Typhoid Fever
Paul Salandanan, MD, FPCP, FPSMID| August 06, 2019
& Endymion Tan, PTRP, MD, FPCP, FAMP, DPSMID
ENTERIC (Typhoid) FEVER
 Systemic disease characterized by fever and abdominal pain
 Caused by S. Typhi or S. Paratyphi
o Gram-negative bacterium
o A very similar but often less severe is caused by:
Salmonella serotype paratyphi (10:1 ratio)
Epidemiology
 S. Typhi and S. Paratyphi serotypes A, B and C have no
known hosts other than humans
 Most commonly, food-borne and water borne
transmission results from fecal contamination by ill or
asymptomatic chronic carriers
 Health care workers acquire after exposure to infected
patients or during processing of clinical specimens and
cultures
Patients or employees who will apply in fast food chains
dapat na screen on enteric infection. Dapat nagpapa fecal
smear sila. Must have 2 negative fecal Smears.
BRIEF STORY OF TYPHOID MARY
Mary Mallon was born in 1869 in Ireland and emigrated to the
US in 1884. She had worked in a variety of domestic positions
for wealthy families prior to settling into her career as a cook.
As a healthy carrier of Salmonella typhi her nickname of
"Typhoid Mary" had become synonymous with the spread of
disease, as many were infected due to her denial of being ill.
She was forced into quarantine on two separate occasions on
North Brother Island for a total of 26 years and died alone
without friends, having evidently found consolation in her
religion to which she gave her faith and loyalty.
  No symptoms. The moment kung kelan ka na infect up
 Typhoid Mary is a FOODHANDLER kapag cook ang
alam mo nakwentuhan ka lang
 Typhoid Mary is a carrier
 Estimated 21-27 million cases with 20,000- 60,000 deaths
annually
o Highest in South- Central and Southeast Asia
(>100 cases/ 100,000 population)
o Medium in rest of Asia, Africa, Latin America and
Oceania (10-100 cases/ 100,000)
 The Philippines figures prominently in the discussion of
typhoid fever in Harrisons
 High incidence correlates with poor sanitation and lack of
access to clean drinking water
 Urban > Rural
 Young children and adolescents > adults
 Most cases are seen in those aged 3-19 years.
 Humans are the only natural host and reservoir.
 Incubation period is usually 8-14 days, but may range from 3
days up to 2 months.
 2-5% of infected people become chronic carriers who
harbour S. typhi in the gallbladder; greatly involved in the
spread of disease
Risk Factors
 Contaminated water or ice
 Flooding
 Food and drinks from street vendors
 Raw fruits and vegetables grown in fields fertilized with
sewage
TRANSCRIBERS Trisha Faye Oberio, Kristine Jean Navarro, Aisle Paler
 Ill household contacts
 Lack of handwashing and toilet access
 Evidence of H. pylori infection
Multi Drug Resistant (MDR) Strains of S.Typhi emerged in
China and Southeast Asia
o Plasmids encoding resistance to Chloramphenicol,
Ampicillin and TMP
o Increased use of Fluoroquinolone- decreased
ciprofloxacin susceptibility (DCS)- ciprofloxacin
resistant- treatment failure
Clinical Course
Susceptibility
 Increased in:
o Gastric achlorhydia
o HIV positive people
 Specific immunity:
o Recovery from chronic disease
o Active immunization
 Enteric fever is a misnomer, hallmark features are variable >75%
fever and 30-40% abdominal pain
o High index of suspicion is necessary when a person
presents with fever and a history of recent travel to a
developing country
 Average incubation period for S. Typhi is 10-14 days (can
range from 5-21 days)
o Depending on the inoculum size and host’s health
and immune status
What do you mean by incubation period?
to the point before you manifest the signs and
symptoms.
Relative bradycardia- very typical feature of patient with
typhoid fever. At the peak of the fever the heart rate is very slow,
typically seen in typhoid fever
 Most prominent symptom: prolonged fever (38.8°- 40.5°C) which
can continue up to 4 weeks if left untreated
 S. Paratyphi A is milder with predominantly GI symptoms
 Early physical findings: Rash (rose spots; 30%),
hepatosplenomegaly (3-6%), epistaxis and relative bradycardia at
the peak of high fever (<50%)
o Rose spots
▪ faint, salmon colored, blanching, maculopapular
rash located primarily at trunk and chest.
▪ Evident on first week and resolves without trace
after 2-5 days
Rose spots is not always visible in all patients. It is only
obvious in patients with very very fair skin. Unlike in patients
with fair or dark complexion
 10% of the patient- relapse- 2-3 weeks of fever resolution
1 of 5
  10% of untreated patients excrete S. Typhi in the feces for Carrier State
up to 3 months  1-5%, depending on age, become chronic carriers harboring S.
 2-5%- chronic asymptomatic carriage, shredding S. Typhi in typhi in the gallbladder
stool or urine for >1 year
Standard Case Definitions/Classifications of Typhoid Fever
Severe Disease
 Development of severe disease depends on: Confirmed  Persistent fever (38°C or more) lasting 3 or
o Host factors (host genetics, immunosuppression, Case more days with laboratory-confirmed
acid suppression therapy, previous exposure and S.typhi (blood, BM, bowel fluid)
vaccination)  Clinical compatible case that is laboratory
o Strain virulence and inoculum confirmed
o Choice of antibiotic therapy
 GI bleeding and intestinal perforation Probable Case  Persistent fever (38°C or more) lasting 3 or
o 3rd- 4th week- hyperplasia, ulceration and necrosis more days with (+) sero-diagnosis or Ag
of ileocecal Peyer’s patches at the initial site of detection test but no S.typhi isolation
Salmonella infiltration  Clinical compatible case that is
Which part of the intestine is more prone to perforation epidemiologically linked to a confirmed case in
due to typhoid fever? an outbreak
 It’s the ileum. So kapag nasa exam, it has to be the
ileum, the common site of perforation in typhoid Chronic  Individual excreting S.typhi in stool or urine
fever Carrier for longer than 1 year after onset of acute
typhoid fever
 Short term carriers also exist
 Some with no history of typhoid fever

