MANAGEMENT OF TYPHOID DISEASE

AND REDUCTION OF THE MENACE OF

UNNECESSARY TREATMENT OF
TYPHOID ALONGSIDE MALARIA: THE
PHARMACIST’S ROLE

Dr. Obiajuru Wayemeru

PharmD., MPSN, MCPAN
CASE STUDY:

A 19year old female missionary volunteer was brought into a

Pharmacy by her brother. 

Chief complaints: Fever, vomiting, abdominal pain, intense

pounding headache, fatigue/weakness, loss of appetite. 
 
Possible known food, chemical and drug allergies: Nil 
 
Past medical or any co-morbid conditions: Recurrent malaria.
 
Address or socioeconomic conditions of the living place: Lives
with parents who are average class and have decent and clean
living environment.
 
On examination: Fever (temp. 39.1°), patient looked very weak and
pale, vomited few minutes after getting to the pharmacy and the
vomitus looked greenish. 
History of present illness:

Fever, weakness and headache started one week after returning

from a mission to a rural area where she spent 1month (these trips
are frequent for her because of her volunteer work). There was no
pipe bourne water in the village and everyone was dependent on
water from the river. She initially thought she had malaria and got
malaria medications on her own and had completed the 3 days
therapy about 5days ago. Yet, the symptoms kept getting worse.
She started having diarrhoea, vomiting, loss of appetite and fatigue
2 days ago, but the diarrhea was mild and abated same day after
taking loperamide. Headache keeps getting worse even after taking
analgesics. 
 
 Medication history:

Artesunate/Amodiaquine combo for 3days

Paracetamol tabs t.d.s for 3days initially.
Loperamide caps. 2caps start.
Questions:

1) What would be this patient's Preliminary diagnosis?

 
2) What would be the Differential Diagnosis?
 
3) What would be the definitive diagnosis.
 
4) What laboratory investigations should be carried out to help with
the definitive diagnosis?
 
5) Should the Community Pharmacist handle this case or refer to the
hospital?
 
6) What would be the Pharmaceutical care plan?
 
7) What medications would be used to manage the patient's condition
and reason for choice of the medications?
 
Preliminary Diagnosis:
 
At first glance using the patient’s presenting symptoms, the
pharmacist would question the following;
- Cholera
- Amoebiasis
- Rotavirus infection
- Appendicitis
- Intestinal worm infestation
- Early Prima Pregnancy
- Hypoglycemia
- Enteric (Typhoid) fever
- Gastroenteritis
- Resistant Malaria
From the patient's history, the 19-year old girl may be unaware of the
early signs of pregnancy.
Again, the rural area where she spent 1month on her missionary work
is purely at high risk of typhoid fever (due to lack of good or properly
treated drinking water), other gastrointestinal infections, Malaria and
enteric parasites infestation ( such as intestinal worms).
The presenting symptoms are peculiar with the conditions listed as
differential diagnosis below.
Loss of appetite, fever, vomiting and stomach pain are common with
typhoid fever, early prima Pregnancy and malaria.
Weakness is associated with the above mentioned disease conditions
as well as hypovolemia following excessive fluid loss due to vomiting.
The patient looks pale. This indicates anaemia which may be due to
recurrent malaria as well as suspected intestinal worm infestation.
The patient due to loss of appetite could not eat for some days. This
left the stomach empty, hence the greenish vomitus.
All cases of viral stomach infestations are self limiting and can resolve
with adequate rehydration, bed rest and animmune booster.
Differential Diagnosis: 
 
- Cholera
Symptoms; Abdominal pain, Nausea, severe/watery diarrhea,
sometimes vomiting, dehydration which can lead to fluid/electrolyte
imbalance (and lead to muscle cramps and shock), and lethargy.
 
Cholera will most likely be ruled out since the diarrhea was mild and
stopped same day and severe headache is not a symptom of cholera.
 
