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Vacunas

www.elsevier.es/vac

Review

Measles. Re-emergence on its path to eradication夽

Fernando A. Moraga-Llop ∗
Pediatra. Asociación Española de Vacunología, Barcelona, Spain

a r t i c l e i n f o a b s t r a c t

Keywords: After the continued decline in measles morbidity and mortality during this century, since
Measle 2017 there has been, for various reasons (vaccination reticence is very important), a re-
Exantematic disease emergence of the disease around the world, when walking towards its eradication. Clinicians
Epidemiology should suspect measles to anyone susceptible to fever and a clinical flulike presentation of
Measles vaccine several days of evolution, with the subsequent appearance of a generalized maculopapu-
lous rash. When a measles case is suspected, epidemiological surveillance service shall be
urgently declared, the specific IgM shall be determined and the patient isolated. If the case
is confirmed, an epidemiological survey and post-exposure prophylaxis of the susceptible
contacts will be carried out. Routine vaccination in childhood with a triple viral vaccine with
two doses from 12 months and in all persons with any age is essential, and vaccine coverage
of 95% or more in the population is essential.
© 2020 Published by Elsevier España, S.L.U.

Sarampión. Reemergencia en el camino de la erradicación

r e s u m e n

Palabras clave: Después de la disminución continuada de la morbilidad y la mortalidad del sarampión

Sarampión durante este siglo, desde 2017 se observa, por diversas razones (la reticencia vacunal es muy
Enfermedades exantemáticas importante), una reemergencia de la enfermedad en todo el mundo, cuando se caminaba
Epidemiología hacia su erradicación. Los clínicos deben sospechar el sarampión ante cualquier persona
Vacunas antisarampión susceptible que presente fiebre y un cuadro catarral de varios días de evolución, con la
aparición posterior de un exantema maculopapuloso generalizado. Cuando se sospeche un
caso de sarampión se declarará de manera urgente al servicio de vigilancia epidemiológica,
se determinará la IgM específica y se aislará al paciente. Si el caso se confirma, se realizarán
una encuesta epidemiológica y la profilaxis post-exposición de los contactos susceptibles.
Es fundamental la vacunación sistemática en la infancia con vacuna triple vírica con dos
dosis a partir de los 12 meses y en todas las personas susceptibles de cualquier edad, y es
imprescindible mantener coberturas vacunales del 95% o más en la población.
© 2020 Publicado por Elsevier España, S.L.U.
People forget diseases, but they don’t forget us, and they return.

DOI of original article: https://doi.org/10.1016/j.vacun.2020.04.001.

夽
Please cite this article as: Moraga-Llop F.A. Sarampión. Reemergencia en el camino de la erradicación. Vacunas. 2020.
https://doi.org/10.1016/j.vacun.2020.04.001
∗
Corresponding author.
E-mail address: fmoraga@acmcb.es
https://doi.org/10.1016/j.vacune.2020.05.003
2445-1460/© 2020 Published by Elsevier España, S.L.U.

VACUNE-147; No. of Pages 9

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that are swiftly deposited when coughing, sneezing or talking.