Diagnosis

 Clinical presentation is nonspecific, diagnosis needs to be

considered in any febrile traveler returning from
developing region (Indian subcontinent, Philippines or Latin
America)
 Differentials: Malaria, hepatitis, bacterial enteritis, dengue
fever, rickettsial infections, leptospirosis, amebic liver
abscesses and acute HIV infection.
 NO SPECIFIC LABORATORY TEST is diagnostic
 15-25%- leukopenia and neutropenia
 Neurologic manifestations  Leukocytosis:
o occur in 2-40% of patients o Children
o Includemeningitis,GBS,neuritisand o First 10 days of illness
neuropsychiatric symptoms (“muttering delirium” or o Cases complicated with intestinal perforation or
“coma vigil”) secondary infection
 Other nonspecific lab findings: moderately elevated
Rare Complication: values in liver function tests and muscle enzyme levels
 DIC  Definitive diagnosis: isolation of S. Typhi and S. Paratyphi
 Hematophagocytic syndrome from blood, bone marrow and other sterile sites, rose spots,
stool or intestinal secretions
 Pancreatitis
 Hepatic and splenic abscesses and granulomas
How do you diagnose patients with Typhoid Fever?
 Endocarditis, Pericarditis, Myocarditis
First is the signs and symptoms of the patient
 Orchitis Common complaint of patient is Fever
 Hepatitis Fever has to be prolonged high grade fever. It
 Glomerulonephritis has to be 10 days or 2 weeks fever.
 Pyelonephritis and HUS Pinaka gold standard is culture
 Severe pneumonia What are the different body specimens? (BUS)
 Blood – 1st week of illness (most sensitive)
 Arthritis, Osteomyelitis
 Urine – 2nd week
 Endophthalmitis and Parotitis  Stool – 3rd week
 Provided that the patient is not treated for the
Chronic Carriage infection
 Women, Infants and Persons with biliary abnormalities Kapag naka antibiotics na yung patient, what
specimen will you send?
 Concurrent bladder infection with S. haematobium
 Bone marrow
 They survive gall bladder environment by forming biofilms on
gallstones and invading gallbladder epithelial cells.
 Chronic carriage- high risk of gallbladder cancer