- Amoebiasis
Symptoms; Mild cramping/abdominal pain, diarrhea, bloody stools,
flatulence, fever, rarely liver abscess in severe cases, fatigue/ loss of
appetite, weight loss.

This may be ruled out since Severe pounding headache and vomiting
are not part of the symptoms and the diarrhea was mild, wasn’t bloody
and stopped same day.
- Rotavirus infection
Symptoms; Severe watery diarrhea, nausea, passing of excessive
amounts of gas, vomiting, abdominal cramps, dehydration, fever,
loss of appetite, weight loss
 
The patient most likely doesn’t have rotavirus infection based on
the fact that the diarrhea stopped same day and the absence of
headache as part of the symptoms.
 
- Appendicitis
Symptoms; Pain at the lower right abdomen that may start around
the navel before moving down, sometimes nausea, vomiting, poor
appetite, fever and chills.
 
This may also be ruled out because severe pounding headache is
not one of the symptoms and the abdominal pain in the patient is
centralized and not on the right side.
 
- Intestinal worm infestation
Symptoms; Abominal pain, diarrhea, nausea, vomiting, gas/bloating,
fatigue and unexplained weight loss.
 
This could be ruled out also because of the absence of headache
and high fever as part of the symptoms. Diarrhea in the patient was
also stopped same day.

- Early Prima Pregnancy

This can be ruled out due to the patient’s severe pounding
headache. But could be ruled out by running a urine/blood PT test.
 
- Hypoglycemia; may be the cause of fatigue and may be a co-
mobidity alongside the patients other disease.
 
- Enteric (Typhoid) fever

Symptoms; High fever, severe pounding headache, abdominal pain,

vomiting, constipation or diarrhea, fatigue, chills, loss of appetite,
malaise, muscle weakness, weight loss, and rarely rose spots and
skin rash.
 
The patient’s symptoms point more towards typhoid disease
because of the presence of most of the symptoms above.
 
 - Gastroenteritis
Symptoms; Abdominal pain/cramps, diarrhea, nausea, vomiting,
indigestion, flatulence, belching, chills, dehydration, fatigue/lethagy,
fever, light-headedness, loss of appetite, palpitation and oliguria
(low urine output).

This may also be ruled out in this patient since diarrhea stopped
same day and a good number of the above symptoms were absent.
There also no severe headache as one of the symptoms of
Gastroenteritis.
- Resistant Malaria
Symptoms; High fever, chills, profuse sweating when fever
suddenly drops, fatigue, headache, muscle aches, abdominal
discomfort, nausea and vomiting.
 
Patient may have resistant malaria, but the malaria fever isn’t
consistently high and often abates briefly with analgesics and
comes back after the analgesic wears off especially towards
evening. Also, headaches associated with malaria isn’t so
severe and pounding. It’s usually a generalized headache.
Definitive Diagnosis:
 
This can be gotten by carrying out specific laboratory
investigations to get the actual diagnosis. But Typhoid fever and
Unresolved Severe malaria are highly suspected.
 
Laboratory Investigations
 
a). Widal test; This may be carried out but this test is more like a
screening test and not a confirmatory test for typhoid fever and is
outdated for typhoid diagnosis. There are several reasons one can
get a false positive widal result.
i). Previous infection with Salmonella typhi or other strains of
salmonella
ii). Previous exposure to Cross-reactive antigens or typhoid
vaccination
iii). High falciparum malaria infection.
iv). Meningitis, Chronic liver disease, immunological disorders etc
Recent completion of antibiotics
 

Laboratory investigations contd.

