Enteric Fever (Typhoid) in Children: Clinical Case and Viva Q&A

Clinical Case of Enteric Fever in Children

A 7-year-old boy is brought to the pediatric clinic with a 5-day history of high-grade fever (up to 40°C), accompanied by abdominal pain, headache, and malaise. The child's mother reports that he has been refusing food but drinking water frequently. She also mentions loose stools for the past 2 days.

On examination:

• Temperature: 39.5°C
• Pulse: 110 beats/min
• Respiratory rate: 24 breaths/min
• Blood pressure: 100/60 mmHg

The child appears lethargic and has a coated tongue. Abdominal examination reveals a slightly distended abdomen with tenderness in the right lower quadrant. The liver is palpable 2 cm below the costal margin, and the spleen is just palpable. No rose spots are visible on the trunk.

Laboratory investigations show:

• WBC count: 4,500/μL with relative lymphocytosis
• Hemoglobin: 10.5 g/dL
• Platelet count: 140,000/μL
• ESR: 35 mm/hr
• ALT: 65 U/L
• AST: 70 U/L

Blood culture is positive for Salmonella Typhi, confirming the diagnosis of enteric fever. The isolate is sensitive to ceftriaxone and azithromycin but resistant to ciprofloxacin.

The child is admitted for intravenous ceftriaxone therapy and supportive care. After 5 days of treatment, the fever subsides, and the patient's condition improves significantly.

Clinical Presentations of Enteric Fever in Children

1. Classical Presentation

   • Gradual onset of fever over several days
   • Fever reaching 39-40°C by the end of the first week
   • Headache, malaise, and anorexia
   • Relative bradycardia (pulse-temperature dissociation)
   • Abdominal pain and constipation (more common than diarrhea in older children)
   • Coated tongue and hepatosplenomegaly
   • Rose spots on trunk (may be difficult to see in dark-skinned children)

2. Atypical Presentation in Young Children

   • More abrupt onset of fever
   • Predominant gastrointestinal symptoms (diarrhea, vomiting)
   • Respiratory symptoms (cough, respiratory distress)
   • Neurological manifestations (febrile seizures, meningismus)

3. Severe or Complicated Presentation

   • High fever with altered mental status
   • Severe dehydration and electrolyte imbalances
   • Intestinal perforation or hemorrhage
   • Hepatitis with jaundice
   • Myocarditis or shock

4. Mild or Subclinical Presentation

   • Low-grade fever
   • Mild gastrointestinal symptoms
   • Fatigue and decreased appetite
   • May be mistaken for viral illness

5. Relapse Presentation

   • Recurrence of symptoms after initial clinical improvement
   • Usually milder than the initial episode
   • Occurs 2-3 weeks after completion of treatment

6. Chronic Carrier State

   • Asymptomatic or with minimal symptoms
   • Intermittent shedding of bacteria in stool or urine
   • More common in children with underlying biliary tract abnormalities

Viva Questions and Answers on Enteric Fever in Children

1. Q: What is the causative agent of enteric fever?

   A: Enteric fever is caused by Salmonella enterica serotype Typhi (S. Typhi) and Salmonella enterica serotype Paratyphi A, B, or C (S. Paratyphi). S. Typhi is responsible for typhoid fever, while S. Paratyphi causes paratyphoid fever.

2. Q: What is the incubation period for enteric fever?

   A: The incubation period typically ranges from 7 to 14 days but can vary from 3 to 30 days, depending on the inoculum size and host factors.

3. Q: How is enteric fever transmitted?

   A: Enteric fever is transmitted through the fecal-oral route, usually by ingestion of contaminated food or water. Person-to-person transmission can occur, especially from asymptomatic carriers.

4. Q: What is the significance of rose spots in enteric fever?

   A: Rose spots are salmon-colored, blanching, maculopapular lesions about 2-4 mm in diameter, typically found on the trunk. They are pathognomonic for enteric fever but are only seen in 5-30% of cases, especially in light-skinned individuals.

5. Q: How does the clinical presentation of enteric fever differ in young children compared to older children and adults?

   A: Young children often present with more abrupt onset, higher rates of diarrhea and vomiting, respiratory symptoms, and neurological manifestations such as febrile seizures. The classical step-ladder pattern of fever is less common in young children.

6. Q: What is meant by relative bradycardia in enteric fever?

   A: Relative bradycardia, also known as pulse-temperature dissociation, refers to a heart rate that is lower than expected for the degree of fever. It is a characteristic finding in enteric fever but may be less prominent in children compared to adults.

7. Q: What are the typical hematological findings in enteric fever?

   A: Typical findings include normal or low white blood cell count (leukopenia) with relative lymphocytosis, mild anemia, and thrombocytopenia. However, in young children, leukocytosis may be observed instead of leukopenia.

8. Q: What is the gold standard for diagnosis of enteric fever?

   A: The gold standard for diagnosis is blood culture, which is positive in 40-60% of cases. Bone marrow culture has higher sensitivity (80-95%) but is more invasive and rarely performed in children.

