Lets imagine it happened

Getting Sick in the Tropics

(Tropical IDs) Part 2: Typhoid

Fever & Malaria
Dr. Rosario
OUTLINE:
Part 1:
Overview
A.
B.
Dengue
A.
B.
C.
D.
E.
F.
G.
H.
I.
J.
K.
L.
M.
N.
O.
P.
Q.
R.
S.
T.
U.

Part 2:
Tropical infectious diseases
III. Typhoid fever
10 leading causes of morbidity
A. Etiologic agents
B. Enteric fever
Dengue virus
C. Complications and
Transmission of dengue virus by
consequences
aedes aegypti
D. Laboratory tests
Dengue infections
E.
Antibiotic therapy
Pathophysiology
F.
Case course
Course of illness
G. Prevention
Old WHO dengue classification
Malaria
Dengue case classification and
A. Etiologic agents
levels of severity
B. Transmission cycle
Diagnosis
C. Laboratory tests
Tourniquet test
D. Clinical features
Step-wise approach to
E.
Major signs of severe
management of dengue
malaria
Group A
F.
Other signs of severe
Home care for dengue
malaria
Admission criteria
G. Drugs for susceptible
Group B
plasmodium
Group C
H. Drugs for MDR
Effects of supportive treatments
I.
Drugs for severe or
for DHF or DSS in children
complicated P.
Group C: emergency treatment
falciparum malaria
Summary of blood transfusion
J.
Primaquine
treatment
K. Other issues
Discharge criteria
Prognosis
Part 3: Leptospirosis
Prevention

TYPHOID FEVER
Case # 2:

25 year old, female, government employee

Intermittent fever and chills for seven days,

relieved temporarily by paracetamol

Headache, myalgia, body malaise and vague

abdominal pain

History of diarrhea x 1 day

She denies travel to remote area

Unremarkable PE except for T= 38.6oC

o

Fever with normal heart rate relative

bradycardia: seen in patients with typhoid fever and
legionella infection) [2013B]

Case # 2: Issues
Absence of focal findings
o Non-specific signs and symptoms
o Clues in the clinical data: historical/ suggestive
physical findings
Possible etiologic agent
o Standard diagnostic procedure
Empiric therapy
o Drug of choice
Resistance patterns
ETIOLOGIC AGENT [Harrisons]
SALMONELLA
S. typhi or S. paratyphi serotypes A, B, C
Gram-negative, non-spore forming, facultative
bacilli
Growth restricted to human hosts

JMA-1, JMA-2, Telma Amit

1

anaerobic

Mode of transmission: ingestion of organisms in

contaminated food or water d/t fecal contamination by ill or
asymptomatic chronic carriers.
Pathogenesis:
o
Penetrates and targets small intestine; phagocytosed
by macrophages
o
Spread to other organs via lymphatics and colonize RES
tissues
o
S/Sx result from cytokine secretion in response to
bacterial products after critical no. of organisms have
replicated
S. paratyphi A causes milder disease than S. typhi
Occurrence of multidrug resistant (MDR) strains of S.
typhi
o
Contain
plasmids
encoding
resistance
to
chloramphenicol, ampicillin, trimethoprim
o
Abx long used to treat typhoid fever
ENTERIC (TYPHOID) FEVER: MANIFESTATIONS
Systemic disease characterized by fever and abdominal pain
and caused by dissemination of S. typhi or S. paratyphi.
Incubation period: 3-21 days (ave. 10-14 days)
Most prominent sx: prolonged fever (38.8-40.5 oC) if
untreated
Early findings: rash, hepatosplenomegaly, epistaxis,
relative bradycardia at peak of high fever
Rose
spots
faint
salmon
colored,
blanching,
maculopapular rash located primarily on the trunk and
chest; evident at end of 1st week; resolves after 2-5 days

COMPLICATIONS AND CONSEQUENCES

[Harrisons]
Development of severe disease depends on host factors
(immunosuppression,
antacid
therapy,
previous
exposure, vaccination), strain virulence and inoculum,
and choice of antibiotic therapy.

