Measles, Rubella and Other Viral Skin Infections

1/26/2021
MEASLES, RUBELLA AND

OTHER VIRAL SKIN
INFECTIONS
Professor (Chief) Patrick Akpaka MBBS, DM
Dept. of Paraclincal Sciences
Faculty of Medical Sciences
The UWI, St. Augustine
Objectives of the lectures

• Describe the Structure, epidemiology, aetiology and
pathogenesis of specific viral infections
• Discuss the predisposing and risk factors for such
infections if any
• Discuss the clinical features of the mentioned viral
infections
• List and discuss the laboratory methods for confirming
the organisms
• Discuss the treatment, prevention and complication of
the viral infection
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OUTLINE
• Background
• Epidemiology
• Pathogenss
• Clinical Manifestations
• Laboratory Diagnosis
• Treatment
• Prevention and Complications
Paramyxovirus
Members of the
Paramyxovirus family of
viruses are negative sense
single-stranded RNA
viruses responsible for a
number of human diseases.
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Paramyxovirus
The family is divided into 3 genera:
• Paramyxovirus: Parainfluenzavirus 1-4;
causes pneumonia, bronchitis and croup,
especially in children, and Mumps
• Pneumovirus: Respiratory Syncytial Virus
(RSV), causes pneumonia
• Morbillivirus: Measles; Canine Distemper
Virus.
• Morphologically – refer to next slide
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Replication
Very similar for all viruses in this group.
Unlike influenza, all the action occurs in
the cytoplasm. However, the overall
strategy very similar to influenza,
although unlike influenza,
Paramyxovirus replication is resistant
to actinomycin D.
Replication
A large excess of nucleocapsids are

produced in infected cells, which form
characteristic cytoplasmic inclusion
bodies. Syncytium formation is quite
common (F glycoprotein).
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(A) MEASLES (Rubeola)

• History: References to measles can be found as far
back as the 7th century A.D.; the disease was
described by Rhazes in the 10th Century A.D. as
"more dreaded than smallpox.
• Before 1963 almost everyone got measles
• 3 to 4 million cases per year in the U.S.
• More than half the population had measles by the
time they were 6 years old
• 90 % had the disease by the time they were 15
MEASLES
• One of the most infectious diseases known!
>106 deaths p.a. in children in the third world,
now part of the WHO, EPI.
- Childhood infection almost universal,
protection resulting from this is probably
lifelong.
- Both man and wild monkeys are commonly
infected, but the virus can also infect rodents
(in wild?).
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Measles
Measles kills nearly
one million children, a
half million of those in
Africa alone single
leading cause of
vaccine-preventable
death among children
in Africa - more than
AIDS, tuberculosis,
and malnutrition
Measles Virus
• Family: Paramyxoviridae: have an affinity for mucus
membranes
• Genus: Morbillivirus
• Virions are pleomorphic spherical structures
• 100-250nm diameter
• Inner nucleocapsid contains coiled helix of ss RNA
and three proteins
• Outer envelope contains three other proteins
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Viral Structures
Nucleocapsid proteins
• N protein:
contains the viral
genome
• L protein
• P protein: involved
in transcription
Viral Structures
Virus envelope proteins
• F protein: glycoprotein
that is involved in the
fusion of the virus with
the host cell
• H protein: adhesion of
the virus with the host
cell
• M protein: virus
development
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* Big Picture Book of Viruses
MEASLES VIRUS
• Can live up to two hours on surfaces
• 30 minutes in aerosol form
• Heat sensitive
• Survives freezing well
• Can survive when freeze-dried with a
protein stabilizer for decades
• Inactivated by solvents like ether,
disinfectants, by acids (pH<5), bases
(pH>10), and by UV and visible light.
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Pathogenesis
• Transmission and initial stages of disease
similar to mumps, but this virus can also
infect via the eye and multiply in the
conjunctivae.
• Incubation period lasts between 7 – 10 days
• Viraemia following primary local
multiplication results in widespread
distribution to many organs.
Pathogenesis contd.
•Virus first causes local infection in
epithelial lining of the upper
respiratory tract
•Spreads to lymph nodes: multiplies
rapidly
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Symptoms
• Runny nose, watery eyes, cough, and
high fever
• Tiny, white spots, appear in the mouth
• 2-4 days, a raised, red rash starts on
the face and spreads down the body
and out to the arms and legs.
• People with measles are contagious
for 1 week before and at least 4 days
after the rash begins
Laboratory Diagnosis
• The virus can be isolated from several clinical
specimens
• In culture, produces characteristic intranuclear
inclusion bodies and syncytial giant cells.
• Enzyme Immunoassay (EIA) can be used if needed, to
detect IgM or IgG levels
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Measles: treatment & prevention

