BackgroundTrachoma is endemic in several Pacific Island states. Recent surveys across the Solomon Islands indicated that whilst trachomatous inflammation—follicular (TF) was present at levels warranting intervention, the prevalence of trachomatous trichiasis (TT) was low. We set out to determine the relationship between chlamydial infection and trachoma in this population.MethodsWe conducted a population-based trachoma prevalence survey of 3674 individuals from two Solomon Islands provinces. Participants were examined for clinical signs of trachoma. Conjunctival swabs were collected from all children aged 1–9 years. We tested swabs for Chlamydia trachomatis (Ct) DNA using droplet digital PCR. Chlamydial DNA from positive swabs was enriched and sequenced for use in phylogenetic analysis.ResultsWe observed a moderate prevalence of TF in children aged 1–9 years (n = 296/1135, 26.1%) but low prevalence of trachomatous inflammation—intense (TI) (n = 2/1135, 0.2%) and current Ct infection (n = 13/1002, 1.3%) in children aged 1–9 years, and TT in those aged 15+ years (n = 2/2061, 0.1%). Ten of 13 (76.9%) cases of infection were in persons with TF or TI (p = 0.0005). Sequence analysis of the Ct-positive samples yielded 5/13 (38%) complete (>95% coverage of reference) genome sequences, and 8/13 complete plasmid sequences. Complete sequences all aligned most closely to ocular serovar reference strains.DiscussionThe low prevalence of TT, TI and Ct infection that we observed are incongruent with the high proportion of children exhibiting signs of TF. TF is present at levels that apparently warrant intervention, but the scarcity of other signs of trachoma indicates the phenotype is mild and may not pose a significant public health threat. Our data suggest that, whilst conjunctival Ct infection appears to be present in the region, it is present at levels that are unlikely to be the dominant driving force for TF in the population. This could be one reason for the low prevalence of TT observed during the study.

Robust surveillance methods are needed for trachoma control and recrudescence monitoring, but existing methods have limitations. Here, we analyse data from nine trachoma-endemic populations and provide operational thresholds for interpretation of serological data in low-transmission and post-elimination settings. Analyses with sero-catalytic and antibody acquisition models provide insights into transmission history within each population. To accurately estimate sero-conversion rates (SCR) for trachoma in populations with high-seroprevalence in adults, the model accounts for secondary exposure to Chlamydia trachomatis due to urogenital infection. We estimate the population half-life of sero-reversion for anti-Pgp3 antibodies to be 26 (95% credible interval (CrI): 21–34) years. We show SCRs below 0.015 (95% confidence interval (CI): 0.0–0.049) per year correspond to a prevalence of trachomatous inflammation—follicular below 5%, the current threshold for elimination of active trachoma as a public health problem. As global trachoma prevalence declines, we may need cross-sectional serological survey data to inform programmatic decisions.

The low population-prevalence of trachomatous trichiasis and high prevalence of trachomatous inflammation-follicular (TF) provide contradictory estimates of the magnitude of the public health threat from trachoma in the Solomon Islands. Improved characterisation of the biology of trachoma in the region may support policy makers as they decide what interventions are required. Here, age-specific profiles of anti-Pgp3 antibodies and conjunctival scarring were examined to determine whether there is evidence of ongoing transmission and pathology from ocular infection. A total of 1511 individuals aged ≥1 year were enrolled from randomly selected households in 13 villages in which >10% of children aged 1-9 years had TF prior to a single round of azithromycin mass drug administration undertaken six months previously. Blood was collected to be screened for antibodies to the antigen Pgp3. Tarsal conjunctival photographs were collected for analysis of scarring severity. Anti-Pgp3 seropositivity was 18% in 1-9 year olds, sharply increasing around the age of sexual debut to reach 69% in those over 25 years. Anti-Pgp3 seropositivity did not increase significantly between the ages of 1-9 years and was not associated with TF (p=0.581) or scarring in children (p=0.472). Conjunctival scars were visible in 13.1% of photographs. Mild (p<0.0001) but not severe (p=0.149) scars increased in prevalence with age. Neither conjunctival scars nor lymphoid follicles were associated with antibodies to suggesting that they are unlikely to be a direct result of ocular infection Clinical signs of trachoma were prevalent in this population but were not indicative of the underlying rates of infection. The current World Health Organization guidelines for trachoma elimination indicated that this population should receive intervention with mass distribution of antibiotics, but the data presented here suggest that this may not have been appropriate.

