This document provides information on measles, including its pathogenesis, epidemiology, clinical characteristics, diagnosis, treatment, immunization, and vaccination history. It discusses how the measles virus infects and spreads in the body, causes a characteristic rash, and can lead to serious complications. It outlines how measles was once very common but widespread vaccination starting in 1963 led to its elimination in the United States by 2000. The importance of a routine two-dose vaccination schedule is emphasized to provide broad protection against the highly contagious virus.

2. Presented by: irfan ahmed
Final year pharm.D

3. introduction
• Measles is an acute, highly infectious disease characterized
by fever, respiratory symptoms, and a maculopapular
rash. Complications are common and may be quite serious.
• Measles has been recognized as a distinct clinical disease for more
than 10 centuries and in the developing world is associated with
high mortality rates in early childhood.
.

4. Pathogenesis and Pathology
• Humans are the only natural host of the virus but other animals can be infected experimentaly
• The virus gains access to the human body via the respiratory tract, where it
multiplies locally; the infection then spreads to the regional lymphoid tissue,
where further multiplication occurs.
• Primary viremia disseminates the virus,which then replicates in the
reticuloendothelial system. Finally, a secondary viremia seeds the epithelial
surfaces of the body, including the skin, respiratory tract, and conjunctiva, where
focal replication occurs.
• Measles can replicate in certain lymphocytes, which aids in dissemination
throughout the body.
• The described events occur during the incubation period, which typically lasts 8–
15 days but may last up to 3 weeks in adults.
• Patients are contagious during the prodromal phase (2–4 days) and the first 2–5
days of rash, when virus is present in tears, nasal and throat secretions, urine,
and blood.
• The characteristic maculopapular rash appears about day 14 just as circulating
antibodies become detectable, the viremia disappears, and the fever falls.
• The rash develops as a result of interaction of immune T cells with virus-infected
cells in the small blood vessels and lasts about 1 week. (In patients with
• defective cell-mediated immunity, no rash develops.)

6. The epidemiology
of
• measles is markedly affected by population size, density,
movement and social behavior. In the absence of vaccination, the
disease infects essentially everyone at some time during life except
in
isolated populations. Beginning of vaccination in 1963.
• Measles has not been endemic in the United States since
1997.
• Indigenous transmission of measles was interrupted in the
Americas in 2002.
• Mathematical models suggest that transmission of measles to
12–18 persons

7. Clinical characteristics
• Fever( more then 40 degree)and malaise ranging from 8-16 days.
• followed shortly thereafter by cough, coryza, and conjunctivitis.
• An enanthem, characterized by small bluish white spots on a red
background (Koplik’s spots), may be seen on the buccal mucosa
within the two days before
• and after the onset of rash. The characteristic maculopapular rash of
measles usually appears an average of 14 days after infection begins
.

8. Clinical characteristics
• classically starts on the face and hairline and then spreads to the
trunk and extremities.
• The patient’s temperature usually peaks 1–3 days following the
onset of rash. The rash, areas of which fade in order of appearance,
typically lasts 5–7 days, and the illness is entirely gone
• by 10–14 days after the onset of symptoms. There are few clinically
in apparent primary infections

9. Clinical characteristics
• The infectious period is usually considered to stretch from four
days before to four days after the onset of rash.
• Measles is usually transmitted in large respiratory droplets,
requiring close contact between patients and susceptible
persons.
• measles virus can survive for at least two hours in fine
droplets, and airborne spread has been documented.
• carrier state nor an animal reservoir is known

10. Other symptoms
• runny nose, and red eyes

11. Complications
• The risk of complications and death is highest in young
children and adults.
• In United states the most common complications are
• 1) otitis media and pneumonia, which occur in 2–14% and in
2–9% of cases, respectively.
• In developing countries
• Complications and case fatality rates may be higher.
• Pneumonia, the most common cause of death, may be caused
by the measles virus itself or by secondary bacterial infection

12. • Secondary viral infections may play a prominent role in
measles pneumonia-related deaths in the developing world.
• Severe diarrhea and malnutrition may result from measles
infection, particularly in the developing world.

