Makassar, November 9th 2017

PBL REPORT MODUL RED SPOT

TROPICAL INFECTION

Tutor : dr. Eny Arlini Wello

Group 15:
Kurnia Junita Sari Risal (11020150023)
Githa Nur Afiefah (11020150034)
Desi Triutami Saleh (11020150068)
Elsa Shafira Prasetyati (11020150117)
M. Fauzan Fahmy (11020150127)
Fitri Lestari (11020150142)
A. Nurul Fajri Ekaputri (11020150077)
Kauzar Hidayat Salam (11020150025)
St. Devi Regina Octavia (11020150050)
Muhammad Fauzan (11020150151)

MEDICAL FACULTY
MUSLIM UNIVERSITY OF INDONESIA
MAKASSAR
2017
Scenario 1

A mother brings a 3-year-old girl to hospital with complaints of red rash throughout
the body since last night. Since 4 days ago the child also experience fever with
cough, runny nose, red eyes, swallowing pain, vomiting, decreased appetite and
mushy feses 2-3x / day.

A. Keywords:
- 3-year-old girl
- Complaints of red rash throughout the body since last night
- Since 4 days ago the child also experience fever with cough, runny nose, red
eyes, swallowing pain, vomiting, decreased appetite and mushy feses 2-3x /
day
B. Questions
1. Explain the mechanism of each symptom from the scenario!
2. Explain the risk factors from the scenario!
3. Explain the differential diagnose!
4. How to prevent the disease?
C. Answers
1. Explain the mechanism of each symptom from the scenario!
Answer:

Humans are the only native host for measles virus. Transmission of measles
occurs droplet through the air, occurs between 1-2 days before clinical
symptoms appear until 4 days after the rash. Infections begin in the nasal
mucosa / pharynx. In the initial place of infection, viral replication is very
minimal and rarely can be found the virus. The virus enters the local
lymphatics, free or related to the mononuclear cells reaching the local lymph
nodes. Serous exudates and mononuclear cell proliferation and some
polymorphonuclear cells occur around the capillaries. The virus then
multiplies very slowly and there begins the spread to lymph nodes (RES)
cells such as the spleen, in which the virus attacks the lymphocytes to find
the reticonuloendothelial giant Warthin-Finkeldey cells due to cell fusion
and intranuclear inclusions seen in lymphoid tissue. Measles virus can
replicate in certain lymphocytes that help spread throughout the body. 5-6
days after initial infection, the focus of infection is formed when the virus
enters the blood vessel (primary viremia) and spreads to the epithelial
surface of the oropharynx, conjunctiva, airways, skin, bladder, and intestine.

On days 9 to 10 the focus of the infection in the airway epithelium and

conjunctiva, necrosis of one to two layers. At that time large numbers of
viruses re-enter the blood vessels (secondary viremia) and cause clinical
manifestations of the respiratory system begins with a cold cough with a
red-conjunctival membrane.

Lesions in particularly prominent skin areas are found around the sebaceous
glands and hair follicles. There was a maculopapular rash on day 14
following the onset of the infection and at that time a humoral antibody
could be detected. Furthermore, the body's resistance decreased, as a result
of the delayed hypersensitivity response to the viral antigen there was a rash
on the skin.

There is a general inflammatory reaction in the buccal and pharyngeal

mucoses that extend into the lymphoid tissue and tracheibronchial mucous
membranes. Intersisial pneumonitis due to measles virus causes the
formation of giant cells from Hecht. Bronchopneumonia that occurs may be
caused by secondary infection by bacteria
 References :

1. Brooks, Geo F., Butel, Janet S., Morse Stephen A. Mikrobiologi Kedokteran.
Edisi I. Terjemahan.Salemba Medika : Jakarta
2. Nelson, Behrman, Kliegman, dkk. Ilmu Kesehatan Anak Nelson Edisi 15
vol.1. Jakarta : EGC
2. Explain the risk factors from the scenario!
Answer:
Several factors that increase the risk of measles include:

1. Age
In most societies, maternal antibodies will protect the infant against measles
for 6 months and the disease will be modified by maternal levels of
antibodies remaining until the first part of the second year of life. However,
in some populations, especially in Africa, the number of cases occurs
significantly at age under 1 year, and mortality rates reach 42% in the age
group less than 4 years. Beyond this period, all ages seem to have the same
vulnerability to infection. Age exposed to measles depends more on
individual habits than on the nature of the virus.

In North America, Western Europe, and Australia, children spend more time
at home, but when entering school the number of children suffering
increases.

Before immunization is widely socialized, most cases of measles in

industrialized countries occur in children aged 4-6 years or primary school
age and in younger children in developing countries. Intensive
immunization coverage results in changes in age distribution where more
cases occur in older children, adolescents, and young adults.

The Casaeri study with case-control design in Kendal district said that
children with vulnerable age of less than 15 years had a 4.9 times greater
risk of being infected with measles than in less vulnerable children

2. Sex

There were no differences in the incidence and extent of measles vaccine in

women or men. However, the female antibody titer is largely taller than the
male. The incidence of measles during pregnancy is associated with high
rates of spontaneous abortion.

Based on Suwono research in Kediri with case control research design get
result that by gender, measles sufferer more in boy that is 62%.

