Multiple Chlamydiaceae species in trachoma: implications for disease pathogenesis and control.
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ABSTRACT:
SUBMITTER: Dean D
PROVIDER: S-EPMC2174965 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Trachoma is the leading cause of preventable blindness. Commercial assays do not discriminate among all Chlamydiaceae species that might be involved in trachoma. We investigated whether a commercial Micro-ArrayTube could discriminate Chlamydiaceae species in DNA extracted directly from conjunctival samples from 101 trachoma patients in Nepal. To evaluate organism viability, we extracted RNA, reverse transcribed it, and subjected it to quantitative real-time PCR. We found that 71 (70.3%) villagers were infected. ArrayTube sensitivity was 91.7% and specificity was 100% compared with that of real-time PCR. Concordance between genotypes detected by microarray and ompA genotyping was 100%. Species distribution included 54 (76%) single infections with Chlamydia trachomatis, C. psittaci, C. suis, or C. pecorum, and 17 (24%) mixed infections that includied C. pneumoniae. Ocular infections were caused by 5 Chlamydiaceae species. Additional studies of trachoma pathogenesis involving Chlamydiaceae species other than C. trachomatis and their zoonotic origins are needed.
| S-EPMC3840858 | biostudies-literature
Project description:BackgroundTrachoma causes blindness through a conjunctival scarring process initiated by ocular Chlamydia trachomatis infection; however, the rates, drivers and pathophysiological determinants are poorly understood. We investigated progressive scarring and its relationship to conjunctival infection, inflammation and transcript levels of cytokines and fibrogenic factors.Methodology/principal findingsWe recruited two cohorts, one each in Ethiopia and Tanzania, of individuals with established trachomatous conjunctival scarring. They were followed six-monthly for two years, with clinical examinations and conjunctival swab sample collection. Progressive scarring cases were identified by comparing baseline and two-year photographs, and compared to individuals without progression. Samples were tested for C. trachomatis by PCR and transcript levels of S100A7, IL1B, IL13, IL17A, CXCL5, CTGF, SPARCL1, CEACAM5, MMP7, MMP9 and CD83 were estimated by quantitative RT-PCR. Progressive scarring was found in 135/585 (23.1%) of Ethiopian participants and 173/577 (30.0%) of Tanzanian participants. There was a strong relationship between progressive scarring and increasing inflammatory episodes (Ethiopia: OR 5.93, 95%CI 3.31-10.6, p<0.0001. Tanzania: OR 5.76, 95%CI 2.60-12.7, p<0.0001). No episodes of C. trachomatis infection were detected in the Ethiopian cohort and only 5 episodes in the Tanzanian cohort. Clinical inflammation, but not scarring progression, was associated with increased expression of S100A7, IL1B, IL17A, CXCL5, CTGF, CEACAM5, MMP7, CD83 and reduced SPARCL1.Conclusions/significanceScarring progressed in the absence of detectable C. trachomatis, which raises uncertainty about the primary drivers of late-stage trachoma. Chronic conjunctival inflammation appears to be central and is associated with enriched expression of pro-inflammatory factors and altered expression of extracellular matrix regulators. Host determinants of scarring progression appear more complex and subtle than the features of inflammation. Overall this indicates a potential role for anti-inflammatory interventions to interrupt progression and the need for trichiasis disease surveillance and surgery long after chlamydial infection has been controlled at community level.
| S-EPMC4430253 | biostudies-literature
Project description:BackgroundTrachoma is thought to be common over large parts of Southern Sudan. However, many areas of the country, particularly west of the Nile, have not yet been surveyed. The aim of this study was to confirm whether trachoma extends into Western Equatoria State from neighboring Central Equatoria, where trachoma is highly prevalent, and whether intervention with the SAFE strategy is required.Methods and findingsPopulation-based cross-sectional surveys were conducted using a two-stage cluster random sampling method to select the study population. Subjects were examined for trachoma by experienced graders using the World Health Organization (WHO) simplified grading scheme. Two counties thought to be most likely to have trachoma were surveyed, Maridi and Mundri. In Maridi, prevalence of one of the signs of active trachoma (trachomatous inflammation-follicular (TF)) in children aged 1-9 years was 0.4% (95% confidence interval (CI), 0.0%-0.8%), while no children showing the other possible sign, trachomatous inflammation-intense (TI), were identified. No trachomatous trichiasis (TT) was found in those aged under 15, and prevalence was 0.1% (95% CI, 0.0%-0.4%) in those aged 15 years and above. In Mundri, active trachoma was also limited to signs of TF, with a prevalence of 4.1% (95% CI, 1.4%-6.9%) in children aged 1-9 years. Again, no TT was found in those aged under 15, and prevalence in those aged 15 years and above was 0.3% (95% CI, 0.0%-0.8%).ConclusionTrachoma prevalence in the east of Western Equatoria State is below the WHO recommended intervention threshold for mass drug administration of antibiotic treatment in all villages. However, the prevalence of TF and TT in some villages, particularly in Mundri County, is sufficiently high to warrant targeted interventions at the community level. These results demonstrate that trachoma is not a major public health problem throughout Southern Sudan. Further studies will be required to determine trachoma prevalence in other areas, particularly west of the Nile, but there are presently no resources to survey each county. Studies should thus be targeted to areas where collection of new data would be most informative.
