Approach Considerations
Although the diagnosis of measles is usually determined from the classic clinical picture (see Clinical), laboratory identification and confirmation of the diagnosis are necessary for the purposes of public health and outbreak control. Laboratory confirmation is achieved by means of serologic testing for immunoglobulin G (IgG) and M (IgM) antibodies, isolation of the virus, and reverse-transcriptase polymerase chain reaction (RT-PCR) evaluation.
A complete blood cell count (CBC) may reveal leukopenia with a relative lymphocytosis and thrombocytopenia. Liver function test (LFT) results may reveal elevated transaminase levels in patients with measles hepatitis.
Consult public health or infectious disease specialists for recommendations and guidelines for diagnostic confirmation of cases and prophylaxis of susceptible contacts.
Case reporting
Because the transmission of indigenous measles has been interrupted in the United States and all recent US epidemics have been linked to imported cases, immediately reporting any suspected case of measles to a local or state health department is imperative, as is obtaining serum for IgM antibody testing as soon as possible (ie, on or after the third day of rash).
The US Centers for Disease Control and Prevention (CDC) clinical case definition for reporting purposes requires only the following:
-
Generalized rash lasting 3 days or longer
-
Temperature of 101.0°F (38.3°C) or higher
-
Cough, coryza, or conjunctivitis
Further, for reporting purposes for the CDC, cases are classified as follows:
-
Suspected - Any febrile illness accompanied by rash
-
Probable - A case that meets the clinical case definition, has noncontributory or no serologic or virologic testing, and is not epidemiologically linked to a confirmed case
-
Confirmed - A case that is laboratory confirmed or that meets the clinical case definition and is epidemiologically linked to a confirmed case; a laboratory-confirmed case need not meet the clinical case definition
Antibody Assays
Immunoglobulin M
The measles virus sandwich-capture IgM antibody assay, offered through many local health departments and through the CDC, is the quickest method of confirming acute measles. Because IgM may not be detectable during the first 2 days of rash, obtain blood for measles-specific IgM on the third day of the rash or on any subsequent day up to 1 month after onset to avoid a false-negative IgM result.
Among persons with confirmed measles infection, the seropositivity rate for first samples is about 77% when collected within 72 hours; the rate rises to 100% when collected 4-11 days after rash onset. [33] Although the measles serum IgM level remains positive 30-60 days after the illness in most individuals, the IgM titer may become undetectable in some subjects at 4 weeks after rash onset. False-positive results can occur in patients with rheumatologic diseases, parvovirus B19 infection, or infectious mononucleosis.
Immunoglobulin G
Laboratories can confirm measles by demonstrating more than a 4-fold rise in IgG antibodies between acute and convalescent sera, although relying solely on rising IgG titers for the diagnosis delays treatment considerably. The earlier the acute serum is drawn, the more reliable the results. IgG antibodies may be detectable 4 days after the onset of the rash, although most cases have detectable IgG antibodies by about a week after rash onset.
Accordingly, it is recommended that specimens be drawn on the seventh day after rash onset. Blood drawn for convalescent serum should be drawn 10-14 days after that drawn for acute serum, and the acute and convalescent sera should be tested simultaneously as paired sera.
Patients with subacute sclerosing panencephalitis (SSPE) have unusually high titers of measles antibody in their serum and cerebrospinal fluid (CSF). The earliest confirmation of measles using IgG antibodies takes about 3 weeks from the onset of illness, a delay too long to permit implementation of effective control measures.
In atypical measles, laboratory evaluation of serum/blood reveals very low titers of measles antibody early in the course of the disease, followed by extremely high measles IgG antibody titers (eg, 1:1,000,000).
IgG levels can be explained by current infection, immunity due to past infection or vaccination, or maternal antibodies present in infants younger than 15 months.
Viral Culture
Throat swabs and nasal swabs can be sent on viral transport medium or a viral culturette swab to isolate the measles virus. Urine specimens can be sent in a sterile container for viral culture.
Viral genotyping in a reference laboratory may determine whether an isolate is endemic or imported. In immunocompromised patients, who may have poor antibody responses that preclude serologic confirmation of measles, isolation of the virus from infected tissue or identification of measles antigen by means of immunofluorescence may be the only feasible method of confirming the diagnosis.
Polymerase Chain Reaction
Reverse-transcription polymerase chain reaction (PCR) evaluation is highly sensitive at visualizing measles virus RNA in blood, throat, nasopharyngeal, or urine specimens and, where available, can be used to rapidly confirm the diagnosis of measles. [9] According to the CDC, the samples should be collected at the first contact with a suspected case of measles when the serum sample for diagnosis is drawn.
Studies for Suspected Complications
Chest radiography
If bacterial pneumonia is suspected, perform chest radiography. The frequent occurrence of measles pneumonia, even in uncomplicated cases, limits the predictive value of chest radiography for bacterial bronchopneumonia.
Lumbar puncture
If encephalitis is suspected, perform a lumbar puncture. CSF examination reveals the following:
-
Increased protein
-
Normal glucose
-
Mild pleocytosis with a predominance of lymphocytes
Tissue Analysis and Histologic Findings
A skin biopsy from a lesion of the morbilliform eruption shows spongiosis and vesiculation in the epidermis with scattered dyskeratotic keratinocytes. Occasional lymphoid multinucleated giant cells (≤ 100 nm in diameter) can be identified in biopsies of Koplik spots, in dermal or epithelial rashes, in hair follicles and acrosyringium and in lung or lymphoid tissue. These findings are not specific, but they are suggestive of a viral exanthem.
Brain biopsies of patients with measles encephalitis can reveal demyelination, vascular cuffing, gliosis, and infiltration of fat-laden macrophages near blood vessel walls.
-
Koplik spots in measles. Photograph courtesy of World Health Organization.
-
Enanthem of measles (Koplik spots).
-
Measles conjunctivitis.
-
Face of boy with measles.
-
Morbilliform rash.