This has often caused misguided treatments of typhoid infection by a

lot of Physicians and Pharmacists. The excessive proliferation of
typhoid treatment has also given patients the false impression that
every likely case of malaria must go together with typhoid, leading to
misuse of antibiotics. This has also led to the false statistics of about
60% Typhoid cases in Nigeria, rather than the actual about 1%.
 
b). Salmonella typhi isolates by Stool, Blood or Urine Analysis/
Microscopy/Culture
c). Stool M/C/S
d). Serum microscopy
e). Malaria test (not RDT),
f). Pregnancy Test,
g). FBC
h). Abdomino-pelvic Ultrasound Scan

For this patient, results of the laboratory investigations ruled out all
other diseases including malaria except Typhoid fever caused by
Salmonella Typhi and a low PCV, which was 30%.
Thyphoid Fever
 
Overview
 
Typhoid fever is caused by Salmonella typhi, which is a
dangerous bacteria. Salmonella typhi is related to the
bacteria that cause salmonellosis, another serious intestinal
infection, but they aren't the same.
 
It is rare in developed countries but is still a serious health
threat in the developing world, especially for children.
 
Contaminated food and water or close contact with an
infected person cause typhoid fever.
Signs and symptoms in early illness usually include:

 - Fever that starts low and increases daily, possibly reaching

as high as 104.9 F (40.5 C)
Severe Headache
- Weakness and fatigue
- Muscle aches
- Sweating and sometimes chills
- Dry cough
- Loss of appetite and weight loss
- Stomach/Abdominal pain
- Diarrhea or constipation
- Rash
- Sometimes, extremely swollen stomach
 
Signs and Symptoms cont’d.

Most people who have typhoid fever feel better a few days after they start
antibiotic treatment, but a small number of them may die of complications.
Vaccines against typhoid fever are only partially effective. Vaccines usually
are reserved for those who may be exposed to the disease or who are
traveling to areas where typhoid fever is common.
 
These Signs and symptoms are likely to develop gradually — often appearing
one to three weeks after exposure to the disease.

Later illness
 
Without treatment, patient may:
- Become delirious
- Lie motionless and exhausted with your eyes half-closed in what's known as
the typhoid state
- Life-threatening complications often develop at this time.
 
In some people, signs and symptoms may return up to two weeks after the
fever has subsided.
Transmission
 
Transmission of typhoid fever is by the Fecal-oral transmission route.
 
Most people in developed countries pick up typhoid bacteria while
they're traveling to endemic regions and after they have been infected,
they can spread it to others through the fecal-oral route.
 
This means that Salmonella typhi is passed in the feces and
sometimes in the urine of infected people. Eating food that has been
handled by a carrier of typhoid fever and who hasn't washed their
hands carefully after using the toilet can cause an infection of a new
host.
 
In developing countries, where typhoid fever is established, most
people become infected by drinking contaminated water. The bacteria
may also spread through contaminated food and through direct
contact with someone who is infected.
Typhoid carriers
 
Even after antibiotic treatment, a small number of people
who recover from typhoid fever continue to harbor the
bacteria. These people, known as chronic carriers, no longer
have signs or symptoms of the disease themselves. However,
they still shed the bacteria in their faeces and are capable of
infecting others
Risk factors
 
Typhoid fever is a serious worldwide threat and affects about 27
million or more people each year. The disease is established in India,
Southeast Asia, Africa, South America and many other areas.
 
Worldwide, children are at greatest risk of getting the disease,
although they generally have milder symptoms than adults do.
 
Risk of contraction of typhoid fever is increased if you;
 
- Work in or travel to areas where typhoid fever is established.
- Work as a clinical microbiologist handling Salmonella typhi bacteria
- Have close contact with someone who is infected or has recently
been infected with typhoid fever
- Drink water polluted by sewage that contains Salmonella typhi
Complications
 
Intestinal bleeding or holes
Intestinal bleeding or holes in the intestine are the most
serious complications of typhoid fever. They usually develop
in the third week of illness. In this condition, the small
intestine or large bowel develops a hole. Contents from the
intestine leak into the stomach and can cause severe
stomach pain, nausea, vomiting and bloodstream infection
(sepsis). This life-threatening complication requires
immediate medical care.
Other, less common complications include:
 
- Inflammation of the heart muscle (myocarditis)
- Inflammation of the lining of the heart and valves (endocarditis)
- Infection of major blood vessels (mycotic aneurysm)
- Pneumonia
- Inflammation of the pancreas (pancreatitis)
- Kidney or bladder infections
- Infection and inflammation of the membranes and fluid surrounding
the brain and spinal cord (meningitis)
- Psychiatric problems, such as delirium, hallucinations and paranoid
psychosis
 
With quick treatment, nearly all people in industrialized nations
recover from typhoid fever. Without treatment, some people may not
survive complications of the disease.
Prevention
 
- Safe drinking water
- Improved sanitation
- Adequate medical care
can help prevent and control typhoid fever.
 
