ARTICULO MEDICO: PREVENTION AND TREATMENT OF MEASLES

Prevention and treatment of measles
Authors
Jorge L Barinaga, MD, MS
Paul R Skolnik, MD, FACP, FIDSA
Section Editor
Martin S Hirsch, MD
Deputy Editor
Elinor L Baron, MD, DTMH
Disclosures
All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: May 2013. | This topic last updated: feb 12, 2013.

INTRODUCTION — Measles is a highly contagious viral infection [1]. Mathematical models have estimated that the average number of secondary infections that follow a single introduction of measles into a susceptible population ranges from 12 to 18 [2]. Infection with measles is highly preventable. Control measures for the prevention and spread of measles and treatment modalities for the virus will be reviewed here. The epidemiology, aims for global eradication, clinical manifestations, and diagnosis are discussed separately. (See "Epidemiology and transmission of measles" and "Clinical presentation and diagnosis of measles".)

CONTROLLING SPREAD — Control of outbreaks is of paramount importance in the prevention of measles. The Centers for Disease Control and Prevention (CDC) defines a measles outbreak as “a chain of transmission with three or more confirmed cases” [3]. Suspected cases of measles should be reported immediately to the local or the state health department, and all such reports should be investigated promptly. Control measures should not be delayed while waiting for laboratory confirmation of the diagnosis [4]. (See 'Outbreak control measures' below.)

Case definitions — Several case definitions have been established to standardize the approach to

measles outbreaks [4,5].

· Suspected case — A suspected case is defined as a febrile illness accompanied by rash.

· Clinical case — A clinical case is defined as an illness characterized by cough, coryza, or conjunctivitis, a generalized rash lasting for more than three days, and a temperature > 38.3ºC (>101ºF).

· Probable case — A probable case meets the clinical case definition, but is not linked epidemiologically to a confirmed case and lacks serologic or virologic proof of disease.

· Confirmed case — A confirmed case meets the laboratory criteria for measles (independent of clinical features) or meets the clinical case definition and is epidemiologically linked to a confirmed case.

Outbreak control measures — Prevention of spread in the setting of an outbreak depends upon prompt administration of vaccine to all susceptible persons. All individuals should provide documentation of measles immunity, which includes one of the following (See 'Establishing evidence of measles immunity'below.):

· Birth before the year 1957

· Clinical measles diagnosis by a physician

· Laboratory evidence of immunity

· Documentation of receipt of two doses of live measles virus-containing vaccine from a physician or healthcare facility Individuals unable to produce documentation of measles immunity should be excluded from the outbreak setting until they have complied with vaccination requirements. Those who are exempt from vaccination for medical, religious, or other reasons should be excluded from the outbreak setting for a minimum of three weeks after the onset of rash in the last measles case. Quarantine measures are not otherwise routinely recommended in outbreak control [4].

Schools — Schools are particularly vulnerable to measles outbreaks. In a number of college and secondary school outbreaks in the United States, some individuals who had received one dose of vaccine still developed infection, suggesting that immunity to measles in such individuals can wane. In 1989, the United States adopted a two-dose strategy; revaccination with measles-mumps-rubella (MMR) vaccine is recommended for all children prior to school entry (age four to six years), their siblings, and school personnel who are unable to provide documentation of measles immunity [6]. Furthermore, in order for vaccination to be considered adequate for school outbreaks, two doses of measles vaccine must have been administered after the age of 12 months and separated by at least 28 days.

The Advisory Committee on Immunization Practices (ACIP) also recommends that vaccination efforts be considered at unaffected schools that may be at risk during an outbreak. Those who are properly vaccinated may reenter the school immediately after vaccination [4]. 

Healthcare facilities — In the setting of a measles diagnosis in a healthcare facility, all employees must provide documentation of measles immunity as outlined above [7]. Any employee who cannot produce such documentation must be excluded from work and administered MMR vaccine promptly. The ACIP recommends that vaccination of those born before 1957 who do not have laboratory evidence of measles immunity also be considered, since some individuals with these characteristics have acquired and transmitted measles in the healthcare setting. (See 'Birth before the year 1957' below.)

