Epidemiology of Measles Epidemiology of Measles

Ahmed Mandil, MBChB, DrPHAhmed Mandil, MBChB, DrPH

Prof of EpidemiologyProf of Epidemiology

Dept of Family & Community MedicineDept of Family & Community Medicine

College of Medicine, King Saud UniversityCollege of Medicine, King Saud University

HeadlinesHeadlines

DistributionDistribution Clinical presentations / complicationsClinical presentations / complications AgentAgent DiagnosisDiagnosis ReservoirReservoir Portals of exit / entryPortals of exit / entry Modes of transmissionModes of transmission SusceptibilitySusceptibility Prevention and controlPrevention and control

Distribution (I)Distribution (I)

Measles is one of the typical viral diseases of Measles is one of the typical viral diseases of childhood. However, unlike other common viral childhood. However, unlike other common viral diseases i.e. Varicella-Zoster Virus, rubella, mumps, diseases i.e. Varicella-Zoster Virus, rubella, mumps, and parvovirus infections, measles often leads to and parvovirus infections, measles often leads to severe complications that may be fatal. In the third severe complications that may be fatal. In the third world, there may be up to 900,000 measles related world, there may be up to 900,000 measles related deaths per year. Therefore, there is a lot of pressure deaths per year. Therefore, there is a lot of pressure on health in different countries in controlling the on health in different countries in controlling the disease through vaccination. Indeed, measles is disease through vaccination. Indeed, measles is targeted by the WHO in its Expanded program of targeted by the WHO in its Expanded program of immunization (EPI).immunization (EPI).

Distribution (II)Distribution (II)

In the Northern Hemisphere, the incidence tends to In the Northern Hemisphere, the incidence tends to rise in the winter. In tropical regions epidemics are rise in the winter. In tropical regions epidemics are less marked. In the pre-vaccination era, the less marked. In the pre-vaccination era, the maximum incidence was seen in children aged 5 - 9 maximum incidence was seen in children aged 5 - 9 years. By the age of 20, approximately 99% of years. By the age of 20, approximately 99% of subjects have been exposed to the virus. With the subjects have been exposed to the virus. With the introduction of vaccine, measles infection has shifted introduction of vaccine, measles infection has shifted to the teens in countries with an efficient to the teens in countries with an efficient immunization programme. immunization programme.

Introduction (III)Introduction (III)

In contrast, in third world countries, measles infection In contrast, in third world countries, measles infection has its greatest incidence in children under 2 years of has its greatest incidence in children under 2 years of age. Here the disease is a serious problem with a age. Here the disease is a serious problem with a high mortality (10%) with malnutrition being an high mortality (10%) with malnutrition being an important factor. In general, measles mortality is important factor. In general, measles mortality is highest in children < 2 years and in adults. Acute highest in children < 2 years and in adults. Acute encephalitis is a severe complication with a encephalitis is a severe complication with a frequency of around 1 in 1000-5000. The mortality frequency of around 1 in 1000-5000. The mortality rate is around 15%, 20-40% are left with residual rate is around 15%, 20-40% are left with residual neurological sequelae.neurological sequelae.

Clinical presentations (I)Clinical presentations (I)

After an After an incubation period incubation period of 10 - 11 days, the patient of 10 - 11 days, the patient enters the enters the prodromalprodromal stage with fever, malaise, stage with fever, malaise, sneezing, rhinitis, congestion, conjunctivitis and sneezing, rhinitis, congestion, conjunctivitis and cough. cough. Koplik's spotsKoplik's spots, which are pathognomonic are , which are pathognomonic are measles, appear on the buccal and lower labial measles, appear on the buccal and lower labial mucosa opposite the lower molars. The distinctive mucosa opposite the lower molars. The distinctive maculo-papularmaculo-papular rash appears about 4 days after rash appears about 4 days after exposure and starts behind the ears and on the exposure and starts behind the ears and on the forehead. From here the rash spreads to involve the forehead. From here the rash spreads to involve the whole body. whole body.

Clinical Presentation (II)Clinical Presentation (II)

ComplicationsComplications

Secondary bacterial infection:Secondary bacterial infection: e.g. otitis media, bronchitis and e.g. otitis media, bronchitis and pneumonia. pneumonia.

