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BACKGROUND: Typhoid fever is endemic in some Pacific Island Countries including Fiji and Samoa yet genomic surveillance is not routine in such settings. Previous studies suggested imports of the global H58 clade of Salmonella enterica var Typhi (Salmonella Typhi) contribute to disease in these countries which, given the MDR potential of H58, does not auger well for treatment. The objective of the study was to define the genomic epidemiology of Salmonella Typhi in Fiji. METHODS: Genomic sequencing approaches were implemented to study the distribution of 255 Salmonella Typhi isolates from the Central Division of Fiji. We augmented epidemiological surveillance and Bayesian phylogenomic approaches with a multi-year typhoid case-control study to define geospatial patterns among typhoid cases. FINDINGS: Genomic analyses showed Salmonella Typhi from Fiji resolved into 2 non-H58 genotypes with isolates from the two dominant ethnic groups, the Indigenous (iTaukei) and non-iTaukei genetically indistinguishable. Low rates of international importation of clones was observed and overall, there were very low levels an antibiotic resistance within the endemic Fijian typhoid genotypes. Genomic epidemiological investigations were able to identify previously unlinked case clusters. Bayesian phylodynamic analyses suggested that genomic variation within the larger endemic Salmonella Typhi genotype expanded at discreet times, then contracted. INTERPRETATION: Cyclones and flooding drove 'waves' of typhoid outbreaks in Fiji which, through population aggregation, poor sanitation and water safety, and then mobility of the population, spread clones more widely. Minimal international importations of new typhoid clones suggest that targeted local intervention strategies may be useful in controlling endemic typhoid infection. These findings add to our understanding of typhoid transmission networks in an endemic island country with broad implications, particularly across Pacific Island Countries

BACKGROUND: Regression discontinuity designs are non-randomized study designs that permit strong causal inference with relatively weak assumptions. Interest in these designs is growing but there is limited knowledge of the extent of their application in health. We aimed to conduct a comprehensive systematic review of the use of regression discontinuity designs in health research. METHODS: We included studies that used regression discontinuity designs to investigate the physical or mental health outcomes of any interventions or exposures in any populations. We searched 32 health, social science, and gray literature databases (1 January 1960 to 1 January 2019). We critically appraised studies using eight criteria adapted from the What Works Clearinghouse Standards for regression discontinuity designs. We conducted a narrative synthesis, analyzing the forcing variables and threshold rules used in each study. RESULTS: The literature search retrieved 7658 records, producing 325 studies that met the inclusion criteria. A broad range of health topics was represented. The forcing variables used to implement the design were age, socioeconomic measures, date or time of exposure or implementation, environmental measures such as air quality, geographic location, and clinical measures that act as a threshold for treatment. Twelve percent of the studies fully met the eight quality appraisal criteria. Fifteen percent of studies reported a prespecified primary outcome or study protocol. CONCLUSIONS: This systematic review demonstrates that regression discontinuity designs have been widely applied in health research and could be used more widely still. Shortcomings in study quality and reporting suggest that the potential benefits of this method have not yet been fully realized.