaccine targets.
| S-EPMC8959170 | biostudies-literature
Project description:Trachoma, caused by Chlamydia trachomatis (Ct), is the leading infectious blinding disease worldwide. Chronic conjunctival inflammation develops in childhood and leads to eyelid scarring and blindness in adulthood. The immune response to Ct provides only partial protection against re-infection, which can be frequent. Moreover, the immune response is central to the development of scarring pathology, leading to loss of vision. Here we review the current literature on both protective and pathological immune responses in trachoma. The resolution of Ct infection in animal models is IFN?-dependent, involving Th1 cells, but whether this is the case in human ocular infection still needs to be confirmed. An increasing number of studies indicate that innate immune responses arising from the epithelium and other innate immune cells, along with changes in matrix metalloproteinase activity, are important in the development of tissue damage and scarring. Current trachoma control measures, which are centred on repeated mass antibiotic treatment of populations, are logistically challenging and have the potential to drive antimicrobial resistance. A trachoma vaccine would offer significant advantages. However, limited understanding of the mechanisms of both protective immunity and immunopathology to Ct remain barriers to vaccine development.
| S-EPMC3573101 | biostudies-other
Project description:BackgroundTrachoma, caused by ocular infection with Chlamydia trachomatis, is hyperendemic on the Bijagós Archipelago of Guinea Bissau. An understanding of the risk factors associated with active trachoma and infection on these remote and isolated islands, which are atypical of trachoma-endemic environments described elsewhere, is crucial to the implementation of trachoma elimination strategies.Methodology/principal findingsA cross-sectional population-based trachoma prevalence survey was conducted on four islands. We conducted a questionnaire-based risk factor survey, examined participants for trachoma using the World Health Organization (WHO) simplified grading system and collected conjunctival swab samples for 1507 participants from 293 randomly selected households. DNA extracted from conjunctival swabs was tested using the Roche Amplicor CT/NG PCR assay. The prevalence of active (follicular and/or inflammatory) trachoma was 11% (167/1508) overall and 22% (136/618) in 1-9 year olds. The prevalence of C. trachomatis infection was 18% overall and 25% in 1-9 year olds. There were strong independent associations of active trachoma with ocular and nasal discharge, C. trachomatis infection, young age, male gender and type of household water source. C. trachomatis infection was independently associated with young age, ocular discharge, type of household water source and the presence of flies around a latrine.Conclusions/significanceIn this remote island environment, household-level risk factors relating to fly populations, hygiene behaviours and water usage are likely to be important in the transmission of ocular C. trachomatis infection and the prevalence of active trachoma. This may be important in the implementation of environmental measures in trachoma control.
| S-EPMC4072588 | biostudies-literature
Project description:An important component of the World Health Organization's comprehensive trachoma elimination strategy is the provision of repeated annual mass azithromycin distributions, which are directed at reducing the burden of ocular chlamydia. Knowledge of characteristics associated with infection after mass antibiotic treatments could allow trachoma programs to focus resources to those most likely to be infected with ocular chlamydia.We monitored 12 communities in rural Ethiopia that had received 3 annual mass azithromycin treatments as part of a cluster-randomized trial for trachoma. One year after the third treatment, a random sample of children from each village received conjunctival examination for follicular trachomatous inflammation (TF) and intense trachomatous inflammation (TI), conjunctival swabbing for chlamydial RNA and DNA, and a household survey. The primary outcome for this study was RNA evidence of ocular chlamydia, which we detected in 41 of 573 swabbed children (7.2%, 95%CI 2.7-17.8). In multivariate mixed effects logistic regression models, ocular chlamydial RNA was significantly associated with ocular discharge (OR 2.82, 95%CI 1.07-7.42), missing the most recent mass azithromycin treatment (OR 2.49, 95%CI 1.02-6.05), having a sibling with ocular chlamydia (OR 4.44, 95%CI 1.60-12.29), and above-median community population (OR 7.81, 95%CI 1.56-39.09). Ocular chlamydial infection was also independently associated with TF (OR 3.42, 95%CI 1.56-7.49) and TI (OR 5.39, 95%CI 2.43-11.98).In areas with highly prevalent trachoma treated with multiple rounds of mass azithromycin, trachoma programs could consider continuing mass azithromycin treatments in households that have missed prior mass antibiotic treatments, in households with clinically active trachoma, and in larger communities.
| S-EPMC3236733 | biostudies-literature
Project description:BackgroundTrachoma, caused by Chlamydia trachomatis, remains the leading infectious cause of blindness worldwide. Persistence and progression of the resulting clinical disease appears to be an immunologically mediated process. Azithromycin, which is distributed at the community level for trachoma control, has immunomodulatory properties. We investigated the impact of one round of oral azithromycin on conjunctival immune responses, C. trachomatis infection and clinical signs three- and six- months post treatment relative to three pre-treatment time-points.MethodologyA cohort of children aged 6 to 10 years were recruited from a trachoma endemic region of northern Tanzania and were visited five times in a 12-month period. They were examined for clinical signs of trachoma and conjunctival swabs were collected for laboratory analysis. C. trachomatis infection was detected and the expression of 46 host genes was quantified using quantitative PCR. All community members were offered azithromycin treatment immediately after the six-month timepoint according to international guidelines.FindingsThe prevalence of C. trachomatis infection and inflammatory disease signs were significantly reduced three- and six- months post-mass drug administration (MDA). C. trachomatis infection was strongly associated with clinical signs at all five time-points. A profound anti-inflammatory effect on conjunctival gene expression was observed 3 months post-MDA, however, gene expression had largely returned to pre-treatment levels of variation by 6 months. This effect was less marked, but still observed, after adjusting for C. trachomatis infection and when the analysis was restricted to individuals who were free from both infection and clinical disease at all five time-points. Interestingly, a modest effect was also observed in individuals who did not receive treatment.ConclusionConjunctival inflammation is the major clinical risk factor for progressive scarring trachoma, therefore, the reduction in inflammation associated with azithromycin treatment may be beneficial in limiting the development of potentially blinding disease sequelae. Future work should seek to determine whether this effect is mediated directly through inhibition of pro-inflammatory intracellular signalling molecules, through reductions in concurrent, sub-clinical infections, and/or through reduction of infection exposure.
| S-EPMC6658141 | biostudies-literature
Project description:BackgroundChlamydia trachomatis (Ct) is the most common infectious cause of blindness and bacterial sexually transmitted infection worldwide. Ct strain-specific differences in clinical trachoma suggest that genetic polymorphisms in Ct may contribute to the observed variability in severity of clinical disease.MethodsUsing Ct whole genome sequences obtained directly from conjunctival swabs, we studied Ct genomic diversity and associations between Ct genetic polymorphisms with ocular localization and disease severity in a treatment-naïve trachoma-endemic population in Guinea-Bissau, West Africa.ResultsAll Ct sequences fall within the T2 ocular clade phylogenetically. This is consistent with the presence of the characteristic deletion in trpA resulting in a truncated non-functional protein and the ocular tyrosine repeat regions present in tarP associated with ocular tissue localization. We have identified 21 Ct non-synonymous single nucleotide polymorphisms (SNPs) associated with ocular localization, including SNPs within pmpD (odds ratio, OR = 4.07, p* = 0.001) and tarP (OR = 0.34, p* = 0.009). Eight synonymous SNPs associated with disease severity were found in yjfH (rlmB) (OR = 0.13, p* = 0.037), CTA0273 (OR = 0.12, p* = 0.027), trmD (OR = 0.12, p* = 0.032), CTA0744 (OR = 0.12, p* = 0.041), glgA (OR = 0.10, p* = 0.026), alaS (OR = 0.10, p* = 0.032), pmpE (OR = 0.08, p* = 0.001) and the intergenic region CTA0744-CTA0745 (OR = 0.13, p* = 0.043).ConclusionsThis study demonstrates the extent of genomic diversity within a naturally circulating population of ocular Ct and is the first to describe novel genomic associations with disease severity. These findings direct investigation of host-pathogen interactions that may be important in ocular Ct pathogenesis and disease transmission.
