**4. Salmonella infection**

Infection with *Salmonella* causes morbidity and mortality all over the world, with the host immune response varied depending on whether the infection is acute or

systemic. In addition to this, anatomical location of *Salmonella* infection plays a huge role in immune response as it evolves multiple mechanisms to subvert immunity to its own benefit.

#### **4.1 In humans**

*S enterica* subsp. *enterica* continues to be a leading source of disease in humans and livestock around the world. The transmission of pathogens caused a huge portion of public health and economic loss. As agricultural production began to increase after World War II, Salmonellosis become more prevalent in different countries as was the case with Europe. Despite the fact that the genus *Salmonella* contains over 2600 serovars, only 05–08 serovars cause the majority of human Salmonellosis cases in the United States. As per CDC, *Salmonella enteric* ser Enteritidis (24.7%), *S*. ser Typhimurium (23.5%), *S.* ser Newport (6.2%), and *S.* ser. Heidelberg were responsible for approximately 60% of human cases. That year, 04 serotypes accounted for 46.4% of non-human isolates. Main reason for infection in humans and other mammals is *S enteric*a which is responsible for 99% of overall infection [28]. Non-invasive non-typhoidal Salmonellosis, Invasive non-typhoidal Salmonellosis, and typhoid fever are the three principal diseases produced by *Salmonella* in humans, and these are all covered in greater depth below.

## *4.1.1 Non-invasive, non-typhoidal Salmonellosis*

The non-typhoidal Salmonellosis (NTS) is associated with all the diseases of humans caused by *Salmonella* serotype except for the distinct typhoidal serotypes: Typhi and Paratyphi A-C. Salmonellosis is contracted orally through contaminated food or water. About 1.3 billion cases are reported annually of Salmonellosis gastroenteritis, causing huge mortality, approximately 03 million deaths globally [29]. According to the recent reports, NTS gastroenteritis is infecting developing countries. Acute enterocolitis is a symptom of Salmonellosis, and it is often followed by inflammatory diarrhea, which is only seen in people infected with invasive serovars (*S. Typhi*). The symptoms appear usually between 6 and 72 h. Primary symptoms of this disease are abdominal pain, diarrhea with or without blood, nausea, and vomiting.

### *4.1.2 Invasive non-typhoidal Salmonellosis*

In Sub-Saharan Africa, a new *Salmonella* strain is emerging, with pathogenesis that is distinct from its genetic equivalents. This novel pathogen is known as Salmonella invasive non-typhoidal (iNTS). *Salmonella* serotypes *S. Typhimurium* and *S. Enteritidis* are the most typically connected with invasive NTS, however other serotypes such as Choleraesuis and Dublin have also been found to produce invasive illness in humans. [30, 31]. In Africa it has been found that invasive isolates have dominating genotype with several biological variations from the isolated strain (ST313) which proves that its genotype has surfaced new pathogenic clade in Sub-Saharan Africa and it may be the reason of invasive disease in humans [32]. In different parts of world other strains have also evolved which include *S. Typhimurium* ST313 strain, which gave an idea that this disease is spreading globally [33]. It was reported that iNTS are the main cause of bloodstream infections in African children [34]. Soon after the detection of AIDS in Africa, iNTS have also been reported in kids and adults and thus

prompting a possible link between HIV and iNTS [34]. In New Jessey, first epidemiological link of iNTYS and AIDS was made with iNTS remained a prevalent bacterial bloodstream infection of kids and adults in Sub-Saharan Africa [32].

## *4.1.3 Typhoid fever*

The main causative agent of Typhoid Fever is *Salmonella Typhi*. Every year about 21 million cases are being reported with almost 200,000 deaths globally. The yearly death rate increased by 39% from year 1990 to 2010 [35]. It has been reported that death rate caused by *Salmonella Typhi* in developing countries is comparatively similar to the death rate caused by breast cancer, prostate cancer, and leukemia in North America [36, 37]. Polysaccharide capsular agent allows *S. Typhi* to adapt to the acidic environment of stomach soon after infection as *S. Typhi* (acapsular) being less virulent [38, 39]. Unlike NTS, which has broad host specificity, *S. Typhi* is only found in humans. [40]. *Salmonella Typhi* inhabits and duplicates in host cells, these cells are used to translocate bacteria to liver, spleen and bone marrow. These cells include dendritic cells, neutrophils and macrophages [41].