Unfortunately, in many developing nations especially in rural areas,
these may be difficult to achieve. For this reason, some experts
believe that vaccines are the best way to control typhoid fever.
 
A vaccine is recommended if you live in or are traveling to areas where
the risk of getting typhoid fever is high.
Typhoid vaccine
 
There are two vaccines to prevent typhoid fever. One is an inactivated
(killed) vaccine and the other is a live, attenuated (weakened) vaccine.
 
- Inactivated typhoid vaccine is administered as an injection (shot). It
may be given to people 2 years and older. One dose is recommended
at least 1-2 weeks before travel. Repeated doses are recommended
every 2 years for people who remain at risk.

- Live typhoid vaccine is administered orally (by mouth). It may be

given to people 6 years and older. One capsule is taken every other day,
for a total of 4 capsules. The last dose should be taken at least 1 week
before travel. Each capsule should be swallowed whole (not chewed)
about an hour before meals with cold or lukewarm water. A booster
vaccine is needed every 5 years for people who remain at risk.
 Important: live typhoid vaccine capsules must be stored in a
refrigerator (not frozen).
 
Typhoid Vaccine cont’d.

Neither vaccine is 100% effective. Both require repeat immunizations

because their effectiveness wears off over time.
 
Typhoid vaccine is recommended for:
 
Travelers to parts of the world where typhoid is common. (NOTE:
typhoid vaccine is not 100% effective and is not a substitute for being
careful about what you eat or drink.)
People in close contact with a typhoid carrier.
Laboratory workers who work with Salmonella typhi bacteria.
Typhoid vaccine may be given at the same time as other vaccines.
Precautions before taking Typhoid vaccine;
 
- Patient has an allergic reaction after a previous dose of typhoid
vaccine, or has any severe, life-threatening allergies.
- Has a weakened immune system.
- Is pregnant or breastfeeding, or thinks she might be pregnant.
- Is taking or has recently taken antibiotics or anti-malarial drugs.
 
In some cases, the health care provider may decide to postpone
typhoid vaccination to a future visit.
 
People with minor illnesses, such as a cold, may be vaccinated.
People who are moderately or severely ill should usually wait until they
recover before getting typhoid vaccine.
Menace of Co-Management of Typhoid fever alongside Malaria

In Nigeria, there are still high cases of supposed Salmonella typhi

infections. This is because most laboratories still depend on just the
Widal test as the diagnostic test for typhoid. This may give erroneous
false positive results for typhoid infection as there are several reasons
why widal tests could give false positive results as already discussed.
This common high titre results for widal has led to a lot unnecessary
drug therapy and misuse of antibiotics. It has also led patients to
believe that they should treat Typhoid infections anytime they self
medicate for malaria fever because most Physicians and Pharmacists
tend to run Widal tests alongside every malaria test, irrespective of the
fact that the patient isn’t showing the classic symptoms for Typhoid.

Also, the proliferation of untrained charlatans “selling” drugs and

managing all sorts of illnesses and who give out malaria and typhoid
medications together at all times has constituted a major menace in
our society. Now Malaria and Typhoid fever are seen as “husband and
wife” by most of the lay Nigerian populace. This has also increased
antibiotic resistance.
Menace of Co-Management of Typhoid fever alongside Malaria Cont’d

Asides from rural areas where there still isn’t pipe bourne/treated
water and where there is poor education of proper hand washing after
the use of toilet, most cities/towns in Nigeria have little exposure to
probable causes of Typhoid and this has led to greatly reduced actual
typhoid cases. The cases are a lot fewer than what the statistics
report because of wrong testing and unnecessary management of the
illness.
 
