Infection, Disease & Health (2016) 21, 192e196

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Research paper

Risk factors and clinical profile of measles infection in

children in Singapore
Vikram Naga Vemula a,*, Ling Li b, Koh Cheng Thoon c,e,f, Chia Yin Chong c,e,f,
Nancy Wen Sim Tee d,f, Matthias Maiwald d,f,g, Natalie Woon Hui Tan c,e,f,h

a
Department of Paediatrics, KK Women’s and Children’s Hospital, Singapore
b
Infection Control Unit, KK Women’s and Children’s Hospital, Singapore
c
Infectious Diseases Service, Department of Paediatrics, KK Women’s and Children’s Hospital, Singapore
d
Department of Pathology and Laboratory Medicine, KK Women’s and Children’s Hospital, Singapore
e
Yong Loo Lin School of Medicine, National University of Singapore, Singapore
f
Duke-National University of Singapore Medical School, Singapore
g
Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
h
Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore

Received 2 October 2016; received in revised form 28 November 2016; accepted 28 November 2016

KEYWORDS Abstract Background: Measles is a highly contagious disease with potentially severe compli-
Measles; cations. A marked increase in the number of cases hospitalized for measles was observed in
Risk factors; children in Singapore between December 2013 and February 2014. This study examined the
Children clinical epidemiology and risk factors of children admitted for measles.
Methods: A retrospective study was conducted between January 2013 and May 2014 that
included all children admitted for measles to KK Women’s and Children’s Hospital (KKH).
Patients were identified from the KKH laboratory database, based on positive detection of
measles virus RNA.
Results: A total of 68 children were identified in this study, of which 63.2% were male, 80.9%
were <24 months and 54.4% <12 months of age (range: 3e130 months). The majority (89.7%)
had not received measles, mumps and rubella (MMR) vaccination and 10.3% had only 1 dose. In
the peak period from December 2013 to February 2014, there were 33 children with measles
identified; out of which, 17 (51.5%) had a travel history to countries with documented measles
outbreaks (Philippines, 52.9%; Indonesia, 35.3%). This was significantly higher compared to
children admitted for measles during other months (OR 5.13, 95% Confidence Interval, CI,
1.686e15.625). Common symptoms of measles included fever (100%), rash (92.6%) and cough
(92.6%). The most common complication was pneumonia (17.6%). All children recovered well.
Infants had a lower risk than children >12 months of developing lymphopenia (OR, 0.029, 95%
CI, 0.003e0.244) and conjunctivitis (OR 0.294, 95% CI 0.103e0.843) but a higher risk of devel-
oping diarrhea (OR 3.248, 95% CI 1.125e9.379).

* Corresponding author. 100, Bukit Timah Road, Singapore 229899, Singapore.

E-mail address: nagavikram.vemula@mohh.com.sg (V.N. Vemula).

http://dx.doi.org/10.1016/j.idh.2016.11.004
2468-0451/ª 2016 Australasian College for Infection Prevention and Control. Published by Elsevier B.V. All rights reserved.
Childhood measles infection in Singapore 193

Conclusion: Apart from absent or incomplete MMR vaccination, risk factors for measles infec-
tion in children included age <24 months (80.9%) and travel history to countries with documen-
ted measles outbreaks. Continued cross border surveillance of measles and, timely
administration of MMR vaccinations are therefore essential.
ª 2016 Australasian College for Infection Prevention and Control. Published by Elsevier B.V. All
rights reserved.

Highlights

 A retrospective study to understand the risk factors and clinical profile of measles infection
in children in Singapore.
 Risk factors included age <24 months, absent or incomplete MMR vaccination and travel to
countries with measles outbreaks.
 Continued cross border surveillance of measles and, timely administration of MMR vacci-
nations are therefore essential.