Susceptible healthcare workers with measles exposure should be vaccinated within 72 hours of exposure. Previous recommendations indicated that if vaccination occurred within 72 hours of exposure, then exclusion from the workplace was not mandatory except in high-risk settings; subsequent guidelines suggest exclusion of all susceptible exposed persons [8]. Any individual who develops a prodromal illness consistent with measles must be excluded from the facility until four days after the appearance of rash; this interval is the period of infectiousness for measles [4].

Isolation is discussed below. (See 'Case isolation' below.)

Outbreaks among infants — Among infants with measles exposure, those aged 6 to 11 months can receive live measles vaccine, although they must be reimmunized at age 12 to 15 months and again prior to school entry. For infants exposed to measles within the household, immunoglobulin administration may be preferable since the risk for acquiring infection is higher than for other types of exposure [4].

Case isolation — When a case of measles is suspected in a healthcare facility, respiratory isolation should be initiated. Specifically, private rooms with negative pressure air ventilation (minimum of six air changes per hour) and the use of masks at all times should be required. Data are insufficient to determine the optimal type of mask or respirator [9]. Susceptible healthcare workers should not enter the room of infected patients. (See 'Healthcare facilities' above.)

The ACIP does not make any specific recommendations about isolation of suspected or confirmed cases of measles in the community. Strict respiratory isolation techniques have been demonstrated to decrease transmission rates in an outbreak situation [10]. Precautions should include respiratory isolation since the transmission of measles virus occurs via aerosol [11].

Use of immune globulin — Intramuscular immune serum globulin can prevent or diminish the severity of disease if administered to susceptible individuals within six days of exposure [4,12]. Administration of immune serum globulin may be especially warranted in exposed individuals for whom the risk of complications of measles is increased, such as pregnant women, individuals less than one year of age, and immunocompromised hosts. Immunocompromised individuals with prior history of vaccination should also receive IG following exposure. Dosing consists of 0.25 mL/kg of body weight to a maximum dose of 15 mL intramuscularly [4,12]. In immunocompromised hosts dosing is 0.5 mL/kg body weight to a maximum dose of 15 mL.

Individuals receiving immune serum globulin should receive live vaccination no earlier than five to six months later, so long as the individual is at least 12 months of age at that time and there is no contraindication to vaccination. The passively-acquired measles antibodies from the immune serum globulin should have been cleared by five to six months. For contacts not belonging to these highrisk groups, the administration of live measles vaccine within 72 hours of the exposure is preferable to immune serum globulin administration.(See 'Contraindications' below.)

Administration of immune serum globulin should not be used for outbreak control [4].

MEASLES VACCINATION — Measles vaccination has markedly reduced the incidence of easles throughout the developed world. However, measles cases still occur in low-incidence countries via importation by travelers. Therefore, maintenance of immunity is important even in countries with a low incidence of measles, since a single imported case can result in large measles outbreaks in the setting of waning immunity. (See "Epidemiology and transmission of measles".) Measles vaccine is recommended for all children and for certain high-risk adolescents and adults. Factors to be considered when determining the need for measles vaccination include the age of the recipient, the date of administration of the first dose of vaccine (if any), and local measles epidemiology, including the potential risk of exposure, the type of measles vaccine administered previously, contraindications to vaccination, travel plans, and evidence of prior measles infection. (See "Measles-mumps-rubella vaccination in high risk adults".)

The importance of maintenance of immunity was underscored by a Centers for Disease Control and Prevention (CDC) analysis of United States measles cases reported in 2011, which found that the majority of cases could have been prevented by vaccination; 89 percent of 118 measles cases occurred in unvaccinated individuals [13]. Immunization is also important for preventing severe sequelae of measles infection, including subacute sclerosing panencephalitis [14]. (See "Clinical presentation and diagnosis of measles".)

Strategies to update immunizations in foreign-born adults are an important component of a comprehensive vaccine program. This is supported by a serologic study of recently arrived immigrants and refugees to Canada, in which 36 percent of participants were nonimmune to at least one of three vaccine-preventable diseases (eg, measles, mumps, or rubella) [15]. (See "Epidemiology and transmission of measles".)

