It is 1962 in a medium-cited city in Wisconsin. A 7-year-old girl comes home from a long, hard day in her second grade class with a cough, a runny nose, and a touch of fever. Over the next three days, the girl's fever intensifies (eventually reaching 40.5ºC) and she exhibits malaise, increased nasal discharge, and mild conjunctivitis with lacrimation. It is the middle of winter (remember, this is happening in Wisconsin of all places), and children have to spend most of their time indoors. Moreover, the annual flu epidemic has reached this family's home town and has been going around in the schools, so the girl's mother figures that this is a case of flu that will soon begin to decrease in intensity.

On the fourth day of the girl's illness, a non-pruritic, maculopapular rash develops behind her ears and quickly spread to her forehead. Over the next 24 hours, the rash continues to spread down the trunk and along the extremities, eventually covering the palms and soles. The rash becomes confluent in some locations and the girl experiences occasional rounds of vomiting and diarrhea. Her mother, of course, realizes that this is not a case of influenza. In fact, her mother has a pretty good idea of what this actually is (as did most mothers during that time period).

Question 5.1: Do you know what this is?

It is a classic case of measles, also known as rubeola. Measles is one of a number of well-known childhood exanthems (diseases that produce a skin eruption).

Question 5.2: What is the differential?

The differential for measles includes several other viral diseases that may lead to development of a skin rash. (Some of these diseases frequently produce a rash, whereas others tend to do so only rarely). Among these viral diseases are German measles (rubella), fifth disease (erythema infectiosum), roseola (exanthema subitum), infections caused by specific strains of coxsackieviurses and echoviruses, primary HIV infection, and infectious mononucleosis. The differential can also include a number of bacterial diseases that are associated with skin rashes, such as scarlet fever, Rocky Mountain spotted fever, epidemic typhus, scrub typhus, and several others. Noninfectious sources of rash, such as allergic reactions to drugs, must also be considered.

Question 5.3: How does this disease differ from similar diseases?

Measles produces one truly unique and characteristic symptom. Just before the onset of the skin rash, Koplik's spots develop on the buccal mucosa alongside the second molars. Koplik's spots appear as 1-2-mm blue-white spots on a bright red background, and they can be quite extensive. They are not associated with any other known diseases. Without adequate lighting for examination, however, they can easily be overlooked. Moreover, they disappear shortly after the onset of the skin rash, so they may be gone by the time most patients are seen by a physician.

Measles also differs from similar diseases in terms of how the rash develops and the detailed appearance of the lesions. Some examples of this are summarized in the following table:

Question 5.4: What is the causative agent?

Measles is caused by the measles virus. It is a member of the Paramyxoviridae family. Like the other viruses in this family, it possesses a negative-sense single-stranded RNA genome surrounded by a helical nucleocapsid and a pleomorphic envelope.

Question 5.5: How is this disease transmitted?

Because the virus initially infects the upper respiratory tract, the disease is transmitted through the air, by droplet infection. It is one of the most contagious diseases known, and transmission is almost certain if person who has not been exposed previously spends time in the same room with an infectious person. Moreover, the early symptoms mimic influenza or a heavy cold, so there is little reason to suspect that the person has measles unless a local outbreak is occurring.

Question 5.6: How does the disease progress?

After replicating in the epithelial tissues of the upper respiratory tract for a while, the virus enters the lymphatic system and bloodstream (viremia). It is then distributed through the body, where it may infect the conjunctiva, additional portions of the respiratory tract, the urinary tract, and, in some cases, the CNS. The maculopapular rash is actually caused by immune T cells targeted to virus-infected endothelial cells lining small blood vessels under the surface of the skin.

Question 5.7: How significant is this disease?

Obviously, measles is now quite rare in countries that make use of the vaccine (which was introduced in 1963). However, it is still quite common in other regions, where it occurs primarily in comparatively young children. Because many of these children are undernourished or have other health-related problems, the diarrhea and vomiting associated with measles can be fairly intense, leading to severe dehydration. Young children's bodies are ill equipped to deal with dehydration in the first place, and they may be partially dehydrated before the disease strikes (because of limited local water supplies). As a result, measles is still the most significant cause of death (worldwide) in children under the age of 5.

Question 5.8: What is this boy's prognosis?

It is actually very good, even though treatment is largely limited to supportive therapy. Ribavirin has been shown to be effective against the measles virus in vitro and might be considered for use in immunocompromised hosts or those who appear to be developing potentially dangerous complications. However, most cases are self-limiting. The rash in the current case resolved in three days, and the girl made a full recovery. Dangerous complications such as viral pneumonia, post-infectious encephalitis, and SSPE are relatively rare. The mortality rate in the U.S. is about 0.3% (as compared to 5-10% in developing countries where the vaccine is not used).