Introduction Methods

Measles is an acute highly infectious disease that is spread
by airborne transmission and has potentially severe com-
plications [1]. The measles virus belongs to the genus
Morbillivirus [2] within the family Paramyxoviridae. Clin-
ical features indicative of measles include rash lasting at
least 3 days, fever for at least 1 day, with temperatures
often above >40  C and at least one of the three Cs: cough,
coryza or conjunctivitis [3].
Before the introduction of the measles vaccine, the
measles virus caused millions of deaths worldwide [4].
However, routine vaccination in many countries have
caused measles to become relatively uncommon. In
Singapore, with the successful implementation of the
National Childhood Immunization Programme using the
monovalent measles vaccine, measles incidence declined
from 88.5 cases per 100,000 in 1984 to 6.9 per 100,000 in
1991 [5]. Resurgences of measles were observed in 1992,
1993 and 1997. A ‘catch-up’ vaccination program using
the trivalent measles, mumps and rubella (MMR) vaccine
was conducted in 1997, followed by introduction of the
two-dose vaccination schedule in January 1998, resulting
in the incidence of measles declining sharply to 2.9 per
100,000 in 1998. Vaccination coverage was maintained at
95% for the first dose and 92e94% for the second dose.
To further eliminate sporadic cases of measles, the na-
tional immunization schedule was amended in December
2011 to bring forward the first MMR vaccine dose from 15
to 18 months to 12 months of age, and the second dose
from 6 years to 15e18 months. Presently, the majority of
the cases in Singapore occur as single cases or in the
form of small clusters of endemic or import-related
cases [5].
A marked increase in number of measles cases was
observed in children admitted to KK Women’s and Chil-
dren’s Hospital (KKH), Singapore between December 2013
and February 2014. Our study examined the clinical
epidemiology, risk factors and clinical profile of children
admitted for measles.
This is a single-institution, retrospective study of patients
with measles infection who were admitted to KKH between
January 2013 and May 2014. Patients were identified from
the KKH laboratory database, based on positive detection
of measles virus RNA.
After identifying the patients, information was gathered
on the demographics (age, gender, positive travel history to
areas with documented measles outbreaks, and whether
they had previously received MMR vaccination), clinical
presentation (including history, physical examination), in-
vestigations, treatment and outcome of the patients. A
positive travel history for measles was defined as measles
resulting from exposure to measles virus during travel
outside Singapore 7e21 days before rash onset, and rash
onset occurring within 21 days of re-entering Singapore,
with no known exposure to measles in Singapore during that
time. A nosocomial case of measles was defined as any
patient with measles who had contact with a confirmed
measles case in the hospital 7e21 days before rash onset
and had no other source identified. Pneumonia was diag-
nosed by chest X-ray, based on the detection of pulmonary
infiltrate or consolidation. Analysis was done using the SPSS
software version 17.0 software (IBM, Armonk, New York,
USA). Differences between categorical variables were
analysed for statistical significance using the chi-square
test and Fisher’s exact test. Differences between contin-
uous variables were analysed for statistical significance
using ManneWhitney U test. P values are considered sta-
tistically significant at <0.05. This study was approved by
the Singhealth institutional review board.
Results
Demographics
A total of 68 children with measles were identified during
the study period. Table 1 shows the demographic
194 V.N. Vemula et al.

Table 1 Demographics of children in the study. Travel to

Philippines
Demographics No. Percentage Positive travel
history to n=9
Gender Male 43 63.2 countries with (52.9%)
Female 25 36.8 documented
measles
Ethnicity Chinese 29 42.6 Total no. of cases admitted outbreaks Travel to
Malay 14 20.6 during the dramatic Indonesia
n=17 (51.5%)
Indian 6 8.8 increase in measles cases n=6
from (35.3%)
Filipino 2 2.9
Dec 2013 to Feb 2014 Negative
Indonesian 1 1.5 travel history
(n=33)
Others 16 23.5 n=16 (49.5%)
Age <12 months 37 54.4
<24 months 55 80.9
Figure 2 Number of children with positive travel history to
countries with documented measles outbreaks.