Introduction This means that transmission is only possible at a distance of
somewhat less than 1 m. It may also be transmitted through
It was 40 years ago now, in 1980, when the World Health Organ-
the air by aerosols of small droplets (< 5 ␮), and by direct
isation (WHO) certified the eradication of smallpox. After
contact with nasal and pharyngeal secretions. Another less
having overcome many obstacles, for some time we have been
common mechanism is by indirect contact through fomites
progressing towards doing the same with poliomyelitis. Two
recently contaminated by nasopharyngeal secretions.6–8
of its causal agents (poliovirus 2 and 3) have now been erad-
The duration of transmittability or contagiousness lasts
icated, and only type 1, which is endemic in Pakistan and
from one to two days prior to the start of symptoms (4 days
Afghanistan, is still circulating. The WHO had set the objective
prior to the start of the exanthema) until 4 days after the
of eradicating a third disease, measles, by 2020.1 Nevertheless,
appearance of the eruption. Children may not return to their
in 2017 this goal was seen to be impossible to achieve because
kindergarten or school until at least 5 days have passed after
the disease had re-emerged, and in 2019 morbidity worldwide
the start of the exanthema, always on condition that their
due to this disease tripled, with high rates of mortality.2
general state makes this possible. Immunodepressed patients
Measles was the first infectious exanthematous disease
have a longer period of viral secretion, and they may still
to be, classified, in as 1627, Sydenham differentiated it from
be contagious for several weeks after the appearance of the
scarlet fever, they became known as, the first, second dis-
exanthema.6–8
ease, respectively. In it was recognised as 1881, different from
Systematic vaccination has changed the epidemiological
the third disease, which was designated rubella or German
pattern: cases are observed in children not vaccinated with 2
Measles (in honour of the German authors who were inter-
doses after one year of age, or when they had not received their
ested in studying it). In and 1885| 1894, Filatow(in honour of
first vaccination (failure to receive their second vaccination is
the German authors who were interested in studying it), Dukes
very rare). The global number of cases has now undergone a
described a fourth disease, which was denominated scarlet
major increase, and this seriously threatens the possibility of
fever-like rubella, which eventually “disappeared” as, such, it
eradication in the next few years.
consisted of clinically mild forms of scarlet fever. In as 1905, a
Although there are several reasons why measles has
fifth disease or infectious erythema was defined, in 1910, rose-
resurged, they always coincide in the reduction of vaccination
ola infantum was mentioned for the first time, as, exanthema
coverage. Reluctance to vaccinate predominates in developed
subitum or a sixth disease.3 From then on exanthematic dis-
countries. This is a broad concept that runs from people who
eases ceased to be, given ordinal numbers.
deeply reject all vaccines, to those that accept them with
Before the introduction of widespread vaccination cam-
doubts and concerns. It also includes people who belong to
paigns measles infected from 95%-98% of children under the
certain political, religious, cultural and lifestyle groups. Isola-
age of 18 years old, causing approximately 135 million cases
tion from the healthcare system may in some cases be decisive
and more than 6 million deaths per year worldwide, with mor-
in not vaccinating. A range of causes and situations exist in
tality rates of approximately 3%-34% in developing countries,
countries that lack economic resources: political, social con-
from 10 to 20 times higher than the rates in industrialised
flict or war, a shortage of supplies or fear about the safety
countries.4,5
of vaccination. Other factors that should be considered and
The worldwide incidence of measles has now increased,
studied are the early loss of transplacental immunity in the
making it necessary to know or recall its clinical signs. This is
children of vaccinated mothers,10 the age when the first dose
so above all in the case of doctors who did not become familiar
