Chapter Enteric Fever in Primary Care Abdulmaleek Idanesimhe Sado and Aduke Oluwambe Sado Abstract Enteric fever is a bacterial infection caused by Salmonella typhi and paratyphi. It is endemic in many parts of Africa and South Asia where there is poor access to safe portable water and below par food quality assurance. It is important to ensure prompt recognition, diagnosis and management of symptoms to forestall complica- tions. Due to the rising global burden, significant effort has to be made to improve primary care services like vaccination, antimicrobial stewardship and encourage- ment of hygiene measures. Hence, it is imperative to be aware of its current burden and options available in primary care for its prevention and treatment. Keywords: Salmonella, enteric fever, typhoid, primary care, typhoid-conjugate vaccine 1. Introduction Typhoid fever (now more appropriately called Enteric fever) is a bacterial infectious disease caused by Salmonella enterica subspecies enterica and serovar typhi. It is mainly transmitted through the faeco-oral route via contaminated food, water and asymptomatic carriers [1]. It is endemic in developing countries and low- resource settings where hygiene and sanitation measures are subpar. In developed countries and high-income settings, it is less common but cases still occur in recent travellers to endemic areas [2]. There are a number of factors which contribute to the disease burden including lack of access to clean, portable water, poor food qual- ity control and lack of public health services (e.g well managed public latrine and hand washing facilities); all of which can be attributed to lack of awareness, low political will and sociocultural factors. Symptoms of enteric fever vary significantly and are generally nonspecific. These include pyrexia, headache, myalgia, arthralgia, nausea, rash, abdominal pain, constipation and occasionally diarrhoea [3]. Enteric fever, if left untreated can be life-threatening and result in a myriad of complications including intestinal haemorrhage and perforation, peritonitis, sepsis, meningitis, osteomyelitis, multiorgan failure and death [1, 3]. Hence, it is expedient to ensure early diagnosis and management to mitigate complications. Central to the actualisation of universal health coverage is an effective primary health care system which is usually the first point of contact for most patients. Hence, the role of the primary care clinician in the prevention, diagnosis and management of enteric fever and its complications cannot be overemphasised. This is what this chapter aims to address. 1 Salmonella - a Challenge from Farm to Fork 2. Epidemiology Enteric fever is a global health problem affecting 21.6 million people (incidence of 3.6 per 1000 population) and resulting in just over 216 000 deaths annually [4]. It is endemic in developing and low and middle income countries of Africa, Asia, Latin America, the Caribbean and Oceania mainly due to poor sanitation and environmental hygiene [2, 4]. Bangladesh, Indonesia, China, India, Laos, Nepal, Pakistan and Vietnam account for 80% of cases [4]. Untreated, 10%–30% of patients will die but mortality reduces to 1%–4% with prompt and appropriate treatment. In the pre-antibiotics era, the USA had a case fatality rate of 9%–13% [5]. This illustrates how much the discovery of antibiotics has revolutionised its management, just like most bacterial infections. However, there is an increasing burden of antimicrobial resistant Salmonella strains emanating from endemic countries mainly due to poor antimicrobial stewardship and measures must be taken to stem the tide. Significant intra- and intercountry variation in disease burden exists in many regions of south and south east Asia and parts of Africa. For instance, surveillance performed in two sites in Kenya between 2006 and 2009 found that the incidence of blood-culture proven typhoid fever in rural and urban sites varied from 29 up to 247-cases/100 000 person-years [6]. Also, data from the Diseases of Most Impoverished areas have described incidence rates varying from 24.2/100 000 in Vietnam to 493.5/100 000 in parts of India [7]. However, most disease burden data from low- and middle-income countries are hospital-based which leaves a huge number of cases unaccounted especially in areas of low health-care usage and accessibility. Hence, it is imperative for countries in endemic regions of the world to develop a national and regional surveillance system to identify factors respon- sible for these variations and adopt guidelines and protocols to improve efficiency in prevention, diagnosis and management. Central to this should be an efficient primary care system where surveillance and data gathering can be co-ordinated and synchronised with hospital-based