We as Pharmacists need to improve our advocacy:
- Against self medication
- Against patronage of Untrained/Unlicensed individuals
- Ensuring the right tests are carried out before commencement of
Typhoid fever treatment.
- Education on the modes of transmission and prevention of typhoid
disease. This will enable clients and the general populace appreciate
the fact that it’s not that easily contractable especially in urban areas.
 
5. Should the Community Pharmacist handle this case or
refer to the hospital?
 
The patient is presenting with worsening symptoms which
makes her unable to tolerate oral medications. Her condition
may therefore require initial parenteral therapy. A Community
pharmacist certified to give injections can give Anti-emetic,
analgesics, an antibiotic through intramuscular injections.
And the patient can continue the other medications orally, if
the nausea and vomiting abates. But if they don’t, then
referral is necessary.
 
6. Pharmaceutical Care Plan By the Community Pharmacist:
 
- Control the vomiting, fever, fatigue

- Run appropriate tests to confirm the right diagnosis.

- Initiate therapy and monitor patient as an outpatient.

- Monitoring and Documenting drug therapy problems(DTPs).

Example is the use of loperamide in bacteria enterocolitis
caused by invasive organisms including salmonella. Adverse
drug reactions associated with loperamide include vomiting,
tiredness/weakness, nausea, diarrhoea, abdominal pain,etc,
which could have exercerbated the patients symptoms. The
choice of loperamide instead of Kaolin(Diastop) suspension
which is appropriate in all cases of diarrhoea, was wrong.
Pharmaceutical Care Plan By the Community Pharmacist
Cont’d

- Monitoring of fluid intake by oral fluids to ensure

replacement of fluids/electrolyte loss, to avoid
complications arising from dehydration e.g hypovolemic
shock, hypotension and death.

- Patient should be educated on proper hand hygiene.

- Monitoring the vital signs

- Preventing spread of infective agent to relatives and

caregivers through advice on care in food-handling.

- Completing the course of antibiotic therapy.

 
Medications.

- I.m metoclopramide 10mg stat or I.m promethazine 50mg stat as

the drowsiness may help the patient relax and sleep, to give time for
the other medications to kick in.
- I.m paracetamol 600mg stat or I.m diclofenac 75mg stat.
- I.m Ceftriaxone 1g 24hrly for 3days,
Samples should be collected for the laboratory investigations before
the dose of antibiotic.
The above will be given pending result of laboratory investigations.
 
In this case, typhoid came back positive, while others including
malaria came back negative, except for the PCV which was 30%.
 
Medications cont’d

Continue with;

- Cefixime 400mg 12hrly x 10/7

Or
- I.m Ceftriaxone stat, then Ciprofloxacin 500mg 12hrly x 2/52
Or
- Amoxicillin 500mg 8hrly x 2/52
Or
- Azithromycin 1000mg 24hrly x 10 to 14 days.
  - Paracetamol tab 1g 8hrly x 2 days
- Iron containing multivitamin syrup 10ml b.d x 2/52
- Probiotics e.g Saccharomyces boulardi 500mg 12hrly × 1/52
- Metoclopramide tab 10mg 12hrly x 2/7
 
If the vomiting and fever isn’t controlled with the stat dose I. m
injections, then the Pharmacist should refer.
Pre-referral care:
 
I.m metoclopramide 10mg stat or I.m promethazine 50mg
stat as the drowsiness may help the patient relax and sleep,
to give time for the other medications to kick in.
I.m paracetamol 600mg stat or I.m diclofenac 75mg stat.
I.m Ceftriaxone 1g stat
 
Recommended In-Hospital Management Plan by the Physician:
 
