**5. Clinical manifestation**

Salmonellosis is a type of food infection that can occur when you eat foods that contain *Salmonella* bacteria. Once ingested, the bacteria may initiate infection and cause illness. The illness's possibility and severity depend largely on the dose, the host's resistance and the specific *Salmonella* strain causing the disease. The bacteria are disseminated by direct contact with the animal or human excrement through faecal to the oral pathway or spread out indirectly by ingesting food contaminated with *Salmonella* from faeces or raw food through cross-contamination. Clinical manifestation in human can be classified into four syndromes: gastroenteritis, enteric fever, septicaemia and asymptomatic chronic carriage.

#### **5.1 Gastroenteritis**

Non-typhoidal salmonellosis caused gastroenteritis, a condition commonly called as food poisoning. It is a condition resulted from the inflammation of the gastrointestinal tract spread by faecal to an oral route such as enteric fever. Frequently related serovars reported caused gastroenteritis related to outbreaks are Enteritidis, Typhimurium and Heidelberg [37]. Non-typhoidal salmonellosis is the leading cause of death and hospitalisations among other foodborne pathogens in the USA [1], and the estimated cases of non-typhoidal salmonellosis worldwide massively exceed the enteric fever cases.

The incubation period is 12–72 hours as a result of ingesting tainted food or drinking tainted water and dose-dependent on bacteria that infect the intestines [38]. Symptomatic disease in healthy adults occurs if they are being infected with 106 –108 CFU/mL *Salmonella*. Common symptoms are diarrhoea, vomiting, abdominal pain, nausea, myalgia and headache. In addition, chills and fever within 38–39°C can also occur to the patient. In severe cases, it can lead to severe dehydration and bloody diarrhoea in rare cases. The duration of the symptoms varied from 2 to 7 days but generally resolved by itself without the need for treatment within a week.

## **5.2 Enteric fever**

Enteric fevers are severe systemic forms of salmonellosis and occasionally life-threatening illness. Enteric fever that is caused by *S*. Typhi and *S*. Paratyphi A, B or C infections is called as typhoid fever and paratyphoid fever, respectively [39–41] . Paratyphoid fever is a similar illness causing a milder form of enteric fever compared to the typhoid fever. *S*. Typhi is responsible for causing the most endemic and epidemic cases of enteric fever worldwide with 200,000 deaths and 23 million illness cases per year [42].

The incubation period varied from 6 to 30 days after infection [43] giving rise to symptoms such as gradual fever (38–40°C) over several days, headache, hepatosplenomegaly, myalgias, diarrhoea and constipation when the onset of the systemic disease takes place. Some people develop a transient skin rash with rose-coloured spots, which can be confused with malaria. Therefore, typhoid fever should be suspected in a traveller who is unresponsive to anti-malarial treatment. If left untreated, the symptoms can last for weeks or months. Without treatment, symptoms may last from weeks or months, and it can be deadly [44]. The fatality rate was reported to be at 10–30% if left without treatment but improved to 1–4% fatality in treated patients [45, 46].

#### **5.3 Bacteraemia/septicaemia**

Bacteraemia is the presence of viable bacteria in the bloodstream that may occur through a wound, injection or a surgical procedure. Septicaemia is referred to the presence and proliferation of germs in the blood. Septicaemia is a medical term that refers to blood poisoning. *Salmonella* bacteraemia is a condition in which the presence of *Salmonella* bacteraemia in the blood elicits a systematic inflammatory response that can be fatal. It is an intermediate stage of infection in which the patient is not showing any symptom and the bacteria cannot be isolated from faecal specimens. Bacteraemia can further progress to septicaemia whereby the bacteria multiply in the blood and giving symptoms such as chills, fever, high respiration rate or very fast heart rate.

Bacteraemia can be caused by all *Salmonella* subspecies but is more commonly associated with *S.* Choleraesuis, *S.* Paratyphi, *S.* Typhi and *S.* Dublin. The increased risk is seen in old, young and immunocompromised persons. The severity of the infection depends on the bacterial dose, immune response of the patient and the virulence of the *Salmonella* strain [47]. The severe development of septicaemia was reported higher to occur in cancer patients and immunecompromised individual infected with human immunodeficiency virus (HIV) [48, 49].

#### **5.4 Chronic carrier**

After treatment for salmonellosis, some patients become *Salmonella* carriers and shed faeces with *Salmonella* for an extended time, making them a reservoir or carrier for the pathogen, thus making them a chronic carrier. *Salmonella* can continue to be excreted in stool for many weeks following resolution of an initial diarrheal episode without symptoms exhibited by the patients. The factors of the host and pathogen that influence the occurrence of carrier state study are limited; hence, the condition is poorly understood [48]. Chronic carrier state occurred higher in patients infected with *S.* Typhi compared to non-Typhi. About 1–4% of patients that recovered from typhoid fever become chronic carriers, while only 0.2–0.6% of patients infected with non-typhoidal salmonellosis progress into the chronic carrier [50]. The chronic carrier state is associated with carcinoma of the gallbladder, which the host could form into the chronic carriage [51].