Types of measles vaccines — The vaccine strain currently in use in the United States is the Enders-Edmonston strain. This live attenuated vaccine was licensed for use in 1968. It is available in combination as a measles-mumps-rubella (MMR) vaccine [5], and as the quadrivalent MMRV vaccine (measles, mumps, rubella, and varicella). Several other vaccines, also derived from attenuated measles virus, are in use in other parts of the world. Previously used measles vaccines include an inactivated Edmonston B strain vaccine distributed in the United States from 1963 to 1967, a live attenuated Edmonston B strain vaccine from 1963 to 1975, and a different live attenuated Schwarz strain vaccine introduced in 1965, which is no longer available in the United States. The inactivated vaccine was associated with severe atypical measles in those exposed to live measles after vaccination.

Management of patients previously vaccinated with prior vaccine types is discussed below. (See 'Prior vaccination with other strains' below.)

MMRV — MMRV vaccine was approved by the United States Food and Drug administration in 2005 for individuals aged 12 months to 12 years. MMRV has comparable immunogenicity to simultaneous MMR and varicella vaccination [16]. In postlicensure studies MMRV was associated with a small increased risk for febrile seizures; this risk was present at the typical age of receipt for the first dose of vaccine, but not at the age of receipt for the second dose [16]. The Advisory Committee on Immunization Practices (ACIP) reviewed the risks and benefits of MMRV compared to simultaneous MMR and varicella vaccineand issued recommendations for use as follows [16,17]:

· For the first dose of measles, mumps, rubella, and varicella vaccines at age 12 to 47 months, either separate MMR and varicella vaccines or MMRV vaccine may be used. Providers considering administration of MMRV vaccine should discuss the benefits and risks of both vaccination options with the parents or caregivers. Unless the parent or caregiver expresses a preference for MMRV vaccine, the CDC recommends that separate MMR and varicella vaccines be administered for the first dose in this age group.

· For the second dose of measles, mumps, rubella, and varicella vaccines at any age (15 months to 12 years) and for the first dose at age ≥48 months, use of MMRV vaccine generally is preferred over separate injections of its equivalent component vaccines (ie, MMR vaccine and varicella vaccine). Considerations should include provider assessment, patient preference, and the potential for adverse events. Provider assessment denotes consideration of “the number of injections, vaccine availability, likelihood of improved coverage, likelihood of patient return, and storage and cost considerations.”

Vaccine effectiveness — In the United States, anti-measles antibody develops in 95 percent of individuals vaccinated at age 12 months, and 98 percent of individuals vaccinated at age 15 months [4]. Measles vaccination usually leads to long-term immunity; more than 90 percent of recipients develop anti-measles antibody if the first dose of the two-dose series is given no sooner than 12 months of age [18]. Waning of immunity after vaccination, known as secondary vaccine failure, has been reported but is relatively rare [4].

In many countries outside the United States, measles vaccination is performed at age nine. Estimates vary for the effectiveness of vaccination at this age; it may be approximately 85 percent [19-23].

General recommendations — For prevention of measles infection in the United States, we agree with the ACIP, which recommends one dose of MMR at age 12 to 15 months, followed by a second dose administered no sooner than 28 days later [4,16,17]. The American Academy of Pediatrics (AAP), the American Academy of Family Physicians (AAFP), and the ACIP all recommend that the second dose of vaccine be given prior to school entry (ages four to six years). (See "Standard immunizations for children and adolescents", section on 'MMR vaccine'.)

In the absence of contraindication, MMR is the vaccine of choice for protection against measles, mumps, and rubella. Doses of MMR and other measles-containing vaccines administered before the first birthday should not be counted when determining the adequacy of measles vaccination [4].

To achieve the goal of administering two doses of MMR to all children from kindergarten to grade 12, the ACIP has recommended that children without evidence of measles immunity not be admitted to school until the first dose of MMR has been administered. The ACIP, AAP, and AAFP all recommend a health maintenance visit for children 11 to 12 years old; this visit can be used to

update vaccinations [4].

International travelers aged 6 to 11 months should have one MMR dose before departure. MMRV is not licensed for children younger than 12 months of age and therefore should not be considered in this setting.