Intestinal hemorrhage
o Severe GI bleeding
Intestinal perforation
Peritonitis
Kidney failure
Orchitis
Chronic carrier states
Myocarditis
Neurologic manifestations
o
Encephalitis (Psychosis)
o
Meningitis, Guillain-Barr syndrome, neuritis, and
neuropsychiatric symptoms (described as "muttering
delirium" or "coma vigil"), with picking at bedclothes or
imaginary objects. [Harrisons]

LABORATORY TESTS

Case 2 Lab Results:

CBC: Hgb= 14.3 Hct= 0.47 RBC = 3.85 WBC = 6.5
N=70 L=26 E=1 M=3
Platelet count= 190,000
Urinalysis (-)
Typhidot: IgM (-); IgG (+)

Page |

 Three-day courses are also effective, particularly in

epidemic containment
The treatment for quinolone resistant typhoid fever has
not been determined.
Azithromycin, the third
generation cephalosporins, 10-14 day course of highdose fluoroquinolones, is effective. Combination of
these is also being evaluated.
3 First-line Agents in Philippines:
1. Chloramphenicol
2. Amoxicillin/ Ampicillin
3. Co-trimoxazole

Question: What laboratory examination would be

the most helpful test before starting any
antibiotic?
A. Complete blood count
B. Urinalysis
C. Immunochromatographic test (Typhi Dot)
D. Blood culture and sensitivity
[2013B]

Immunochromatographic Test (Typhi Dot)

o
Antibody test; tells previous exposure; it may
not truly tell if there is a disease

Blood culture and sensitivity

o
Isolates organisms; best tool

[Harrisons]
Prompt administration of appropriated antibiotic therapy
prevents severe complications and results in a case
fatality rate of <1%
Drug susceptible typhoid fever
o
Fluoroquinolones most effective class of
agents
Patients with nalidixic acid-susceptible strains
o
Ceftriaxone, azithromycin, or high dose
ciprofloxacin
Most preferred

RATIONALE FOR THE DIAGNOSTIC TEST

To determine the etiologic agent
o Better care
o Cost efficient
In suspected cases of typhoid fever
o Isolation via cultures remains the gold
standard
o Blood in the 1st and 2nd week
o Stool in the 3rd week
o Urine culture may become (+) on the 3 rd
week

ANTIBIOTIC THERAPY FOR TYPHOID FEVER

resistantQuinolone
resistantMulti-drug
susceptibleFully
biltySuscepti

Question: Which of the following antibiotics

would you give?
A. Chloramphenicol
B. Amoxicillin
C. Cotrimoxazole
D. Ciprofloxacin

Figure 9. Trends in Antimicrobial Resistance among

Salmonella Typhi Isolates 1988-2009 ARSP

[2013B]
Antibiotic Therapy for Typhoid fever
Optimal Therapy
Alternative effective drugs
Antibiotic
Dail
Da
Antibiotic
Daily
day
y
ys
dose
s
dos
mg/k
e
g
mg/
Fluoroquinolo
ne
e.g.
ofloxacin,
ciprofloxacin

15

Fluoroquinolo
ne
Or
Cefixime

15
1520

Azithromycin

8-10

5-7

5-7
714

Chlorampheni
col
Amoxicillin
TMP-SMX

50-75
75100

1421
14
14

Azithromycin
Cefixime

8-10
15-20

7
7-14

Cefixime

20

7-14

JMA-1, JMA-2, Telma Amit

Page | 2

Figure 10. Trends in Antimicrobial Resistance among

Non-typhoidal Salmonellae 1988-2009 ARSP

CASE COURSE

Case # 2 Course:
The patient was started on oral chloramphenicol
However, he continued to have fever
2nd HD: abdominal pain increased in intensity
hematochezia
Blood culture is positive after 48 hours
Question: How would you modify your antibiotic
therapy?
A. Shift initial antibiotic to a parenteral form
B. Change the initial antibiotic to an IV
fluoroquinolone

C. Add an IV third generation cephalosporin

(e.g. Ceftriaxone)
D. Continue initial antibiotic therapy and
wait for the susceptibility results
[2013B]

Continue initial antibiotic therapy and wait for the

susceptibility result
o
Because chloramphenicol is not good when
given IV; youre already dealing with the
complicated type of typhoid fever (note
hematochezia) + resistant typhoid = change
Abx

Blood CS result (related to case course):

Salmonella sp.
o
Sensitive to ciprofloxacin, ceftriaxone,
amikacin
o
Resistant to chloramphenicol, ampicillin

The antibiotic was shifted to intravenous

ciprofloxacin 400 mg every 12 hours

Abdomen was regularly examined; no signs of

peritonitis were observed on subsequent days
o
No episode of hematochezia was reported
o
Urine output was adequate

After 3 days of IV ciprofloxacin, temperature

levels started to go down; lysis of fever was
noted on the 5th day of the antibiotic

o
o

Drug of choice
Drug resistance

ETIOLOGIC AGENTS
PLASMODIUM FALCIPARUM
Only species associated
with severe or
complicated malaria
o Almost all deaths caused by this specie
[Harrisons]

Problem with therapy: Multidrug resistance

o Philippines: increasing chloroquine and
sulfadoxine- pyrimethamine resistance
DOH surveillance rate: 35- 65%
Highest in Palawan
Clue: in a smear, you should see multiple affected RBC
presenting with rings [2013B]