IM Typhoid Fever 2 of 5
 Culture Sensitivity  FIRST AND SECOND GEN CEPHALOSPORINS and
 Blood: 40-80%, high rates of antibiotic use in endemic areas AMINOGLYCOSIDES are INEFFECTIVE in the treatment of
and small number of S. Typhi organisms clinical infections
 Bone marrow: >80%, its yield is not reduced by up to 5  Uncomplicated enteric fever: oral antibiotics and
days of prior antibiotic therapy antipyretics
 Blood, bone marrow and intestinal secretions: >90%  Pxs with persistent vomiting, diarrhea, and/ or
 Bone marrow is the best specimen, even if you are given abdominal distention should be hospitalized and given
3 days of antibiotics, your bone marrow will still be positive supportive therapy
 Stool: negative in 60-70% during 1st week, can become o Parenteral 3rd gen cephalosporin or
positive during the 3rd week of infection in untreated fluoroquinolone- should be administered for at least
10 days or for 5 days after fever resolution
patients
 Chronic carriage: 4 weeks with oral Ciprofloxacin and other
Fluoroquinolones
Serologic Test:
 Widal Serologic Test
o Test for “febrile agglutinins”- simple and rapid,
limited sensitivity and specificity in endemic areas
 In the states, Typhoid is endemic
 Widal test in the Philippines has high titer and for
you to be able to interpret the widal, you have to know
the titer of the community. And titer natin is already
high that’s why it not useful here.
 Rapid point of care tests- detects Abs to outer
membrane proteins or to Vi or O:9 Ag- moderately
sensitive and specific

Action and Alert Threshold

 The alert threshold for typhoid is 1 case.
 The action threshold is 5 suspected cases per 50,000
population.

Typhoid Fever VS Enteric Fever

What is the choice of modality to use? CULTURE
Ex. Patient has the picture of this Typhoid Fever pero
kapag ginawa yung culture ay walang tumubo.you
use the generic term Enteric Fever
 Enteric Fever- If the culture is negative but you have
all the symptoms of Typhoid Fever
 Typhoid Fever – Positive culture (S.typhi)
 Most of the cases is culture negative – Early initiation
of antibiotics
As long as na diagnose mo na, it’s best to start your
antimicrobial therapy because ayaw mo magkaroon ng
complications
Treatment
 Initial choice of antibiotics depends on the susceptibility of
the S. Typhi and S. Paratyphi strains in the area of residence
or travel
 For drug susceptible typhoid fever- Fluoroquinolones
are effective ; cure rates of 98% and relapse and fecal
carriage rates of <2%
o Ciprofloxacin
o Ofloxacin- quinolone susceptible strain
 The available evidence suggests that the fluoroquinolones
(Ciprofloxacin) are the optimal choice for the treatment of
typhoid fever in age groups.
 DCS typhoid fever- Ceftriaxone, Azithromycin or high
dose Ciprofloxacin (not be used in Ciprofloxacin resistant
enteric fever)
 Ceftriaxone, Cefotaxime and (oral) Cefixime- MDR enteric
fever
 Azithromycin- DSC strains, lower rates of treatment failure
and shorter durations of hospital stay
NOTES
 Drug of Choice for Typhoid in the Philippines is
Chloramphenicol
 If Pregnant, give 3rd Generation Cephalosporin. 1st and
2nd Generation Cephalosporin is ineffective
 May Allergy, give Azithromycin
 Remember that the drug of choice for me might not be the
drug of choice for her
 The reason they removed chloramphenicol is because of
their toxicity
 Fluroquinolones should not be given to children
because it inhibits bone development
 Even if you treat your typhoid fever correctly with
chloramphenicol, the fever will only lies after 3 to 5 days.
Especially when you’re dealing with typhoid fever. If you
get better after 1 day, you are about to get well, and
knowing the resistance rate of Salmonella against
chloramphenicol. After 5 days, kapag may lagnat ka pa,
hindi ka typhoid. You need to explain that to your patient.
 They remove chloramphenicol in the recommendation
due to aplastic anemia. But yung aplastic anemia niya
may dose related and idiosyncratic
o The treatment of typhoid fever using
chloramphenicol is 50-75 mg/kg/day for an adult
60 kg that is equivalent to 3-4 g until the fever
lies. That means 3-5 days after the fever lies
you bring it down to 30mg/kg to avoid the dose
related aplastic anemia.

