GENERAL DATA & CHIEF COMPLAINT

BV, 5 years old

Male
Filipino, Born-again
Admitted for the 1 time
st

SEIZURE
 HISTORY OF PRESENT ILLNESS
4 days PTA

Fever (Tmax= 37.9 C)

Paracetamol Syrup (Brand: Calpol, 5ml, 250mg/5ml) every four hours but with no
relief.
Loss of appetite
Poor activity
Mild cough and colds
 HISTORY OF PRESENT ILLNESS
3 DAYS PTA

Fever persisted (Tmax= 38.0)

Consult was done at our institution with a private physician
Vivalyte, Erceflora, and Paracetamol Syrup (Brand: Calpol, 250mg/5ml) every
four hours but still with no relief of symptoms.
 HISTORY OF PRESENT ILLNESS
2 DAYS PTA

Persistence of fever
Intermittent abdominal pain specifically located at the epigastric area
Post prandial projectile vomiting with mucoid appearance,
Cough and colds.
 HISTORY OF PRESENT ILLNESS
1 DAY PTA

persistently afebrile
Persistence of intermittent epigastric pain
Episode of postprandial vomiting
Non-projectile and watery.
 HISTORY OF PRESENT ILLNESS
DOC

episode of abrupt hematemesis characterized as a handful of blood with associated

epistaxis
still afebrile but with decreased sensation of epigastric pain.
 REVIEW OF SYSTEMS
GENERAL: (-) weight loss; (-) loss of activity; (+) poor activity; (-) easy fatigability
SKIN: (-) rash; (-) pruritus; (-) diaphoresis
HEENT (-) ear pain; (-) ear, eye discharge (+) nasal discharge; (-) dizziness; (-) epistaxis
NECK & THROAT (-) lymphadenopathy; (-) muscle stiffness; (-) sore throat (-) hypertrophic tonsils
CVS (-) cyanosis; (-) orthopnea; (-) easy fatigability; (-) palpitation; (-) chest pain
RESPI (-) dyspnea; (-) cough
GIT (-) vomiting; (-) diarrhea; (-) abdominal pain; (-) constipation; (-) jaundice;
GUT (-) dysuria; (-) discharge; (-) frequency; (-) oliguria (+) loss of appetite
ENDOCRINE (-) polydipsia; (-) heat intolerance
NERVOUS (-) eating problems; (-) sleep problems
MSS (-) weakness
HEMATOPOIETIC (-) bleeding: (-) easy bruisability; (-) pallor
 Birth and maternal history
Prenatal
36 year old G3P3 (3-0-0-3)
10 prenatal checkups : ultrasound (unremarkable)
No infection/spotting/preeclampsia/DM
Mother took multivitamins and ferrous sulfate

Perinatal
Uncomplicated delivery

Postnatal
Term, VSD, no complications
 PAST MEDICAL HISTORY
Patient had history of Typhoid fever when he was younger.
No history of previous illnesses such as measles, mumps, chickenpox,
tuberculosis, pneumonia, asthma, allergies, eye or ear problems, or seizures
No history of operations or injuries.
 FAMILY HISTORY

The patients maternal side has history of asthma.

The patient has no history of heredofamilial diseases such as cancer, allergies,
kidney disease, blood dyscrasia, lung disease and tuberculosis on both sides of
the family.
 NUTRITIONAL HISTORY

BREASTFEEDING: birth to 6 months

FORMULA : 6 moths
COMPLEMENTARY FEEDING: 6 months
TABLE FOOD: 12 months
Eats 3 meals/day and snacks in between
Good appetite, no feeding difficulties, food intolerance
 Immunization HISTORY
VACCINES DOSES
BCG 1
Hepatitis B 3
DPT 3
OPV/IPV 3
H. influenza B 3
Pneumococcal -
Rotavirus -
Measles 1
MMR 2
Varicella -
Influenza 2
 DEVELOPMENTAL HISTORY