3. Age of Immunization

The remaining antibodies received from the mother through the placenta are
important factors in determining the age of measles immunization to be
given to infants. Maternal antibodies may affect the immune response to live
measles vaccine and early immunization does not always result in adequate
immunity or immunity.

At 9 months of age, about 10% of babies in some countries still have

maternal antibodies that can interfere with the response to immunization.
Delaying immunization may increase the number of seroconversions.
Generally in developing countries there will be more than 85%
seroconversion if the vaccine is given at 9 months of age. Whereas in
developed countries, children will lose maternal antibodies at the age of 12-
15 months so that at that age recommended measles vaccine. However,
immunization delays can lead to an increase in morbidity and mortality due
to measles high enough in most developing countries.

A cohort study in Arkansas said that when compared with children who
were vaccinated at age> 15 months, children who received measles vaccine
at <12 months had a 6-fold risk for measles. While children who get measles
vaccine at 12-14 months of age have a 3 times risk for measles compared
with children who get vaccinated at the age of 15 months.

Meanwhile, a case-control study conducted in Arkansas mentioned that

children who received measles vaccine at 12-14 months of age had a 5.6
times greater risk of measles than children who received the vaccine at 15
months or older.

4. Work

In poor socioeconomic environments, children are more susceptible to

cross-infection. Poverty is responsible for the disease found in children. This
is because poverty reduces the capacity of parents to support adequate health
care in children, tend to have poor hygiene, poor diet, poor education. The
relative frequency of children of low-income parents is 3 times greater
having the risk of late immunization and 4 times higher causing child
mortality than children whose parents earn enough.

5. Education

The level of education greatly affects how a person acts and seeks causes
and solutions in his life. Higher educated people will usually act more
rationally. Therefore an educated person will be more receptive to new
ideas. Education also influences the pragmatic and rational pattern of
thinking about custom, with higher education people can more easily accept
new ideas or problems.

Agunawan research in Saung Naga village, West Baturaja Subdistrict with

cross sectional design mentioned that there is a correlation between mother
education and measles disease incidence in balita (p = 0,000).

6. Immunization

Measles vaccine is an attenuated viral preparation and is derived from a

variety of isolated measles strains. Vaccines can protect the body from
infection and have an important effect in the epidemiological disease that is
changing the relative distribution of case age and shifting to an older age.
Immunization in infancy will reduce transmission of infectious agents and
reduce the chances of someone vulnerable to exposure to the agent.
Unimmunized children will grow into large or mature without ever being
exposed to the infectious agent. In measles, the most severe disease
manifestations usually occur in children younger than 3 years.

Immunization at 8-9 months is predicted to lead to seroconversion in at least

85% of infants and can prevent most cases and deaths.

By administering one dose of measles vaccine, the incidence of measles can

be reduced by more than 90%. However, because measles is a highly
contagious disease, it can still occur in school-age children, although 85-
90% of children already have immunity.

A cohort study of 627 students in Arkansas found that children who were
not vaccinated were 20 times more likely to get measles than children who
had a history of vaccination at 15 months or older.

Based on I Made Suardiyasa research in Tolitoli district, Central Sulawesi

stated that children who are not immunized risk 29 times to get measles than
children who get immunization.

7. Nutrition Status

The incidence of measles deaths is higher in malnutrition, but there is no

distinction between the effects of malnutrition on measles and the effects of
measles on nutrients due to decreased appetite and the ability to digest food.
Scrimshaw noted that measles deaths in children in Guatemalan villages
decreased from 1% to 0.3% annually when the children were given a high
protein-protein supplement. Whereas in the control village where the
children were not given protein supplements,

the mortality rate is 0.7%. But since only 27% of these children regularly
consume extra protein, it can be concluded that the rate changes obtained in
the observation case are not entirely caused by dietary supplements.

From a study stated that the main nutritional elements that cause measles
emergency is not protein and calories but vitamin A. When vitamin A
deficiency occurs, death or blindness accompanies measles. Regardless of
the sequence of events, deaths associated with measles reach high levels,
usually more than 10% occur in the state of malnutrition.

Research I Made Suardiyasa in Tolitoli district of Central Sulawesi stated

that the risk of children who have less nutritional status for measles is 5.4
times than children with good nutritional status.
 While Elderly research at Puskesmas Kori Subdistrict of North Kodi West
Sumba Regency with cross sectional design toward 6 -15 year old children
got result that the incidence of measles has something to do with nutritional
status where child with less nutritional status has a risk probability 2.9 times
bigger for exposed to measles.

8. Exclusive breastfeeding

More than thirty types of immunoglobulins are present in breast milk that
can be identified with the latest techniques. Eighteen of these are from the
mother's serum and the rest are found only in breast milk / colostrum. The
most important immunoglobulin that can be found in colostrum is IgA, not
only because of its high concentration but also its biological activity.

IgA in colostrum and breast milk is very nutritious to protect the baby's body
against infectious diseases. In addition, G immunoglobulin can penetrate the
placenta and is in a high enough concentration in the fetus / infant's blood
until the age of several months, so as to provide protection against some
types of diseases. The types of antibodies that can be transferred properly
through the placenta are diphtheria, tetanus, measles, rubella, parotitis,
polio, and staphylococci.

