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ORIGINAL ARTICLE

Epidemiologic and laboratory surveillance of the measles outbreak in the


Federation of Bosnia and Herzegovina, February 2014–April 2015

I. Salimovi
c-Besi 
c1, M. Seremet1
, J. M. Hübschen8, M. Hukic2,3, N. Tihic6, S. Ahmetagic7, Z. Delibegovic6, A. Pilav4,
c5, J. Ravlija5, C. P. Muller8 and A. Dedeic-Ljubovic1
M. Mulaomerovi
1) Department of Clinical Microbiology, University Clinical Centre Sarajevo, 2) Department of Genetics and Bioengineering, International Burch University,
Ilidza, 3) Department of Medical Sciences, Academy of Sciences and Arts of Bosnia and Herzegovina, 4) Department for Public Health, Monitoring and Evaluation,
Federal Ministry of Health, 5) Department of Epidemiology, Institute for Public Health of Federation Bosnia and Herzegovina, Sarajevo, Bosnia and
Herzegovina, 6) Department of Microbiology, Polyclinic of Laboratory Diagnostics, 7) Department for Infectious Diseases, University Clinical Center Tuzla, Tuzla,
Bosnia and Herzegovina and 8) Department of Infection and Immunity, WHO European Regional Reference Laboratory for Measles and Rubella, Luxembourg
Institute of Health, Esch-sur-Alzette, Luxembourg

Abstract

A measles outbreak with two epidemic waves involving 4649 probable and laboratory-confirmed cases was recorded in six out of ten
cantons of the Federation of Bosnia and Herzegovina between February 2014 and April 2015. The majority of the patients had never
received measles vaccination (3115/4649, 67.00%), and the vaccination status of another 23% was unknown (1066/4649). A total of 281
blood samples were tested serologically. Virus detection was performed using 44 nasopharyngeal swabs. About 57% (161/281) of the
laboratory-investigated sera were immunoglobulin M positive, and 95% (42/44) of the swabs were reverse transcriptase–PCR positive.
Phylogenetic analysis of sequences obtained from 30 swab samples showed circulation of two variants of genotype D8, but no genotype
D4 strains as detected in 2007. Similar involvement of all age groups indicates a problem with vaccine refusal resulting from
antivaccination activities in addition to gaps in immunization coverage during the war and postwar period (1992–1998). Differences in
ethnicity, vaccine coverage, compliance with review policies of vaccination records and potentially also travel habits may partially explain
why only six of ten cantons were affected by the outbreak. The second epidemic wave may in part be due to large-scale migrations
due to catastrophic floods in 2014. As a result of the epidemic, 6- to 12-month-old children may now be vaccinated against measles
during outbreaks, and public health recommendations for interventions have been strengthened. Additional efforts are required to
implement the measures throughout the cantons.
© 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Keywords: Bosnia and Herzegovina, measles, measles–mumps–rubella (MMR) vaccine, outbreaks, vaccine-preventable diseases, vaccines
and immunization
Original Submission: 8 October 2015; Revised Submission: 18 January 2016; Accepted: 19 February 2016
Editor: L. Kaiser
Article published online: 27 February 2016

Introduction
Corresponding author: I. Salimovic-Besic, University Clinical
Centre Sarajevo, Department of Clinical Microbiology, Bolnicka 25,
71000 Sarajevo, Bosnia and Herzegovina
E-mail: irma.salimovic_besic@yahoo.com Measles is a highly contagious viral disease caused by the
measles virus, which belongs to the genus Morbillivirus within
the family Paramyxoviridae [1]. A characteristic rash develops
several days after infection in the face and the upper neck and
gradually spreads to the rest of the body. In some cases measles

Clin Microbiol Infect 2016; 22: 563.e1–563.e7


© 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved
http://dx.doi.org/10.1016/j.cmi.2016.02.005
563.e2 Clinical Microbiology and Infection, Volume 22 Number 6, June 2016 CMI

can cause serious complications, including pneumonia, ear in- number of cases within the total population in a given area
fections, blindness, encephalitis and severe diarrhoea [1]. during a defined period of the outbreak, were calculated for
The World Health Organization (WHO) currently recog- each canton and the entire FB&H [8].
nizes eight clades of measles virus and 24 genotypes (A, B1–B3,
C1, C2, D1–D11, E, F, G1–G3, H1 and H2) [2]. Sequence Sample collection
variants within genotypes provide a more sensitive epidemio- Between 1 February 2014 and 30 April 2015 a total of 281
logic surveillance of measles strains [2]. patient sera and 44 nasopharyngeal swab samples were
Immunoprophylaxis is the best protection against measles received for laboratory analysis. Sera only were available from
and its complications, and the benefit of vaccination by far 254 patients, swabs only from 17 patients and paired serum and
exceeds its potential adverse effects. In the Federation of Bosnia nasopharyngeal swabs from 27 patients. Thus, overall, 298 pa-
and Herzegovina (FB&H), children have been vaccinated against tients were laboratory investigated. Their average age was
measles since 1970, and since 1981 the combined measles– 17.86 years (range <1–68 years). A single blood sample was
mumps–rubella (MMR) vaccine is in use, as recommended by taken at first contact with a healthcare provider and, as rec-
the WHO. The first dose is normally given at 12 months of age ommended, within 28 days after rash onset [8]. The swabs
and the second dose at the age of 6 years (http://www.zzjzfbih. were obtained within 7 days of rash onset from patients hos-
ba/wp-content/uploads/2014/02/VODI%C4%86-ZA-NAD- pitalized at University Clinical Centre Sarajevo (Sarajevo
ZOR-NAD-MORBILIMA.pdf) [3]. In 2013, 17 825 children up Canton), University Clinical Center Tuzla (Tuzla Canton) or
to 2 years of age in FB&H received the first and 17 754 children Cantonal Hospital Zenica (Zenica-Doboj Canton). One serum
at the age of 6 years received the second dose of MMR vaccine, sample and a nasopharyngeal swab were collected from a pa-
and no adverse effects or serious complications were reported tient with meningitis hospitalized at the University Clinical
(http://www.zzjzfbih.ba/wp-content/uploads/2014/02/VODI% Center Tuzla but originating from outside of FB&H (District
C4%86-ZA-NADZOR-NAD-MORBILIMA.pdf). Brcko).
In recent years FB&H has faced several outbreaks of vaccine-
preventable diseases. In 2009–2010 a rubella epidemic involved Serology
1900 cases [4]. This was followed by an epidemic of mumps in Routine laboratory confirmation of suspected cases was based
2010–2012 with 7895 reported cases [5,6] and a measles on detection of measles-specific immunoglobulin (Ig) M anti-
outbreak in 2014–2015. After the last measles outbreak in bodies performed either at the University Clinical Centre
FB&H in 2007 caused by genotype D4 [7] until the beginning of Sarajevo, Department for Clinical Microbiology or University
2014 (February) only sporadic cases of measles were reported Clinical Center Tuzla, Polyclinic of Laboratory Diagnostics,
(http://www.zzjzfbih.ba/page/6/?s=morbili). Department of Microbiology, using a commercial indirect
The purpose of this article is to describe the ongoing measles enzyme immunoassay kit (Enzygnost Anti-Measles Virus/IgM;
outbreak in FB&H combining both epidemiologic and labora- Siemens, Marburg, Germany) and the fully automated instru-
tory data. The causes of the outbreak as well as potential mentation system BEP 2000 Advance (Siemens, Marburg,
measures to prevent future outbreaks of vaccine-preventable Germany). Serologic results were expressed as the difference in
diseases in FB&H are discussed. absorbance ΔA multiplied by the correction factor (ΔA nomi-
nal value/mean ΔA valueReference P/P). On the basis of the criteria
of the test, the samples were classified as follows: IgM results
Methods were scored as negative (ΔA < 0.100), equivocal
(0.100  ΔA  0.200) or positive (ΔA > 0.200), as recom-
Case investigation mended by the manufacturer.
Clinical case definition of suspected measles involved any per-
Measles virus PCR
sons with fever along with generalized maculopapular rash, and
Detection of virus RNA was used alone or to complement
cough, coryza or conjunctivitis [8]. Suspected cases are re-
serologic testing and was carried out at the University Clinical
ported by medical doctors to the Institute for Public Health of
Centre Sarajevo. RNA extraction was done according to the
FB&H, which collects all relevant patient information. Between
QIAamp Viral RNA Mini kit protocol (Qiagen, Hilden, Ger-
February 2014 and April 2015 epidemiologic data of 4649
many). For nested reverse transcriptase (RT)-PCR, previously
clinically suspected measles cases were collected (http://www.
published primer sets were used (MN1/MN2 and MN3/MN4)
zzjzfbih.ba/morbili/). The vaccination status of patients was
[9], with the difference that reverse transcription and first
obtained from their medical records or, if unavailable for adults,
round amplification were done in a one-step format.
was recorded during anamnesis. Attack rates, expressing the
© 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved, CMI, 22, 563.e1–563.e7
CMI Salimovi
c-Besi
c et al. Measles outbreak in FB&H, 2014–2015 563.e3