Children who receive a dose of measles vaccine before their first birthday should be revaccinated with two doses of MMR vaccine, the first of which should be administered when the child is aged 12 to 15 months (12 months if the child remains in a high risk area) and the second at least 28 days later [24]. Other international travelers should have documentation of two doses of live measles vaccine.

It is safe to administer most vaccines with MMR during the same visit including [4]:

· Diphtheria toxoid/tetanus toxoid/acellular pertussis vaccine (DTaP) or diphtheria toxoid/tetanus toxoid/whole-cell pertussis vaccine (DTP)

· Haemophilus influenzae type b vaccine (Hib)

· Inactivated polio vaccine (IPV) or oral polio vaccine (OPV) — current recommendations are to use IPV instead of OPV in most countries [25]

· Hepatitis B vaccine

· Varicella vaccine (See 'MMRV' above.)

Live measles and yellow fever vaccines can be administered simultaneously at separate anatomical sites in separate syringes. Limited data exist regarding interactions between MMR and Japanese encephalitis vaccine, meningococcal vaccine, or typhoid vaccine, but a significant interaction is not expected to occur [4].

Approach in high risk areas — In the United States, high risk regions are defined by the ACIP as counties with a large inner-city population, counties with a recent measles outbreak among unvaccinated preschool children, and counties with more than five cases of measles among preschool-aged children during the preceding five years [4]. In such regions, the first dose of measles vaccine should be given at age 12 months rather than 15 months. The benefit of preventing measles cases among children aged 12 to 15 months outweighs the risk of slightly reduced vaccine efficacy at this age. Individuals with inadequate response to the first vaccination are likely to develop sufficient immunity with the second vaccination.

Timing of vaccination — The World Health Organization (WHO) recommends that in highprevalence settings, the first dose of MMR be administered at age nine months (given high risk of transmission), whereas in low-prevalence areas it can be given at 12 months (given higher likelihood of seroconversion as discussed below) [26].

Children are at risk for measles following clearance of transplacentally-acquired maternal antibodies [27-30]. Lower levels of measles antibodies have been observed among vaccinated mothers than mothers who had had natural infection [30]. Maternal antibody levels correlated with neonatal antibody levels at birth (r=0.93), and the median time to loss of immunity was shorter for infants of vaccinated women than for infants of naturally immune women (0.97 months versus 3.78 months, respectively). At six months of age, immunity waned in more than 99 percent of neonates born to vaccinated mothers and 95 percent of neonates born to naturally immune mothers [30]. This suggests that by age six months, children are at risk for becoming infected with measles, and that the number of children at risk may grow as vaccination reduces the number of mothers with natural

immunity [31]. Such observations have led to the suggestion that an early two-dose vaccination program may be beneficial [31-33]. An interim analysis of a randomized trial of measles vaccine at age 4.5 months found that, in a coincidental outbreak, the monthly incidence of measles was 0.7 percent in the early-vaccination group versus 3.1 percent in the control group [31]. The investigators cautioned that the results likely only applied to the measles vaccine used in the study (Edmonston-Zagreb), and an accompanying editorial recommended that early vaccination not replace vaccine doses given at age 9 to 15 months [32].

Other research shows that children vaccinated at a younger age are less likely to respond to measles vaccine. The 2009 World Health Organization (WHO) vaccination guidelines estimate that at age 8 to 9 months, a median 89.6 percent of infants seroconvert after one dose of measles vaccine (interquartile range (IQR): 82 to 95 percent), and at age 11 to 12 months a median 99 percent of infants seroconvert (IQR: 93 to 100 percent). A review on vaccine effectiveness noted that the median effectiveness for a single dose of measles vaccine was higher when given at age older than12 months than at age 9 to 11 months; 92.5 percent (IQR: 85 to 97 percent) versus 84 percent (IQR: 72 to 95 percent), respectively [34]. In addition, among Canadian teenagers who developed measles in spite of two doses of childhood measles vaccine, the susceptibility to measles was twoto fourfold higher among those who received the first dose at age 12 months compared with those who received the at age >15 months [35].

