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  1. 1. Measles (Rubeola) Prof. Dr. Saad S Al Ani Senior Pediatric Consultant Head of Pediatric Department Khorfakkan Hospital Sharjah ,UAE [email_address]
  2. 2. Measles (Rubeola) <ul><li>It is an acute viral infection characterized by a final stage with a maculopapular rash erupting successively over the neck and face, trunk, arms, and legs, and accompanied by a high fever. </li></ul>
  3. 3. Etiology <ul><li>Measles virus, the cause of measles, is an RNA virus of the genus Morbillivirus in the family Paramyxoviridae. </li></ul><ul><li>Only one serotype is known </li></ul>
  4. 4. Epidemiology <ul><li>Measles is endemic throughout the world. </li></ul><ul><li>In the past, epidemics tended to occur irregularly , appearing in the spring in large cities at 2-4-yr intervals as new groups of susceptible children were exposed. </li></ul>
  5. 5. Epidemiology (Cont.) <ul><li>It is rarely subclinical . </li></ul><ul><li>Prior to the use of measles vaccine, the peak incidence was among children 5-10 yr of age. </li></ul>
  6. 6. Epidemiology (Cont.) <ul><li>Individuals born before 1957 are considered to have had natural infection and to be immune </li></ul>
  7. 7. TRANSMISSION <ul><li>Measles is highly contagious ; approximately 90% of susceptible household contacts acquire the disease. </li></ul><ul><li>Maximal dissemination of virus occurs by droplet spray during the prodromal period ( catarrhal stage ). </li></ul>
  8. 8. TRANSMISSION (Cont.) <ul><li>Transmission to susceptible contacts often occurs prior to diagnosis of the index case </li></ul><ul><li>Infants acquire immunity transplacentally from mothers who have had measles or measles immunization. </li></ul>
  9. 9. TRANSMISSION (Cont.) <ul><li>This immunity is usually complete for the first 4-6 mo of life and wanes at a variable rate. </li></ul><ul><li>Some protection persists that may interfere with immunization administered before 12 mo of age . </li></ul>
  10. 10. TRANSMISSION (Cont.) <ul><li>Most women of childbearing age in the United States now have measles immunity by means of immunization rather than disease </li></ul>
  11. 11. TRANSMISSION (Cont.) <ul><li>infants of mothers with measles vaccine-induced immunity lose passive antibody at a younger age than infants of mothers who had measles infection . </li></ul>
  12. 12. TRANSMISSION (Cont.) <ul><li>Infants of mothers who are susceptible to measles have no measles immunity and may contract the disease simultaneously with the mother before or after delivery </li></ul>
  13. 13. Incidence and percentage of import-associated measles cases, by year – United States, 1985 to 2003 Centers for Disease Control and Prevention. Epidemiology of Measles – United States, 2001–2003. MMWR 2004;53:713–716.)
  14. 14. Number of measles cases, by import status and week of rash onset – United States, 2004 Centers for Disease Control and Prevention. Measles – United States. MMWR 2005;54:1229–1231
  15. 15. Number of confirmed measles cases and percentage of routine infant measles vaccination coverage – the Americas, 1980–2000. Centers for Disease Control and Prevention. Progress toward interrupting indigenous measles transmission – region of the Americas, January 1999–September 2000. MMWR 2000;40:986–990
  16. 16. Pathogenesis <ul><li>The essential lesion of measles is found in the skin , conjunctivae , and the mucous membranes of the nasopharynx , bronchi , and intestinal tract . </li></ul><ul><li>Serous exudate and proliferation of mononuclear cells and a few polymorphonuclear cells occur around the capillaries . </li></ul>
  17. 17. Pathogenesis (cont.) <ul><li>Hyperplasia of lymphoid tissue usually occurs, particularly in the appendix, where multinucleated giant cells of up to 100 μm in diameter ( Warthin-Finkeldey reticuloendothelial giant cells ) may be found. </li></ul><ul><li>In the skin , the reaction is particularly notable about the sebaceous glands and hair follicles. </li></ul>
