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Title: Using alternate indicators to define need for public health intervention for trachoma : evidence from the Pacific Islands
Author: Butcher, Robert M. R.
ISNI:       0000 0004 6425 1095
Awarding Body: London School of Hygiene & Tropical Medicine
Current Institution: London School of Hygiene and Tropical Medicine (University of London)
Date of Award: 2017
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Introduction: Trachoma is the most common infectious cause of blindness worldwide. The presentation of trachoma in the Pacific small island states varies. This study focuses on Fiji, where the trichiasis prevalence recorded prior to this study was very high, and the Solomon Islands, where the prevalence of trachomatous inflammation – follicular (TF) is high enough to warrant intervention with mass antibiotic treatment, but there is apparently little or no trachomatous trichiasis (TT). This study aims to supplement clinical data with photographic and molecular tools to better characterise presentation and microbiological correlates of disease. Methods: Pre-intervention population-based prevalence surveys for trachoma were carried out independently and in conjunction with the Global Trachoma Mapping Project (GTMP). Additionally, one focused post-intervention survey was performed. Standardised clinical data collection was supplemented with ocular swab, dried blood spot and photograph collection. Quantitative and sequence-based nucleic acid techniques were used for targeted and nontargeted pathogen detection and characterisation. Enzyme immunoassays were used for serological analysis. Clinical data was supplemented with photographs. Results: Within the mosaic pattern of clinical trachoma in the Pacific, the prevalence of TT was found to be very low in Fiji and the Solomon Islands. Prevalence of ocular Chlamydia trachomatis (Ct) infection in these countries was also very low. Further investigations in the Solomon Islands demonstrated Ct isolates found to be most closely related to ocular reference strains. Several pathogens that are known to cause follicular conjunctivitis were found, but neither frequency nor load of infection was associated with TF. Amplification of 16S ribosomal RNA amplicons showed diverse ocular microbial communities but no dominant metagenomic communities associated with TF. There is evidence of accumulation of mild scarring as age increases, but little evidence of severe scarring, or association between any trachoma phenotype and exposure to Ct. Conclusion: In Solomon Island communities studied, no evidence was found of significant burden of Ct infection, Ct transmission, trachomatous inflammation – intense, accumulation of severe scarring in older people or TT. We therefore suspect TF in the Solomon Islands to be of an as-yet unidentified aetiology. The WHO simplified grading system also appeared to lack diagnostic accuracy in Fiji. There are direct implications for implementation of control measures in the Pacific. There are additional connotations worldwide; as the global elimination effort continues and phenotypically similar conditions are unmasked, we suspect the positive predictive value of simplified clinical grading to drop. Use of molecular tools could differentiate communities with a high burden of infection, a key correlate of blinding disease, from those where resources may be better allocated elsewhere.
Supervisor: Roberts, C. H. ; Solomon, A. W. Sponsor: Fred Hollows Foundation ; Wellcome Trust ; Department for International Development
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral