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TYPHOID FEVER
CONTENTS:
• INTRODUCTION
• PROBLEM STATEMENT
• EPIDEMIOLOGICAL DETERMINANTS
• CLINICAL FEATURES
• LABORATORY DIAGNOSIS OF TYPHOID
• CONTROL OF TYPHOID FEVER
What is typhoid fever?
Result of systemic infection caused by S. typhi.
May occur sporadically, epidemically or endemically.
Found only in human.
SALMONELLA
TYPHOIDAL NON-TYPHOIDAL
CAUSES TYPHOID &
PARATYPHOID FEVER
CAUSES GASTROENTERITIS &
FOOD POISONING
e.g :
SALMONELLA TYPHI,
SALMONELLA PARATYPHI A,
B, C.
e.g :
All other SALMONELLA
serotypes
Important note:
Enteric fever
• Includes both typhoid & paratyphoid fevers.
Problem statement :
typhoid occurs in all parts of the world
where water supplies & sanitation are sub-standard.
• World:
Global disease burden is 21 million cases annually,
( 2,10,00,000 cases).
With deaths of 2,16,000 – 6,00,000 per year.
Majority of this burden occurs in Asia.
• India:
• Typhoid fever is endemic in India.
Data shows 1.53 million cases & 361 deaths in
2013.
EPIDEMIOLOGICAL DETERMINANTS
1. Agent factors
2. Host factors
3. Environmental & social factors
4. Incubation period
5. Mode of transmission
AGENT FACTORS:
AGENT:
1. Typhoid Fever mainly caused by the
bacterium Salmonella typhi.
2. S. typhi has three main antigens- O, H & Vi.
3. Onset of typhoid is based on infecting dose &
virulence of the organism.
4. The bacteria grows best at 37 C.
Three main antigens- O, H & Vi. of S. typhi
H : flagella Ag
O : somatic or cell wall Ag
Vi : polysaccharide virulence
Vi-antigen
AGENT FACTORS:
Reservoir of infection: human is the only reservoir.
1. Cases
• A case is infectious as long as bacilli appears in
stools or urine.
• Case may be mild, moderate or severe.
2. Carriers
• Temporary/incubatory-excrete bacilli for 6 to 8
weeks.
• Chronic- excrete bacilli for more than a year,
organism persist in gall bladder/biliary tract.
e.g. “Typhoid Mary” real name Mary Mallon
“TYPHOID MARY”
Mary Mallon was a cook in Oyster Bay, New York in
early 1900s.
Gave rise to more than 1300 cases in her life time.
She died of pneumonia after 26 years in
quarantine.
Source of infection:
Primary sources
1.Faeces & urine of cases.
2. Carriers.
Secondary sources
• Contaminated
– Water
– Food
– Fingers
– Flies
HOST FACTORS
(a) Age- occur at any age but highest incidence in 5-19 yrs age
group.
(b) Sex- cases more in Males >Female
carrier rate is more in females.
(c) Immunity- Antibody may be stimulated by infection or
immunization.
Antibody against (O) antigen is higher in diseased patient
Antibody against (H) antigen is higher in immunized person.
S.Typhi is intracellular organism so cell mediated immunity
plays a major role in combating the infection.
Ingestion of contaminated food or water Salmonella bacteria
Invade small intestine and enter the bloodstream
Carried by white blood cells in the liver, spleen, and bone
marrow
Multiply and re-enter the bloodstream
Bacteria invade the gallbladder, biliary system, and the
lymphatic tissue of the bowel and multiply in high numbers.
Then pass into the intestinal tract and can be identified for
diagnosis in cultures from the stool tested in the laboratory.
ENVIRONMENTAL & SOCIAL FACTORS
1. Typhoid fever regarded as “Index of general sanitation”
in any country.
2. Increase incidence in July-September.
3. Outside human body bacilli found in :
1. water-2 to 7 days but not multiply
2. soil irrigated with sewage- 35 to 70 days
3. ice & ice cream- over a month
4. food- multiply & survive for sometime
5. milk- grow rapidly without altering its taste
4. Vegetables grown in sewage areas.
5. Pollution of drinking water supplies.
6. Open area defecation & urination.
7. Low personal hygiene.
8. Health ignorance.
INCUBATION PERIOD
Usually 10-14 days
(but it may be as short as 3 days or
as long as 21 days)
depending upon the dose of the
bacilli ingested.
