Overview
Definition:
Typhoid fever is a systemic febrile illness caused by infection with the bacterium *Salmonella enterica* serovar Typhi (S
Typhi)
It is characterized by prolonged fever, headache, abdominal pain, and sometimes a rash.
Epidemiology:
Typhoid fever is endemic in many developing countries, particularly in South Asia, Southeast Asia, and parts of Africa and Latin America
Children are disproportionately affected due to lower levels of hygiene and sanitation
Incidence rates can be as high as 100-300 per 100,000 population in endemic areas
Approximately 10-20 million cases and 200,000 deaths occur annually worldwide, with children accounting for a significant proportion.
Clinical Significance:
Typhoid fever in children poses a significant public health challenge due to its potential for severe morbidity and mortality if left untreated or if drug-resistant strains are involved
Prompt and accurate diagnosis, appropriate antibiotic therapy, and effective prevention strategies are crucial for reducing disease burden and improving outcomes, making this a critical topic for pediatricians and those preparing for DNB and NEET SS examinations.
Clinical Presentation
Symptoms:
Insidious onset of fever, typically gradually increasing in temperature over several days
Relative bradycardia (pulse rate slower than expected for the degree of fever)
Headache
Abdominal pain, often diffuse or in the right lower quadrant
Loss of appetite
Constipation or diarrhea (sometimes pea-soup stools)
Cough
Malaise
Rash (rose spots) may appear in about 10-15% of cases, typically on the trunk.
Signs:
Fever (may reach 39-40°C)
Relative bradycardia
Abdominal tenderness, particularly on palpation of the right iliac fossa
Hepatosplenomegaly may be present
Neurological symptoms such as confusion, delirium, or stupor can occur in severe cases
Rose spots: faint, rose-colored, blanching macules appearing on the abdomen and chest
Signs of dehydration may be evident.
Diagnostic Criteria:
There are no definitive clinical criteria for typhoid fever due to its nonspecific presentation
Diagnosis relies on a combination of clinical suspicion, epidemiological factors, and microbiological confirmation
However, in resource-limited settings, clinical suspicion based on prolonged fever, abdominal symptoms, and epidemiological risk is often the basis for empirical treatment
Definitive diagnosis is based on isolation of S
Typhi from blood, stool, urine, or bone marrow
Serological tests like the Widal test have limited reliability for early diagnosis and are prone to false positives and negatives, especially in endemic areas.
Diagnostic Approach
History Taking:
Detailed history of fever onset and progression
Travel history to or residence in endemic areas
Exposure to contaminated food or water
Symptoms of gastrointestinal distress (abdominal pain, diarrhea, constipation)
Associated symptoms like headache, cough, or rash
Immunization status, particularly against typhoid vaccines
Previous episodes of typhoid fever.
Physical Examination:
Assess vital signs, including temperature and heart rate (looking for relative bradycardia)
Perform a thorough abdominal examination for tenderness, distension, hepatosplenomegaly, and bowel sounds
Examine the skin for characteristic rose spots
Assess hydration status and for signs of neurological involvement.
Investigations:
Blood culture: Gold standard for diagnosis, positive in 50-70% of cases in the first week of illness, decreasing thereafter
Stool culture: Can be positive from the second week onwards, becoming more sensitive as illness progresses
Urine culture: Less sensitive but can be positive
Bone marrow culture: Highly sensitive (90-95%), especially in prolonged or complicated cases, but invasive
Complete blood count (CBC) may show leukopenia with a left shift, anemia, and thrombopenia
Liver function tests may show mild elevation
Polymerase chain reaction (PCR) for S
Typhi DNA is a rapid diagnostic method but is not widely available
Serological tests (Widal test): Often used but has low specificity and sensitivity, especially in endemic regions and with prior vaccination
Typhidot (IgM and IgG antibodies against OMP) is more specific but can have varying sensitivity.
Differential Diagnosis:
Other febrile illnesses with gastrointestinal symptoms, such as malaria, dengue fever, viral gastroenteritis, bacterial gastroenteritis (e.g., *Salmonella Paratyphi*, *Shigella*, *Campylobacter*), tuberculosis, viral hepatitis, rickettsial infections, and brucellosis
Non-infectious causes of fever and abdominal pain should also be considered.
Management
Initial Management:
Prompt initiation of appropriate antibiotic therapy based on local resistance patterns
Adequate hydration and nutritional support
Monitoring for complications
Isolation of the patient to prevent further transmission.
