Acta Pædiatrica ISSN 0803-5253
SHORT COMMUNICATION
Could a fever and rash after the measles, mumps and rubella vaccination indicate wild-type measles? Chun Yi Ting ([email protected])1, Nancy Wen Sim Tee2,3, Koh Cheng Thoon3,4,5 1.Department of Paediatrics, KK Women’s and Children’s Hospital, Singapore 2.Department of Pathology and Laboratory Medicine, KK Women’s and Children’s Hospital, Singapore 3.Duke-National University of Singapore Graduate Medical School, Singapore 4.Infectious Disease Service, Department of Paediatrics, KK Women’s and Children’s Hospital, Singapore 5.Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Correspondence Chun Yi Ting, Department of Paediatrics, KK Women’s and Children’s Hospital, 100 Bukit Timah Road, Singapore 229899. Tel: +65 63948408| Fax: +65 62917923| Email: [email protected] Received 12 September 2014; revised 10 January 2015; accepted 29 January 2015. DOI:10.1111/apa.12961
The measles, mumps and rubella (MMR) vaccine is generally safe and has a good reactogenicity profile. Common post-vaccination side effects include fever, rash and coryza (1). However, a temporal association between vaccination and symptom onset does not necessarily imply a causal relationship, as demonstrated by a double-blinded crossover study conducted on twin pairs, which showed that the true frequency of side effects caused by the MMR vaccine was between 0.5% and 4% (2). In children who develop measles after the MMR vaccination, the strain of measles may either be wild-type or vaccine-associated, and this can be difficult to distinguish clinically. There are 23 known genotypes of the measles virus (3), with the measles vaccine virus belonging to genotype A. In Singapore, the MMR vaccine is given in two doses at 12 and 15–18 months (4). Currently, it is compulsory by law for all children to be vaccinated against measles and the MMR vaccine coverage in Singapore from 2007 to 2009 was 95% to 95.2% after the first dose of MMR vaccine (5). In Singapore, virological investigations are not normally carried out on children who develop a fever and rash after their MMR vaccine, as the clinical symptoms are often attributed to the vaccine. However, several children have recently developed wild-type measles following the MMR vaccination. This short communication describes the clinical epidemiology and aetiology of post-MMR vaccine fever and rash in hospitalised children, and, in those cases with diagnosed measles, identifies the genotyping results. This is the first such study conducted in Singapore. This is a retrospective, descriptive study of a subset of children identified through an active surveillance system for adverse events following immunisation at the KK Women’s and Children’s Hospital (KKH), Singapore, from March
e232
2010 to June 2013. All children aged between birth and 16 years who were admitted to KKH for various illnesses within 28 days of receiving the MMR vaccine were reviewed and those who presented with both fever and rash were included in this analysis. We retrieved their clinical records and collected the following data: demographic details, relevant clinical features on history and examination, the presence of underlying comorbidities, relevant investigation results – including haematology, biochemistry, microbiological and radiological results – and clinical diagnosis on discharge. Measles confirmation was based on the analysis of nasopharyngeal specimens using two main methods. These were detection of the measles-specific antigen by immunofluorescence or detection of the measles virus ribonucleic acid using real-time reverse transcriptase polymerase chain reaction (RT-PCR), based on an assay by Hummel et al. (6). The nasopharyngeal specimens or nucleic acid extracts from children with confirmed measles were sent to the National Public Health Laboratory (NPHL), Ministry of Health, Singapore, for measles genotyping. Genotyping involves amplifying a 450 base-pair region of the nucleoprotein (N) gene, sequencing it and subsequently comparing it with known sequences of both wild-type measles virus and vaccine strains to determine the genotype (7). Descriptive statistics were applied to both categorical and continuous data. The study was approved by the institutional review board of KKH. We identified 125 children admitted within 28 days of MMR immunisation during this period, including 26 with fever and rash. Of these, 20 (76.9%) presented after the first dose of the MMR vaccine, and five (19.2%) had simultaneously received other vaccines in addition to the MMR,
©2015 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd 2015 104, pp. e232–e234
Ting et al.
