This document provides information about typhoid fever, including its pathogenesis, epidemiology, risk factors, prevention, management, and a case presentation. Typhoid fever is caused by the Salmonella typhi bacteria and spreads through the fecal-oral route. It commonly presents with fever, abdominal pain, and diarrhea. Treatment involves antibiotics like ciprofloxacin and supportive care. A case is presented of a 30-year-old male trader diagnosed with typhoid fever based on symptoms and a positive widal test who was successfully treated with ciprofloxacin and paracetamol.

1. TYPHOID FEVER
BY
BASSEY, AMAOBONG OKON
FNPH INTERN PHARMACIST

2. OUTLINE OF PRESENTATION
• INTRODUCTION
• PATHOGENESIS
• PATHOPHYSIOLOGY
• EPIDEMIOLOGY
• RISK FACTORS
• PREVENTION
• MANAGEMENT
• CASE PRESENTATION
• REFERENCES

3. INTRODUCTION
• Typhoid is a systemic disease caused by a bacteria
,salmonella transmitted mainly by ingestion of
contaminated fluids or foods. It spreads through faecal-oral
route and is characterized by high fever, chills, abdominal
pain, muscle pain, generalized body weakness, diarrhea,
headache.

4. PATHOGENESIS

5. PATHOGENESIS
• Once fluids or food contaminated with the bacteria are ingested,
the bacteria enters the stomach to the small intestine, invades the
peyer’s patch of the intestinal wall where it attaches and is
engulfed by the macrophages.
• It enters the bloodstream via the lymphatics to the liver, spleen
and reticuloendothelial system and multiplies in high numbers
until some critical density is reached.

6. PATHOGENESIS
• The bacteria induces macrophage apoptosis breaking out into the
bloodstream to attack the rest of the body.
• From the blood or liver via the bile ducts it infects the gall
bladder, reenters the gastrointestinal tract in the bile spreading to
other hosts via stool. It occasionally invades the urinary tract and
spreads via urine.

7. PATHOPHYSIOLOGY
Invasion of the intestinal epithelial cell membrane and macrophages
will subsequently lead to inflammation and ulceration of the
intestinal wall which will result in abdominal pain, diarrhea, malaise.
As bacteremia develops patients often experience chills, fever,
anorexia, headache and myalgias.

8. Clinical Manifestations
Week 1
GIT symptoms develop together with dry cough,
dull frontal headache, delirium
abdominal pain and tenderness and, in some
cases, fierce colicky right upper quadrant pain.
constipation.
Week 2
Symptoms worsen
Salmon colored rose spots. Distended, abdomen
becomes distended, soft splenomegaly is
common
Week 3
Neurological involvement. Significant weight
loss. Complications may cause death.
Abdominal distension is severe. foul, green-
yellow, liquid diarrhea. apathy, confusion, and
even psychosis.
Week 4
The fever, mental state, and abdominal
distension slowly improve over a few days.
Intestinal and neurologic complications may still
occur in surviving untreated individuals.. Some
survivors become asymptomatic S typhi carriers

9. EPIDEMIOLOGY

10. EPIDEMIOLOGY
• In developing areas of Africa, South-East Asia and the Western pacific regions
typhoid fever is still a public health problem. WHO estimates the global
typhoid fever disease burden at 11-20 million cases annually.
• Typhoid incidence ranges from 3.9%- 18.6% in Nigeria. Although the true
incidence of typhoid fever is difficult to evaluate in Nigeria due to lack of
proper coordinated surveillance system, some researchers have documented
information on typhoid prevalence in some states ranging from 0.071% in Oyo
to 47.1% in Osun.

11. RISK FACTORS
• Travel to endemic areas
• Poor hygiene habits and poor sanitation
• Immunosuppressive illnesses
• Consumption of raw fruits and foods that may be contaminated with sewage

12. INVESTIGATIONS AND DIAGNOSIS
• A positive culture is the gold standard for the diagnosis of
typhoid fever. Specimens for culture may be obtained from the
blood, stool, urine, bone marrow, gastric and intestinal secretions.
• In Nigeria, the general test for typhoid is the widal test although
there’s the risk of false positives and negatives.