Sequence analysis 2015 (Table 1). According to the latest estimation of the
A total of 30 nasopharyngeal swabs were forwarded to the population density (http://www.fzs.ba/Podaci/Brojke2014.pdf)
WHO European Regional Reference Laboratory for Measles Central Bosnia Canton had the highest attack rate (1283/
and Rubella in Luxembourg for sequencing and genotyping. 253 149, 0.51%) (Table 1). Two distinct epidemic waves were
Sequences were analysed by SeqScape Software 2.5 (Thermo observed. The first wave occurred between week 7 (February)
Fisher Scientific Life Sciences, Waltham, MA, USA), BioEdit and week 36 (September) of 2014 and the second from week
version 7.0.9.0 [10] and molecular evolutionary genetics anal- 37 (September) of 2014 to at least week 18 (April) of 2015. A
ysis (MEGA4) software [11]. Neighbour-joining phylogenetic drop in case numbers was observed in weeks 36 and 37 of
trees based on the Kimura two-parameter model were con- 2014, with only 19 cases each (Fig. 1). Central Bosnia and
structed using 450 nucleotides coding for the COOH-terminal Sarajevo had the highest numbers of cases during the first
150 amino acids of the measles virus nucleoprotein. The rec- epidemic wave (2063/2407, 85.71%), while during the second
ommended set of reference sequences [2], current sequence wave mainly the cantons of Una Sana and Tuzla were affected
variants of genotype D8 and close BLAST (Basic Local Align- (1696/2242, 75.64%).
ment Search Tool) fits of sequences from FB&H were included The highest proportion of cases was found in the 15- to 19-
in the phylogenetic analysis. All new sequences were submitted year age group (814/4649, 17.51%) and the lowest in children
to the MeaNS (http://www.who-measles.org/Public/Web_ under 1 year of age (484/4649, 10.41%) (Fig. 2).
Front/main.php) and GenBank databases. Two-thirds of the patients had never received the measles
vaccine (3115/4649, 67.00%), and the vaccination status of
about one quarter was unknown (1066/4649, 22.92%). About
Results
8% of the patients (376/4649, 8.09%) were immunized with
one dose of measles-containing vaccine, while only about 2%
Description of outbreak (92/4649, 1.98%) had received two doses of the MMR vaccine.
The first two measles cases reported from Bugojno beginning Figure 2 suggests that the proportion of patients without
of February 2014 were teenage siblings who had recently vaccination decreased with age, while the proportion with
visited Germany [12]. The first laboratory-confirmed measles unknown vaccination status increased. Children below 1 year
case (11 February 2014) linked to the outbreak was an un- of age are not eligible for vaccination according to the immu-
vaccinated 13-year-old girl. The disease spread among school- nization schedule in FB&H, but for some of them (21/484,
children from different municipalities of the Central Bosnia 4.34%) an unknown status was declared since their vaccination
Canton. Beside this canton, another five cantons of FB&H were records were not available. Children aged <6 years were in
affected: Sarajevo, Una-Sana, Tuzla, Zenica-Doboj and principle not eligible for the second dose of vaccine, as indi-
Herzegovina-Neretva (Fig. 1); a single sporadic case was cated by the average percentage of patients with a single vac-
recorded in the Posavina Canton. A total of 4649 suspected cine dose in the age brackets 1–4 and 5–9 years (10.99 vs.
cases were reported between 1 February 2014 and 30 April 8.09%, Fig. 2).