is administered11,12 and concordance between the circulating
with this disease during their training, as diagnosis must be
virus genotype and those of the vaccines.13
a suspicion during anamnesis and patient examination. This
This situation must not continue, as measles fulfils all of
review analyses the most relevant epidemiological, clinical
the criteria for eradication: it is an infection which is limited
and diagnostic aspects of measles, together with preventive
to humans and is transmitted from person to person, there
measures.
are no chronic carriers, there is a single causal agent, the
transmissibility period is short, a safe and effective vaccine is
Epidemiology available and natural or vaccinated immunity lasts for a long
time.8
Measles is a highly contagious disease, with a secondary If the global situation of measles continues as it is, the WHO
attack rate close to or above 90%. It is seasonal, and is most should consider declaring this resurgence to be an interna-
common at the end of winter and the beginning of spring. In tional public health emergency, so that firstly the disease can
a susceptible population one case will originate from 12 to 18 be controlled, followed by its eradication.14
secondary cases. This figure is denominated R◦ or the basic
reproduction number, and it is one of the highest in infec- Measles in the world
tiology. As measles is one of the most contagious diseases,
immunity levels of 95% or higher are needed in the popula- According to WHO data corresponding to December 2019,
tion to interrupt its transmission and eliminate it from the before the vaccine came into general use in 1963, every 2-3
community.6–9 years there were major epidemics that caused up to 2 mil-
The disease has an exclusively human reservoir, and its lion deaths per year. From 2000 to 2016 vaccination against
mechanism of transmission is direct by person to person con- measles reduced the number of deaths by 84%, down from
tact through Flügge droplets (> 5 ␮) of respiratory secretions 550,000 to 90,000 individuals, most of them under the age of
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5 years old. Nevertheless, this figure rose to 110,000 in 2017
(total incidence: 6.7 million cases) and to 140,000 in 2018.15 It is
estimated that during the period from 2000-2018 vaccination
against measles prevented 23.2 million deaths worldwide.16 In
2018, 86% of newborn babies received their first vaccine dose
before their first birthday, vs. 72% in the year 2000, although
only 69% received the second dose.
The number of cases of measles tripled from 2017 to 2019,
although the WHO, taking into account the fragility of moni-
toring systems in many countries, estimates that this increase
is probably up to 10 times greater. Current worldwide mortal-
ity is higher than 300 deaths per day, the majority of them
younger than 5 years old. This increase in the incidence of
measles has varied from one WHO region to another, and
Africa stands out with an increase of 900% in 2019 over the
previous year.
Although North and South America were free of measles
from 2016, more than 15,000 cases were reported in 2019 in 14
countries, with 18 deaths. Brazil stands out with more than
13,000 cases and 15 deaths, together with the United States
with 1,282 cases and Venezuela with more than 500 cases and
2 deaths.
The largest outbreak in the United States since 1992
occurred from 30 September 2018 to 3 September 2019. There
were 654 cases in New York, the majority in Brooklyn and
Rockland County, caused by a fall in vaccination rates, most
especially in the community of Orthodox Jews. Although
measles had been declared to have been eliminated from the
United States in the year 2000, there were a total of 1,282 cases
in 2019.17
Outbreaks of measles have been reported in many South
East Asian and Pacific countries since 2017. An outbreak has
been running in the Philippines since the end of 2017, with
more than 20,000 cases and 199 deaths in 2018. This outbreak
increased notably in 2019, as the population ceased vaccinat-
ing due to a loss of trust after the failure and controversies
arising from the introduction of a Dengue fever vaccine. An
outbreak was declared in the islands of Samoa in October
