MM 463-466; ID 892-902

NAME OF DISEASE:      14-day measles
                                                Hard measles
                                                Hemorrhagic measles
                                                Measles
                                                Rubeola
                                                Black measles
                                                Tropical measles

OVERVIEW:

Measles is a viral disease of leukocytes and lymphatic tissue that occurs in childhood with the incidence peaking at 5 years of age. It is characterized by a prominent prodromal phase of cough, coryza and conunctivititis followed by Koplic spots and a descending macular/papular rash.
 

ETIOLOGICAL AGENT:

Measles virus. A paramyxovirus which contains an envelope and RNA. It replicates in the nucleus.

EPIDEMIOLOGY:

Man and monkeys are the only known natural hosts. Spread by direct contact, contaminated fomites or droplet inhalation. One of the most contagious of the childhood exanthems.--90% attack rate.

PATHOLOGY:

Inoculation of the upper respiratory tract or conjunctival sac with measles is followed by a period of viral replication in the oral mucosa and in the regional lymph nodes. Shortly thereafter, on the second or third day of illness, a primary viremia disseminates the virus to lymphoid tissues throughout the body, where it multiplies to high titer. A more extensive and prolonged secondary viremia, from the fifth or sixth day onward, is responsible for the widespread, focal infection of the tissues that later show involvement. Multiplication of the virus and inflammation with necrosis progress in involved organs; by the 11th day prodromal symptoms are generally evident. On or about coincident with the appearance of measurable amounts of circulating antibody, viremia ceases and symptoms begin to abate.

During the biphasic viremia, the measles virus is disseminated mainly within leukocytes. Viral multiplication within leukocytes accounts for the leukopenia and the increased incidence of chromosomal breaks seen in measles.

During the prodromal period, hyperplasia of lymphoid tissues is present in various organs including the lymph nodes, tonsils, adenoids, Peyer's patches, appendix, spleen, and thymus. A more specific finding is the presence of large, multinucleated giant cells (Warthin-Finkeldey cells) that contain as many as 100 nuclei along with cytoplasmic and intranuclear eosinophilic inclusion bodies.

The exanthem begins with hyaline necrosis of epidermal cells followed by endothelial proliferation, exudation of serum and necrosis of epithelial cells with the formation of minute vesicles that rapidly break down and desquamate. Destructive changes may occur in hair follicles and sebaceous glands.
 

DIAGNOSIS (clinical signs):

    1. Incubation Stage

        Shortly after infection, at a time corresponding to the primary viremia-during the incubation period but before the appearance of
        prodromal symptoms-a mild illness may occur that is accompanied in some instances by a faint rash.

    2. Prodromal Stage

        Ten to twelve days after infection, the very prominent and characteristic prodromal symptoms appear: coryza; a persistent,
        barking cough; keratoconjunctivitis, often with photophobia; and fever. General lymphadenopathy and splenomegaly are also
        frequent at this time. During this period, Koplik's spots, the exanthema of measles, appear on the buccal mucosa. They are
        generally first seen on the inner lip or opposite the lower molars - in Koplik's words, appearing as "...small, irregular spots, of a
        bright red color. In the center of each spot, there is noted, in strong daylight, a minute bluish white speck." Although few in
        number and often difficult to find during the early stages of the prodrome, they rapidly spread, involving the entire mucous
        membrane, resembling at their height small grains of white sand on a red background. These spots are usually gone by the
        time the skin rash reaches its peak. Similar spots have occasionally been observed on the conjunctiva, and labia, and in the
        gastrointestinal tract. Although true Koplik spots are considered absolutely pathognomonic of measles, an exanthema
        somewhat similar in appearance has been reported in patients with echovirus 9 and coxsackievirus A-16 infections.

    3. Exanthem Stage

        The rash of measles appears after a three to five-day prodrome, some 14 days after exposure. It is first evident as faintly pink
        macules located behind the ears or on the forehead near the hairline. The rash quickly becomes maculopapular and spreads
        rapidly downward over the face, neck, trunk, and extremities during the next three days. As the rash progresses, the areas
        initially involved develop additional lesions that tend to coalesce, especially on the face. At its height, the eruption deepens to
        a reddish purple, and it may be associated with edema of the skin. Thereafter, the fever begins to fall, and systemic
        manifestations usually diminish over the succeeding several days. The rash fades from above downward, progressing as it
        evolved. As clearing occurs the lesions become brown, and a fine, branny desquamation often appears, usually sparing the
        hands and feet and thus distinguishable from the heavier, flaky desquamation seen in scarlet fever. Although the rash
        blanches on pressure, the brown staining that is the residual from capillary hemorrhages does not. Rash is not on palms and
        soles.

COMPLICATIONS:

1. Hemorrhagic measles (black measles)

2. Bronchiolitis - secondary bacterial pneumonia is the main cause of death in measles

3. Giant-cell pneumonia (Hecht's pneumonia) - a protracted, fatal, interstitial viral pneumonitis seen only in children

4. Subacute sclerosing panencephalitis (SSPE)

5. Otitis media

6. Thrombocytopenic purpura

7. Myocarditis/pericarditis
 

TREATMENT:

The treatment of uncomplicated measles is symptomatic. General measures include bed rest, maintenance of fluid intake, and aspirin for fever and headache. Attempts to suppress the cough with cough mixtures containing narcotics or sedatives should be avoided.

PREVENTION:

Live attenuated measles virus vaccine is currently recommended as part of the routine primary immunization series for all children over 12 months of age.

Although administration of live measles vaccine is routinely delayed until 15 months of age or later to eliminate the possible interfering effect of maternally derived antibody, the vaccine may be given to younger infants (as early as six months) if measles is prevalent or the risk of exposure is high. In such cases, a booster does of vaccine should be given after 12 months of age to assure an adequate antibody response.

Elective use of live vaccine should be delayed for at least eight weeks and preferably for 12 weeks after administration of whole blood, plasma, or gamma globulin because the measles antibody content of these preparations may be enough to neutralize the vaccine.

Contraindications to live measles virus vaccine administration include:

    1. Active untreated tuberculosis

    2. Pregnancy

    3. Leukemia

    4. Diseases or medications which suppress cell-mediated immunity or antibody response.

    5. Hypersensitivity to Neomycin (in the case of Attenuvax)

The vaccines available are either:

    1. Bivalent (measles and rubella)         ) Given in a single
    2. Trivalent (measles, mumps, rubella) ) injection at 15 months of age

Pooled adult gamma globulin is effective in preventing or modifying natural measles if given within six to eight days after exposure.