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ENTERIC FEVER
MANOJIT SARKAR
MBBS 3RD PROF,PART-11
Introduction
Fever (Caused) by Infection in Intestine
An Acute Generalized Infection of Intestinal
Lymphoid Tissues, RES , Gall Bladder
Typhoid – 90 % cases
Paratyphoid - 10 % cases
Historical Background
• Typhoid = Typhus ( Rickettsial ) like
• Typhos (Gk) = Smoke (cause), Cloudy (sensorium)
• Phytos (Gk) = Putrefaction (of food as cause)
• Identified as a separate identity by : Huxlam(1972),
Louis(1829), Gerhardt(1837), Shoenlein(1839),
Jenner(1850), Budd(1873), Gaffkey(1884)
The Organism
• Gram Negative, Nonacid fast, Noncapsulated,
Nonsporing bacilli
• A Very Diehard Organism Life Long Carriers
• Types :
– Salmonella typhi
– Salmonella paratyphoid A
– Salmonella paratyphoid B
– Salmonella paratyphoid C
The Organism – Antigenic Structure
• O – Cell Wall Polysaccharide – Heat Stable
• H – Flagellar – Heat Labile
• Vi – Surface – Virulence – Heat Labile
( Useful in Serodiagnoses e.g Widal Test)
Epidemiology
Occurs Exclusively in Humans
Spread – Contaminated Food, Milk, Water
- By Flies from Human Excreta to Food
- Poor Personal Hygiene
- Poor Sanitation
Age – Older Children, Young Adults
<5 Years = only 10 %
<2 Years = only 2 %
Gender - Equal
Epidemiology – Contd..
Areas – Underdeveloped, Poor
Annual Occurrence – Throughout the year
Peak Time – July to August (Summer/Early Rains)
Incubation Period – 1 to 2 weeks (3-60 days)
∞ Dose of Inoculation
Infectivity Period – Long (>2 to 3 m)
Carriers (5%) – 20-50 years; Females more
Epidemiology- Global Distribution
Patient Chronic Carrier
Dissemination
Stool
Vomit
Urine
Indirect
Infection
> 90 %
Direct
Infection
< 10 %
Infected
Water
Food
Healthy Subject
Typhoid Fever
Routes of Transmission
S.Typhi
Ingestion
Intraluminal Multiplication
Intestinal Lymphoid Tissue
Release of Liver, Spleen Blood Stream
Toxemia Reinfect Blood,
Damage Alimentary Tract
Endotoxins
Multiply
Infects
Bones, Skin, CNS
other systems
eg CNS
(Excreted in stool)
Pathogenesis of Typhoid Fever
Typhoid Bacilli
Intestinal Villi
Blood Vessels
To Liver and Spleen
Perforation
Ulcers
Intestinal Lesions
Peyer’s Patches
Liver and Gallbladder Spleen
Typhoid Fever
Bones and Bone marrow Solid Viscera
Heart and Major Vessels
Multi - Organ Effects
Clinical Features
• Fever :
– Acute Onset
– Continuous (+ Morning Remission )
– Moderate To High Grade
– Persisting since 6-7 Days
– Classic Step Ladder Pattern Not Seen in children
Classic Step Ladder Fever of Typhoid
Other Symptoms
• Toxic Look
• Pain in Abdomen
• Diarrhoea / Constipation
• Anorexia, Vomiting
• Headache, Myalgia
• Cough
Clinical Examination
• Coated ( Typhoid V ) Tongue
• Tympanitis of Abdomen
• Soft Splenomegaly(≥ 1 week fever)
• Hepatomegaly ±
• Chest : Rhonchi / Crepts
• Skin : Rosy Spots - Chest / Paraumblicus - not seen in
Indian Children
• Mild / Moderate Anemia
• Meningismus ±
• Jaundice ( Rare)
Complications in Typhoid
Otitis Media, Unilateral Parotitis, Purpuric Eruptions/
Epistaxis, Thrombosis
Miscellaneous
UTI in 20 to 25 % casesRenal
Alopecia, FarunclesSkin
Chronic Osteomyelitis, ArthritisSkeletal
Myocarditis ( Bradycardia, systolic murmur)CVS
Early – Bronchitis