In regions with high prevalence of HIV, rapid waning of measles antibody in HIV-infected children suggests that measles vaccination campaigns may need to be repeated more frequently [36]. In a prospective study of 696 children, antibody titers 27 months after vaccination were detectable less frequently in the HIV-infected group than the HIV-negative group (50 percent versus 89 percent, respectively) [37]. A subset of 12 children with HIV infection incidentally received repeat vaccination; antibody titers were detectable in 92 percent of these children, although the durability of this response was not assessed. (See"Immunizations in HIV-infected patients", section on 'Measles, mumps, and rubella vaccine' and "Clinical presentation and diagnosis of measles".).

Prior vaccination with other strains — Previous vaccination with live attenuated Edmonston B measles vaccine (1963 to 1975) is considered an effective first dose of vaccine if given at age 12 months or older. If indicated, a second dose of MMR vaccine should be administered. All other individuals are considered unvaccinated including: those receiving a further attenuated strain (Schwarz or Moraten), especially if coadministered with IG or a high-titer measles immune globulin (no longer available in the United States); those vaccinated with an unknown strain with or without globulin coadministration; and those receiving inactivated measles vaccine or vaccine of unknown type between 1963 and 1967.

These persons should receive two doses of live vaccine separated by at least 28 days. Those who received inactivated vaccine followed within three months by live vaccine should also be revaccinated with two doses of live vaccine separated by at least 28 days.

Lack of association with autism — Concern has been raised periodically about a possible link between receipt of MMR and autism. Several studies have now been performed which fail to demonstrate any such association. (See "Autism and chronic disease: Little evidence for vaccines as a contributing factor".)

ESTABLISHING EVIDENCE OF MEASLES IMMUNITY — Evidence for measles immunity is important to establish whether subsequent vaccination is needed. The criteria below are accepted by the Advisory Committee on Immunization Practices (ACIP) as presumptive evidence of measles immunity. Nonetheless, transmission of infection can occur even among individuals who meet criteria for presumptive immunity. Local criteria may differ from those listed below.

Birth before the year 1957 — Most individuals born before 1957 have had natural measles infection, given the widespread measles epidemics in the United States before the introduction of measles vaccine. Among hospital workers born before 1957, 5 to 9 percent do not have serologic evidence of immunity to measles [38].

Given the risk of occupational exposure to measles and the risk that healthcare workers with measles may transmit infection to others in a healthcare setting, in a provisional update to its guidelines the Centers for Disease Control and Prevention (CDC) recommend that healthcare facilities consider administration of two doses of measles-mumps-rubella (MMR) vaccine to healthcare workers born prior to 1957 (in the absence of other evidence for measles immunity) [39].

Public health authorities should be contacted to determine local vaccination policies for healthcare workers.

Clinical measles diagnosis — A clinical diagnosis of measles documented by a physician is considered acceptable presumptive evidence for immunity [4,39].

Laboratory evidence of immunity — Anti-measles antibody unequivocally detected by any serologic test is considered evidence for measles immunity. A negative serology should prompt vaccination except in individuals who are pregnant or have other contraindications (See 'Contraindications' below.)

Screening in non-outbreak situations is most effective when follow up is assured (eg, hiring of new healthcare workers). If follow-up for reporting results and administering vaccine is not possible, screening should not be performed. Screening is not advised during an outbreak situation; vaccination should be administered.

Documentation of vaccination — Only written documentation of vaccination is considered valid; a self report or parent report of measles vaccination is inadequate. The definitions of adequate measles vaccination differ by group.

· Students in kindergarten through twelfth grade should have documentation of receipt of two doses of vaccine.

· One dose of vaccine administered on or after the first birthday is considered adequate immunization for preschool-aged children, and for persons who (1) are considered at low risk for measles infection; (2) were born 1957 or later; (3) are eighteen or over. Adults at high risk for measles infection and transmission include international travelers, persons attending colleges and other post-high school educational institutions, and persons who work at healthcare facilities.