PREVENTION
Proper hygiene
Avoid possibly contaminated food and water
Vaccines for high risk groups

Figure 11. Malaria blood smear showing ring forms

[Harrisons]
Two Typhoid vaccines are commercially available:
o
Ty21a, an oral live attenuated S. typhi vaccine
(given on days 1, 3, 5, and 7, with a booster
every 5 years)
o
Vi CPS, a parenteral vaccine consisting of purified
Vi polysaccharide from the bacterial capsule
(given in 1 dose, with a booster every 2 years)

OTHER PLASMODIUM SPECIES

Plasmodium vivax and ovale
o Both can cause relapse
A proportion of the intrahepatic

MALARIA

Case # 3:
A 35 year old male who had a recent travel to
Palawan
1 week after arriving in manila, sudden onset of
fever, chills, severe headache, and body malaise
Consulted 2 days later: CBC, malarial smear and
urinalysis showed normal results
Given Ciprofloxacin 750 mg BID x 5 days with no
lysis of fever
Admitted because of subsequent development of
oliguria and ictericia

Case # 3: Issues
Disease severity/ comorbid conditions or factors
o Ictericia
o Oliguria
Etiologic agent involved
JMA-1, JMA-2, Telma Amit
Page | 3

forms
(hypnozoites) remain dormant for a period
ranging from 3 weeks to a year or longer
before reproduction begins
Hypnozoites are the cause of relapses
[Harrisons]

Plasmodium malariae
o Causes nephropathy
Plasmodium knowlesi
o Similar to plasmodium malaria but behaves like
P.falciparum infection

MALARIA TRANSMISSION CYCLE

[Harrisons]
Malaria
Protozoan disease; transmitted by the bite of an infected
female Anopheles mosquitoes
Principal determinants of the epidemiology of malaria:
number (density), human-biting habits, longevity of
anopheline mosquito vectors
Transmission of malaria is directly proportional to the
density of vector

Figure 12. Plasmodium sporozoites 1st vector

(Plasmodium sp.) initial human host liver infection
blood infection 2nd vector next human host
[2013B]

LABORATORY TESTS
Question: Which diagnostic test would be most
helpful?
A. Complete blood count
B. Renal and liver function tests
C. Malarial smear
D. Blood C/S
E. Microcapsular agglutination test
[Harrisons]
Remember: The diagnosis of malaria rests on the
demonstration of asexual forms of the parasite in stained
peripheral blood smears.
LABORATORY FINDINGS
Normochromic, normocytic anemia is usual
Leukocyte count: generally normal (may be raised in
severe infections)
Slight monocytosis, lymphopenia, eosinopenia w/
reactive lymphocytosis and eosinophilia weeks after
acute infection
ESR, plasma viscosity, C-reactive protein and other
acute-phase protein: High
Platelet count is usually reduced to 105/L

Case # 3 Lab results:

CBC: Hb=9.0, Hct=28.7, RBC=2.95 WBC=14.0
(N=81, L=17 M=2), platelet count=95,00
LFTs: ALT = 120 Iu/l, AST = 96 Iu/l, AP = 54 Iu/l, B2
=15mol/l, TB = 65mol/l, Crea = 200mol/l.
MAT = positive at 1:100
Blood CS: NG after 24 hours
[2013B]
In most malaria cases, patients would present with
elevated white blood cells, but some may present with
thrombocytopenia
Liver function test results in a patient w/ Malaria:
o
Slightly elevated ALT
o
Slightly elevated AST
o
Normal alkaline phosphatase
o
Creatinine is elevated = 200
o
MAT = 1: 100
Philippine cut-off : 1:1600

JMA-1, JMA-2, Telma Amit

Page | 4

CLINICAL FEATURES OF MALARIA [Harrisons]

Nonspecific first symptoms: lack of sense of well-being,
headache, fatigue, abdominal discomfort, and muscle
aches followed by fever
Headache present but no neck stiffness or photophobia
resembling meningitis. Myalgia may be prominent but
not usually as severe as in dengue; and muscles are
not tender as in leptospirosis or typhus.
When fever spikes, chills and rigors occur at regular
intervals suggest P. vivax or P. ovale infection.
Irregular fever Falciparum malaria
Few abnormal physical findings other than fever,
malaise, mild anemia, palpable spleen (some cases).
Slight enlargement of liver particularly among children.
Mild jaundice is common among adults and develops
in patients with uncomplicated falciparum malaria;
usually resolves over 1-3 weeks.
Malaria is not associated with rashes.

