Measles: How Soon Forgotten (FL INITIAL Autonomous Practice - Differential Diagnosis)

Molecular epidemiology of measles viruses is an important component in outbreak investigations and for global surveillance of circulating wild-type measles strains, i.e., measles viruses that are endemic to certain populations around the globe. During outbreaks, the measles vaccine is administered to help control the outbreak, and in these situations, vaccine reactions may be mistakenly classified as measles cases. A small proportion of measles vaccine recipients experience rash and fever 10 – 14 days following vaccination. The vaccine strain of the measles virus can be distinguished from wild-type measles viruses by determining the genotype from clinical samples or virus isolates.

Wild-type measles viruses have been divided into distinct genetic groups, referred to as genotypes, based on the nucleotide sequences of their hemagglutinin (H) and nucleoprotein (N) genes, which are the most variable genes on the viral genome.

The continued circulation of measles in a community depends on the generation of susceptible hosts by children's birth. In communities that generate insufficient new hosts, the disease will die out. This concept was first recognized in measles by Bartlett in 1957, who referred to the minimum number of people capable of supporting measles as the critical community size (CCS). Analysis of outbreaks in island communities suggested that the CCS for measles is about 250,000. In order to achieve herd immunity, more than 95% of the community must be vaccinated due to the ease with which measles is transmitted from individual to individual.

Measles is one of the first diseases to reappear when vaccination coverage rates decline. Ongoing measles outbreaks occur in European countries where vaccination coverage rates are lower than those in the United States.

Sustaining elimination requires high MMR vaccine coverage rates, particularly among preschool and school-aged children. High coverage levels provide herd immunity, decreasing everyone's risk for measles exposure and affording protection to individuals who cannot be vaccinated. However, herd immunity does not provide 100% protection, especially in communities with large numbers of unvaccinated individuals.

For the foreseeable future, measles importations into the United States will continue because measles is still prevalent in Europe and other world regions. Within the United States, the current national MMR vaccine coverage rate is adequate to prevent the sustained spread of measles. However, importations of measles likely will continue to cause outbreaks in communities with sizeable clusters of unvaccinated individuals. An outbreak of measles is defined as a chain of transmission with three or more confirmed cases.

A measles case is considered confirmed if it is laboratory-confirmed or meets the clinical case definition, i.e., an illness characterized by a generalized rash lasting 3 or more days, a temperature of ≥ 101°F [≥38.3°C], and cough, coryza, or conjunctivitis and is linked epidemiologically to a confirmed case. Confirmed measles cases in the United States are reported to the CDC by state and local health departments using standard case definitions and case classifications.

Measles cases are reported by state health departments to the CDC, and confirmed cases are reported via the National Notifiable Disease Surveillance System (NNDSS) using standard case definitions.

When the measles vaccine was first licensed in 1963, administering two doses of live-attenuated measles vaccine to children was implemented to prevent school outbreaks. The immunization program resulted in a decrease of more than 99% in the reported incidence of measles.

From 1989 to 1991, a significant resurgence of measles occurred, which affected primarily unvaccinated preschoolers. This measles resurgence resulted in 55,000 cases and 130 deaths. This resurgence prompted the recommendation that the second dose of the measles vaccine is given to preschoolers. This mass vaccination campaign led to the effective elimination of the endemic transmission of the measles virus in the United States.

By 1997-1999, the incidence of measles had been reduced to a historic low (less than 0.5 cases per million individuals). In 2000, endemic measles transmission was declared eliminated in the United States.

In 2004, 34 cases of measles were reported to the CDC. After that all-time low, however, the annual incidence began to increase, with most cases linked either directly or indirectly to international travel. Incomplete vaccination rates facilitated the spread of measles once the virus was imported to the United States.

January 1 - July 31, 2008, remains the highest year-to-date since 1996. 131 cases of measles were reported to the CDC from 15 states. This increase resulted from greater viral transmission after importation into the United States, leading to more importation-associated cases. These importation-associated cases occurred largely among school-aged children eligible for vaccination but whose parents chose not to have them vaccinated.

Summary 2001 through 2011: According to the CDC, cases continued to be caused by the measles virus being brought into the country by travelers from abroad, with spread occurring largely among unvaccinated individuals. 2 out of every 3 individuals who developed measles were unvaccinated. A review by the CDC in 2014 concluded that "the elimination of endemic measles, rubella, and Congenital Rubella Syndrome (CRS) has been sustained in the United States."

January 1 to August 24, 2013: The WHO European Region continues to be the source of imported cases, a popular destination for travelers from the United States and an area where measles continues to circulate. Measles importations were reported by United States residents, most of whom were 6 months or older and unvaccinated.

January 1 to May 23, 2014: 288 confirmed measles cases were reported to the CDC. Of the 288 cases, 280 (97%) were associated with importations from 18 countries. Almost half (22 or 49%) of these importations were travelers returning from the Philippines, where a large outbreak occurred in October 2013. Fifteen outbreaks accounted for 227 (79%) of the 288 cases.

December 2014 to February 2015: The CDPH issued a press release and an Epidemic Information Exchange (Epi-X) notification regarding the California outbreak. This outbreak originated in late December 2014 in Disney theme parks in Orange County, California. As of February 11, 2015, 125 measles cases with a rash had been confirmed in residents of the United States connected with the California outbreak (CDPH, 2015).

International travel to countries where measles is endemic is a well-known risk factor for measles, and measles importations continue to occur in the United States. United States residents can also be exposed to measles in the United States itself at venues with large international visitors, such as tourist attractions and airports. This illustrates the continued importance of ensuring high measles vaccination coverage in the United States.