characteristics. There were 43 boys (63.2%), 55 (80.9%) travel history to countries with documented measles out-
were <24 months and 37 (54.4%) <12 months of age (age breaks at the time-Philippines, 52.9%; Indonesia, 35.3%
range: 3e130 months). (Fig. 2); others, 11.8%. This was significantly higher
The majority of patients (89.7%) did not receive MMR compared to the children admitted for measles during the
vaccination, and 10.3% received only 1 dose (incomplete other months (OR 5.13, 95% CI 1.686e15.625).
vaccination). Of the 7 cases who only received 1 dose of There were 3 nosocomial cases of measles (between 7
MMR, we had the date MMR was administered for 5 of them, January and 24 February 2014). Two of these were girls
and 4 out of 5 patients (80%) received 1 dose of MMR < 14 (66.7%), and the ages ranged from 6 months to 20 months.
days prior to date of admission for measles (insufficient None of the 3 cases received MMR vaccine. To prevent
time for them to mount an adequate immune response). further nosocomial transmission of measles, KKH Children’s
The remaining patient received 1 dose of MMR 2 years prior Emergency was alerted in January 2014 to pre-emptively
to admission for measles. isolate all children with fever and rash without prior history
The infection control unit in KKH tracks all inpatients of completing their MMR vaccines, especially in those who
diagnosed with measles, and does the contact tracing for have travelled in the last 21 days. There were no further
any exposed patients and staff. During late 2013, the hos- nosocomial cases of measles after 24 February 2014.
pital noticed an increase in the number of children
admitted with measles, with 5 cases in December 2013, and
Clinical presentation
11 cases in January 2014. This increased to 17 cases in
February 2016. This represented a 500e1000% year-on-year
All children (100%) presented with fever. Other common
increase, since KKH usually admitted about one case of
symptoms and signs were rash (92.6%), cough (92.6%), rhi-
measles per month or per two months (unpublished find-
norrhea (70.6%), vomiting (41.2%), diarrhea (36.8%),
ings). Fig. 1 shows the increase in the numbers of measles
conjunctivitis (33.8%), Koplik spots (19.1%), mouth ulcers
cases admitted between December 2013 and February
(13.2%), dyspnea (13.2%), sore throat (7.4%), purulent eye
2014.
discharge (4.4%) and febrile seizures (2.9%). The most
Of the 33 patients admitted during the peak period from
common complication was pneumonia (17.6%) followed by
December 2013 to February 2014, 17 (51.5%) had a positive
gastroenteritis complicated by dehydration (10.3%).
Infants had a lower risk compared to children >12
months of age of developing lymphopenia and conjuncti-
18 vitis (OR 0.029, 95% CI 0.003e0.244 and 0.294, 95% CI
16 0.103e0.843 respectively) but had a higher risk of devel-
oping diarrhea (OR 3.25, 95% CI 1.13e9.38).
Number of measles cases per month

14
All the patients in the study were treated in the general
12
ward, and none required admission to the high dependency
10 or intensive care unit. All children recovered well. None of
8 the children received Vitamin A treatment. There was no
6 difference in outcome between community-acquired and
4
nosocomial cases of measles (median length of stay 3.0
versus 3.0 days, p Z 0.900).
2