700 Una-Sana Canton

600 Tuzla Canton

500 Zenica-Doboj Canton


Number of cases

400 Central Bosnia Canton


300 Herzegovina-Neretva
Canton
200 Sarajevo Canton
100 FB&H
0

Month/Year
FIG. 1. Number of cases by month in six most affected cantons in Federation of Bosnia and Herzegovina.
© 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved, CMI, 22, 563.e1–563.e7
563.e4 Clinical Microbiology and Infection, Volume 22 Number 6, June 2016 CMI

TABLE 1. Outbreak attack rate estimated for involved cantons of the FB&H during the first and the second wave of the outbreak

No. of cases Attack rate (%) No. of cases Attack rate (%) No. of casesb Attack rate (%)

Canton Population no. a


Outbreak’s first wave Outbreak’s second wave Total

Una-Sana 287 621 151 0.05 546 0.19 697 0.24


Posavina 3896 0 NA 1 0.00 1 0.00
Tuzla 498 911 16 0.00 1150 0.23 1166 0.23
Zenica-Doboj 398 655 142 0.04 138 0.03 280 0.07
Central Bosnia 253 149 1259 0.50 24 0.01 1283 0.51
Herzegovina-Neretva 224 388 35 0.02 36 0.02 71 0.03
Sarajevo 442 669 804 0.18 347 0.08 1151 0.26
FB&H 2 337 200 2407 0.10 2242 0.10 4649 0.20

The attack rate expresses the number of cases among the total population in a given area during a defined period of the outbreak [8].
a
Estimation as of 30th June 2013 (http://www.fzs.ba/Podaci/Brojke2014.pdf).
b
Number of cases until 30th April 2015.

Laboratory results Slovenia, Sweden and Austria as well as the United States
About 57% (161/281) of the serum samples were IgM positive. (Fig. 3). The second variant (n = 8) was found only during the
Among all swab samples analysed by RT-PCR, 95.45% (42/44) second outbreak wave, and no identical strains were identified
were positive. The two negative samples were also negative by by BLAST (Fig. 3). Sequences from Germany and Slovenia
nested PCR. Of the 27 patients with paired serum and swab differed by at least one nucleotide from this new variant (Fig. 3).
samples, 26 were IgM/RT-PCR double positive and 1 was IgM/
nested RT-PCR double negative.
Discussion
A total of 30 samples (18 from the first wave collected
during 11 February–23 July 2014 and 12 from the second wave
collected during 6 to 21 February 2015) were sequenced Most patients with measles were not vaccinated or had an
(GenBank accession nos. KR632648–KR632676 and unknown vaccination status. Gaps in the immunization program
KR704878). in the war (1992–1995) and postwar period (1996–1998) left
All sequences belonged to genotype D8. The two sequence many children susceptible to measles, rubella and mumps
variants differed by two nucleotides in the 450 nucleotide re- [4–6]. At the time of the current outbreak, the war generation
gion of the measles virus N gene. One variant was found in both had reached the age of 16 to 23 years, largely falling into the
the first and second outbreak waves (n = 22) and had previously most affected age bracket. The high incidence in the 1- to 9-
been reported from different European countries such as Italy, year-old children may be related to the insufficient

Unknown vaccination status 0 doses 1 dose 2 doses

Total 1066 3115 376 92 100% (4649)

≥ 30 years 363 290 42 8 15.12% (703/4649)

20-29 years 216 308 51 14 12.68% (589/4649)


Age group

15-19 years 191 521 71 31 17.51% (814/4649)

10-14 years 100 419 50 16 12.58% (585/4649)

5-9 years 85 500 78 22 14.73% (685/4649)

1-4 years 90 614 84 1 16.97% (789/4649)

< 1 year 21 463 10.41% (484/4649)

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
Number of cases and percentage