• Treatment: None
• Prevention: Both live and killed vaccines exist.
Vaccination with the live attenuated vaccine has
been practiced in the US since the 1960's with a
dramatic decline in the incidence of the disease,
but has only been used more recently in the UK.
Trivalent live attenuated vaccine (MMR) usually
given - all of these viruses best avoided during
pregnancy!
Complications
• Complications include bronchopneumonia and
otitis media (with or without secondary bacterial
infections) (relatively common), and encephalitis
(~1:2000 cases).
• Subacute schlerosing pan encephalitis (SSPE)
results from a rare (~1 : 300,000 cases of measles),
chronic infection in which the virus multiplies in the
brain with the expression of a limited repertoire of
virus genes, resulting in neurodegenerative disease.
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Vaccine
• First vaccine released in
1963; number of cases
decreased by 98%
• Between 1985-1988 children
who had received the vaccine
still developed measles
• 2nd dose between 5-19
years of age *Data from Center for Disease Control
Measles Epidemic
1989-1991
• 55,622 cases were reported
• Most of the cases occurred in children under
5 years of age
• unvaccinated Hispanic and African American
• 123 people died from measles-related illnesses
• half were under 5 years old
• 90% of those who died had not been
vaccinated
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Measles Outbreaks
• Largest number of outbreaks occur in
populations that refuse the vaccine
• Outbreaks of measles have been small
• Less than 50 cases
• Unvaccinated high school and college
students, or those who haven’t received
one vaccine dose
• No large preschool-type outbreak has
been reported since 1992
Measles in the Americas

• March of 2000, CDC concluded that Measles
are no longer an epidemic in the U.S.
• All cases are importations
• Europe and Asia
• Pan American Health Organization
• measles incidence is now very low in Latin
America and the Caribbean
• Elimination in the Americas a feasible goal
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Measles Cases Imported into the United

States 1990-1999
*Data from Center for Disease Control

(B) Rubella virus

• Rubella was first described by two German physicians
in the mid-eighteenth century and recognized as a
distinct disease in 1881 by the International Congress
of Medicine.
• Its association with congenital defects was not
recognized until 1941 when Sir McAlister Gregg
reported 78 babies with congenital cataract born after
an extensive epidemic of rubella in Australia in 1940.
• These findings were subsequently confirmed by
numerous retrospective and prospective studies.
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Properties of the Virus

• Non-arthropod-borne togavirus, only member of the
genus Rubivirus, ssRNA enveloped virus, 60nm in
diameter, nucleocapsid 33nm symmetry thought to be
icosahedral but virus particle has a pleomorphic
appearance.
• +ve 40S RNA consists of 3 structural proteins - E1, E2
membrane bound glycoproteins, and C capsid protein
• E1 has 6 distinct antigenic determinants; Associated with
haemagglutination, and neutralization
• Only one serotype of Rubella virus
Properties of the Virus contd.

