Measles is also called rubeola, which is a highly contagious, acute, exanthematous respiratory disease. The characteristic clinical features and have a pathognomonic (the word pathognomonic means a clinical feature seen only in that particular disease and not in any other disease) enanthem, known as Koplik's spots (which are white or bluish lesion with an erythematous halo on the buccal mucous membranes).

Measles still continues to be a major cause of mortality and morbidity among children in many developing countries, despite availability of a highly effective vaccine. The measles vaccine, which is highly effective, is available since the year 1963. Measles is only sporadically seen in most of the advanced and industrialized countries, due to extensive use of measles vaccines as part of Universal Immunization.

Epidemiology of measles:

Measles is seen all over the world (worldwide distribution). Humans are the only natural hosts of measles virus, although other primates can be experimentally infected. Measles is still seen commonly in many developing countries, especially in the Sub-Saharan Africa, where it causes large number of deaths of children every year.

During the prevaccination era measles epidemics used to occur every 2-5 years. After the effective vaccine became available the number of measles cases came down drastically in the countries where the vaccination became part of routine immunization, especially in the developed countries.

The mortality from measles is highest among children below 2 years of age and in adults. The mortality rate also vary in different countries, e.g. in the United States mortality from measles is approximately 0.3% whereas in developing countries it is more than 1% and in many cases the mortality may be as high as 10%, due to malnutrition and associated infections.

In United States sometimes there is resurgence of measles, as occurred in 1990s, due to failure to immunize young children (especially in inner-city areas), primary vaccine failure (which is approximately 5%) and rarely due to waning of immunity developed by vaccination.

What is the cause of measles?

The etiological agent of measles is “measles virus” which is an RNA virus and belongs to member of the genus Morbillivirus and is the only virus of the genus which infects humans. Measles virus belongs to Paramyxoviridae family. There is only one antigenic type of the virus, which makes the measles vaccine highly effective.

The “measles virus” particles or virions are pleomorphic spheres and have a diameter of 100–250 nm and consist of six proteins. The inner capsid of the virus is composed of RNA and three proteins and the outer envelope consists of a matrix protein which has surface-glycoprotein projections, one a hemagglutinin (H) and the other one is a fusion (F) protein. The measles virus has cellular receptors the CD46 and CD150 molecules, which are expressed on many human cells and help in invading the host (infection).

How measles infection is transmitted?

Measles virus is transmitted by respiratory route. Transmission is mainly through exposure to aerosols but also occur by direct contact with larger droplets. Measles patients are contagious from 1-2 days before symptoms of measles appear until 4 days after the rash appears.

Pathogenesis of measles:

Measles virus invades the respiratory epithelium and spreads to the reticuloendothelial system via the bloodstream. From reticuloendothelial system the infection spreads to the white blood cells, skin, respiratory tract, and other organs. At this stage measles viruses are present in blood and urine and can be detected. Multinucleated giant cells (Warthin-Finkeldey cells) with inclusion bodies in the nucleus and cytoplasm are found in respiratory and lymphoid tissues at this stage.

The monocytes are mostly infected cells in the blood. The characteristic cough and coryza of measles are due to infection of the entire respiratory tract. Infection of respiratory tract may also result in croup, bronchiolitis, and pneumonia. Pneumonia and otitis media may occur as a complication due to secondary bacterial infections.

What are the symptoms of measles?

Measles starts with malaise, cough, running nose, nasal discharge, conjunctivitis with tearing (lacrimation) and fever (may be 105°F or 40.6°C) which gradually rises, may be due to multiplication of measles virus in blood. Just before onset of rash, Koplik's spots appear which are 1-2 mm (millimeter) bluish and/or white spots on a bright red background or halo. Koplik's spots may be overlooked, if proper illumination is not there for examination. Koplik's spots are located on the buccal mucosa, against the second molars, which may be extensive. Koplik's spots are not associated with any other infectious disease (pathognomonic) and are diagnostic of measles. Koplik's spots wane and disappear soon after appearance of rash. Sometimes lips, entire buccal and inner labial mucosa may be inflamed. Lymphadenopathy, diarrhea, vomiting, and splenomegaly are other symptoms, which may occur. Chest x-ray may be abnormal even in uncomplicated cases due to involvement of respiratory tract.

The erythematous, nonpruritic (no itching), maculopapular rash of measles begins at the hairline and behind the ears and than spreads down the trunk and limbs to palms and soles. When the rash reaches palms and soles the disease is severe most. The rash begins to fade by the 4^th day in the order in which it appeared, i.e. the rashes disappear from head first and palms and soles last. The skin may become brownish (among white people).

Fever of measles generally resolves by 4^th or 5^th day of onset of rash. If fever remains longer than 4 or 5 days, it suggests complication.

The illness of measles last for approximately 10 days and is generally more severe in adults than children. Adults with measles have higher rates of complications, higher fever and more prominent rashes.

