Measles

Clinical Description

Identification
An acute, highly communicable viral disease with prodromal fever, conjunctivitis, coryza, cough, and small spots with white or bluish-white centers on an erythematous base on the buccal mucosa (Koplik spots). A characteristic red blotchy rash appears on the third to seventh day; the rash begins on the face, then becomes generalized, lasts 4–7 days, and sometimes ends in brawny desquamation. Leukopenia is common. The disease is more severe in infants and adults than in children. Complications may result from viral replication or bacterial superinfection, and include otitis media, pneumonia, laryngotracheobronchitis (croup), diarrhea, and encephalitis.
 
The case-fatality rate in developing countries is estimated to be 3%–5%, but may reach 10%–30% in some localities. Both acute and delayed mortality in infants and children have been documented. Measles is a more severe disease in the very young and in malnourished children, in whom it may be associated with hemorrhagic rash, protein-losing enteropathy, otitis media, oral sores, dehydration, diarrhea, blindness, and severe skin infections. Children with clinical or subclinical vitamin A deficiency are at particularly high risk of severe disease. In children whose nutrition status is borderline, measles often precipitates acute kwashiorkor and exacerbates vitamin A deficiency that may lead to blindness. Very rarely (in about 1/100 000 cases), subacute sclerosing panencephalitis (SSPE) develops several years after infection; over 50% of SSPE cases had measles diagnosed in the first 2 years of life. The WHO clinical case-definition for measles reads “any person with fever and maculopapular rash and cough/coryza/conjunctivitis.”
 
Infectious Agent
Measles virus, a member of the genus Morbillivirus of the family Paramyxoviridae.
 

Diagnosis

Diagnosis is usually on clinical and epidemiological grounds, although laboratory confirmation is preferred. The detection of measles-specific IgM antibodies, present 3–4 days after rash onset, or a significant rise in antibody concentrations between acute and convalescent sera, confirms the diagnosis. Less commonly used techniques include identification of viral antigen in nasopharyngeal mucosal swabs by FA techniques, or virus isolation in cell culture from blood or nasopharyngeal swabs collected before day 4 of rash, or from urine specimens before day 8 of rash. RT-PCR can be used to identify measles RNA in urine, blood, and nasopharyngeal mucus.
 

Epidemiology

Mode of Transmission
Airborne by droplet spread, direct contact with nasal or throat secretions of infected persons; less commonly by articles freshly soiled with nose and throat secretions. Measles is one of the most highly communicable infectious diseases.
 
Incubation Period
About 10 days, but may be 7 to 18 days from exposure to onset of fever, usually 14 days until rash appears; rarely, as long as 19–21 days. Immune globulin given for passive protection early in the incubation period may extend this period.
 
Period of Communicability
From 1 day before the beginning of the prodromal period (usually about 4 days before rash onset) to 4 days after rash appearance; minimal after the second day of rash. The vaccine virus has not been shown to be communicable.
 
Reservoir
Humans.
 
Susceptibility
All persons who have not had the disease or been successfully immunized are susceptible. Acquired immunity after illness is permanent. Infants born to mothers who have had the disease are protected against disease for the first 6–9 months or more, depending on the amount of residual maternal antibody at the time of pregnancy and the rate of antibody degradation. Maternal antibody interferes with response to vaccine. Immunization at 12–15 months induces immunity in 94%–98% of recipients; re-immunization increases immunity levels to about 99%. Children born to mothers with vaccine-induced immunity receive less passive antibody; they may become susceptible to measles and require measles immunization at an earlier age than is usually recommended.
 
Occurrence
Prior to widespread immunization, measles was common in childhood, so that more than 90% of people had been infected by age 20; few went through life without becoming infected. In the pre-vaccine era, there were an estimated 100 million cases and 6 million measles deaths a year. Measles, endemic in large metropolitan communities, attained epidemic proportions about every second or third year. In smaller communities and areas, outbreaks tended to be more widely spaced and somewhat more severe. With longer intervals between outbreaks, as in some Sahelian populations, in the Arctic and some islands, measles outbreaks often involved a large proportion of the population, with a high case-fatality rate. In temperate climates, measles occurs primarily in the late winter and early spring. In tropical climates, measles occurs primarily in the dry season.
 
With effective childhood immunization programs, measles cases in many industrialized countries have dropped by 99%, and generally occur in young un-immunized children or older children, adolescents or young adults who received only one dose of vaccine.
 
In 1994, the countries of the western hemisphere established a regional target of elimination of indigenous measles transmission by the end of the year 2000, through a comprehensive measles immunization strategy. This included the provision of measles vaccine to at least 95% of children aged 12–15 months, through routine immunization services, with another opportunity for measles immunization to all children, and careful measles surveillance. The second opportunity for measles immunization provides immunity to children who escaped routine immunization and those who failed to respond immunologically to the first vaccine, and is usually provided through Supplementary Immunization Activities (SIAs). One-off “catch-up” campaigns target all children aged 9 months to 14 years regardless of disease history or previous vaccination status, and “follow-up” campaigns are conducted every 3–4 years, targeting all children 9 months to 4 years. In Canada and the USA, the second opportunity for measles immunization is provided through routine immunization services, generally at school entry.
 