2019. This affected 5,697 people and caused 83 deaths, and
it occurred due to a fall in vaccination coverage because of
an error in administering a vaccine that led to the deaths of
2 children.18 Another major outbreak occurred in the Demo-
cratic Republic of the Congo in June 2019, simultaneously with
an outbreak of Ebola, with more than 250,000 cases and 6,000
deaths.
Measles in Europe
A highly important fact that must be pointed out is that,
according to data from the first half of 2019, the WHO with-
drew measles elimination certification from 4 countries: the
United Kingdom, Greece, Albania and the Czech Republic,
because their vaccination programs did not maintain coverage
of 95% or more.19 The current situation regarding the elimina-
tion of measles in the world is that it has been achieved in
83 (42%) of the 194 WHO member states, and in 70% of the
countries in the WHO European region.
In 2017, several countries in the WHO European Region
recorded outbreaks in children and adults, including France,
Georgia, Greece, Italy, Rumania, the Russian Federation, Ser-
3
bia and Ukraine. Since then (as the lowest figure was achieved
in 2016, with 5,273 cases) the number of cases has quadrupled
(25,863, 88,693 and 101,280 cases in 2017, 2018 and January -
October 2019, respectively). It should be underlined that there
were 74 deaths in 2018, vs. 42 in 2017.
The largest outbreak with a death in a decade occurred
in Israel in 2018. This affected the Orthodox population of
Jerusalem above all due to their refusal to vaccinate, with vac-
cination rates of 85% that in the schools with the highest rates
of morbidity did not attain 50%.20
Measles in Spain
On 26 September 2017 the WHO declared Spain free of
endemic measles transmission, recognising that the few cases
and outbreaks reported in the previous 3 years had been the
result of importations (while in Catalonia the disease had been
declared to have been eliminated in the year 200021 ); in 2019
the WHO ratified the elimination of measles in our country.22
The number of confirmed cases of measles has risen from
a rate of 0.8 cases per million inhabitants in 2015 up to 4.8
in 2018 and approximately 6 (provisional data) in 2019. Of the
287 cases in the past year (vs. 222 in 2018), 36 were imported,
237 were connected and 14 were of unknown origin; there
were no autochthonous cases.22 Of the 157 cases of measles
recorded in 2017, 66.9% were in individuals over the age of
19 years old, and all of them were imported or connected with
imported cases, of which 86% corresponded to European coun-
tries (Rumania, Italy, the United Kingdom and France) while
14% correspond to Asia (China, Indonesia and Japan).23
Clinical manifestations
Measles is an infectious disease caused by a virus of the Morbil-
livirus genus of the Paramyxoviridae family. Only one serotype
of the measles virus exists, and there are a great many circu-
lating genotypes due to its high genetic variability. It is a very
labile virus, and it is vulnerable to external agents such as light
and heat, which render it inactive. This disease is the first of
the long list of maculopapular exanthemas, and it gave the
name of “morbiliform” exanthemas to cutaneous eruptions
with different aetiologies with morphological characteristics
similar to those of measles.
Measles has highly uniform clinical manifestations
(Figs. 1 and 2), and 4 periods after contagion are distinguished
in its evolution:
1 The incubation period: this runs from the moment of expo-
sure to the virus and its penetration in the organism until
the start of prodromic or catarrhal symptoms. This coin-
cides with the secondary viremia and involvement of the
respiratory mucosa, and it lasts for 8-12 days. The time lapse
until the moment exanthema commences may be up to 21
days, with an average of 14 days. The duration is longer
after the administration of general purpose immunoglobu-
lin, which forms part of the post-exposure prophylaxis or in
patients undergoing replacement therapy, in breast-feeding
babies due to the persistence of maternal antibodies, and in
immunodeficient individuals. This period may be shortened
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Fig. 1 – Measles. A. Koplik spots in the oral mucosa. B. Start of exanthema behind the ears.