  18. 18. Pathogenesis (cont.) <ul><li>Koplik spots consist of serous exudate and proliferation of endothelial cells similar to those in the skin lesions. </li></ul><ul><li>A general inflammatory reaction of the buccal and pharyngeal mucosa extends into the lymphoid tissue and the tracheobronchial mucous membrane. </li></ul>
  19. 19. Pathogenesis (cont.) <ul><li>Interstitial pneumonitis resulting from measles virus takes the form of Hecht giant cell pneumonia . </li></ul><ul><li>Bronchopneumonia may occur from secondary bacterial infection . </li></ul>
  20. 20. Pathogenesis (cont.) <ul><li>In fatal cases of encephalomyelitis , perivascular demyelinization occurs in areas of the brain and spinal cord. </li></ul><ul><li>In subacute sclerosing panencephalitis (SSPE), there may be degeneration of the cortex and white matter with intranuclear and intracytoplasmic inclusion bodies </li></ul>
  21. 21. <ul><li>Measles has three clinical stages: </li></ul><ul><li>1. an incubation stage </li></ul><ul><li>2. a prodromal stage with an enanthem (Koplik spots) and mild symptoms </li></ul><ul><li>3. a final stage with a maculopapular rash accompanied by high fever. </li></ul>Clinical Manifestations
  22. 22. The incubation period <ul><li>lasts approximately 10-12 days to the first prodromal symptoms and another 2-4 days to the appearance of the rash; rarely, it may be as short as 6-10 days . </li></ul><ul><li>Body temperature may increase slightly 9-10 days from the date of infection and then subside for 24 hr or so. </li></ul><ul><li>The patient may transmit the virus by the 9th-10th day after exposure and occasionally as early as the 7th day, before the illness can be diagnosed </li></ul>
  23. 23. The prodromal phase <ul><li>usually lasts 3-5 days and is characterized by: </li></ul><ul><li>* low-grade to moderate fever </li></ul><ul><li>* dry cough </li></ul><ul><li>* coryza </li></ul><ul><li>* conjunctivitis . </li></ul><ul><li>These symptoms nearly always precede the appearance of Koplik spots , the pathognomonic sign of measles, by 2-3 days . </li></ul>
  24. 24. The prodromal phase (cont.) <ul><li>The conjunctival inflammation and photophobia may suggest measles before Koplik spots appear. </li></ul><ul><li>In particular, a transverse line of conjunctival inflammation , sharply demarcated along the eyelid margin, may be of diagnostic assistance in the prodromal stage . As the entire conjunctiva becomes involved, the line disappears. </li></ul>
  25. 25. Koplik spots <ul><li>An enanthem or red mottling is usually present on the hard and soft palates </li></ul><ul><li>the pathognomonic sign of measles : </li></ul>
  26. 26. Koplik spots (cont.) <ul><li>are grayish white dots , usually as small as grains of sand, that have slight, reddish areolae ; occasionally they are hemorrhagic . </li></ul><ul><li>tend to occur opposite the lower molars but may spread irregularly over the rest of the buccal mucosa. </li></ul>
  27. 27. Koplik spots (cont.) <ul><li>Rarely they are found within the midportion of the lower lip , on the palate , and on the lacrimal caruncle . </li></ul><ul><li>They appear and disappear rapidly , usually within 12-18 hr . </li></ul><ul><li>As they fade , a red , spotty discoloration of the mucosa may remain. </li></ul>
  28. 28. The prodromal phase (cont.) <ul><li>Occasionally , the prodromal phase may be severe , being ushered in by a sudden high fever , sometimes with convulsions and even pneumonia . </li></ul><ul><li>Usually the coryza, fever, and cough are increasingly severe up to the time the rash has covered the body. </li></ul><ul><li>The temperature rises abruptly as the rash appears and often reaches 40°C (104°F) or higher. </li></ul>
