Active trachoma cases in the Solomon Islands have varied polymicrobial community structures but do not associate with individual non-chlamydial pathogens of the eye

Butcher, Robert; Sokana, Oliver; Jack, Kelvin; Kalae, Eric; Sui, Leslie; Russell, Charles J.; Houghton, Joanna; Palmer, Christine D.; Holland, Martin J.; Mesurier, Richard T Le; Solomon, Anthony W.; Mabey, David

doi:10.1101/134213

Cited by 6 publications

(12 citation statements)

References 43 publications

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“…The World Health Organization guidelines for implementing mass drug administration (MDA) are based largely on TF prevalence. We have previously argued that whilst the Solomon Islands has sufficiently prevalent clinical signs (TF) of trachoma to qualify for implementation of MDA, the prevalence of infection and trichiasis [ 3 , 5 ], as well as severe scarring and serological signs of prior infection [ 6 ] are all too low to suggest that clinical diagnosis with TF has the necessary specificity to be used as an indicator of need for intervention in this population. By showing that the transcriptional profile of TF ( Ct uninfected) cases in the Solomon Islands share some, but not all, the components of typical trachoma responses seen elsewhere, the current findings add to those of our previous studies to suggest that the majority of TF disease we observe there is not related to Ct .…”

Section: Resultsmentioning

confidence: 99%

“…From the whole population sample, three subsets of specimens were selected for the microarray-based gene expression profiling experiment. Group N ( n = 7) were children who had neither TF, nor Ct infection [ 3 ] , nor any of other common ocular infections (as listed in the introduction) [ 6 ]. Group D ( n = 7) were children who did have TF, but had neither Ct nor any of the other infections.…”

Section: Methodsmentioning

confidence: 99%

“…and Adenoviridae ), we found no association between TF and any of these bacteria and viruses. A broad screen for changes in bacterial communities of the conjunctiva in TF cases was similarly null [ 6 ]. It could therefore be reasonably concluded that TF in this population is unlikely to be linked to any bacterial infection.…”

Section: Introductionmentioning

confidence: 99%

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Conjunctival transcriptome profiling of Solomon Islanders with active trachoma in the absence of Chlamydia trachomatis infection

et al. 2018

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BackgroundClinical signs of active (inflammatory) trachoma are found in many children in the Solomon Islands, but the majority of these individuals have no serological evidence of previous infection with Chlamydia trachomatis. In Temotu and Rennell and Bellona provinces, ocular infections with C. trachomatis were seldom detected among children with active trachoma; a similar lack of association was seen between active trachoma and other common bacterial and viral causes of follicular conjunctivitis. Here, we set out to characterise patterns of gene expression at the conjunctivae of children in these provinces with and without clinical signs of trachomatous inflammation-follicular (TF) and C. trachomatis infection.MethodsPurified RNA from children with and without active trachoma was run on Affymetrix GeneChip Human Transcriptome Array 2.0 microarrays. Profiles were compared between individuals with ocular C. trachomatis infection and TF (group DI; n = 6), individuals with TF but no C. trachomatis infection (group D; n = 7), and individuals without TF or C. trachomatis infection (group N; n = 7). Differential gene expression and gene set enrichment for pathway membership were assessed.ResultsConjunctival gene expression profiles were more similar within-group than between-group. Principal components analysis indicated that the first and second principal components combined explained almost 50% of the variance in the dataset. When comparing the DI group to the N group, genes involved in T-cell proliferation, B-cell signalling and CD8+ T cell signalling pathways were differentially regulated. When comparing the DI group to the D group, CD8+ T-cell regulation, interferon-gamma and IL17 production pathways were enriched. Genes involved in RNA transcription and translation pathways were upregulated when comparing the D group to the N group.ConclusionsGene expression profiles in children in the Solomon Islands indicate immune responses consistent with bacterial infection when TF and C. trachomatis infection are concurrent. The transcriptomes of children with TF but without identified infection were not consistent with allergic or viral conjunctivitis.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Conjunctival transcriptome profiling of Solomon Islanders with active trachoma in the absence of Chlamydia trachomatis infection

et al. 2018

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“…Data from the Solomon Islands investigating this pattern suggest that the cause may not be bacterial. 36 Another marker of interest for assessing severity of disease is intense inflammation. Intense inflammation is consistently demonstrated to be associated with incidence and progression of scarring in longitudinal studies and prevalence and load of Ct infection are higher in people with TI than in those with TF.…”