Medical Management:
Antibiotic therapy is the mainstay of treatment
Choice depends on local susceptibility patterns
- First-line agents (where susceptible):
- Azithromycin: 10-20 mg/kg/day once daily for 7-14 days (oral or IV)
Commonly used in children due to good efficacy and favorable safety profile
- Ceftriaxone: 50-100 mg/kg/day IV in 1-2 divided doses for 7-14 days
Effective for severe infections and parenteral use
- Alternative agents (for multidrug-resistant strains or allergies):
- Ciprofloxacin or Levofloxacin (fluoroquinolones): Generally avoided in children under 8 years due to concerns about cartilage damage, but may be used in severe cases in older children or if no alternatives exist (e.g., 10-15 mg/kg/day IV or PO for 10-14 days)
- Trimethoprim-sulfamethoxazole (TMP-SMX): 8-10 mg/kg/day (TMP component) divided into 2 doses for 14 days
May be used if susceptible
- Duration of treatment: Typically 7-14 days
Shorter courses (e.g., 5-7 days with azithromycin) are being evaluated
- Treatment of asymptomatic carriers: Usually involves fluoroquinolones or TMP-SMX for longer durations (e.g., 4-6 weeks), but this is less common in children
*Dosage adjustments may be needed for renal or hepatic impairment.*
Surgical Management:
Rarely indicated
Primarily for complications such as intestinal perforation, hemorrhage, or toxic megacolon
Management is surgical resection and repair, often with broad-spectrum antibiotics and intensive supportive care.
Supportive Care:
Fluid and electrolyte management is crucial, especially in cases of diarrhea or vomiting
Oral rehydration solution (ORS) for mild to moderate dehydration
Intravenous fluids (e.g., Ringer's lactate, normal saline) for severe dehydration or inability to tolerate oral intake
Nutritional support: Maintain adequate caloric intake
bland, easily digestible diet
Antipyretics (e.g., paracetamol) for fever
Careful monitoring for complications such as intestinal perforation, hemorrhage, encephalitis, or sepsis
Antiemetics may be used for nausea and vomiting.
Complications
Early Complications:
Intestinal perforation: Occurs in 1-3% of cases, typically in the third or fourth week of illness, most commonly at the ileocecal junction
Presents with sudden onset of severe abdominal pain, fever, vomiting, and signs of peritonitis
Intestinal hemorrhage: Can occur from Peyer's patches, presenting as melena or hematochezia
Encephalitis: Neurological manifestations like delirium, stupor, coma, seizures, and focal neurological deficits.
Late Complications:
Relapse: Occurs in 5-10% of patients, usually 1-2 weeks after defervescence, with similar symptoms
Sepsis: Disseminated infection leading to multi-organ failure
Abscesses: Formation of abscesses in the liver, spleen, or bone
Cholecystitis or cholangitis
Chronic carrier state: Persistent shedding of S
Typhi in feces or urine, more common in adults but can occur in children who have had severe disease
Osteomyelitis or endocarditis (rare).
Prevention Strategies:
Improved sanitation and access to clean water are the most effective long-term prevention strategies
- Vaccination:
- Vi polysaccharide vaccine (ViPS): Licensed for children >2 years old, provides moderate protection
Requires booster doses
- Conjugate vaccines (e.g., Vi-TT, Vi-PS-rEPA): Licensed for infants and children from 6 months to <2 years old
Generally offer better and longer-lasting immunity
Recommended for children in endemic areas or traveling to such regions
- Food and water safety: Educate communities on safe food handling practices, proper cooking, and avoiding raw or undercooked foods and contaminated water
- Personal hygiene: Emphasis on regular handwashing, especially after defecation and before meals.
Prognosis
Factors Affecting Prognosis:
Timeliness and adequacy of antibiotic treatment
Strain virulence and antibiotic susceptibility
Presence of complications (e.g., perforation, sepsis)
Nutritional status and immune status of the child
Age (infants and young children have a higher risk of severe disease).
Outcomes:
With appropriate antibiotic treatment, mortality rates are low (<1%)
However, in untreated cases or those with complications, mortality can be significant (10-30%)
Children who survive may experience a carrier state or sequelae from severe disease
Prompt and effective management leads to complete recovery in most cases.
Follow Up:
Children treated for typhoid fever should have follow-up to ensure complete recovery and monitor for relapses or complications
Stool cultures may be recommended a few weeks after treatment to assess for clearance of the organism
Education on preventive measures for the child and family is essential.
Key Points
Exam Focus:
Diagnosis of typhoid fever in children relies on clinical suspicion combined with microbiological confirmation
Blood culture is the gold standard for early diagnosis
Antibiotic choice for children is guided by local resistance patterns, with azithromycin and ceftriaxone being common choices
Relative bradycardia and rose spots are classic but not always present findings
Prevention through vaccination and improved sanitation is paramount.
Clinical Pearls:
Always consider typhoid fever in a febrile child from or returning from an endemic area, even with nonspecific symptoms
Remember to check for relative bradycardia, which is a key differentiator
In resource-limited settings, do not delay empirical antibiotic treatment based on clinical suspicion if microbiological confirmation is unavailable
Be vigilant for complications, especially intestinal perforation, which is a surgical emergency
Recognize the importance of local antibiotic resistance patterns when choosing therapy.
Common Mistakes:
Over-reliance on Widal test for diagnosis, especially in endemic areas where false positives are common
Delaying treatment while awaiting definitive culture results in critically ill children
Using inappropriate antibiotics for multidrug-resistant strains
Underestimating the importance of supportive care and hydration
Neglecting to counsel families on preventive measures, leading to recurrent infections.