| S-EPMC5828069 | biostudies-literature
Project description:Although trachoma control programs frequently use the World Health Organization (WHO) simplified grading system for trachoma to monitor the clinical response after repeated mass azithromycin treatments, the programmatic relevance of this evaluation after multiple rounds of antibiotic treatments is unclear.Three rounds of annual mass azithromycin were distributed to 12 villages in Ethiopia. Twelve months after the third treatment, children were assessed for follicular trachomatous inflammation (TF) and intense trachomatous inflammation (TI) using the WHO simplified grading system and for ocular chlamydial infection using DNA-based and RNA-based tests. Test characteristics for predicting chlamydial infection were computed assuming a chlamydial RNA-based gold standard. As a secondary analysis, test characteristics were also assessed using a latent class analysis.The prevalence of RNA evidence of ocular chlamydia was 7.1% (95% confidence interval [CI], 2.7-17.4). A DNA-based test and TF had sensitivities of 61.0% (95% CI, 47.1-73.3) and 65.9% (95% CI, 41.6-83.9), specificities of 100% (95% CI, 99.3-100) and 67.5% (95% CI, 61.0-73.5), and positive predictive values of 100% (95% CI, 86.3-100) and 13.4% (95% CI, 5.5-29.3) compared with an RNA-based gold standard. The latent class analysis confirmed that the RNA-based test was a reasonable choice for a gold standard, with a sensitivity of 100% (95% CI, 67.1-100) and specificity of 99.6% (95% CI, 98.1-100).Basing treatment decisions after mass azithromycin distributions on the WHO simplified grading system will maximize the treatment of infected persons compared with a DNA-based test but will also result in more uninfected persons being treated. The RNA-based test was considerably more sensitive, and almost equivalently specific, compared with a DNA-based test. (ClinicalTrials.gov number, NCT00322972.).
| S-EPMC3292361 | biostudies-literature
Project description:The prevalence of trachomatous inflammation–follicular (TF) in Solomon Island children aged 1–9 years is high enough to warrant, among other interventions, mass distribution of azithromycin. However, over 90% of those with TF did not have concurrent Chlamydia trachomatis infection. We analysed the transcriptome of children with TF and Ct infection, children diagnosed with TF but no Ct infection and children with neither TF nor Ct infection to better understand host responses during an episode of TF, and investigate whether it can provide any clues about the aetiology of TF in this context.
2018-02-28 | GSE106961 | GEO
Project description:BackgroundTrachoma is the leading infectious cause of blindness and is caused by ocular infection with the bacterium Chlamydia trachomatis (Ct). While the majority of the global disease burden is found in sub-Saharan Africa, the Western Pacific Region has been identified as trachoma endemic. Population surveys carried out throughout Fiji have shown an abundance of both clinically active trachoma and trachomatous trichiasis in all divisions. This finding is at odds with the clinical experience of local healthcare workers who do not consider trachoma to be highly prevalent. We aimed to determine whether conjunctival infection with Ct could be detected in one administrative division of Fiji.MethodsA population-based survey of 2306 individuals was conducted using the Global Trachoma Mapping Project methodology. Population prevalence of active trachoma in children and trichiasis in adults was estimated using the World Health Organization simplified grading system. Conjunctival swabs were collected from 1009 children aged 1-9 years. DNA from swabs was tested for the presence of the Ct plasmid and human endogenous control.ResultsThe prevalence of active trachoma in 1-9 year olds was 3.4%. The age-adjusted prevalence was 2.8% (95% CI: 1.4-4.3%). The unadjusted prevalence of ocular Ct infection in 1-9 year-olds was 1.9% (19/1009), and the age-adjusted infection prevalence was 2.3% (95% CI: 0.4-2.5%). The median DNA load was 41 Ct plasmid copies per swab (min 20, first quartile 32, mean 6665, third quartile 161, max 86354). There was no association between current infection and follicular trachoma. No cases of trachomatous trichiasis were identified.DiscussionThe Western Division of Fiji has a low prevalence of clinical trachoma. Ocular Ct infections were observed, but they were predominantly low load infections and were not correlated with clinical signs. Our study data suggest that trachoma does not meet the WHO definition of a public health problem in this Division of Fiji, but the inconsistency with previous studies warrants further investigation.
| S-EPMC4942140 | biostudies-literature