It is generalized type of infection of reticuloendothelial system with predilection for intestinal lymphoid tissue and gallbladder. It is most common cause of fever without focus.

Term enteric fever includes:

  • Typhoid fever caused by Salmonella typhi (around 80% of all cases)
  • Paratyphoid fever caused by Salmonella paratyphi A or B (20% of all cases)

It is transmitted through contaminated food or water and is more prevalent in developing countries with poor sanitation and hygiene. Children below 15 are particularly susceptible to typhoid fever due to their developing immune systems.

History and examination

  • History of travel to endemic areas or exposure to contaminated food or water
  • Risk factors: Poor sanitation, lack of clean water, and close contact with an infected individual
  • Ask for immunization status

Symptoms

  • Fever (High grade, increasing trends over 5-7 days associated with seating and chills )
  • Headache
  • Abdominal pain
  • Constipation or diarrhea (Common)
  • Anorexia, and fatigue, sweating
  • Malaise

Signs

  • High fever (step-ladder pattern)
  • Toxic looks, lethargic, dehydrated
  • Coated tongue
  • Relative bradycardia
  • Hepatosplenomegaly
  • Rose spots (rash)

Fever, vomiting, and diarrhea is common symptoms in infant to children up to 5 years.

Differential diagnosis (D/D) & Complication:

D/D

  • Malaria (paroxysmal fever, chills, anemia, travel history)
  • Dengue fever (sudden onset fever, joint pain, rash, thrombocytopenia)
  • Scrub typhus

Complications

  • Intestinal perforation (Due to hyperplasia and necrosis of Peyer’s patches of the terminal ileum manifested as sever abdominal pain, high grade fever, abdominal rigidity and guarding)
  • Intestinal Hemorrhage (High-grade fever, generalized abdominal pain, diarrhea, weight loss, and decreased appetite)
  • Hepatitis and cholecystitis
  • Encephalopathy (Altered state of alertness, delirium, muttering, confusion, convulsion, and coma)
  • Myocarditis or endocarditis
  • Pneumonia
  • Anemia
  • Bacteremia
  • Septicemia
  • Multiple organ failure

Investigation

  • Complete blood count (CBC): Neutrophilia and thrombocytopenia. Eosinopenia is remarkably consistent with typhoid fever.
  • Liver function test : Mild elevation of transaminases
  • Blood cultures (Gold standard): Salmonella is an easy organism to culture and antimicrobial sensitivity results are important for treatment. 90% yield in first week and up to 40% in the fourth week of illness. Send paired cultures (two seprate set of blood culture drawn from different peripheral venous site) with total volume of blood to be sent as 5–10 mL with a blood: broth ratio of 1:5

Note: Stool and urine culture give poor yield so not recommended. Bone marrow culture done in later stage of illness and remain positive even after antibiotic therapy.

  • Serology
    • Widal test:
      • Detects presence of immunoglobulin M (IgM) and IgG antibodies against H (flagellar antigen) and O (somatic antigen) of S. typhi and paratyphi A and B in the second week of illness.
      • It is less specific and limited sensitivity.Not diagnostic, may be supportive and should not be relied upon fully.
      • Tube method better than slide method.
      • In qualitative test (interpretation based on observation), serum is mixed with antigen O, H, AH, BH and agglutination is observed. Then dilution is done for antigen that is positive. Dilution is serially taking small amount of patient serum. For example: 1:40 is 40microliter of patient serum with 1drop of antigen. Similarly, 1:80, 1:160, and 1:320 dilution done by taking 20, 10, and 5 microliter of patient’s serum respectively. If agglutination is seen in higher dilution level, it indicated severe infection.
      • Interpretation:
        • S typhi O positive means active infection of typhoid fever.
        • S typhi H positive means there is a past infection or it shows the result of the immunized person’s serum test report.
        • Antibody titer of both O and H in range of 1:160 dilution or more is taken as a positive test.
      • False positive seen in malaria, rickettsial infection, or infection with other Enterobacteriaceae. It may come false negative in patients treated with prior antibiotics.
    • Typhidot:
      • It detects IgM and IgG antibodies against 50 kd outer membrane protein antigen which is specific for S. typhi. Specificity is only 37% and anamnestic reactions may be seen in other infections.

Note: In typhoid, anamnestic reaction occurs when a person previously infected with Salmonella typhi is re-exposed to the same pathogen. Memory cells recognize the bacterium, triggering a rapid and robust immune response that helps in clearing the infection more efficiently and provides long-lasting immunity against future typhoid infections.

