Enteric/ Typhoid Fever: Progression, Diagnosis, Complication and Prevention

Enteric/ Typhoid Fever: Progression, Diagnosis, Complication and Prevention

Enteric fever encompasses typhoid fever, caused by S. typhi, and paratyphoid fever, caused by S. paratyphi A, B, C. Enteric fever is endemic in the Indian subcontinent. Transmission is by fecal-oral route through contaminated water or food. Humans are the only natural reservoir of S. typhi. Multidrug resistance isolates are a present day problem in managing Enteric fever.

The inoculum size required to cause disease is 105 -109 S. typhi organisms. After attachment to the microvilli of the ileal brush borders, the bacteria invade intestinal epithelium, transported to mesenteric glands and then into the blood stream causing bacteremia. The organisms reach the reticuloendothelial cells in the liver, spleen, and bone marrow and may seed other organs particularly gall bladder.

After proliferation in reticuloendothelial system, the bacteremia recurs and produces the clinical illness. Hyperplasia of Peyer patches with necrosis and sloughing of overlying epithelium, producing ulcers, is typical. Circulating endotoxin, a component of the bacterial cell wall, cause the prolonged fever and toxic symptoms. Alternatively, endotoxin-induced cytokine production by human macrophages may cause the systemic symptoms. Cell-mediated immunity is important in protecting host against typhoid fever.

Progression: The incubation period is usually 7-14 days and inversely related to the inoculum size.

First week: The onset is insidious with fever, malaise, anorexia, myalgia, headache, and abdominal pain develops over 2-3 days. The fever, which rises in a step-wise fashion, becomes unremitting and high within first week, often reaching 40°C (104°F). Diarrhea is more common in children under-5. There may be mild cough, sore throat. Physical examination reveals a toxic individual with bradycardia relative to the degree of fever. Epistaxis may occur.

Second week: The patient sustains high temperature. In about 50% of patients with enteric fever, a macular ( rose spots) or maculopapular rash appears, slightly raised and blanch on pressure. They appear in crops of 10-15 on the lower chest and abdomen and last 2 or 3 days and leave a slight brownish discoloration of the skin on healing. Culture of the lesions has a 60% yield of salmonella organisms. Abdominal symptoms increase in severity. Splenomegly is present in about 75% and hepatomegaly in about 30% of cases.

Third week (week of complication): The patients become toxic and ill. High fever continues and delirium and stupor may be observed. Marked abdominal distension with diffuse tenderness and "pea soup" diarrhoea is common. Intestinal hemorrhage and perforation are likely.

Fourth week: The week of convalescence. The abdominal distension and mental state begins to improve over a 7-10 days period.

Enteric fever during late pregnancy may be transmitted vertically to the neonate. The neonatal disease usually begins within 3 days of delivery. Vomiting, diarrhea and abdominal distention are common. Hepatomegaly, jaundice, anorexia and weight loss can be marked.

Differential diagnosis:

The clinical diagnosis may mistakenly be gastroenteritis, viral syndrome, bronchitis, or bronchopneumonia; sepsis with other bacterial pathogens; tuberculosis, brucellosis, rickettsial diseases; infectious mononucleosis, anicteric hepatitis; malignancies, such as leukemia and lymphoma.


Isolation of the organism:

Blood culture is one of the definitive methods of diagnosis in the first week. Bone marrow culture (iliac crest) is the single most sensitive method of diagnosis (positive in 85-90%), less influenced by prior antimicrobial therapy and even positive when blood culture may become sterile. Stool and urine culture also may yield the organism after the first week of the disease.