Late – Secondary Pneumococcal Bronchopneumonia
Respiratory
Hemorrhage 1-2%, Perforation 0.5%, (Shock, Distension of
Abdomen) Peritonitis, Hepatitis, Cholangitis
GIT
Encephalopathy (Altered Sensorium), Convulsions ( Toxic
Cases), Meningism, Psychoses
CNS
Diagnosis
Fever of more than seven days
With/Without
Toxemia
Abdominal Pain/ Typanitis
Altered Sensorium
Mild Hepatosplenomegaly
Investigations
Urine CultureU4th Week
Stool CultureS3rd Week
Agglutination Test (Widal)A2nd Week
Blood / Clot Culture
(Bone Marrow Culture, rarely)
B1st Week
“BASU”
Agglutination (WIDAL) Test
• Agglutinins appear in blood by end of 1st week
• O agglutinin : Rises Rapidly ( 4 fold in 10-14 days )
Persists for months
Disappears in a year
• H agglutinin : Rises Slowly
Persists for years
• Hence, O agglutinin is important in recent infection
• Diagnostic levels: >1/80 or 1/160 or Rising Titres (7-10
days apart)
• H agglutinin indicates past infection/ immunization
False Positives and Negatives in Widal
Test
False Positives Immunization with Typhoid Vaccine
Repeated Sub clinical Infections
Past Clinical Infection
Healthy Carriers of S.typhi
Anamnestic Response
Patients of Cirrhosis and Hepatitis
False Negatives Too Early collection of blood sample
Patients on Antibiotics
5 to 10 % do not respond by antibody formation
Non Specific Lab Findings in Typhoid
Fever
• Mild Normochromic Anemia
• Mild Thrombocytopenia
• Leucopenia with Relative Lymphocytosis
• (Leucocytosis suggests either perforation or an incorrect diagnosis)
• Eosinopenia – Presence heralds recovery
• An Increased ESR
• Laboratory Evidence of Mild DIC
• Hyponatremia and Hypokalemia
• Elevation of Liver Enzymes
• Urine : Some Proteins and White Cells
• Stool : Leucocytes and Blood common
Differential Diagnosis
• Infective Diarrhoea : Stool Examination
• Viral Fever : Self limiting (< 7 days)
• UTI : Urinalysis
• Malaria : Blood smear examination
• Miliary TB : F/H, CXR, Mantoux
• Appendicitis : White cell count
• Bacterial Endocarditis : Blood Culture
• Viral Hepatitis : LFTs
• Kala – Azar : Double rise temperature, good appetite, no
toxemia
Treatment - General
• Tepid Sponging
• Paracetamol
• Adequate Water and Food intake
• Hospitalize if : Toxemic / Complications
• Needs Fluids/ Therapy by IV Route
Treatment - Medical
Before 1980s
• Chloaemphenicol 50-100 mg/kg/day/ O or IV in 4 doses x 14 days
• Ampicillin / Amoxycillin 100-200 mg/day/ O or IV in 4 doses x 14 days
• Trimethoprim – Sulphamethaxazole 10 mg of TMP/ kg/day/O or IV
in two divided doses x 14 days
After 1980s(MDRTF)
• Ciprofloxacin 20mg/kg/day/O or 15 mg/kg/day/IV in 2 doses x 7 days
• Ofloxacin 15mg/kg/day/O or 10 mg/kg/day/IV in 2 doses x 7 days
Treatment – Medical – Contd..
Presently
• Cefixime : 10-20 mg / kg/day/O in 2 doses x 7-10 days
• Cefuroxime : 30-40 mg/kg/day/O in 2-3 doses into 7-10 days
• Ceftriaxone : 80-100 mg/kg/day/IV in 2 doses x 7 days
• Cefotaxime : 200mg/kg/day/IV in two doses x 7 days
• Azithromycin : 10mg/kg/day/O single dose x 5 days
Treatment of Complications
• INTESTINAL PERFORATION
– Surgical intervention
– Clindamycin / Metronidazole
• INTESTINAL HAEMORRHAGE
– Bed rest / foot end raised
– Nothing orally
– Repeated blood transfusions
– Morphine sc.