13. PREVENTION
• Vaccination
• Ensuring proper sanitation and hygiene
• Eat food that has been thoroughly cooked and are still hot
• When eating raw fruits and vegetables ensure they are wellwashed
• Avoid foods and beverages from street vendors

14. MANAGEMENT
NON- PHARMACOLOGICAL:
• Fluids and electrolytes should be monitored and replaced
diligently
• Oral nutrition with well cooked, soft digestible diet is preferable in
the absence of abdominal distension or ileus
• Sanitation and good hygiene should be optimized

15. MANAGEMENT

16. MANAGEMENT

17. DRUGS USED IN MGT
 FLOUROQUINOLONES e.g ciprofloxacin
 Optimal for the treatment of typhoid fever. Relativel
y inexpensive, well tolerated and more rapidly and rel
iably effective than the former first-line drugs, viz. ch
loramphenicol, ampicillin, amoxicillin and trimethopr
im-sulfamethoxazole.
 Attain excellent tissue penetration, kill S.typhi in its i
ntracellular stationary stage in monocytes/macropha
ges and achieve higher active drug levels in the gall bl
adder than other drugs.
 Rapid therapeutic response, i.e. clearance of fever an
d symptoms in three to five days, and very low rates
of post-treatment carriage.

18. DRUGS USED IN MGT
Trimethoprim and sulfamethoxaz
ole
• Inhibits bacterial growth by inhibiting synthesis
of dihydrofolic acid.
• Dosing
Adult: 6.5-10 mg/kg/d PO bid/tid; can be giv
en IV if necessary; 160 mg TMP/800 mg SMZ
PO q12h for 10-14 d
Pediatric <2 months: Do not administer
>2 months: 15-20 mg/kg/d PO, based on TM
P, tid/qid for 14 d
Dexamethasone
Prompt administration of high-dose dexam
ethasone reduces mortality in patients with
severe typhoid fever without increasing inci
dence of complications, carrier states, or rel
apse among survivors.
• Initial dose of 3 mg/kg by slow i.v. infus
ion over 30 minutes.
• 1 mg/kg 6 hourly for 2 days.

19. DRUGS USED IN MGT
Cephalosporin
• They arrest bacterial cell wall synth
esis which inhibits bacterial growth
• Ceftriaxone: 50-75 mg per kg per d
ay one or two doses
• Cefotaxime: 40-80 mg per kg per da
y in two or three doses
• Cefoperazone: 50-100 mg per kg pe
r day
Amoxicillin
• Interferes with synthesis of cell wall mucopeptides duri
ng active multiplication, resulting in bactericidal activity
against susceptible bacteria.
• At least as effective as chloramphenicol in rapidity of de
fervescence and relapse rate.
• Convalescence carriage occurs less commonly than with
other agents when organisms are fully susceptible.
• Usually given PO with a daily dose of 75-100 mg/kg tid
(three times a day) for 14 d.
Adult : 1 g PO q8h
Pediatric: 20-50 mg/kg/d PO divided q8h for 14 d

20. CASE PRESENTATION
• Patient T.I a 30yr old male trader reported to the hospital on the 15th of January with complains of
high fever, generalized body weakness, diarrhea and abdominal pain for 5 days. Symptoms were
insidious at onset but later became worse.
• Demographics: Name: TIO. Age:30years. Sex: male. Occupation- trader. Address: Richard H. Street,
CalabarSouth. Tribe: Efik
• Chief Complaint: high fever, diarrhea, severe abdominal pain, bodyweakness for 5 days.
• Family and Social History: Christian, single, zero culinary skills, orphan with unknown family history,
non smoker, trader, occasionally takes alcohol, no illicit drug use.

21. CASE PRESENTATION
• Past medical history: no past surgical history, not hypertensive, not a sickler, not diabetic, no
known allergy, previously got treated for malaria.
• Past Medication History: antimalarial(Arthemether/Lumefanthrine80/480mg), ibuprofen,
multivitamin, paracetamol.
• History of present illness: patient developed mild stomach ache few hours after patronizing
his food vendor, 3 days before reporting to the hospital. Began stooling frequently the next
day and as the stomach ache became severe, he took 2 tablets of pcm. On the night of the
second day, he was feverish and debile. He reported to the hospital the next day.