Because measles remains endemic in countries in five out of the six WHO regions of the world, this underscores the importance of ensuring age-appropriate vaccination for all individuals before international travel to any region.

Because of ongoing importations of measles to the United States, healthcare providers should suspect measles in individuals with a febrile rash illness and clinically compatible symptoms (e.g., cough, coryza, or conjunctivitis) who have recently traveled abroad or have had contact with travelers.

Individuals with measles often seek medical care. Early recognition of suspected measles cases and the implementation of appropriate infection control measures are vital to reduce transmission in healthcare settings. Where possible, because of the high transmissibility of measles, individuals with suspected measles should be promptly screened before entering waiting rooms and appropriately isolated:

• in an airborne isolation room
• if not available, in a separate room with the door closed; or
• have their office appointments scheduled at the end of the day to prevent exposure to other individuals

In order to assist state and local public health departments with rapid investigation and control efforts to limit the spread of disease, suspected measles cases should be reported to local health departments immediately, and specimens obtained for measles testing, including viral specimens for confirmation genotyping. State health departments should notify the CDC about measles cases within 24 hours of detection.

In the United States, recommendations for the MMR vaccination include a single dose at age 12 - 15 months and a second dose at the time of school entry (ages 4 – 6). Vaccination as early as 6 months of age is recommended for United States children traveling abroad and is sometimes recommended within communities in the United States during measles outbreaks.

All individuals who intend to travel internationally should be up-to-date on their measles vaccination, and other vaccinations recommended for countries they might visit. These recommendations include:

• a single dose of the MMR vaccine for infant travelers aged 6 - 11 months prior to international travel and
• 2 doses of the MMR vaccine are administered at least 28 days apart for children age 12 months or older or who have other evidence of immunity to measles
• For adults with no evidence of immunity to measles, 1 dose of the MMR vaccine is recommended unless the adult is in a high-risk group (i.e., healthcare personnel, international travelers, or students at post-high school educational institutions), in which case, 2 doses of the MMR vaccine are recommended unless they have other evidence of immunity

The Advisory Committee on Immunization Practices (ACIP) routine immunization schedule is essential to limit measles importation and the spread of the disease. To help expedite public health containment strategies, healthcare providers should be aware of measles, implement appropriate infection control measures when measles is suspected, and promptly report suspected cases to their local health departments.

Healthcare providers should remind individuals who plan to travel internationally, including travel to large international events and gatherings, of the increased risk of exposure and encourage timely vaccination of all individuals six months or older who lack evidence of immunity to measles. Healthcare providers should encourage vaccination of all eligible individuals who do not have other evidence of measles immunity.

Maintaining high 2-dose MMR vaccine coverage has been crucial in limiting the spread of measles from importations in the United States. Most measles importations occur when citizens of the United States travel abroad and have not been appropriately vaccinated. Therefore, it is important to encourage the timely delivery of measles vaccination to United States residents before overseas travel. In addition, early detection of cases and rapid public health response to outbreaks can limit the spread of illness.

Importing measles into communities with unvaccinated individuals can lead to measles cases and outbreaks in the United States. Maintaining high vaccination coverage, ensuring timely vaccination before travel, and early detection and isolation of cases are key factors in limiting importations and the spread of the disease.

Even though a safe and cost-effective vaccine is available, in 2017, there were 110,000 measles deaths globally, mostly among children under the age of five. In developing countries, measles causes 15,000 - 60,000 cases of blindness per year.

Measles vaccination resulted in an 80% drop in measles deaths between 2000 and 2017 worldwide. In 2017, about 85% of the world's children received one dose of measles vaccine by their first birthday through routine health services, up from 72% in 2000. From 2000-to 2017, measles vaccination prevented an estimated 21.1 million deaths making the measles vaccine one of the best buys in public health (WHO, 2019).

In 2013 - 2014 there were almost 10,000 cases in 30 European countries. Most cases occurred in unvaccinated individuals, and over 90% of cases occurred in the following five European nations: Germany, Italy, the Netherlands, Romania, and the United Kingdom.

The following are the reported measles cases in regions of the world, over time (WHO, 2019b).

Measles, historically, has been thought to be a disease of childhood. However, measles infection can occur in unvaccinated or partially vaccinated individuals or those with compromised immunity.

Unvaccinated young children are at the highest risk. Age-specific attack rates may be highest in susceptible infants younger than 12 months, school-aged children, or young adults, depending on local immunization practices and the incidence of the disease.

In densely populated, underdeveloped countries, measles is most common in children younger than 2 years.

Unvaccinated males and females are equally susceptible to infection by the measles virus. Following acute measles, increased mortality has been observed among females of all ages, but it is most marked in adolescents and young adults. Excessive non-measles-related mortality has also been observed among female recipients of high-titer measles vaccines in Senegal, Guinea Bissau, and Haiti.

Measles affects people of all races.

In temperate areas, the peak incidence of measles infection occurs during late winter and spring.

Any of the following constitutes evidence of immunity to measles:

• Documentation of age-appropriate vaccination with a live measles virus-containing vaccine (one dose for preschool-aged children, the second dose for children in kindergarten through 12th grade)
• Laboratory evidence of immunity to measles
• Laboratory confirmation of having had measles
• Birth before 1957

Risk factors for Measles viral infection in all age groups include the following:

• Underlying immunodeficiency caused by HIV or AIDS
• Immunosuppression following receipt of an organ or a stem cell transplant
• Leukemia, alkylating agents, or corticosteroid therapy, regardless of immunization status
• Travel to areas where measles is endemic
• Contact with travelers returning from areas where measles is endemic
• Malnutrition
• Pregnancy
• Vitamin A deficiency
• Loss of passive transferred maternal antibodies, usually between the first four to eight months, before the age of routine immunization

Healthcare providers should consider measles when evaluating individuals with a febrile rash. Ascertain the individuals:

• vaccine status
• recent travel history
• contact with individuals who have a febrile rash
• exposure to the measles virus

The incubation period from exposure to onset of measles symptoms ranges from 7 to 14 days (10 - 12 days). Individuals are contagious from 1 - to 2 days before symptoms. Healthy children are considered contagious from 4 days before to 4 days after the rash appears. Immunocompromised individuals can be contagious during the duration of the illness.

The prodromal Phase (Early or Premonitory Symptoms of the Disease) typically begins with:

• High fever (often greater than104o F or 40o C) that typically lasts 4 - 7 days
• The classic triad of (the "3 Cs")
  • Conjunctivitis
    • Ocular symptoms may also include:
      • Periorbital edema
      • Burning pain
      • Exudate in the conjunctival sac
    • Cough
    • Coryza (runny nose)

Catarrhal inflammation of the respiratory tract occurs concomitantly with the ocular symptoms or resulting in coughing, sneezing and coryza.

Other symptoms may include:

• Malaise
• Myalgias
• Anorexia
• Laryngeal involvement (less common):
  • Hoarseness
  • Aphonia

Enanthem (Mucous Membrane Eruption) generally appears 2 - 4 days after the onset of the prodromal phase and lasts 3 - 5 days. Koplik spots - bluish-gray specks or "grains of sand" on a red base – usually develop on the buccal mucosa opposite the second molars.

Koplik spots generally appear 1 - 2 days before the appearance of the rash and last 3 - 5 days after the rash appears. This enanthem begins to slough as the rash appears. Although Koplik spots are diagnostic for measles, they are temporary and rarely seen. Their absence does not exclude the diagnosis of measles. Recognizing these spots before an individual reaches their maximum infectiousness can help healthcare providers reduce the spread of the disease.

Exanthem (Rash), on average, develops about 14 days after exposure. The characteristic measles rash is classically described as a generalized red maculopapular rash that begins several days after the fever. The measles rash appears 3 – 5 days after the symptoms begin and may last up to eight days. Before disappearing, the rash is said to "stain," changing color from red to dark brown. Overall, the disease from infection with the measles virus usually resolves after about three weeks. The exanthem (rash) often appears 1 - 2 days after the appearance of Koplik spots. Blanching, erythematous macules and papules typically start behind the ears or on the face or neck at the hairline. Mild pruritus may also occur.

Immunocompromised individuals may not develop a rash. The rash may be absent in individuals with underlying deficiencies in cellular immunity.

Within 48 hours, the lesions coalesce into patches and plaques that spread cephalocaudally to the trunk and extremities, including the palms and soles. It begins to regress cephalocaudally, starting from the head and neck. Lesion density is greatest above the shoulders, where macular lesions may coalesce. The eruption may also be petechial or ecchymotic. Individuals appear most ill during the first or second day of the rash.

Individuals are considered contagious from 4 days before to 4 days after the rash appears. The exanthem lasts 5 - 7 days before fading into coppery-brown hyperpigmented patches, desquamate.

The entire course of uncomplicated measles, from late prodrome to resolution of fever and rash, is 7 - 10 days. The cough may be the final symptom to disappear.

Modified measles is a milder form of measles that occurs in individuals who have received serum immunoglobulin after exposure to the measles virus. Similar but milder signs and symptoms may still occur. The incubation period may be as long as 21 days.

Atypical measles occurs in individuals vaccinated with the original killed-virus measles vaccine between 1963 and 1967. These individuals failed to elicit long-lived protective antibodies and a cytotoxic T-lymphocyte response to the measles virus. These individuals have developed incomplete immunity to the measles virus. The live-attenuated vaccine replaced the killed-virus measles vaccine in 1967 and is not associated with atypical measles.

After exposure to the measles virus, a mild (sometimes severe) or subclinical prodrome of prolonged high fever, headache, cough, absence of Koplik spots, abdominal pain, myalgias and pneumonia precedes a rash that begins on the hands and feet and spreads centripetally. The atypical rash is accentuated in the skin folds and may be macular, vesicular, petechial, or urticarial.

Laboratory tests reveal a very low measles antibody titer early in the disease, followed by an extremely high measles immunoglobulin G (IgG) antibody titer (e.g., 1:1,000,000) in the serum.

Subacute sclerosing panencephalitis (SSPE), a rare, fatal complication of measles, is a degenerative CNS disease resulting from a persistent measles infection acquired earlier in life. SSPE generally develops 7 to 10 years (the mean incubation period for SSPE is approximately 10.8 years) after an individual has measles, even though the individual seems to have fully recovered from the illness. Among individuals who contracted measles during the resurgence in the United States from 1989 to 1991, 4 to 11 out of every 100,000 were estimated to be at risk for developing SSPE. The risk of developing SSPE may be higher for an individual who gets measles before two years of age. Since measles was eliminated in 2000, SSPE has been rarely reported in the United States. SSPE is characterized by the onset of behavioral and intellectual deterioration and seizures years after an acute infection.

In children with malignant lymphoid diseases, delayed-acute measles encephalitis may develop 1 - 6 months after the acute infection and is generally fatal.

The diagnosis of measles is usually determined from the classic clinical picture, including the classic triad of cough, coryza, conjunctivitis, pathognomonic Koplik spots and the characteristic cephalocaudal progression of the morbilliform exanthem.

