Background: Salmonella Typhi is a human pathogen that causes typhoid fever. It is a major cause of morbidity and mortality in developing countries and is responsible for several outbreaks in developed countries. Studying certain parameters of the pathogen, such as the incubation period, provides a better understanding of its pathophysiology and its characteristics within a population. Outbreak investigations and human experimental studies provide an avenue to study these relevant parameters.
Methods: In this study, the authors have undertaken a systematic review of outbreak investigation reports and experimental studies, extracted reported data, tested for heterogeneity, identified subgroups of studies with limited evidence of heterogeneity between them and identified factors that may contribute to the distribution of incubation period. Following identification of relevant studies, we extracted both raw and summary incubation data. We tested for heterogeneity by deriving the value of I2 and conducting a KS-test to compare the distribution between studies. We performed a linear regression analysis to identify the factors associated with incubation period and using the resulting p-values from the KS-test, we conducted a hierarchical cluster analysis to classify studies with limited evidence of heterogeneity into subgroups.
Results: We identified thirteen studies to be included in the review and extracted raw incubation period data from eleven. The value of I2 was 84% and the proportion of KS test p-values that were less than 0.05 was 63.6% indicating high heterogeneity not due to chance. We identified vaccine history and attack rates as factors that may be associated with incubation period, although these were not significant in the multivariable analysis (p-value: 0.1). From the hierarchical clustering analysis, we classified the studies into five subgroups. The mean incubation period of the subgroups ranged from 9.7 days to 21.2 days. Outbreaks reporting cases with previous vaccination history were clustered in a single subgroup and reported the longest incubation period.
Conclusions: We identified attack rate and previous vaccination as possible associating factors, however further work involving analyses of individual patient data and developing mathematical models is needed to confirm these as well as examine additional factors that have not been included in our study.
Keywords: Experimental studies; Incubation period; Observational studies; Salmonella Typhi; Systematic review.