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Rhynchyll Faith Bartolaba

April 9, 2018
Sources:
Nelson’s Textbook of Pediatrics 19th Edition
Robbins and Cotran Pathologic Basis of Disease 9th Edition
Jawetz Medical Microbiology 24th Edition
Definition of Terms:
Exanthema: skin rash
Enanthema: rash seen in the mucosa
Other names: Measles, Hard measles, 14-day measles, Morbilli
► An acute viral disease

► Highly contagious

► Measles virus – single-stranded, lipid-enveloped RNA virus in the family


Paramyxoviridae and genus Morbillivirus

► Humans are the only host of measles virus


► The measles vaccine has changed the epidemiology of measles dramatically

► 251 confirmed measles (253.52% higher than the previous year)


► 5 deaths (1.99%)
Source: Department of Health Epidemiology Bureau Public Health Division
Measles-Rubella Cases for January 1-December 2, 2017
► AIRBORNE

► Portal of entry of measles virus is through the respiratory tract or


conjunctivae

► Patients are infectious from 3 days before up to 4-6 days after the onset of
rash

► Approximately 90% of exposed susceptible individuals experience measles


► Measles infection causes necrosis of the respiratory tract epithelium and an
accompanying lymphocytic infiltrate

► Produces small vessel vasculitis on the skin and on the oral mucous membranes.

► Warthin-Finkeldey giant cells: pathognomonic for measles, formed by fusion


of infected cells, with up to 100 nuclei and intracytoplasmic and intranuclear
inclusions
1. Incubation Period

2. Prodromal Symptoms

3. Exanthemous Phase

4. Recovery Period
INCUBATION PERIOD

[EXPOSURE] ► 9-10 days to onset of 1st symptoms


► Rash occurs 14 days after exposure

infection migrates to the regional lymphoid


tissue (multiplies further)

primary viremia disseminates the virus to


the reticuloendothelial system

secondary viremia seeds the epithelial


surfaces of the body, including the skin,
respiratory tract, and conjunctiva, where
focal replication occurs
INCUBATION PERIOD ► Begins after the secondary viremia; associated with
epithelial necrosis, giant cell formation & virus
shedding
PRODROMAL ILLNESS
1. Mild Fever
2. Conjunctivitis and photophobia, coryza, cough, and
increasing fever (40-40.5 C)

► Koplik’s spots: pathognomonic sign of measles


o Appear 1-4 days prior to the onset of rash
o Gray-white, sand grain-sized dots on the buccal mucosa
opposite the lower molars

► Symptoms increase in intensity for 2-4 days until the


1st day of the rash
INCUBATION PERIOD ► With onset of the rash, antibody production begins & viral
replication & symptoms begin to subside

PRODROMAL ILLNESS ► Cephalocaudal pattern; fades in the same pattern

► Red maculopapular eruption: forehead (aroundhehairline),


behind the ears, and on the upper neck
EXANTHEMOUS ► Reaching the palms and soles in up to 50% of cases
PHASE
► Rash becomes map like  hyperpigmented  undergoes
brownish desquamation (sign of true measles)

► Persists 5-6 days


INCUBATION PERIOD ► When the rash appears, symptoms begin to subside.

► Rash fades over 7 days


PRODROMAL ILLNESS
► Cough lasts the longest, up to 10 days

► In severe cases, generalized lymphadenopathy, prominently


EXANTHEMOUS cervical and occipital nodes, may be present.
PHASE

RECOVERY
The diagnosis of measles is almost always based on clinical and epidemiologic
findings.

Laboratory Tests:

► Isolation of measles virus from a clinical specimen(e.g., nasopharynx,


urine) -still the gold standard

► Positive serologic test for measles IgM antibody


1. Penumonia – most common cause of death in measles
2. Croup, tracheitis, and bronchiolitis – most common complications in infants and
toddlers
3. Acute Otitis Media – most common complication
4. Sinusitis and mastoiditis
5. Febrile seizures – in <3% of children with measles
6. Measles Encephalitis
7. Hemorrhagic/Black Measles – hemorrhagic skin eruption; often fatal
8. Myocarditis – rare
9. Measles Subacute Sclerosing Panencephalitis

► Fatal degenerative disease of central nervous system


► Chronic complication of measles
► Result from a persistent infection with an altered measles virus that is
harbored intracellularly in the CNS for several years
► Change in personality, gradual onset of mental deterioration & myoclonus
► Measles vaccination protects against SSPE
1. Management of measles is supportive

2. Maintenance of hydration, oxygenation, and comfort are goals of


therapy.