• Rubella grows in a wide range of cell lines.
• It induces a CPE only in continuous cell lines such as RK13
(rabbit kidney) and Vero.
• Immunofluourescense is used to identify the presence of the
virus in culture.
• Rubella virus infects various primates and other mammals
e.g. monkeys, chimpanzees, rabbits and mice.
• Attempts to reproduce the teratogenic effects of Rubella
virus in animal models have produced inconsistent and
irreproducible results.
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Epidemiology
• Rubella has a worldwide distribution.
• Before the introduction of vaccination outbreaks
tend to occur Spring and Summer.
• Infection is uncommon in preschool children but
outbreaks involving school children and young
adults were common.
• In general, about 50% of 10 year olds have rubella
antibodies.
Epidemiology Contd.
• 80% of women of childbearing age were found
to be immune in the pre vaccination era.
• In the UK major epidemics occur every few
years. The last one was in 1978. Children 3-10
yrs are most frequently affected.
• Despite the vaccination program 5-10 % of
women reach child bearing are susceptible to
Rubella infection.
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Clinical Features
• Transmission is by the respiratory route.
• IP is 13 to 20 days, during which a viraemia occurs
and virus disseminates throughout the body.
• Onset is abrupt in kids with the appearance of the
rash. In adults a prodromal phase may be present
with fever and malaise for a day or two before the
rash develops. Rash is typically a maculopapular
rash, which first appears on the face and then
spreads to the trunk and the limbs, seldom lasts >
3 days.
Clinical Features Contd.

• Exact mechanism of how the rash is induced is
uncertain but an immunopathological mechanism
may be present.
• Lymphadenopathy may precede the rash by up to
a week and persists up to 2 weeks after the rash
has gone.
• Joint involvement is the commonest complication
and occurs in up to 60% of adult females.
• The fingers, wrists knees and ankles are most
frequently affected.
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Clinical Features contd.

• The arthralgia lasts usually 3-4 days.
• Arthralgia is rare in males and pre-pubertal
females. An encephalitis develops in 1 /
10000 but the prognosis is good.
• Thrombocytopenic purpura may occur which
may present as purpuric rash, epistaxis,
haematuria and GI bleeding.
Congenital Rubella Syndrome (CRS)

(1) TRANSIENT:- Intra uterine growth retardation
(IUGR), thrombocytopenic purpura,
hepatoslenomegaly and haemolytic anaemia.
• These abnormalities are present during the first few
weeks of life and are not associated with permanent
sequelae. Transient bone lesions occur in 20% of
congenitally infected infants.
• 25% have a meningoencephalitis which may or not
leave neurological sequelae. Jaundice is commonly
present.
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(2) Developmental
• Sensorineural deafness, mental retardation, insulin-dependent
diabetes. Developmental defects may take months before they
become apparent but persists permanently.
• Congenital rubella remains the commonest cause of congenital
deafness in developed countries. Rubella deafness may be
unilateral or bilateral and varies considerably in severity.
• IDDM is actually a common manifestation of CRS ( up to 20%).
However onset may be delayed till adolescence or adulthood.
Autoimmune mechanisms may be involved. Between 3 - 12
months some infants develop a rubbelliform rash, persistent
diarrhoea and pneumonitis which is referred to as "late onset
disease". This carries a high mortality.
(3) Permanent
• Heart defects (patent ductus, VSD, pulmonary valve
stenosis), eye defects (retinopathy, cataract,
microopthalmia, glaucoma, severe myopia), CNS defects
(microcephaly, psychomotor retardation). In the early
sixties before the advent of vaccination, a large outbreak of
CRS occurred in America.
• A follow-up study was conducted 25 years later and it was
found that one-third of those affected were leading normal
independent lives, one-third had to live with their parents,
and one-third were institutionalized. Late sequelae,
especially those affecting the heart were commonly seen.
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Laboratory Diagnosis
1. Serological diagnosis of rubella infection - Serology
is the mainstay of diagnosis of rubella infection. A
recent rubella infection can be diagnosed by:
• (a) detection of rubella-specific IgM,
• (b) rising titres of antibody in HAI and ELISA tests,
and
• (c) seroconversion. It is essential to obtain accurate
information relating to the date and time of
exposure, the date of onset of illness.
• Haemagglutination inhibition
(HAI) assay remains the
mainstay test for diagnosis of
rubella infection. HAI Abs may
be detected on the first day of
the rash and rise rapidly to peak
titres.
• EIA and RIA have replaced HAI
for the diagnosis of rubella in
some laboratories.
• Detection of rubella-specific IgM
by EIA or RIA. The most sensitive
and reliable techniques in use
are tM - antibody capture ELISA
and radioimmunoassay).
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Laboratory Diagnosis contd.

