Diagnosis and Management of Typhoid Fever, Presented by a Medical Student (MBBS 3) Fiji School of Medicine

1. PRESENTATION SCENARIO 2
Adarsh Sushil Chand
MBBS Year 2
2015

2. CASE DESCRIPTION

3. CASE SUMMARY: SAKIUSA
 Sakiusa, a 29-year-old man, is admitted to Lautoka Hospital with a history of abdominal pain, fever, and chills for the
past week.
 He had diarrhoea two weeks ago which lasted for several days, but now says he feels constipated.
 He has had no vomiting.
 On physical examination, his temperature is 39.5°C, his heart rate is 55/minute, his blood pressure is normal.
 He has diffuse abdominal tenderness, and his liver and spleen are enlarged.
 On admission, his FBC shows a normal haemoglobin and haematocrit, his WBC count is 3200/mm3 with 35%N,
65%L, his platelet count is normal.
 His liver enzymes are normal.
 His blood culture is positive

4. BLOOD CULTURE RESULT
Blood Agar
XLD Agar
MacKonkeys Agar

5. BLOOD AGAR CULTURE OF BACTERIA
The blood agar plate shows:
• White colonies with black
pigmentation
• No form of haemolysis

6. MAC’KONKEYS AGAR CULTURE
MacKonkeys Agar culture
showing:
• Pale colonies: non lactose
fermenter

7. XLD AGAR CULTURE
XLD agar culture showing:
• Pink colonies: xylose
fermenter
• Black pigmentation

8. DIAGNOSIS OF INFECTIOUS CAUSE AND PATHOGENESIS
Considering the blood culture the organism is diagnosed as Salmonella typhi
PATHOGENESIS
Salmonella typhi enters the GI tract and is ingested by phagocytic cells
Bacteria multiply inside phagocytic cell
Cell ruptures and bacteria released into blood stream (bacteraemia)
Causes fevers, chills and diarrhoea followed by constipation

9. NATURAL HISTORY
Progression to Become Carriers

10. THE CHRONIC CARRIER STATE IN TYPHOID
 The chronic (carrier) state is rare but it does happen
 A carrier is an asymptotic person who carries the disease causing organism but is not showing the signs of infection
 Persons in the carrier state carry the bacteria in the gall bladder and release them into faeces for several months; e.g.
TYPHOID MARY who was responsible for multiple outbreaks and three deaths

11. THE PHYSICAL EXAMINATION
Basis for Findings

12. PHYSICAL EXAMINATION FINDINGS
On examination the following are present:
Fever: 39.50C – high grade fever
Heart rate: 55 beats/minute – bradycardia (PR<60 beats/minute)
Blood pressure: normal
Diffuse abdominal tenderness
Hepatomegaly
Splenomegaly

13. MECHANISMS OF FINDINGS: 1
High Grade Fever: 39.50C
Bacteria phagocytised by macrophages
Release of interleukin-1 (pyrogen)
Resets thermostat Stimulate PGE2
Heat retaining mechanisms stimulated
FEVER
Heart Rate: 55 beats/minute
Known as relative bradycardia: <10 beats/min/10C increase in
temperature thus at temperature of 39.50C the pulse must be
about 120 beats/min but is not.
The exact mechanism of relative bradycardia is unknown
Source:
1. Cunha BA. The diagnostic significance of relative bradycardia in infectious disease.
Clin Microbiol Infect 2000; 6: 633-634
2. Aronoff DM, Watt G. prevalence of relative bradycardia in Orientia Tsutusamushi
infection. Am. J. Trop. Med. Hyg 2003; 68: 477 – 479
3. Cunha BA. Clinical features of Legionnaires Disease. Semin Respir Infect 1998; 13:
116 - 127

14. MECHANISM OF FINDINGS 2
Normal Blood Pressure:
The decreased HR does not affect BP because the
pericardium does not allow for excessive ventricular
stretching thus the recoil force is maintained and cardiac
output is not affected and BP remains normal
Diffuse abdominal tenderness
Bacteria causes inflammation of the intestinal epithelium
and thus leading to pain on palpation

15. MECHANISM OF FINDINGS 3
Hepatomegaly
Systemic sepsis of bacteria
Englufed by Kuffer Cells in liver
Infiltration of monocytes that become macrophages
Enlargement of Liver
Splenomegaly
Bacteria in blood
Activation of specific immune system
B cell and T cell proliferation
Growth of white pulp
Spleen enlarges

16. PUBLIC HEALTH MEASURES
Modes of Transmission
Risk Factors for Transmission

17. TRANSMISSION OF TYPHOID FEVER
 Typhoid fever is transmitted by the faecal – oral route through the 5 F’s of transmission
Food
Fluids
Flies
Fingers/formites
Faeces

18. RISK FACTORS FOR TRANSMISSION
Some risk factors for transmission are:
Unsanitary living conditions e.g. squatters
Not cooking food especially meat properly
Poor sanitary habits e.g. not washing hands
Not boiling water from unsafe sources such as rivers