9. Q: What is the Widal test, and what are its limitations in diagnosing enteric fever?

   A: The Widal test is a serological test measuring antibodies against O and H antigens of S. Typhi. Its limitations include low sensitivity and specificity, cross-reactivity with other Salmonella species, and the need for paired sera for accurate interpretation. It is not recommended for routine diagnosis in endemic areas.

10. Q: What are the indications for hospitalization in a child with enteric fever?

    A: Indications include severe illness, persistent vomiting, severe diarrhea, abdominal distension, neurological manifestations, age <2 years, and the presence of comorbidities or complications.

11. Q: What is the first-line antibiotic treatment for uncomplicated enteric fever in children?

    A: The current first-line treatment is oral azithromycin (10-20 mg/kg/day for 7 days) or cefixime (15-20 mg/kg/day for 7-14 days). In areas with known susceptibility, fluoroquinolones may be used in children >12 years old.

12. Q: What antibiotic is recommended for severe or complicated enteric fever in children?

    A: Intravenous ceftriaxone (50-75 mg/kg/day) or cefotaxime (40-80 mg/kg/day) for 10-14 days is recommended for severe or complicated cases.

13. Q: What is meant by ESBL-producing Salmonella Typhi, and how does it affect treatment?

    A: ESBL (Extended-Spectrum Beta-Lactamase) producing S. Typhi are resistant to most beta-lactam antibiotics, including third-generation cephalosporins. Treatment options for ESBL-producing strains include carbapenems (e.g., meropenem) or azithromycin.

14. Q: What is the significance of Extensively Drug-Resistant (XDR) typhoid fever?

    A: XDR typhoid refers to S. Typhi strains resistant to first-line antibiotics (chloramphenicol, ampicillin, trimethoprim-sulfamethoxazole), fluoroquinolones, and third-generation cephalosporins. It poses significant treatment challenges and has been reported in several countries, particularly in South Asia.

15. Q: What are the most common complications of enteric fever in children?

    A: Common complications include gastrointestinal bleeding, intestinal perforation, encephalopathy, hepatitis, myocarditis, and pneumonia. In young children, neurological complications such as meningitis may occur.

16. Q: How is intestinal perforation in enteric fever managed?

    A: Management includes aggressive fluid resuscitation, broad-spectrum antibiotics (including anaerobic coverage), and urgent surgical intervention. The preferred surgical procedure is usually primary closure or resection with anastomosis, depending on the number and location of perforations.

17. Q: What is the recommended fluid management in enteric fever?

    A: Careful fluid management is crucial. Isotonic fluids (e.g., normal saline) should be used for maintenance and deficit correction. Oral rehydration is preferred when possible. In severe cases, close monitoring of electrolytes and urine output is essential to guide fluid therapy.

18. Q: What dietary recommendations should be given for a child with enteric fever?

    A: A high-calorie, easily digestible diet should be encouraged as tolerated. Small, frequent meals are often better tolerated. There's no need for specific dietary restrictions unless complications like intestinal hemorrhage are present.

19. Q: What is a typhoid carrier state, and how is it managed in children?

    A: A carrier state occurs when an individual continues to shed S. Typhi in stool or urine for >1 year after acute infection. Management includes prolonged antibiotic therapy (e.g., ciprofloxacin for 4-6 weeks) and investigation for gallbladder abnormalities. In some cases, cholecystectomy may be necessary.

20. Q: How effective are typhoid vaccines, and which types are available for children?

    A: Two main types of typhoid vaccines are available: 1) Vi capsular polysaccharide vaccine (ViCPS), given as a single dose to children ≥2 years old, with 50-80% efficacy for 2-3 years. 2) Ty21a live attenuated oral vaccine, given as 3-4 doses to children ≥6 years old, with 50-80% efficacy for 5-7 years. A newer conjugate vaccine (Typbar-TCV) can be given to infants as young as 6 months and provides longer-lasting immunity.

21. Q: What public health measures are important for controlling enteric fever?

    A: Key measures include improving water quality and sanitation, promoting hand hygiene, safe food handling practices, identifying and treating carriers, and implementing vaccination programs in endemic areas.

22. Q: How does one differentiate enteric fever from malaria in endemic areas?

    A: Differentiation can be challenging as both present with fever and similar symptoms. Key differences: malaria often has a more cyclical fever pattern, may cause more pronounced splenomegaly, and typically doesn't cause relative bradycardia. Definitive diagnosis requires blood smear or rapid diagnostic test for malaria and blood culture for enteric fever.

23. Q: What is the significance of leukopenia in enteric fever?

    A: Leukopenia (WBC count <4000/μL) is a characteristic finding in enteric fever, occurring in about 20-25% of cases. It results from depression of bone marrow by endotoxins and cytokines. The presence of leukopenia in a febrile child from an endemic area should raise suspicion for enteric fever.

24. Q: How does one manage a child with suspected enteric fever who has a penicillin allergy?

    A: For mild cases, azithromycin is a good option as it's not related to penicillin. For more severe cases or where azithromycin resistance is a concern, fluoroquinolones (in children >12 years) or carbapenem antibiotics can be used. In cases of non-severe penicillin allergy, ceftriaxone might still be considered under close monitoring.

