Dengue

Varicella Zoster
Rubella
Rubeola
Clinical Clerk Aljane Mae F. Manalo
Objectives
1. Discuss the epidemiology, etiology, and
transmission of Dengue, VZV, Rubella, and Rubeola

2. Learn the pathophysiology of the diseases

3. Discuss the clinical manifestations of every disease

4. Discuss the diagnosis and management of each

disease

5. Discuss the prevention of these viral diseases

Contents

01 02 03 04 05
Dengue Varicella Rubella Rubeola Summary
Zoster
I. Dengue
Introduction
- most common insect-transmitted
virus in the world
- “breakbone” fever
- Dengue viruses 1–4
- nonhuman primates, mosquitoes
- Aedes aegypti, A. albopictus
Epidemiology
o >40% of the world’s population is
at risk of dengue infection

o 390 million dengue infections occur

around the world

o 500,000 cases develop into severe

dengue, or dengue haemorrhagic
fever
SPECTRUM OF DENGUE INFECTION

- 4 to 7 days incubation period

- asymptomatic or have a
spectrum of illness

- systemic and dynamic disease

with clinical, haematological and
serological profiles changing from
day to day
CLINICAL COURSE

i. Febrile Phase
- high grade fever
- last 2-7 days
- facial flushing, rash, generalised body ache,
vomiting and headache

- petechiae & mucosal membrane bleeding

- progressive decrease in total white cell
count followed by platelet reduction
CLINICAL COURSE
ii. Critical Phase
- around defervescence; lasts about 24-48h
- thrombocytopaenia and haemoconcentration

- clinical manifestations:
ü abdominal pain
ü persistent vomiting
ü diarrhoea
ü restlessness
ü altered conscious level
ü clinical fluid accumulation
ü mucosal bleed or tender liver
CLINICAL COURSE

iii. Recovery/Reabsorption Phase

- 24-48 hours after critical phase

- improves, appetite returns, GI
symptoms improve,
haemodynamic status
stabilises and diuresis ensues

- “isles of white in the sea of red”

- HCT level stabilises
- WBC count normalizes first
Pathophysiology of Plasma Leakage in
Severe Dengue
- acute increase in vascular permeability
- haemoconcentration and hypovolaemia or
shock

Clinical manifestations of vasoconstriction:

v Skin - coolness, pallor and delayed capillary refill time

v Cardiovascular system - raised diastolic blood pressure and a

narrowing of pulse pressure

v Renal system - reducing urine output

v Gastrointestinal system - persistent vomiting, persistent

diarrhoea and abdominal pain

v Central nervous system – lethargy, restlessness, apprehension,

reduced level of consciousness

v Respiratory system – tachypnea

WHO Classification 2009
This classification addresses the levels of severity of dengue infection which is more practical
to be used in the management decision of the patient
Diagnosis
- rapid combo tests
- ELISA
NS1 antigen
dengue IgM/IgG antibodies
- real time RT-PCR
- dengue viral isolation assay
Management
Group A — Patients are sent home

Group B — Patients are referred for hospital

management

Group C — Patients are admitted for

emergency treatment and intensive care
Group A
- provide appropriate guidance about
caring for the patient at home including:
ü Typical clinical course
ü Warning signs
ü When to follow up
ü Request daily follow-up visits
• patient’s hemodynamic status
• look out for the critical phase
• medical complications
• presence of warning signs
• CBC
Group A
• Control the fever
✓ Acetaminophen q6h
✓ Tepid sponging

• Prevent dehydration
>5 glasses of water, milk, or fruit juices

• Prevent spread of dengue within the house

• Watch for warning signs as temperature

declines 3 to 8 days after symptoms began
Group B
-warning signs
- without warning signs but with
co-existing conditions
- social circumstances
- referring facility has no capability
to manage dengue with
warning signs and/or severe
dengue
Group B
Without Warning Signs

ü Encourage oral fluids

- If not tolerated, start I.V. fluid
therapy of 0.9% saline or Ringer
Lactate w/ or w/o dextrose at
maintenance rate
- Patients may be able to take oral
fluids after a few hours of I.V. fluid
therapy
Group B
With Warning Signs
• reference HCT

• give only isotonic solution

o Start with 5-7 ml/kg/hr for 1-2 hrs, then
o reduce to 3-5 ml/kg/hr for 2-4 hrs, then
o reduce to 2-3 ml/kg/hr or less