0
Jan Apr May Aug Sep Oct Nov Dec Jan Feb Mar Apr May Discussion
2013 2014
Calendar Month
The marked increase in measles cases identified during this
study serves as a reminder for health-care providers to be
Figure 1 Number of measles cases admitted per month in aware of the possibility of measles infection occurring in
the study period. the Singaporean community when there are documented
Childhood measles infection in Singapore
measles outbreaks in neighbouring countries, such as the
Philippines or Indonesia. In the USA, as of November 15,
2015, the annual number of measles cases was 189. Of
those cases, 113 were related to the outbreak of measles
linked to Disneyland (CA, USA) at the beginning of 2015,
thought to have been caused by a visitor to the amusement
park who had become infected overseas and then visited
the park while being infectious. This outbreak together
with another one in Ohio’s Amish country in 2014, in which
383 people fell ill after unvaccinated missionaries travelled
to the Philippines and returned with measles infection, has
raised concerns over the efficiency of the American na-
tional health-care system [6].
In our study, the majority of measles patients (89.7%) did
not receive any MMR vaccination, and a smaller proportion
(10.3%) received only 1 dose. When it comes to the measles
vaccine, two vaccinations after 12 months of age are better
than one, resulting in 97% protection compared to 93%. A
report on a measles outbreak in Lyon, France, in 2010e2011
highlighted the importance of being vaccinated with 2
doses of measles-containing vaccine, which was the only
measure which prevented and allowed elimination of
measles [7]. After the outbreak in early 2015, California
made the vaccination booster against measles mandatory.
In some provinces of Canada, such as Ontario, proof of
vaccination is required for children to attend school [6].
However, exemption for medical, religious, and personal
reasons is still allowed. In Australia, vaccinations are not
mandatory, but parents who do not immunize their children
are not entitled to a variety of tax benefits and child-care
reimbursements [5].
Our study looked into the clinical profile of children with
measles. The most common complications identified in this
study are pneumonia, followed by gastroenteritis compli-
cated by dehydration. Infants had a higher risk of devel-
oping diarrhea (OR 3.25, 95% CI 1.13e9.38) compared to
older children. A study on the measles outbreak in
Macedonia in 2010e2011 also showed that most patients
suffered from bronchopneumonia or diarrhea; and infants
had the highest rate of diarrhea at 53.2% [8].
There were 3 nosocomial cases of measles in our study.
None of them had received MMR vaccine. Incomplete or
partial vaccination, under age for routine vaccination and
hospital admission were associated with measles infection
in a matched case-control study in Merseyside, UK during an
outbreak in 2012 [9]. A case-control study in Guangxi, China
during an outbreak in 2013 also revealed 2 independent risk
factors for measles-low education level of the main care-
givers (OR 2.86; 95% CI 1.31e6.22) and visiting a hospital
7e21 days before the date of symptoms onset (OR 9.84, 95%
CI, 4.27e22.67). The population attributable fraction
(contribution of a risk factor to a disease) of the latter was
52.8% [10].
All children in our study recovered well. There was no
difference in outcome in terms of length of stay between
community-acquired and nosocomial cases of measles in
our study. A possible reason is that none of the 3 nosocomial
cases of measles were immunocompromised. In contrast,
one review of nosocomial transmission of measles showed
that nosocomial measles transmission was associated with
high mortality and morbidity [11]. Marshall et al. reported a
series of 14 children with hospital-acquired measles; all
195
suffered complications, and two died. In that outbreak, 50%
of the measles-infected children were HIV-positive [12].
Thus, patients exposed to measles in hospital settings may
be at increased risk for a severe outcome given their un-
derlying medical condition [13].
To prevent nosocomial transmission of measles, KKH
Children’s Emergency was alerted in January 2014 to pre-
emptively isolate all children with fever and rash without
prior history of completing their MMR vaccines, especially
those who travelled during the last 21 days. There were no
further nosocomial cases of measles after 24 February
2014. In the KKH guideline for isolation precautions, all
pediatric patients presenting with fever and rash and nil or
incomplete MMR vaccination should be isolated as soon as
possible, even before measles is confirmed by laboratory
testing, in order to reduce the risk of exposing other
people to measles. The use of strict respiratory isolation
with the deployment of masks and alcohol-based hand
hygiene is recommended. The use of private rooms with
negative pressure air ventilation, where feasible, is also
recommended [14].
In our hospital, treatment with vitamin A was only
routinely implemented in 2014, thus we were not able to
evaluate the efficacy of vitamin A in our study. Vitamin A is
effective for the treatment of measles and can result in a
reduction in morbidity and mortality. Acute measles pre-
cipitates vitamin A deficiency by depleting vitamin A stores
and by increasing its utilization, which leads to severe in-
fections [15]. The World Health Organization (WHO) rec-
ommends the administration of once daily doses of 200,000
IU of vitamin A for 2 consecutive days to all children aged 12
months or older who have measles, while lower doses are
administered for younger children [16].
In our study, 54.4% of the children were younger than 1
year of age, and had not received MMR vaccination. For
adults in Singapore aged 20e40 years of age, over 95% of
them were seropositive for measles [5]. Babies born to
women in Singapore who are 20e40 years of age could be
protected from measles in the first few months of life due
to maternal antibodies. In countries where measles inci-
dence remains high in infants, the first dose of MMR is given
at 6e9 months of age [17,18]. Hanley’s paper has suggested
that initiating MMR vaccination at an earlier age (6e9
months of age) can be a consideration in Singapore should
epidemiological trends in the future warrant such a
change [5].
The spike in measles cases in Singapore was reported in
the local newspaper on May 10 2014, with the 2014’s figure
already exceeding that of 2012e2013. Members of the
public were urged to go for MMR vaccination if they were
eligible for vaccination and not yet completed 2 doses of
vaccine [19].
Conclusions
Apart from absent or incomplete MMR vaccination, which
was observed in all (100%) of our cases, risk factors for
measles infection in children included age <24 months
(80.9%) and positive travel history to countries with
documented measles outbreaks. Continued cross border
surveillance and monitoring of measles and, timely
196
administration of MMR vaccinations therefore constitute
essential measures to prevent acquisition and transmission
of measles.
Ethics
The study was approved by the Singhealth institutional re-
view board (IRB).
Authorship statement
The undersigned warrant that the article is original, does
not infringe upon any copyright or other proprietary right of
any third party, is not under consideration by another
journal and has not been previously published. The authors
confirm that they have reviewed and approved the final
version of the manuscript and that they have taken due
care to ensure its integrity.
Conflict of interest
The authors declare that there is no conflict of interest.
Funding
There has been no funding provided for the creation of this
manuscript.
Provenance and peer review
Not commissioned; externally peer reviewed.
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