Modified measles may occur sometimes among individuals with preexisting partial immunity induced by active or passive vaccination. Modified measles have milder illness with low grade fever, milder rashes and less intense symptoms. Modified measles may occur among infants of less than one year of age, as they contain some maternal antibodies and modified measles can also sometimes occur among individuals with a history of measles immunization.

Diagnosis of Measles:

Measles can be easily diagnosed clinically by Koplik’s spots (and if associated with cough, coryza, conjunctivitis, and a rash beginning on the head), as they are seen only in measles and no other infections.

A specific laboratory diagnosis of measles can be made quickly in case of doubt, by immunofluorescent staining of a smear of respiratory secretions for measles antigen. The measles virus can be demonstrated either by culture (of respiratory secretions or urine) or polymerase chain reaction.

Multinucleated giant cells known as Warthin-Finkeldey cells (with inclusion bodies in the nucleus and cytoplasm) are found in respiratory and lymphoid tissues and are diagnostic (pathognomonic) for measles.

There are also a number of serological tests for measles, although non specific. Enzyme immunoassay measurement of specific IgM (immunoglobulin M) can be used for diagnosis of measles on the basis of an acute-phase serum sample. Specific IgM antibodies can be detected within 1–2 days after onset of rash, but the IgG titer rises significantly only after 10 days.

Laboratory findings of measles:

Lymphopenia and neutropenia may be seen due to invasion of white blood cells by the measles virus and cell death. Measles encephalitis (a complication of measles) has elevated protein level in CSF (cerebrospinal fluid) as well as lymphocytosis. Leukocytosis may result in bacterial superinfection.

Differential diagnosis of measles:

A number of diseases can have similar symptoms of measles and may be mistaken. Kawasaki disease, infectious mononucleosis, toxoplasmosis, scarlet fever, drug eruption, infection of Mycoplasma pneumoniae etc. can have similar clinical picture of measles. Modified measles can be very difficult to diagnose, as it may not have the typical clinical features of measles. Current epidemiology of measles in the community and past history of measles vaccination and foreign travel can help in diagnosing and differentiating measles from other diseases which can have similar clinical features.

Treatment of Measles:

Treatment of measles is mainly nonspecific and symptomatic. Fever should be managed with antipyretic drugs such as paracetamol and coryza treated with antihistamines. In case of malnutrition and children below 2 years of age, or in case of severe measles high doses of vitamin A (50,000 IU for infants 1–6 months old; 100,000 IU for infants 7–12 months old and 200,000 IU for children more than 1 year old) can be beneficial as seen in controlled trials. Vitamin A treatment should be given to young children hospitalized for measles, patients with immunodeficiency, clinical evidence of vitamin A deficiency, impaired intestinal absorption and moderate to severe malnutrition. There may be transient vomiting and/or headache after administration of large dose of vitamin A in measles patient.

Ribavirin (an antiviral antibiotic) is effective against measles virus (although only in vitro and not well studies on patients) and may be considered in immunocompromised adult measles patients, who are at high risk of complications.

What are the Complications of Measles?

The complications of measles can be divided into three groups, respiratory, gastrointestinal and CNS (central nervous system) complications.

Respiratory complications of measles:

The respiratory complications of measles include respiratory tract involvement (laryngitis, croup, and bronchitis), otitis media, pneumonia etc. The respiratory tract involvement generally does not cause any serious problem and seen in majority of cases of measles. Otitis media (infection of middle ear) is the most common complication in children. In adults pneumonia is the commonest complication and need hospitalization. The pneumonia is generally viral, but may cause secondary bacterial infection (most commonly by streptococci, pneumococci, and staphylococci). Immunocompromised and/or malnourished measles patients may suffer from primary giant-cell (Hecht's) pneumonia.

Gastrointestinal complications of measles:

Gastroenteritis (may cause life threatening diarrhea among infants), hepatitis, appendicitis, ileocolitis, and mesenteric adenitis are the gastrointestinal complications of measles.

CNS (central nervous system) complications of measles:

The CNS (central nervous system) complications of measles include acute measles encephalitis, subacute sclerosing panencephalitis (SSPE) etc. Acute measles encephalitis has a mortality of approximately 10% and many of the survivors have permanent sequelae such as mental retardation or epilepsy. The cause of acute measles encephalitis appears to be not due to viral infection of the CNS, but due to an immune-mediated response to myelin proteins (postinfectious encephalomyelitis). The symptoms are fever, headache, drowsiness, coma, or seizures which generally start within days after the onset of rash. Immunocompromised patients may develop encephalitis even 6 months after measles.

Subacute sclerosing panencephalitis (SSPE) is a serious, chronicand extremely rare form of measles complication, may be seen among children of below 2 years with measles. Dementia (loss of memory) develops over several moths. SSPE has disappeared from most of the developed countries due to widespread measles vaccination.

Rare complications of measles include myocarditis, glomerulonephritis, and post-measles thrombocytopenic purpura. Measles can exacerbate preexisting tuberculosis by reducing cell-mediated immunity.