At par with age of 5 years and 3 months old

 ENVIRONMENTAL HISTORY

Not exposed to cigarette smoke or any form of air pollutants

Household garbage is not segregated, and not regularly collected
every week
Drinking water is mineral, while their water for washing is tap water
Sewage disposal is a closed canal
Objective
 GENERAL SURVEY/ VITAL SIGNS (ER)

conscious, well nourished, coherent, well developed, weak looking and irritable, not in
cardiorespiratory distress. and appears his chronological age of 5 years old and 3 months

VITAL SIGNS
Blood Pressure 90-50mmHg N:95-110/60-75mmHg
Pulse Rate 114 bpm N:65-110bpm
Respiratory Rate 22cpm N:20-25cpm
Temperature 36.8C N: 36.5-37.5C
O2 Saturation 99% N: 100-95%
 ANTHROPOMETRIC MEASUREMENTS

Height: 116 cm Ideal Height: 107cm

Weight: 25 kg Ideal Weight: 18kg
BMI 18.58 kg/m2
Above 2
NORMAL
Below 2
Normal
ABOVE 2:
Overweight
 REGIONAL EXAMINATION

SKIN
Inspection
moist, mild pallor, acyanotic
Palpation
good skin turgor, good capillary refill
Nail unit
pink, no nail clubbing or koilonychia, no cyanosis.
 REGIONAL EXAMINATION

HEAD
Inspection
hair color is black, thin and well distributed, smooth with no patterns of hair
loss.
No lumps and scales and flakes in scalp
Skull is normocephalic with no lump.
Palpation
No cervical lymphadenopathy
Trachea is in midline and thyroid cartilage moves with deglutition
 REGIONAL EXAMINATION

EYES
Inspection MOUTH
Symmetrical Inspection
Eyebrows are well distributed Dry lips, chappy with dried blood
Pink palpebral conjunctiva Pink oral mucosa
gum bleeding and hyperemic
tonsils and posterior palate
EARS
No erythema, lesions, tenderness
 REGIONAL EXAMINATION

RESPIRATORY
Inspection
Symmetrical chest expansion, no use of accessory muscles A:P diameter 1:2
Percussion
Resonant on all lung fields
Auscultation
Equal vesicular and bronchovesicular sounds on anterior lung fields
No adventitious sounds were noted; (-) crackles, wheezes, stridor
 REGIONAL EXAMINATION

CARDIOVASCULAR
Inspection
No precordial bulge
Palpation
(-) heaves (-) thrills
Auscultation
Normal rate, regular rhythm
No murmurs
 REGIONAL EXAMINATION

ABDOMEN
Inspection
Not distended, no scars
Auscultation
Normoactive bowel sounds
Palpation
Soft (+)abdominal guarding (-) abdominal tenderness (-) hepatosplenomegaly
(-) Rovsings and Murphys sign
Abdominal circumference: 67 cm
 REGIONAL EXAMINATION

EXTREMITIES
Inspection
no swelling noted on both extremities
Palpation
No tenderness, good equal pulses
No loss of motion
 REGIONAL EXAMINATION

NEUROLOGIC EXAM
GCS 14-15/15
Normal general behavior
Scarce stream of talk
Appropriate mood
No hallucinations
Oriented to 3 spheres
No sensory and motor deficits
(-) Kernigs (-) Brudzinski (-) Nuchal rigidity
 REGIONAL EXAMINATION
Cranial nerves
II (+) direct and consensual light reflex
Pupils EBRTL 2-3mm
III. IV, V Intact EOM
V Good masseter tone
Intact facial sensation
VII No facial symmetry
IX (-) drooling of saliva
(+) swallow
(+) cough
(+) lingual and guttural sounds
(-) nasal twang
(-) dysphonia