3. Antipyretics for comfort and fever control are useful.

4. Vitamin A supplementation-reduced morbidity and mortality from


measles

Single dose of 200,000 IU orally for children ≥1 yr of age (100,000 IU for


children 6 mo–1 yr of age and 50,000 IU for infants <6 mo of age)
Isolation
from 7 days after exposure to 4-6 days after the onset of rash

Vaccine or immunoglobulin
vaccine is effective in prevention or modification of measles only if given within
72 hr of exposure. Immunoglobulin may be given up to 6 days after exposure to
prevent or modify infection.

Immunoglobulin
for susceptible household contacts younger than 6 months of age, pregnant women
& immunocompromised persons

Immunization during an outbreak


immunize infant as young as 6 months of age; additional dose at 12-15 months of age
Other names: German Measles, 3-day measles
► Mild exanthemous disease of infants and children

► Young children rarely have prodromal symptoms

► Major clinical significance: fetal damage as part of the congenital rubella syndrome

► Transmission: Oral droplet, Transplacental

► Droplet infection can only be transferred within 3 feet

► Peak incidence: 5 – 14 years


► Rubella virus is a member of the family
Togaviridae; only species of the genus Rubivirus.

►Single-stranded RNA virus with a lipid


envelope and 3 structural proteins
► 448 confirmed rubella (187.21% higher than the previous year)
Source: Department of Health Epidemiology Bureau Public Health Division
Measles-Rubella Cases for January 1-December 2, 2017
Incubation Period

► 14-21 days
► Rash occurs 17 days after exposure
► Viremia: most intense 10 to 17 days after infection
► Viral shedding from the nasopharynx begins about 10 days after infection
► Period of highest communicability: 5 days before to 6 days following
appearance of the rash.

Prodrome

► Low-grade fever, malaise, anorexia, lymphadenopathy


► In adolescents and adults: eye pain, sore throat, headache
► Most characteristic sign:
ü RETROAURICULAR LYMPHADENOPATHY
ü POST CERVICAL LYMPHADENOPATHY
ü POSTOCCIPITAL LYMPHADENOPATHY

► Exanthem: erythematous, maculopapular and discreet


starts centrally and spreads centrifugally
o 2nd day: pinpoint appearance on the trunk
o 3rd day: eruption clears

► Rash is less prominent than with measles and pruritic


particularly in adults
► Enanthem: Discrete rose spots on the soft palate (Forchheimer spots) coalesce
as a red blush extended over the face

► Other clinical manifestations:


o Pharyngitis: pharyngeal mucosa and conjunctiva slightly inflamed.
o No photophobia
o Temperature elevation not marked (LOW-grade fever x1-3 days)
1. JOINT INVOLVEMENT
► Arthralgia and arthritis are the most common complications in adolescents and
adults.

2. THROMBOCYTOPENIA
► Rare complication, occurring in 1 on 3000 cases

3. NEUROLOGIC MANIFESTATIONS
► Encephalitis is a rare complication and occurs with greater frequency in children.

4. MILD HEPATITIS
► Rarely reported complication of rubella

5. PROGRESSIVE RUBELLA PANENCEPHALITIS (PRP)


► Extremely rare complication of either acquired rubella or CRS;
► PRP rubella virus may be isolated from brain tissue, suggesting an infectious
pathogenesis, albeit a “slow” one;
► Death occurs 2–5 yr after onset
► Result of in utero fetal infection

► Acquiring the infection within the first 8 weeks of pregnancy gives the highest
risk for congenital abnormality.

► Patent Ductus Arteriosus is the most common congenital heart disease associated
with rubella.

