The symptoms of acute measles are so distinctive that
laboratory diagnosis is seldom required. However, as the
vaccination program progresses, atypical forms of measles have
emerged and laboratory diagnosis may be required.
1. Microscopy - production of multinucleate giant
cells with inclusion bodies is pathognomonic for measles.
During the prodrome phase, such cells are detectable in
the NPS (nasopharyngeal secretions). This is more rapid
and practical than virus isolation.
2. Immunofluorescence - direct and indirect
immunofluorescence have been used extensively to
demonstrate MV antigens in cells from NPS specimens. This
technique can also be applied to the urine as such cells
may be present in the urine 2 to 5 days after the
appearance of the rash. (Although like mumps, measles
virus is also excreted in the urine, this route is
unlikely to play a significant role in the spread of the
virus infection.)
3. Virus isolation - measles virus can be isolated
form a variety of sources, e.g. throat or conjunctival
washings, sputum, urinary sediment cells and lymphocytes.
Primary human kidney (HEK) cells are the best, although
primary monkey kidney can be used as well. Continuous
cell lines such as vero cells can also be used although
they are not as efficient as primary cell lines. A CPE
develops between 2 to 15 days, and consist of either a
broad syncytium or a stellate form with inclusion bodies
visible. The presence of measles can be confirmed by
haemadsorption. In acute measles, the isolation rate is
difficult and the success rate is low. Isolation is most
likely to be successful from material taken in the
prodrome phase but not in the later stages after the rash
has developed. Therefore isolation should only be
attempted in complicated cases such as suspected SSPE
where the lymphocytes may carry the virus, and in
immunocompromised individuals developing pneumonia.
4. Serology - diagnosis of measles infection can
be made if the antibody titres rise by 4 fold between the
acute and the convalescent phase or if measles-specific
IgM is found. The methods that can be used include HAI,
CF, neutralization and ELISA tests. Neutralization tests
are the most sensitive but are not practical to perform.
CFTs have a reduced sensitivity and thus are not useful
for immune status screening.
Diagnosis of SSPE - the presence of measles specific
antibodies in the CSF is the most reliable means of laboratory
diagnosis of SSPE. Demonstration of MV-specific antibodies in the
CSF may be sufficient with, if necessary, demonstration of
MV-specific restricted heterogeneity by isoelectric focusing.
Virus isolation from SSPE brain tissue is complicated.
Alternately, brain biopsy material can be examined
microscopically for inclusion bodies and virus antigen by
immunofluorescence.
Syncytial formation caused by measles virus in cell
culture (Courtesy of Linda Stannard, University of Capetown,
S.A.)
F. Management
In the majority of patients, measles is an acute self-limiting
disease that will run its course without the need for specific
treatment. However, it is far more serious in the
immunocompromised, the undernourished, and children with chronic
debilitating diseases. Such patients can be protected by the
administration of human anti-measles gammaglobulin if given
within the first 3 days after exposure. Alternatively, the
exposed individual can simply be vaccinated within 72 hours of
exposure.
Pneumonia - antibiotics may be indicated in cases
of secondary bacterial pneumonia or otitis media.
Encephalitis - treatment of acute measles
encephalitis is only symptomatic and supportive. A wide
variety of treatment has been tried for SSPE but no
convincing effects have been demonstrated.
G. Prevention
With no animal reservoir, it must be possible to eradicate the
virus through a controlled vaccination campaign. In the USA,
where vaccination of all children is required before commencing
school, case reports have fallen by over 99% but eradication has
not been achieved. The following vaccines are available
Inactivated Vaccine - this vaccine was intended
for use in young children less than 1 year of age who are
most prone to severe complications. It was thought to be
advisable to avoid the use of a live vaccine. It was
found that at least 3 doses were needed to elicit a
protective antibody response but the antibody levels soon
waned. This leave the vaccinees open to attack by the
natural virus. In some cases, the nature of the partial
immunity led to serious hypersensitivity reactions to
infection (Atypical measles). The exact mechanism is
still uncertain but it was thought that the vaccine
lacked an important antigen of the virus and thus
immunity was not complete. In view of the above and the
fact that antibody levels decline rapidly after
administration of the killed vaccine, live vaccination is
now generally recommended and individuals previously
immunized with the killed vaccine should be reimmunized
with the live vaccine. The killed vaccine has now been
withdrawn.
Live vaccine - live vaccines are now usually used.
The seroconversion rate is 95% and the immunity lasts for
at least 10 years or more, possibly lifelong. The
virulence of the attenuated strain now in use is so low
that encephalitis has only been noted in 1 in 1 million
recipients. SSPE has been reported in children given the
live vaccine. However, the rate is lower than that
following natural infection. Therefore the vaccine is
safe for use in very young children. The live vaccine is
now incorporated as part as the MMR vaccine. As
vaccine-induced measles antibody develops more rapidly
than following natural infection, MMR vaccine can be used
to protect susceptible contacts during a measles
outbreak. To be effective, the vaccine must be
administered within three 3 days of exposure. If there is
doubt about a child’s immunity, vaccine should be
given since there are no ill effects from immunizing
individuals who are already immune. Immunoglobulin should
be given to those for whom the vaccine is
contraindicated.
The vaccination programme has been most effective in the USA,
where measles immunization is compulsory. The incidence rate has
also declined dramatically in the UK but without the rigorously
pursued vaccination as practiced in the US, it is not likely to
be as effective as that in N. America. In the third world,
malnutrition aggravates measles infection and there are 900,000
measles related deaths per year. Vaccination in these areas has
failed to yield dramatic results. The problem is that the vaccine
is usually given at 12 months of age (it should not be given in
younger individuals because the presence of maternal antibodies
may lead to a poor response.) but infection in these areas often
occurs earlier in life. Vaccination should therefore be performed
on younger children than in the developed world. However, this
must be balanced with the fact that the success rate is lower in
younger children (50-75% in 6-month-old-children as opposed to
95% for 12-month-old children.). Measles is highly infectious and
has a very high attack rate and thus it would be extremely
difficult to eradicate the virus altogether through vaccination.
Management of Outbreaks
Measles outbreaks are most deleterious in wards with
immunocompromised children or adults e.g. children with leukaemia
and bone marrow transplant recipients. Measles is definitely as
dangerous as VZV in that setting. HNIG should be given to all
severely immunocompromised children irrespective of their
immunization status since it has been reported that severe
measles infection can occur in those who had been immunized and
had a documented low-level antibody response. Therefore, the
routine screening of children for measles antibody before
admission is probably unjustified since there would be no
difference in the management. The same argument applies to the
screening of patients for immunity before the administration of
HNIG. The use of live-attenuated vaccine for postexposure
prophylaxis is contraindicated. The same protocol applies to
immunocompromised adults who come into contact with measles.
Immunocompetent children under 12 months in whom there is a
particular reason to avoid measles, such as a recent severe
illness, can also be given immunoglobulin. MMR vaccine should
then be given after an interval of at least 3 months, at around
the usual age.