– Ultrasound or CT scan: To assess for complications like intestinal perforation or abscess formation

Admission criteria

  • Children with severe symptoms, complications, or those unable to tolerate oral medications

Management

 Medical

  • Empirical therapy
    • Severe illness, In-patient, or any complication
      • 1st line
        • Ceftrixone (100 mg/kg/day BD; Max: 4g per day)
        • Cefotaxime (Below 1 years or concomitant hepatitis)
          • (150-200 mg/kg/day BD; Max: 8g per day)
      • 2nd Line
        • Aztrenam (Penicillin allergy)
          • (50-100 mg/kg/day BD; Max: 8g per day)
  • Out patient
    • 1st line
      • Cefixime (20mg/kg/day BD; Max: 1.2g per day)
  • 2nd Line
    • Azithromycin (Penicillin allergy)
      • (20 mg/kg/day BD; Max: 4g per day)

Give medication for at least 7 days after fever subsided or total of 14 days, whichever is later. Give Azithromycin for 7 days only.

  • Supportive care
    • For fever: PCM or Flexon if fever did not subside with paracetamol (If fever did not subside with paracetamol, increase the frequency up to four times a day or change to Flexon)
    • Hydration
    • Electrolyte replacement

If by day 7 of antibiotics, defervescence has not occurred but child looks less toxic, there is increase in duration between fever spikes or quick response to antipyretics, same antibiotics can be continued till day 10.

Role of steroid

  • Used only in severe illness. In case of shock, coma, or in altered sensorium, dexamethasone 3 mg/kg followed by 1 mg/kg every 6 hours for 2 days may be given.
  • Steroid increase the relapse rate and cause adverse effects, hence use it wisely.

Surgical: In cases of intestinal perforation or abscess formation, surgical intervention may be required

Advices:

– Encourage proper hand hygiene and safe food handling practices

– Ensure completion of the full course of antibiotics

– Consider vaccination for children traveling to endemic areas

Referral:

– Refer to  for complex cases or complications

Follow up:

– Schedule a follow-up appointment 1-2 weeks after initiating treatment to assess response and monitor for complications

– Continue follow-up visits as needed to ensure complete resolution of the infection and monitor for relapse

Additional points:

  • Carrier state:
    •  Asymptomatic person who sheds Salmonella in stool or urine beyond 3 months of an episode of enteric fever. It is uncommon in pediatric age group hence post illness screening for S. typhi carriage is not recommended.
    • If detected treat with trimethoprim-sulfamethoxazole (10 mg/kg/day for 6–12 weeks) or high dose amoxicillin (75–100 mg/kg/day for 4–6 weeks) to decrease the risk to close contacts.
  • Relapse:
    • Even after adequate treatment, enteric fever has a relapse rate of 5–20%.
    • Recurrence of fever 2–3 weeks after its initial resolution is called relapse. It is usually milder. Treatment of relapse is with the same drug used for initial therapy. Relapse can be differentiated from reinfection only by molecular typing.
  • Clinical failure
    • No defervescence and child looks toxic with increase in fever spikes after 7 days of starting optimal treatment is clinical failure.
    • Rule out: Abscess formation, malaria, hepatitis A, drug fever, thrombophlebitis
    • Repeat investigation  and take careful history
    • Quinolones are contraindicated in pediatric age group
    • Aminoglycosides like amikacin have no role in management as their site of action is extracellularwhile Salmonella is an intracellular organism.
    • Prevents unnecessary use of azithromycin which must be kept as a reserve drug. Azithromycin is the drug of choice in ceftriaxone resistant isolates.
    • If such a child is hemodynamically unstable or the disease is severe, then meropenem may be used.
  • Typhoid vaccine:
    • Three types:
      • Typhoid conjugate vaccine (TCV)
      • Live attenuated Ty21a vaccine
      • Vi capsular polysaccharide vaccine (Vi-PS)
      • For vaccination, in Nepal, currently Typhoid conjugate vaccine (TCV)  is used.
        • Schedule
          • Regular: 15 months of age, Left thigh
          • On campaign
            • 15-23 months: Left Medio lateral aspect of thigh
            • 2-15 years :  Right arm deltoid
        • Dose: 0.5ml, single dose
        • Contraindication
          • Allergy
          • Pregnant and breastfeeding
          • AIDS
          • High fever, sick child

References:

1. Parry CM, Hien TT, Dougan G, White NJ, Farrar JJ. Typhoid fever. N Engl J Med. 2002;347(22):1770-1782.