Other diagnoses to be considered include the following:

• Dengue fever
• Dermatologic manifestations of viral hemorrhagic fevers
• Drug eruptions
• Emergent treatment of acute conjunctivitis
• Enteroviral infections
• Erythema infectiosum (Fifth Disease)
• Infectious mononucleosis
• Kawasaki disease
• Meningitis
• Parvovirus B19 infection
• Pediatric fever
• Pediatric scarlet fever
• Pediatric sepsis
• Pediatrics, Roseola Infantum
• Rocky Mountain spotted fever
• Rubella
• Serum sickness
• Syphilis
• Systemic lupus erythematosus
• Toxic shock syndrome

Although the diagnosis of measles is usually determined from the classic clinical picture, laboratory identification and confirmation of the diagnosis are necessary for public health and outbreak control.

Laboratory confirmation is achieved by means of the following:

• Serologic testing for measles-specific IgM or IgG titers (Antibody Assays)
• Isolation of the Virus (Viral Cultures)
• Reverse-Transcriptase Polymerase Chain Reaction (RT-PCR) Evaluation

Measles-specific IgM titers (Immunoglobulin M): The measles virus sandwich-capture IgM antibody assay, offered by many local health departments and the CDC, is the quickest method to confirm acute measles. Because IgM may not be detectable during the first 2 days of the rash, blood specimens for measles-specific IgM titers should be drawn on the third day of the rash or on any subsequent day up to 1 month after the onset of the rash to avoid a false-negative IgM result.

The seropositivity rate for first blood samples is about 77% among individuals with confirmed measles infection when collected within 72 hours of rash onset. The seropositivity rate rises to 100% when collected 4 - 11 days after the rash onset. Although the measles serum IgM level remains positive 30 - 60 days after the illness in most individuals, the IgM titer may become undetectable in some individuals at 4 weeks after rash onset. False-positive results can occur in individuals with rheumatologic diseases, parvovirus B19 infection, or infectious mononucleosis.

Measles-specific IgG titers (Immunoglobulin G): Laboratories can confirm measles by demonstrating more than a 4-fold rise in IgG antibodies between acute and convalescent sera, although relying solely on rising IgG titers for the diagnosis delays treatment considerably. The earlier the acute serum is drawn, the more reliable the results. IgG antibodies may be detectable 4 days after the onset of the rash, although most cases have detectable IgG antibodies by about a week after rash onset.

Accordingly, it is recommended that blood serum be drawn on the seventh day after the onset of the rash. Blood drawn for convalescent serum should be drawn 10 - 14 days after that drawn for acute serum, and the acute and convalescent sera should be tested simultaneously as paired sera.

Individuals with SSPE have unusually high measles antibody titers in their serum and cerebrospinal fluid (CSF). The earliest confirmation of measles using IgG antibodies takes about three weeks from the onset of the illness, a delay too long to permit the implementation of effective outbreak control measures.

In atypical measles, laboratory evaluation of serum/blood reveals very low titers of measles antibody early in the disease, followed by extremely high measles IgG antibody titers (e.g., 1:1,000,000).

IgG levels can be explained by current infection, immunity due to past infection or vaccination, or maternal antibodies present in infants younger than 15 months.

Blood for serologic testing can be collected by venipuncture or by finger/heel stick in tubes without additives - either a plain, red-top tube or a serum separator tube. The preferred volume for IgM or IgG testing at the CDC is 0.5 – 1.0 ml of serum, but testing can be done with as little as 0.1 ml if necessary.

Throat swabs and nasal swabs can be sent on a viral transport medium or a viral culturette swab to isolate the measles virus.

Urine specimens can be sent in a sterile container for viral culture.

Viral genotyping in a reference laboratory may determine whether an isolate is endemic or imported.

In immunocompromised individuals who may have poor antibody responses that preclude serologic confirmation of measles, isolation of the virus from infected tissue or identification of measles antigen by means of immunofluorescence may be the only feasible method of confirming the diagnosis.

RT-PCR evaluation is highly sensitive to visualizing measles virus RNA and can rapidly confirm the diagnosis in blood, throat, nasopharyngeal, or urine specimens. The samples should be collected upon the first contact with a suspected case of measles when the serum sample for diagnosis is drawn.

A complete blood cell count (CBC) may reveal leukopenia with a relative lymphocytosis and thrombocytopenia. Liver function test (LFT) results may show elevated transaminase levels in individuals with measles hepatitis.

If bacterial pneumonia is suspected, a chest X-ray should be taken. The frequent occurrence of measles pneumonia, even in uncomplicated cases, limits the predictive value of chest radiography for bacterial bronchopneumonia.

If encephalitis is suspected, a lumbar puncture should be performed. CSF examination may reveal:

• Increased protein
• Normal glucose
• Mild pleocytosis with a predominance of lymphocytes

Tissue Analysis and Histologic Findings: A skin biopsy from a lesion of the morbilliform eruption may show spongiosis and vesiculation in the epidermis with scattered dyskeratotic keratinocytes. Occasional lymphoid multinucleated giant cells (≤ 100 nm in diameter) can be identified in Koplik spots biopsies, dermal or epithelial rashes, hair follicles, and acrosyringium and lung or lymphoid tissue. These findings are not specific, but they suggest a viral exanthem. Brain biopsies of individuals with measles encephalitis can reveal demyelination, vascular cuffing, gliosis, and infiltration of fat-laden macrophages near blood vessel walls.