| S-EPMC2710503 | biostudies-literature
Project description:BackgroundTrachoma, the worldwide leading infectious cause of blindness, is due to repeated conjunctival infection with Chlamydia trachomatis. The effects of control interventions on population levels of infection and active disease can be promptly measured, but the effects on severe ocular sequelae require long-term monitoring. We present an age-structured mathematical model of trachoma transmission and disease to predict the impact of interventions on the prevalence of blinding trachoma.Methodology/principal findingsThe model is based on the concept of multiple reinfections leading to progressive conjunctival scarring, trichiasis, corneal opacity and blindness. It also includes aspects of trachoma natural history, such as an increasing rate of recovery from infection and a decreasing chlamydial load with subsequent infections that depend upon a (presumed) acquired immunity that clears infection with age more rapidly. Parameters were estimated using maximum likelihood by fitting the model to pre-control infection prevalence data from hypo-, meso- and hyperendemic communities from The Gambia and Tanzania. The model reproduces key features of trachoma epidemiology: 1) the age-profile of infection prevalence, which increases to a peak at very young ages and declines at older ages; 2) a shift in this prevalence peak, toward younger ages in higher force of infection environments; 3) a raised overall profile of infection prevalence with higher force of infection; and 4) a rising profile, with age, of the prevalence of the ensuing severe sequelae (trachomatous scarring, trichiasis), as well as estimates of the number of infections that need to occur before these sequelae appear.Conclusions/significanceWe present a framework that is sufficiently comprehensive to examine the outcomes of the A (antibiotic) component of the SAFE strategy on disease. The suitability of the model for representing population-level patterns of infection and disease sequelae is discussed in view of the individual processes leading to these patterns.
| S-EPMC2691478 | biostudies-literature
Project description:Recent taxonomic developments, based on 16s and 23s rRNA gene sequences, have divided the family Chlamydiaceae into two genera and nine species, of which five have been found to infect humans. Few simple methods are available to detect and identify all species sensitively and specifically. In this study the suitability of the omp2 gene as a target for molecular identification of Chlamydiaceae is demonstrated. Phylogenetic analysis of partial omp2 gene sequences from all nine species agrees with the recently published taxonomic changes based on the ribosomal genes. The use of a family-specific PCR primer pair, which is able to amplify the 5' end of the omp2 gene from all Chlamydiaceae except some Chlamydophila pecorum strains, is described. Identification of all nine species was achieved using restriction fragment length polymorphism analysis with a single enzyme, AluI, confirmed by DNA sequencing. A PCR enzyme-linked oligonucleotide assay was developed which can detect a single chlamydial genome and may be applied to DNA extracts from any specimen or culture for the detection of single or mixed human chlamydial infection.
| S-EPMC88299 | biostudies-literature
Project description: Not available
| S-EPMC3358148 | biostudies-literature
Project description:BackgroundWe describe molecular processes that can facilitate pathogenesis of Alzheimer's disease (AD) by analyzing the catalytic cycle of a membrane-imbedded protease ?-secretase, from the initial interaction with its C99 substrate to the final release of toxic A? peptides.ResultsThe C-terminal AICD fragment is cleaved first in a pre-steady-state burst. The lowest A?42/A?40 ratio is observed in pre-steady-state when A?40 is the dominant product. A?42 is produced after A?40, and therefore A?42 is not a precursor for A?40. The longer more hydrophobic A? products gradually accumulate with multiple catalytic turnovers as a result of interrupted catalytic cycles. Saturation of ?-secretase with its C99 substrate leads to 30% decrease in A?40 with concomitant increase in the longer A? products and A?42/A?40 ratio. To different degree the same changes in A? products can be observed with two mutations that lead to an early onset of AD, ?E9 and G384A. Four different lines of evidence show that ?-secretase can bind and cleave multiple substrate molecules in one catalytic turnover. Consequently depending on its concentration, Notch?E substrate can activate or inhibit ?-secretase activity on C99 substrate. Multiple C99 molecules bound to ?-secretase can affect processive cleavages of the nascent A? catalytic intermediates and facilitate their premature release as the toxic membrane-imbedded A?-bundles.ConclusionsGradual saturation of ?-secretase with its substrate can be the pathogenic process in different alleged causes of AD. Thus, competitive inhibitors of ?-secretase offer the best chance for a successful therapy, while the noncompetitive inhibitors could even facilitate development of the disease by inducing enzyme saturation at otherwise sub-saturating substrate. Membrane-imbedded A?-bundles generated by ?-secretase could be neurotoxic and thus crucial for our understanding of the amyloid hypothesis and AD pathogenesis.