A study with a cohort design conducted in Sweden found out that

breastfeeding for> 3 months can provide protection against measles
infection in other words breastfeeding is a protective factor against measles
incidence (OR = 0.69).

Reference: Bong Stevana. Penyebaran Penyakit Campak. Universitas

Diponegoro. Semarang. 2013 eprints.undip.ac.id.

3. Explain the differential diagnose!

Answer:
A. Measles

Definition

Measles also known as the morbili or morbillia and rubeola ( latin ),

which then in german called by the name of masern, in the language of
the icelanders known as the mislingar and measles in english. Measles
is the disease a very contagious infection caused by a virus, with
symptoms eksantem acute, fever, sometimes catarrhal mucous
membrane and respiratory, symptoms eyes, followed eruption
maculopapula that is colored red and ends with desquamation of leather.

Infectious agents
 Measles agent is a measles virus that included in family
paramyxoviridae members of the genus morbilivirus .The measles virus
is highly sensitive to temperature so that this virus become inactive at a
temperature 37 degrees centigrade or if put in a refrigerator for a few
hours . By freezing slow so infection will be lost.

Stage of disease

- Stadium kataral (prodormal)

Usually stadium this went on for 4-5 day with the symptoms of
fever, malaise , cough , photofobia , conjunctivitis and koriza. By the
end of the stadium catarrhal and 24 hours before arising exanthema,
arising patches koplik. Patches koplik white gray , the tip of a needle
arising the first time at mucous buccal who comes to the molar teeth
and coming about day to 3 or 4 from the prodormal can extends up to
all mucous the mouth .Clinically , picture disease resembling influenza
and often diagnosed as influenza .

- Stadium erupsion

Stadium this went on for 4-7 day. The Symptoms usually

happens are koriza and coughing increase. Arising exanthema in
palatum durum and palatum mole. Sometimes look also patches koplik
.The rash or erythema shaped macula-papula accompanied the
increasing the temperature of a body .First erythema arising behind the
ear, at the top of the neck , along hair and the back below. Sometimes
there are bleeding light on the skin. The itching , the swollen. Rash will
then spread to the chest and abdomen and ultimately achieve a member
of the bottoms on the third day and would have disappeared with the
order as the which ended in 3-2 day.

- Stadium konvalesens

Eruption reduced leaving a who colored more parent (

hyperpigmentasi ) long time would have disappeared own. Besides
hiperpigmentasi on child indonesia often there is also the skin
scaly.Next temperature dropping until to be normal unless there are
complications.

Transmission of measles
 Measles is transmitted through the droplet, direct contact, sekret
through the nose or throat of the infected. The contagion from the first
day will go before the onset of symptoms prodormal usually about 4
days before the rash, at least the second day after the rash occurs.

Clinical Sign

The patient history is notable for exposure to the virus. The incubation
period from exposure to onset of measles symptoms ranges from 7 to
14 days (average, 10-12 days). Patients are contagious from 1-2 days
before the onset of symptoms. Healthy children are also contagious
during the period from 3-5 days before the appearance of the rash to 4
days after the onset of rash. On the other hand, immunocompromised
individuals can be contagious during the duration of the illness.

The first sign of measles is usually a high fever (often >104o F [40o C])
that typically lasts 4-7 days. This prodromal phase is marked by
malaise, fever, anorexia, and the classic triad of conjunctivitis, cough,
and coryza (the 3 Cs). Other possible associated symptoms include
photophobia, periorbital edema, and myalgias.

Measles conjunctivitis.

The characteristic enanthem generally appears 2-4 days after the onset
of the prodrome and lasts 3-5 days. Small spots (Koplik spots) can be
seen inside the cheeks during this early stage
Koplik spots in measles. Photograph courtesy of World Health
Organization.

The exanthem usually appears 1-2 days after the appearance of Koplik
spots; mild pruritus may be associated. On average, the rash develops
about 14 days after exposure, starting on the face and upper neck (see
the image below) and spreading to the extremities.
Immunocompromised patients may not develop a rash.

Face of boy with measles.

The entire course of uncomplicated measles, from late prodrome to
resolution of fever and rash, is 7-10 days. Cough may be the final
symptom to appear.

Modified and atypical measles

Modified measles is a milder form of measles that occurs in individuals

who have received serum immunoglobulin after their exposure to the
measles virus. Similar but milder symptoms and signs may still occur,
but the incubation period may be as long as 21 days.

Atypical measles occurs in individuals who were vaccinated with the

original killed-virus measles vaccine between 1963 and 1967 and who
have incomplete immunity. After exposure to the measles virus, a mild
or subclinical prodrome of fever, headache, abdominal pain, and
myalgias precedes a rash that begins on the hands and feet and spreads
centripetally. The eruption is accentuated in the skin folds and may be
macular, vesicular, petechial, or urticarial. The live-attenuated vaccine
replaced the killed vaccine in 1967 and is not associated with atypical
measles.

Physical Examination

Enanthem

Near the end of the prodrome, Koplik spots (ie, bluish-gray specks or
grains of sand on a red base) appear on the buccal mucosa opposite
the second molars

Enanthem of measles (Koplik spots).