Fig. 2 – Measles. A. Measles facies (conjunctivitis, rhinitis and stomatitis). B. Characteristic maculopapular exanthema.

in exceptional cases, such as direct infection of a cutaneous
wound with infected secretions, or parenteral infection.
This is an asymptomatic period, except for fleeting tem-
perature variations, slight discomfort or mild respiratory
symptoms that are almost always hard to notice and
detect.
2 The prodromic, catarrhal or pre-exanthematic period: this
lasts for an average of 4 days, although not uncommonly
it may last longer, up to 10 days. As is the case during the
exanthematic period, the symptoms may vary or attenuate
due to the previous administration of immunoglobulin or
vaccine. Prodromes are manifested by constant high fever
which may sometimes give rise to feverish convulsions,
cephalea, somnolence, general discomfort and catarrhal
symptoms due to involvement of the conjunctival, nasal
and oropharyngeal mucosa and that in the upper airways
(the larynx and trachea). Ocular, nasal and oral alter-
ations, with a certain degree of facial swelling, configure
the characteristic measles facies. The oral exanthema (Kop-
lik spots) was described by Flindt in 1860; Koplik described
their pathognomic nature in 1896, and Rembold and Flindt
published this observation in 1905. They consist of small
pointed raised spots, white in colour (“like salt spots”), sur-
rounded by a reddish halo or an erythematous base. They
occur in the jugular mucosa and on the internal face of the
cheeks opposite to the molars in 70%-90% of cases. They
appear at the end of the prodromic period immediately
before the exanthema (1-2 days), and they disappear within
24-48 hours of the start of the latter. The exanthema makes
it possible to diagnose measles prior to the appearance of
the characteristic exanthema. Similar spots to Koplik spots
may appear on the mucosa of the lips, eyelid, conjunctiva,
nose and vagina, as well as on the outer wall of the pharynx,
although these locations are rarely involved.
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3 The period corresponding to the condition or exanthe-
matic period: fever rises when the cutaneous eruption
starts, when catarrhal eye-nose-pharynx-larynx-trachea-
bronchial symptoms and general involvement are at their
most intense, while the Koplik spots disappear. This period
lasts from 3 to 5 days (up to 7 days), during which the symp-
toms evolve. The exanthema is maculopapular, violet red in
colour and very numerous, not confluent at first and gener-
ally not pruriginous; it commences in the area behind the
ears and spreads over 3 days, descending over the rest of
the face and neck, the trunk and limbs, without involving
the palms of the hands or the soles of the feet and converg-
ing. If the fever increases or reappears then a complication
of the measles must be suspected.
4 The convalescence, decline or desquamation period: this
starts on the third or fourth day of the exanthematic period,
with reduction and disappearance of the fever and catarrhal
symptoms except for the cough, which may last for a few
days or weeks, and the skin eruption, in the same order
in which they arose, together with an important improve-
ment in general condition. The presence of a bran-like small
scale desquamation is characteristic of this phase, leaving
the skin violet or brown in colour and enabling retrospec-
tive diagnosis. The cough and bronchial symptoms are the
last to disappear.24–28
Other infections are often present while convalescing from
measles (influenza, whooping cough, diphtheria, tuberculo-
sis, parotitis, scarlet fever, varicella and aphthous stomatitis).
This had been observed in the time before vaccination, when
measles was described as an anergising disease because the
measles virus eliminates antibodies that protect against infec-
tions which the body had been immune to, and specific
immunity memory cells that had been generated against other
diseases. This phenomenon of amnesia or immunity dysfunc-
tion against other infectious diseases may still be observed
five years after suffering measles, so that anti-measles vac-
cine may be said to protect against more than measles itself,
as it also protects against other infectious diseases.29,30
Clinical forms
The clinical manifestations of measles may change and have
characteristics other than those described. It takes the follow-
ing clinical forms:24,26,31
none- Abortive or modified measles: the exanthema has
fewer elements and colouration is paler, while the
symptoms are mild; sometimes this is experienced in a
subclinical form. The incubation period is longer. This
clinical form occurs after the administration of general
purpose immunoglobulin during the incubation period
or in the first half of the prodromic period, or after
the previous administration of anti-measles vaccine.
This form may also be seen in breastfeeding babies
due to the persistence of maternal antibodies. These
patients may suffer a second clinical infection if con-
ferred immunity is incomplete.
none- Attenuated measles: this is an adverse reaction which
occurs 5 to 12 days after vaccination. It develops with
5
little fever and mild catarrhal symptoms, with a pale
maculopapular exanthema with few elements.