13. Measles encephalitis
• occurs typically 4–7 days after the onset of rash (range generally 1–
15 days), is reported approximately
• once in every 1000 cases of measles.
• Approximately 15% of patients with measles encephalitis die, and
another 25–35% have permanent neurologic residua.
• Less common complications include bronchiolitis, sinusitis,
mastoiditis, myocarditis, keratoconjunctivitis,mesenteric adenitis,
hepatitis, and thrombocytopenic purpura

14. • In United states the reported death to case ratio is 1-3 per
1000 cases
• And in developing countries it is 5-10% or even higher.
• Atypical measles syndrome, characterized by high fever,
pneumonia, pleural effusions, edema of the hands and feet,
hepatic abnormalities, and an unusual rash, is a rare
manifestation of measles infection
• sometimes seen in persons who received killed measles
vaccine in the past and who were subsequently exposed to
measles virus

15. • Measles infection during pregnancy is associated with
spontaneous abortion and with delivery of low birth weight
infants.
• Although there have been rare reports of congenital
malformations associated with measles infection during the
first trimester,
• there is no good evidence for the existence of a congenital
measles syndrome

16. sub acute sclerosing pan
encephalitis (SSPE)
• measles virus can cause a degenerative disorder of the central
nervous system known as) sub acute sclerosing pan
encephalitis (SSPE. The reported risk of SSPE ranges from 1
case per 100,000 measles cases in persons infected after four
years of age
• 18 cases per 100,000 measles cases in persons infected in
infancy.
• A recent study in the U.S. noted a rate of 22 cases of SSPE per
100,000 reported measles cases.
• This illness begins insidiously an average of seven years
following the initial infection and is characterized by
progressively severe personality changes, myoclonic seizures,
motor impairment,coma, and death over the course of several
months to years

17. Epidemiology
• Before the introduction and widespread use of measles vaccine,
• measles infection was essentially universal in the United States.
• Approximately 95% of persons living in urban areas were infected by
age 15 years.
• The disease typically appeared in cycles with major peaks every 2–3
years. A marked seasonal pattern was apparent with peaks during
the late spring months.
• The highest reported age-specific incidence rates were in children 5–
9 years old.
• In the decade from 1950–1959, an annual average of more than
500,000 cases was reported.
• The true number of infections was estimated to be nearly 10 times
as high.
• During the same period, nearly 500 measles deaths were recorded
each year.

18. Etiology
• Measles is caused by a single-stranded RNA virus of the
paramyxovirus group.
• It is very sensitive to acid conditions, drying, and light,but can
survive in aerosolized droplets.
• Three membrane proteins appear to play critical roles in the
pathogenesis.
• The hemagglutinin protein (H), which projects from the virion,
attaches to cell surfaces.
• The fusion (F) protein allows cell-to-cell spread.
• Finally, the matrix(M) protein, associated with the inner surface of
the viral envelope,
• appears important for successful generation of intact viral particles.
• Abnormalities in the synthesis of these proteins have been
postulated to play an important role in the pathogenesis of SSPE

20. • Measles virus infection with either wild type measles or live virus
vaccine induces the production of a variety of antibodies.
• Immunoglobulin M (IgM) antibodies are detectable in approximately
80% of cases within the first 72 hours after rash onset and in nearly
100% of cases there after.
• IgM antibodies decline to undetectable levels within 1–2 months,
they provide evidence of recent infection.
• Testing a single specimen for measles IgM antibody is the preferred
method for evaluating suspected measles in most countries.

21. Diagnosis
• IgG antibodies appear shortly after rash onset, and peak 2–4
weeks later and appear to last a lifetime.
• Therefore single serum IgG antibody tests are typically used to
assess immunity to measles.
• A significant rise in total antibody (IgG and IgM) in paired
titers, with acute serum drawn shortly after rash onset and
convalescent serum two weeks later, provides laboratory
confirmation of acute measles infection.
• Although testing of paired sera is less convenient and takes
longer than IgM testing, it is more accurate and may help to
validate IgM results in some situations.
• Serologic tests cannot distinguish between antibody produced
by wild type infection and that resulting from live measles
virus vaccination.