MAJOR SIGNS OF SEVERE MALARIA

Unarousable
coma/ cerebral
malaria
Severe
normocytic,
normochromic
anemia
Renal failure

Pulmonary
edema/ adult
respiratory
distress
syndrome
Hypoglycemia

Hypotension/sh
ock

Bleeding/
Disseminated
intravascular
coagulation
Convulsions
Acidemia/
acidosis
Hemoglobinuri
a

Failure to localize or respond

appropriately to noxious stimuli;
coma should persist for >30 min
after generalized convulsion
Hematocrit <15% or haemoglobin
<5g/dl with parasitemia level
>10,000 per L
Urine output <400 mL/24 h in
adults or 12 mL/kg per 24 hr in
children; no improvement with
rehydration;
serum
creatinine
>265 mol/L 93 mg/dl)
Noncardiogenic pulmonary edema
often aggravated by overhydration
[Harissons 18th ed]

Glucose <2.2 mmol/L (<40mg/dl)

Systolic blood pressure <50 mmHg

in children 1-5 years or
< 80
mmHg in adults ; core skin

temperature difference >10 C

Significant
bleeding
and
hemorrhage from the gums, nose,
GIT,
and/
or
evidence
of
disseminated
intravascular
coagulation
More than 2 generalized seizures
in 24 hours
Arterial pH< 7.25 or plasma
bicarbonate< 15 mmol/ L, venous
lactate > 6 mmol/ L
Macroscopic black, brown, red
urine, not associated with effects
of oxidant drugs and red blood cell
enzyme defects (such as G6PD
deficiency)

OTHER SIGNS OF SEVERE MALARIA

Impaired
consciousness

Unable to sit or stand

without support

Extreme weakness

Prostration; unable to sit

unaided

Hyperparasitemia

Parasitemia >5% in
nonimmune patients
Serum bilirubin level >50
mmol/ L (>3 mg/dl)
Rectal Temperature
>40C

Contraindications:
Patients with G6PD deficiency hemolysis
Not used for active disease

[Harrisons 18th ed]

OTHER ISSUES
1.
2.

[Harrisons 18th ed]

Jaundice
Hyperpyrexia

DRUGS FOR SUSCEPTIBLE PLASMODIUM SP.

Question: Which of the following anti-microbials
would you give?
A. Chloroquine
+
Sulfadoxine/Pyrimethamine
B. Quinine + Doxycycline
C. Artemether + Lumefantrine
D. Primaquine
Uncomplicated malaria
o Susceptible P. Falciparum
Chloroquine can

cause

Management of Complications
[2013B]
Regarding hypoglycemia, quinine can induce insulin
release which can aggravate hypoglycaemia
Pulmonary edema: unknown reason why patients
develop this, so ventilatory support should be given
Acidosis: give bicarbonate
Renal failure: require dialysis

tinnitus

[2013B]

3.

Management of Complications
Adverse events related to drug interventions
and interactions
Prevention

Prevention
Chemoprophylaxis
Use mosquito nets. It is more effective if the mosquito

Sulfadoxine/pyrimethamine
Other susceptible Plasmodium sp.
Chloroquine

One criteria that you have to consider in choosing drugs

is resistance of species
In the Philippines, more than 60% is resistant especially
in Palawan

DRUGS FOR MULTI-DRUG RESISTANCE

PLASMODIUM FALCIPARUM MALARIA
Artemether-lumefantrine (Co-Artem) 1.5/9
mg/kg BID with food for 3 days (or artesunate
4mg/kg qd)
PLUS
Mefloquine 15-25 mg base/kg for 3 days

DRUGS FOR SEVERE OR COMPLICATED P.

FALCIPARUM MALARIA
Drug/s of choice: IV quinine (or quinidine) +
Doxycycline or clindamycin
Alternative: Artemisinin derivatives

PRIMAQUINE
For radical cure
Used as gametocidal drug for P. Falciparum
malaria
Used as a hypnozoiticidal drug for P. Vivax or P.
Ovale infection to prevent relapse
[2013B]

JMA-1, JMA-2, Telma Amit

Page | 5

net is treated with insecticide

Use long sleeves and pants
Use repellants and screens on doors and windows
Clear hanging branches of trees along the streams
Have your blood examined if you have the signs and
symptoms of malaria
Follow the advice of health workers on how to take antimalaria drugs.
Primary area where Malaria is endemic- PALAWAN
Avoidance of exposure to mosquitoes at their peak
feeding times (usually dusk to dawn) as well as the use
of insect repellents containing 1035% DEET

1.
2.
3.

What Plasmodium species causes relapse

in malaria?
Which among the dengue serotype causes
the more severe disease?
What is the drug of choice for the
treatment of typhoid fever in the
Philippines?

Answers: (1) P. vivax & P.ovale; (2) Serotype 2; (3)

Chloramphenicol

QUIZ:

JMA-1, JMA-2, Telma Amit

Page | 6