► Classical CRS triad: cataract, sensorineural hearing loss & congenital heart
disease
► Supportive history of exposure or consistent clinical findings
► Rubella specific IgM enzyme immunosorbent assay (4-72 days)
► Fourfold rise in IgG in sequential sera
► Rubella virus culture from nasopharynx & blood by tissue culture system or PCR

WHO definition of PROBABLE infection:


fever, maculopapular rash, lymphadenopathy or arthralgia/arthritis

WHO definition of CONFIRMED infection:


probable case with IgM positivity within 28 days of onset of rash
TREATMENT
► Supportive Care
►If rash is really itchy, give an antihistamine

PREVENTION
► MMR Vaccine:
o 12 – 15 months
o 2nd dose: 4- 6 years
§ 4-6 years is when the child is again brought to the pediatrician
before schooling to update with immunizations.
o Females should be advised not to become pregnant 3 months
after receiving rubella vaccine
Other names: tigdas hangin”, exanthema subitum, “sudden rash”,
rose rash of infants, sixth disease
► Human Herpes virus 6 (HHV-6): major cause of illness

► Illness non-seasonal but peaks reported during summer (In the


Philippines: December-June)

► Peak age incidence: 7 to 13 months (virtually all cases in less than 2 years
old)

*HHV 7: similar type of exanthema

► HHV-6 and HHV-7 are the sole members of the Roseolovirus


genus in the Betaherpesvirinae subfamily of human herpesviruses
► Primary infection with HHV-6: ALL children following loss of maternal antibodies

► Peak age: 6-9 months

► Transmission: transplacental and chromosomal integration (86% of infections)


► Abrupt onset of high grade fever; resolves in 72h and gradually fade with the
appearance of rash

► Rash: faint pink or rose-colored, nonpuritis, 2-3mm morbilliform rash on the trunk;
lasts for 1-3 days
► History of: infant (6-12 months), high grade fever esp. at night (39-
40C), CBC is normal; after 3-4 days of fever, once the patient started to
have rashes, the fever will disappear

► Viral culture – gold standard


► Supportive care

► Maintain hydration

► Use antipyretics for fever


RUBEOLA RUBELLA ROSEOLA
True Measles German Measles Tigdas Hangin

(+) cough and coryza, fever, LGF (+) spiky fever (39-40)
conjunctivitis (+) preauricular nodes (+) BFS

RASH: RASH: RASH:


(+) desquamation Disappears on the 3rd day Fever disappears on rash
Cephalocaudal pattern Starts centrally and onset
spreads centrifugally Cephalocaudal Pattern

ENANTHEM: ENANTHEM:
(+) Koplik spots (+) Forchheimer spots
Occurs in <13 months old
Other names: Chicken Pox
►Primary infection – manifested as varicella (chicken pox); establishes a
lifelong latent infection of sensory ganglion neurons

► Reactivation of latent infection – causes herpes zoster (shingles)


► VZV is a neurotropic human
herpesvirus with similarities to
herpes simplex virus

► Enveloped with double-stranded DNA


genomes that encode
more than 70 proteins
► Transmission: oropharyngeal secretions and fluid of skin lesions by airborne
spread or direct contact

Incubation period
(10-21 days): During the late Host immune
replication in the local incubation period-VZV responses limit viral
lymphoid tissue transported back to the replication and
primary viremia  mucosa of the upper facilitate recovery from
disseminates the virus respiratory tract & infection
to the oropharynx, permitting
reticuloendothelial spread to susceptible Immunocompromised
system  secondary contacts 1-2 days child-continued viral
viremia spreads virus before the replication -
to body surfaces appearance of rash disseminated infection
leading to widespread
cutaneous lesions
►14-16 days post exposure

► Prodromal symptoms: fever, malaise, anorexia, headache, abdominal pain 24-48h


before rash
► Systemic symptoms resolve within 2-4 days after rash onset

► Order of appearance: scalp face  trunk

► Rash: intensely pruritic erythematous macules  papular stage  clear fluid-filled


vesicles  clouding and umbilication of lesions in 24-48h  crusting

► Distribution of the rash: central or centripetal

► At any point in time, lesions in various stages are observed


► Transmission: airborne, contact

► Most contagious 1-2 days before and shortly after onset of rash

► Airborne and contact precautions:


o Minimum of FIVE days after onset of rash and as long as the rash remains
VESICULAR.
► In infants born to women who have varicella before 20 wk of gestation

