**4. Clinical presentation**

Enteric fever presents with a number of nonspecific symptoms and a wide variation in severity. Symptoms must be correlated with laboratory investigation to reach a diagnosis. Symptoms generally include fever, constipation, diarrhoea, abdominal pain, lethargy, nausea and vomiting, malaise, headache, truncal rash (rose spot), anorexia etc. The incubation period for enteric fever is 1–3 weeks and symptoms progressively get worse over the course of illness if not promptly treated [17].

In the first week, patients may complain of headache, malaise, intermittent fever, cough and constipation. Bradycardia may also be elicited on clinical examination. In the presence of fever, this is termed Faget sign or sphygmothermic dissociation. This is also seen in yellow fever, Brucellosis, Tularaemia and Colorado Tick fever.

In the second week, the patient appears dull with diarrhoea and apathy, sustained pyrexia, distended, tender abdomen and sometimes red macules (rose spots). Splenomegaly may also be present in 75% of cases.

In the third week if still untreated, patient become very ill, delirious and toxic with high pyrexia, intestinal haemorrhage and perforation. Toxic myocarditis may also ensue.

10% of cases relapse within the first 3 weeks of apparent recovery or completion of treatment, hence adequate monitoring and follow up should be arranged.

In the United Kingdom, any *Salmonella* infection is notifiable to Public Health England. Most cases occur in travellers returning from endemic areas. The PHE has developed certain criteria which would serve as an invaluable tool especially for primary care physicians in the early identification of suspicious cases for further escalation, assessment and confirmation.

According to Public Health England (PHE), cases can be classified into confirmed, possible and probable cases based on the following criteria (**Table 1**) [18]:


#### **Table 1.**

*PHE classification of Enteric fever cases*

It must be noted that the typical presentation of course of enteric fever may deviate significantly from that described above. These may include pneumonia, delirium, arthralgias and severe jaundice. Younger children, people living with AIDS and one third of immunocompetent adults may present with diarrhoea instead of the classical constipation. The typical step ladder pyrexia is now only seen I 12% of cases with the fever pattern now mostly of the insidious persistent type [7]. Untreated or poorly treated infections may result in orchitis, intestinal ileitis, haemorrhage and perforation, meningitis, osteomyelitis.

#### **5. Diagnosis**

The diagnosis of enteric fever is made by correlation of clinical and laboratory investigations. The current gold standard as recommended by the world health

#### *Enteric Fever in Primary Care DOI: http://dx.doi.org/10.5772/intechopen.96047*

organisation (WHO) is blood culture, although this may be culture of bone marrow, stool or urine depending on the time in the course of infection at which the sample was taken [4, 7, 15]. Even blood culture has been found to be an imperfect gold standard, hence there is an advocacy in some quarters for the use of a composite reference standard (CRS) to improve estimation of diagnostic accuracy [19]. The CRS involves combination of several diagnostic tests to increase the sensitivity rather than relying on individual tests. However, at present there is no consensus as to which tests should be included in the CRS [19]. This may be the future gold standard but further research is needed.

In low- and middle-income countries where the disease is endemic, access to contemporary diagnostic tests may be a challenge and a lot of patient in these countries pay out of pocket for health service delivery which they may not be able to afford. Hence, there is a case for empirical treatment based on clinical symptoms. However, this should be seen as a last resort and priority should be given to improving access to a simple, effective rapid diagnostic test (RDT) which is both reliable and valid. At present, although there are RDTs available commercially in endemic areas such as Typhidot, TUBEX and Test-it, their diagnostic accuracy is uncertain [20].

A lot of laboratories in low resource settings are still very much dependent on the Widal test. The Widal test is a serologic agglutination test developed by F Widal in 1896 [21]. The test is based on the presence of antibodies against the flagellar H and somatic O antigens of *Salmonella* typhi. Over the years, it has become a lot more controversial and largely abandoned in developed countries [21]. The main limitations with the test include a high cross- reactivity with other infectious agents (like nontyphoidal *salmonella*, plasmodium and tuberculosis), past enteric fever and BCG vaccination history. Other limitations include poor performance technique and result interpretation. Therefore, its use should be restricted to situations where there is no other supportive confirmatory test [21].

There are lots of other tests in development which hold promise for the future of enteric fever diagnosis. The antibody-in lymphocyte-supernatant (ALS) test has demonstrated good sensitivity and specificity in endemic settings [7, 22]. Others include PCR-based assays and high through-put technologies on clinical specimens using mass spectrometry [23].