The Koplik spots generally are first seen 1-2 days before the appearance
of the rash and last until 2 days after the rash appears. This enanthem
begins to slough as the rash appears. Although this is the
pathognomonic enanthem of measles, its absence does not exclude the
diagnosis.

Exanthem

Blanching, erythematous macules and papules begin on the face at the

hairline, on the sides of the neck, and behind the ears. Within 48 hours,
they coalesce into patches and plaques that spread cephalocaudally to
the trunk and extremities, including the palms and soles, while
beginning to regress cephalocaudally, starting from the head and neck.
Lesion density is greatest above the shoulders, where macular lesions
may coalesce. The eruption may also be petechial or ecchymotic in
nature.

Morbilliform rash.

Patients appear most ill during the first or second day of the rash. The
exanthem lasts for 5-7 days before fading into coppery brown
hyperpigmented patches, which then desquamate. The rash may be
absent in patients with underlying deficiencies in cellular immunity.

Complications

Most complications of measles occur because the measles virus

suppresses the hosts immune responses, resulting in a reactivation of
latent infections or superinfection by a bacterial pathogen.
Consequently, pneumonia, whether due to the measles virus itself, to
tuberculosis, to or another bacterial etiology, is the most frequent
complication. Pleural effusion, hilar lymphadenopathy,
hepatosplenomegaly, hyperesthesia, and paresthesia may also be noted.

Complications of measles are more likely to occur in persons younger

than 5 years or older than 20 years, and complication rates are increased
in persons with immune deficiency disorders, malnutrition, vitamin A
deficiency, and inadequate vaccination. Immunocompromised children
and adults are at increased risk for severe infections and
superinfections.

Common infectious complications include otitis media, interstitial

pneumonitis, bronchopneumonia, laryngotracheobronchitis (ie, croup),
exacerbation of tuberculosis, transient loss of hypersensitivity reaction
to tuberculin skin test, encephalomyelitis, diarrhea, sinusitis, stomatitis,
subclinical hepatitis, lymphadenitis, and keratitis, which can lead to
blindness. In fact, measles remains a common cause of blindness in
many developing countries.

Rare complications include hemorrhagic measles, purpura fulminans,

hepatitis, disseminated intravascular coagulation (DIC), subacute
sclerosing panencephalitis (SSPE), thrombocytopenia, appendicitis,
ileocolitis, pericarditis, myocarditis, acute pancreatitis, and
hypocalcemia. Transient hepatitis may occur during an acute infection.

Approximately 1 of every 1,000 patients develops acute encephalitis,

which often results in permanent brain damage and is fatal in about 10%
of patients. In children with lymphoid malignant diseases, delayed-
acute measles encephalitis may develop 1-6 months after the acute
infection and is generally fatal.

An even rarer complication is SSPE, a degenerative CNS disease that

can result from a persistent measles infection. SSPE is characterized by
the onset of behavioral and intellectual deterioration and seizures years
after an acute infection (the mean incubation period for SSPE is
approximately 10.8 years).

The complications of measles in the pregnant mother include

pneumonitis, hepatitis, subacute sclerosing panencephalitis, premature
labor, spontaneous abortion, and preterm birth of the fetus. Perinatal
transmission rates are low.

Approach Considerations

Treatment of measles is essentially supportive care with maintenance

of good hydration and replacement of fluids lost through diarrhea or
emesis. Intravenous (IV) rehydration may be necessary if dehydration
is severe.

Vitamin A supplementation, especially in children and patients with

clinical signs of vitamin A deficiency, should be considered.
Postexposure prophylaxis should be considered in unvaccinated
contacts; timely tracing of contacts should be a priority.

Patients should receive regular follow-up care with a primary care

physician for surveillance of complications arising from the infection
(see Complications).

Supportive Care

Supportive care is normally all that is required for patients with

measles. Hospitalization may be indicated for treatment of measles
complications (eg, bacterial superinfection, pneumonia, dehydration,
croup).

Secondary infections (eg, otitis media or bacterial pneumonia) should

be treated with antibiotics; Patients with severe complicating infections
(eg, encephalomyelitis) should be admitted for observation and
antibiotics, as appropriate to their clinical condition.

Occasionally, IV rehydration is required; patients may be markedly

febrile and consequently may become dehydrated. Fever management
with standard antipyretics is appropriate.

Airborne precautions are indicated for hospitalized children during the

period of communicability (ie, 3-5 day before the appearance of a rash
to 4 days after the rash develops in healthy children and for the duration
of illness in patients who are immunocompromised). Susceptible health
care workers should be excused from work from the fifth to the 21st
day after exposure.

Antiviral Therapy

Measles virus is susceptible to ribavirin in vitro. Although ribavirin

(either IV or aerosolized) has been used to treat severely affected and
immunocompromised adults with acute measles or subacute sclerosing
panencephalitis (SSPE), [33] no controlled trials have been conducted;
ribavirin is not approved by the US Food and Drug Administration
(FDA) for this indication, and such use should be considered
experimental.

Vitamin A Supplementation
 Vitamin A supplements have been associated with reductions of
approximately 50% in morbidity and mortality and appear to help
prevent eye damage and blindness.