CHARACTERIZED BY:
►Cicatricial skin scarring in a zoster-like distribution, limb hypoplasia
► Neurologic abnormalities: microcephaly, cortical atrophy, seizures & mental
retardation
► Eye abnormalities: chorioretinitis, microphthalmia & cataracts
► Renal abnormalities: hydroureter & hydronephrosis
► Autonomic nervous system abnormalities: neurogenic bladder, swallowing
dysfunction & aspiration pneumonia
► CLINICAL

► Leukopenia during the 1st 72 hours after onset of rash; followed by a


relative & absolute lymphocytosis

► Elevated hepatic enzymes

► Specific diagnosis of VZV infection: needed in immunocompromised


children
► Bacterial superinfection of skin lesions (usually seen in pediatric
patients due to scratching: itch-scratch-itch cycle) due to S. pyogenes or
flesh-eating bacteria

► Thrombocytopenia
► Arthritis
► Hepatitis
► Cerebellar ataxia, encephalitis, meningitis
► Glomerulonephritis
► Normal adults: benign in children; complicated in adults and scabs are deeper

► Immunocompromised persons

► Newborns with maternal rash onset within 5 days before to 48 hours after
delivery
► Supportive treatment for fever & itching

Indications for acyclovir in children:


► Malignancies
► Chmotherapy or high dose steroid treatment
► HIV infection
► Severe varicella
► Chronic skin disease
► Long term salicylate therapy
► Chlidren >12 years
Treatment should be initiated within 24 hr of the onset of rash
ACTIVE IMMUNIZATION: VARICELLA VACCINE

FOR CHILDREN
► 2 doses
o 1st dose: 12 months
o 2nd dose: 4-6 years old (can be given as early as 15 months of age)
o Children < 12 years: 3 month interval
o Children > 12 years: 4 weeks interval

FOR ADOLESCENTS AND ADULTS


► 2 doses, 4-8 weeks apart
► one of the more distinctive rash syndromes

► most frequently caused by coxsackievirus A16, sometimes in large


outbreaks

► can also be caused by enterovirus 71; coxsackie A viruses 5, 7, 9, and


10; coxsackie B viruses 2 and 5; and some echoviruses

► Mode of transmission: person-to person, oral-fecal route, respiratory


route, vertical transmission

► Incubation period: 3-6 days


► usually a mild illness, with or without low-grade
fever

► oropharynx is inflamed and contains scattered


vesicles  ulcerate (4- to 8-mm shallow lesions
with surrounding erythema)

► Lesions on the hands and feet:


tender, 3- to 7-mm vesicles that occur more
commonly on dorsal surfaces

► Vesicles resolve in about 1 wk


► May be diagnosed clinically based on characteristic findings

► Lab tests unnecessary: Viral culture, PCR


► Supportive
► Family Herpesviridae

► Double-stranded linear DNA

► Covered by lipid bilayer envelope that


contains ~12 viral glycoproteins (viral DNA
polymerase and thymidine kinase)
► Only natural host: humans

► Mode of transmission: Direct contact between mucocutaneous surfaces

► HSV-1 – oral infections; from contact with contaminated oral secretions

► HSV-2 – genital infections; from anogenital contact

► High prevalence in developing countries and lower socioeconomic groups

Neonatal Herpes
► uncommon but potentially fatal infection of the fetus or newborn
► >90% of cases are the result of maternal-fetal transmission
► infants born to dunally infected mothers (HIV & HSV-2) are at higher risk of
acquiring HIV than those born to mothers with HIV only
PRIMARY INFECTION
► not been previously infected with either HSV-1 or HSV-2

NONPRIMARY FIRST INFECTION


► previously infected with one type of HSV who have become infected for
the first time with the other HSV
► less severe than true primary infection

RECURRENT INFECTION
► reactivation of the latent status of HSV
► Symptomatic – less severe, shorter duration than first infections
► Asymptomatic – no physical distress but contagious
Cutaneous portal of entry

Local replication Enter nerve endings

Inflammatory reactions Spread to sensory ganglia by


intraneuronal transport

VESICLES AND ULCERS

Virus replicate in Neurons do not


sensory neurons support replication

Replicate
further in Progeny virions sent Virus established
skin/mucosal back to the periphery latent infection
surfaces