none- Measles without exanthema or without fever: both of
these forms are very rare and may occur in one family
member during an outbreak. Retrospective diagnosis is
by means of specific IgM determination, as the disease
does not appear in anamnesis.
none- Black and haemorrhagic measles: the exanthema ele-
ments undergo a haemorrhagic transformation due
to the rupture of the papular capillaries (black form).
This clinical form does not indicate greater severity
if there is no haemorrhagic diathesis with cutaneous
and mucosal manifestations in other locations, due
to thrombocytopenia or more severe disseminated
intravascular coagulation (haemorrhagic form).
none- Vesiculosus or blistering measles: this may appear
in children with intense hyperhydrosis in hot humid
environments.
none- Converging scarlatiniform measles: catarrhal symp-
toms help to differentiate this from scarlet fever.
none- Pseudoappendicular measles: abdominal pains fre-
quently occur in the prodromic and condition periods.
They are sometimes intense and located in the right
iliac fossa, and this may lead to an appendectomy, in
which the existence of mesenteric adenitis is observed,
and more rarely true appendicitis.
none- Atypical measles: this occurs in individuals immu-
nised with inactivated virus vaccine that was used
from 1963 to 1967 in the United States and Canada,
and atypical measles occurs when they are subse-
quently exposed to the wild virus. The disease usually
runs in two phases, at first as immunisation-modified
measles, followed after 2 weeks by high fever and atyp-
ical exanthema. The latter spreads centripetally and
involves the hands and feet, and it is occasionally
vesiculosus and purpuric. Pulmonary complications
are common, with hilar adenopathies, pleural bleed-
ing and diffuse nodular infiltrates. This is considered
to be an immunocomplex-delayed hypersensitivity
phenomenon.32
none- Adult measles: this clinical form is more severe than
measles in childhood and it has more complications,
chiefly pneumonia, bacterial respiratory infections,
bronchospasm and hepatitis.
none- Severe measles in patients with cellular immunity
disorders: this may develop without exanthema and
it frequently leads to complications, among which
progressive acute encephalitis with measles inclusion
bodies stands out, together with giant cell pneumonia.
none- Measles during pregnancy: the most important effect
of the virus on the mother is that it increases her risk
of suffering complications, most especially respiratory
ones (pneumonitis), and for the foetus, as it may cause
an abortion or premature birth. The measles virus has
not been proven to have teratogenic effects.
Complications
The most important and frequent complications of measles
are respiratory and neurological, and they almost always
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occur during or after the exanthematic period. In general,
complications with measles should always be suspected
when the fever persists or reappears. The most common
complications are acute otitis media, diarrhoea, mastoiditis,
sinusitis, cervical lymphadenitis, stenosing laryngitis, laryn-
gotracheobronchitis, pneumothorax, pneumomediastinum
and subcutaneous emphysema, pneumonia or bronchopneu-
monia (viral, bacterial or mixed), enteritis, thrombocytopenic
purpura, pyodermitis, feverish convulsions, hepatitis, appen-
dicitis, myocarditis and acute post-infectious encephalitis
with permanent brain damage (one in every 1,000-2,000 cases
of measles). The most frequent microorganisms in bacterial
infections are Streptococcus pneumoniae, Streptococcus pyogenes
and Staphylococcus aureus.24,26,28
Subacute sclerosing panencephalitis is a chronic degener-
ative disease of the central nervous system which develops
with behavioural disorders, intellectual deterioration and
myoclonic epilepsy, and it is caused by the chronic activa-
tion of the measles virus. More than half of patients had been
diagnosed with measles in the first 2 years of life. Clinical
manifestations commence after an average 7-11 year period
of latency after having had the disease. The risk of subacute
sclerosing panencephalitis amounts to 4-11 cases per 100,000
cases of measles.
Death caused by measles is due to respiratory and neu-
rological complications, and the mortality rate is higher
in children younger than 5 years old, adults and immun-
odepressed individuals, including children with leukaemia,
individuals with human immunodeficiency virus infection
and those with severe malnutrition. Lethality varies from 1%
to 15% in developing countries.31,33
Diagnosis
Although diagnosis is based on symptoms and epidemiology,
it must always be confirmed in the current stage of resur-
gence to ensure proper epidemiological vigilance. This has to
include the determination of the specific IgM after the fourth
day of the appearance of the exanthema (preferentially from
day 4 to 8 and before day 28), or the specific IgG in 2 samples
separated by an interval of 2-4 weeks; diagnosis is late in the
latter case. Early confirmation of IgM positivity is very impor-
tant to enable the urgent adoption of preventive measures in
contacts and in the social circle of the patient (their home,