Widal test:

This measures antibodies against O and H antigens of S. typhi. Widal test is done after the first week for the detection of salmonella antibodies in the patient's serum. The Interpretation are as follows:

a) No single titre is diagnostic, it may be presumptive;

b) In the non-immunized child O agglutinin litres of more than 1:160 are suggestive of infection, a rising titre over a period of 7-10 days is more significant.

c) Elevation of antibody titre against O (somatic) antigen has a better diagnostic value.

d) If a child had a previous attack of enteric fever, or had immunization with TAB vaccine, the H antibody titre rises rapidly with non-typhoid fevers, but the titre of O antibodies doses not rise. This is called anamnestic (does not forget) reaction. High anti-H and low anti-O suggest anamnestic reaction;

e) High anti-O and low anti H suggest active infection,

f) High anti-Vi suggests carrier state (usually more than 1/25).

Others: Leukopenia is common, but leukocytosis may reach 20,000-25,000/cmm when abscesses complicated and may have associated thrombocytopenia. Proteinuria is also common. There may be mild elevation of liver enzymes.

Complications :

i) Intestinal hemorrhage and perforation: Usually occurs after the first week and in distal ilium manifested by abdominal pain, tenderness, vomiting, and signs of peritonitis,

ii) Septicemia: Bacteremia may lead to sepsis. Disseminated intravascular coagulation may develop,

iii) Pneumonia often caused by superinfection with organisms other than Salmonella. In children, pneumonia or bronchitis is common. Bone marrow necrosis, pyelonephritis, nephrotic syndrome, meningitis, endocarditis, parotitis, orchitis, and suppurative lymphadenitis. Osteomyelitis and septic arthritis are more frequently seen in children with hemoglobinopathies.

iii) Toxic myocarditis may be manifested by arrhythmias, sinoatrial block, ST-T changes, cardiogenic shock

iv) Neurologic complications include increased intracranial pressure, cerebral thrombosis, acute cerebellar ataxia, chorea, aphasia, deafness, psychosis, and transverse myelitis, peripheral and optic neuritis.

v) Relapse: About 10% suffer relapse 1-3 weeks after clinical recovery, usually occurs 2 weeks after stopping therapy. Blood culture again becomes positive,

vi) Chronic carrier state: Chronic carrier is defined as person who excretes bacilli for more than one year after an attack and the potential source of infection.


Improved sanitation and clean, running water are essential to control enteric fever. Personal hygiene measures, hand washing, and attention to food preparation practices are necessary.


Typhoid vaccine is generally given in an oral form (Vivotif Berna) consisting of four capsules taken on alternate days until completed. The capsules should be kept refrigerated and taken with cool liquid. Protection is achieved seven days after the last dose. Side-effects are uncommon and may include abdominal discomfort, nausea, and rash or hives. Oral typhoid vaccine should not be taken with antibiotics, because they may interfere with its effectiveness. If all four doses are not taken, the entire series must be restarted to achieve protection.The oral vaccine is approved for travelers at least six years old, whereas the injectable vaccine is approved for those aged two or above.

Vi polysaccharide typhoid vaccine for children aged more than 2 years and immunity persist for at least 3 years. It contains 25µg of cell surface Vi polysaccharide extracted from salmonella typhi Ty2 strain.Two safe and effective vaccines are now licensed and available. One is based on defined subunit antigens, the other on whole-cell live attenuated bacteria.

The first of these vaccines, containing Vi polysaccharide, is given in a single dose subcutaneous (s.c.) or i.m. Protection begins seven days after injection, maximum protection being reached 28 days after injection when the highest antibody concentration is obtained.

The vaccine is approved for persons aged over two years. Revaccination is recommended every three years for travellers. If you are traveling to a country where typhoid (Salmonella serotype Typhi) is common, you should consider being vaccinated against typhoid. Visit a doctor or travel clinic to discuss your vaccination options.

Remember that you will need to complete your vaccination at least 1 week before you travel so that the vaccine has time to take effect. Typhoid vaccines lose effectiveness after several years; if you were vaccinated in the past, check with your doctor to see if it is time for a booster vaccination.


The prognosis is excellent with mortality rate less than 1% with early diagnosis and treatment. Deaths are mainly due to complication particularly dehydration and renal failure. Relapse occurs in 4-8% of cases despite appropriate antibiotic treatment. Chronic carriers may be 1-5% and biliary tract disease is higher.


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