Purpose: We sought to complete the baseline trachoma map of the Solomon Islands by establishing prevalences of active trachoma and trichiasis in the provinces of Choiseul, Western, Rennell-Bellona, and Temotu. Methods: Using the standardized methodology developed for the Global Trachoma Mapping Project, we conducted cross-sectional community-based surveys from September to November 2013. Choiseul and Western provinces were each mapped as separate evaluation units (EUs); Rennell-Bellona and Temotu were combined to form a third EU. Results: A total of 9819 individuals were sampled for inclusion, with 9224 (93.3%) consenting to examination, of whom 4587 (46.3%) were female. Survey teams visited 82 villages, and surveyed 2448 households. Two EUs had prevalences of trachomatous inflammation – follicular (TF) in 1–9-year-olds over the 10% threshold at which WHO recommends mass distribution of azithromycin for at least 3 years (Western 20.4%, 95% confidence interval, CI 15.6–26.3%; Rennell-Bellona/Temotu 22.0%, 95% CI 18.5–26.0%). Choiseul had a TF prevalence of 6.1% (95% CI 4.1–8.6%), and met the criterion for a single round of mass antibiotic distribution before re-survey. The adjusted prevalences of trichiasis in those aged 15+ years were 0.0% (95% CI 0.0–0.2%) in Choiseul, 0.16% (95% CI 0.0–0.5%) in Western, and 0.10% (95% CI 0–0.3%) in Rennell-Bellona/Temotu provinces. All three EUs require implementation of the facial cleanliness and environmental improvement components of the trachoma elimination strategy. Conclusion: Active trachoma is prevalent in the Solomon Islands. However, there is little evidence of the blinding complications of trachoma being a public health problem there. Further research into the explanation for this phenomenon is warranted.

BackgroundSeveral non-chlamydial microbial pathogens are associated with clinical signs of active trachoma in trachoma-endemic communities with a low prevalence of ocular Chlamydia trachomatis (Ct) infection. In the Solomon Islands, the prevalence of Ct among children is low despite the prevalence of active trachoma being moderate. Therefore, we set out to investigate whether active trachoma was associated with a common non-chlamydial infection or with a dominant polymicrobial community dysbiosis in the Solomon Islands.MethodsWe studied DNA from conjunctival swabs collected from 257 Solomon Islanders with active trachoma and matched controls. Droplet digital PCR was used to test for pathogens suspected to be able to induce follicular conjunctivitis. Polymicrobial community diversity and composition were studied by sequencing of hypervariable regions of the 16S ribosomal ribonucleic acid gene in a subset of 54 cases and 53 controls.ResultsAlthough Ct was associated with active trachoma, the number of infections was low (cases, 3.9%; controls, 0.4%). Estimated prevalence (cases and controls, respectively) of each non-chlamydial infection was as follows: Staphylococcus aureus: 1.9 and 1.9%, Adenoviridae: 1.2 and 1.2%, coagulase-negative Staphylococcus: 5.8 and 4.3%, Haemophilus influenzae: 7.4 and 11.7%, Moraxella catarrhalis: 2.3 and 4.7%, and Streptococcus pneumoniae: 7.0 and 6.2%. There was no statistically significant association between the clinical signs of trachoma and the presence or load of any of the non-Ct infections that were assayed. Interindividual variations in the conjunctival microbiome were characterized by differences in the levels of Corynebacterium, Propionibacterium, Helicobacter, and Paracoccus, but diversity and relative abundance of these specific genera did not differ significantly between cases and controls.DiscussionIt is unlikely that the prevalent trachoma-like follicular conjunctivitis in this region of the Solomon Islands has a dominant bacterial etiology. Before implementing community-wide azithromycin distribution for trachoma, policy makers should consider that clinical signs of trachoma can be observed in the absence of any detectable azithromycin-susceptible organism.

Active trachoma cases in the SolomonAll rights reserved. No reuse allowed without permission.(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/134213 doi: bioRxiv preprint first posted online May. 11, 2017; Running header: Microbial correlates of active trachoma in the Solomon Islands 2 Abstract 31 32

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Background: The low population-prevalence of trachomatous trichiasis and high prevalence of trachomatous inflammation–follicular (TF) provide contradictory estimates of the magnitude of the public health threat from trachoma in the Solomon Islands. Improved characterisation of the biology of trachoma in the region may support policy makers as they decide what interventions are required. Here, age-specific profiles of anti-Pgp3 antibodies and conjunctival scarring were examined to determine whether there is evidence of ongoing transmission and pathology from ocular Chlamydia trachomatis (Ct) infection. Methods: A total of 1511 individuals aged ≥1 year were enrolled from randomly selected households in 13 villages in which >10% of children aged 1–9 years had TF prior to a single round of azithromycin mass drug administration undertaken six months previously. Blood was collected to be screened for antibodies to the Ct antigen Pgp3. Tarsal conjunctival photographs were collected for analysis of scarring severity. Results: Anti-Pgp3 seropositivity was 18% in 1–9 year olds, sharply increasing around the age of sexual debut to reach 69% in those over 25 years. Anti-Pgp3 seropositivity did not increase significantly between the ages of 1–9 years and was not associated with TF (p=0.581) or scarring in children (p=0.472). Conjunctival scars were visible in 13.1% of photographs. Mild (p<0.0001) but not severe (p=0.149) scars increased in prevalence with age. Conclusions: Neither conjunctival scars nor lymphoid follicles were associated with antibodies to Ct, suggesting that they are unlikely to be a direct result of ocular Ct infection . Clinical signs of trachoma were prevalent in this population but were not indicative of the underlying rates of Ct infection. The current World Health Organization guidelines for trachoma elimination indicated that this population should receive intervention with mass distribution of antibiotics, but the data presented here suggest that this may not have been appropriate.