kindergarten, school, waiting rooms, primary care emergency
services and in hospitals). Another method is the detection
of the virus in urine or pharyngeal swab by polymerase chain
reaction in the 8 days following the appearance of the exan-
thema. Genotyping the virus is important for epidemiological
vigilance, the study of outbreaks and evaluation of the efficacy
of vaccines.7,8,34
Actions, preventive measures and treatment
If there is the suspicion of measles in a patient the epidemio-
logical vigilance service must be notified urgently, the specific
IgM must be determined and the patient is to be isolated or
wear a surgical mask. If the case if confirmed the epidemiolog-
ical questionnaire will be applied, together with post-exposure
prophylaxis for susceptible contacts.34
Post-exposure prophylaxis
After exposure to the measles virus a susceptible individual
will act according to the time that has transpired from the
moment of contact:7
none- In the first 72 hours after contact: vaccination if this is
not contraindicated. In babies younger than 6 months
old, pregnant women and immunodepressed patients,
general purpose immunoglobulin will be administered
even if they have been vaccinated.
none- From 4 to 6 days after contact: general purpose
immunoglobulin will be administered to all susceptible
and immunodepressed individuals, even if they have
been vaccinated.
Treatment
The patient will continue in isolation, preferentially in their
own home, although if their clinical situation makes it neces-
sary they will be admitted to hospital in a negative pressure
room. If a vulnerable person has to enter the room, as well
as the standard safety measures they will have to take pre-
cautions to prevent airborne transmission while the disease
is transmissible.
Treatment will be symptomatic and supportive, as well
as preventing possible bacterial complications. Additionally,
vitamin A will be administered once a day during 2 days, at
the following doses: 200,000 UI for children over 12 months
old, 100,000 UI in babies aged from 6 to 11 months old, and
50,000 UI for those under the age of 6 months old. A third dose
will be given from 2 to 4 weeks afterwards to children with
clinical signs of vitamin A deficiency.7
Vaccination
The first vaccines were developed by Enders, who together
with Peebles isolated and cultivated the measles virus in 1954.
It originated in a student named Edmonston, who gave its
name to one of the most widely used vaccine strains of live
attenuated virus. The first vaccine was approved in the United
States in 1963.8
Research was conducted into inactivated vaccines in the
United States in the 1960s, and in 1963 the first one derived
from the Edmonston strain was authorised. Al though this vac-
cine had fewer side effects, it was also less effective, and when
a vaccinated individual subsequently came into contact with
the wild virus they developed atypical measles. This disease
is caused by antigen-antibody immune complexes (delayed
reaction hypersensitivity) (see the Clinical Forms section), so
that it ceased to be used 4 years later.8,32
Two attenuated Edmonston B strain vaccines were used
in Barcelona in 2 pioneering clinical trials in Europe in 1961
and 1962.35 Given the high reactogenicity (high fever and
exanthema) observed in the first clinical trial, in the second
one immunoglobulin was administered after vaccination in 3
 ARTICLE IN PRESS
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groups, on the same day and on the third and sixth days, to
reduce the side effects.
The first measles vaccination campaign in Spain com-
menced in 1968 in 11 provinces, vaccinating children aged
from 9 to 24 months old; the vaccine used contained the Beck-
enham 31 strain, which was found to be highly reactogenic.36
With this strain a severe reaction (encephalitis) was observed
in England, and it was withdrawn. This contributed to the
suspension of vaccination in Spain in 1970.
Parallel research took place into obtaining hyperattenuated
strains, one of which, the Schwarz strain (1964), originated in
the Edmonston A strain but was far less reactogenic. This was
used in the first monovalent anti-measles vaccine (Rouvax® ),
which was utilised in the first systematic vaccination calen-
dar in Spain by Barcelona Town Hall in 1973, at 12 months
of age.37 This vaccine was included in Spain in the calendar
drawn up by the Dirección General de Sanidad in 1977, for use
at 9 months old.36 In comparison with the previous attenuated
vaccine, this hyperattenuated strain caused side effects less
often and they were less severe, making it possible to eliminate
the use of immunoglobulin.
Two live hyperattenuated vaccines were authorised in 1965
and 1968. These too were derived from the Edmonston strain,
and they contained the Schwarz and Moraten strains (MORe
ATtenuated ENders), respectively.
The current attenuated live virus vaccine which is adminis-
tered in the form of the triple viral vaccine is available in Spain
in two forms, one with the Schwarz strain and the other with
the Enders’ Edmonston strain. This vaccine was included in
the calendar of all of the autonomous communities in 1981,
and in the second dose in 1996,38 although Catalonia had
already done so in 1988.36 The vaccine must not be admin-