• reassess the clinical status and repeat the HCT

• HCT remains the same or rises only minimally,
continue same rate for another 2-4 hours
• worsening of vital signs and rapidly rising HCT,
increase the rate to 5-10 ml/kg/hour for 1-2 hours
• Reassess the clinical status, repeat HCT and
review fluid infusion rates accordingly
Group B
• give IV fluids required to maintain good perfusion
and urine output of at least 0.5 ml/kg/hr

• reduce IV fluids gradually when the rate of plasma

leakage decreases towards the end of the critical
phase

Indicated by:
ü adequate urine output and/or oral fluid intake
ü HCT decreases
Group C
Severe dengue

• Severe plasma leakage with shock and/or

fluid accumulation with respiratory distress
• Severe bleeding
• Severe organ impairment
• Severe liver involvement (inc AST and ALT)
• Impaired consciousness (GCS<15 or BCS<5)
Hemorrhagic Complication
- result of endothelial activation
- thrombocytopaenia and coagulation activation

SEVERE BLEEDING
Unstable hemodynamic status + any of below:
• persistent and/or severe overt bleeding
• decreased HCT after fluid resuscitation
• hypotensive shock with low/normal HCT before
fluid resuscitation
• shock is refractory if isotonic fluid of > 40-
60mL/kg has been administered
• Persistent metabolic acidosis ± a normal systolic
blood pressure
DISCHARGE CRITERIA

The following should be taken into consideration

before discharging a dengue patient:

ü improved general well-being

ü afebrile for 24-48 hours
ü rising white cell count followed by platelet
ü stable haematocrit
ü resolution or recovery of organ dysfunction
Prevention
Enhanced 4S Strategy
S - earch and Destroy
S - eek Early Consultation
S - elf Protection Measures
S - ay yes to fogging only during outbreaks

VACCINE
DENGVAXIA???
- live attenuated tetravalent chimeric vaccine
- indicated for the prevention of dengue
- approved for use in individuals 9-16 years of
age with laboratory-confirmed previous dengue
infection and living in endemic areas
II. Varicella Zoster
Introduction
- varicella (chickenpox) and herpes
zoster (shingles)

- chickenpox: ubiquitous and

extremely contagious
- benign illness of childhood
- exanthematous vesicular rash

- herpes zoster : reactivation

- dermatomal vesicular rash
- severe pain
Etiology
- Herpesviridae
- structural characteristics:
lipid envelope surrounding a
nucleocapsid with icosahedral
symmetry
diameter of ~180–200 nm
centrally located dsDNA (~125,000bp)

- eosinophilic intranuclear inclusions and

multinucleated giant cells
Pathophysiology
PRIMARY INFECTION
- respiratory route
- localized replication of the virus in nasopharynx
- seeding and development of viremia
- diffuse and scattered nature of the skin lesions
- presence of cloudy vesicular fluid
-vesicles either rupture and release their fluid
or are gradually reabsorbed
Pathophysiology
RECURRENT INFECTION
- infects dorsal root ganglia

-Histopathologic examination:
hemorrhage, edema, lymphocytic infiltration
- Pulmonary involvement :
interstitial pneumonitis, multinucleated giant
cell formation, intranuclear inclusions, and
pulmonary hemorrhage
- CNS infection:
perivascular cuffing
CHICKENPOX

- humans are the only known reservoir for VZV

- highly contagious and both sexes and all races
- incubation ranges from 10 to 21 days
- patients are infectious at:
ü ~48h before vesicular rash onset
ü during the period of vesicle formation
ü until all vesicles are crusted
Clinical Manifestations

Rash Low grade fever Malaise

Complications
Secondary Bacterial Superinfection of the Skin
- most common infectious complication of varicella
- S. pyogenes or S. aureus
- excoriation
- Gram's staining

CNS
- most common extracutaneous site in children
- syndrome of acute cerebellar ataxia and meningeal
inflammation appears ~21 days after onset of the rash

Varicella Pneumonia
- most serious complication and more often in adults
- severe in pregnant women
- onset 3–5 days into the illness
- tachypnea, cough, dyspnea, and fever
HERPES ZOSTER

