1.2 The clinical description and complications of measles

Measles is an illness characterized by generalized maculopapular rash lasting 3 or more days with a temperature of 38.3°C or higher, and typical symptoms include one or more of the “3 c’s”: cough, coryza, or conjunctivitis. Clinically, the diagnosis of measles is supported by the appearance of irregular red lesions with bluish white centres in the buccal mucosa (Koplik spots) that appear 1-2 days before the onset of rash [5]. Otitis media is a common respiratory complication. The rash, which appears about 14 days after exposure, progresses from the head to the trunk and out to the extremities. Refer to Figure 1.2, Clinical features of primary measles infection – time course from onset of illness.

The non-specific nature of the prodromal signs and the existence of mild cases, however, makes clinical signs and symptoms unreliable as the sole diagnostic criteria of measles disease. Other viral illnesses that may produce a rash suggestive of a measles infection include rubella, dengue, enteroviruses, coxsackie virus, parvovirus B19, zika, and human herpesvirus 6 (HHV6). A rash resembling that of measles may also accompany bacterial infections such as toxic shock syndrome, certain medical conditions such as Kawasaki’s disease, or as a consequence of allergic reactions to treatment with antibiotics. Despite the existence of alternative etiologies for rash and fever, it is critical that measles infection is considered in the differential diagnosis. As the incidence of measles declines, medical practitioners may overlook the possibility of measles, particularly when such cases occur outside the context of an outbreak.

Many factors can contribute to the severity of measles in developing countries including poor nutrition, exposure to high doses of virus in crowded conditions, and an early age at which infants are exposed to the community at large. Death resulting from measles infection is usually attributed to the immunosuppression associated with measles infection that can lead to secondary bacterial and viral infections resulting in life-threatening pneumonia [6]. Diarrhoea is a complication of measles that can be particularly severe among malnourished young children in developing countries. Measles-specific immune suppression begins with the onset of clinical disease before the rash appears, and continues for several weeks after apparent recovery. Patients with defects in cell-mediated immunity often suffer severe progressive measles infections and have a significantly increased risk of death. Immunocompromised individuals may develop giant cell pneumonia as well as measles inclusion body encephalitis.

Measles can have serious complications such as deafness and blindness among immune-competent individuals. In addition, severe neurological sequelae can result from acute encephalomyelitis, which occurs in about 1 in 1,000 cases. Symptoms appear within 1-2 weeks after rash onset and can result in death (5-30%) or permanent impairments among about 30% of the survivors [1].

Measles infection is the cause of subacute sclerosing panencephalitis (SSPE), a progressive neurodegenerative disease that manifests 4-10 years after acute infection with wild-type measles virus and is invariably fatal. Although SSPE is considered a rare complication of measles, revised estimates of the rate of SSPE have been reported using denominators derived from defined outbreaks or populations. These studies have calculated rates of SSPE that are much higher than the earlier estimates, approximately 10 cases of SSPE per 100,000 cases of measles compared to 10 per million cases. The risk of SSPE is higher among children who contracted measles at less than 5 years of age and the likelihood of developing SSPE may be highest when measles infection occurs at less than 1 year of age [7,8,9].