Because vitamin A deficiency is associated with severe disease from

measles, The World Health Organization recommends all children
diagnosed with measles should receive vitamin A supplementation
regardless of their country of residence, based on their age, as follows:

Infants younger than 6 months 50,000 IU/day PO for 2 doses

Age 6-11 months - 100,000 IU/day PO for 2 doses
Older than 1 year - 200,000 IU/day PO for 2 doses
Children with clinical signs of vitamin A deficiency The first 2 doses
as appropriate for age, then a third age-specific dose given 2-4 weeks
later

Postexposure Prophylaxis

Postexposure prophylaxis should be considered in unvaccinated

contacts. Prevention or modification of measles in exposed susceptible
individuals involves the administration of measles virus vaccine or
human immunoglobulin (Ig).

Measles virus vaccine

In the United States, the measles virus vaccine is routinely administered

along with the mumps and rubella vaccines as the measles-mumps-
rubella (MMR) vaccine. The vaccine is preventive if administered
within 3 days of exposure.

Contraindications to the vaccine include immunodeficiency;

generalized cancers (eg, leukemia, lymphoma); active, untreated
tuberculosis; and therapy with immunosuppressants. HIV infection is
only a contraindication in the presence of severe immunosuppression
(ie, CD4 counts lower than 15%). The vaccine should be deferred until
after delivery in pregnant patients and for at least 5 months in anyone
who has received antibody (ie, plasma, whole blood, any immune
globulin).

Human immunoglobulin

Human Ig prevents or modifies disease in susceptible contacts if

administered within 6 days of exposure. Human Ig is given to the
following individuals:

Those who are immunocompromised

 Infants aged 6 months to 1 year (morbidity is high in children younger
than 1 year
Infants younger than 6 months who are born to mothers without measles
immunity
Pregnant women

In contacts for whom the vaccine should be deferred (eg, pregnant

patients), human Ig 0.25 mL/kg (not to exceed 15 mL) should be
administered intramuscularly (IM) immediately after exposure, and the
measles vaccine should be given 6 months later. Exposed
immunocompromised patients with a contraindication to vaccination
should receive human Ig 0.5 mL/kg (not to exceed 15 mL) IM.

Reference:

American Academy of Pediatrics. Measles. Pickering LK, ed. Red

Book: Report of the Committee on Infectious Disease. Elk Grove, Ill:
AAP; 2006. 441-52.

B. Roseola

Background

Roseola is a common childhood disease. The cause is primary

infection with human herpesvirus 6 (HHV-6). The classic presentation
of roseola infantum is a 9- to 12-month-old infant who acutely
develops a high fever and often a febrile seizure. After 3 days, a rapid
defervescence occurs, and a morbilliform rash appears.

Like other herpes viruses, HHV-6 then remains latent in most

patients who are immunocompetent. Although clinical disease is
uncommon in patients who are immunocompetent, HHV-6 is a major
cause of morbidity and mortality in patients who are
immunosuppressed, particularly in patients with AIDS and in those
who are transplant recipients (eg, liver transplantation).

Epidemiology

Frequency

United States
Serologic tests indicate that human herpesvirus 6 (HHV-6) infection
is nearly universal. In emergency clinics, HHV-6 has been reported to
be responsible for 10-45% of cases of febrile illness in infants. A 2005
population-based study revealed primary HHV-6 infection cumulative
percentages of 40% by age 12 months and 77% by age 24 months. The
peak age of acquisition of primary HHV-6 infection is 9-21 months.

Race

With rare geographic exceptions, no racial differences seem to occur

in HHV-6 infection.

Sex

Zerr et al reported HHV-6 acquisition is associated with female sex

and having older siblings.

Age

Antibody titers are high in newborns because of maternal antibody.

Transplacental infection occurs in about 1% of cases. Titers decrease
from 3-9 months of age and then begin to rise because of primary
infections. Titers remain high for HHV-6B until after age 60 years.
Infection with HHV-6A appears later in life. In roseola infantum, age
ranges from 2 weeks to 3 years. In one study, almost one fourth of the
patients were younger than 6 months. In a Brazilian study, 75% of
HHV-6 infections occurred in children aged 6-17 months.

Etiology

The causative agent of roseola infantum was discovered in

1986. The Roseolovirus genus of the beta herpes virus hominis
subfamily contains human herpesvirus (HHV)6 and HHV-7. HHV-
6 has 2 variants: HHV-6A and HHV-6B. Their major differences are
cellular tropism. Debate has existed whether they represent 2 species.
HHV-6A infection is rarely associated with roseola infantum. HHV-
6A is associated with infection in adults who are
immunocompromised. HHV-6A infection occurs later in life, and
details are lacking. HHV-6B is the cause of roseola in infants. Because
seropositivity is nearly 100% in older children, most primary
infections with HHV-6B are asymptomatic. HHV-7 has been
identified in a few cases of roseola infantum. Recurrences of roseola
infantum are not common. A well-documented case of a 13-month-
old child who had a second episode of roseola exists. In the acute
phase of the second episode, HHV-7 was identified and excreted in
the saliva. This was followed by excretion of HHV-6.