MODE OF TRANSMISSION:
WATER
SOIL
FLIES
FINGERS
FAECES &
URINE
FROM
CASES ,
CARRIERS
RAW OR
COOKED
FOODS
MOUTH OF A
HEALTHY PERSON
Signs and symptoms:
• Classically, the course of untreated
typhoid fever is divided into four
distinct stages, each lasting about a
week. Over the course of these
stages, the patient becomes
exhausted.
INITIAL WEEKS OF THE INFECTION:
• In the first week:
• fever in step ladder fashion
• relative bradycardia (Faget sign),
• malaise,
• headache
• Cough, sore throat.
• A bloody nose (epistaxis) is seen in a quarter of cases, and
abdominal pain is also possible with constipation or pea
soup Diarrhoea.
• A decrease in the number of circulating white blood cells
(leukopenia) occurs with eosinopenia and
relative lymphocytosis;
• blood cultures are positive for Salmonella Typhi or S.
paratyphi.
• The Widal test is usually negative in the first week.
Rose spots:
• The rash commonly appears in 2nd week on
trunk mainly.
• Is a pink papule 2-3 mm in diameter.
Later stages of infection:
Serious complications occur in upto 10% of cases, if illness prolong
beyond 2 weeks.
Third week: Intestinal hemorrhage and perforation.
Signs of shock, sudden drop in temperature
Dark or fresh blood in stools,
• Rare complications:
Urine retention, Pneumonia, Thrombophlebitis, Myocarditis,
Cholecystitis, Nephritis, Osteomyelitis, and Psychosis.
2-5% patients may become Gall-bladder carriers.
LABORATORY DIAGNOSIS:
•Microbiological procedures
• Serological procedures
• New diagnostic tests
Blood Cultures: is mainstay to diagnosis!!!!!
Blood Cultures are positive in:
1st week in 90%
2nd week in 75%
3rd week in 60%
4th week and later in 25%
Microbiological procedure:
Definitive diagnosis is by isolation of S.
typhi from blood, bone marrow, stools.
Measures agglutinating Antibodies levels against
O & H antigens
Serum agglutinins raise abruptly during
the 2nd or 3rdweek
SEROLOGICAL PROCEDURE:
FELIX-WIDAL TEST
Limitations of Widal test:
Test has moderate sensitivity and specificity.
Test can be negative in 30% of culture proven
cases.
This thest gives false positive results due to
other clinical conditions.
NEW DIAGNOSTIC TESTS:
• IDL Tubex detects IgM09 antibodies with in
few minutes.
• Typhidot test that detects presence of IgM
and IgG in three hour against 50 kD antigen.
• Typhidot-M: that detects IgM only.
• IgM dipstick test: detects IgM abs against
S.typhi lipopolysacaride
Important Laboratory diagnosis :
‘BASU’ (MNEMONIC)
TEST OF DIAGNOSIS TIME OF DIGNOSIS
BLOOD CULTURE
(MAINSTAY FOR DIGNOSIS)
1ST WEEK
ANTIBODIES
(WIDAL TEST)
2ND WEEK
STOOL CULTURE 3RD WEEK
URINE TEST 4ST WEEK
CONTROL OF TYPHOID FEVER:
1. Control of :
reservoirs
cases
carriers
2. Control of sanitation
3. immunization
TREATMENT :
Susceptibility Antibiotic Days
OPTIMAL
THERAPY
FULLY
SENSITIVE
Fluoroquinolone:
Ofloxacin or
ciprofloxacin
5-7
MULTI-DRUG
RESISTANCE
Fluoroquinolone or
cefixime
5-7
7-14
QUINOLONE
RESISTANCE
Azithromycin or
ceftriaxone
7
10-14
Control of reservoirs:
Identification, isolation, treatment
& disinfection.
Control of cases:
Early diagnosis, notification,
isolation, treatment, follow-up.
Control carriers:
Identification, treatment, surgery,
surveillance, health education.
Control of cases:
Early diagnosis : Blood & stool cultures are imp. in
diagnosis of the cases.
Notification: inform the officials .
Isolation: separate the patients to prevent spread
of inf.
Treatment: drug of choice : fluoroquinolones.
Follow-up: Examination of stools & urine for 3-4
months after discharge.
Control of carriers:
Identification: To prevent ultimate source -typhoid.
Treatment: Ampicillin or Amoxycillin with
Probenecid for 6 weeks.
Surgery: Cholecystectomy , nephrectomy can be
done.
Surveillance: Carriers to be prevented from food
handling.
Health Education: Regarding hand washing and
sanitation.
CONTROL OF SANITATION
• Protection & purification of drinking water
supplies.
• Improvement of basic sanitation.
• Promotion of food hygiene.
Sanitation combined with health
education results in reduction of typhoid
morbidity.
IMMUNIZATION
Vaccination recommended to-
Any person above 2yrs of age
1- those live in endemic area
2- household contacts
3- Groups at risk like school children and
hospital staff etc.
4- those attending melas & yatras,
5- travellers to endemic areas.
THREE TYPES OF VACCINES
1) Old parenetral killed whole cell vaccine was effective,
but produced strong side effects.
2) The Vi polysaccharide vaccine:
Given s/c or i/m.
Not given to child below 2yrs.
Only 1 dose it required & takes 7 days to start protection .
Re-vaccination given after 3yrs.
3) THE Ty21a Vaccine:
Orally admin. Live attenuated strain.
Used in persons >5yrs
A 3 –dose regimen followed.
Protective immunity achieved 7 days after last dose.
KEY POINTS:
• Clean water, sanitation and hygienic handling of
foodstuffs are the keys to prevention & control of
the disease.
Q & A:
• The freshly prepared ORS should not be used
after:
1. 6hrs
2. 12hrs
3. 18hrs
4. 24hrs
• The usual incubation period of typhoid fever is:
1. 10-14 days
2. 3-5 days
3. 21-25 days
4. Less than 3 days
4
1
• Not a antigen of salmonella typhi?
1. O Ag
2. H Ag
3. Vi Ag
4. S Ag
“Typhoid mary” is a good example of :
1. Infectious case
2. Temporary carrier
3. Chronic carrier
4. reservoir
4
3
• Drug of choice for carriers of typhoid is:
1. Ampicillin
2. Chloramphenicol
3. Co-trimoxazole
4. Clindamycin
• Isolation in patient with typhoid is done till:
1. Till Fever subsides
2. Till widal becomes negative
3. Till 3 stool test are negative
4. For 48 hrs of antibiotic treatment
1
3

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Typhoid fever

  • 2. CONTENTS: • INTRODUCTION • PROBLEM STATEMENT • EPIDEMIOLOGICAL DETERMINANTS • CLINICAL FEATURES • LABORATORY DIAGNOSIS OF TYPHOID • CONTROL OF TYPHOID FEVER
  • 3. What is typhoid fever? Result of systemic infection caused by S. typhi. May occur sporadically, epidemically or endemically. Found only in human.
  • 4. SALMONELLA TYPHOIDAL NON-TYPHOIDAL CAUSES TYPHOID & PARATYPHOID FEVER CAUSES GASTROENTERITIS & FOOD POISONING e.g : SALMONELLA TYPHI, SALMONELLA PARATYPHI A, B, C. e.g : All other SALMONELLA serotypes
  • 5.
  • 6. Important note: Enteric fever • Includes both typhoid & paratyphoid fevers.
  • 7. Problem statement : typhoid occurs in all parts of the world where water supplies & sanitation are sub-standard. • World: Global disease burden is 21 million cases annually, ( 2,10,00,000 cases). With deaths of 2,16,000 – 6,00,000 per year. Majority of this burden occurs in Asia. • India: • Typhoid fever is endemic in India. Data shows 1.53 million cases & 361 deaths in 2013.
  • 8. EPIDEMIOLOGICAL DETERMINANTS 1. Agent factors 2. Host factors 3. Environmental & social factors 4. Incubation period 5. Mode of transmission
  • 9. AGENT FACTORS: AGENT: 1. Typhoid Fever mainly caused by the bacterium Salmonella typhi. 2. S. typhi has three main antigens- O, H & Vi. 3. Onset of typhoid is based on infecting dose & virulence of the organism. 4. The bacteria grows best at 37 C.