Wild-type measles after vaccination
Table 1 Comparison of demographics, clinical characteristics and investigations
Patient characteristics Age, months, median (IQR) Sex, male, n (%) Race, n (%) Chinese Malay Indian Others Dose of MMR vaccine First Second Interval from vaccine to symptom onset, days, median (IQR) Clinical presentation, n (%) Cough Coryza Conjunctivitis Koplik’s spots Investigations, median, (IQR) Haemoglobin (g/dL) White cell count (9109/L) Platelet (9109/L) C-reactive protein (mg/L) Investigations for other viruses Respiratory viruses antigen, positive, n (%) Enterovirus PCR, positive, n (%) Measles genotype Genotype A Genotype B3 Genotype D9
Laboratory-confirmed wild-type measles (n = 4)
Laboratory-confirmed vaccine-associated measles (n = 2)
Post-MMR febrile exanthem with other virological diagnosis(n = 5)
Post-MMR febrile exanthem with no virological diagnosis (n = 15)
33.37 (15.99–42.08) 2 (50%)
18.45 (15.34–21.56) 2 (100%)
16.20 (15.73–16.43) 2 (40%)
15.90 (15.53–16.22) 6 (40%)
1 3 0 0
(25%) (75%) (0%) (0%)
4 (100%) 0 (0%) 4.50 (3.50–5.75)
4 3 4 2 12.20 3.55 200 8.60
(100%) (75%) (100%) (50%) (11.95–13.25) (3.38–4.13) (175–209) (7.75–12.15)
2 0 0 0
(100%) (0%) (0%) (0%)
0 (0%) 2 (100%) 4.50 (4.25–4.75)
0 0 0 0 11.75 6.95 294 36.70
(0%) (0%) (0%) (0%) (11.28–12.23) (6.10–7.81) (281–307) (19.25–54.15)
4 0 0 1
(80%) (0%) (0%) (20%)
4 (80%) 1 (20%) 2.00 (2.00–5.00)
3 2 0 0 12.1 6.82 234 9.80
(60%) (40%) (0%) (0%) (11.90–12.10) (4.81–7.17) (223–262) (7.40–12.20)
8 5 1 1
(53.33%) (33.33%) (6.67%) (6.67%)
12 (80%) 3 (20%) 5.00 (4.00–8.00)
4 6 1 1 11.85 6.52 252.50 44.8
(26.67%) (40%) (6.67%) (6.67%) (11.30–12.65) (5.74–11.45) (160.50–283.00) (20.50–67.80)
0 (0%)
0 (0%)
4 (80%)
0 (0%)
0 (0%)
1 (50%)
1 (20%)
0 (0%)
NA 1 (25%) 3 (75%)
2 (100%) NA NA
NA NA NA
NA NA NA
IQR, interquartile range; PCR, polymerase chain reaction.