There is no specific antiviral therapy for measles. Medical care is primarily supportive and focused on relieving symptoms and treating complications such as bacterial infections. Supportive care in the treatment of measles is as follows:

• Maintenance of proper hydration and replacement of fluids lost through diarrhea or emesis
• IV rehydration if dehydration is severe, either through the loss of fluids and electrolytes from emesis or diarrhea or elevated fevers
• Fever management with standard antipyretics as appropriate
• Treatment of secondary infections (e.g., otitis media or bacterial pneumonia etc.) with appropriate antibiotics
• Consideration of vitamin A supplementation, especially in children and individuals with clinical signs of vitamin A deficiency
• Consideration of post-exposure prophylaxis in unvaccinated contacts
• Timely tracing of contacts should be made a priority

Hospitalization may be indicated to treat measles complications (e.g., bacterial superinfection, pneumonia, dehydration, croup, etc.). Individuals with severe complicating infections (e.g., encephalomyelitis) should be admitted for observation and antibiotics given, as appropriate, to their clinical condition.

Individuals should receive regular follow-up care with a primary care physician for surveillance of complications that may arise from the measles infection.

Airborne precautions are indicated for:

• Hospitalized children during the period of communicability (i.e., 3 - 5 days before the appearance of a rash to 4 days after the rash develops in healthy children)
• Hospitalized adults
• The duration of illness in individuals who are immunocompromised

In healthcare settings, healthcare providers should follow respiratory etiquette and airborne precautions. Regardless of presumptive immunity status, all healthcare staff entering the room should use respiratory protection consistent with airborne infection control precautions (using an N95 respirator or a respirator with similar effectiveness in preventing airborne transmission). Because of the possibility, albeit low, of MMR vaccine failure in healthcare staff exposed to infected individuals, they should all observe airborne precautions in caring for individuals with measles. The preferred placement for individuals who require airborne precautions is in a single-patient airborne infection isolation room (AIIR).

Healthcare providers without evidence of immunity who have been exempted from measles vaccination for medical, religious, or other reasons and who do not receive appropriate PEP within the appropriate timeframe should be excluded from affected institutions in the outbreak area until 21 days after the onset of rash in the last case of measles.

Medications used to prevent or treat measles include measles virus vaccines, human immunoglobulin (IG), vitamin A, and antivirals (e.g., ribavirin).

The measles, mumps and rubella vaccine (M-M-R II) (MMR) are available worldwide. The MMR vaccine is most commonly used in the United States. The MMR vaccine may provide some protection if administered within 72 hours of exposure to the measles virus. The MMR vaccine does not alter the course of mumps or rubella following post-exposure to either the mumps or rubella viruses.

Live measles, mumps, rubella, and varicella virus vaccine (ProQuad) (MMRV). This live measles vaccine is usually given along with the attenuated rubella and mumps viruses to induce active immunity against the viruses that cause measles, mumps and rubella.

MMR Vaccine Recommendations:

• Children
  • The CDC recommends that all children get two doses of MMR vaccine:
    • the first dose of 0.5 ml SC at 12 through 15 months of age
    • second dose of 0.5 ml SC at 4 through 6 years of age
  • Children can receive the second dose earlier as long as it is at least 28 days after the first dose
  • Students at Post-High School Educational Institutions
  • Students at post-high school educational institutions who do not have evidence of immunity against measles need two doses of MMR vaccine, separated by at least 28 days
• Adults
  • Adults born before 1957 are considered immune to measles and mumps
  • All adults born in 1957 or later should have documentation of one or more doses of MMR vaccine unless contraindicated or laboratory evidence of immunity
  • Adults who do not have evidence of immunity against measles should get at least one dose of the MMR vaccine
  • Ages 19 - 49: 0.5 mL SC; the second dose may be administered at least 28 days after the first dose
  • Older than 50 years: administer 1 dose only
  • All adults in the following risk categories should get the second dose of MMR vaccine:
    • Students in postsecondary education
    • Recent exposure
    • Occupational risk
    • Previously vaccinated with the killed measles vaccine
    • Vaccinated with an unknown type of measles vaccine during 1963 - 67
• International Travelers
  • Before departure from the United States for international travel, individuals 6 months of age and older should be protected against measles
  • Infants 6 through 11 months of age should receive one dose of MMR vaccine. Infants who get one dose of MMR vaccine before their first birthday should get two more doses (one dose at 12 through 15 months of age and another dose at least 28 days later)
  • Children 12 months of age and older should receive 2 doses of MMR before departure. The first dose should be administered on or after age 12 months and the second dose at least 4 weeks later
  • Teenagers and adults born during or after 1957 who do not have evidence of immunity against measles should get two doses of MMR vaccine separated by at least 28 days prior to departure
• Catch-up Vaccination
  • All school-aged children and adolescents should have received 2 doses of 0.5 mL SC each
  • The minimum time between 1st and second dose of the MMR vaccine is 4 weeks
• Immunization in Pregnancy
  • Pregnant women who do not have evidence of immunity should receive the MMR vaccine upon delivery or termination of pregnancy and before discharge from the healthcare facility
  • Pregnancy should be avoided for 28 days following MMR vaccine administration
• Revaccinate individuals who were vaccinated before the establishment of effective antiretroviral therapy (ART) with 2 appropriately spaced doses of MMR vaccine once effective ART has been established
  • 12 Months or Older with HIV Infection
  • Vaccinate all individuals with HIV infection who do not have evidence of current severe immunosuppression

• Prevention or modification of measles in exposed susceptible individuals may involve the administration of the MMR vaccine. The MMR vaccine is preventative if administered within 72 hours of exposure
• Infants 6 through 11 months should be given the MMR vaccine if administered within 72 hours of exposure
• Unvaccinated individuals who receive their first dose of the MMR vaccine within 72 hours after exposure may return to childcare, school or work except for healthcare workers

Healthcare personnel should have documentation against measles, according to the recommendations of the Advisory Committee on Immunization Practices. Healthcare personnel without evidence of immunity should get two doses of MMR vaccine, separated by at least 28 days.

Since birth before 1957 is not a guarantee of measles immunity, healthcare facilities should consider vaccination of unimmunized healthcare personnel who lack laboratory evidence of immunity born before 1957.