Pathophysiology

In the primary infection, replication of the virus occurs in the

leukocytes and the salivary glands. HHV-6 is present in saliva. A
study monitoring HHV-6 and HHV-7 DNA in saliva samples during
the acute and convalescent phases demonstrated a significantly higher
rate of detection in children aged 3-9 years versus adults, suggesting
that children in the convalescent phase of roseola infantum are the
more probable source of infection. Early invasion of the CNS is
believed to occur, thus accounting for seizures and other CNS
complications. Evidence suggests that high serum levels of matrix
metalloproteinase 9 and tissue inhibitor of metalloproteinases 1 in
infants infected with HHV-6 may lead to blood-brain barrier
dysfunction, which may result in febrile seizures. Study of
cerebrospinal fluid levels of interleukin 1 and basic fibroblast growth
factor may indicate a role in contributing to HHV-6B growth and the
onset of encephalitis. Although rare in the primary disease of infancy,
generalized organ involvement has been reported with
gastrointestinal, hematopathic syndromes; hepatitis; and
hepatosplenomegaly.

Following the acute primary infection, HHV-6 remains latent

in lymphocytes and monocytes and has been found in low levels in
many tissues. Peripheral blood mononuclear cell cultures develop
enlarged balloonlike cells. Cells supporting virus growth are CD4+ T
lymphocytes. HHV-6 down-regulates the host immune response
through several mechanisms, including molecular mimicry by
production of functional chemokine and chemokine receptors.
The two variants of HHV-6 are A and B. The genomes of HHV-
6A/B have been sequenced. HHV-6B, the main cause of roseola,
consists of 97 unique genes. CD46 is the cell receptor for HHV-6,
which imparts the virus' broad tissue tropism. A possible association
of HHV-6 and multiple sclerosis has been suggested but is still
inconclusive. HHV-6 has been isolated in Kaposi sarcoma (caused by
human herpesvirus 8), in which it may contribute to tumor
progression. HHV-6 may facilitate oncogenic potential in lymphoma
and has been associated with chronic fatigue syndrome.
History

The classic roseola infantum patient is a 9- to 12-month-old

infant in previously good health and who has an abrupt onset of high
fever (40C), which lasts for 3 days with nonspecific complaints. A
febrile seizure occurs in 15% of patients. Rapid defervescence is
striking with the onset of a mild, pink, morbilliform exanthem. In
roseola infantum patients who are immunocompromised, the onset of
symptoms is usually abrupt, with fever, malaise, and CNS and other
organ system involvement.

Physical Examination

Despite the high fever, few clinical findings are observed early
in the course of roseola infantum. The lack of upper respiratory tract
infection is notable, and meningeal signs and encephalopathy are not
present. Gastrointestinal symptoms, signs of electrolyte imbalance, or
evidence of dehydration are rarely present. In addition to these
symptoms, some patients will also experience swollen glands in the
neck, mild diarrhea, and swelling of the eyelids.

A febrile seizure, with no residual findings, may have occurred. After

an abrupt loss of fever, the characteristic rash appears. The eruption is
generalized and subtle. It is composed of either discrete, small, pale
pink papules or a blanchable, maculopapular exanthem that is 1-5 mm
in diameter. This rash may last 2 days.

The characteristic enanthem (Nagayama spots) consists of

erythematous papules on the mucosa of the soft palate and the base of
the uvula. The enanthem may be present on the fourth day in two
thirds of patients with roseola.
 Picture 1. Roseola infantum. Image courtesy of Wikimedia
Commons.

Picture 2. Nagayama Spots

Laboratory Studies

In response to the early acute febrile presentation, laboratory

studies may include a CBC count, urinalysis, blood cultures, and
cerebrospinal fluid examination. If the patient presents with a febrile
seizure, a seizure workup may be indicated.

Roseola infantum diagnosis may be confirmed by virus isolation,

seroconversion (immunoglobulin M), or detection of viral DNA
sequences in peripheral blood mononuclear cells. Specific antibodies
to differentiate human herpesvirus (HHV)6A- and HHV-6B can be
determined using a serological assay based on immunoblot analysis
using recombinant HHV-6A p100 and HHV-6B 101K.

Histologic Findings

Typical ballooning cells may be seen in any organ system

affected with HHV-6 infection.
Medical Care

At present, no medical antiviral therapy is available for human

herpesvirus 6 (HHV-6) infection that causes roseola. Thus, treatment
of roseola infantum is supportive. However, in 2002, Rapaport et al
reported that antiviral prophylaxis with ganciclovir may prevent
HHV-6 reactivation in high-risk bone marrow transplant patients.
Further double-blinded randomized studies are needed. Short- or long-
term antiseizure medications are not recommended for infants who
have had a febrile seizure secondary to roseola. Inpatient care for
roseola infantum consists of support with antipyretics and treatment
of gastroenterologic, respiratory, hematologic, or CNS complications.

Complications

In roseola infantum, complications are rare. Given that

seroconversion is practically universal, finding any of the
complications that have been reported in the gastrointestinal, central
nervous, pulmonary, and hematopoietic systems is rare. Children who
have seizures with roseola are not expected to have further febrile or
nonfebrile seizures.