XII No tongue deviation, fasciculations

 laboratory
CBC 08/20/17 URINALYSIS 08/20/17
Patient Normal Color
Hemoglobin 115-148 g/L Character
Hematocrit 0.38-0.44 Specific Gravity
WBC 4.0-11.0 pH
RBC 3.8-5.4 Protein
Platelet Count 150-400 Sugar
Segmenters 0.45-0.55 WBC
Lymphocytes 0.38-0.05 RBC
Eosinophils Bacteria
Basophils Cast
Monocyte
 laboratory
CHEMISTRY 08/20/17
Patient Normal
BUN 3.0-9.2
SEROLOGY (08/20/2017)
Creatinine 53-97
Reference Values: 1032-1495 mg/L
Calcium 2.23-2.50

Magnesium 0.66-1.07 IMMUNOLOGY (08/20/2017)

Potassium 3.5-5.1
Reference Values: <200
Sodium 136-145

Phosphorus 0.74-1.52
 laboratory
CHEST, AP/L VIEWS
laboratory
laboratory
 laboratory
KUB ULTRASOUND
 COURSE IN THE WARDS
S O A P
ER
 Primary Impression
DENGUE WITH WARNING SIGNS
 SALIENT FEATURES

History of fever followed by afebrile state

Persistent vomiting
Cough and colds
Poor activity and loss of appetite
Hematemesis upon consult
Abdominal pain and tenderness
 Differential diagnosis

1. Malaria
Patient had history of fever, cough, abdominal pain,
anorexia, nausea, and vomiting. PE finding of abdominal
tenderness.

2. Influenza
Considered due to history of fever, poor activity,
cough, and colds.
 Differential diagnosis

3. Typhoid fever
Considered due to history of fever,
abdominal pain, cough, and poor
activity. PE finding of abdominal
tenderness.
 Differential diagnosis

4. Japanese encephalitis
Considered due to history of fever. JE virus is a
flavivirus related to dengue.

5. Yellow fever
A possibility due to symptoms of fever,
anorexia, nausea, and vomiting.
 Differential diagnosis

6. Bleeding dyscrasia:
Hemophilia A & B
Von Willebrand disease
Disseminated Intravascular Coagulation
Idiopathic Thrombocytopenic Purpura
 DHF: Pathogenesis
Secondary infection with another serotype leads to
antibody mediated enhancement
Heterotypic antibodies are non protective and fail to
neutralise the virus
Virus-antibody complexes taken up by monocytes
Virion multiplication in human monocytes is promoted
Activation of CD4+ and CD8+ lymphocytes release of
cytokines
Complement system activated with depression of C3 & C5
Homologous Antibodies Form
Non-infectious Complexes

Dengue 1 virus
Neutralizing antibody to Dengue 1 virus
Non-neutralizing
antibody
Complex formed by neutralizing antibody
and virus
 Hypothesis on Pathogenesis
of DHF (Part 2)

In a subsequent infection, the pre-existing

heterologous antibodies form complexes with the
new infecting virus serotype, but do not neutralize
the new virus
Heterologous Antibodies
Form Infectious Complexes

Dengue 2 virus
Non-neutralizing antibody to Dengue 1
2
virus
Complex formed by non-neutralizing
antibody and virus
 Hypothesis on Pathogenesis
of DHF (Part 3)
Antibody-dependent enhancement
is the process in which certain strains
of dengue virus, complexed with
antibodies, can enter a greater
proportion of cells of the
mononuclear lineage, thus increasing
virus production
 Plasma leaks - Pathophysiology
Host response
Subsequent infection

Previous IgG
Neutralizing (protective)
non neutralizing (replication enhancing)

Increased viremia increased TNF, interferon, interleukin-2 and

hypocomplementemia endothelial injury and increased
leakage
 Pathophysiology of DHF
Increased capillary permeability
Protein rich fluid exudes into the interstitial space - Pleural effusion , Ascites etc.