Post-exposure Prophylaxis:

• If a healthcare worker without evidence of immunity is exposed to measles, the MMR vaccine should be given within 72 hours of exposure
• Healthcare personnel without evidence of immunity should be excluded from duty from day 5 after the first exposure to day 21 after the last exposure regardless of post-exposure MMR vaccine

The dosage of the MMR vaccine varies by age. Be aware of potential drug interactions and adverse effects, cautions and contraindications in usage, and precautions when used during pregnancy and lactation.

Contraindications to the MMR vaccine include:

• Allergy to the antibiotic neomycin, gelatin or any other component of the MMR vaccine
• Any individual who has ever had a life-threatening allergic reaction to a previous dose of the MMR vaccine
• Pregnant women should not get the MMR vaccine until after delivery because of the theoretical risk of vaccine virus transmission to the fetus
• Women should avoid getting pregnant for 4 weeks after vaccination with the MMR vaccine
• An individual in close contact with a pregnant female may receive the vaccine
• HIV/AIDS: CD4+ count less than 200 cells/mcL
• Severely immunocompromised individuals such as may occur in leukemia, lymphoma, generalized malignancy, congenital immunodeficiency
• Warning against giving live-virus measles vaccines to immunocompromised individuals with disorders associated with increased severity of viral infections (except individuals with HIV who do not have evidence of severe immunosuppression)
• Receiving immunosuppressive therapy such as alkylating agents, antimetabolites, radiation or large doses of corticosteroids
• Postpone the MMR vaccination in individuals for at least a month after completion of a high-dose course of corticosteroids, such as prednisone
• Active, untreated tuberculosis
• Current febrile respiratory illness or febrile infection
• Individuals diagnosed with blood dyscrasias
• Individuals who have received antibodies (i.e., plasma, whole blood, any immune globulin) should have the MMR vaccine deferred for at least 5 months

Precautions to the MMR vaccine include:

• Syncope accompanied by transient visual disturbances reported with vaccines
• Postpone vaccination on individuals with moderate to severe acute illness (with or without fever)
• Postpone vaccination on children who have severe diarrhea, moderate otitis media or moderate to severe vomiting with or without a fever
• Postpone vaccination on any individual who is experiencing a moderate or severe illness
• Use caution in individuals with a history of cerebral injuries, seizures, or conditions where stress to fever should be avoided
• Immune globulins may interfere with an immune response if administered recently or concurrently

Individuals may be vaccinated who are:

• Experiencing a minor illness (e.g., upper respiratory infections with or without fever)
• Breast-feeding (Vaccination of a woman who is breastfeeding poses no risk to the infant being breastfed)
• Children who have experienced a severe egg allergy. (The ACIP recommends routine vaccination of egg-allergic children without the use of special protocols or desensitization procedures)

MMRV is a live vaccine that induces active immunity against viruses that cause measles, mumps, rubella, and varicella (Chickenpox).

• Children
  • Two doses of MMRV vaccine are recommended:
    • the first dose of 0.5 ml SC at 12 through 15 months of age
    • the second dose of 0.5 ml SC at 4 through 6 years of age, but the second dose may be given up to 12 years of age if it is at least 3 months after the first dose

Contraindications to the MMRV vaccine include:

• Adults
• Children should not get the MMRV vaccine if they:
  • Have you ever had a life-threatening allergic reaction to a previous dose of MMRV vaccine or either MMR or varicella vaccine
  • Have you ever had a life-threatening reaction to gelatin or the antibiotic neomycin
  • Have blood dyscrasia, leukemia, lymphoma, malignancy affecting bone marrow/lymphatic system or any other form of cancer
  • Have HIV/AIDS or another disease that renders the child immunodeficient
  • Are being treated with drugs that affect the immune system, including high doses of oral steroids for 2 weeks or longer
  • Are being treated for cancer with radiation or drugs
  • Have active untreated TB
  • Are pregnant
  • Have a fever >101.3°F (38.5°C)

Precautions to the MMRV vaccine include:

• History of cerebral injury, individual/family history of seizures, or any other condition where stress due to fever needs to be avoided
• Hypersensitivity to eggs
• Hypersensitivity to neomycin - may cause contact dermatitis
• Febrile seizures

Early findings from an ongoing CDC study show that children who get an MMRV vaccine may be twice more likely to have a febrile seizure 7 - 10 days after getting the vaccine than children who get MMR and varicella vaccines (by 2 separate injections) at the same healthcare visit.

Children may also get these vaccines as two separate shots: MMR (measles, mumps, rubella) and varicella vaccines. The essential question remains: 1 Shot (MMRV) or 2 Shots (MMR and Varicella)?

• Both options give the same protection
• There is one less shot with MMRV
• Children who got the first dose of MMRV have had more fevers and fever-related seizures (about 1 in 1,250) than children who got the first dose as separate shots of MMR and varicella vaccines on the same day (about 1 in 2,500)
• Anyone 13 or older who needs protection from these diseases should get MMR and varicella vaccines as separate shots
• MMRV may be given at the same time as other vaccines

Human Immunoglobulin (IG) prevents or modifies the measles virus in susceptible contacts if administered within 6 days of exposure. Post-exposure prophylaxis should be considered in unvaccinated contacts. Timely tracing of contacts should be a priority. These individuals should receive regular follow-up care with a primary care physician for surveillance of complications arising from the infection.

Intramuscular IG (IGIM) is a transient source of IG. Pooled human immune globulins from donors are pharmacologically used as replacement therapy for primary and secondary immunodeficiencies, and IGG antibodies against viral, bacterial, parasitic, and mycoplasma antigens. These pooled human immune globulins also provide passive immunity by increasing antibody titer and antigen-antibody reaction potential.

Post-exposure prophylaxis with human immunoglobulin (IG) should be administered to individuals at risk for severe illness and complications from measles, such as infants younger than 12 months of age, pregnant women without evidence of measles immunity, and individuals with severely compromised immune systems.

• Intramuscular IG (IGIM) should be given to all infants younger than 12 months of age who have been exposed to measles.
• For infants aged 6 through 11 months, the MMR vaccine can be given in place of IG if administered within 72 hours of exposure.
• Because pregnant women might be at higher risk for severe measles and its complications, intravenous IG (IGIV) should be administered to pregnant women who have been exposed to the measles without evidence of measles immunity.
• People with severely compromised immune systems exposed to measles should receive IGIV regardless of immunologic or vaccination status because the MMR vaccine might not protect them.

IG should not be used to control measles outbreaks but rather reduce the risk of infection and complications in the individuals receiving it. IGIM can be given to other individuals who do not have evidence of immunity against measles, but priority should be given to individuals exposed in settings with intense, prolonged, close contact, such as households, daycare settings, or classrooms where the risk of transmission is highest.

After receiving IG, individuals exposed to the measles virus cannot return to work in healthcare settings. In other settings, such as childcare, school, or work, factors such as immune status, intense or prolonged contact, and the presence of populations at risk should be considered before allowing individuals exposed to return. These factors may decrease the effectiveness of IG or increase the risk of disease and complications depending on the setting to which they are returning.

If a healthcare worker without evidence of immunity is exposed to measles, the MMR vaccine should be given within 72 hours, or IG should be given within 6 days of exposure. All healthcare personnel without evidence of immunity should be excluded from duty from day 5 after first exposure to day 21 after last exposure, regardless of post-exposure prophylaxis.

Human immunoglobulin administration varies by age, dosage based on individuals' clinical response and serum IgG trough levels, route of administration, potential drug interactions, potential adverse effects, contraindications and cautions, pregnancy and lactation status.

Human immunoglobulin can be found under such brand names as Bivigam, Carimune, Flebogamma, GamaSTAN, Gamunex-C, Gammagard, Hizentra, HyQvia, and Privigen.

IG is indicated for all contacts of individuals with measles who have no evidence of immunity against measles and who:

• Reside in the same household
• Are pregnant
• Are immunocompromised
• Are age 6 months to 1 year (morbidity is high in children younger than 1 year)
• Are younger than 6 months who were born to mothers without measles immunity
• Are children and adolescents with HIV infection who were exposed to measles, regardless of their measles immunization status, unless they received IGIV (400 mg/kg as part of routine immunoprophylaxis) within 3 weeks of exposure to the measles virus

Contraindications to Human Immunoglobulin (IG) include:

• Black Box Warnings
• Thrombosis
• Thrombosis may occur with immune globulin products
• Risk factors include advanced age, prolonged immobilization, hypercoagulable conditions, and history of thrombosis, estrogen use, indwelling central vascular catheters, hyperviscosity, and cardiovascular risk factors
• For high-risk individuals, the lowest possible dose and infusion rate should be administered, adequate hydration ensured before administration, blood viscosity assessed, and signs and symptoms of thrombosis continuously assessed
• Hypersensitivity to immune globulins or solution components
• Selected IgA deficiency with known antibody against IgA
• Severe thrombocytopenia or coagulation disorders
• Hyperprolinemia (Hizentra contains the stabilizer L-proline)

Precautions to Human Immunoglobulin (IG) include:

• Initial treatment should be done in a clinical setting due to the possibility of anaphylactic reactions
• May transiently impair the efficacy of live attenuated viruses
• Passive transmission of antibodies may yield false-positive serological tests (e.g., Coombs)
• Products made from human plasma can contain infectious agents (e.g., viruses and, theoretically, Creutzfeldt-Jakob disease [CJD])
• Subcutaneous administration is associated with an increased risk of hematoma
• Hemolytic anemia was reported, so monitor the individual's CBC
• Renal dysfunction or renal failure has been associated with IG therapy, so renal monitoring function and urine output are important
• Hyperproteinemia and hyponatremia may occur
• Aseptic meningitis syndrome has been reported

Vitamin A supplementation has been associated with an approximately 50% reduction in morbidity and mortality and appears to help prevent eye damage and blindness.

Because Vitamin A deficiency is associated with severe disease from measles, the WHO recommends that all children diagnosed with measles should receive vitamin A supplementation regardless of their country of residence, based on their age, as follows:

• Infants younger than 6 months - 50,000 IU/day PO for 2 doses
• Age 6 - 11 months - 100,000 IU/day PO for 2 doses
• Older than 1 year - 200,000 IU/day PO for 2 doses
• Children with clinical signs of vitamin A deficiency – the first 2 doses as appropriate for age, then a third age-specific dose given 2 - 4 weeks later

Vitamin A supplementation plays a role in embryonic development, visual adaptation to darkness, immune function, and maintenance of epithelial cells. Vitamin A is a fat-soluble vitamin needed for the growth of skin, bones, and male and female reproductive organs. Vitamin A can be found in liver, butter, eggs, green leafy vegetables, and colorful fruits and vegetables such as carrots, mango, pumpkin and sweet potatoes.

Vitamin A supplementation varies by age, dosage recommendations, route of administration, potential drug interactions, potential adverse effects, contraindications and cautions, pregnancy and lactation status.

Vitamin A supplementation can be found under Retinol, Aquasol A, Vitamin A, retinyl acetate, retinyl palmitate, A-25, and Gordons-Vite A.