with four receiving the varicella zoster virus vaccine. Two children had significant comorbidities, but were not considered immunosuppressed. We tested 10 children (38.5%) for measles and, of these, five were confirmed by PCR, and one had the measles antigen confirmed by immunofluorescence. Of the six children with laboratory-confirmed measles, four were found to have wild-type measles, and two had vaccine-associated measles (Table 1). None of the children with laboratory-confirmed measles had a significant contact or travel history. One of the children with vaccine-associated measles was also found to be positive for enterovirus by RT-PCR. Of the remaining 20 children who were not diagnosed with measles, 18 were tested for respiratory viruses, one was tested for rubella, and all the virological investigations came back negative. The three most common final diagnoses for these 20 children included gastroenteritis/gastritis, viral exanthem and upper respiratory tract infection. None were tested for the parvovirus. Our results demonstrate that fever and rash after MMR vaccine may not always be associated with the vaccine
and can be due to either wild-type measles or other viral illnesses. However, given the similar clinical presentations, it may be difficult to distinguish between these causes. Two criteria have been used to clinically differentiate between wild-type and vaccine-associated measles, namely the presence of respiratory symptoms and the time interval from the vaccination to symptom onset. Firstly, Dietz et al. (8) mentioned that vaccine-associated measles did not tend to present with cough and coryza, and this was confirmed by the results of our study. Secondly, Dietz et al. (8) stated that a rash that appeared within seven to 14 days after a vaccination containing measles was likely to be vaccine associated. However, in the study by Kobune et al. (9), six of the seven vaccinated children who were suspected of having vaccine-associated measles, based on the abovementioned criteria, were found to have wild-type measles. From our case series, patients with both vaccine-associated and wild-type measles had the same median time interval of 4.5 days. Therefore, this further highlights the limitations that clinical presentation can play in distinguishing between vaccine-associated and wild-type measles.
©2015 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd 2015 104, pp. e232–e234
e233
Wild-type measles after vaccination
Ting et al.
Given that clinical history and examination may overdiagnose measles, laboratory-confirmation of measles is necessary. Brown et al. showed that in notified cases of measles, only 15% of children vaccinated and 47% of children not vaccinated demonstrated serological confirmation of measles (10). In Singapore in 2013, only 56 of 138 suspected measles cases were confirmed to be measles (11). The study by Davidkin et al. (12) on 993 children who presented with measles-like symptoms after the MMR vaccine demonstrated that 37% of them had a true viral aetiology, with parvovirus being the most common. There were several limitations to our study. Firstly, the sample size was small and only reflects hospitalised patients; thus, the results may not be a true representation of the general population. Secondly, as only patients with fever and rash were selected, patients with measles who presented with either symptom would have inadvertently been excluded. Besides, only 38.5% of the patients who presented with fever and rash were tested for measles and, as a result, some cases of measles might have been missed. In addition, the majority of the children were not tested for rubella, which could have explained the clinical features. Furthermore, patients were not tested for all possible viruses that cause fever and rash, although this is not usually indicated in clinical practice. In conclusion, our study illustrates that not all cases of fever and rash after the MMR vaccination were associated with the vaccine and may have been due to wild-type measles or other viral infections. As such, virological investigations should be considered and molecular characterisation is also required to determine measles virus genotypes. The importance of differentiating between these causes is important from both a vaccine confidence and public health viewpoint. This will allow more targeted public health intervention policies, such as isolation and contact tracing, to be carried out to terminate the further spread of disease, as well as to enable healthcare professionals to advise parents appropriately, thereby improving public awareness. Having knowledge of the various measles virus genotypes is also useful when it comes to investigating vaccine virus behaviour and aid in the mapping of regional measles genotype variations.
CONFLICT OF INTEREST The authors report no conflict of interests.
e234
FUNDING There are no financial relationships relevant to this article to disclose, and no funding was secured for this study.