  29. 29. The prodromal phase (cont.) <ul><li>In uncomplicated cases , as the rash appears on the legs and feet, the symptoms subside rapidly within about 2 days , usually with an abrupt drop in temperature to normal. </li></ul><ul><li>Patients up to this point may appear desperately ill, but within 24 hr after the temperature drops, they appear well . </li></ul>
  30. 30. The rash <ul><li>usually starts as faint macules on the: </li></ul><ul><li>* upper lateral parts of the neck </li></ul><ul><li>* behind the ears </li></ul><ul><li>* along the hairline </li></ul><ul><li>* posterior parts of the cheek . </li></ul>
  31. 31. The rash (cont.) <ul><li>The individual lesions become increasingly maculopapular as the rash spreads rapidly over the: </li></ul><ul><li>* entire face </li></ul><ul><li>* neck </li></ul><ul><li>* upper arms </li></ul><ul><li>* upper part of the chest </li></ul><ul><li>within approximately the first 24 hr </li></ul>
  32. 32. Korting GW: Hautkrankheiten bei Kindern und Jugendlichen , 3rd ed. Stuttgart, FK Schattauer Verlag, 1982 Maculopapular rash of measles
  33. 33. The rash (cont.) <ul><li>During the succeeding 24 hr the rash spreads over the back, abdomen, entire arm, and thighs. </li></ul><ul><li>As it finally reaches the feet on the 2nd-3rd day , it begins to fade on the face. </li></ul>
  34. 34. Typical rash on day 2–3 of measles   (Courtesy of J.H. Brien.)
  35. 35. Rash on day 5 of measles showing typical confluence and density on head with scattered lesions on the trunk.   (Courtesy of J.H. Brien.)
  36. 36. The rash (cont.) <ul><li>The rash fades downward in the same sequence in which it appeared. </li></ul><ul><li>The severity of the disease is directly related to the extent and confluence of the rash. </li></ul><ul><li>In mild measles the rash tends not to be confluent , and in very mild cases there are few, if any, lesions on the legs. </li></ul>
  37. 37. The rash (cont.) <ul><li>In severe cases the rash is confluent , the skin is completely covered, including the palms and soles, and the face is swollen and disfigured. </li></ul><ul><li>The rash is often slightly hemorrhagic ; in severe cases with a confluent rash, petechiae may be present in large numbers, and there may be extensive ecchymoses </li></ul>
  38. 38. The rash (cont.) <ul><li>The appearance of the rash may vary markedly. </li></ul><ul><li>Infrequently a slight urticarial , faint macular , or scarlatiniform rash may appear during the early prodromal stage, disappearing in advance of the typical rash. </li></ul>
  39. 39. The rash (cont.) <ul><li>Complete absence of rash is rare except : </li></ul><ul><li>1. in patients who have received </li></ul><ul><li>immunoglobulin (Ig) during the incubation </li></ul><ul><li>period </li></ul><ul><li>2. in some patients with HIV infection </li></ul><ul><li>3. occasionally in infants younger than 9 mo of </li></ul><ul><li>age who have appreciable levels of maternal </li></ul><ul><li>antibody. </li></ul>
  40. 40. The rash (cont.) <ul><li>In the hemorrhagic type of measles ( black measles ), bleeding may occur from the mouth, nose, or bowel. </li></ul><ul><li>In mild cases the rash may be less macular and more nearly pinpoint , somewhat resembling that of scarlet fever or rubella </li></ul>
  41. 41. The rash (cont.) <ul><li>Itching is generally slight . </li></ul><ul><li>As the rash fades , branny desquamation and brownish discoloration occur and then disappear within 7-10 days. </li></ul>
  42. 42. The prodromal phase (cont.) <ul><li>Otitis media </li></ul><ul><li>bronchopneumonia </li></ul><ul><li>gastrointestinal symptoms such as diarrhea and vomiting </li></ul><ul><li>Are more common in infants and small children (especially if they are malnourished) than in older children. </li></ul>
  43. 43. Diagnosis <ul><li>The diagnosis is usually apparent from the characteristic clinical picture ; laboratory confirmation is rarely needed </li></ul><ul><li>Testing for measles IgM antibodies is recommended in some situations </li></ul><ul><li>Measles IgM is detectable for 1 mo after illness , but sensitivity of IgM assays may be limited in the first 72 hr of the rash illness. </li></ul>