- aka as “shingles”
- reactivation of latent VZV
- no history of recent exposure to dse
- incidence is highest among individuals
in the sixth decade of life and beyond
Clinical Manifestations
-unilateral vesicular dermatomal
eruption associated with severe pain
- T3 to L3
- heralded by pain within the
dermatome, which may precede
lesions by 48–72 h
- lesions may remain few and
continue to form for only 3–5 days
- 7–10 days duration but may take as
long as 2–4 weeks for the skin to
normalize
erythematous maculopapular rash
evolves rapidly into vesicular lesions
Clinical Manifestations
- ophthalmic branch of the
trigeminal nerve is involved

- lesions may appear on the

face, in the mouth, in the
eye, or on the tongue

- usually a debilitating
condition that can result in
blindness in the absence of
antiviral therapy
Zoster ophthalmicus
Clinical Manifestations

- pain and vesicles appear in

the external auditory canal
- patients lose their sense of
taste in the ant. 2/3 of tongue
-ipsilateral facial palsy
- geniculate ganglion of the
sensory branch of the facial
nerve is involved

Ramsay-Hunt Syndrome
Acute neuritis and postherpetic neuralgia
- most debilitating complication in IMCH

Meningoencephalitis
- headache, fever, photophobia, meningitis, and vomiting

Granulomatous angiitis
- rare; contralateral hemiplegia, which can be diagnosed
by cerebral arteriography
 - more severe in immunocompromised

- lesions continue to form for >1wk

- scabbing is not complete in most

cases until 3 weeks into the illness

- patients with Hodgkin’s disease

and non-Hodgkin’s lymphoma are at
greatest risk for progressive herpes
zoster
Cutaneous dissemination develops in ~40% of
immunocompromised patients.
Laboratory Findings
- isolation of VZV in susceptible tissue-culture cell lines
- demonstration of seroconversion or rise in Ab titer
- detection of VZV DNA by PCR

Specimens for PCR: lesions, blood, and saliva

Tzanck smear
- scraping of the base of the lesions
- multinucleated giant cells
- low sensitivity (~60%)

The most frequently employed serologic tools:

1. Immunofluorescent detection of antibodies to VZV mem Ag
2. fluorescent antibody to membrane antigen (FAMA) test***
3. immune adherence hemagglutination
4. enzyme-linked immunosorbent assay (ELISA)***
Treatment
Chickenpox

- good hygiene: daily bathing and soaks

- meticulous skin care
- topical dressings or antipruritic drugs
- tepid water baths and wet compresses
- aspirin should be avoided

-Acyclovir (800 mg five times daily)

valacyclovir (1 g three times daily)
famciclovir (250 mg three times daily)
-for 5–7 days is recommended for
adolescents and adults with chickenpox of
≤24 h duration
Treatment
Herpes Zoster
- Aluminum acetate soaks
- oral antiviral therapy
- Acyclovir 800 mg five times daily for 7–10d

- Valacyclovir: accelerates healing and

resolution of zoster-associated pain

- zoster ophthalmicus should be referred

immediately to an ophthalmologist
Prevention

Live Attenuated Varicella-Zoster

Varicella immune globulin Prophylaxis
Vaccine (VZIG)
- individuals who are - beyond the 96-h window
- recommended for all
susceptible, are at high risk after direct contact
children >1 year of age (up
for developing -Therapy 7 days after
to 12 years of age) who
complications of varicella, intense exposure
have not had chickenpox
and had a significant
and for adults known to be
exposure
seronegative for VZV
- should be given within 96h
(within 72 h) of the
exposure.
III. Measles
Rubeola
Introduction

- highly contagious viral disease

- prodromal illness of fever, cough,
coryza, and conjunctivitis
- followed by the appearance of a
generalized maculopapular rash
Etiology
- spherical, nonsegmented, ssRNA virus

- Morbillivirus genus, Paramyxoviridae family

- antigenically monotypic virus

- killed by ultraviolet light and heat

Epidemiology
- one of the most highly contagious
- directly transmitted pathogens
- infectious for several days before
and after the onset of rash
- household contacts, school-age children,
and health care workers
- maintenance of a high index of suspicion
- use of appropriate isolation precautions
- administration of measles vaccine
Pathogenesis
- respiratory droplets
- aerosols suspended in the air
- airborne transmission
- direct contact with infected secretions but
does not survive for long on fomites
- incubation period for measles is ~10 days to
fever onset and 14 days to rash onset
- shorter in infants and longer in adults
Pathogenesis