22. VITAL SIGNS AND DIFFERENTIAL
DIAGNOSIS
• Bp- 120/70mmHg
• pulse rate: 72beats per min.
• Body weight:70kg
• Body temperature: 40°C
DIFFERENTIAL DIAGNOSIS:
• Malaria
• Shigellosis
• Amoebic dysentery

23. LABORATORY INVESTIGATIONS
parameter Values Normal range
WBC 8200 cells/cu.mm 4000-11000cells/cu.mm
Neutrophils 72% 20-45%
Lymphocytes 17% 40-70%
Basophils 0% 0-2%
Monocytes 10% 2-10%
Eosinophils 01% 01-06%
HB 11.0g/dl 11-14.0g/dl
PCV 34% 34-40%
Fbs 4.5mmol/l 3.0-5.5mmol/l

24. LABORATORY INVESTIGATIONS
• Mp: no strain of plasmodium seen
• Widal:
• O. H
• S. typhi 1/160 1/80
• S. Paratyphi A. 1/80. 1/20
• S. Paratyphi B. 1/160. 1/60
• S. Paratyphi C. 1/80. 1/20
• Significant titre : 1/80

25. Goal Of Therapy
• Reduction in disease condition
• Resolution of symptoms
• Improved quality of life

26. PHARMACEUTICAL CARE PLAN
DAY HTP Intervention Monitoring
parameters
Expected
Outcome
Outcome
Day 1 Highgrade fever-
40°C
Diarrhea
Abdominal pain
Salmonellosis
Pcm injection
300mg/2ml stat
then tab. Pcm 1g
tds×3 days
I. V Ciprofloxacin
400mg 12hourly × 1
day
Then tab
Ciprofloxacin
500mg 12hrly × 7
days.
Oral Rehydration
therapy
Counseling on
Temperature
Stool frequency
Stool quality
To reduce
temperaturefrom
40-37°C.
To resolve
abdominal pain and
diarrhea
To prevent
complications
To Prevent chronic
carrierstatus
Temperaturereduce
d to 37°C
Abdominal pain
was no more severe
and diarrhea
resolved
Complications
prevented
Patient qualify of
life improved

27. DAY HTP Intervention Monitoring
parameters
Expected
Outcome
Outcome
Day 3
Abdominal pain
Salmonellosis
Weakness
tab. Pcm 1g tds×3
days
tab Ciprofloxacin
500mg 12hrly × 4
days.
Oral Rehydration
therapy
Counseling on
prevention
Severity of pain
Severity of
weakness
To resolve
abdominal pain
To prevent
complications
To Prevent chronic
carrierstatus
Abdominal pain was
resolved
Patient was
regaining strength
Complications
prevented
Patient qualify of
life improved

28. DRUGS USED IN MGT.
Ciprofloxacin:
Belong to the fluoroquinolone class. It is
available in oral and parenteral form.
• MOA: Inhibits relaxation of DNA; inhibits
DNA gyrase in susceptible organisms;
promotes breakage of double-stranded
DNA.
• Pharmacokinetics: widely distributed
throughout the body with oral bioavailability
of 50-85%. It is metabolized in the liver with
half life of 3-5 hours.
Paracetamol:
A non narcotic analgesic and antipyretic
• MOA: Acts on hypothalamus to produce
antipyresis. May work peripherally to block
pain impulse generation; may also inhibit
prostaglandin synthesis in CNS.
• Pharmacokinetics: achieves peak plasma
concentration in 10-60 minutes.It is
metabolized in the liver with elimination
half-life of 2-3 hours in adults.

29. Therapeutic Endpoint
• Reduction in disease condition 24 hours after initiation of therapy
• Resolution of symptoms day 3 post therapy initiation
• Improved quality of life

30. PHARMACIST ASSESSMENT
• Patient was assessed for 3 days after initiation of treatment and the following
was observedon each day:
• Day1: reduction in severity of abdominal pain and frequency of stooling,
fever reduced to 39°C.
• Day 2: Diarrhea had resolved although patient was still debile. Fever had
reduced to 37°C aabdominal pain was mild.

31. PHARMACIST ASSESSMENT
• Day 3: on the third day, the following was observed:
• Fever reduced to 37°C
• Abdominal pain was eliminated
• Patient was recuperating well.

32. REFERENCES
Akinyemi KO, Oyefolu AOB, Mutiu WB, Iwalokun BA, Ayeni ES, Ajose SO, et al.
Typhoid fever: Tracking the trend in Nigeria. Am J Trop Med Hyg 2018;
99(3_Suppl): 41-47.
Obaro SK, et al. 2015. Salmonella bacteremia among children in central and
northwest Nigeria, 2008–2015. Clin Infect Dis 61: S325–S331.
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