DENGUE AND OTHER VIRAL HEMORRHAGIC FEVER

INTRODUCTION

NEGATIVE STRAND OF
RNA VIRUS
FOUND IN CENTRAL
AFRICA
DIVIDED INT 4 SUB-TYPES
Zaire
Sudan
Ivory Coast
Reston
HAS OCCURRED IN
EXPLOSIVE OUTBREAKS
IN ZAIRE & SUDAN WITH
HIGH MORTALITY
TRANSMITTED BY DIRECT
CONTACT WITH BLOOD ,
BODY FLUID, ORGAN OR
SEMEN
SPREAD MAINLY BY
CLOSE PERSON-TOPERSON CONTACT

PATHOPHYSIOLOGY
VIRUS SPREAD FROM INITIAL
SITE OF INFECTION via
monocytes & dendritic cell
to lymph nodes , liver and
spleen via hematogenously

SERIES OF EVENTS OCCUR

LEAD TO VIRUS INDUCED
IMMUNO-SUPPRESSION & TLYMPHOCYTES APOPTOSIS
AS DZ PROGRESSES , NK
APOPTOSIS IS ALSO OCCUR
----> lead to innate response is
restricted

VIRAL REPLICATION --> INC.

LEVEL OF PROIMFLAMMATORY
CYTOKINES->COAGULATION CASCADE
INCUBATION PERIOD :
WILL TRIGGERED--> RESULT
AVERAGE 6.2 DAYS (2-21
IN DIVC , HEMORRHAGIC
DAYS
SHOCK WITH MOF, AND
DEATH
RECOMMENDED
QUARANTINE OF
CONTACT FOR 3 WEEKS

FILOVIRIDAE VIRUS
EBOLA VIRUS
RISK FACTORS

close contact via body

fluid
nosocomial infection
via contaminated
fomites
Handling the dead
(Burial services)
Laboratory workers /
animal care takers
Outing/hunting/spelun
king in the endemic
areas with infected
bats
BLEEDING SIGNS
GUM BLEEDING
HAEMATEMESIS
MELAENA
HEMATURIA
PUNCTURE SITES
BLEEDING
BLOODY STOOL
PETECHIAE
EPITAXIS

SIGN AND SYMPTOMS

CLINICAL SYMPTOMS
DIARRHEA
NAUSEA &
VOMITING
ABDOMINAL PAIN
HEADACHES
DYSPHAGIA
ANOREXIA
LUMBAR PAIN
TINNITUS

DIAGNOSIS

Diagnostic studies for

& MARBURG virus sh
undertaken only in B
Virus isolation serum
in Vero cell
Serological test (+ve
Antigen detection by F
staining of impressio
smears prepared from
infected tissue
RT-PCR using specific p

CLINICAL SIGN
PREVENTION
HEPATOSPLENOME
NO ANTIVIRAL AVAILAB
GALY
SPLENOMEGALY
VACCINE-UNDER
FETAL LOSS
DEVELOPMENT
CONVULSIONS
TRAVELERS SHOULD A
DELIRIUM
AREAS OF EBOLA
CONJUCTIVAL
OUTBREAKS OCCURIN
INJECTION
TACHYPNEA
HICCUPS

INTRODUCTION

SINGLE STRANDED RNA

VIRUS
HAS FOUR ANTIGENICITY
DEN 1
DEN 2
DEN 3
DEN 4
INFECTION WITH ONE OF
THE TYPES PROVIDES
ENDURING IMMUNITY
AGAINST THAT TYPE , but
only short lived immunity
against other types
TRANSMITTED BY AEDES
AEGYPTI & AEDES
ALBOPICTUS (daytime
feeder)-principal vectors
COMMON IN ASIA, AFRICA
AND AUSTRALIA
(distributed throughout
tropical regions of the
world)
COMMON IN URBAN
AREAS
GENETIC VARIATION
WITHIN SEROTYPES
ALL SEROTYPES CAN
CAUSES SEVERE & FATAL
DZ
SOME GENETIC VARIANTS
WITHIN EACH SEROTYPES

FILOVIRIDAE VIRUS
FLAVIVIRIDAE
DENGUE VIRUS
PATHOPHYSIOLOGY
CLINICAL SYNDROMES
VIRUS INOCULATED INTO HUMAN with
mosquito saliva
VIRUS LOCALIZED & REPLICATED IN
VARIOUS TARGET ORGAN (ex . local
lymph nodes and liver)
VIRUS RELEASED FROM THIS TISSUE &
SPREADS THROUH BLOOD
WBC & OTHER LYMPHATIC TISSUE B/C
AFFECTED
VIRUS IS THEN RELEASED FROM
THESE TISSUE AND CIRCULATED IN
BLOOD
MOSQUITO WILL INGEST THE
AFFECTED BLOOD
VIRUS WILL REPLICATES IN MOSQUITO
MIDGUT, OVARIES, NERVE TISSUE
AND FAT BODY
IT THEN ESCAPE INTO CAVITY AND
LATER INFECTS THE SALIVARY