| S-EPMC3316526 | biostudies-literature
Project description:BackgroundThe Alliance for the Global Elimination of Trachoma has set the target for eliminating trachoma as a public health problem by 2020. However, challenges remain, including socio-cultural issues. Districts in Northern Tanzania, predominantly inhabited by the Maasai ethnic group, remain endemic for trachoma. We explored socio-cultural factors that may impact the elimination of trachoma.Methods/findingsThis study was nested within a larger ethnographic study of trachoma among Maasai in Northern Tanzania. We used stratified random sampling and semi-structured interviews to examine knowledge and understanding. Interviews were conducted and recorded in Maa, by a native Maa speaking trained interviewer. Transcripts were translated into English. A framework method for a content analysis was used. There was awareness of trachoma and basic symptoms. Yet understanding of etiology and prevention was poor. Trachoma was attributed to pollen, dust, and smoke. Water was recognized as beneficial, but seen as treatment and not prevention. Traditional medicines were most often used for treating conjunctival inflammation, with the most common being a rough leaf used to scratch the inside of the eyelid until it bleeds. Knowledge of mass drug administration (MDA) was inconsistent, although many thought it helped the community, but it was perceived as only for children and the sick. Many participants reported not taking azithromycin and some had no recollection of MDA six months earlier. There was little connection between childhood infection, trichiasis and related blindness. Trichiasis was often seen as a problem of old women, and treated locally by epilation.Conclusion/significanceUnderstanding indigenous knowledge may help guide control programs, tailor them to local contexts, address local beliefs and dispel misunderstandings. There is an essential need to understand the social, cultural and political context of the target community to deliver effective programs. Despite limited knowledge, the community recognized trachoma as a public health problem. Results have implications for disease control programs in other marginalized communities.
| S-EPMC6611635 | biostudies-literature
Project description:As a contagious bacterial infection that affects the conjunctival covering of the eye, the cornea and the eyelids, trachoma is controlled by an endorsed integrated strategy consisting of surgery for trichiasis, antibiotic therapy, facial cleanliness and environmental improvement, namely, the SAFE strategy developed by World Health Organization. Developed based on evidence from previous field trials and constantly modified in practice, SAFE strategy has greatly boosted the progress in trachoma control. Regardless of the fact that there are still many pending questions, national program coordinators are convinced that trachoma control initiative based on SAFE strategy would be effective.
| S-EPMC6288535 | biostudies-literature
Project description:Trachoma, the leading infectious cause of blindness, is caused by Chlamydia trachomatis (Ct), a bacterium of the phylum Chlamydiae. Recent investigations revealed the existence of additional families within the phylum Chlamydiae, also termed Chlamydia-like organisms (CLOs). In this study, the frequency of Ct and CLOs was examined in the eyes of healthy Sudanese (control) participants and those with trachoma (case). We tested 96 children (54 cases and 42 controls) and 93 adults (51 cases and 42 controls) using broad-range Chlamydiae and Ct-specific (omcB) real-time PCR. Samples positive by broad-range Chlamydiae testing were subjected to DNA sequencing. Overall Chlamydiae prevalence was 36%. Sequences corresponded to unclassified and classified Chlamydiae. Ct infection rate was significantly higher in children (31.5%) compared to adults (0%) with trachoma (p < 0.0001). In general, 21.5% of adults and 4.2% of children tested positive for CLOs (p = 0.0003). Our findings are consistent with previous investigations describing the central role of Ct in trachoma among children. This is the first study examining human eyes for the presence of CLOs. We found an age-dependent distribution of CLO DNA in human eyes with significantly higher positivity in adults. Further studies are needed to understand the impact of CLOs in trachoma pathogenicity and/or protection.
| S-EPMC5943520 | biostudies-literature