![]() Epithelial cells and phagocytic cells, including macrophages, neutrophils, and dendritic cells recognize the pathogen associated molecular pattern (PAMP) found in bacteria. Successful elimination of Salmonella species depends on interactions between macrophages that have internalized Salmonella and T lymphocytes, despite the involvement of other cells. by macrophages and dendritic cells in the intestinal submucosa. cells, which is followed by the uptake of Salmonella spp. The course of infection of Salmonella begins when bacteria are ingested and settle in intestinal microfold M. Similarly, the report evaluated by The International Vaccine Institute in 2010 states that there were 11.9 million typhoid fever illnesses which resulted in 129,000 deaths in low- and middle-income nations (Yasin et al., 2018). The study previously done indicated that among Asian countries, Pakistan ranked second in the incidence of typhoid fever with an estimated rate of 412.9 for every 100,000 individuals. ![]() The most prevalent instances with greater mortality are seen in south central and Southeast Asian countries. The worldwide report indicates that approximately 27 million new typhoid cases are reported every year. The prevalence of typhoid fever is alarmingly high with approximately 200,000 deaths each year in developing countries. In the 21 st century, enteric fever is responsible for causing a significant number of mortalities in high risk regions of the world. Enteric fever in people from developed countries is usually associated with travel to an area of high endemicity, it might also be associated with individuals preparing the food who are chronic carriers of infection. Another factor that contributes to the transmission of typhoid infection includes poor sanitation and probably lack of access to safe and hygienic food and water. The risk of infection is particularly great in developing countries where the infection remains endemic. Typhi is predominately transmitted via a fecal-oral route, particularly by consumption of contaminated water. Salmonella typhi is a gram-negative rod-shaped flagellated bacteria responsible for causing typhoid fever with humans being the only reservoir host. Results of the current study suggest that a large population sizes would be needed to examine the functional relevance of IL-12/IFN- γ axis genes with recurrent typhoid fever. Applying WES to the patient with recurrent typhoid fever detects variants that are not much important as other genes in the IL-12/IFN- γ axis. Other pathogenic mutations were found, but they were not considered likely to cause disease based on various mutation predictors. These variations were rare and include mutations in IL23R and ZNFX I. Out of 25 possible variations in the IL-12/IFN- γ axis genes, only 2 probable disease-causing mutations were identified. Each variant was assessed by using various bioinformatics mutational analysis tools such as SIFT, Polyphen2, LRT, MutationTaster, and MutationAssessor. Following alignment and variant calling, exomes were screened for mutations in 25 genes that are involved in the IL-12/IFN- γ axis pathway. WES using next-generation sequencing was performed on a single patient diagnosed with recurrent typhoid fever. The study is aimed at using whole exome sequencing (WES) to screen out genetic defects in IL-12/IFN- γ axis in patients with recurrent typhoid fever. The IL-12/IFN- γ axis pathways play a vital role in the control of intracellular pathogens such as Salmonella typhi.
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