22. Diagnosis
• Because of the widespread availability and ease of use,
enzyme linked immunosorbent assays (ELISA) tests are the
most commonly used method to measure measles IgM and
IgG antibodies.
• Several commercial ELISA kits have been shown to be sensitive
and specific.
•Plaque reduction neutralization(PRN)
assays are considered the gold standard for antibody testing
because they provide a quantitative measure of the
antibodies.
• However, PRN testing is laborious and generally confined to
research settings. In addition to the humoral immunity
represented by the antibodies,

23. Diagnosis
• Measles virus can be cultured from respiratory secretions,
urine or whole blood or detected by reverse transcriptase
polymerase chain reaction (RT-PCR) in these specimens.
• These tests can support the laboratory diagnosis of measles
but they do not currently serve as frontline diagnostic tools
because they take too much time to provide results and the
sensitivity of the tests is highly dependent on the timing and
quality of the specimen collection and on proper shipping.
• However, testing of viral specimens by culture and RT-PCR
allows determination of the genotype of the virus, which
enhances the ability to identify sources of infection and track
chains of transmission.

24. Limitations
• Both serologic and virologic specimens require a cold chain for
storage and transport.
• Methods are currently being developed to allow both serologic and
virologic testing from a single specimen and to limit the invasiveness
of the collection method and the need for a cold chain. The two most
promising are oral fluid collection and filter paper blood spots.
• Oral fluids specimens have been used successfully without cold chain
in the United Kingdom for measles surveillance.
• since the mid-1990s, initially with a radioimmunoassay and more
recently with ELISA tests with reasonably high sensitivity and
specificity. However, these tests are not currently commercially
available.

25. Treatment
• There is no specific treatment for measles. Most people with
uncomplicated measles will recover with rest and supportive
treatment.
• Symptomatic treatment,
• Vitamin A on recommendation of WHO to reduce blindness.
• A specific drug treatment for measles ERDRP-0519 has shown
promising results in animal studies, but has not yet been tested in
humans.
• In May 2015, the journal Science, published a report in which
researchers found that the measles infection can leave a population
at increased risk for mortality from other diseases for 2 to 3 years.

26. Immunization
•Passive immunity
• Passive immunity against measles disease can be induced by the
administration of commercially prepared immune globulin (IG)
(formerly called immune serum globulin [ISG]).
• Administration of 0.25 mL of IG per kilogram (maximum dose 15 mL)
can modify or prevent the development of measles in the exposed
person.
• The IG preparation is most effective if administered within six days of
exposure, preferably as soon after the exposure as possible.
• IG is particularly indicated for susceptible household contacts,
especially those who are immunocompromised.

27. Immunity
• Almost all infants acquire passive immunity against measles from the
transfer of maternal antibodies across the placenta. Such infants are usually
immune to measles for at least the first six months of life. Immunity
• gradually wanes thereafter, and by 12–15 months essentially 100% of
infants are susceptible. Children born to mothers who have vaccine induced
antibodies tend to become seronegative earlier than infants born to
mothers who have had measles disease.
• Measles disease induces higher levels of antibodies than measles
vaccination.
• “Modified” measles is a mild form of illness occasionally seen in persons
with passively acquired antibody.
• The incubation period may be prolonged up to 20 days.

28. Active Immunity.
• In 1963, two types of measles vaccine were licensed in the
United States. One was a vaccine prepared from live
attenuated virus grown in chick embryo tissue culture
(Edmonston B strain).
• Because there was a high rate of reactions to this vaccine,
including fever, rash, and catarrhal symptoms, the
concomitant administration of IG was recommended.
• A second vaccine used the same virus, but the virus had been
inactivated (killed) by formaldehyde.
• Immunity to the killed measles virus vaccine (KMV), or to KMV
followed by live measles vaccine within three months, was
short lived and induced hypersensitivity to measles virus in
some persons, resulting in atypical measles syndrome

29. Vaccination history
• Beginning in 1965, vaccines prepared from further-attenuated
strains of measles virus and not requiring the concomitant
administration of IG became available and quickly became the
most common vaccines
• The use in the United States (Schwarz strain licensed in 1965
and Moraten strain licensed in 1968).
• From 1965–1989, when one dose of measles vaccine was
recommended, more than 172 million doses of measles
containing vaccines were distributed in the United States.
• Following the recommendation of a routine two-dose
schedule in late 1989.