· Students at post high school educational institutions (including colleges, universities, vocational schools, and technical schools) and persons working in healthcare facilities (including volunteers, students, non-medical workers, part time workers, and persons without patient care responsibilities) should have documentation of two doses of live measles vaccine, preferably with MMR, separated by at least 28 days.

· International travelers aged 6 to 11 months should have documentation of one MMR dose before departure. Children who receive a dose of measles vaccine before their first birthday should be revaccinated with two doses of MMR vaccine, the first of which should be administered when the child is aged 12 to 15 months (12 months if the child remains in a high risk area) and the second at least 28 days later [24]. Other international travelers should have documentation of two doses of live measles vaccine.

CONTRAINDICATIONS — Contraindications to measles vaccination are summarized below. In the setting of measles exposure, individuals with contraindications to vaccination should receive immune globulin [4]. (See 'Use of immune globulin' above.)

Pregnancy — There is a theoretical risk of birth defects among children born to mothers who receive live measles or measles-mumps-rubella (MMR) vaccine during pregnancy. Thus, the vaccine is considered contraindicated in pregnant women. Women of childbearing age should be counseled to avoid pregnancy for 30 days after vaccination [4].

Immunocompromised patients — Live measles vaccine or MMR should be used with caution in severely immunocompromised individuals. Issues related to immunizations in patients with immune suppression due to various causes are discussed separately. (See "Immunizations in HIV-infected patients", section on 'Measles, mumps, and rubella vaccine' and "Immunizations in patients with cancer", section on 'Measles, mumps, and rubella vaccines' and"Immunizations after hematopoietic cell transplantation", section on 'Measles, mumps, and rubella' and "Immunizations in solid organ transplant candidates and recipients", section on 'Measles, mumps, and rubella'.). MMR or live measles vaccination should be postponed in patients receiving prednisone (>2 mg/kg or 20 mg daily or every other day for more than 14 days). Vaccine should not be administered until at least one month after the cessation of treatment.

Close contacts of immunocompromised patients should receive routine measles vaccination; secondary transmission associated with vaccination has not been reported [40].

Thrombocytopenia — Individuals with a history of thrombocytopenia are at increased risk of developing significant thrombocytopenia after MMR vaccination [4]. However, the benefits of primary vaccination usually outweigh the risks. It may be prudent to avoid a second dose of MMR in individuals with history of thrombocytopenia within six weeks of initial vaccination [4].

Recent blood products or immunoglobulin — Vaccine efficacy is diminished significantly by prior passive administration of antibody. Vaccination should be delayed for 3 to 11 months after antibody administration; the length of time varies depending upon the amount of antibody in the preparation.

The interval is six months for those who have received packed red blood cells (unwashed) or whole

blood, and seven months for plasma/platelet preparations [4].

Allergy — A history of anaphylaxis after ingestion of gelatin is associated with an increased risk of anaphylaxis from the MMR or measles vaccine [4]. This history should warrant a skin test for gelatin allergy. Individuals with anaphylaxis (not contact dermatitis) due to neomycin also should not receive these vaccines because they contain a small amount of this antibiotic. In contrast, a history of anaphylaxis after egg ingestion is not a contraindication to measles immunization. (See "Allergic reactions to vaccines".)

Concurrent illness — Vaccination should be delayed in persons with moderate to severe febrile illnesses until resolution of the acute phase of the illness, as long as the vaccine is not being administered for an exposure [4]. However, mild febrile or nonfebrile illnesses do not mandate delay of vaccination.

ADVERSE EVENTS — A variety of adverse reactions have been reported following measles and

measles-mumps-rubella (MMR) vaccine administration [24]. Transient fever (39.4ºC or higher occurring one to two weeks after vaccination) develops in 5 to 15 percent of vaccinees. Transient rash occurs in approximately 5 percent. Most hypersensitivity reactions to the vaccine are minor.

Anaphylaxis can occur, but is extremely rare. Epinephrine should be available for use at any site that administers the vaccine.

Thrombocytopenia has been observed in prospective studies (1 case in 25,000 to 40,000 vaccine doses) [4]. In general, it is transient and occurs within two months of the receipt of vaccine, most commonly at two to three weeks. The risk may be higher in individuals who experienced thrombocytopenia following previous vaccination with MMR. (See 'Thrombocytopenia' above.)