Initiation Day 2-4 Day 5-7 Day 8-12

-deposited -proliferates locally - further replication - replication in target

in the RT, in the respiratory - secondary viremia organs, together with
oropharynx, mucosa, primarily -spread throughout the host’s immune
or in dendritic cells response, is
the body responsible for the
conjunctivae and lymphocytes,
signs and symptoms
-spreads to after infection
draining LN - mark the end of the
- primary viremia incubation period
- infection in RES
Approach to the Patient

ü fever and generalized erythematous rash

ü recent outbreak or history of travel to endemic areas
ü precautions to prevent nosocomial transmission
ü laboratory confirmation for diagnosis
ü supportive treatment
ü administration of vitamin A and antibiotics

Complications:
secondary bacterial infections and encephalitis
Clinical Manifestations

- fever and malaise ~10 days after exposure

- 3Cs: cough, coryza, and conjunctivitis

- Koplik’s spots ~2 days before the rash

- rash begins 2 weeks after infection

- headache, abdominal pain, vomiting,

diarrhea, and myalgia
Clinical Manifestations

Koplik’s spots

- are pathognomonic of measles

- bluish white dots ~1 mm in diameter
- surrounded by erythema
- appear first on the buccal mucosa
opposite the lower molars
- they fade with the onset of rash
Clinical Manifestations

- erythematous macules
- behind the ears, neck and hairline
- face, trunk, and arms; legs & feet
- areas of confluent rash:
trunk & extremities
- petechiae may be present
Diagnosis

The CDC case definition for measles:

(1) gen. maculopapular rash at least 3 days duration
(2) fever of at least 38.3°C (101°F)
(3) cough, coryza, or conjunctivitis

- serology is the most common method

- detection of measles virus–specific IgM* or a
fourfold/greater increase in measles virus–specific
IgG antibody levels
- antibodies that are detectable within 1–3 days of
rash onset and reach peak levels in 2–4 weeks
Diagnosis

- neutralization tests are sensitive and specific

- enzyme immunoassays are most frequently used
- cell culture from respiratory secretions,
nasopharyngeal or conjunctival swabs, blood, or urine
- direct detection of giant cells by biopsy
- RT-PCR
Treatment
- no specific antiviral therapy for measles
- general supportive measures: hydration and antipyretic
- antibiotic treatment
- Vitamin A: once-daily doses of 200,000 IU for 2
consecutive days to all children with
measles who are ≥12 months of age
- 100,000 IU/day for children 6–12 months of age
- 50,000 IU per day for children <6 months old
Complications
§ Acute laryngotracheobronchitis (croup)
§ Giant-cell pneumonitis
§ Diarrhea
§ Secondary bacterial infections
§ Otitis media and bronchopneumonia are most common
§ Post-measles encephalomyelitis
§ Encephalomyelitis - occurs within 2 weeks of rash onset
and is characterized by fever, seizures, and a variety of
neurologic abnormalities
§ Measles inclusion body encephalitis (MIBE) and subacute
sclerosing panencephalitis (SSPE)
Prevention
Passive Immunization
- Human immunoglobulin: administration within 72h
- administered up to 6 days after exposure
- prophylaxis is recommended
- dose is 0.25 mL/kg given intramuscularly
- usual dose of 100–400 mg/kg
- immunocompromised: 0.5 mL/ kg
Prevention
Active Immunization
- inactivated by light and heat
- lose about half their potency at 20°C and
almost all their potency at 37°C