• 2. Serological techniques used for rubella antibody screening;- Single
Radial Haemolysis (SRH) and latex agglutination (LA), and .ELISA are
used for screening for immunity against rubella. SRH is reckoned to be
slightly less sensitive than LA or ELISA.
• 3. Virus isolation and identification;- Virus isolation is now seldom
used for diagnosing postnatally acquired rubella infection.
• 4. Diagnosis of congenital acquired infection: This is made by:
(a) The presence of rubella IgM in cord blood or serum samples taken
in infancy. (b) Detection of rubella antibodies at a time when maternal
antibodies should have disappeared (approx.6 months of age) (c)
Isolation of rubella virus from infected infants in the first few months of
life.
5. Prenatal diagnosis of Congenital rubella infection

Prenatal diagnosis of congenital infection may be of value when
maternal infection occurred after the first trimester, in cases of
maternal reinfection and in cases where equivocal serology results
from the mother were obtained. Possible methods include:
(i) The testing of fetal blood samples obtained by fetoscopy for
rubella specific IgM. However the fetus does not produce sufficient
IgM for detection before 22 weeks.
(ii) Virus may be isolated from amniotic fluid but the reliability of
this technique has not been demonstrated.
(iii) The detection of rubella RNA or viral proteins in chorionic villus
biopsies and amniotic is currently being evaluated.
6. Diagnosis using molecular methods
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Prevention Measles and Rubella

• There is no treatment
• The first vaccines were developed in the early 60's (HPV77.DE5 and
Cendehill) and were licensed for use in 1969.
• In 1979 the HPV77.DE5 strain was replaced with RA27/3 and
Cendehill is no longer available.
• RA 27/3 is now the most widely used vaccine strain and is made by 7
manufacturers.
• All vaccines are administered subcutaneously and are well tolerated
and produced a response in 95% of recipients.
• Although the virus is excreted by vaccines, it is not transmitted to
susceptible contacts.
The MMR Vaccine

• The safest way that parents can protect their
children against measles, mumps and rubella
• Over 500 million doses of MMR have been used in
over 90 countries around the world since the early
1970s.
• WHO states that MMR is a highly effective vaccine
with an outstanding safety record.
• Evidence is that the vaccine does not cause autism
or inflammatory bowel disease. There are now
numerous studies that do not support a link
between autism the MMR vaccine.
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Measles Initiative
“Together we can save a life”
So what is the Measles Initiative?

• Control deaths by vaccinating 200 million
children and preventing 1.2 million deaths
over 5 years
• American Red Cross, United Nations
Foundation, CDC, WHO, UN Children’s Fund
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(C) Varicella-Zoster Virus

• Varicella-zoster virus (VZV) causes two distinct clinical
diseases. Varicella, more commonly called chickenpox, is the
primary infection and results from exposure of a person
susceptible to the virus.
• Chickenpox is ubiquitous and extremely contagious, but for
the most part, it is a benign illness characterized by a
generalized exanthematous rash. It occurs seasonally and in
epidemics.
• Recurrence of infection results in the more localized
phenomenon known as herpes zoster, often referred to as
shingles, a common infection among the elderly.
Historical Overview
• Shingles has been recognized since ancient times as a
unique clinical entity because of the dermatomal
vesicular rash; however, C-pox was often confused
with smallpox.
• In 1875, Steiner successfully transmitted VZV by
inoculation of the vesicular fluid from a person
suffering from C-pox to “volunteers.” The infectious
nature of VZV was further defined by von Bokay, who
observed C-pox in persons who had close contact with
others suffering from herpes zoster.
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Overview contd.
• Von Bokay correctly described the mean IP for the
development of C-pox in susceptible patients as well
as the average range in days.
• Kundratitz in 1925 showed that the inoculation of
vesicular fluid from patients with herpes zoster into
susceptible persons resulted in C-pox.
• Similar observations were reported by Brunsgaard and
others, and in 1943 Garland suggested that herpes
zoster was the consequence of the reactivation of
latent VZV.
The Pathogen and Its Replication