  44. 44. Diagnosis (cont.) <ul><li>Isolation of measles virus from clinical samples is also useful in identifying the genotype of the strain to track transmission patterns. </li></ul><ul><li>All suspected measles cases should be reported immediately to local or health departments. </li></ul><ul><li>During the prodromal stage multinucleated giant cells can be demonstrated in smears of the nasal mucosa. </li></ul>
  45. 45. Diagnosis (cont.) <ul><li>Antibodies become detectable when the rash appears ; </li></ul><ul><li>testing of acute and convalescent sera demonstrates the diagnostic seroconversion or fourfold increase in titer. </li></ul><ul><li>Measles virus can be isolated by tissue culture in human embryonic or rhesus monkey kidney cells. </li></ul>
  46. 46. Diagnosis (cont.) <ul><li>Cytopathic changes , visible in 5-10 days, consist of multinucleated giant cells with intranuclear inclusions . </li></ul><ul><li>The white blood cell count tends to be low with a relative lymphocytosis </li></ul><ul><li>Cerebrospinal fluid in patients with measles encephalitis usually shows an increase in protein and a small increase in lymphocytes . The glucose level is normal. </li></ul>
  47. 47. The rash of rubeola must be differentiated from that of: <ul><li>Rubella </li></ul><ul><li>Roseola infantum (human herpesvirus 6) </li></ul><ul><li>Infections resulting from: </li></ul><ul><li>* echovirus * coxsackievirus * adenovirus </li></ul><ul><li>Infectious mononucleosis </li></ul><ul><li>Toxoplasmosis </li></ul><ul><li>Meningococcemia </li></ul><ul><li>Scarlet fever </li></ul><ul><li>Rickettsial diseases </li></ul><ul><li>Kawasaki disease </li></ul><ul><li>Serum sickness </li></ul><ul><li>Drug rashes </li></ul>
  48. 48. Treatment <ul><li>There is no specific antiviral therapy; </li></ul><ul><li>treatment is entirely supportive . </li></ul><ul><li>Antipyretics (acetaminophen or ibuprofen) for fever </li></ul><ul><li>bed rest </li></ul><ul><li>maintenance of an adequate fluid intake </li></ul><ul><li>are indicated. </li></ul>
  49. 49. Treatment (cont.) <ul><li>Humidification may alleviate symptoms of laryngitis or an excessively irritating cough; it is best to keep the room comfortably warm rather than cool. </li></ul><ul><li>Patients with photophobia should be protected from exposure to strong light . </li></ul><ul><li>Bacterial complications of otitis media and bronchopneumonia require appropriate antimicrobial therapy. </li></ul>
  50. 50. Treatment (cont.) <ul><li>Complications such as encephalitis, subacute sclerosing panencephalitis, giant cell pneumonia, and disseminated intravascular coagulation must be assessed individually . </li></ul><ul><li>Good supportive care is essential. </li></ul><ul><li>Immunoglobulin and corticosteroids are of limited value. </li></ul><ul><li>Currently available antiviral compounds are not effective. </li></ul>
  51. 51. Treatment (cont.) <ul><li>the American Academy of Pediatrics recommends consideration of vitamin A supplementation for: </li></ul><ul><li>children 6 mo to 2 yr of age who are hospitalized for measles and its complications </li></ul><ul><li>children older than 6 mo of age with measles and immunodeficiency ; </li></ul>
  52. 52. Treatment (cont.) <ul><li>The recommended regimen is a single dose of: </li></ul><ul><li>100,000 IU orally for children 6 mo to 1 yr </li></ul><ul><li>200,000 IU for children 1 yr of age or older </li></ul><ul><li>Children with ophthalmologic evidence of vitamin A deficiency should be given additional doses the next day and 4 wk later . </li></ul>
  53. 53. Complications <ul><li>The chief complications of measles are: </li></ul><ul><li>otitis media </li></ul><ul><li>pneumonia </li></ul><ul><li>encephalitis . </li></ul>
