Longitudinal changes in tear cytokines and antimicrobial proteins in trachomatous disease.

BACKGROUND: Trachoma is a neglected tropical disease caused by ocular infection with Chlamydia trachomatis, where repeated infections and chronic inflammation can ultimately result in scarring, trichiasis and blindness. While scarring is thought to be mediated by a dysregulated immune response, the kinetics of cytokines and antimicrobial proteins in the tear film have not yet been characterised. METHODOLOGY: Pooled tears from a Gambian cohort and Tanzanian cohort were semi-quantitatively screened using a Proteome Profiler Array to identify cytokines differentially regulated in disease. Based on this screen and previous literature, ten cytokines (CXCL1, IP-10, IFN-γ, IL-1ß, IL-8, IL-10, IL-12 p40, IL-1RA, IL-1α and PDGF), lysozyme and lactoferrin were assayed in the Tanzanian cohort by multiplex cytokine assay and ELISA. Finally, CXCL1, IP-10, IL-8, lysozyme and lactoferrin were longitudinally profiled in the Gambian cohort by multiplex cytokine assay and ELISA. RESULTS: In the Tanzanian cohort, IL-8 was significantly increased in those with clinically inapparent infection (p = 0.0086). Lysozyme, IL-10 and chemokines CXCL1 and IL-8 were increased in scarring (p = 0.016, 0.046, 0.016, and 0.037). CXCL1, IP-10, IL-8, lysozyme and lactoferrin were longitudinally profiled over the course of infection in a Gambian cohort study, with evidence of an inflammatory response both before, during and after detectable infection. CXCL1, IL-8 and IP-10 were higher in the second infection episode relative to the first (p = 0.0012, 0.044, and 0.04). CONCLUSIONS: These findings suggest that the ocular immune system responds prior to and continues to respond after detectable C. trachomatis infection, possibly due to a positive feedback loop inducing immune activation. Levels of CXC chemokines in successive infection episodes were increased, which may offer an explanation as to why repeated infections are a risk factor for scarring.

The introduction of syphilis point of care tests in resource limited settings.

INTRODUCTION: Syphilis remains an important and preventable cause of stillbirth and neonatal mortality. About 1 million women with active syphilis become pregnant each year. Without treatment, 25% of them will deliver a stillborn baby and 33% a low birth weight baby with an increased chance of dying in the first month of life. Adverse pregnancy outcomes due to syphilis can be prevented by screening pregnant women, and treating those who test positive with a single dose of penicillin before 28 weeks' gestation. Areas covered: This manuscript covers the impact of syphilis on pregnancy outcome, the diagnosis of syphilis, with a special focus on point of care (POC) tests, and challenges to the introduction of POC tests, and their potential impact on the control and prevention of syphilis in resource limited settings. Expert commentary: POC tests for syphilis are available which meet the ASSURED criteria, and could make syphilis screening accessible to all women anywhere in the world who attend an antenatal clinic. High quality dual POC tests for HIV and syphilis could ensure that well-funded programmes for the prevention of mother to child transmission of HIV can contribute towards increased coverage of antenatal syphilis screening, and prevent more than 300,000 adverse pregnancy outcomes due to syphilis annually. Alongside investment to increase availability of syphilis POC tests, operational research is needed to understand how best to improve screening of pregnant women and to translate test availability into improved pregnancy outcomes.

The conjunctival microbiome in health and trachomatous disease: a case control study.

BACKGROUND: Trachoma, caused by Chlamydia trachomatis, remains the world's leading infectious cause of blindness. Repeated ocular infection during childhood leads to scarring of the conjunctiva, in-turning of the eyelashes (trichiasis) and corneal opacity in later life. There is a growing body of evidence to suggest non-chlamydial bacteria are associated with clinical signs of trachoma, independent of C. trachomatis infection. METHODS: We used deep sequencing of the V1-V3 region of the bacterial 16S rRNA gene to characterize the microbiome of the conjunctiva of 220 residents of The Gambia, 105 with healthy conjunctivae and 115 with clinical signs of trachoma in the absence of detectable C. trachomatis infection. Deep sequencing was carried out using the Roche-454 platform. Sequence data were processed and analyzed through a pipeline developed by the Human Microbiome Project. RESULTS: The microbiome of healthy participants was influenced by age and season of sample collection with increased richness and diversity seen in younger participants and in samples collected during the dry season. Decreased diversity and an increased abundance of Corynebacterium and Streptococcus were seen in participants with conjunctival scarring compared to normal controls. Abundance of Corynebacterium was higher still in adults with scarring and trichiasis compared to adults with scarring only. CONCLUSIONS: Our results indicate that changes in the conjunctival microbiome occur in trachomatous disease; whether these are a cause or a consequence is yet unknown.