GLANS
VIRUS WILL REPLICATED IN THE
SALIVA AND INFECTED TO OTHER
HUMAN
VIRUS WILL CIRCULATE IN THE BLOOD
-> VIRAEMIA LAST FOR ABOUT 5
DAYS
IN THE MOSQUITO,VIRUS REPLICATES
DURING EXTRINSIC INCUBATION OF 8-12
DAYS
SYMPTOMS BEGIN TO APPEAR 4-7 DAYS

DIAGNOSIS

FEBRILE PHASE
LAB INVESTIGATION
Last 2-7 days
Isolation of dengu
High grade fever , facial flushing ,
ELISA--> IgM Ab
myalgias , atralgia , generalized
detected within 5
body aches & headaches
of fever
Sore throat & conjuctival infection
Detection of deng
Nausea & vomiting are common
antigen by
Warning sign appearances
Immunochemistr
o Lab
ELISA, IF
Inc. HCT with concurrent
Virus Specific nuc
raid decrease of plasma
acid sequences d
count
by PCR
o Clinical
PREVENTION
Abd.pain or tenderness
Persistent vomiting
PREVENTION AND CON
Clinical fluid accumulation
Health education
Lethargy, restlessness
campaign
Mucosal bleed
House inspections
Liver enlargement > 2 cm
Vector control
CRITICAL PHASE
Bednets usage
Temp drop to 37.5-38 or less
Insecticides
3-7 days of illness
Inc.capiliary permeability in parallel NO ANTIVIRAL THERAP
rise to HCT level
Significant plasma leakage period
SUPPORTIVE
(24-48 hours)
Correction of elect
Plasma leakage degree is varied
abnormalities
Those who improve after
Replacements of b
defervescence are said to have
poducts
nom-severe dengue
Some will deteriorate and b/c
SEVERE DEN
severe dengue case.

APPEARS TO BE
VIRULENCE OR HAVE
GREATER EPIDEMC
POTENTIAL

AFTER BITE (INTRINSIC INCUBATION

PERIOD WITHIN HUMAN)
SYMPTOMS MAY LAST 3-10 DAYS
AVERAGE I/P CAN BE RANGE FROM 3-14
DAYS
VIRAEMIA BEGINS SLIGHTLY BEFORE ONST
OF SYMPTOMS .

PATHOGENESIS
1. Immune response develop to the dengue serotypes after infected
2. Immune response produced specific Ab to the subtypess surface
protein THAT PREVENTS THE VIRUS FROM BINDING TO
MACROPHAGE CELLS
3. If another subtypes infects individual, virus will ACTIVATE THE
IMMUNE SYSTEM TO ATTACK it as if it the first subtypes
4. Ab bind to surface proteins but IT DO NOT INACTIVATE THE VIRUS
5. Numerous macrophages attracted by immune respond , virus
proceed to infect since it has NOT activated (Ab DEPENDENT
ENHANCEMENT)
6. Viral infection will b/come much more ACUTE .
7. CYTOKINE RELEASED--> Endothelial tissue b/c permeable->Inc.vascular permeability DIVC and death

INTRODUCTION

Defines as by 1/mo
the following :
Plasma leakage
lead to SHOCK
accumulation w
RESP. DISTRESS
Severe bleedin
Severe organ im

RECOVERY PHASE
Pt survives 24-48 hrs of critical
period, gradual reabsorption of
extravas. Fluid will take place
following 48-72 hrs.
General well-being improved ,
appetite return, hemodynamically
stable & diuresis ensues
WBC start to rise , then platelet
recovery
Acute pulm.oedema (APO) and resp.
distress may occur dt excessive
fluid administration .

FLAVIVIRIDAE
YELLOW FEVER VIRUS
PATHOGENESIS
CLINICAL MANIFESTATIONS

DIAGNOSIS

 Is in the genus Flavivirus in TRANSMISSION OF VIRUS BY MOSQUITO --->

the family Flaviviridae
MONOCYTES , MACROPHAGES & DENDRITIC
Single stranded RNA virus
CELL B/C INFECTED
with positive sense
VIRUS WILL REACH
Occur exclusively in areas of
LIVER & INFECTS
SUB-SAHARAN AFRICA &
EOSINOPHILS
HEPATOCYTES
SOUTH AMERICA
DEGRADATION &
Transmitted by Female
RELEASE OF
Aedes Aegypti
CYTOKINE
Illness ranges from a selfNECROTIC MASSES
limited febrile illness to
(COUNCILMAN
severe hepatitis and
INC.CYTOKI
BODIES) APEARS IN
hemorrhagic fever
NE
Epidemics occur in
CYTOPLASM OF
HEPATOCYTES
unvaccinated populations ,
fatality cases range from
CVS SHOCK &
15% to more than 50%
MOF