Prognosis

Practically all patients who are immunocompetent survive

roseola infantum without sequelae. In patients who are
immunosuppressed, multisystem complications are not unusual.
Infection may be chronic, leading to viral progression and death.
Primary infection with HHV-6 may be asymptomatic, or it may cause
the exanthem subitum/roseola syndrome. reference_ids_tool_tip reference_ids [8]
Within that complex, otitis, gastroenteritis, respiratory distress, and
seizures may occur. Primary infection in infants is rarely complicated
by serious disease and is very rarely fatal. Case reports of many organ
systems being involved indicate a potential morbidity, although this is
rarely observed. The second stage of HHV-6 infection occurs in
healthy children and adults. The virus replicates in the salivary glands
and is latent in peripheral blood mononuclear cells. A form of latent
infection is found in the integration of the virus in host chromosomes.
In adults who are immunocompetent, infection or reactivation of
HHV-6 is rare. These few patients have been reported to have
lymphadenopathy, hepatitis, and a mononucleosis like syndrome. In
patients who are immunocompromised, a more serious disease is seen.
 Transplant recipients (eg, marrow, kidney, liver) may have marrow
suppression, pneumonitis, encephalitis, hepatitis, fever, and an
eruption. Organ rejection and death may occur. Studies of these
patients are complicated by frequent concomitant reactivation of
human herpesvirus 7 (HHV-7) and cytomegalovirus. HHV-6 was
implicated as the cause of 30% of cases of pneumonitis in patients
who underwent bone marrow transplantation. Patients with AIDS
comprise the second at-risk group; however, antiretroviral therapy has
reduced morbidity. HHV-6 infection in patients with AIDS results in
viremia, lymphadenopathy, disseminated organ involvement, active
CNS infection, retinitis, and death. HHV-6A is more common in
patients with AIDS than in other patients.

Prevention

Because seroconversion in the United States is nearly 100%, isolation

is not indicated. The infection is spread through saliva in both the
acute phase and the chronic phase. No risk appears to be present to
pregnant women exposed to roseola. Care must be taken to distinguish
this from rubella. No reports of infection or complications following
exposure exist. This is probably because of the nearly universal
seroconversion and latent infection. No sequelae of intrauterine
infection are known. Isolation is not indicated.

Reference: Christopher R Gorman. Roseola Infantum. MD Avenues

Dermatology, Private Practice.
(https://emedicine.medscape.com/article/1133023-overview )

C. Rubella

A. Etiologic Agent Rubella is caused by the rubella virus, an enveloped,

positive-stranded RNA virus (family Togaviridae, genus Rubivirus).

B. Clinical Description When contracted after birth, rubella is usually a mild

disease characterized by a generalized maculopapular rash (which
sometimes begins on the face), swollen lymph nodes, and slight fever.
The rash presentation can be quite variable. Up to 50% of infections
occur without recognized rash. Transient inflammation of the joints
rarely occurs in children but is common in adolescents and adults,
especially women. Encephalitis (1 per 6,000 cases) and
thrombocytopenia (1 per 3,000 cases) are rare complications. Rubella is
of greatest danger to the unborn fetus. Up to 90% of infants born to
 mothers infected in the first trimester will develop the physical anomalies
referred to as congenital rubella syndrome (CRS). CRS is characterized
by any of a number of complications and findings, including blindness,
heart defects, deafness, behavioral disorders, mental retardation, growth
retardation, bone disease, enlarged liver and spleen, thrombocytopenia,
and purple skin lesions. Some effects may not be apparent at birth.
Reinfection has been demonstrated on rare occasions, but only very
rarely has resulted in CRS.

C. Vectors and Reservoirs Humans are the only known host for rubella.

D. Modes of Transmission Postnatal rubella is transmitted from person to

person by droplet or direct contact with the nasopharyngeal secretions of
an infected person or with the nasopharyngeal secretions or urine of an
infant with CRS. Transplacental infection resulting in CRS occurs in
infants who are born to women with rubella occurring at 20 weeks or less
of gestation.

E. Incubation Period The incubation period is usually 1618 days, with a

range of 1423 days.

F. Period of Communicability or Infectious Period The infectious period is

usually from seven days before to seven days after rash onset. Studies
have shown presence of rubella virus in nasopharyngeal secretions
ranging from 514 days after rash onset. However, infectiousness
decreases significantly after day five in most individuals. Rubella is
similar to influenza and mumps in infectiousness and is not as contagious
as measles or chickenpox. A person who is asymptomatic but laboratory-
confirmed and epidemiologically-linked to a laboratory-confirmed case
that is clinically consistent with rubella should be considered infectious
for 530 days after exposure that resulted in infection. Infants with CRS
shed virus in nasopharyngeal secretions and urine for a longer period; a
small proportion continue to be infectious for one year or more.

G. Epidemiology Rubella occurs worldwide. In temperate zones, peak

incidence is in late winter and early spring. Before the widespread use of
rubella vaccine, which was licensed in 1969, peaks of rubella incidence
occurred in the U.S. every 69 years, and most cases occurred in children.
Most reported rubella in the U.S. since the mid-1990s has occurred
among Hispanic young adults who were born in areas where rubella
vaccine is not routinely given and who were never exposed to rubella in
their countries of origin. The percentage of susceptible people may be
 higher in certain immigrant population groups, especially adolescent and
adult males from Latin America. Most adults born in the U.S. before
1957 have been infected naturally and are probably immune to rubella.
Recent serologic surveys indicate that about 10% of young adults are
susceptible to rubella. In recent years in the U.S. and in Massachusetts,
outbreaks have occurred among immigrant populations due to lack of
rubella vaccination programs in their countries of origin. Outbreaks now
occur predominantly in workplaces and communities at large, although
school settings have been affected. CRS now disproportionately affects
infants born to foreign-born women. Identifying and managing
susceptible pregnant women who may have been exposed to rubella is
particularly challenging, especially in community-wide outbreaks.

