Measles (Rubeola) : Epidemiology, Symptoms, Diagnosis, Treatment & Prevention
- Measles is an highly infectious respiratory disease of childhood caused by an RNA paramyxovirus & it is characterized by a prodromal illness of fever, catarrhal symptoms of respiratory tract (cough, coryza), and conjunctivitis followed by the appearance of a generalized maculopapular rash.
- The CDC case definition for measles requires (1) a generalized maculopapular rash of at least 3 days’ duration; (2) fever of at least 38.3°C (101°F); and (3) cough, coryza, or conjunctivitis.
- It is a serious disease in the malnourished, vitamin-deficient or immunocompromised, in whom the typical rash may be missing and persistent infection with a giant cell pneumonitis or encephalitis may occur.
- It does not cause congenital malformation but may be more severe in pregnant women.
- Causing agent : RNA paramyxovirus (so far only one serotype known).
- Humans are the only known reservoir for RNA paramyxovirus.
- Measles is endemic virtually in all parts of the world. It tends to occur in epidemics when the proportion of susceptible children reaches about 40%.
- Mortality clusters at the extremes of age, averaging 1 : 1000 in developed countries and up to 1 : 4 in developing countries.
Mode of Infection
- Measles virus is transmitted primarily by respiratory droplets (secretions of the nose, throat & respiratory tract of a case of measles during the prodromal period & the early stages of rash) over short distances and, less commonly, by small-particle aerosols that remain suspended in the air for long periods.
- The virus can be transmitted by direct contact with infected secretions but does not survive for long on fomites.
- The only source of infection is a case of measles.
- Incubation period for measles is ~10 days from exposure to onset of fever onset and 14 days to rash onset. This period may be shorter in infants and longer (up to 3 weeks) in adults.
- When measles infection is artificially induced bypassing the respiratory tract (as with injection of live measles vaccine), the incubation period is somewhat shortened, averaging 7 days.
- Period of Communicability : 4 days before and 5 days after the appearance of rash.
- Infection is initiated when measlesvirus is deposited on epithelial cells in the respiratory tract, oropharynx, or conjunctivae.
- During the first 2–4 days after infection, virus proliferates locally in the respiratory mucosa and spreads to draining lymph nodes.
- Virus then enters the bloodstream in infected leukocytes (primarily monocytes), producing the primary viremia that disseminates infection throughout the reticuloendothelial system.
- Further replication results in secondary viremia that begins 5–7 days after infection and disseminates measlesvirus throughout the body.
- Replication of virus in these target organs, together with the host’s immune response, is responsible for the signs and symptoms of measles that occur 8–12 days after infection and mark the end of the incubation period.
In most persons, the signs and symptoms ofmeasles are highly characteristic. There are 3 stages in the natural history of measles as following :
1. Prodromal Stage
- It begins 10 days after infection, and lasts until day 14.
- Fever and malaise beginning ~10 days after exposure are followed by cough, coryza with sneezing & nasal discharge, and conjunctivitis. These signs and symptoms increase in severity over 4 days.
- Koplik’s spots develop on the buccal mucosa ~2 days before the rash appears. Koplik’s spots are like table salt crystals appears on the buccal mucosa opposite the first & second lowers molars. They are small (~1 mm in diameter), bluish-white dots on a red base. Their presence is pathognomonic of measles.
2. Eruptive Phase :
- The rash of measles begins as erythematous macules behind the ears and on the neck and hairline. The rash progresses to involve the face, trunk, and arms, with involvement of the legs and feet by the end of the second day. Areas of confluent rash appear on the trunk and extremities, and petechiae may be present.
- The rash fades slowly in the same order of progression as it appeared, usually beginning on the third or fourth day after onset. Resolution of the rash may be followed by desquamation, particularly in undernourished children.
- Because the characteristic rash of measles develops as a result of interaction of immune T-cells with virus-infected cells in the small blood vessels, it may not develop in persons with impaired cellular immunity (e.g., those with AIDS). These persons have a high case-fatality rate and frequently develop giant-cell pneumonitis caused by measles virus. T lymphocyte defects due to causes other than HIV-1 infection (e.g., cancer chemotherapy) also are associated with increased severity of measles.
3. Post- Measles Stage :
- The child will have lost weight & will remain weak for a number of days.
- There may be failure to recover & gradual deterioration into chronic illness.
Most complications of measles involve the respiratory tract and include the effects of measles virus replication itself and secondary bacterial infections. Most complications of measles result from secondary bacterial infections of the respiratory tract that are attributable to a state of immune suppression lasting for several weeks to months after acute measles. Complications are more common in older children and adults.
- The most common complications are – measles associated diarrhoea, pneumonia, gneralised lymphadenopathy, & otitis media.
- The more serious are the neurological complications which include febrile convulsions, encephalomyelitis, MeaslesInclusion Body Encephalitis (MIBE), & Subacute Sclerosing Pan-Encephalitis (SSPE).