FIG. 2. Measles cases and their vaccination status by age group during epidemic in Federation of Bosnia and Herzegovina, February 2014–April 2015
(n = 4649).
© 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved, CMI, 22, 563.e1–563.e7
MVs/Tuzla.BIH/6.15
MVs/Gradacac.BIH/6.15
MVs/Lukavac.BIH/5.15/2
MVs/Lukavac.BIH/5.15
MVs/Lukavac.BIH/6.15
MVs/Lukavac.BIH/7.15
MVs/Tuzla.BIH/6.15/2
MVs/Lukavac.BIH/6.15/2
MVs/Fuerth.DEU/31.14 D8 KM586153
MVs/Celje.SVN/3.15/2 D8 KP835278
MVs/Hadzici.BIH/23.14
MVs/Sarajevo.BIH/23.14/2
MVs/Sarajevo.BIH/13.14/2
MVs/Florida.USA/12.15 D8 KR914665
MVs/Brcko.BIH/7.15
MVs/Fojnica.BIH/23.14
MVs/Sarajevo.BIH/23.14
MVs/Banovici.BIH/7.15
MVs/Bolzano.ITA/04.15 D8 KR349627
MVs/Sarajevo.BIH/23.14/3
MVs/Tuzla.BIH/7.15
89
MVs/Sarajevo.BIH/30.14/2
MVs/Bugojno.BIH/07.14/2
MVs/Sarajevo.BIH/13.14
MVs/Tuzla.BIH/5.15
MVs/Malmo.SWE/19.15/2 D8 KT099182
MVs/Visoko.BIH/16.14
MVs/Sarajevo.BIH/30.14
MVs/Sarajevo.BIH/13.14/4
99
MVs/Bugojno.BIH/07.14
MVs/Sarajevo.BIH/23.14/4
MVs/Fojnica.BIH/23.14/2
MVs/Visoko.BIH/16.14/2
MVs/NovaGorica.SVN/15.15/2 D8 KR780259
MVs/Sarajevo.BIH/13.14/3
MVs/Bugojno.BIH/07.14/3
98 MVs/Gaenserndorf.AUT/51.13 D8 KJ494386
MVs/Frankfurt Main.DEU/17.11 D8 KF683445
MVi/Villupuram.IND/03.07 D8 FJ765078
99
MVs/Taunton.GBR/27.12 D8 JX984461
94 MVs/Swansea.GBR/4.13 D8 KF214761
MVi/Manchester.GBR/30.94 D8 AF280803
88 MVi/Hulu Langat.MYS/26.11 D8 JX486001
MVi/Menglian.Yunnan.CHN/47.09 D11 GU4405
MVi/Victoria.AUS/16.85 D7 AF243450
78 MVi/Illinois.USA/50.99 D7 AY037020
MVi/Montreal.CAN/0.89 D4 U01976
MVi/Victoria.AUS/12.99 D9 AF481485
MVi/Illinois.USA/0.89/1 D3 U01977
MVi/Palau/0.93 D5 L46758
MVi/Bangkok.THA/0.93/1 D5 AF079555
MVi/Johannesburg.ZAF/0.88/1 D2 U64582
MVi/Kampala.UGA/51.01/1 D10 AY923185
MVi/Bristol.GBR/0.74 D1 D01005
MVi/New Jersey.USA/0.94/1 D6 L46750
81 MVi/Amsterdam.NLD/49.97 G2 AF171232
71 MVi/Gresik.IDN/17.02 G3 AY184217
MVi/Berkeley.USA/0.83 G1 U01974
MVi/Hunan.CHN/0.93/7 H1 AF045212
85 MVi/Beijing.CHN/0.94/1 H2 AF045217
MVs/Madrid.ESP/0.94(SSPE) F X84865
99 MVi/Maryland.USA/0.77 C2 M89921
MVi/Erlangen.DEU/0.90 C2 X84872
MVi/Tokyo.JPN/0.84 C1 AY043459
MVi/Goettingen.DEU/0.71 E X84879
MVi/Maryland.USA/0.54 A U01987
MVi/Libreville.GAB/0.84 B2 U01994
FIG. 3. Phylogenetic tree showing MVi/Yaounde.CMR/12.83 B1 U01998
89
MVi/New York.USA/0.94 B3 L46753
measles viruses involved in outbreak in
74 MVi/Ibadan.NGA/0.97/1 B3 AJ232203
Federation of Bosnia and Herzegovina
during February 2014–April 2015. 0,01

© 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved, CMI, 22, 563.e1–563.e7
563.e6 Clinical Microbiology and Infection, Volume 22 Number 6, June 2016 CMI