• PNEUMONIA
– ↑ Antimicrobial spectrum
• ANAEMIA : Blood replacement
• ENCEPHALOPATHY
– Anticonvulsants
– Dexamethasone
Prevention
• Maintain Personal Hygiene
• Safe Drinking water and food habits
• Public health measures for
– Disposal of Excreta
– Ban on sale of contaminated food
• Tracing & Treatment of Carriers
• Active immunization with vaccine
Carriers
• Convalescent carrier: Patients who continue to shed bacilli
in feces for 3 weeks to 3 months after cure
• Temporary carrier: Those who shed for 3 months to 1 year
• Chronic Carrier: Those who shed more than 1 year (2 – 4%
patients become chronic carrier)
• Healthy carrier / Intermittent carrier:
– Harbours infection without suffering from the disease
– Bacilli persists in gall bladder or kidney
• Treatment:
– Prolonged treatment with qunilones or Cephlosporins
– May require gall bladder removel
Typhoid Vaccines
Earlier:
– Parenteral killed whole cell vaccine (TAB/TA)
– To children above one year
– Three doses S/C at 4-6 weeks interval
– Booster every year
Later :
– Live oral attenuated Ty21a Vaccine
– To children above 6 years
– Total of 3 capsules on A/D
– Repeated every 3 years
Presently :
– Vi Polysacchride subunit vaccine IM single dose
– To children > 2 years, repeated every three years
Thank you

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Enteric fever

  • 2. Introduction Fever (Caused) by Infection in Intestine An Acute Generalized Infection of Intestinal Lymphoid Tissues, RES , Gall Bladder Typhoid – 90 % cases Paratyphoid - 10 % cases
  • 3. Historical Background • Typhoid = Typhus ( Rickettsial ) like • Typhos (Gk) = Smoke (cause), Cloudy (sensorium) • Phytos (Gk) = Putrefaction (of food as cause) • Identified as a separate identity by : Huxlam(1972), Louis(1829), Gerhardt(1837), Shoenlein(1839), Jenner(1850), Budd(1873), Gaffkey(1884)
  • 4. The Organism • Gram Negative, Nonacid fast, Noncapsulated, Nonsporing bacilli • A Very Diehard Organism Life Long Carriers • Types : – Salmonella typhi – Salmonella paratyphoid A – Salmonella paratyphoid B – Salmonella paratyphoid C
  • 5. The Organism – Antigenic Structure • O – Cell Wall Polysaccharide – Heat Stable • H – Flagellar – Heat Labile • Vi – Surface – Virulence – Heat Labile ( Useful in Serodiagnoses e.g Widal Test)
  • 6. Epidemiology Occurs Exclusively in Humans Spread – Contaminated Food, Milk, Water - By Flies from Human Excreta to Food - Poor Personal Hygiene - Poor Sanitation Age – Older Children, Young Adults <5 Years = only 10 % <2 Years = only 2 % Gender - Equal
  • 7. Epidemiology – Contd.. Areas – Underdeveloped, Poor Annual Occurrence – Throughout the year Peak Time – July to August (Summer/Early Rains) Incubation Period – 1 to 2 weeks (3-60 days) ∞ Dose of Inoculation Infectivity Period – Long (>2 to 3 m) Carriers (5%) – 20-50 years; Females more
  • 9. Patient Chronic Carrier Dissemination Stool Vomit Urine Indirect Infection > 90 % Direct Infection < 10 % Infected Water Food Healthy Subject Typhoid Fever Routes of Transmission
  • 10. S.Typhi Ingestion Intraluminal Multiplication Intestinal Lymphoid Tissue Release of Liver, Spleen Blood Stream Toxemia Reinfect Blood, Damage Alimentary Tract Endotoxins Multiply Infects Bones, Skin, CNS other systems eg CNS (Excreted in stool) Pathogenesis of Typhoid Fever
  • 11. Typhoid Bacilli Intestinal Villi Blood Vessels To Liver and Spleen Perforation Ulcers Intestinal Lesions
  • 12. Peyer’s Patches Liver and Gallbladder Spleen Typhoid Fever Bones and Bone marrow Solid Viscera Heart and Major Vessels Multi - Organ Effects
  • 13. Clinical Features • Fever : – Acute Onset – Continuous (+ Morning Remission ) – Moderate To High Grade – Persisting since 6-7 Days – Classic Step Ladder Pattern Not Seen in children
  • 14. Classic Step Ladder Fever of Typhoid
  • 15. Other Symptoms • Toxic Look • Pain in Abdomen • Diarrhoea / Constipation • Anorexia, Vomiting • Headache, Myalgia • Cough
  • 16. Clinical Examination • Coated ( Typhoid V ) Tongue • Tympanitis of Abdomen • Soft Splenomegaly(≥ 1 week fever) • Hepatomegaly ± • Chest : Rhonchi / Crepts • Skin : Rosy Spots - Chest / Paraumblicus - not seen in Indian Children • Mild / Moderate Anemia • Meningismus ± • Jaundice ( Rare)
  • 17. Complications in Typhoid Otitis Media, Unilateral Parotitis, Purpuric Eruptions/ Epistaxis, Thrombosis Miscellaneous UTI in 20 to 25 % casesRenal Alopecia, FarunclesSkin Chronic Osteomyelitis, ArthritisSkeletal Myocarditis ( Bradycardia, systolic murmur)CVS Early – Bronchitis Late – Secondary Pneumococcal Bronchopneumonia Respiratory Hemorrhage 1-2%, Perforation 0.5%, (Shock, Distension of Abdomen) Peritonitis, Hepatitis, Cholangitis GIT Encephalopathy (Altered Sensorium), Convulsions ( Toxic Cases), Meningism, Psychoses CNS
