Epidemiology of Measles

1. Epidemiology of Measles Ahmed Mandil, MBChB, DrPH Prof of Epidemiology Dept of Family & Community Medicine College of Medicine, King Saud University

2. Headlines Distribution Clinical presentations / complications Agent Diagnosis Reservoir Portals of exit / entry Modes of transmission Susceptibility Prevention and control

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

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

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

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

7. Clinical Presentation (II)

8. Complications Secondary bacterial infection:e.g. otitis media, bronchitis and pneumonia. Measles Pneumonia: mainly in immuno-compromised patients Subacutesclerosingpanencephalitis (SSPE): in children and 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 acute measles. Half the SSPE patients have contracted measles before the age of 2 years. Acute measles encephalitis Myocarditis Thrombocytopenic purpura

9. Cycle of Communicable Disease Transmission Agent Reservoir Portal of exit Modes of transmission Portal of entry Susceptible host

10. Agent Member of the family of ParamyxovirusesssRNA enveloped virus, helical symmetry lacks virion neuraminidase and thus grouped into a separate genus, the morbillivirus Envelope consists of haemagglutinin protein and the fusion protein embedded in the lipid bilayer M protein (membrane or matrix protein) lies immediately below the membrane. ssRNA is encased in a helix of N (nucleocapsid protein). The ssRNA molecule is of negative sense. The HA protein acts as a means of attachment to susceptible cells. Measles is an antigenically stable virus. There is one serotype only and there are very little differences between different isolates.

11. Diagnosis • History • Clinical examination • Laboratory investigations • Microscopy • Immuno-fluorescence: direct and indirect immunofluorescence have been used extensively to demonstrate MV antigens in cells from NPS specimens. • Virus isolation: measles virus can be isolated form a variety of sources, e.g. throat or conjunctival washings, sputum, urinary sediment cells and lymphocytes. • Serology:diagnosis of measles infection can be made if the antibody titres rise by 4-fold between the acute and the convalescent phase or if measles-specific IgM is found. The methods that can be used include: Hemagglutinationlnhibition (HAI), Complement Fixation (CF), neutralization and Enzyme-Labeled Immuno-Sorbent Assay (ELISA) tests.

12. Reservoir Humans in the form of Carriers (sub-clinical, during the incubation period) Cases (through-out the course of the clinical sydrome) In contrast to the influenza virus, measles does not have an animal reservoir, which makes it candidate for “elimination” if we manage to successfully prevent infection among human reservoirs.

13. Portals of exit / entry Respiratory system Exit (from reservoir): exhalation Entry (into susceptible host): inhalation

14. Modes of Transmission Direct – Droplet Indirect – Airborne The virus spreads by the respiratory route via aerosol droplets and respiratory secretions which can remain infectious for several hours. The infection is acquired through the upper respiratory tract or conjunctiva.

15. Susceptibility Natural immunity to measles is known to last at least 65 years (i.e. for those who get the infection itself) In nations with efficient immunization programmes, measles infection has shifted to the teens in countries with an efficient immunization programme. In others, measles infection has its greatest incidence in children under 2 years of age. Cases of measles have been seen in partially immunized children, in babies with residual antibodies, and in people who have been given serum immune globulin for protection. Non-immunized and immune-compromised are most susceptible

16. Prevention (I) The 2 vaccines currently available • Inactivated Vaccine - this vaccine was intended for use in young 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: • At least 3 doses were needed to elicit a protective antibody response but the antibody levels soon waned. This leave the vaccinees open to attack by the natural virus. • In some cases, the nature of the partial immunity led to serious hypersensitivity reactions to infection (Atypical measles). The exact mechanism is still uncertain but it was thought that the vaccine lacked an important Ag of the virus, thus immunity was incomplete. • antibody levels decline rapidly after administration • In view of the above and the fact that, live vaccination is now generally recommended and individuals previously immunized with the killed vaccine should be re-immunized with the live vaccine. The killed vaccine has now been withdrawn.

17. Prevention (II) Live vaccine- live vaccines are now usually used. The sero-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 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. However, the rate is lower than that following natural infection. 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-induced measles antibody develops more rapidly than following natural infection, MMR vaccine can be used to protect susceptible contacts during a measles outbreak. To be effective, the vaccine must be 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 from immunizing individuals who are already immune. Immunoglobulin should be given to those for whom the vaccine is contraindicated.

18. Control: Management of Cases In the majority of patients, measles is an acute self-limiting disease that will run its course without the need for specific treatment. However, it is far more serious in the immuno-compromised, the undernourished, and children with chronic debilitating diseases. Such patients can be protected by the administration of human anti-measles gamma-globulin if given within the first 3 days after exposure. Alternatively, the exposed individual can simply be vaccinated within 72 hours of exposure. Pneumonia - antibiotics may be indicated in cases of secondary bacterial pneumonia or otitis media. Encephalitis- treatment of acute measles encephalitis is only symptomatic and supportive. A wide variety of treatment has been tried for SSPE but no convincing effects have been demonstrated.

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

20. Headlines Distribution Clinical presentations / complications Agent Diagnosis Reservoir Portals of exit / entry Modes of transmission Susceptibility Prevention and control

21. References • Porta M. A dictionary of epidemiology. 5th edition. Oxford, New York: Oxford University Press, 2008. • Heymann DL. Control of communicable diseases manual. 18th edition. Washington DC: APHA, 2005 • Wong L. Wong’s virology. http://virology-online.com/index.html

22. Thanks for your kind attention and listening