In this low-prevalence setting, infected individuals without signs of active trachoma constitute a significant reservoir of infection. Treatment of a defined unit of people who live with someone with clinically active trachoma would effectively target antibiotic treatment to infected people without signs of disease.

BackgroundTrachoma, caused by ocular infection with Chlamydia trachomatis, remains the leading infectious cause of blindness and in 2002 was responsible for 3.6% of total global blindness. Although transmission can be successfully interrupted using antibiotics and improvements in public and personal hygiene, the long-term success of the control programmes advocated by the World Health Organization are still uncertain. For the complete control and prevention of trachoma, a vaccine would be highly desirable. Currently there are no licensed vaccines for trachoma, and no human vaccine trials have been conducted since the 1960s. A barrier to new attempts to design and introduce a vaccine is the identification of immunologic correlates of protective immunity or immunopathology. We studied important correlates of the immune response in a trachoma-endemic population in order to improve our knowledge of this disease. This is essential for the successful development of a vaccine against both ocular and genital C. trachomatis infection.Methods and FindingsWe used quantitative real-time PCR for C. trachomatis 16S rRNA to identify conjunctival infection. The expression of IFN-γ, IDO, IL-10, and FOXP3 mRNA transcripts was measured. We evaluated the role of immune effector and regulatory responses in the control of chlamydial infection and in the resolution of clinical signs of trachoma in endemic communities in Gambia. All host transcripts examined were detectable even in normal conjunctiva. The levels of these transcripts were increased, compared to normal uninfected conjunctiva, when infection was detected, with or without clinical disease signs. Interestingly, when clinical disease signs were present in the absence of infection, the expression of a regulatory T cell transcription factor, FOXP3, remained elevated.ConclusionsThere is evidence of an increase in the magnitude of the local anti-chlamydial cytokine immune responses with age. This increase is coupled to a decline in the prevalence of infection and active trachoma, suggesting that effective adaptive immunity is acquired over a number of years. The anti-chlamydial and inflammatory immune response at the conjunctival surface, which may control chlamydial replication, is closely matched by counter inflammatory or regulatory IL-10 expression. Differences in the level of FOXP3 expression in the conjunctiva may indicate a role for regulatory T cells in the resolution of the conjunctival immune response, which is important in protection from immunopathology. However, the expression of cytokines that control chlamydial replication and those that regulate the conjunctival immune response is not simply juxtaposed; the interaction between the infection and the clinical disease process is therefore more complex.

Experimental evidence implicates interferon gamma (IFNg) in protection from and resolution of chlamydial infection. Conversely, interleukin 10 (IL10) is associated with susceptibility and persistence of infection and pathology. We studied genetic variation within the IL10 and IFNg loci in relation to the risk of developing severe complications of human ocular Chlamydia trachomatis infection. A total of 651 Gambian subjects with scarring trachoma, of whom 307 also had potentially blinding trichiasis and pair-matched controls with normal eyelids, were screened for associations between single-nucleotide polymorphisms (SNPs), SNP haplotypes and the risk of disease. MassEXTEND (Sequenom) and MALDI-TOF mass spectrometry were used for detection and analysis of SNPs and the programs PHASE and SNPHAP used to infer haplotypes from population genetic data. Multivariate conditional logistic regression analysis identified IL10 and IFNg SNP haplotypes associated with increased risk of both trachomatous scarring and trichiasis. SNPs in putative IFNg and IL10 regulatory regions lay within the disease-associated haplotypes. The IFNg þ 874A allele, previously linked to lower IFNg production, lies in the IFNg risk haplotype and was more common among cases than controls, but not significantly so. The promoter IL10-1082G allele, previously associated with high IL10 expression, is in both susceptibility and resistance haplotypes.

No abstract

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.