  54. 54. Respiratory tract complications <ul><li>Interstitial pneumonia may be caused by the measles virus ( giant cell pneumonia ). </li></ul><ul><li>Bacterial superinfection and bronchopneumonia are more frequent, however, usually with pneumococcus , group A Streptococcus , Staphylococcus aureus , and Haemophilus influenzae type b . </li></ul><ul><li>Laryngitis , tracheitis , and bronchitis are common and may be due to the virus alone </li></ul>
  55. 55. Respiratory tract complications (cont.) <ul><li>Measles may exacerbate underlying Mycobacterium tuberculosis infection </li></ul><ul><li>There may also be a temporary loss of hypersensitivity reaction to tuberculin skin testing. </li></ul><ul><li>Measles pneumonia in HIV-infected patients is often fatal and is not always accompanied by rash </li></ul>
  56. 56. Cardiovascular complications <ul><li>Noma of the cheeks may occur in rare instances </li></ul><ul><li>Gangrene elsewhere appears to be secondary to : </li></ul><ul><li>purpura fulminans </li></ul><ul><li>disseminated intravascular coagulation </li></ul><ul><li>following measles </li></ul><ul><li>Myocarditis is an infrequent serious complication, although transient electrocardiographic changes may be relatively common . </li></ul>
  57. 57. Neurologic complications <ul><li>Are more common in measles than in any of the other exanthematous diseases. </li></ul><ul><li>Encephalomyelitis </li></ul><ul><li>The i ncidence is estimated to be 1-2/1,000 cases of measles. </li></ul><ul><li>There is no correlation between the severity of the : </li></ul><ul><li>* Rash illness and that of the neurologic involvement </li></ul><ul><li>* Initial encephalitic process and the prognosis. </li></ul>
  58. 58. Neurologic complications (cont.) <ul><li>Infrequently , encephalitic involvement is manifest in the pre-eruptive period , but more often its onset occurs 2-5 days after the appearance of the rash . </li></ul><ul><li>The cause of measles encephalitis remains controversial . </li></ul><ul><li>1. Encephalitis early in the course of the disease : </li></ul><ul><li>direct viral invasion may be operative for </li></ul><ul><li>2. Encephalitis that occurs later is predominantly demyelinating and may reflect an immunologic reaction . </li></ul><ul><li>Fatal encephalitis has occurred in children receiving immunosuppressive treatment. </li></ul>
  59. 59. Neurologic complications (cont.) <ul><li>Other central nervous system complications, including: </li></ul><ul><li>Guillain-Barré syndrome </li></ul><ul><li>Hemiplegia </li></ul><ul><li>Cerebral thrombophlebitis </li></ul><ul><li>Retrobulbar neuritis </li></ul><ul><li>occur rarely . </li></ul>
  60. 60. Prognosis <ul><li>Case fatality rates in the United States have decreased in recent years to low levels for all age groups, largely because of : </li></ul><ul><li>Improved socioeconomic conditions </li></ul><ul><li>Effective antibacterial therapy for the treatment of secondary bacterial infections. </li></ul><ul><li>Despite the decline in measles cases and fatalities in the United States, the case fatality rate is still 1-3/1,000 cases . </li></ul>
  61. 61. Prognosis (cont.) <ul><li>Deaths are primarily due to pneumonia or secondary bacterial infections . </li></ul><ul><li>In developing countries measles frequently occurs in infants ; possibly because of concomitant malnutrition, the disease is very severe in these locations and has a high mortality . </li></ul><ul><li>When measles is introduced into a highly susceptible population , the results may be disastrous . </li></ul>
  62. 62. Prevention. <ul><li>Isolation precautions , especially in hospitals and other institutions, should be maintained from the 7th day after exposure until 5 days after the rash has appeared. </li></ul>
  63. 63. VACCINE <ul><li>The initial measles immunization, usually as measles-mumps-rubella ( MMR ) vaccine , is recommended at 12-15 mo of age </li></ul><ul><li>MMR vaccine may be given for: </li></ul><ul><li>1. Measles postexposure </li></ul><ul><li>2. Outbreak prophylaxis as early as 6 mo </li></ul><ul><li>of age . </li></ul>