At time of writing in early 2008, strong country and regional measles surveillance systems indicate that the western hemisphere has been free of endemic measles since November 2002, thereby achieving the goal of measles elimination—although importations continue to occur, requiring maintenance of very high population immunity through vaccination. Also at time of writing, WHO is discussing the possibility of adding the goal of global measles elimination, rather than control.
 
Despite the existence of a safe, effective and inexpensive measles vaccine for 40 years, measles remains a leading vaccine-preventable killer of children worldwide. WHO estimates that there were approximately 17 million cases and 242 000 measles deaths worldwide in 2006. Over 95% of measles deaths occur in countries with per capita gross national products lower than $1 000, with over 85% in children aged under 5 years, and over 80% in southeast Asia and Africa. After achieving the global goal to halve measles mortality by 2005, the World Health Assembly adopted the new target of reducing global measles deaths by 90% from the 2000 level of 757 000 before the end of 2010; it recommended that all countries fully implement the WHO/UNICEF comprehensive immunization strategy for sustainable measles mortality reduction.
 

Prevention and Control

1)  Preventive measures:
a) Public education by health departments and private physicians should encourage measles immunization for all susceptible infants, children, adolescents and young adults. Those for whom vaccine is contraindicated, and un-immunized persons identified more than 72 hours after exposure to measles in families or institutions, may be partially or completely protected by IG given soon after exposure.
 
b) Immunization: Live attenuated measles vaccine is the vaccine of choice, indicated for all persons not immune to measles, unless specifically contraindicated. A single injection of live measles vaccine, often combined with other live vaccines (mumps, rubella), can be administered concurrently with other inactivated vaccines or toxoids; it should induce active immunity in 94%–98% of susceptible individuals, probably for life, by producing a mild or inapparent noncommunicable infection. Another dose of measles vaccine may increase immunity levels up to 99%.
 
About 5%–15% of non-immune vaccinees may develop malaise and fever to 39.5°C (103°F) within 5–12 days after immunization; this lasts 1–2 days, with little disability. Rash, coryza, mild cough and Koplik spots may occasionally occur. Febrile seizures occur infrequently and without sequelae; the highest incidence is in children with a previous history or a close family (parents or siblings) history of seizures. Encephalitis and encephalopathy have been reported (at the rate of less than one case per million doses distributed) following measles immunization—this is lower than the background rate and consequently may not be caused by the vaccine.
 
Current recommendations in the USA and other industrialized countries advise a routine 2-dose measles vaccination schedule. The initial dose is at 12–15 months or as soon as possible thereafter; the following dose, usually at school entry (4–6 years), can be administered as early as 4 weeks after the initial dose where the risk of exposure to measles is high. Both doses are generally given as combined measles, mumps and rubella vaccine (MMR).
 
Routine immunization with MMR at 12 months is particularly important in areas where measles cases occur. During community outbreaks, the recommended age for immunization using monovalent vaccine can be lowered to 6–11 months. A second dose of measles vaccine is then given at 12–15 months, and a third dose at school entry.

The optimal age for immunization in developing countries depends on the persistence of maternal antibodies in the infant and the increased risk of exposure to measles at a younger age. In most developing country settings, WHO recommends measles immunization of all children at 9 months, with another opportunity for measles immunization, generally through SIAs. In Latin America, due to the markedly decreased risk of an infant being exposed to measles virus, PAHO recommends routine immunization at 12–15 months for all children, with another opportunity for measles immunization through periodic SIAs.
 
i)  Vaccine shipment and storage: Immunization may not produce protection if the vaccine has been improperly handled or stored. Prior to reconstitution, freeze-dried measles vaccine is relatively stable and can be stored with safety for a year or more in a freezer or at refrigerator temperatures (2°–8°C/35.6°–46.4°F). Reconstituted vaccine must be kept at refrigerator temperatures and discarded after 8 hours; both freeze-dried and reconstituted vaccine must be protected from prolonged exposure to ultraviolet light, which may inactivate the virus.
 
ii) Re-immunizations: In the USA and other industrialized countries, in addition to routine re-immunization of children entering school, measles re-immunization is offered at entry to high school and colleges, and to international travelers and health care workers, unless they have a documented history of measles disease or immunization with 2 doses of vaccine, or serological evidence of measles immunity. In those who have received only inactivated vaccine, re-immunization may produce reactions such as local edema and induration, lymphadenopathy and fever, but will protect against the atypical measles syndrome. Use of inactivated measles vaccine was discontinued more than 30 years ago.
 
iii) Contraindications to the use of live virus vaccines:
 
(1) Patients with primary immune deficiency diseases affecting T-cell function or acquired immune deficiency due to leukemia, lymphoma or generalized malignancy, or those undergoing therapy with corticosteroids, irradiation, alkylating drugs or antimetabolites, should not receive live virus vaccines. Infection with HIV is not an absolute contraindication: unless severely immunocompromised, WHO recommends measles immunization of HIV-infected infants at 6 months of age followed by an additional dose at 9 months. The USA and other industrialized countries recommend measles vaccination only in asymptomatic HIV-positive individuals; low CD4 counts are a contraindication to measles vaccine because of the risk of viral pneumonia.
 