  • 10. Three main antigens- O, H & Vi. of S. typhi H : flagella Ag O : somatic or cell wall Ag Vi : polysaccharide virulence Vi-antigen
  • 11. AGENT FACTORS: Reservoir of infection: human is the only reservoir. 1. Cases • A case is infectious as long as bacilli appears in stools or urine. • Case may be mild, moderate or severe. 2. Carriers • Temporary/incubatory-excrete bacilli for 6 to 8 weeks. • Chronic- excrete bacilli for more than a year, organism persist in gall bladder/biliary tract. e.g. “Typhoid Mary” real name Mary Mallon
  • 12. “TYPHOID MARY” Mary Mallon was a cook in Oyster Bay, New York in early 1900s. Gave rise to more than 1300 cases in her life time. She died of pneumonia after 26 years in quarantine.
  • 13. Source of infection: Primary sources 1.Faeces & urine of cases. 2. Carriers. Secondary sources • Contaminated – Water – Food – Fingers – Flies
  • 14. HOST FACTORS (a) Age- occur at any age but highest incidence in 5-19 yrs age group. (b) Sex- cases more in Males >Female carrier rate is more in females. (c) Immunity- Antibody may be stimulated by infection or immunization. Antibody against (O) antigen is higher in diseased patient Antibody against (H) antigen is higher in immunized person. S.Typhi is intracellular organism so cell mediated immunity plays a major role in combating the infection.
  • 15. Ingestion of contaminated food or water Salmonella bacteria Invade small intestine and enter the bloodstream Carried by white blood cells in the liver, spleen, and bone marrow Multiply and re-enter the bloodstream Bacteria invade the gallbladder, biliary system, and the lymphatic tissue of the bowel and multiply in high numbers. Then pass into the intestinal tract and can be identified for diagnosis in cultures from the stool tested in the laboratory.
  • 16. ENVIRONMENTAL & SOCIAL FACTORS 1. Typhoid fever regarded as “Index of general sanitation” in any country. 2. Increase incidence in July-September. 3. Outside human body bacilli found in : 1. water-2 to 7 days but not multiply 2. soil irrigated with sewage- 35 to 70 days 3. ice & ice cream- over a month 4. food- multiply & survive for sometime 5. milk- grow rapidly without altering its taste 4. Vegetables grown in sewage areas. 5. Pollution of drinking water supplies. 6. Open area defecation & urination. 7. Low personal hygiene. 8. Health ignorance.
  • 17. INCUBATION PERIOD Usually 10-14 days (but it may be as short as 3 days or as long as 21 days) depending upon the dose of the bacilli ingested.
  • 18. MODE OF TRANSMISSION: WATER SOIL FLIES FINGERS FAECES & URINE FROM CASES , CARRIERS RAW OR COOKED FOODS MOUTH OF A HEALTHY PERSON
  • 19. Signs and symptoms: • Classically, the course of untreated typhoid fever is divided into four distinct stages, each lasting about a week. Over the course of these stages, the patient becomes exhausted.
  • 20. INITIAL WEEKS OF THE INFECTION: • In the first week: • fever in step ladder fashion • relative bradycardia (Faget sign), • malaise, • headache • Cough, sore throat. • A bloody nose (epistaxis) is seen in a quarter of cases, and abdominal pain is also possible with constipation or pea soup Diarrhoea. • A decrease in the number of circulating white blood cells (leukopenia) occurs with eosinopenia and relative lymphocytosis; • blood cultures are positive for Salmonella Typhi or S. paratyphi. • The Widal test is usually negative in the first week.
  • 21. Rose spots: • The rash commonly appears in 2nd week on trunk mainly. • Is a pink papule 2-3 mm in diameter.
  • 22. Later stages of infection: Serious complications occur in upto 10% of cases, if illness prolong beyond 2 weeks. Third week: Intestinal hemorrhage and perforation. Signs of shock, sudden drop in temperature Dark or fresh blood in stools, • Rare complications: Urine retention, Pneumonia, Thrombophlebitis, Myocarditis, Cholecystitis, Nephritis, Osteomyelitis, and Psychosis. 2-5% patients may become Gall-bladder carriers.
  • 23. LABORATORY DIAGNOSIS: •Microbiological procedures • Serological procedures • New diagnostic tests
  • 24. Blood Cultures: is mainstay to diagnosis!!!!! Blood Cultures are positive in: 1st week in 90% 2nd week in 75% 3rd week in 60% 4th week and later in 25% Microbiological procedure: Definitive diagnosis is by isolation of S. typhi from blood, bone marrow, stools.