• VZV is a member of the Herpesviridae family and
shares structural characteristics with other members
of the family.
• The virus has icosapentahedral symmetry and
contains centrally located double-stranded DNA with a
surrounding envelope. The size of the virus is
approximately 150 to 200 nm, and it has a lipid-
containing envelope with glycoprotein spikes.
• The naked capsid has a diameter of approximately 90
to 95 nm.
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The VZV Replication Contd.

• The DNA contains 125,000 base pairs, or approximately
80 megadaltons, and encodes about 75 proteins.
• The organization of the viral genome is similar to that of
other herpesviruses. There are unique long (105-kb)
and unique short (5.2-kb) regions of the viral genome.
• Each unique sequence contains terminal repeat
sequences.
• With replication, the unique short (Us) region can invert
upon itself and result in two isomeric forms.
Epidemiology of V-ZV Infections

• Humans are the only known reservoir for VZV. C-pox
follows exposure of the susceptible or seronegative
person to VZV and represents the primary form of
infection.
• Although it is assumed that the virus is spread by the
respiratory route and replicates in the nasopharynx or
upper respiratory tract, retrieval of virus from persons
incubating VZV has been uncommon.
• Overall, C-pox is a disease of childhood, because 90%
of cases occur in children younger than 13 years.
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Pathogenesis
• Chickenpox occurs in susceptible persons who are exposed
to virus after close personal contact.
• Histopathologic findings in human VZV infections, whether
chickenpox or herpes zoster, are virtually identical.
• The vesicles involve the corium, or dermis.
• As viral replication progresses, the epithelial cells undergo
degenerative changes characterized by ballooning, with the
subsequent appearance of multinucleated giant cells and
prominent eosinophilic intranuclear inclusions.
Pathogenesis Contd.
• Transmission is likely by the respiratory route,
followed by localized replication at an undefined site,
which leads to seeding of the reticuloendothelial
system and, ultimately, viremia.
• The occurrence of viremia in patients with chickenpox
is supported by the diffuse and scattered nature of
the skin lesions and can be verified in selected cases
by the recovery of virus from the blood.
• The mechanism of VZV reactivation that results in
herpes zoster is unknown.
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Clinical Manifestations
• C-pox is generally a benign, self-limited disease in kids who are
immunocompetent children. Incidence has markedly decreased
vaccine is widely used. Presenting manifestations are a rash,
low-grade fever, and malaise. A prodrome of symptoms may
occur 1 to 2 days before the onset of the exanthem in a few
patients. Constitutional symptoms include malaise, pruritus,
anorexia, and listlessness; these gradually resolve as the illness
abates. The skin manifestations, which are the hallmark of
infection, consist of maculopapules, vesicles, and scabs in
varying stages of evolution. The lesions initially contain clear
vesicular fluid, but over a very short period of time they
pustulate and scab
Clinical skin manifestations
Vesicular eruption on the