(2)  In patients with severe acute illness with or without fever, immunization should be deferred until recovery from the acute phase; minor febrile illnesses such as diarrhea or upper respiratory infections are not a contraindication.
 
(3)  Persons with anaphylactic hypersensitivity to a previous dose of measles vaccine, gelatin or neomycin should not receive measles vaccine. Egg allergy, even if anaphylactic, is no longer considered a contraindication.
 
(4)  Purely on theoretical grounds, vaccine should not be given to pregnant women; mothers should be advised of the theoretical risk of fetal damage if they become pregnant within 1 month after receipt of measles-containing vaccine.
 
(5)  Vaccine should be given at least 14 days before IG or blood transfusion. IG or blood products can interfere with the response to measles vaccine for varying periods depending on the dose of IG. The usual dose administered for hepatitis A prevention can interfere for 3 months; very large doses of intravenous IG can interfere for up to 11 months.
2)  Control of patient, contacts and the immediate environment:
a)  Report to local health authority: Obligatory case report in most countries, Class 2. Early reporting (within 24 hours) provides opportunity for better outbreak control.
 
b)  Isolation: Impractical in the community at large; if practicable, children with measles should be kept out of school for 4 days after appearance of the rash. In hospitals, respiratory isolation from onset of catarrhal stage of the prodromal period up to and including the fourth day of rash reduces the exposure of other patients at high risk.
 
c)  Concurrent disinfection: Not applicable.
 
d)  Quarantine: Usually impractical. Quarantine of institutions, wards or dormitories can sometimes be of value; strict segregation of infants if measles occurs in an institution.
 
e)  Immunization of contacts: Live virus vaccine should be administered within 72 hours of exposure. Alternatively, IG may be given (0.25 ml/kg or 0.11 ml/lb; for immunocompromised persons, 0.5 ml/kg or 0.22ml/lb up to a maximum of 15 ml within 72 hours of exposure, for maximal protection). IG should be used within 6 days of exposure for susceptible household or other contacts with high risk of complications (contacts under 1 year of age, pregnant women or immunocompromised persons), or where measles vaccine is contraindicated. Live measles vaccine should be given 5–6 months later to those for whom vaccine is not contraindicated.
 
f)  Investigation of contacts and source of infection: Search and immunize exposed susceptible contacts to limit the spread of disease. Healthy carrier state does not occur.
 
g)  Specific treatment: None. During measles infection, vitamin A reserves fall rapidly (especially in malnourished children), which further weakens immunity. Vitamin A supplementation at the time of measles diagnosis replaces body reserves, prevents blindness due to corneal ulceration and keratomalacia, and significantly reduces measles fatality. The following Vitamin A schedule is recommended:
 
Age Immediately Next Day
<6 months 50,000 IU 50,000 IU
6-11 months 100,000 IU 100,000 IU
12 months 200,000 IU 200,000 IU
h)  A third dose of vitamin A should be given 2–4 weeks later if there are signs of vitamin A deficiency on diagnosis (night blindness, Bitot spots, conjunctival or corneal dryness, corneal clouding or ulceration).
3)  Epidemic measures:
a) Prompt reporting (within 24 hours) of suspected cases, and comprehensive immunization programs for all susceptibles, are needed to limit spread. In day care, school and college outbreaks, all persons without documentation of 2 doses of live virus vaccine at least 1 month apart on or after the first birthday should be immunized unless they have documentation of prior physician-diagnosed measles, or laboratory evidence of immunity.
 
b)  In institutional outbreaks, new admissions should receive vaccine or IG.
 
c)  In many developing countries, measles has a relatively high case-fatality rate. If vaccine is available, prompt use at the beginning of an epidemic is essential to limit spread; if vaccine supply is limited, priority should be given to young children for whom the risk is greatest.
4)  Disaster implications:
Introduction of measles into refugee populations with a high proportion of susceptibles can result in devastating epidemics with high fatality rates. Providing measles vaccine to displaced persons living in camp settings within a week of entry is a public health priority.
5)  International measures: 
Persons traveling to measles-endemic areas should ensure that they are immune to measles.
 
Source: Heymann (Ed.). (2008). Control of Communicable Diseases Manual, 19th edition. Washington, DC: American Public Health Association.

Available Vaccines

 
Common Disease Taxonomy: