32 Enteric Fever
Typhoid and Paratyphoid Fevers
32.1 Definition
Typhoid fever is a life-threatening infection caused by the bacterium Salmonella Typhi. It is usually spread through contaminated food or water. Once Salmonella Typhi bacteria are ingested, they multiply and spread into the bloodstream. It causes an acute generalised infection of the reticuloendothelial system, intestinal lymphoid tissue, and the gall bladder.
32.2 Incidence/prevalence
As of 2019 estimates, there were 9 million cases of typhoid fever annually, resulting in about 110,000 deaths annually.(WHO 2023) In 2023, information from LHIMS, Komfo Anokye Teaching Hospital, Kumasi indicated a rate of 0.4% or 4/1000 admissions through the Paediatric Emergency Unit (PEU) were diagnosed as enteric fever.
32.3 Aetiology
An infectious feverish disease caused by the bacterium Salmonella typhi (Salmonella enterica Serovar Typhi) and less commonly by Salmonella paratyphi.
32.4 Pathogenesis
S. typhi and S. paratyphi are transmitted through ingestion of fecally contaminated food or water, improper hygiene, and unsafe food/water handling practices. Individual-level risk factors include contaminated water supply, patronizing food vendors, ingestion of raw fruits and vegetables and a history of contact with a case or a chronic carrier. The risk of environmental transmission of typhoid fever is higher in the rainy season, proximity to open sewers and highly contaminated water bodies and residing in areas of low elevation.(Adesegun et al. 2020) Ingested organisms survive exposure to gastric acid before gaining access to the small bowel, where they penetrate the epithelium, enter the lymphoid tissue, and disseminate via the lymphatic or hematogenous route. A chronic carrier state is established in an estimated 1 to 5 per cent of cases.(Andrews and Charles 2023)
32.5 Signs and symptoms
The incubation period ranges from 7-14 days on average but can range from 3 days to two months. Symptoms include prolonged high fever, fatigue, headache, nausea, abdominal pain, constipation or diarrhoea, and in some cases a rash. Typhoid can affect every system of the body. Other manifestations include drowsiness, seizures, coma, psychosis, meningitis, acute renal failure, osteomyelitis, and septic arthritis. Severe cases may lead to serious complications including terminal ileal perforation or even death.
32.6 Investigations
In the first and second weeks of the presentation, blood culture and sensitivity are recommended. Stool culture is also relevant more in the first week as compared to the second week. Bone marrow aspirate and culture are important after the second week. Recently, antibodies (IgM) have been used as a diagnostic tool. Local studies are needed to validate these antibody tests. Depending on the system involved, other tests must be requested.
32.7 Treatment
Treatment is supportive (Antipyretics, hydration, nutrition, transfusion) and specific (antibiotics are given starting with the empiric regimen: Third generation cephalosporin or quinolone eg. Ciprofloxacin). The choice of antibiotics should be changed to a narrower spectrum when culture and sensitivity results are available. Where there is poor response attributed to a focus e.g. abscess formation, source control should be pursued. Safe water, sanitation, and hygiene (WASH) interventions are critical to preventing the spread of typhoid. Typhoid is spread via the faecal-oral route when bacteria pass into people’s mouths through food, water, hands, or objects contaminated with faecal matter. Solutions such as water treatment or filtration, installation and management of toilets and sanitation systems, and education about proper handwashing and food-handling practices can save lives and protect people from typhoid infection. Three types of typhoid vaccines of demonstrated safety and efficacy are available on the international market:-
- A conjugated vaccine in which the Vi polysaccharide vaccine is bound to a carrier protein,
- A non-conjugated Vi polysaccharide vaccine, and
- A live attenuated Ty21a vaccine.
32.8 Complications
These include anicteric hepatitis, bone marrow suppression, paralytic ileus, myocarditis, psychosis, cholecystitis, osteomyelitis, peritonitis, pneumonia, haemolysis, and syndrome of inappropriate release of antidiuretic hormone (SIADH)
32.9 Prognosis
The prognosis among persons with typhoid fever depends primarily on the speed of diagnosis and initiation of correct treatment. Generally, untreated typhoid fever carries a mortality rate of 15%-30%. In properly treated diseases, the mortality rate is less than 1%. (emedicine 2024)
32.10 Differential diagnosis
Differential diagnosis will depend on the types of presentation. The most common are malaria, liver abscesses, tuberculosis, and meningitis.
32.11 Sample questions
A 5-year-old boy complained of general body weakness, abdominal pain and a fever of two weeks duration. He had 2 courses of antimalarial treatment even though the RDT was negative. On examination, he was lethargic and had a body temperature of 39.9oC. If you suspect enteric fever, what will be the best test to perform?
Urine culture
Stool culture
Blood culture
Widal test
All the options are feasible but with the duration of illness, blood culture with sensitivity testing will provide the best yield. Widal tests are widely used in some facilities but have a high tendency of false positive results.
A 10-year-old known sickle cell disease patient genotype SS presented with severe pain in the right leg of 3-week duration. She is on her routine medications but has yet to be initiated on hydroxyurea. On examination, there was tenderness in the right leg, especially at the knee joint with evidence of inflammation. Blood culture isolated Salmonella typhi. What is your best management approach?
A more detailed history and examination is warranted. Before the blood culture results came out, the child would have been on empiric antibiotics. This must be changed to a narrower spectrum based on the sensitivity results. Remember to request for ultrasound of the inflamed knee for possible effusion. If there is fluid collection, this must be drained to achieve source control. This will optimize antibiotic response.
32.12 Practice question
Concerning question 2 (above) if the child was started on ceftriaxone, discuss what must be done after microbiology provides the sensitivity results as shown in the table below.
| Sensitive | Resistant |
|---|---|
| Meropenem Ciprofloxacin Amikacin | Ceftriaxone, Linezolid |