B. Laboratory Testing Services Available Note:

1. Rubella IgM Test It is very important to obtain laboratory confirmation

of cases of rubella and suspect cases of rubella. Due to crossreacting
antibodies and other test issues, there are problems related to the
sensitivity and specificity of commercially available IgM tests. The
specimen should be drawn at least three days after onset of rash (to
minimize the possibility of false negative results) and within six weeks
of rash onset. (If serum is collected prior to the third day, a follow-up
specimen may be requested.) This test is performed at the MDPH State
Laboratory Institute (SLI), and the amount of serum required is 2 mL.

2. Rubella Total Antibody Paired-Titer Test Paired total antibody testing can
be helpful when rubella IgM results are not interpretable. Acute serum
should be collected as soon as possible after rash onset; convalescent
serum should be collected 14 days later. The amount of serum required
is 2 mL.

3. Virus Isolation/Molecular Characterization of Rubella Virus isolation is

much less useful for disease control purposes than serologic testing
because results are not available for several weeks. However, molecular
characterization of isolated rubella virus is an extremely important tool
in epidemiologic research to determine, for example, the source of the
infection and which cases and outbreaksare linked to each other. Also, in
cases where serology is not useful or possiblefor example, when a
suspect case has been recently vaccinated with the measles, mumps, and
rubella (MMR) vaccinevirus isolation can be used for confirmation,
and molecular characterization can distinguish wild-type virus from
vaccine virus. Specimens for rubella virus isolation should be submitted,
 along with the SLI Specimen Submission Form (found at the end of this
chapter or on the MDPH website at
www.mass.gov/dph/bls/generalform.pdf), to the SLI Virus Isolation
Laboratory, which will forward them to the Centers for Disease Control
and Prevention (CDC). Please contact a MDPH immunization
epidemiologist at (617) 983-6800 or (888) 658-2850 about submitting
specimens for virus isolation, and consult Attachment B: Instructions for
Collection of Serologic Specimens from Suspect Cases (Including CRS
Infants) at the end of this chapter.

4. Polymerase Chain Reaction (PCR) PCR can be used to detect the presence
of rubella virus in tissue culture or directly in clinical specimens. It can
also be used for molecular characterization. Specimens submitted to the
SLI Virus Isolation Laboratory for rubella virus PCR and
characterization will be forwarded to the CDC.

References:

- Institute for Clinical Systems Improvement. Immunnizations.

Bloomington, Mn:ICSI;2008
- Morgan-Capner P. Diagnosing rubella.BMJ:820-1

4. How to prevent the disease?

Answer:
1. Prevention of Transmission
Prevention can be done through Health Promotion action, both at home
and environment and of course specific transmission.
A. Health Promotion of the host.
Public education is provided by the Ministry of Health and private
practice doctors who advocate measles immunization for all infants,
young children and young adults who are still vulnerable.
B. Prevention of measles virus transmitted through the spit of saliva air
of measles patients
C. Isolate after rash appears on 4 days of contact in order to heal the
contagion.
2. Prevention of Disease Prevention of measles is divided into several
stages as follows.
A. In case of contact with a person with measles under 3 days of direct
immunization against measles can provide immunity that has not
arisen symptoms of the disease.
 B. In case of contact with measles sufferer after 3-6 days immuno
globulin treatment 0.25ml / kgBB.On the compromised immuno
individuals given is immuno globulin 0,5ml / kgBB with a
maximum dose of 15 ml or IGIV 400mg / kgBW.
3. Immunization
Measles virus that contains attenuated virus is the vaccine of choice
used for everyone not immune to measles. A single dose of live
(attenuated) live vaccine is usually combined with other live vaccines
(mumps, rubella), may be given together with toxoid, may provide
active immunity in 94- 98% of susceptible individuals, life, kolahi form
of infection is very mild or infection is not visible and not transmitted
The second dose of measles vaccine can increase the rate to 99%. To
reduce the number of vaccine failures, in the United States routine 2-
dose measles vaccine schedule is given, with the initial dose given at
12-15 months of age or as soon as possible after that age. The second
dose is given at the time of admission (age 4-6 years). However, this
second dose may be given as early as possible, 4 weeks after the first
dose in circumstances where for measles exposure is very high. Both
doses are given as a combination vaccine MMR (mzales, mumps and
rubella). Routine immunization with MMR at 12 months is important
in areas where lead measles cases. During outbreaks in the community,
the age for immunization using monovalent measles vaccine can be
reduced to 6-11 months. The second dose of measles vaccine is then
given at 12-15 months of age and the third dose at the time of admission.

Reference: Bong Stevana. Penyebaran Penyakit Campak. Universitas

Diponegoro. Semarang. 2013 eprints.undip.ac.id.