- Encephalomyelitis occurs within 2 weeks of rash onset and is characterized by fever, seizures, and a variety of neurologic abnormalities.
- Measles inclusion body encephalitis (MIBE) and subacute sclerosing panencephalitis (SSPE) are rare late complication caused by persistent measles virus infection which occurs up to 7 years after infection.
- MIBE is a rare but fatal complication that affects individuals with defective cellular immunity and typically occurs months after infection.
- SSPE is a slowly progressive disease characterized by progressive mental deterioration leading to paralysis, involuntary movements, muscular rigidity & coma.
Diagnosis of measles can be made through following methods :
- Clinically : Measles is readily diagnosed on clinical grounds by clinicians familiar with the disease, particularly during outbreaks. Koplik’s spots are especially helpful because they appear early and are pathognomonic.
- Detection of measles virus–specific antibody (serum IgM, seroconversion or salivary IgM) : Several methods for measurement of antibodies to measles virus are available such as : enzyme immunoassays, neutralization tests.
- Isolation of the virus in cell culture from respiratory secretions, nasopharyngeal or conjunctival swabs, blood, or urine.
- Direct detection of giant cells in respiratory secretions, urine, or tissue obtained by biopsy.
- Detection of measles virus RNA : Reverse-transcriptase polymerase chain reaction
There is no specific antiviral therapy for measles.
- Treatment consists of symptomatic & general supportive measures, such as hydration and administration of antipyretic agents.
- Normal immunoglobulin attenuates the disease in the immunocompromised (regardless of vaccination status) and in non-immune pregnant women, but must be given within 6 days of exposure.
- Antibiotic therapy is reserved for bacterial complications. Effective case management involves prompt antibiotic treatment for patients who have clinical evidence of bacterial infection, including pneumonia and otitis media.
- Vitamin A is effective for the treatment of measles& can markedly reduce rates of morbidity and mortality.
The WHO recommendations for Vitamin A dosing during measles management :
- Children of ≥12 months of age : once-daily doses of 200,000 IU of vitamin A for 2 consecutive days
- Younger children : 100,000 IU per day for children 6–12 months of age
- Children <6 months old : 50,000 IU per day
- A third dose is recommended 2–4 weeks later for children with evidence of vitamin A deficiency.
- Most persons with measles recover and develop long-term protective immunity to reinfection.
- Measlescase-fatality proportions vary with the average age of infection, the nutritional and immunologic status of the population, measles vaccine coverage, and access to health care.
- Among previously vaccinated persons who do become infected, disease is less severe and mortality rates are significantly lower.
Control & Prevention
The following guidelines are significant in combating themeasles :
- Achieving an immunization rate of >95%, &
- On-going immunization against measles through successive generation of children.
1. Passive Immunization (Immunoglobulins) :
- Measles may be prevented by administration of human immunoglobulin early in the incubation period.
- It should be given within 3-4 days of exposure.
- Administered up to 6 days after exposure, immunoglobulin will still prevent or modify the disease.
- The recommended dose is 0.25 mL/kg givenb intramuscularly. Immunocompromised persons should receive 0.5 mL/ kg. The maximum total dose is 15 mL.
- IV immunoglobulin contains antibodies to measles virus; the usual dose of 100–400 mg/kg generally provides adequate prophylaxis for measles exposures occurring as long as 3 weeks or more after IV immunoglobulin administration.
2. Active Immunization (Measles Vaccine) :
- Only live attenuated vaccines are recommended for use; they are both safe & effective.
- Lyophilized measlesvaccines are relatively stable, but reconstituted vaccine rapidly loses potency.
- Live attenuated measlesvaccines are inactivated by light and heat and lose about half their potency at 20°C and almost all their potency at 37°C within 1 h after reconstitution. Therefore, a cold chain must be maintained before and after reconstitution.
- Antibodies first appear 12–15 days after vaccination, and titers peak at 1–3 months.
- Measles vaccines are often combined with other live attenuated virus vaccines, such as those for mumps and rubella (MMR) and for mumps, rubella, and varicella (MMR-V).
- Standard doses of currently licensed measlesvaccines are safe for immunocompetent children and adults.
The standard guidelines for MeaslesVaccination are as following :
1. Age : The recommended age of first vaccination varies from 6 to 15 months and represents a balance between the optimal age for seroconversion and the probability of acquiring measles before that age.
- The WHO Expanded Programme on immunization recommends vaccination at 9 months age as adopted in INDIA.
- The age can be lowered to 6 months if there is measles outbreak in community.
- For infants immunized between 6 months & 9 months of age, a 2nd dose should be administered ASAP after child reaches the age of 9 months provided that at least 4 weeks have elapsed since the last dose.
2. Route : The reconstituted vaccine is generally injected subcutaneously , but it is also effective when administered intramuscularly.
3. Immunity : Immunity develops 11-12 days after vaccination. The duration of vaccine-induced immunity is at least several decades if not longer.