  64. 64. VACCINE (cont.) <ul><li>A second immunization , also as MMR, is recommended routinely at 4-6 yr of age </li></ul><ul><li>MMR may be administered at any time during childhood provided at least 4 wk have elapsed since the first dose . </li></ul><ul><li>Second measles immunization should be given to : </li></ul><ul><li>1. Children who have not previously received the </li></ul><ul><li>second dose should be immunized by 11-12 yr of </li></ul><ul><li>age . </li></ul><ul><li>2.Adolescents entering college or the workforce </li></ul>
  65. 65. VACCINE (cont.) <ul><li>A tuberculin test prior to or concurrent with active immunization against measles is desirable if tuberculosis is under consideration. </li></ul>
  66. 66. VACCINE (cont.) <ul><li>* Measles vaccine is not recommended for: </li></ul><ul><li>1. Pregnant women </li></ul><ul><li>2. Children with primary immunodeficiency </li></ul><ul><li>3. Untreated tuberculosis, cancer, or organ </li></ul><ul><li>transplantation </li></ul><ul><li>4. Those receiving long-term immunosuppressive </li></ul><ul><li>therapy </li></ul><ul><li>5. severely immunocompromised HIV-infected </li></ul><ul><li>children </li></ul>
  67. 67. VACCINE (cont.) <ul><li>HIV-infected children without : </li></ul><ul><li>1. Severe immunosuppression </li></ul><ul><li>2. Evidence of measles immunity </li></ul><ul><li>may receive measles vaccine . </li></ul>
  68. 68. POSTEXPOSURE PROPHYLAXIS <ul><li>Passive immunization with immune globulin is effective for prevention and attenuation of measles within 6 days of exposure . </li></ul><ul><li>Susceptible household and hospital contacts who are: </li></ul><ul><li>1. younger than 12 mo of age </li></ul><ul><li>2. pregnant </li></ul><ul><li>should receive immune globulin ( 0.25 mL/kg ; maximum: 15 mL) intramuscularly as soon as possible after exposure, but within 5 days . </li></ul>
  69. 69. POSTEXPOSURE PROPHYLAXIS (cont.) <ul><li>Immunocompromised persons should receive immune globulin ( 0.5 mL/kg; maximum: 15 mL) intramuscularly regardless of immunization status. </li></ul><ul><li>Infants 6 mo of age or younger born to nonimmune mothers should receive immune globulin ; </li></ul><ul><li>infants 6 mo of age or younger born to immune mothers are considered protected by maternal antibody . </li></ul>
  70. 70. POSTEXPOSURE PROPHYLAXIS (cont.) <ul><li>Susceptible children 6-12 mo of age should also be vaccinated ; this vaccination does not count as one of the two required measles vaccinations. </li></ul><ul><li>Susceptible children 12 mo of age or older should receive vaccine alone within 72 hr . </li></ul><ul><li>Pregnant women and immunocompromised persons should receive immune globulin but not vaccine </li></ul>
  71. 71. References <ul><li>Centers for Disease Control and Prevention. : Epidemiology of measles – United States, 2001–2003.   MMWR   2004; 53:713-716 </li></ul><ul><li>Progress towards measles elimination, western hemisphere, 2002–2003 :  Wkly Epidemiol Rec.   2004; 79:149-151 </li></ul><ul><li>Yeung LF, Lurie P, Dayan G, et al: A limited measles outbreak in a highly vaccinated US boarding school. Pediatrics 2005; 116:1287. </li></ul><ul><li>Parker AA, Staggs W, Dayan GH, et al: Implications of a 2005 measles outbreak in Indiana for sustained elimination of measles in the United States. N Engl J Med 2006; 355:447-455 </li></ul><ul><li>Centers for Disease Control and Prevention. : Licensure of a combined live attenuated measles, mumps, rubella, and varicella vaccine. MMWR 2005; 54:1212-1214 </li></ul><ul><li>Bellini WJ, Rota JS, Lowe LE, et al: Subacute sclerosing panencephalitis: more cases of this fatal disease are prevented by measles immunization than was previously recognized. J Infect Dis 2005; 192:1686-1693. </li></ul>