COMPLICATION
2 Bacterial infection & kidney failure
Symptoms of weakness & fatigue may last several months in people who
recover
Those who are recover, generally have lasting immunity against
subsequent infections
PREVENTION
Avoid Mosquito Bites
Vaccines
Insect repellent
A live virus vaccines
Proper clothing
Highly recommended to
Vector control
travellers
A single dose confers last for
10 yrs
If a person at continued risk ,
nd

Pt may be viraemic (3-6 days)

Presumptive diagnosis
before demonstrating symptoms
based on the pts clini
I/P : (3-60 days)
feature , places and d
INITIAL SYMPTOMS (ACUTE PHASE)
travel , activites and t
Fever & chills
epidemiology history o
Severe headaches , back
location where infectio
pain
occurred
General m. aches
Nausea
LAB INVESTIGATION
Fatigue & weakness

ELISA - IgM & IgG

**this phase may followed by
detection (in the
a short period of symptoms
serum/CSF)
remission
Virus culture of bio
autopsy tissues on
TOXIC PHASE develops the fever
plasma (1-4 weeks
returns, with clinical symptoms
Histopathology wit
including high fever , headaches,
immunohistochem
back pain, nausea & vomiting,
Nucleic acid amplifi
abdominal pain and fatigue .
(RT-PCR)
MANAGEMEN
HEPATIC COAGULOPATHY may cause
Symptomatic treatmen
hemorrhagic symptoms
includes DEHYDRATIO
PAIN RELIEF
LATE STAGE ,
Acetylsalicylic acid (e.g
Hypotension
aspirin) should not giv
Shock
Metabolic acidosis
haemodiluting effec
ATN
Hospitalization is advis
Cardiac arrhythmias
and intensive care ma
Seizures & coma
necessary d/t rapid
deterioration in som
cases

a booster dose is needed in

every 10 yrs
Suitable for adult & children
over 9 months
Not recommended for
pregnant woman
CANNOT give to pt who
allergic with egg d/t vaccine is
made from the egg

BUNYAVIRIDAE VIRUS
HANTAVIRUS
INTRODUCTION
NEGATIVE STRAND OF
RNA VIRUS , SPHERICAL
& ENVELOPE
UNIQUE AMONG
BUNYAVIRIDAE GENERA
---> they are not a/w
arthropod vector
DISTINCT RODENT
SPECIES is a reservoir
Transmission occur via
INHALATION OF
AEROSOLIZED, VIRUSLATENT RODENT
EXCRETA
RODENT BITES
OTHER DIRECT

CLINICAL PRESENTATION

MOST FREQUENT
Fever
Myalgias
Nausea & vomiting
Cough

OTHER
-Dizziness
-Arthalgia
-SOB (late course of the dz)

RARE
- Rhinorrhea
- Sore Throat

CLINICAL SIGN
1) TACHYCARDIA
2) TACHYPNEA

DIAGNOSIS

HAEMATOLOGY
- Low platelet
count
- Atypical
lymphocytes
- Inc. HCT
- Inc. WBC

MICROBIOLOGY

Serologydetection of IgM
Ab to sin nombre
virus is a

MANAGEMEN

BIOCHEMISTRY
SUPPORTIVE THERA
- Low albumin
Early aggressiv
- Elevated LDH
intensive care
- Elevated AST/ALT
Early usage of
inotropic agent
(dobutamine)
Early ventilatio
Careful monitor
o Fluid balance
o Oxygenatio
o Blood press
RADIOGRAPHIC
FINDINGS

PREVENT

CONTACT OF
INFECTIOUS MATERIAL
WITH MUCOSAL
MEMBRANES OR
BROKEN SKIN.
VIRUS IS HORIZONTALLY
TRANSMITTED B/W
RODENTS THROUGH
AGGRESSIVE
BEHAVIOURS such as
biting
Can cause Hantavirus
Pulm.Syndromes (HPS) or
Hemorrhagic Fever with
renal Syndromes (HFRS)

HPS
First recognized in Southwestern US
Illness was quickly linked to a newly discovered
hantavirus now known as sin nombre virus
I/P : ( 1-4 weeks)

3) HYPOTENSION
4) CRACKLES ON LUNG
EXAMINATION

Pathogenesis :
Damage the capillaries & small vessels wall resulting
vasodilation & hemorrhages congestion
Damage b/c more severe during hypotensive and
oliguric phases, when widespread hemorrhages occur

mainstray of
diagnosis

IIF,IHC

Western Blot
detection for IgG
& IgM Ab

RT-PCR
(serum/plasma/tis
sue)

Avoid contact with rod

and their habitat
Do not keep rodents a
Keep all food in seal co
Virions may be stable
days on the dry surfa
disinfect (10%) areas
contaminated by rod