Section: Discussionmentioning

confidence: 99%

Ocular Chlamydia trachomatis infection, anti-Pgp3 antibodies and conjunctival scarring in Vanuatu and Tarawa, Kiribati before antibiotic treatment for trachoma

Butcher

Handley

Garae

et al. 2020

Journal of Infection

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Introduction: In the peri-elimination setting, the positive predictive value of trachomatous inflammationfollicular (TF), the primary marker used to determine need for antibiotics for trachoma, is suboptimal. Here, three non-TF measures are used to compare two regions where TF prevalence exceeds the threshold for intervention, but where the Chlamydia trachomatis (Ct) prevalence is different. Methods: Population prevalence of trachoma was measured in Vanuatu (n = 3470) and Kiribati (n = 2922). Dried blood spots (DBS) and conjunctival photographs were collected from every survey participant, and conjunctival swabs were collected from those aged 1-9 years. Individuals were tested for blood anti-Pgp3 antibodies, Ct DNA at the conjunctiva and severity of conjunctival scarring. Results: The prevalence of TF in 1-9-year-olds was 16.5% in Vanuatu and 38.2% in Tarawa. 7% of people aged ≥1 year in Vanuatu had conjunctival scarring compared to 27% in Tarawa. The prevalence of ocular Ct infection in 1-9-year-olds was 1.5% in Vanuatu and 27.4% in Tarawa. The seroconversion rate amongst 1-9-year-old children in Vanuatu and Tarawa was 0.018 and 0.197 events per child per year, respectively. Conclusions: Comparing Vanuatu to Tarawa demonstrates several markers that could be used to differentiate the trachoma status of populations in these (and other) locations.

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“…This may affect the presence of other organisms in the conjunctiva. Indeed, although conflicting evidence exists, studies of human trachoma have reported that chlamydial disease is associated with a decrease in microbial richness and diversity compared to healthy controls [31,32]. Innate immune responses form a key part of the host response to chlamydial infection and, although only speculation, it is possible that upregulation of these processes at the mucosal surface may inadvertently impact on infection by other organisms such as the novel virus detected in this study [30].…”

Section: Discussionmentioning

confidence: 73%

Identification of a Novel Picorna-Like Virus, Burpengary Virus, That Is Negatively Associated with Chlamydial Disease in the Koala

Harvey¹,

Madden²,

Holmes

2019

Preprint

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Koalas (Phascolarctos cinereus) are native Australian marsupials whose populations are in decline from a range of threats. Infectious diseases caused by the bacterium Chlamydia pecorum and other pathogens are of particular concern. We analysed 26 poly-A selected RNA-sequencing libraries from a data set designed to study the immune response of koalas to ocular chlamydial infection. Using virus discovery techniques, we identified the coding-complete genome sequence of a novel picorna-like virus, denoted Burpengary virus, that was most common in south-east Queensland. Notably, abundance measurements of the virus across all 26 libraries revealed an inverse relationship in prevalence with ocular disease in Koalas, suggesting that co-infection between Burpengary virus and Chlamydia pecorum is inhibited.

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Active trachoma cases in the Solomon Islands have varied polymicrobial community structures but do not associate with individual non-chlamydial pathogens of the eye

Cited by 6 publications

References 43 publications

Conjunctival transcriptome profiling of Solomon Islanders with active trachoma in the absence of Chlamydia trachomatis infection

Conjunctival transcriptome profiling of Solomon Islanders with active trachoma in the absence of Chlamydia trachomatis infection

Ocular Chlamydia trachomatis infection, anti-Pgp3 antibodies and conjunctival scarring in Vanuatu and Tarawa, Kiribati before antibiotic treatment for trachoma

Identification of a Novel Picorna-Like Virus, Burpengary Virus, That Is Negatively Associated with Chlamydial Disease in the Koala

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