19. CONFIRMATION OF
DIAGNOSIS
The Widel Test

20. THE WIDEL TEST
The bacteria causing typhoid i.e. S. typhi is mixed with serum from an infected person (the infected
person will have antibodies). In cases of infection the result is O-soma false positive. It is demonstrated
by agglutination in a test tube.
Note: Used to detect O (lipopolysaccharide) and H (flagella) antigens. Need to use two different
samples (usually taken a 7-10 days intervals) to prove a rise in agglutinins in the patient serum.
 O titres: > 1:320
 H titres: > 1:640
It is not used anymore since it is not specific to an acute infection; cannot differentiate carriers from
acute infections

21. TREATMENT
Antibiotics

22. PHARMACOLOGIC MANAGEMENT
Typhoid is treated using the following regime:
1. Combination treatment with ceftriaxone (3rd Generation cephalosporin's) and
ciprofloxacin (quinolone)
2. If not MDR then use a combination of TMP/SMZ
3. Fluroquinilones in susceptible cases
4. 3rd generations cephalosporins

23. MECHANISM OF ACTION: CEPHALOSPORIN AND
FLUROQUINILONE
Contain a β lactam ring and blocks cell wall synthesis by interfering with transpeptidase
which links the cell wall layers. It also inactivates the inhibitor of autolysis
Quinolone inhibits DNA synthesis by blocking the enzymes needed for DNA replication

24. MECHANISM OF ACTION OF TMP/SMZ
SMP also called sulphamethoxazole is a structural analogue of para-amino benzoic acid and
binds to dihydroptroid synthase as an antagonist thus folic acid cannot be used to produce
nucleic acids
TMP also called trimethoprim inhibits dihydrofolate synthase and inhibits production of
folic acid by the bacteria thus no nucleic acids are synthesised

25. PHARMACOLOGY
Pharmacodynamics
Pharmacokinetics

26. CEPHALOSPORINS
1. PHARMACOKINETICS
Ceftriaxone: completely absorbed, V=5.78-13.5l and crosses blood-placenta barrier, 85-95% is protein bound, plasma clearance =
0.58-1.45L/h, renal clearance = 0.32-0.73L/h, half life = 5.8-8.7 hours
DRUG INTERACTIONS
1. Ceftriaxone increases risks of haemorrhage with NSAID’s e.g. aspirin use; additive for platelet inhibition; avoid use if patient
needs aspirin e.g. heart patients
2. Probenecid: decreases renal clearance for cephalosporins (thus results in increased plasma concentration and potential for
toxicity). Note that is does not affect ceftriaxone

27. TRIMETHOPRIM AND SULPHAMETHOXAZOLE
PHARMACOKINETICS
a) Trimethoprim: peak concentration is reached in 2 hours, distributes into tissues, 60% excreted in urine in first 24
hours
b) Sulphamethoxazole: peaks in 4 hours in plasma, distributes in ECF and 25-50% excreted by kidneys in 24 hours
DRUG INTERACTIONS:
1. Cyclosporins/tacrolimus: increased risk of nephrotoxicity
2. Methotrexate: reduce renal clearance therefore increase bone marrow suppression; use other antibiotic
3. Phenytoin: inhibits metabolism and increases risks of toxicity
4. Warfarin: metabolism is inhibited and thus increases risk of bleeding; monitor INR and change dose of warfarin as
needed

28. QUINOLONES
PHARMACOKINETICS
 Ciprofloxacin: well absorbed, F=70%, 10% distributes in CSF, 20-40% binds with plasma proteins, renal
clearance=300mL/minute, half life of renal clearance=4h, 40-50% excreted in urine unchanged. Inhibitor of CYP450.
DRUG INTERACTIONS
A) Theophylline: reduces elimination of theophylline and prolongs half life
B) Caffeine: interferes with metabolism of caffeine
C) Forms chelates with multivalent cations – reduced absorption of Cipro
D) Omeprazole: reduces plasma peak concentration of Ciprofloxacin and reduced AUC mean

29. DRUG INTERACTIONS CONTINUED
A) Phenytoin: can increase or decrease plasma levels
B) Oral antidiabetics: intensifies the antidiabetics effect – may lead to severe hypoglycaemia and even death
C) Cyclosporins: increase serum creatinine in patients receiving ciprofloxacin with cyclosporins
D) Oral anti-coagulants: intensifies action of anti-coagulants such as warfarin
E) Probenecid: reduces renal clearance of ciprofloxacin
F) Methotrexate: reduces renal clearance of methotrexate
G) Metoclopramide: increases absorption of ciprofloxacin
H) NSAID’s (except aspirin): may cause convulsions
I) Rorpinirole: increased effects of rorpinirole

30. DRUG INTERACTIONS CONTINUED
A) Lidocaine: increased effects of lidocaine
B) Clozapine: increased serum levels of clozapine
C) Sildenafil: increase serum levels (peak) of sildenafil
D) QT Interval prolonging drugs: additive effects with ciprofloxacin i.e. prolongs QT interval further
E) Alcohol: no effect
F) Dairy food: decreases absorption of ciprofloxacin

31. ANY QUESTIONS
???