trunk demonstrating Dewdrop on rose petal Typical zoster in the
papules, vesicles, and crusts characteristic vesicle of vicinity of right
chickenpox popliteal fossa in a
vertebral nerve L4
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Diagnosis
• The diagnosis of both C-pox and shingles is
usually made by history and physical
examination.
• Specimen – saliva, skin swab, blood, CSF
• Microscopy - A Tzanck smear, performed by
scraping the base of the lesion, can demonstrate
multinucleated giant cells
• Culture - Viral isolation susceptible tissue culture
cell lines
Diagnosis Contd.
• Direct fluorescent antibody (DFA)staining of smears
obtained from scraping vesicular lesions.
• Antibody assays of acute and convalescent serum
specimens - immune adherence haemagglutination
assay (IAHA), Fluorescence antibody to membrane
antigen (FAMA), ELISA.
• PCR is a useful diagnostic tool; however, its expense
and lack of uniform performance standards
preclude routine diagnostic use.
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Treatment
• Medical management of C-pox and shingles in the normal host is
directed toward reduction of complications.
• Hygiene is important, including bathing, astringent soaks, and closely
cropped fingernails. Pruritus can be decreased with topical dressing or
the administration of antipruritic drugs. Soaks with aluminum acetate,
or Burow's solution, in the management of herpes zoster can be both
soothing and cleansing.
• Acetaminophen should be used to reduce fever in patients with
chickenpox because of the association between aspirin and Reye's
syndrome.
• Acyclovir – In the USA used for treating C-pox and Shingles
Prevention
• In the normal host, prophylaxis of chickenpox is achieved via
vaccination. The potential for transmission of VZV within the hospital
to immunosuppressed patients, particularly children. A vaccine is
licensed for the prevention of chickenpox in immunocompetent
persons
• Two doses of recombinant zoster vaccine (RZV) (Shingrix) 2-6 months
apart to adults aged 50 years or older regardless of past episodes of
herpes zoster or receipt of zoster vaccine live (ZVL) (Zostavax).
• Two doses of RZV 2-6 months apart to adults who previously received
ZVL at least 2 months after ZVL.
• For adults aged 60 years or older, administer either RZV or ZVL (RZV is
preferred).
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1/26/2021

MEASLES, RUBELLA AND

Objectives of the lectures

1/26/2021 Prof Akpaka PE: Measles, Rubella and other infections 3

1/26/2021 Prof Akpaka PE: Measles, Rubella and other infections 4

1/26/2021 Prof Akpaka PE: Measles, Rubella and other infections 6

1/26/2021 Prof Akpaka PE: Measles, Rubella and other infections 7

A large excess of nucleocapsids are

1/26/2021 Prof Akpaka PE: Measles, Rubella and other infections 8

(A) MEASLES (Rubeola)

1/26/2021 Prof Akpaka PE: Measles, Rubella and other infections 13

* Big Picture Book of Viruses

1/26/2021 Prof Akpaka PE: Measles, Rubella and other infections 15

1/26/2021 Prof Akpaka PE: Measles, Rubella and other infections 18

1/26/2021 Prof Akpaka PE: Measles, Rubella and other infections 19

1/26/2021 Prof Akpaka PE: Measles, Rubella and other infections 20

1/26/2021 Prof Akpaka PE: Measles, Rubella and other infections 22

Measles: treatment & prevention

1/26/2021 Prof Akpaka PE: Measles, Rubella and other infections 25

Measles in the Americas

1/26/2021 Prof Akpaka PE: Measles, Rubella and other infections 28

Measles Cases Imported into the United

*Data from Center for Disease Control

(B) Rubella virus

Properties of the Virus

1/26/2021 Prof Akpaka PE: Measles, Rubella and other infections 31

Properties of the Virus contd.

1/26/2021 Prof Akpaka PE: Measles, Rubella and other infections 33

1/26/2021 Prof Akpaka PE: Measles, Rubella and other infections 34

Clinical Features Contd.

Clinical Features contd.

1/26/2021 Prof Akpaka PE: Measles, Rubella and other infections 37

Congenital Rubella Syndrome (CRS)

Laboratory Diagnosis contd.

5. Prenatal diagnosis of Congenital rubella infection

Prevention Measles and Rubella

The MMR Vaccine

So what is the Measles Initiative?

1/26/2021 Prof Akpaka PE: Measles, Rubella and other infections 47

1/26/2021 Prof Akpaka PE: Measles, Rubella and other infections 48

(C) Varicella-Zoster Virus

The Pathogen and Its Replication

The VZV Replication Contd.

Epidemiology of V-ZV Infections

1/26/2021 Prof Akpaka PE: Measles, Rubella and other infections 55

Clinical skin manifestations

Vesicular eruption on the

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