Measles Pneumonia:Measles Pneumonia: mainly in immuno-compromised patients mainly in immuno-compromised patients Subacute sclerosing panencephalitis (SSPE):Subacute sclerosing panencephalitis (SSPE): in children and in children and

young adults and occurs 6 - 8 years after the initial attack of young adults and occurs 6 - 8 years after the initial attack of measles. The incidence is of the order of 1 in 100,000 cases of measles. The incidence is of the order of 1 in 100,000 cases of acute measles. Half the SSPE patients have contracted acute measles. Half the SSPE patients have contracted measles before the age of 2 years. measles before the age of 2 years.

Acute measles encephalitis Acute measles encephalitis Myocarditis Myocarditis Thrombocytopenic purpuraThrombocytopenic purpura

Cycle of Communicable Cycle of Communicable Disease TransmissionDisease Transmission

AgentAgent ReservoirReservoir Portal of exitPortal of exit Modes of transmissionModes of transmission Portal of entryPortal of entry Susceptible hostSusceptible host

AgentAgent

Member of the family of Member of the family of ParamyxovirusesParamyxoviruses ssRNA enveloped ssRNA enveloped virus, helical symmetry lacks virion neuraminidase and thus virus, helical symmetry lacks virion neuraminidase and thus grouped into a separate genus, the grouped into a separate genus, the morbillivirus morbillivirus

Envelope consists of haemagglutinin protein and the fusion Envelope consists of haemagglutinin protein and the fusion protein embedded in the lipid bilayer M protein (membrane or protein embedded in the lipid bilayer M protein (membrane or matrix protein) lies immediately below the membrane. matrix protein) lies immediately below the membrane.

ssRNAssRNA is encased in a helix of N (nucleocapsid protein). The is encased in a helix of N (nucleocapsid protein). The ssRNA molecule is of negative sense. The HA protein acts as a ssRNA molecule is of negative sense. The HA protein acts as a means of attachment to susceptible cells.means of attachment to susceptible cells.

Measles is an Measles is an antigenically stable antigenically stable virus. There is virus. There is one serotype one serotype only and there are very little differences between different only and there are very little differences between different isolates.isolates.

DiagnosisDiagnosis

History History Clinical examinationClinical examination Laboratory investigationsLaboratory investigations

– MicroscopyMicroscopy– Immuno-fluorescence:Immuno-fluorescence: direct and indirect direct and indirect

immunofluorescence have been used extensively to immunofluorescence have been used extensively to demonstrate MV antigens in cells from NPS specimens. demonstrate MV antigens in cells from NPS specimens.

– Virus isolation:Virus isolation: measles virus can be isolated form a measles virus can be isolated form a variety of sources, e.g. throat or conjunctival washings, variety of sources, e.g. throat or conjunctival washings, sputum, urinary sediment cells and lymphocytes. sputum, urinary sediment cells and lymphocytes.

– Serology:Serology: diagnosis of measles infection can be made if the diagnosis of measles infection can be made if the antibody titres rise by 4-fold between the acute and the antibody titres rise by 4-fold between the acute and the convalescent phase or if measles-specific IgM is found. The convalescent phase or if measles-specific IgM is found. The methods that can be used include: Hemagglutination methods that can be used include: Hemagglutination lnhibition (HAI), Complement Fixation (CF), neutralization lnhibition (HAI), Complement Fixation (CF), neutralization and Enzyme-Labeled Immuno-Sorbent Assay (ELISA) tests. and Enzyme-Labeled Immuno-Sorbent Assay (ELISA) tests.

ReservoirReservoir

Humans in the form ofHumans in the form of Carriers (sub-clinical, during the incubation period)Carriers (sub-clinical, during the incubation period) Cases (through-out the course of the clinical Cases (through-out the course of the clinical

sydrome)sydrome)

In contrast to the influenza virus, measles does not In contrast to the influenza virus, measles does not have an animal reservoir, which makes it candidate have an animal reservoir, which makes it candidate for “elimination” if we manage to successfully prevent for “elimination” if we manage to successfully prevent infection among human reservoirs. infection among human reservoirs.