References 1. Lim FS, Han HH, Bock HL. Safety, reactogenicity and immunogenicity of the live attenuated combined measles, mumps and rubella vaccine containing the RIT 4385 mumps strain in healthy Singaporean children. Ann Acad Med Singapore 2007; 36: 969–73. 2. Peltola H, Heinonen OP. Frequency of true adverse reactions to measles-mumps-rubella vaccine – a double-blind placebocontrolled trial in twins. Lancet 1986; 1: 939–42. 3. Mosquera MM, de Ory F, Echevarria JE, Network of Laboratories of the Spanish National Measles Elimination Plan. Measles virus genotyping and circulating genotypes. Open Vaccine J 2010; 3: 76–85. 4. National Immunisation Registry. National Childhood Immunisation Schedule. Singapore: National Immunization Registry; 2013 [updated 2013 September 3]; Available from: http://www.nir.hpb.gov.sg/nir/sv/eservices/eservicesv? ACTION=DISPLAY_IMMUNSCH (accessed on July 5, 2014). 5. Jayawardena A, Yong CC, Martin R, Ling C. Immunization uptake in Singapore. Singapore Fam Physician 2011; 37: 31–5. 6. Hummel KB, Lowe L, Bellini WJ, Rota PA. Development of quantitative gene-specific real-time RT-PCR assays for the detection of measles virus in clinical samples. J Virol Methods 2006; 132: 166–73. 7. Rota PA, Feathersone DA, Bellini WJ. Molecular epidemiology of measles virus. Curr Top Microbiol Immunol 2009; 330: 129–50. 8. Dietz V, Rota J, Izurieta H, Carrasco P, Bellini W. The laboratory confirmation of suspected measles cases in settings of low measles transmission: conclusions from the experience in the Americas. Bull World Health Org 2004; 82: 852–7. 9. Kobune F, Funato M, Takahashi H, Fukushima M, Kawamoto A, Iizuka S, et al. Characterization of measles viruses isolated after measles vaccination. Vaccine 1995; 13: 370–2. 10. Brown DWG, Ramsay MEB, Richards AF, Miller E. Salivary diagnosis of measles: a study of notified cases in the United Kingdom, 1991–3. BMJ 1994; 308: 1015–7. 11. World Health Organization. Country profile - measles elimination - Singapore. WHO Regional Office for the Western Pacific; 2014 [updated 2014 May 20]; Available from: http:// www.wpro.who.int/immunization/documents/measles_ country_profile_apr2014_sgp.pdf (accessed on November 1, 2014). 12. Davidkin I, Valle M, Peltola H, Hovi T, Paunio M, Roivainen M, et al. Etiology of measles- and rubella- like illnesses in measles, mumps and rubella-vaccinated children. J Infect Dis 1998; 178: 1567–70.
©2015 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd 2015 104, pp. e232–e234
Copyright of Acta Paediatrica is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
SHORT COMMUNICATION
Could a fever and rash after the measles, mumps and rubella vaccination indicate wild-type measles? Chun Yi Ting ([email protected])1, Nancy Wen Sim Tee2,3, Koh Cheng Thoon3,4,5 1.Department of Paediatrics, KK Women’s and Children’s Hospital, Singapore 2.Department of Pathology and Laboratory Medicine, KK Women’s and Children’s Hospital, Singapore 3.Duke-National University of Singapore Graduate Medical School, Singapore 4.Infectious Disease Service, Department of Paediatrics, KK Women’s and Children’s Hospital, Singapore 5.Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Correspondence Chun Yi Ting, Department of Paediatrics, KK Women’s and Children’s Hospital, 100 Bukit Timah Road, Singapore 229899. Tel: +65 63948408| Fax: +65 62917923| Email: [email protected] Received 12 September 2014; revised 10 January 2015; accepted 29 January 2015. DOI:10.1111/apa.12961
The measles, mumps and rubella (MMR) vaccine is generally safe and has a good reactogenicity profile. Common post-vaccination side effects include fever, rash and coryza (1). However, a temporal association between vaccination and symptom onset does not necessarily imply a causal relationship, as demonstrated by a double-blinded crossover study conducted on twin pairs, which showed that the true frequency of side effects caused by the MMR vaccine was between 0.5% and 4% (2). In children who develop measles after the MMR vaccination, the strain of measles may either be wild-type or vaccine-associated, and this can be difficult to distinguish clinically. There are 23 known genotypes of the measles virus (3), with the measles vaccine virus belonging to genotype A. In Singapore, the MMR vaccine is given in two doses at 12 and 15–18 months (4). Currently, it is compulsory by law for all children to be vaccinated against measles and the MMR vaccine coverage in Singapore from 2007 to 2009 was 95% to 95.2% after the first dose of MMR vaccine (5). In