vaccination coverage due to the more recently emerging anti- FB&H during the first quarter of 2007 (MVs/Sarajevo.BIH/
vaccination activities in FB&H and abroad [12–14], but also to 11.07/1) [7], was no longer found in 2014–2015. Instead, all
the often late and inadequate control measures to primary new sequences belonged to genotype D8, which seems to
outbreaks in school settings [12]. have replaced D4 as endemic genotype in FB&H [12]. Geno-
For the successful elimination of measles, a vaccine type D8 is currently widespread in Europe and beyond, and
coverage of at least 95% is required (http://apps.who.int/iris/ several sequence variants such as Taunton, Villupuram,
bitstream/10665/44855/1/9789241503396_eng.pdf). In FB&H, Frankfurt Main, Swansea and Hulu Langat have already been
the average coverage rate of MMR1 between 1998 to 2014 defined (http://www.who-measles.org/Public/Web_Front/main.
was 87.05% (lowest in 1999 with 80.70%; highest in 2007 with php). One of two genotype D8 variants from FB&H had also
96.20%), and for MMR2 was 83.92% (minimum 53.00% in been found in several European countries and the United
2006; maximum 91.90% in 2008) (Institute for Public Health States and may be part of a larger transmission chain. The
FB&H, unpublished data). Vaccine coverage is particularly low second variant was unique and has not yet been reported from
in Roma children in B&H [15]: only 22% of 18-month-old anywhere else in the world. While epidemiologic evidence
children had received their MMR1 dose, which is recom- points to an introduction of the first variant from Germany,
mended at 12 months of age. The Roma population was members of the FB&H diaspora are known to live in Austria,
affected by the current outbreak, but unfortunately ethnicity Italy, Slovenia, Sweden and the United States, all of which
is not recorded in the questionnaires. According to unpub- reported the same sequence variant. All eight sequences of the
lished data, the largest number of Roma live in Tuzla Canton, second variant were from samples obtained during the second
followed by Sarajevo Canton, which were two of the three outbreak wave from the municipalities of Tuzla, Lukavac and
cantons with the highest incidence rates. Differences in Gradacac (Tuzla Canton). During the second wave, both var-
ethnicity, vaccine coverage, compliance with review policies of iants were circulating only in the municipality of Tuzla. Since
vaccination records and potentially also travel habits may only contacts with cases or cities/cantons affected by variant 1
partially explain why essentially only six of the ten cantons of were known, possibly the new variant emerged during the
FB&H were affected by the outbreak. The second epidemic current epidemic.
wave may be partially explained by large-scale migrations Besides the previously described contributions to outbreak
between May and September 2014 due to catastrophic floods, control [12], the Institute for Public Health of FB&H published a
in particular in Zenica-Doboj, Tuzla, Una-Sana and Posavina ‘Guideline for Measles Surveillance’ for healthcare professionals
cantons. (http://www.zzjzfbih.ba/wp-content/uploads/2014/02/VODI%
The 92 patients (1.98%) who were fully immunized may have C4%86-ZA-NADZOR-NAD-MORBILIMA.pdf) to support the
had primary or secondary vaccine failure [16]. WHO’s measles elimination efforts (http://apps.who.int/iris/
No discrepancy was observed between IgM serology and bitstream/10665/44855/1/9789241503396_eng.pdf). Further-
nested RT-PCR for 27 patients with paired samples collected more, according to a recent decree, children from 6 to
between day 1 and 12 after rash onset. However, the low 12 months of age may be vaccinated against measles in outbreak
overall IgM positivity (56.58%) may be partly the result of situations, provided that they are revaccinated at the age of 15
cocirculation of other rash/fever-causing agents such as rubella to 24 months. Immunization against measles and rubella may be
virus, parvovirus B19 or human herpesvirus 6. Unfortunately, carried out in people aged 15 to 18 years who have not
data on the differential diagnosis of febrile rash illness were not received two doses of measles- and at least one dose of rubella-
available, except for 38 patients, two of whom were IgM pos- containing vaccine until the age of 14 years. Administration of
itive for other pathogens (rubella and Coxsackie virus). Because one or two doses of monovalent measles vaccine (with an in-
laboratory request forms are often poorly filled out, it cannot terval of 3 months) or a single dose of monovalent vaccine
be completely excluded that a few of the sera were for checking against rubella is recommended (http://www.fmoh.gov.ba/
measles immunity rather than IgM antibodies. Given the huge images/federalno_ministarstvo_zdravstva/preporucujemo/
extent of the outbreak and the high number of suspected cases, Naredba_imunizacija_21_15.pdf). Other established supple-
we do, however, not expect this number to be very high. mentary immunization activities include vaccination of in-
Despite the possibility of false-negative IgM results in samples dividuals who had contacts with measles patients within
collected before 72 hours after rash onset, no later samples 72 hours of contact. However, adherence to the recommended
were available for investigation. guidelines must be strictly enforced. Despite all these measures,
A total of 30 PCR-positive samples were sequenced and refusal of vaccines and antivaccination activities will continue to
genotyped. Interestingly, genotype D4, which was present in lead to increasing numbers of susceptible children.