Circulatory volume collapses SHOCK

Sympathetic over activity

Vasoconstriction, tachycardia

Loss of volume
Reduces pulse pressure

Blood becomes thick due to loss of fluid

Rising hematocrit and delayed capillary filling

Compromised renal and hepatic perfusion

Reduced urine output and tender hepatomegaly
 Pathophysiology of DHF

But there is one important consideration:

Fluid is not being lost out but it is going to 3rd space and will be resorbed
back
so
Over-enthusiastic fluid replacement

during the critical phase when the fluid is oozing out - would result in
 Pathophysiology of DHF
People do not die of hemorrhage in DHF

They die
Either due to shock and 20 organ failure

Or due to Pulmonary edema & fluid over load during the recovery
phase
 EPIDEMIOLOGY

most rapidly spreading mosquito-borne viral disease in the world

incidence: 30-fold increase

increasing geographic expansion to new countries, and from urban to
rural settings
50 million dengue infections annually
EPIDEMIOLOGY
 EPIDEMIOLOGY

2001-2008: 1, 020,333 cases in Cambodia, Malaysia,

Philippines and Vietnam

highest reported deaths in 2008

Cambodia
Philippines
 Burden of Disease

WHO estimates that 2.5 billion peopleover

40% of the worlds population-- are at risk for
dengue infection.

Approximately 50-100 million infections (1

million confirmed) occur each year resulting in
500,000 hospitalizations and 20,000 deaths.
 Philippines

Jan 1 to July 18, 2015

40593 suspect dengue cases
Region IV-A (15.8%)
Region III (12.5%)
NCR (11.7%)
Region X (10%)
Males (53.8%)
Case fatality Rate of (0.33%)
 Dengue Virus Profile

Genus Flavivirus
Family Flaviviridae
Single-stranded RNA
4 serotypes (DEN-1 to 4)

50 nm diameter with
multiple copies of 3
structural proteins (( membrane
membrane
bilayer
bilayer and
and single-stranded
single-stranded RNA)
RNA)
 Vector Profile

Aedes mosquitoes
A.
A. aegypti
aegypti
A.
A. albopictus
albopictus
A.
A. polynesiensis
polynesiensis
Tropical and
subtropical species
Urban places
Immature stages are
found in water-filled
habitats
 The Host

Incubation period: 4-10 days

Primary infection induce

lifelong immunity to the
infecting serotype

Protection from different

serotype within 2-3
months of primary
infection
No long-term cross-
protective immunity
 The Host

Individual risk factors:

Age, ethnicity, chronic diseases

Seroepidemiological studies (Cuba and Thailand)

Secondary heterotypic infection
Time interval between infections
Antibody-dependent enhancement of
infection
 Replication and Transmission

Blood meal Released in

circulation

Viral
Replication WBC and
Lymphatics
 Replication and Transmission

Replication in
the salivary
gland

Viral Extrinsic Incubation

replication in 8--12 days
midgut

Female
mosquito ingests
infected blood
 Dengue Fever

Wide spectrum of clinical presentation, with

unpredictable clinical evolution and outcome

Three phases
Febrile phase
Critical phase
Recovery phase

Previously classified into

undifferentiated fever, dengue fever and DHF
Grade 1-IV
Dengue Fever

Febrile Phase

Critical Phase

Recovery Phase
 Febrile Phase

facial flushing
skin erythema
Sudden onset of generalized body ache
myalgia and arthralgia
high-grade fever headache
Lasts for 2-7 days sorethroat, injected pharynx,
and conjunctival injection
anorexia, nausea and
vomiting
 Febrile Phase

(+) TT increases the

probability of dengue

(+) hemorrhagic
manifestations

earliest abnormality: progressive decrease

in total wbc
 Critical Phase

temperature drops to 37.5-38 (days 3-7)