Singapore, virological investigations are not normally carried out on children who develop a fever and rash after their MMR vaccine, as the clinical symptoms are often attributed to the vaccine. However, several children have recently developed wild-type measles following the MMR vaccination. This short communication describes the clinical epidemiology and aetiology of post-MMR vaccine fever and rash in hospitalised children, and, in those cases with diagnosed measles, identifies the genotyping results. This is the first such study conducted in Singapore. This is a retrospective, descriptive study of a subset of children identified through an active surveillance system for adverse events following immunisation at the KK Women’s and Children’s Hospital (KKH), Singapore, from March
e232
2010 to June 2013. All children aged between birth and 16 years who were admitted to KKH for various illnesses within 28 days of receiving the MMR vaccine were reviewed and those who presented with both fever and rash were included in this analysis. We retrieved their clinical records and collected the following data: demographic details, relevant clinical features on history and examination, the presence of underlying comorbidities, relevant investigation results – including haematology, biochemistry, microbiological and radiological results – and clinical diagnosis on discharge. Measles confirmation was based on the analysis of nasopharyngeal specimens using two main methods. These were detection of the measles-specific antigen by immunofluorescence or detection of the measles virus ribonucleic acid using real-time reverse transcriptase polymerase chain reaction (RT-PCR), based on an assay by Hummel et al. (6). The nasopharyngeal specimens or nucleic acid extracts from children with confirmed measles were sent to the National Public Health Laboratory (NPHL), Ministry of Health, Singapore, for measles genotyping. Genotyping involves amplifying a 450 base-pair region of the nucleoprotein (N) gene, sequencing it and subsequently comparing it with known sequences of both wild-type measles virus and vaccine strains to determine the genotype (7). Descriptive statistics were applied to both categorical and continuous data. The study was approved by the institutional review board of KKH. We identified 125 children admitted within 28 days of MMR immunisation during this period, including 26 with fever and rash. Of these, 20 (76.9%) presented after the first dose of the MMR vaccine, and five (19.2%) had simultaneously received other vaccines in addition to the MMR,
©2015 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd 2015 104, pp. e232–e234
Ting et al.
Wild-type measles after vaccination
Table 1 Comparison of demographics, clinical characteristics and investigations
Patient characteristics Age, months, median (IQR) Sex, male, n (%) Race, n (%) Chinese Malay Indian Others Dose of MMR vaccine First Second Interval from vaccine to symptom onset, days, median (IQR) Clinical presentation, n (%) Cough Coryza Conjunctivitis Koplik’s spots Investigations, median, (IQR) Haemoglobin (g/dL) White cell count (9109/L) Platelet (9109/L) C-reactive protein (mg/L) Investigations for other viruses Respiratory viruses antigen, positive, n (%) Enterovirus PCR, positive, n (%) Measles genotype Genotype A Genotype B3 Genotype D9
Laboratory-confirmed wild-type measles (n = 4)
Laboratory-confirmed vaccine-associated measles (n = 2)
Post-MMR febrile exanthem with other virological diagnosis(n = 5)
Post-MMR febrile exanthem with no virological diagnosis (n = 15)
33.37 (15.99–42.08) 2 (50%)
18.45 (15.34–21.56) 2 (100%)
16.20 (15.73–16.43) 2 (40%)
15.90 (15.53–16.22) 6 (40%)
1 3 0 0
(25%) (75%) (0%) (0%)
4 (100%) 0 (0%) 4.50 (3.50–5.75)
4 3 4 2 12.20 3.55 200 8.60
(100%) (75%) (100%) (50%) (11.95–13.25) (3.38–4.13) (175–209) (7.75–12.15)
2 0 0 0
(100%) (0%) (0%) (0%)
0 (0%) 2 (100%) 4.50 (4.25–4.75)
0 0 0 0 11.75 6.95 294 36.70
(0%) (0%) (0%) (0%) (11.28–12.23) (6.10–7.81) (281–307) (19.25–54.15)
4 0 0 1
(80%) (0%) (0%) (20%)
4 (80%) 1 (20%) 2.00 (2.00–5.00)
3 2 0 0 12.1 6.82 234 9.80
(60%) (40%) (0%) (0%) (11.90–12.10) (4.81–7.17) (223–262) (7.40–12.20)
8 5 1 1
(53.33%) (33.33%) (6.67%) (6.67%)
12 (80%) 3 (20%) 5.00 (4.00–8.00)
4 6 1 1 11.85 6.52 252.50 44.8
(26.67%) (40%) (6.67%) (6.67%) (11.30–12.65) (5.74–11.45) (160.50–283.00) (20.50–67.80)
0 (0%)
0 (0%)
4 (80%)
0 (0%)
0 (0%)
1 (50%)
1 (20%)
0 (0%)
NA 1 (25%) 3 (75%)
2 (100%) NA NA
NA NA NA
NA NA NA
IQR, interquartile range; PCR, polymerase chain reaction.