  • 18. Diagnosis Fever of more than seven days With/Without Toxemia Abdominal Pain/ Typanitis Altered Sensorium Mild Hepatosplenomegaly
  • 19. Investigations Urine CultureU4th Week Stool CultureS3rd Week Agglutination Test (Widal)A2nd Week Blood / Clot Culture (Bone Marrow Culture, rarely) B1st Week “BASU”
  • 20. Agglutination (WIDAL) Test • Agglutinins appear in blood by end of 1st week • O agglutinin : Rises Rapidly ( 4 fold in 10-14 days ) Persists for months Disappears in a year • H agglutinin : Rises Slowly Persists for years • Hence, O agglutinin is important in recent infection • Diagnostic levels: >1/80 or 1/160 or Rising Titres (7-10 days apart) • H agglutinin indicates past infection/ immunization
  • 21. False Positives and Negatives in Widal Test False Positives Immunization with Typhoid Vaccine Repeated Sub clinical Infections Past Clinical Infection Healthy Carriers of S.typhi Anamnestic Response Patients of Cirrhosis and Hepatitis False Negatives Too Early collection of blood sample Patients on Antibiotics 5 to 10 % do not respond by antibody formation
  • 22. Non Specific Lab Findings in Typhoid Fever • Mild Normochromic Anemia • Mild Thrombocytopenia • Leucopenia with Relative Lymphocytosis • (Leucocytosis suggests either perforation or an incorrect diagnosis) • Eosinopenia – Presence heralds recovery • An Increased ESR • Laboratory Evidence of Mild DIC • Hyponatremia and Hypokalemia • Elevation of Liver Enzymes • Urine : Some Proteins and White Cells • Stool : Leucocytes and Blood common
  • 23. Differential Diagnosis • Infective Diarrhoea : Stool Examination • Viral Fever : Self limiting (< 7 days) • UTI : Urinalysis • Malaria : Blood smear examination • Miliary TB : F/H, CXR, Mantoux • Appendicitis : White cell count • Bacterial Endocarditis : Blood Culture • Viral Hepatitis : LFTs • Kala – Azar : Double rise temperature, good appetite, no toxemia
  • 24. Treatment - General • Tepid Sponging • Paracetamol • Adequate Water and Food intake • Hospitalize if : Toxemic / Complications • Needs Fluids/ Therapy by IV Route
  • 25. Treatment - Medical Before 1980s • Chloaemphenicol 50-100 mg/kg/day/ O or IV in 4 doses x 14 days • Ampicillin / Amoxycillin 100-200 mg/day/ O or IV in 4 doses x 14 days • Trimethoprim – Sulphamethaxazole 10 mg of TMP/ kg/day/O or IV in two divided doses x 14 days After 1980s(MDRTF) • Ciprofloxacin 20mg/kg/day/O or 15 mg/kg/day/IV in 2 doses x 7 days • Ofloxacin 15mg/kg/day/O or 10 mg/kg/day/IV in 2 doses x 7 days
  • 26. Treatment – Medical – Contd.. Presently • Cefixime : 10-20 mg / kg/day/O in 2 doses x 7-10 days • Cefuroxime : 30-40 mg/kg/day/O in 2-3 doses into 7-10 days • Ceftriaxone : 80-100 mg/kg/day/IV in 2 doses x 7 days • Cefotaxime : 200mg/kg/day/IV in two doses x 7 days • Azithromycin : 10mg/kg/day/O single dose x 5 days
  • 27. Treatment of Complications • INTESTINAL PERFORATION – Surgical intervention – Clindamycin / Metronidazole • INTESTINAL HAEMORRHAGE – Bed rest / foot end raised – Nothing orally – Repeated blood transfusions – Morphine sc. • PNEUMONIA – ↑ Antimicrobial spectrum • ANAEMIA : Blood replacement • ENCEPHALOPATHY – Anticonvulsants – Dexamethasone
  • 28. Prevention • Maintain Personal Hygiene • Safe Drinking water and food habits • Public health measures for – Disposal of Excreta – Ban on sale of contaminated food • Tracing & Treatment of Carriers • Active immunization with vaccine
  • 29. Carriers • Convalescent carrier: Patients who continue to shed bacilli in feces for 3 weeks to 3 months after cure • Temporary carrier: Those who shed for 3 months to 1 year • Chronic Carrier: Those who shed more than 1 year (2 – 4% patients become chronic carrier) • Healthy carrier / Intermittent carrier: – Harbours infection without suffering from the disease – Bacilli persists in gall bladder or kidney • Treatment: – Prolonged treatment with qunilones or Cephlosporins – May require gall bladder removel
  • 30. Typhoid Vaccines Earlier: – Parenteral killed whole cell vaccine (TAB/TA) – To children above one year – Three doses S/C at 4-6 weeks interval – Booster every year Later : – Live oral attenuated Ty21a Vaccine – To children above 6 years – Total of 3 capsules on A/D – Repeated every 3 years Presently : – Vi Polysacchride subunit vaccine IM single dose – To children > 2 years, repeated every three years