IM Typhoid Fever 3 of 5

NOTES
 Long time ago, when wala pa masyadong resistance
the best drug of choice is chloramphenicol but
your chloramphenicol is notorious to cause bone
marrow suppression, its because if the increase
resistance kaya di na siya binibigay masyado
 Empiric Treatment : Ceftriaxone (3rd Generation
cephalosporin) Before lumabas yung culture
results, shotgun management according to the
guidelines
 Ceftriaxone: Can be given as once a day frequency
as high as 3 g per day (IV)
 What if mataas ang crea? Pangit ang kidney
function. Do you have to adjust or not? NO, because
Ceftriaxone is more of hepatic excretion
 Ano pa yung isang cephalosporin na may hepatic
excretion? Cefoperazone
 Pinaka gold standard na treatment ay Ceftriaxone
 For example, lumabas na result ng culture tapos
susceptible sa Ceftriaxone, then give Ceftriaxone
 Pero paano kung nag-iimprove na si patient, you
want to send him home. Ceftriaxone is IV tapos
lumabas sa results na susceptible naman siya sa
Quinolones (Fluoroquinolones, Ciprofloxacin). Meron
naman siyang oral counterpart then shift to oral
medication
 Full susceptible Treatment : Ciprofloxacin
 Drug of Choice according to Guidelines is
Ceftriaxone
Prevention and Control
 Travelers should be advise to monitor their food and water
intake carefully and to strongly consider immunization
against S. Typhi
Education
 Notably food handlers and people in group settings such as
day care/Crèche staff and attendees; closed institutions
like boarding schools residential homes for the elderly,
orphanages and prisons.
 Practice hand washing with soap and running water before
food preparation and eating, after using the toilet, handling
soiled diapers, bed linen, etc., and maintain a high standard
of personal hygiene in general.
 Maintain rigorous standards of cleanliness in food
preparation and handling of food, especially salads and
other cold-serve foods.
 Make sure to properly refrigerate food where possible.
 Report all deaths due to diarrhoeal diseases to health
workers.
and many travellers get sick from food bought from
street vendors.
 Treat all drinking water by bringing it to a rolling boil for 1
minute or using Aqua-tablettes /jik or other household water
treatment products before you drink it.
o Ask for drinks without ice unless the ice is made
from boiled or chlorine treated water.
o Avoid flavoured ices and juice because they may
have been made with contaminated water.
Prophylaxis
 Immunization is not routinely recommended except for travellers
to areas where Typhoid is endemic.
VACCINES AVAILABLE:
Ty21a ViCPS
Oral live attenuated Parenteral Vaccine
Given on 1,3,5 and 7 Single Dose
Revaccination every 5
Every 2 years
years
Can be given as early as Can be given as early as
6 y/o 2 y/0
 Not required for international travel but it is recommended for
travelers to areas where there is a moderate to high risk of
exposure to S. Typhi
 Immunization is an adjunct and not a substitute for the avoidance
of high risk foods and beverages.
o Immunization is not recommended for adults residing in
typhoid- endemic areas or for the management of
persons who may have been exposed in common-
source outbreak
Between the two vaccines. Which one do you think is
Passive Immunization?
 Wala. Those two are active Immunization
Between the two, which is a live vaccine?
 Ty21a, Therefore di siya pwede sa patients with HIV,
on chemo, Cancer patients, inborn defiency of
immune system. Lahat ng may complement
deficiency basta bagsak yung immune system. YOU
CANNOT GIVE YOUR LIVE VACCINE. Ang PWEDE
lang sa kanila ay Polysaccharide vaccine
Ty21a booster : Every 5 years
Polysaccharide Vaccine : every 2 years
In the exam, this will be in cases

Communities
 Eat foods that have been thoroughly cooked and that are still
hot and steaming.
 Ensure that cooked food is covered to protect it from flies.
 Avoid raw vegetables and fruits that cannot be peeled. USE AT YOUR OWN RISK!!!
Vegetables like lettuce are easily contaminated and are very
hard towash well. REFERENCES
o When you eat raw fruit or vegetables that can be
peeled, peel them yourself. (Wash your hands with
1. Harrison’s 20th Edition
soap first.) Do not eat the peelings. 2. WHO Guidelines
3. Recordings
o Avoid foods and beverages from street vendors. It Dr. Salandanan
is difficult for food to be kept clean on the street, Dr. Tan

IM Typhoid Fever 4 of 5