Human Genetic Variation Influences Enteric Fever Progression

Abstract

In the 21st century, enteric fever is still causing a significant number of mortalities, especially in high-risk regions of the world. Genetic studies involving the genome and transcriptome have revealed a broad set of candidate genetic polymorphisms associated with susceptibility to and the severity of enteric fever. This review attempted to explain and discuss the past and the most recent findings on human genetic variants affecting the progression of Salmonella typhoidal species infection, particularly toll-like receptor (TLR) 4, TLR5, interleukin (IL-) 4, natural resistance-associated macrophage protein 1 (NRAMP1), VAC14, PARK2/PACRG, cystic fibrosis transmembrane conductance regulator (CFTR), major-histocompatibility-complex (MHC) class II and class III. These polymorphisms on disease susceptibility or progression in patients could be related to multiple mechanisms in eliminating both intracellular and extracellular Salmonella typhoidal species. Here, we also highlighted the limitations in the studies reported, which led to inconclusive results in association studies. Nevertheless, the knowledge obtained through this review may shed some light on the development of risk prediction tools, novel therapies as well as strategies towards developing a personalised typhoid vaccine.

Association of Typhoid Fever Severity with Polymorphisms at Nucleotide Oligomerization Binding Domain 2 (NOD2) and Natural Resistance Associated Macrophage Protein 1 (NRAMP1) Genes in A Sample of Iraqi Patients

“…Also, the study of Ma et al . (16) was consistent with the present study that showed no association between typhoid fever severity and polymorphism in the NRAMP1 gene when they studied human genetic variation influences enteric fever progression in Malaysia. The change in the SNP from G to C will lead to a change in the type of amino acid produced and included in the protein structure of the NOD2 receptor, and it is discussed whether the new amino acid will change the structure of the receptor and its functional ability.…”

“…The results of the distribution of S. typhi according to age revealed that the highest number of typhoid fever infection was located in the age group (1-10) years that represented 20 patients with a percentage (38.46%) of the total number, followed by (11)(12)(13)(14)(15)(16)(17)(18)(19)(20) years that showed 17 patients with a percentage (32.70%) , whereas the last three groups seemed almost equal in the age groups (21-30)years with 6 (11.60%), and (31-40) years that showed 5 (9.60%), lastly 4(7.70%) for the age group (41-50) years with a highly significant difference (P≤ 0.01), as shown in Table (4).…”

Revisiting Persistent Salmonella Infection and the Carrier State: What Do We Know?

“…Several studies have initiated identification of host chromosomal loci responsible for resistance to acute S . Typhi in man [ 135 , 136 , 137 , 138 ], S. Typhimurium in mice [ 139 ] and Salmonella in chickens [ 140 , 141 ].…”

“…Slc11a1 is not associated with typhoid susceptibility in man [ 138 ] although it, aided by other host genes, is a prerequisite for establishing the carrier state in mice with virulent strains of S . Typhimurium [ 4 , 85 , 142 ].…”

Whole Exome Sequence Analysis for Inborn Errors of IL‐12/IFN‐γ Axis in Patient with Recurrent Typhoid Fever

“…In the 21 st century, enteric fever is responsible for causing a significant number of mortalities in high risk regions of the world [16]. The prevalence of typhoid fever is alarmingly high with approximately 200,000 deaths each year in developing countries [25].…”