- Antibodies first appear 12–15 days after

vaccination and titers peak at 1–3 months

- often combined with other live attenuated virus

vaccines: MMR and MMR-V

- recommended age: 6 to 15 months

IV. German Measles
Rubella
Etiology
- Togaviridae family, genus Rubivirus
- ssRNA enveloped virus
- 40–80 nm
- single-layer lipoprotein envelope with
spike-like projections containing E1 and E2
- only one antigenic type of rubella virus
- humans are its only known reservoir
Pathophysiology
- person to person
- respiratory droplets
- primary implantation & replication: nasopharynx
- spread to the lymph nodes -> viremia
- clinical and subclinical infections are contagious
- Infants with CRS may shed large quantities of virus from
bodily secretions (throat and urine) up to 1 year
Epidemiology
- no longer endemic
- important public health problem globally
- underestimated because it is often mild
- despite an increase in countries with rubella
vaccination programs, more than half of the world’s
children remained unvaccinated against rubella
Clinical Manifestations
Acquired Rubella
- generalized maculopapular rash lasts up to 3d
- In children, rash is usually the first sign of illness
- in older children and adults:
a 1- to 5-day prodrome often precedes
the rash and may include low-grade
fever, malaise, and upper respiratory
symptoms
- incubation period is 14 d (12-23d)
- occipital and postauricular lymphadenopathy
- arthralgia and arthritis
- thrombocytopenia and encephalitis
Clinical Manifestations
Congenital Rubella Syndrome
- most serious consequence
- particularly during the first trimester
- complications:
miscarriage
fetal death
premature delivery
congenital defects

- most commonly relate to the eyes,

ears, and heart (TRIAD: deafness,
cardiac abn, and cataract)
Clinical Manifestations
Congenital Rubella Syndrome
- thrombocytopenia with purpura/petechiae
- “blueberry muffin syndrome”

- “infants w/ congenital rubella infection only”

infants with congenital rubella virus
infection with no apparent
signs/symptoms of CRS
Diagnosis: Acquired Rubella
Laboratory
Documentation:
Serologic and Virologic Methods
-Serologic diagnosis is most
common
- IgG and IgM
Mature (high avidity)
IgG Antibodies
- most likely indicate an infection
occurring at least 2 months
previously - this test helps
distinguish primary infection
from reinfection
ELISA IgM capture technique
- most accurate
- IgM up to 6weeks detected
- Acute disease: IgG Ab titer
~specimen collected 7-
10 days after onset of
illness
~convalescent phase
specimen: 14-21 days
after the 1st specimen
Low avidity antibodies
- indicate recent infection.
Diagnosis: Acquired Rubella
- isolated from the blood and
nasopharynx during prodromal period

- 2 weeks after rash onset

- secretion of virus is maximal before or

up to 4 days after rash onset

- viral RNA detection in a RT-PCR assay

Diagnosis: Congenital Rubella Syndrome

classic triad of CRS:

cataracts
hearing impairment
heart defects

- hearing impairment: most common single defect

- serologic assays and virus detection
- serum IgM antibodies: 6mos- 1yr
- serum IgG titer: passive transfer of maternal IgG
- throat swabs
- can be detected by RT-PCR
Diagnosis: Pregnant women

- (+) IgG antibody are considered immune

- vaccination postpartum for susc. patients

- IgM and/or IgG test after exposure

- clinically monitored and gestational age

- assess the possibility of risk to the fetus

- first 11 weeks of gestation: 90% having CRS

Treatment
- no specific therapy
- symptom-based treatment
- Immunoglobulin does not prevent rubella
virus infection after exposure
Ø exposed pregnant woman will not
consider termination of the pregnancy
under any circumstances

- IM administration of 20 mL of Ig w/in 72 h of
rubella exposure may reduce—but does not
eliminate the risk of rubella
Prevention
- vaccination with an RCV
- immunity is long-term and
probably lifelong
- RA27/3 virus strain
- pregnancy should be
avoided for 28 days
after receipt of RCV
 Summary
DENGUE VZV RUBEOLA RUBELLA

Other names Breakbone fever Chickenpox Measles German Measles

Shingles

Etiologic agent Dengue virus Varicella-zoster Rubeola virus Rubella virus

Mode of transmission Bite of an infected Respiratory Respiratory Respiratory

Aedes spp.

Incubation 5-7 d 10-21 d 10d to fever onset 14 d

and 14 d to rash
onset

Rash Isles of white in a sea vesicular rash maculopapular in maculopapular

of red -trunk and face cephalocaudal
Herman's rash -diff stages distribution

Fever 1st sign 1-2 d before rash 4d before rash 1-5d before rash
Thank you for listening!
Do you have any questions?

References
§ Harrison's Principle of Internal Medicine, 20th edition
§ CPG for Dengue 2015, 3rd edition
§ https://www.doh.gov.ph/national-dengue-prevention-and-control-program
§ https://www.cdc.gov/dengue/training/cme/ccm/page45744.html