Administration of MMR has been associated with febrile seizures, anaphylaxis, and measles inclusion body encephalitis in immunodeficient individuals [41]. The incidence of vaccine associated seizures has been estimated to be 1 in 3000 MMR doses [4], but is increased in vaccinees with a history of seizures or with a family history in first degree relatives. Most are simple febrile seizures.

In most cases, the benefits of vaccination outweigh the risk of seizures. The incidence of anaphylaxis is unknown but is estimated by the Centers for Disease Control and Prevention (CDC)

to be less than one per every one million MMR doses distributed [4].

TREATMENT OF MEASLES INFECTION — The treatment of measles is largely supportive; there is a role for vitamin A in certain settings, discussed below [42,43]. The World Health Organization (WHO) has published a comprehensive guide to the treatment of measles [44]. Supportive therapy includes antipyretics, fluids, and treatment of bacterial superinfections, such as bacterial pneumonia and otitis. Treatment of other complications, such as seizures and respiratory failure, may also be necessary. (See "Clinical presentation and diagnosis of measles".)

Vitamin A — The benefit of vitamin A for treatment of measles was suggested in 1932 [45]. The mechanism of action is not known; it may correct a viral-induced state of hyporetinemia. The WHO and UNICEF recommend that vitamin A (100,000 to 200,000 IU orally) be administered to all children with measles in areas where vitamin A deficiency is prevalent or where the mortality from measles exceeds one percent [24]. This dose recommendation is lower than the 400,000 IU dose (200,000 IU given on successive days) used in the trials below [46,47]:

· In one randomized trial including 180 Tanzanian children hospitalized with measles, mortality was reduced in patients treated with vitamin A (7 versus 13 percent); statistical significance was observed in the subgroup of patients under the age of two years [46].

· In another randomized trial including 189 South African children hospitalized with measles complications, including pneumonia, diarrhea, and croup, vitamin A was beneficial with respect to recovery time from pneumonia (mean of 6 versus 12 days), diarrhea (mean of 5 versus 8 days), incidence of croup (13 versus 27 cases), hospital stay (mean 10 versus 14 days), and overall mortality (2 versus 10 deaths) [47]. The risk of death or a major complication in the control group was twice that of the treated group. Among 156 infected patients in the study, 143 were found to have markedly depressed serum retinol levels.

A Cochrane review of randomized trials on the use of vitamin A for measles concluded that there was no overall significant reduction in mortality with vitamin A therapy for children with measles, but there was evidence that two doses were associated with a reduced risk of mortality and pneumoniaspecific mortality in children under the age of two years [48].

The use of vitamin A for treatment of measles in developed countries has not been evaluated in a clinical trial. The American Academy of Pediatrics recommends that vitamin A supplementation be considered for children with measles in developed countries in the following circumstances [49]:

· Children (6 months to 12 years) hospitalized with measles or its complications (eg, croup, pneumonia, or diarrhea).

· Children (older than six months of age) with measles and any of the following risk factors: immunodeficiency, ophthalmologic evidence of vitamin A deficiency, impaired intestinal absorption, moderate to severe malnutrition, and recent immigration from areas where high mortality rates from measles have been observed.

The recommended regimens for vitamin A supplementation are:

· Children 6 to 12 months — 100,000 IU (50,000 IU/mL) as a single oral dose.

· Children older than 12 months — 200,000 IU (50,000 IU/mL) as a single oral dose.

· For children with ophthalmologic evidence of vitamin A deficiency, repeat doses should be administered on day 2 and day 28.

Ribavirin — Measles virus is susceptible to ribavirin in vitro; there have been no randomized controlled trials to assess its clinical benefit [24]. Data on use of ribavirin are limited to case reports.

In one case report of three HIV-infected children with measles who received aerosolized ribavirin, two of the three survived initially, but died within the subsequent three months [50]. Another case series reported a favorable outcome in five of six adults with severe measles pneumonitis who received intravenous ribavirin. Those who recovered received the drug on day two to day five of illness; the patient who died of progressive respiratory failure received the drug on day 22 of infection [51]