- Full Strength Darrow's solution or Ringers Lactate 1000ml over 1hour
- Switch over to Ivf 5% Dextrose Saline 1Litre 
While the intravenous infusions are still running, blood samples
should be collected for quick Microscopy for malaria, Packed Cell
Volume (PCV) to r/o hypovolemia following excessive vomiting and
widal tests while stool sample should also be collected for quick
analysis to r/o enteric parasites (worms).
- I.m Metoclopramide 10mg or Promethazine 50mg PRN until
vomiting is abated.
- Ivf Metronidazole 500mg 8hourly x 2-3days
- Ivf Ciprofloxacin 200mg 12hourly x 2-3days OR Ceftriaxone 1g
daily x 2-3days.
- I.m paracetamol 600mg stat or I.m diclofenac 75mg stat
Recommended In-Hospital Management Plan by the Physician cont’d:
 
Then revert to Oral medications as soon as patient can tolerate them
as below:

- Probiotics e.g Saccharomyces boulardi 500mg 12hrly × 1/52

- Amoxicillin 500mg 8hourly x 10/7 (patients who do not tolerate
penicillins, can be placed on Ciprofloxacin).
Or
- Tab Ciprofloxacin 500mg 12hourly x 2/52
Or
- Azithromycin 1000mg 24hourly x 10 to 14days.
  Or
- Cefixime 400mg 12hrly x 10/7
  - Iron containing multivitamin syrup 10ml b.d x 2/52
- Paracetamol tab 1g 8hrly x 2 days
 
Hospital Pharmacist’s Pharmaceutical Care plan
 
- Monitoring and Documenting drug therapy problems(DTPs).
Example is the use of loperamide in bacteria enterocolitis caused by
invasive organisms including salmonella. Adverse drug reactions
associated with loperamide include vomiting, tiredness/weakness,
nausea, diarrhoea, abdominal pain,etc, which could have exercerbated
the patients symptoms. The choice of loperamide instead of Kaolin
(Diastop) suspension which is appropriate in all cases of diarrhoea,
was wrong.

- Monitoring of fluid intake/output to avoid heart failure from

hyperhydration.

- Monitoring of serum electrolyte level to avoid hyperkalemia from

excessive use of potassium-containing fluids.
Hospital Pharmacist’s Pharmaceutical Care plan Cont’d

- Patient should be educated on proper hand hygiene.

- Patient should be monitored against complications arising
from dehydration e.g hypovolemic shock, hypotension and
death.
- Achieving adequate hydration
- Monitoring the vital signs
- Preventing spread of infective agent to relatives and
caregivers through advice on care in food-handling.
- Patient should be counseled on completion of the course of
antibiotic therapy.
 
 Counselling Tips
 
- Patient should avoid self medication e.g in treatment of malaria and
other diseases.
- Education on proper hand hygiene practice. Washing hands with
clean running water and soap or disinfecting the hands using alcohol-
based hand sanitizer.
- Avoid drinking untreated water. Contaminated drinking water is a
particular problem in areas where typhoid is endemic. At best, patient
should have bottled water next time she travels to such areas.
- Patient should be educated on proper food handling hygiene. Ensure
fresh fruits and vegetables are washed thoroughly with clean water
and salt or vinegar.
- Bananas can help in potassium electrolyte replacement.
- Patient should know the need for adequate and copious water intake.
- Patient should avoid improperly or incompletely cooked food or sea
meats and eat more of hot foods.
 
 
References:

T Pang, ZA Bhutta, et al – Trends in Microbiology, 1995

JA Crump, SP Luby et al – Bulletin of World Health…, 2004

ZA Butta – BMJ, 2006

RB Hornick, SE Greisman et al. - New England Journal of Medicine 283

(14), 1970

D House, A Bishop et al…. Current Opinion in Infectious Diseases

(Lippincott Williams & Wilkins, Inc.) 2001

LA Olopoenia, AL King, Postgraduate Medical Journal, 2000

O Enabulele, SN Awunor – Nigerian Medical Journal, 2016

THANK YOU!!!