istered prior to the age of 12 months old, except in situations
of pre-exposure and post-exposure prophylaxis, in which case
it can be given after the age of 6 months (although the techni-
cal data sheet states that it is for after the age of 9 months, the
medical authorities have authorised this). When the vaccine
is administered at 6-11 months it is indispensible to prescribe
2 further doses after the age of 12 months.
A dose administered at 12 months of age induces an
immune response with seroconversion in more than 95% of
vaccinated individuals; a second dose between 2 to 4 years
old makes it possible to rescue nearly all of the others (4.5%),
i.e., the initial failures. After modification of the first strategy a
second recall dose is administered after at least 4 weeks, with
the aim of rescuing those who have not responded. The max-
imum response occurs at from 6-8 weeks after vaccination. It
has been found that vaccine-conferred immunity lasts for at
least 20 years, and it is believed that it lasts for the whole life
of the majority of individuals.7–9 The most frequent adverse
reactions after vaccination are local, although sometimes a
case of attenuated measles may occur (as described under the
heading Clinical forms).
The protective efficacy of the measles vaccines in sev-
eral studies was found to range from 93% to 97% after one
and 2 doses, respectively.7–9 To achieve herd immunity a
second dose vaccination coverage rate higher than 95% is
necessary. Excellent vaccination was achieved in Spain in
2017 and 2018, higher than 97% for the first dose but only
93.1% and 94.1% for the second dose, respectively; moreover,
7
9 autonomous communities were below 95%, and this aspect
must be improved.39
Pre-exposure prophylaxis
When a susceptible individual has to travel to a place where
the measles virus is circulating, the following action will be
taken:7,8
none- Babies under 6 months old: if the mother is suscep-
tible, intramuscular general purpose immunoglobulin
will be administered.
none- Babies aged from 6 to 11 months: a dose of triple viral
vaccine will be administered and this will be consid-
ered to be dose 0. At 12 months a 2 dose pattern will
commence, with an interval of at least 28 days.
none- Children over the age of 12 months and adults: it must
be confirmed whether they have received the recom-
mended 2 doses after the age of 12 months, or if they
have had the disease. If the individual is susceptible
they will be vaccinated with 2 triple viral vaccine doses
separated by an interval of one month (and if they had
been vaccinated with a single dose, they will be given
a second dose).
none- Susceptible children and adults for whom the vaccine
is contraindicated (those under the age of 6 months,
pregnant women and immunodepressed individuals,
including those who have been vaccinated): general
purpose intramuscular immunoglobulin at a dose of
0.5 ml/kg (maximum dose: 15 ml); in high risk immun-
odepressed individuals this dose will be administered
intravenously.
Conclusions
none- After the continuous fall in the morbidity and mor-
tality caused by measles during this century, from
2017 onwards a global resurgence of the disease has
occurred due to a range of reasons. This situation has
arisen when progress was being made towards the
eradication of the disease, which had been foreseen to
take place in this year, 2020. This resurgence has even
occurred in Europe and in countries where measles had
been eliminated, and the primary cause is very worry-
ing: the fall in vaccination coverage due to reluctance
to vaccinate.
none- Doctors (pedestrians and family doctors) must suspect
measles in any individual, after anamnesis to evalu-
ate their immunity status and possible contacts, who
has fever and catarrhal symptoms that have evolved
over several days, with the subsequent appearance of
a generalised maculopapular exanthema.
none- The epidemiological vigilance department is to be
urgently informed when there is the suspicion of a case
of measles, determining its specific IgM and isolating
the patient.
none- If the suspected case is confirmed then an epidemi-
ological survey will be performed and post-exposure
 ARTICLE IN PRESS
8 v a c u n a s . 2 0 2 0;x x x(x x):xxx–xxx
prophylaxis will be administered to susceptible con-
tacts.
none- Systematic vaccination must take place infancy with
the 2 dose triple viral vaccine after the age of 12
months, with a check that vaccination has taken place
in all age groups for susceptible individuals, if vaccina-
tion is not contraindicated. Pre-exposure prophylaxis
by vaccination must take place over the age of 6
months.
none- The great paradox is that vaccines save us from dis-
eases and then lead us to forget the ones they saved us
from.
Informed consent
The author declares that he has the informed consent of all
of the tutors of the patient for the publication of the clinical
images in this paper, and that their personal data have been
protected, according to the protocols of the institution.
Conflict of interests
The author has no conflict of interests to declare. The author
of this paper declares that he is a member of the Editorial
Committee of the journal Vacunas.
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