Portals of exit / entryPortals of exit / entry

Respiratory systemRespiratory system ExitExit (from reservoir): exhalation (from reservoir): exhalation EntryEntry (into susceptible host): inhalation (into susceptible host): inhalation

Modes of TransmissionModes of Transmission

DirectDirect – Droplet – Droplet IndirectIndirect – Airborne – Airborne The virus spreads by the respiratory route via aerosol The virus spreads by the respiratory route via aerosol

droplets and respiratory secretions which can remain droplets and respiratory secretions which can remain infectious for several hours. The infection is acquired infectious for several hours. The infection is acquired through the upper respiratory tract or conjunctiva.through the upper respiratory tract or conjunctiva.

SusceptibilitySusceptibility

Natural immunity to measles is known to last at least Natural immunity to measles is known to last at least 65 years (i.e. for those who get the infection itself)65 years (i.e. for those who get the infection itself)

In nations with efficient immunization programmes, In nations with efficient immunization programmes, measles infection has shifted to the teens in countries measles infection has shifted to the teens in countries with an efficient immunization programme.with an efficient immunization programme.

In others, measles infection has its greatest incidence In others, measles infection has its greatest incidence in children under 2 years of age. in children under 2 years of age.

Cases of measles have been seen in partially Cases of measles have been seen in partially immunized children, in babies with residual immunized children, in babies with residual antibodies, and in people who have been given antibodies, and in people who have been given serum immune globulin for protection.serum immune globulin for protection.

Non-immunized and immune-compromised are most Non-immunized and immune-compromised are most susceptiblesusceptible

Prevention (I)Prevention (I)

The 2 vaccines currently available The 2 vaccines currently available Inactivated Vaccine Inactivated Vaccine - this vaccine was intended for use in young - this vaccine was intended for use in young

children less than 1 year of age who are most prone to severe children less than 1 year of age who are most prone to severe complications, to avoid the use of a live vaccine, but it was found that:complications, to avoid the use of a live vaccine, but it was found that:

– At least At least 3 doses 3 doses were needed to elicit a protective antibody were needed to elicit a protective antibody response but the antibody levels soon waned. This leave the response but the antibody levels soon waned. This leave the vaccinees open to attack by the natural virus. vaccinees open to attack by the natural virus.

– In some cases, the nature of the partial immunity led to serious In some cases, the nature of the partial immunity led to serious hypersensitivityhypersensitivity reactions to infection (Atypical measles). The exact reactions to infection (Atypical measles). The exact mechanism is still uncertain but it was thought that the vaccine mechanism is still uncertain but it was thought that the vaccine lacked an important Ag of the virus, thus immunity was incomplete. lacked an important Ag of the virus, thus immunity was incomplete.

– antibody levels decline antibody levels decline rapidly after administrationrapidly after administration In view of the above and the fact that, In view of the above and the fact that, live vaccination is now generally live vaccination is now generally

recommended recommended and individuals previously immunized with the killed and individuals previously immunized with the killed vaccine should be re-immunized with the live vaccine. The killed vaccine should be re-immunized with the live vaccine. The killed vaccine has now been withdrawn. vaccine has now been withdrawn.

Prevention (II)Prevention (II)

Live vaccineLive vaccine - live vaccines are now usually used. The sero-- live vaccines are now usually used. The sero-conversion rate is 95% and the immunity lasts for at least 10 years or conversion rate is 95% and the immunity lasts for at least 10 years or more, possibly lifelong. The virulence of the attenuated strain now in more, possibly lifelong. The virulence of the attenuated strain now in use is so low that encephalitis has only been noted in 1 in 1 million use is so low that encephalitis has only been noted in 1 in 1 million recipients. SSPE has been reported in children given the live vaccine. recipients. SSPE has been reported in children given the live vaccine. However, the rate is lower than that following natural infection. However, the rate is lower than that following natural infection. Therefore the vaccine is safe for use in very young children. The live Therefore the vaccine is safe for use in very young children. The live vaccine is now incorporated as part as the MMR vaccine. As vaccine-vaccine is now incorporated as part as the MMR vaccine. As vaccine-induced measles antibody develops more rapidly than following natural induced measles antibody develops more rapidly than following natural infection, infection, MMR vaccine MMR vaccine can be used to protect susceptible contacts can be used to protect susceptible contacts during a measles outbreak. To be effective, the vaccine must be during a measles outbreak. To be effective, the vaccine must be administered within three 3 days of exposure. If there is doubt about a administered within three 3 days of exposure. If there is doubt about a child’s immunity, vaccine should be given since there are no ill effects child’s immunity, vaccine should be given since there are no ill effects from immunizing individuals who are already immune. Immunoglobulin from immunizing individuals who are already immune. Immunoglobulin should be given to those for whom the vaccine is contraindicated. should be given to those for whom the vaccine is contraindicated.