© 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved, CMI, 22, 563.e1–563.e7
CMI Salimovi
c-Besi
c et al. Measles outbreak in FB&H, 2014–2015 563.e7

Conclusions [4] Hukic M, Hübschen JM, Seremet M, Salimovic-Besic I,


Mulaomerovic M, Mehinovic N, et al. An outbreak of rubella in the
Federation of Bosnia and Herzegovina between December 2009 and
May 2010 indicates failure to vaccinate during wartime (1992–1995).
Awareness campaigns highlighting the benefits of vaccination to
Epidemiol Infect 2011;28:1–7.
support the implementation of the WHO strategic plan for [5] Hukic M, Ravlija J, Dedeic Ljubovic A, Moro A, Arapcic S, Muller CP,
2012–2020 for measles and rubella elimination should improve et al. Ongoing large mumps outbreak in the Federation of Bosnia and
Herzegovina, Bosnia and Herzegovina, December 2010 to July 2011.
vaccine coverage and measles control. Since molecular sur-
Euro Surveill 2011;16:19959.
veillance has shown that endemic genotypes can change rela- [6] Hukic M, Hajdarpasic A, Ravlija J, Ler Z, Baljic R, Dedeic Ljubovic A,
tively quickly, constant monitoring of cases and outbreaks is et al. Mumps outbreak in the Federation of Bosnia and Herzegovina
necessary, and the timely sharing of data is critical. with large cohorts of susceptibles and genetically diverse strains of
genotype G, Bosnia and Herzegovina, December 2010 to September
In addition to gaps in vaccination coverage during the war 2012. Euro Surveill 2014;19:20879.
and postwar period (1992–1998), vaccine refusal due to anti- [7] Kremer JR, Brown K, Jin L, Santibanez S, Shulga V, Aboudy Y, et al.
vaccination activities contributed to the recent measles High genetic diversity of measles virus, World Health Organization
European Region, 2005–2006. Emerg Infect Dis 2008;14:107–14.
outbreak. Differences in ethnicity, vaccine coverage, compli-
[8] Response to measles outbreaks in measles mortality reduction settings.
ance with review policies of vaccination records and potentially Geneva: World Health Organization; 2009. WHO/IVB/09.03.
also travel habits may partially explain why only certain cantons [9] Tischer A, Santibanez S, Siedler A, Heider A, Hengel H. Laboratory
investigations are indispensable to monitor the progress of measles
were affected. Public health recommendations for interventions
elimination—-results of the German Measles Sentinel 1999–2003.
have been strengthened, but additional efforts are required to J Clin Virol 2004;31:165–78.
implement them throughout the cantons. [10] Hall TA. BioEdit: a user-friendly biological sequence alignment editor
and analysis program for Windows 95/98/NT. Nucl Acids Symp Ser
1999;41:95–8.
Transparency Declaration [11] Tamura K, Dudley J, Nei M, Kumar S. MEGA4: Molecular Evolutionary
Genetics Analysis (MEGA) software version 4.0. Mol Biol Evol
2007;24:1596–9.
[12] Hukic M, Ravlija J, Karakas S, Mulaomerovic M, Dedeic Ljubovic A,
All authors report no conflicts of interest relevant to this Salimovic-Besic I, et al. An ongoing measles outbreak in the Federation
article. of Bosnia and Herzegovina, 2014 to 2015. Euro Surveill 2015;20:
21047.
[13] Kata A. Anti-vaccine activists,Web 2.0, and the postmodern para-
References digm—an overview of tactics and tropes used online by the anti-
vaccination movement. Vaccine 2012;30:3778–89.
[14] Kata A. A postmodern Pandora’s box: anti-vaccination misinformation
on the Internet. Vaccine 2010;28:1709–16.
[1] Bellini WJ, Rota JS, Rota PA. Virology of measles virus. J Infect Dis
[15] Ministry for Human Rights and Refugees of Bosnia and Herzegovina;
1994;170(Suppl. 1):S15–23.
Agency for Statistics of Bosnia and Herzegovina. Multiple indicator
[2] World Health Organization. Measles virus nomenclature update: 2012.
cluster survey (MICS) 2011–2012, Bosnia and Herzegovina: Roma
Wkly Epidemiol Rec 2012;9:73–80.
survey, final report. Sarajevo: UNICEF; 2013.
[3] World Health Organization. Measles vaccines: WHO position paper.
[16] M-M-R II. Measles, mumps, and rubella virus vaccine live. Kenilworth,
Wkly Epidemiol Rec 2009;35:349–60.
NJ: Merck & Co.; revised October 2015.

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