ENTERIC FEVER in pediatrics

1. DR.MAHROOF ENTERIC FEVER in pediatrics

2. ETIOLOGY: • Caused by Salmonella entericaserovarTyphi(S. Typhi). (Gram negative bacterium). • Similar but less-severe disease is caused by Salmonella Paratyphi A and rarely by S. Paratyphi B (Schotmulleri) and S. Paratyphi C (Hirschfeldii). • Ratio of disease caused by S. Typhi to S. Paratyphi is approximately 10 : 1 • Polysaccharide capsule Vi (virulence) is present in 90% of S. Typhi . (Protects the bacteria)

3. PATHOGENESIS Ingestion Invade body through gut mucosa in terminal ileum. Pass through intestinal mucosa S. Typhienter mesenteric lymphoid system Lymphatics Bloodstream (Asymptomatic bacteremia, Culture negative) Colonize Reticuloendothelial system (replicate in macrophages) Shed back into blood (Secondary bacteremia-Symptoms appear)

4. PATHOGENESIS • Surface Vi polysaccharide capsular antigen interferes with phagocytosis by preventing binding of C3 to bacterial surface. • Ability to survive within macrophages is an important virulence trait encoded by PhoPregulon. • Occasional occurrence of diarrhea: Due to presence of a toxin,related to cholera toxin and E.coli heat-labile enterotoxin. • Clinical syndrome of fever and systemic symptoms: Due to release of proinflammatory cytokines (IL-6, IL-1β, and TNF-α) from infected cells. • Patients with Helicobacter pylori infection have an increased risk of acquiring typhoid fever.

5. CLINICAL FEATURES: • Incubation period: 7 - 14 days (3-30 days) • Clinical presentation varies from mild illness with low-grade fever, malaise, and slight, dry cough to Severe clinical picture with abdominal discomfort & multiple complications. • Diarrhea, toxicity, & complications such as disseminated intravascular coagulopathy are more common in infancy. (increased fatality) • However, some features & complications seen in adults, like relative bradycardia,neurologicmanifestations,and gastrointestinal bleeding are rare in children.

6. CLINICAL FEATURES: • FEATURE RATE (%) • High-grade fever 95 • Coated tongue 76 • Anorexia 70 • Vomiting 39 • Hepatomegaly 37 • Diarrhea 36 • Toxicity 29 • Abdominal pain 21 • Pallor 20 • Splenomegaly 17 • Constipation 7 • Headache 4 • Jaundice 2 • Obtundation 2 • Ileus 1 • Intestinal perforation 0.5

7. CLINICAL FEATURES: • In children diarrhea may occur in earlier stages and may be followed by constipation. • Classic stepladder rise of fever is rare. • In 25% of cases, a macular or maculopapular rash (rose spots)around the 7th-10th day; May appear in crops of 10-15 on the lower chest and abdomen and last 2-3 days. • If no complications occur, symptoms and physical findings gradually resolve within 2-4 wk;

8. COMPLICATIONS: • Altered liver function is found in many patients. • However, clinically significant hepatitis, jaundice, and cholecystitis are rare.

9. COMPLICATIONS: • Extra intestinal complications: • Central nervous system (3-35%): Encephalopathy, cerebral edema, subdural empyema, cerebral abscess, meningitis, ventriculitis, transient parkinsonism, motor neuron disorders, ataxia, seizures, Guillain-Barré syndrome, psychosis. • Cardiovascular system (1-5%): Endocarditis, myocarditis,pericarditis, arteritis, congestive heart failure. • Pulmonary system (1-6%): Pneumonia, empyema, bronchopleural fistula. • Hepatobiliary system (1-26%): Cholecystitis, hepatitis, hepatic abscesses, splenicabscess,peritonitis, paralytic ileus

10. DIAGNOSIS • Mainstay: Culture from blood or another anatomic site. • Blood cultures are positive in 40-60% , early in the course. • Stool & urine culture become positive after 1st wk.

11. DIAGNOSIS • Results of other lab investigations are nonspecific. • Although WBC counts are frequently low in relation to fever and toxicity, there is a wide range in counts; in younger children leukocytosis is common & may reach 20,000-25,000 cells/μL. • Thrombocytopenia may be a marker of severe illness & may accompany disseminated intravascular coagulopathy. • Liver function test results may be deranged, but significant hepatic dysfunction is rare.

12. DIAGNOSIS • Widal test measures antibodies against O and H antigens of S. Typhibut lacks sensitivity and specificity in endemic areas. • O antibodies appear on days 6-8 and • H antibodies on days 10-12 after the onset of the disease. • 'O' titer is considered to be of greater diagnostic significance.

13. DIAGNOSIS: Other tests: • Nested PCR using H1-d primers • Typhidot: Test kit uses 50 kD antigen to detect specific IgM and IgG antibodies to S. typhi • Typhidot-M • IDL Tubex: detects IgM antibodies but not IgG • Dip-S-Ticks test

14. TREATMENT: (WHO, Nelson)

15. TREATMENT: (WHO, Nelson)

16. TREATMENT: (IAP) • 3rd generation cephalosporins, both oral and injectables are recommended for first line treatment. • Oral:Cefixime , Cefpodoximeproxelil • Parenteral:Ceftriaxone, Cefotaxime, Cefoperazone. • Oral 3rd generation cephalosporin to be used in higher dose in typhoid fever. • Azithromycin: Alternative in uncomplicated typhoid. • Aztreonam,Imepenemare potential 2nd line drugs. • For life threatening infection resistant to all other recommended antibiotics fluoroquinolones may be used.

17. PROGNOSIS: • 2-4% of infected children may experience relapse after initial clinical response to treatment. • Individuals who excrete S. Typhi for 3 months or longer after infection are regarded as chronic carriers. The risk for becoming a carrier is low in children (<2% for all infected children) and increases with age. • A chronic urinary carrier state can develop in children with schistosomiasis.

18. PREVENTION: Vaccines: • Oral, live-attenuated Ty21a strain of S. Typhi has good efficacy (67-82%) for up to 5 yr. • Vi capsular polysaccharide for 2 yr of age and older. Booster every 2 yr. Protective efficacy of 70-80%. • Vi-conjugate vaccine has a protective efficacy > 90% in younger children.

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