  • 25. Measures agglutinating Antibodies levels against O & H antigens Serum agglutinins raise abruptly during the 2nd or 3rdweek SEROLOGICAL PROCEDURE: FELIX-WIDAL TEST
  • 26. Limitations of Widal test: Test has moderate sensitivity and specificity. Test can be negative in 30% of culture proven cases. This thest gives false positive results due to other clinical conditions.
  • 27. NEW DIAGNOSTIC TESTS: • IDL Tubex detects IgM09 antibodies with in few minutes. • Typhidot test that detects presence of IgM and IgG in three hour against 50 kD antigen. • Typhidot-M: that detects IgM only. • IgM dipstick test: detects IgM abs against S.typhi lipopolysacaride
  • 28. Important Laboratory diagnosis : ‘BASU’ (MNEMONIC) TEST OF DIAGNOSIS TIME OF DIGNOSIS BLOOD CULTURE (MAINSTAY FOR DIGNOSIS) 1ST WEEK ANTIBODIES (WIDAL TEST) 2ND WEEK STOOL CULTURE 3RD WEEK URINE TEST 4ST WEEK
  • 29. CONTROL OF TYPHOID FEVER: 1. Control of : reservoirs cases carriers 2. Control of sanitation 3. immunization
  • 30. TREATMENT : Susceptibility Antibiotic Days OPTIMAL THERAPY FULLY SENSITIVE Fluoroquinolone: Ofloxacin or ciprofloxacin 5-7 MULTI-DRUG RESISTANCE Fluoroquinolone or cefixime 5-7 7-14 QUINOLONE RESISTANCE Azithromycin or ceftriaxone 7 10-14
  • 31. Control of reservoirs: Identification, isolation, treatment & disinfection. Control of cases: Early diagnosis, notification, isolation, treatment, follow-up. Control carriers: Identification, treatment, surgery, surveillance, health education.
  • 32. Control of cases: Early diagnosis : Blood & stool cultures are imp. in diagnosis of the cases. Notification: inform the officials . Isolation: separate the patients to prevent spread of inf. Treatment: drug of choice : fluoroquinolones. Follow-up: Examination of stools & urine for 3-4 months after discharge.
  • 33. Control of carriers: Identification: To prevent ultimate source -typhoid. Treatment: Ampicillin or Amoxycillin with Probenecid for 6 weeks. Surgery: Cholecystectomy , nephrectomy can be done. Surveillance: Carriers to be prevented from food handling. Health Education: Regarding hand washing and sanitation.
  • 34. CONTROL OF SANITATION • Protection & purification of drinking water supplies. • Improvement of basic sanitation. • Promotion of food hygiene. Sanitation combined with health education results in reduction of typhoid morbidity.
  • 35. IMMUNIZATION Vaccination recommended to- Any person above 2yrs of age 1- those live in endemic area 2- household contacts 3- Groups at risk like school children and hospital staff etc. 4- those attending melas & yatras, 5- travellers to endemic areas.
  • 36. THREE TYPES OF VACCINES 1) Old parenetral killed whole cell vaccine was effective, but produced strong side effects. 2) The Vi polysaccharide vaccine: Given s/c or i/m. Not given to child below 2yrs. Only 1 dose it required & takes 7 days to start protection . Re-vaccination given after 3yrs. 3) THE Ty21a Vaccine: Orally admin. Live attenuated strain. Used in persons >5yrs A 3 –dose regimen followed. Protective immunity achieved 7 days after last dose.
  • 37. KEY POINTS: • Clean water, sanitation and hygienic handling of foodstuffs are the keys to prevention & control of the disease.
  • 38. Q & A: • The freshly prepared ORS should not be used after: 1. 6hrs 2. 12hrs 3. 18hrs 4. 24hrs • The usual incubation period of typhoid fever is: 1. 10-14 days 2. 3-5 days 3. 21-25 days 4. Less than 3 days 4 1
  • 39. • Not a antigen of salmonella typhi? 1. O Ag 2. H Ag 3. Vi Ag 4. S Ag “Typhoid mary” is a good example of : 1. Infectious case 2. Temporary carrier 3. Chronic carrier 4. reservoir 4 3
  • 40. • Drug of choice for carriers of typhoid is: 1. Ampicillin 2. Chloramphenicol 3. Co-trimoxazole 4. Clindamycin • Isolation in patient with typhoid is done till: 1. Till Fever subsides 2. Till widal becomes negative 3. Till 3 stool test are negative 4. For 48 hrs of antibiotic treatment 1 3