Reactivation
(upon trigger)

Progeny virions produced and


transported to nerve fibers
HSV Infection in Newborns
► complicated by their immunologic immaturity
► Transmission: generally during delivery
► Most common points of entry: conjunctivae, mucosal epithelium of the nose and
mouth, breaks or abrasions in the skin during forceps delivery or scalp electrode
use
► Virus may extend to the respiratory tract  penumonia; CNS  encephalitis;
hematogenous route  visceral organs and brain
► HALLMARK: skin vesicles and shallow ulcers
► 2-4mm vesicles surrounded by an erythematous base (days)  shallow,
minimmaly erythematous ulcers
Presentations:

1. Acute Oropharyngeal Infections


2. Herpes Labialis
3. Cutaneous Infections
4. Genital Herpes
5. Occular Infections
6. Central Nervous System Infections
7. Infections in Immunocompromised Persons
8. Perinatal Infections
Acute Oropharyngeal Herpes Labialis Cutaneous Infections Genital Herpes
Infections
Herpes Gingivostomitis HSV-1 infection: -symptoms similar to -common in sexually
-6mo to 5yr old -fever blisters/cold sores herpes labialis but experienced adolescents
-Sudden onset, pain in (most common) on the involves a larger surface and young adults
mouth, drooling, refusal vermilion border of the area -shed virus in anogenital
to eat, 40-40.5C, swollen lip sites
gums, (+) vesicles -burning, tingling, Herpes -local burning and
extensively distributed itching, pain 3-6h before gladiatorum/scrumpox tenderness  vesicles
 ulcers covered with lesion -in healthy individuals develop
yellow gray membrane -ulcers are short lived -if severe: (+)urinary
-Resolves in -14 days and dries and develops a Herpes whitlow retention, bilateral,
(untreated) crusted scab -HSV infection of fingers tender inguinal and
-complete healing in 6- and toes pelvic lymphadenopathy,
Pharyngitis & Tonsillitis 10days discharges
-older children to college - At least 1 recurrent
-course of illness longer infection the following
than untreated Strep year
pharyngitis
Occular Infections CNS Infections Infections in Perinatal Infections
Immunocompromised
Persons
-involved the -leading cause of Most common -may be acquired in
conjunctiva, cornea, or sporadic, nonepidemic presentations: utero, during the birth
retina encephalitis in the USA mucositis, esophagitis process, or during
-may be primary or -acute necrotizing neonatal period
recurrent infection, Atypical lesions: slowly -risk increases in infants
-unilateral, associated frontal/temporal cortex enlarge, ulcerate, become born to mothers with
with blepharitis & tender and limbic system necrotic, and extend to primary infection
preauricular -nonspecific findings: deeper tissues -clinical presentation
lymphadenpathy fever, headache, nichal reflects timing of
-Vesicular lesions on the rigidity, nausea, Other infections: infection, portal of entry
lid margins and vomiting, generalized Tracehobronchitis, and extent of spread
periorbital skin seizures, alteration of pneumonitis, anodenital
-Resolves in 2-3 weeks consciousness infections
(untreated)
Perinatal Infections

Intrauterine infection: skin vesicles, chorioretinites, keratoconjunctivitis

Infected during delivery or postpartum: present with one of the ff


1. Disease localized in the skin, eyes, or mouth – present at day 5-11; may progress to
encephalitis or disseminated infection if not treated

2. Encephalitis with or without SEM disease – present at day 8-17; skin vesicles in 60% of
cases

3. Disseminated infection involving multiple organs (brain, lungs, liver, heart, adrenals,
skin) – present at day 5-11; clinical picture siimlar to bacterial sepsis; skin vesicles in 75% of
cases
► Isolation of virus or viral DNA detection by polymerase chain reaction (PCR)

► HSV IgM tests – notoriously unreliable

► Virus culture – GOLD STANDARD

► HSV-2 type-specific antibody tests for sexually active young adults with
recurrent nonspecific urogenital signs and symptoms
► Acyclovir, valacyclovir, famciclovir

► Prevent skin-to-skin contact or contact with contaminated secretions