data providing a broad-based approach and a better reflection of disease burden. The incidence of enteric fever varies by age. In endemic areas, incidence is higher in younger children but similar across age groups in low burden areas [8]. In general, children are at a higher risk of complications including ileitis and intestinal perforation. When perforation sets in, mortality has been reported to be as high as 62% [9, 10]. Therefore, it is imperative that signs and symptoms of enteric fever are identified and treated early in primary care. Due to the wide disparity in incidence between developed and low and middle-income countries, primary care physicians in the latter will most likely see a lot more cases and have a high pre-test probability. This poses a challenge for a lot of primary care practitioners in developed countries who are less likely to be familiar with its presentation and may result in delay in diagnosis. In England and Wales, any case of Salmonella infection is a notifiable disease which must be reported to Public Health England and may require urgent community investigation to forestall an outbreak [11]. 3. Aeotiopathogenesis Salmonella is a flagellated, non-capsulated facultative anaerobic gram-negative bacilli and non-lactose fermenter of the Enterobacteriaceae family which has flagellar, somatic and outer coat antigens [7, 12]. Its outermost covering is made up of the somatic O antigen while the flagellae are composed of the H antigen. Each 2 Enteric Fever in Primary Care DOI: http://dx.doi.org/10.5772/intechopen.96047 O and H antigen have a unique code number and a varied combination of these form the basis for the determination of serotypes [12]. Of the over 2500 serotypes of Salmonella that have been identified, only 100 are thought to be responsible for most human infections [7]. These infections can be broadly divided into nonty- phoidal and typhoidal. The typhoidal infection is mainly caused by S. typhi and less commonly paratyphi. Salmonella typhi and paratyphi A are thought to be restricted to humans alone. A key virulence factor in most strains of S.typhi is the Vi capsular antigen which possesses immunomodulatory properties that are thought to contrib- ute to disease pathogenesis, including limiting complement deposition, reducing immune activation, assisting with phagocytosis evasion, and inhibiting serum bactericidal activity [7, 13, 14]. Without it, S. typhi will be more susceptible to attack and destruction by the host immune system. Hence, the Vi antigen has been harnessed as a major component of typhoid vaccines including the new conjugate vaccines [7]. Transmission is through the faeco-oral route from contaminated food, water and unrestricted contact with chronic carriers especially in an unhygienic environment. When Salmonella typhi is ingested, it evades degradation by enzymes and gastric acid before entering the host’s system primarily through the terminal ileum [15]. At the distal ileum, through specialised structures called fimbrae, they attach to the epithelial cells overlying clusters of lymphoid tissues called Peyer patches. These serve as a relay point for macrophages travelling from the gut to the lymphatic sys- tem. Activation of the macrophages at the Peyer’s patches release cytokines which attract more macrophages to the site. These macrophages serve as a vehicle by which S. typhi is transported to several parts of the reticuloendothelial system including the liver, spleen and bone marrow where they replicate up to a critical density at this point [16], they break into the bloodstream and invade other parts of the body. One of such places invaded is the gall bladder. The gall bladder is infected haematog- enously or through infected bile. Infected bile is then secreted into the gut where it once again comes in contact with the Peyer patches at the distal ileum. This second sensitization of the macrophages at this site results in inflammation and hypertro- phy of the lymphoid tissues (typhoid ileitis) [15, 16]. This enlargement encroaches on the blood supply resulting in ischaemic coagulative necrosis and consequently perforation and peritonitis. Some of the salmonella is excreted in the stool which is serves as a source of infection spread. This is the source of transmission of Salmonella in chronic carriers where the salmonella is thought to avoid enzymatic and chemical degradation in the gall bladder for a long time by forming biofilms or entering an intracellular ‘comfort zone’ in the gall bladder epithelium. 4. Clinical presentation Enteric fever presents with a number of nonspecific symptoms and a wide varia- tion in severity. Symptoms must be correlated with laboratory investigation to reach a diagnosis. Symptoms generally include fever, constipation,