Vitamin A supplementation is indicated for all individuals with measles who are:

• Vitamin A deficient, whether children or adults
• Children with acute measles, regardless of their country of residence, due to the reduction in morbidity and mortality rates (WHO recommendation)
• United States children with severe measles have low serum concentrations of vitamin A. Thus, two doses of vitamin A given 24 hours apart are recommended. A third age-specific dose should be given 2 to 4 weeks later to children with clinical signs and symptoms of vitamin A deficiency

Contraindications to Vitamin A supplementation include:

• Hypersensitivity to vitamin A
• IV use
• Hypervitaminosis A
• Malabsorption syndrome (Vitamin A is poorly absorbed orally)
• Pregnancy (dose > RDA)

Precautions to Vitamin A supplementation include:

• Use caution if the dosage is greater than 25,000 units/day
• Evaluate additional vitamin deficiencies if the diagnosis of vitamin A deficiency occurs (single vitamin A deficiency is rare)
• Use with caution in renal impairment since Vitamin A toxicity has been reported
• Monitor prolonged administration over 25,000 units/day, taking into account vitamin A intake from other dietary and supplement sources

Ribavirin, a guanosine analog, is for experimental use only. Its mechanism of action is not fully defined, but it may inhibit the initiation and elongation of RNA fragments by inhibiting polymerase activity, which results in the inhibition of viral protein synthesis.

The measles virus is susceptible to ribavirin in vitro. Although ribavirin (either IV or aerosolized) has been used to treat severely affected and immunocompromised individuals with acute measles or subacute sclerosing panencephalitis (SSPE), no controlled trials have been conducted.

Ribavirin dosage varies by age, route of administration, potential drug interactions, possible adverse effects, cautions and contraindications, pregnancy and lactation precautions and toxicity.

Antiviral therapy can be found under such brand names as Ribavirin, Moderiba, Virazole, Rebetol, Ribasphere, RibaPak, and Copegus.

Ribavirin is not approved by the United States Food and Drug Administration (FDA) for any indication, and such use should be considered experimental.

Contraindications to antiviral therapy include:

• Black Box Warnings
• Oral
  • Monotherapy is not effective for the treatment of chronic hepatitis C virus (HCV) infection and should not be used alone for this indication
  • Hemolytic anemia is the primary toxicity, which may worsen cardiac disease and lead to fatal and nonfatal MI. Not to be used if a history of significant or unstable cardiac disease
  • Significant teratogenic or embryocidal effects were demonstrated in all animal species exposed to ribavirin
  • Half-life is 12 days, and the drug may persist in non-plasma compartments for as long as 6 months
  • Contraindicated during pregnancy and in the male partners of pregnant women
  • Extreme care must be taken to avoid pregnancy during therapy and for 6 months after completion of treatment in both females and female partners of men taking ribavirin
  • At least two reliable forms of effective contraception must be used during treatment and the 6-month post-treatment follow-up period
• Inhalation
  • Aerosolized ribavirin in individuals requiring mechanical ventilator assistance should be administered only by healthcare personnel and support staff familiar with this mode of administration and the specific ventilator being used
  • Strictly follow procedures that minimize drug precipitate accumulation to avoid mechanical ventilator dysfunction
  • Sudden respiratory function deterioration in infants may occur during the initiation of aerosolized ribavirin
  • Carefully monitor respiratory function during treatment
  • If sudden deterioration of respiratory function occurs, stop treatment and reinstitute only with extreme caution, continuous monitoring, and possibly bronchodilator coadministration
  • Aerosolized ribavirin is not indicated for adults
  • Produces testicular lesions in rodents and is teratogenic in all animal species in which adequate studies have been conducted (rodents and rabbits)

Contraindications to antiviral therapy include:

• General: hypersensitivity
• Virazole: pregnancy; adults; nonsevere RSV infections
• CrCl <50 mL/min
• Pancreatitis
• Hemoglobinopathies (e.g., thalassemia major, sickle cell anemia)
• Coadministration with didanosine
• Pregnancy or planning pregnancy, including men whose female partners are pregnant/planning to get pregnant
• In combination with alpha interferons
• Autoimmune hepatitis
• Hepatic decompensation in individuals with cirrhosis
• Precautions to antiviral therapy include
• Virazole: Mechanically ventilated patients
• HCV
• Preexisting cardiac disease
• May need interruption if cardiovascular status deteriorates
• Risk of hemolytic anemia
• Do NOT use it for influenza
• Only Copegus was studied in HCV/HIV coinfectees; however, the modified dose is CDC recommended
• Use with caution with corresponding peginterferons
• Ribavirin may cause birth defects or death of the fetus
• Avoid pregnancy
• Risk of hemolytic anemia
• Anemia associated with treatment may result in worsening cardiac disease
• Genotoxic and mutagenic: potential carcinogen
• Ocular disorders are reported when ribavirin is used in combination therapy with alpha interferons (e.g., decrease or loss of vision, retinopathy including macular edema, retinal artery or vein thrombosis, retinal hemorrhages, cotton wool spots, optic neuritis, papilledema, serous retinal detachment)
• Study in boys showed growth rate inhibited (i.e., height percentile decreases) with peginterferon alfa-2b plus ribavirin
• Pancytopenia and bone marrow suppression was reported when coadministered with pegylated interferon and azathioprine
• Hepatic decompensation
• Individuals with chronic hepatitis C (CHC) and cirrhosis may be at risk of hepatic decompensation and death when treated with alpha interferons, including PEGASYS
• Cirrhotic CHC individuals coinfected with HIV receiving highly active antiretroviral therapy (HAART) and interferon alfa-2a with or without ribavirin appear to be at increased risk for the development of hepatic decompensation compared to individuals not receiving HAART