Prevention of Measles:

Enders and colleagues developed live attenuated measles vaccine in the year 1963 and since being used for routine immunization for measles. The measles vaccine induces seroconversion in approximately 95% of recipients and probably confers lifelong immunity and protection against measles as waning of immunity after measles immunization is rare.

In developed countries such as United States the measles vaccine is given to children at 12–15 months of age as MMR and a second dose of MMR vaccine is recommended for school-age children. The two dose vaccination for measles was adapted to prevent measles outbreak in the United States. In the developing countries such as India, the measles vaccination is given as part of UIP (Universal Immunization Program which include 6 vaccines for tuberculosis, polio, diphtheria, pertussis, tetanus and measles) at the age of 9 months and repeated as MMR (mumps, measles and rubella) at 15 to 18 moths of age. The vaccine is given earlier in developing countries because of higher risk of exposure to measles virus and infection in developing countries.

MMR vaccine is most likely to be supplanted by MMRV vaccine, which will have also cover varicella (chickenpox) and licensed (by U.S. Food and Drug Administration in 2005) in the US for children 1–13 years of age.

Older people should be immunized for measles if they are susceptible to measles. An older individual should be considered susceptible to measles if they do not have documentation of physician-diagnosed measles or receipt of two doses of vaccine or do not have laboratory evidence of measles immunity, and individuals at risk of exposure to measles such as health care workers, teachers, and international travelers and they should be tested for measles antibody and immunized if necessary.

What are the problems of measles vaccination?

Fever may occur in approximately 10% of the healthy reciepients of measles vaccine. Fever temperatures up to 39.4°C (103°F) generally occurs 5 days to 1 week after vaccination and lasts up to 5 days and is accompanied by a transient rash. Febrile seizures are the only complication of measles vaccination. Anaphylaxis is extremely rare.

Who should not be vaccinated with measles vaccine?

The measles vaccine is contraindicated in case of impaired cell-mediated immunity, in pregnant women, and in persons with a history of anaphylaxis due to egg protein or neomycin. Minor illnesseses such as fever and history of convulsions, are not contraindications to measles vaccination. Asymptomatic HIV infection is not a contraindication of measles vaccination. Contrary to belief measles vaccination is not a causative factor of autism.

What are the causes of measles vaccine failure?

Measles vaccination may fail due to faulty vaccine storage, the presence of maternally derived antibodies in infants (if given before age of 6-9 months), and simultaneous administration of measles vaccine and immune globulin.

Measles vaccination should be donef 6–11 months after the receiving immune globulin or of blood products containing antibodies and at least 3 months after the discontinuation of immunosuppressive treatment.

Postexposure prevention of measles:

Postexposure preventive measures for measles should be done if a susceptible individual is exposed to measles. Immune globulin can be given intramuscularly within 6 days of exposure and can be protective. The dose is 0.25 ml/kg for healthy persons and 0.5 ml/kg for immunocompromised persons the maximum dose should not exceed 15 ml. Immune globulin is strongly indicated for susceptible family members of measles patient, especially those below 1 year of age, and for immunocompromised persons. Immune globulin is also indicated in HIV patients.

Measles vaccination within 72 hours of exposure may also provide protection against clinical measles.

Special situations in measles:

Measles in adults:

Adults develop measles due to lack of immunization and rarely due to waning of vaccine-induced immunity. As a result waning of vaccine-induced immunity or lack of immunization there is very low titers of antibody to measles virus and infection due to lack of protection.

Measles is a childhood disease and is generally more severe among adults in compare to measles in children. Complications of measles are more common among adults, such as pneumonia, hepatitis, bacterial superinfection and bronchospasm etc. Rashes are also more severe among adults. More than one-third of adults with bacterial superinfection develop respiratory complications such as otitis media, sinusitis, and pneumonia.

Measles in immunocompromised individuals:

Immunocompromised individuals with defects in cell-mediated immunity are at risk for severe protracted and fatal measles due to high risk of complications. Immunocompromised individuals who are at higher risk of severe protracted and fatal measles include patients with congenital cellular immune defects, patients with cancer, recipients of immunosuppressive therapy, persons infected with HIV and AIDS. In immunocompromised individuals measles may not have a rash. The common complications include pneumonia, progressive encephalitis and progression of HIV infected individuals to AIDS.

Atypical measles:

Atypical measles has been reported among individuals who were vaccinated with formalin-inactivated measles vaccine and subsequently exposed to measles virus. Formalin-inactivated measles vaccines were used more than 40 years back till 1970 in some countries. The illness was self limiting, despite severe symptoms.

Atypical measles after a several-day of fever, myalgia, and headache, the rash appears (which begins peripherally instead of head in typical measles, and can be urticarial, maculopapular, hemorrhagic, and/or vesicular). Fever used to be high and resembled Rocky Mountain spotted fever, meningococcemia, drug allergy, toxic shock syndrome due to staphylococcus, and varicella. Atypical measles was believed to be due to hypersensitivity to measles virus induced by the inactivated vaccine, as measles virus can not be isolated from these patients.

Due to discontinuation of formalin-inactivated measles vaccine the atypical measles has virtually disappeared.