eMedicine Specialties > Dermatology > Viral Infections

Measles, Rubeola

Author: Paul Krusinski, MD, Director of Dermatology, Professor, Department of Internal Medicine, Fletcher Allen Health Care, University of Vermont
Contributor Information and Disclosures

Updated: Dec 2, 2009

Introduction

Background

Measles has been called the greatest killer of children in history. Despite the availability of an effective vaccine that was developed more than 30 years ago, the measles virus still affects 50 million people annually and causes more than 1 million deaths. The highest incidence of measles and its associated morbidity and mortality is observed in developing countries. However, it still occurs infrequently in the United States and other industrialized nations.^1,2

Pathophysiology

The measles virus initially infects the respiratory epithelium and is transmitted via respiratory droplets. It is highly transmissible with an infectivity rate of 76%, even greater than that of varicella. Prior to the measles vaccine, infection with the measles virus was simply considered a part of life.

Instead of replicating in the respiratory epithelium, as was once thought, replication appears to occur in the regional lymph nodes. Replication in regional lymph nodes eventually leads to viremia. Infection of the endothelial cells ensues, causing an enanthem (Koplik spots). Epithelial cells are also infected, leading to the well-known cutaneous eruption of measles.

The measles virus is a single stranded RNA virus of the genus Morbillivirus and family Paramyxoviridae. Measles virus has 2 membrane glycoproteins called hemagglutinin and fusion. Both of these glycoproteins appear to be important for infection with the measles virus.
Hemagglutinin appears to be involved with receptor binding and fusion, with fusion of the virus with host cells. Expression of hemagglutinin activates the alternative complement pathway.
The Edmonston strain of the measles virus and vaccines derived from this strain bind to the cell surface protein CD46, also known as membrane cofactor protein. CD46 is a regulator of the complement activation gene and inhibits activation of the alternative complement pathway. Four isoforms of CD46 exist in humans, and all are capable of binding measles virus.^3,4,5

An additional cellular receptor for the measles virus has recently been identified called SLAM (signaling lymphocyte-activation molecule) or CDw150 expressed on some T and B cells. SLAM is capable of binding strains of the measles virus that also bind CD46 (the Edmonston strain) as well as strains that do not bind CD46 such as the KA strain.⁶

Infection with the measles virus leads to a prolonged immunosuppression, which accounts for much of the morbidity and mortality associated with this disease. Cell-mediated immunity decreases, clinically evidenced by the conversion of positive tuberculin skin test results to negative following infection or vaccination. The mechanism of this immunosuppression is being elucidated.

Following infection with the measles virus, a shift from cell-mediated immunity (a TH-1 response) to humoral immunity (a TH-2 response) occurs. Expression of the TH-2 cytokine interleukin (IL)–2 is increased, supporting antibody formation, and TH-1 cytokines IL-2, IL-12, interferon (IFN)–gamma decrease.

IL-12 is a crucial cytokine for the development of cell-mediated immunity. It is necessary for delayed-type hypersensitivity, induces production of IFN-gamma, and plays a role in activation of T cells and natural killer cells. Karp et al⁷ found that infection of monocytes, the primary producer of IL-12, with the measles virus via CD46 led to decreased production of this cytokine. Fugier-Vivier et al⁸ found that activated dendritic cells also had a significant decrease in production of IL-12, leading to proliferation of the measles virus and apoptosis of infected dendritic cells and T cells. These findings support the hypothesis that measles virus infection of antigen-presenting cells plays a critical role in the immunosuppression observed following infection with the measles virus.

Primates are the only hosts for measles virus, and no animal model exists that replicates the clinical findings of measles infection typical in children.

Frequency

United States

The US Centers for Disease Control and Prevention (CDC) support strict surveillance of measles both in the United States and abroad.⁹ The CDC defines a case of measles as one that is confirmed by (1) serologic laboratory tests, such as enzyme immunoassays for measles IgM antibodies; (2) cases epidemiologically linked to a laboratory confirmed case; or (3) clinically confirmed cases (ie, cases of measles suspected clinically but neither confirmed by serologic laboratory tests nor epidemiologically linked to a laboratory confirmed case). In countries that are trying to eliminate measles, the category of clinically confirmed cases represents a failure of the surveillance system because all cases ideally should be confirmed serologically or epidemiologically linked to a laboratory confirmed case.

According to an epidemiologic report by the CDC in 1999¹⁰ , the measles virus is no longer indigenous to the United States. Most reported measles cases are importation associated, meaning that they are linked to a strain of the measles virus outside of the United States.

