Infectious Disease Epidemiology BMTRY 713 (A. Selassie, DrPH) Lecture 25 Measles Learning Objectives 1. Explain the disease burden of measles and why it still occurs 2. Identify the biologic characteristics of measles virus 3. Describe pathogenesis of measles and the immune system 4. Describe the epidemiological characteristics of measles 5. Explain the current control strategies Measles (Rubeola) An acute febrile illness resulting from infection with the measles virus Highly contagious virus Acute symptoms include high fever, runny nose, red eyes, followed by generalized rash Left untreated, it can lead to ear infection, pneumonia, and encephalitis May last in 3-4 days Biology of measles virus RNA Virus in the Family of Paramyxoviridae, Genus Morbilivirus Closely related to rinderpest (cattle) and canine distemper viruses (CDV), suggesting that measles might have evolved from cattle Two membrane envelop proteins Fusion protein (F) for fusion and Hemagglutinin (H) protein for adsorption of the virus to cells The virus is rapidly inactivated by heat and light Selassie AW (DPHS, MUSC) 1
(1) One of the oldest child disease, first noted in 1224 Epidemic reported in Faroe Island in 1846 In 2015, there were 134,200 measles deaths globally about 367 deaths every day or 15 deaths every hour Only one antigenic type making it effectively controllable by the vaccine (2) Prior to the development of the measles vaccine, there were 30 million cases/year During 2000-2015, measles vaccination prevented an estimated 20.3 million deaths making measles vaccine one of the best buys in public health. Measles is still one of the leading causes of death in young children despite availability of vaccine Number of measles cases by year since 2010, in the USA *Cases as of December 31, 2016. Year Cases 2010 63 2011 220 2012 55 2013 187 2014 667 2015 188 2016* 70 2017** 28 Selassie AW (DPHS, MUSC) 2
(3) Susceptibility to measles is universal, with no differences by gender, ethnicity, race, SES, or geography Higher incidence in densely populated areas Some data suggest higher delayed mortality in females than in males (4) Protein-calorie malnutrition aggravates the severity of measles Measles in children with vitamin A deficiency leads to severe keratitis, corneal scarring, and blindness Incidence rate of measles is hard to determine because of milder cases (5) Complication rate of measles explains regional differences in mortality rates, Death rate in healthy children in developed countries is 1 Death rate in healthy children in developing countries 10% Death rate in immune compromised children 30% Two most serious complications of measles are encephalitis (1 ) and pneumonia. Selassie AW (DPHS, MUSC) 3
(6) Measles is highly contagious, with basic reproductive rate (Ro) of 12-17 vs. 5-7 small pox, 2-3 SARS A heard immunity threshold of 83-94% is needed to contain the spread of measles in a susceptible population Modes of transmission is droplet infection released during the prodromal stage by sneezing and coughing (7) Direct contact with infected secretions and contact through fomites can also transmit measles infection Humans are the only reservoir for measles While nonhuman primates are also infected with similar symptoms as in humans, they are not sources of human infection Pathogenesis of Measles (1) Respiratory droplets from infected person transferred to URT epithelial cells of the host Incubation period is 10-14 days where replication in the local lymph nodes takes place followed by viremia Initial pathological changes are seen at the portal of entry (epithelial cells of the buccal cavity) Koplik spots during the prodromal stage Selassie AW (DPHS, MUSC) 4
Prodromal Measles, Koplik spots Koplik spots are seen with measles. They are small, white spots (often on a reddened background) that occur on the inside of the cheeks early in the course of measles. Pathogenesis of Measles (2) Virus-specific antibodies appear in stages, First IgM is detected in blood, Followed by IgA in mucosal secretions, In late stage (~18-20 days), IgG appears in all body fluids providing long-lasting, active, immunity After intense immune response to measles infection, there is suppression of the immune system lasting several weeks Pathogenesis of Measles (3) Period of infectiousness is difficult to determine, but infectiousness starts during the prodrome and resolves after a few weeks of resolution of symptoms This obscurity in stages of infectiousness hinders the effectiveness of quarantine measures Measles outbreak can occur even when <10% of the population is susceptible Selassie AW (DPHS, MUSC) 5
Immunity (1) Maternally acquired antibody, IgG, protects the infant for the first 9 months An active transport mechanism in the placenta is responsible for the transfer of IgG from the maternal circulation to the fetus Thus, immunization is not recommended prior to the 9 th month after birth Immunity (2) The patency of maternally acquired immunity depends upon three factors: The level of maternal anti-measles antibodies The efficiency of placental transfer The rate of catabolism of the antibody in the child Sufficient number of susceptible is required to maintain infection with 5-10 thousand births/year Measles Vaccines Formalin-Inactivated Measles Vaccine and atypical measles (measles-like) Withdrawn because of its tendency to lead to develop atypical measles~60% of kids High-Titer Measles Vaccines High immunogenicity but led to higher mortality than the Standard-Titer Measles Vaccine, the preferred measles vaccine Selassie AW (DPHS, MUSC) 6
Vaccine protection Vaccine Efficacy (Under ideal condition) as in clinical trial or experimental setting; Vaccine Effectiveness is in real life situation. ; Where Relative Risk is the risk ratio in vaccinated group vs. the unvaccinated ; Where PPV is the proportion of the population vaccinated against measles; PCV is the proportion of measles cases among the vaccinated Duration of Vaccine Protection Determinants of duration of vaccineinduced immunity Evidence of protective antibody titers based on the dose and the strain of the vaccine virus Age of child at vaccine administration 85% at 9 months 90-95% at 12 months Treatment (1) No specific antiviral treatment exists for measles virus. Severe complications from measles can be avoided through supportive care, good nutrition, adequate fluid intake and treatment of dehydration. WHO recommends two daily doses of 200,000 IU of Vitamin A Selassie AW (DPHS, MUSC) 7
Treatment (2) Hydration and external cooling of body temperature is important Immune compromised children can receive interferon-γ or Immune gamma globulin (IgG) Aggressive treatment with antibiotic for secondary bacterial infection Selassie AW (DPHS, MUSC) 8