30. History
• more than 213 million doses were distributed from 1990 to
2005.
• The age at which measles vaccine is administered represents a
balance between the ability of the vaccinee to respond to
vaccination and the risk of measles.
• The proportion of vaccine recipients who developed
antibodies to measles virus increases with increasing age at
administration up to 12–15 months of age

31. History
• When measles vaccine was first introduced in the United
States, it was administered at nine months of age because of
the high risk of measles,
• even though seroconversion rates were not optimal.
• As the risk of measles declined, the age at administration was
raised to 12 months (1965) and 15 months (1976) to assure
maximal seroconversion rates.

32. Vaccination schdule
• Recent studies, performed when an increasing proportion of infants
are born to mothers with vaccine-induced immunity, indicate
seroconversion rates at 12 months are comparable to rates at 15
months.
• Thus,in 1994 the Advisory Committee for Immunization Practices
(ACIP) recommended that the first dose of measles vaccine as part
of measlesmumps- rubella (MMR) vaccine could be administered
any time between 12 and 15 months of age.
• Administration of further-attenuated live measles vaccine to
children at 12–15 months of age or older can be expected to
produce measurable circulating antibodies in 95% or more of
recipients.
• During measles outbreaks, vaccine can be given to children as
young as six months of age with subsequent revaccination.
• The vast majority of persons with seroconversion have long-term,
probably lifelong immunity.

33. Vaccination schdule
• Because measles transmission had been documented among
the 2–5% of persons who did not respond to a first dose of
measles vaccine,
• in 1989, both the Committee on Infectious Diseases of the
American Academy of Pediatrics (AAP) and the ACIP
recommended
• a change from a one-dose schedule to a routine two-dose
schedule for measles vaccination.
• The second dose recommendation focused on school children.
States and localities generally implemented second dose
vaccination for one school grade cohort at a time

34. Risk of infections
• In addition to school age children, other groups of people are at
• increased risk of exposure to measles including persons who work in
health-care facilities, students in post high school institutions and
international travelers.
• Persons in these groups should receive two doses of measles
vaccine if they do not have other evidence of measles immunity
• Because almost half of imported measles cases occur in United
States residents returning from overseas trips, infants 6–11 months
of age traveling internationally should receive a dose of measles
vaccine before departure
• and persons over 13 months of age should receive the second dose
of measles vaccine before departure,given at least 28 days after the
first dose.

35. ADR risk
• Fever higher than 103°F (39.4°C) and fleeting rash are reported in 5–15% of
recipients of measles vaccine.
• Encephalitis has been reported after the use of measles vaccine Comparing the
number of cases reported to have occurred within the 30 days after immunization to
the number of doses distributed in the United States yields an estimate of
approximately one case of encephalitis per million doses of vaccine distributed.
• This rate is similar to that of reported encephalitis of unknown cause seen in a
comparable period in the general population in the same age group.
• The Institute of Medicine has concluded that available evidence is not sufficient to
prove that vaccination causes encephalopathy or encephalitis.

36. ADR risk
• Some have raised concerns that MMR vaccine can cause
autism.
• However, an exhaustive review by the Institute of Medicine of
at least 13 studies that addressed the question concluded that
the evidence favors rejection of a causal relationship between
MMR and autism.

37. Contraindications
• Measles vaccine is contraindicated in persons with
immunodeficiency or immunosuppression.
• However, it should be administered to persons with
asymptomatic human immunodeficiency virus (HIV) infection
since measles disease may be severe or fatal in such persons

38. Contraindications
• MMR vaccination causes clinically evident thrombocytopenia
in
• 1:30,000 to 1:40,000 vaccinations.
• Because persons with a history of idiopathic
thrombocytopenic purpura (ITP) may be at increased risk for
thrombocytopenia following measles vaccination.
• a history of ITP is a contraindication to measles vaccination.

39. Contraindications
• Vaccination of persons who received IG, whole blood, or other
antibody-containing blood products should be postponed for
3–7 months or longer depending on the product and dose
received to avoid potential interference with seroconversion.
• Vaccination should be postponed in persons with severe
febrile illnesses.
• Persons with mild illnesses such as upper respiratory tract
infections may be vaccinated.

40. Impact of Vaccination on
Disease