Control: Management of Cases Control: Management of Cases

In the majority of patients, measles is an acute self-limiting In the majority of patients, measles is an acute self-limiting disease that will run its course without the need for specific disease that will run its course without the need for specific treatment. However, it is far more serious in the immuno-treatment. However, it is far more serious in the immuno-compromised, the undernourished, and children with chronic compromised, the undernourished, and children with chronic debilitating diseases. Such patients can be protected by the debilitating diseases. Such patients can be protected by the administration of administration of human anti-measles gamma-globulin human anti-measles gamma-globulin if given if given within the first 3 days after exposure. Alternatively, the exposed within the first 3 days after exposure. Alternatively, the exposed individual can simply be vaccinated within 72 hours of exposure. individual can simply be vaccinated within 72 hours of exposure.

PneumoniaPneumonia - antibiotics may be indicated in cases of - antibiotics may be indicated in cases of secondary bacterial pneumonia or otitis media. secondary bacterial pneumonia or otitis media.

EncephalitisEncephalitis - treatment of acute measles encephalitis is only - treatment of acute measles encephalitis is only symptomatic and supportive. A wide variety of treatment has symptomatic and supportive. A wide variety of treatment has been tried for SSPE but no convincing effects have been been tried for SSPE but no convincing effects have been demonstrated. demonstrated.

Control of outbreaksControl of outbreaks Measles outbreaks are most deleterious in wards with immuno-Measles outbreaks are most deleterious in wards with immuno-

compromised children or adults e.g. children with leukaemia and bone compromised children or adults e.g. children with leukaemia and bone marrow transplant recipients. Measles is definitely as dangerous as marrow transplant recipients. Measles is definitely as dangerous as VZV in that setting. HNIG should be given to all severely immuno-VZV in that setting. HNIG should be given to all severely immuno-compromised children irrespective of their immunization status since it compromised children irrespective of their immunization status since it has been reported that severe measles infection can occur in those has been reported that severe measles infection can occur in those who had been immunized and had a documented low-level antibody who had been immunized and had a documented low-level antibody response. Therefore, the routine screening of children for measles response. Therefore, the routine screening of children for measles antibody before admission is probably unjustified since there would be antibody before admission is probably unjustified since there would be no difference in the management. The same argument applies to the no difference in the management. The same argument applies to the screening of patients for immunity before the administration of HNIG. screening of patients for immunity before the administration of HNIG. The use of live-attenuated vaccine for post-exposure prophylaxis is The use of live-attenuated vaccine for post-exposure prophylaxis is contraindicated. The same protocol applies to immuno-compromised contraindicated. The same protocol applies to immuno-compromised adults who come into contact with measles. Immuno-competent adults who come into contact with measles. Immuno-competent children under 12 months in whom there is a particular reason to avoid children under 12 months in whom there is a particular reason to avoid measles, such as a recent severe illness, can also be given measles, such as a recent severe illness, can also be given immunoglobulin. MMR vaccine should then be given after an interval of immunoglobulin. MMR vaccine should then be given after an interval of at least 3 months, at around the usual age. at least 3 months, at around the usual age.

HeadlinesHeadlines

DistributionDistribution Clinical presentations / complicationsClinical presentations / complications AgentAgent DiagnosisDiagnosis ReservoirReservoir Portals of exit / entryPortals of exit / entry Modes of transmissionModes of transmission SusceptibilitySusceptibility Prevention and controlPrevention and control

ReferencesReferences

1.1. Porta M. Porta M. A dictionary of epidemiologyA dictionary of epidemiology. 5. 5thth edition. edition. Oxford, New York: Oxford University Press, 2008. Oxford, New York: Oxford University Press, 2008.

2.2. Heymann DL. Heymann DL. Control of communicable diseases Control of communicable diseases manualmanual. 18. 18thth edition. Washington DC: APHA, 2005 edition. Washington DC: APHA, 2005

3.3. Wong L. Wong L. Wong’s virologyWong’s virology. . http://virology-online.com/index.html

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