with four receiving the varicella zoster virus vaccine. Two children had significant comorbidities, but were not considered immunosuppressed. We tested 10 children (38.5%) for measles and, of these, five were confirmed by PCR, and one had the measles antigen confirmed by immunofluorescence. Of the six children with laboratory-confirmed measles, four were found to have wild-type measles, and two had vaccine-associated measles (Table 1). None of the children with laboratory-confirmed measles had a significant contact or travel history. One of the children with vaccine-associated measles was also found to be positive for enterovirus by RT-PCR. Of the remaining 20 children who were not diagnosed with measles, 18 were tested for respiratory viruses, one was tested for rubella, and all the virological investigations came back negative. The three most common final diagnoses for these 20 children included gastroenteritis/gastritis, viral exanthem and upper respiratory tract infection. None were tested for the parvovirus. Our results demonstrate that fever and rash after MMR vaccine may not always be associated with the vaccine
and can be due to either wild-type measles or other viral illnesses. However, given the similar clinical presentations, it may be difficult to distinguish between these causes. Two criteria have been used to clinically differentiate between wild-type and vaccine-associated measles, namely the presence of respiratory symptoms and the time interval from the vaccination to symptom onset. Firstly, Dietz et al. (8) mentioned that vaccine-associated measles did not tend to present with cough and coryza, and this was confirmed by the results of our study. Secondly, Dietz et al. (8) stated that a rash that appeared within seven to 14 days after a vaccination containing measles was likely to be vaccine associated. However, in the study by Kobune et al. (9), six of the seven vaccinated children who were suspected of having vaccine-associated measles, based on the abovementioned criteria, were found to have wild-type measles. From our case series, patients with both vaccine-associated and wild-type measles had the same median time interval of 4.5 days. Therefore, this further highlights the limitations that clinical presentation can play in distinguishing between vaccine-associated and wild-type measles.
©2015 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd 2015 104, pp. e232–e234
e233
Wild-type measles after vaccination
Ting et al.
Given that clinical history and examination may overdiagnose measles, laboratory-confirmation of measles is necessary. Brown et al. showed that in notified cases of measles, only 15% of children vaccinated and 47% of children not vaccinated demonstrated serological confirmation of measles (10). In Singapore in 2013, only 56 of 138 suspected measles cases were confirmed to be measles (11). The study by Davidkin et al. (12) on 993 children who presented with measles-like symptoms after the MMR vaccine demonstrated that 37% of them had a true viral aetiology, with parvovirus being the most common. There were several limitations to our study. Firstly, the sample size was small and only reflects hospitalised patients; thus, the results may not be a true representation of the general population. Secondly, as only patients with fever and rash were selected, patients with measles who presented with either symptom would have inadvertently been excluded. Besides, only 38.5% of the patients who presented with fever and rash were tested for measles and, as a result, some cases of measles might have been missed. In addition, the majority of the children were not tested for rubella, which could have explained the clinical features. Furthermore, patients were not tested for all possible viruses that cause fever and rash, although this is not usually indicated in clinical practice. In conclusion, our study illustrates that not all cases of fever and rash after the MMR vaccination were associated with the vaccine and may have been due to wild-type measles or other viral infections. As such, virological investigations should be considered and molecular characterisation is also required to determine measles virus genotypes. The importance of differentiating between these causes is important from both a vaccine confidence and public health viewpoint. This will allow more targeted public health intervention policies, such as isolation and contact tracing, to be carried out to terminate the further spread of disease, as well as to enable healthcare professionals to advise parents appropriately, thereby improving public awareness. Having knowledge of the various measles virus genotypes is also useful when it comes to investigating vaccine virus behaviour and aid in the mapping of regional measles genotype variations.