(+) increase in capillary permeability with

increasing hematocrit levels

significant plasma leakage lasts for 24-48 hours

progressive leukopenia followed by rapid

decrease in platelet precedes plasma leakage
 Critical Phase

if (-) increase in capillary permeability

improve
if (+) increase in capillary permeability
pleural effusion and ascites

degree of increase above the baseline

hematocrit reflects the severity of plasma
leakage
 Critical Phase

shock: critical volume of plasma is lost

temperature may be subnormal
prolonged shock organ hypoperfusion organ
impairment, metabolic acidosis, and DIC severe
hemorrhage
severe hepatitis, encephalitis or myocarditis
 Recovery Phase

gradual reabsorption of extravascular compartment

fluid (48-72 hours)
general well-being improves, appetite returns, GI
symptoms abate, hemodynamic status stabilizes and
diuresis ensues
(+) rash: isles of white in the sea of red
 Recovery Phase

hematocrit stabilizes or may be lower due to dilutional

effect of reabsorbed fluid
wbc starts to rise
recovery of platelet count occurs later
PLAN
Diagnostics
 Laboratory Testing

RT-PCR
NS1
IgM
IgG
CBC
TREATMENT
 GROUP B
Obtain a reference
hematocrit before Reassess the
Give the minimum
fluid therapy clinical status,
intravenous fluid volume
repeat HCT and
required to maintain good
review fluid
perfusion and urine output
infusion rates
of about 0.5 mL/kg/hr
accordingly
Isotonic solutions
5-7 mL/kg/hour for
1-2h If there are
worsening of vital Reduce intravenous fluids
3-5 mL/kg/hr for 2- signs and rapidly gradually when the rate of
4h rising HCT, increase plasma leakage decreases
2-3 mL/kg/hr or less the rate to 5-10 towards the end of the
according to mL/kg/hour for 1-2 critical phase
clinical response hours

HCT remains the

same or rises only
Reassess the minimally
clinical status and continue with the
repeat the HCT same rate (2-3
mL/kg/hr) for
another 2-4 hours
 Management of Hemorrhagic
Complications

5-10ml/kg of fresh packed RBC or

10-20ml/kg of fresh whole blood at an appropriate rate
 DISCHARGE

All of the following conditions must be

present
No fever for 48 hours
Improvement in clinical
Increasing trend of platelet count
Stable hematocrit without intravenous fluids
PREVENTION
 DENGUE VACCINATION

Tetravalent vaccine (DENV-1,2,3,4)

1st dose
2nd dose - 6 months after the 1st dose
3rd dose 6 months after the 2nd dose

NOT RECOMMENDED
Children < 9 y/o and Adults > 45 y/o
Allergic to dengue vaccine
Immunocompromised individuals
Pregnant or Breastfeeding individuals
 Chloroquine use
Improves Dengue-
related Symptoms
M.C. Borges, L.A. Castro, et al.
 Objective

The objective of this study is to find

out if Chloroquine is an effective
treatment for dengue
 Chloroquine

Primarily used as an antimalarial agent

Secondary drug in treating chronic diseases
Rheumatoid arthritis
Systemic Lupus erythematosus

Exerts viral effects by inhibiting the replication of

flaviviruses
 Patients, Materials, Methods

Double-blind, randomized study that administered

Chloroquine vs Placebo (BID for 3 days)
3 diagnostic test were performed
RT-PCR
IgM antibody capture ELISA
NS1

Re-evaluated 1 week later and dengue symptoms were recorded

 Results

12 dengue patients (63%) CHLOROQUINE

Substantial reduction in the intensity of pain
Great improvement in their health status

No improvements in patients who took the PLACEBO

Symptoms returned after stopping the treatment

 CHLOROQUINE

Antiviral effect
Raising the intracellular pH -> interfere with endosome-mediated entry
Interfere with the post-translational processing of viral glycoproteins

Anti-inflammatory activity
TNF-a inhibitor
 Limitations of the Study

Small number of patients treated with chloroquine

Pain amelioration was not quantified by pain-scale
 Conclusion

Chloroquine promoted a reduction in the intensity of pain and an

improvement in the well-being of patients with dengue infection

But did not alter the duration of the disease or the intensity and days of fever

Further studies are needed

 Recommendation

Chloroquine should be further tested in dengue disease

larger number of patients
different chloroquine dosages
times of administration

To confirm the drugs clinical effect and to assess the

side effects of chloroquine in dengue patients