25. Q: What is the role of glucocorticoids in the management of enteric fever?

    A: Glucocorticoids are not routinely recommended in enteric fever. However, they may be considered in severe cases with shock, delirium, or other life-threatening complications. Dexamethasone (3 mg/kg as a single dose, followed by 1 mg/kg every 6 hours for 48 hours) has been shown to reduce mortality in some studies of severe typhoid fever. However, their use should be carefully considered due to potential risks.

26. Q: How does the pathophysiology of enteric fever explain its clinical manifestations?

    A: The pathophysiology involves several stages: 1) Ingestion and survival in stomach acid 2) Invasion of intestinal mucosa and replication in Peyer's patches 3) Spread to mesenteric lymph nodes, liver, spleen, and bone marrow 4) Secondary bacteremia This explains the gradual onset of symptoms, abdominal pain, hepatosplenomegaly, and systemic symptoms. The infected reticuloendothelial system releases cytokines, contributing to fever and other systemic manifestations.

27. Q: What is the significance of gallbladder involvement in enteric fever?

    A: Gallbladder involvement is significant because: 1) It can lead to acute acalculous cholecystitis as a complication 2) It's the primary site of persistence in chronic carriers 3) Gallbladder abnormalities (e.g., gallstones) increase the risk of becoming a chronic carrier 4) It may necessitate cholecystectomy in some chronic carriers resistant to antibiotic therapy

28. Q: How does enteric fever affect the cardiovascular system in children?

    A: Cardiovascular effects include: 1) Relative bradycardia (pulse-temperature dissociation) 2) Myocarditis (in severe cases) 3) Endocarditis (rare complication) 4) Vasculitis (can lead to peripheral gangrene in extreme cases) 5) Shock (in severe cases due to myocardial dysfunction, vasodilation, or volume depletion)

29. Q: What are the neurological complications of enteric fever in children?

    A: Neurological complications include: 1) Encephalopathy (most common) 2) Meningitis 3) Cerebellar ataxia 4) Guillain-Barré syndrome 5) Transient parkinsonism 6) Acute psychosis These complications are more common in children than adults and can occur in 5-35% of cases, depending on the setting and severity of the infection.

30. Q: How does one interpret the results of a blood culture in enteric fever?

    A: Interpretation of blood culture: 1) Positive culture with S. Typhi or S. Paratyphi confirms the diagnosis 2) Sensitivity is highest in the first week of illness (80-100%) 3) Sensitivity decreases with duration of illness and prior antibiotic use 4) Negative culture doesn't rule out enteric fever 5) Antibiotic susceptibility testing of isolates is crucial for guiding therapy 6) Time to positivity is typically 24-48 hours but may take up to 5 days

31. Q: What is the role of PCR testing in diagnosing enteric fever?

    A: PCR testing for enteric fever: 1) Can detect S. Typhi and S. Paratyphi DNA in blood 2) Has higher sensitivity than blood culture, especially after antibiotic use 3) Provides faster results (usually within 24 hours) 4) Can't provide antibiotic susceptibility data 5) Not widely available in resource-limited settings 6) May be particularly useful in culture-negative cases or when rapid diagnosis is crucial

32. Q: How does one manage antibiotic-associated diarrhea in a child being treated for enteric fever?

    A: Management of antibiotic-associated diarrhea: 1) Ensure adequate hydration (oral or IV as needed) 2) Consider probiotics (e.g., Lactobacillus, Saccharomyces boulardii) 3) If severe or bloody diarrhea occurs, test for C. difficile 4) In C. difficile-negative cases, symptom management and continuation of typhoid treatment 5) For C. difficile-positive cases, treat with oral vancomycin or metronidazole 6) Avoid antimotility agents as they may prolong bacterial shedding

33. Q: What factors contribute to antibiotic resistance in S. Typhi, and how does this impact treatment choices?

    A: Factors contributing to antibiotic resistance: 1) Overuse and misuse of antibiotics 2) Incomplete treatment courses 3) Use of poor-quality or counterfeit antibiotics 4) Horizontal gene transfer between bacteria Impact on treatment: 1) First-line antibiotics (chloramphenicol, ampicillin, co-trimoxazole) often ineffective 2) Increasing fluoroquinolone resistance limits their use 3) Emergence of ESBL and XDR strains necessitates use of carbapenems or azithromycin 4) Requires careful antibiotic stewardship and tailoring therapy based on local resistance patterns

34. Q: How does one counsel families about preventing the spread of enteric fever?

    A: Counseling should include: 1) Importance of hand hygiene, especially after toilet use and before food preparation 2) Boiling or treating drinking water 3) Washing fruits and vegetables thoroughly 4) Avoiding raw or undercooked foods 5) Proper food storage and reheating practices 6) Importance of completing the full course of antibiotics 7) Need for follow-up testing to ensure cure and detect carrier state 8) Consideration of typhoid vaccination for family members 9) Importance of seeking medical care early if symptoms recur