CONFLICT OF INTEREST The authors report no conflict of interests.
e234
FUNDING There are no financial relationships relevant to this article to disclose, and no funding was secured for this study.
References 1. Lim FS, Han HH, Bock HL. Safety, reactogenicity and immunogenicity of the live attenuated combined measles, mumps and rubella vaccine containing the RIT 4385 mumps strain in healthy Singaporean children. Ann Acad Med Singapore 2007; 36: 969–73. 2. Peltola H, Heinonen OP. Frequency of true adverse reactions to measles-mumps-rubella vaccine – a double-blind placebocontrolled trial in twins. Lancet 1986; 1: 939–42. 3. Mosquera MM, de Ory F, Echevarria JE, Network of Laboratories of the Spanish National Measles Elimination Plan. Measles virus genotyping and circulating genotypes. Open Vaccine J 2010; 3: 76–85. 4. National Immunisation Registry. National Childhood Immunisation Schedule. Singapore: National Immunization Registry; 2013 [updated 2013 September 3]; Available from: http://www.nir.hpb.gov.sg/nir/sv/eservices/eservicesv? ACTION=DISPLAY_IMMUNSCH (accessed on July 5, 2014). 5. Jayawardena A, Yong CC, Martin R, Ling C. Immunization uptake in Singapore. Singapore Fam Physician 2011; 37: 31–5. 6. Hummel KB, Lowe L, Bellini WJ, Rota PA. Development of quantitative gene-specific real-time RT-PCR assays for the detection of measles virus in clinical samples. J Virol Methods 2006; 132: 166–73. 7. Rota PA, Feathersone DA, Bellini WJ. Molecular epidemiology of measles virus. Curr Top Microbiol Immunol 2009; 330: 129–50. 8. Dietz V, Rota J, Izurieta H, Carrasco P, Bellini W. The laboratory confirmation of suspected measles cases in settings of low measles transmission: conclusions from the experience in the Americas. Bull World Health Org 2004; 82: 852–7. 9. Kobune F, Funato M, Takahashi H, Fukushima M, Kawamoto A, Iizuka S, et al. Characterization of measles viruses isolated after measles vaccination. Vaccine 1995; 13: 370–2. 10. Brown DWG, Ramsay MEB, Richards AF, Miller E. Salivary diagnosis of measles: a study of notified cases in the United Kingdom, 1991–3. BMJ 1994; 308: 1015–7. 11. World Health Organization. Country profile - measles elimination - Singapore. WHO Regional Office for the Western Pacific; 2014 [updated 2014 May 20]; Available from: http:// www.wpro.who.int/immunization/documents/measles_ country_profile_apr2014_sgp.pdf (accessed on November 1, 2014). 12. Davidkin I, Valle M, Peltola H, Hovi T, Paunio M, Roivainen M, et al. Etiology of measles- and rubella- like illnesses in measles, mumps and rubella-vaccinated children. J Infect Dis 1998; 178: 1567–70.
©2015 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd 2015 104, pp. e232–e234
Copyright of Acta Paediatrica is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
