Measles: Pathogenesis, Clinical Features, Diagnosis, Treatment, Prevention by NJE

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Measles: An acute highly infectious disease of children, characterized by cough, coryza, fever, and rash. Humans are the only natural host.

The virus

• A member of the family Paramyxoviridae, genus Morbillivirus; ssRNA, enveloped virus; covered with short surface projections: haemagglutinin (H) and fusion (F) glycoproteins.

Epidemiology of Measles

• Found in every country in the world. Without vaccination, epidemics lasting 3–4 months would occur every 2–5 years.

• Airborne, spread by contact with aerosolized respiratory secretions, and one of the most communicable of the infectious diseases. Sensitive to light and drying, but can remain infective in droplets for some hours.

• Patients are most infectious during the late prodromal phase when coughing is at its peak. Immunity after infection is lifelong.

Pathogenesis of Measles

• The virus invades the respiratory epithelium, and local multiplication leads to viraemia and leucocyte infection. Reticulo-endothelial cells become infected, and their necrosis leads to secondary viraemia. The major infected blood cell is the monocyte.

• Tissues that become infected include the thymus, spleen, lymph node, liver, skin, and lung. Secondary viraemia leads to infection of the entire respiratory mucosa, with consequent cough and coryza. Croup, bronchiolitis, and pneumonia may also occur.

• Koplik’s spots and rash appear a few days after respiratory symptoms—may represent host hypersensitivity to the virus.

Clinical features of Measles

• Incubation is 2 weeks (longer in adults than children). A prodromal phase (coinciding with secondary viraemia) of malaise, fever, anorexia, conjunctivitis, and cough is followed by Koplik’s spots (blue-grey spots with a red base, classically found on the buccal mucosa opposite the second molars), then rash. Patients feel most unwell around day 2 of the rash. From late prodrome to resolution of fever and rash is around 7–10 days. Rash begins on the face and proceeds down, involving the palms and soles last. Erythematous and maculopapular, and may become confluent. It lasts around 5 days and may desquamate as it heals.

• Complications—bacterial superinfection (pneumonia and otitis media); acute encephalitis (1 in 2000 and probably due to host hypersensitivity to virus), characterized by fever recurrence, headache, seizures, and consciousness changes during convalescence; subacute sclerosing panencephalitis (SSPE)—chronic degenerative neurological condition, occurring years after measles, due to persistent CNS infection with measles virus, despite a vigorous host immune response; spontaneous abortion and premature labour—unlike rubella, there is no association with fetal malformations, but the disease can be more severe in pregnancy, and infants can acquire it. Infants born to mothers with active infection should be given immunoglobulin at birth.

• Prior to vaccination, measles was a common cause of viral meningitis and remains so in unvaccinated populations, usually occurring with a rash.

• Special conditions:

• modified measles—a very mild form of the disease seen in people with some degree of passive immunity, e.g. those receiving immunoglobulin or babies under 1 year;

• atypical measles—seen in those who received early killed measles vaccines and are later infected by wild-type virus. The rash is atypical and may resemble Henoch–Schönlein purpura (HSP), varicella, spotted fever, or a drug eruption. High fever, peripheral oedema, pulmonary infiltrates, and effusions may occur. The disease is more severe, has a longer course, and is thought to be due to hypersensitivity to the virus in a partially immune host. It is rare now, but those who have received only killed vaccine should be offered live vaccine;

• immunocompromised patients (including the malnourished) may experience severe disease, e.g. primary viral giant cell pneumonia, encephalitis, SSPE-like encephalitis. They may not develop a rash, making diagnosis difficult. Immunocompromised people should be passively immunized following exposure, even if previously vaccinated.

Diagnosis of Measles

Diagnosis can usually be made clinically. Laboratory confirmation is useful in atypical cases or the immunocompromised. Suspected and confirmed cases should be reported to public health.

• Other—immunofluorescence microscopy of cells in secretions, RT-PCR.

• Virus isolation—possible in renal cell lines, growth slow. Useful in the immunodeficient where antibody responses may be minimal.

• Serology—a 4-fold increase in measles antibody titre between acute and convalescent specimens is diagnostic. IgM is detectable from day 3 after rash onset, and IgG from days 7–14.

Treatment of Measles

• Supportive therapy and treatment of bacterial superinfection.

• Vitamin A 100000-200 000IU PO has been shown to reduce disease 

severity amongst children in developing countries. It may have benefit in developed countries in those with, or at risk of, complications. It should be avoided at or after immunization when it appears to reduce seroconversion.

Prevention of Measles

• Measles vaccine is given as part of MMR (measles, mumps, rubella) at 12 months and preschool. It can be given earlier in at-risk populations, but responses are suppressed, and an additional dose should be given later.

• The UK saw an increase in measles cases in 2012/2013 amongst 10–16-year-olds. Over 2000 cases were reported, of which 20% required hospitalization. This was probably a result of those who missed vaccination in the late 1990s/2000s, as a result of concern (now discredited) over a possible link between MMR and autism. Vaccine coverage fell to <80%. A catch-up programme for 10–16-year-olds was announced in 2013.

• Passive immunization with immunoglobulin is recommended for those exposed susceptible people at risk of severe or fatal measles—it must be given within 6 days of exposure to be effective. Such groups include children with defects in cell-mediated immunity, those with HIV or malignant disease, and unvaccinated pregnant women. Details are available on the PHE website (under ‘Immunoglobulin’ in Infections A-Z’).

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