In 2005, the CDC reported that 66 cases of measles were confirmed in the United States. Fifty of these cases were in unvaccinated individuals and 17 were contracted while traveling abroad. A large outbreak in Indiana in 2005 infected 34 people, the largest outbreak since 1999. This outbreak was linked to a young woman who acquired the infection while on a brief trip (2 wk) to Romania. As recently as June 2006, a measles outbreak occurred in Boston, Mass and was linked to a recent immigrant from India. Thirteen cases of measles were confirmed in this outbreak, and they were linked to a common Indian strain of this virus.
 
More concerning was the report of 2 infected individuals who worked at the Christian Science Center in downtown Boston. Many members of this church are unvaccinated, which raised concern that the virus would spread further.

Importation-associated strains of measles may be acquired outside of the United States (internationally imported), have a known chain of transmission from an internationally imported source (epi-linked), or have a genotype that matches a known international strain without a clear chain of transmission or individual source (imported).

The number of non–importation-associated measles cases has significantly decreased since 1995, when 85% of all reported cases of measles in the United States were considered indigenous and not linked to importation. In addition, only 6 measles outbreaks were reported in 1998, the lowest ever recorded. The data collected by the CDC suggest that indigenous measles has been eliminated in the United States. Despite this, cases of measles will continue to arise, as it is not as well controlled in other parts of the world.

International

Cases of measles will continue to arise even in developed nations with a high percentage of vaccinated individuals because of the millions of people still infected worldwide. Vaccination campaigns in many developing nations have fallen short, making measles deaths the most common cause of childhood death from vaccine-preventable disease.¹¹ In the World Health Report in 2002, the World Health Organization (WHO) reported 30-40 million cases of measles annually, with 745,000 deaths attributable to the virus. In Africa in the 1990s, an estimated 400,000 children died annually from complications related to measles.

An Australian report from 2009 describes 3 cases of secondarily acquired measles from an index case (acquired in China) during air travel. Two of the infected persons were fully immunized and 1 was partially immunized.¹²

Mortality/Morbidity

• The acute child fatality rate in industrialized nations is only 0.1-0.2%, compared with a 2-10% fatality rate in children in the developing world. The larger incidence of measles in developing nations combined with the higher fatality rate contributes to close to 1 million childhood deaths per year.
• Conditions possibly (unproven) associated with measles include multiple sclerosis, osteosclerosis (hearing loss), lung cancer,¹³ and some autoimmune disorders.

Race

Infection with measles has no race predilection. Prevalence is linked to inadequate vaccination in developing countries.

Sex

Measles infection has no sex predilection.

Age

Historically, measles is a disease of childhood and continues to affect children in developing countries. In industrialized nations, infection is seen in unvaccinated individuals of any age or those with waned immunity.

Clinical

History

Measles was the first exanthem described historically.

• It has an incubation period of 7-14 days (average, 10-11 d).
• It is communicable just before the beginning of the prodromal symptoms, until approximately 4 days following the onset of the exanthem.
• The prodrome develops on day zero following incubation.
  • The prodrome consists of the well-known 3 C's of measles: cough, coryza, and conjunctivitis.
  • Fever and photophobia are also common during this period.
  • These symptoms increase in severity up to 3-4 days prior to the onset of the morbilliform rash.

Physical

• The enanthem (Koplik spots) predate the exanthem by 24-48 hours and last approximately 2-4 days.
  • These blue-white spots, about the size of kosher salt grains, are surrounded by a red halo.
  • They appear on the buccal mucosa opposite the premolar teeth and are pathognomonic for measles.
• The exanthem itself begins on the fourth or fifth day following the onset of symptoms.
  • The rash appears as slightly elevated papules 0.1-1 cm in diameter that begin on the face and behind the ears.
  • Within 24-36 hours following the onset of the rash, it spreads to the entire trunk and the extremities.
  • Initially, the color is dark red and reaches its maximum intensity in approximately 3 days. It slowly fades to a purplish hue and then to yellow-brown lesions with a fine scale over the following 5-10 days.
• The appearance of the signs and symptoms of measles are as follows:
  • Days 0-1: Prodrome begins.
  • Days 2-3: Koplik spots appear.
  • Days 4-5: Morbilliform rash appears.
  • Day 6: Koplik spots regress.
  • Days 7-8: Rash is most intense.
  • Day 10: Rash begins to resolve.

Causes

See Pathophysiology.

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