Occurrence of measles genotype D8 during a 2014 outbreak in Banjarmasin, South Kalimantan, Indonesia

Occurrence of measles genotype D8 during a 2014 outbreak in Banjarmasin, South Kalimantan, Indonesia

Accepted Manuscript Title: Occurrence of measles genotype D8 during a 2014 outbreak in Banjarmasin, South Kalimantan, Indonesia Author: Edi Hartoyo Ag...

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Accepted Manuscript Title: Occurrence of measles genotype D8 during a 2014 outbreak in Banjarmasin, South Kalimantan, Indonesia Author: Edi Hartoyo Ageng Wiyatno Ungke Anton Jaya Chairin Nisa Ma’roef Corina Monagin Khin Saw Myint Dodi Safari PII: DOI: Reference:

S1201-9712(16)31213-9 http://dx.doi.org/doi:10.1016/j.ijid.2016.10.029 IJID 2760

To appear in:

International Journal of Infectious Diseases

Received date: Revised date: Accepted date:

28-3-2016 25-10-2016 26-10-2016

Please cite this article as: Hartoyo E, Wiyatno A, Jaya UA, Ma’roef CN, Monagin C, Myint KS, Safari D, Occurrence of measles genotype D8 during a 2014 outbreak in Banjarmasin, South Kalimantan, Indonesia, International Journal of Infectious Diseases (2016), http://dx.doi.org/10.1016/j.ijid.2016.10.029 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Short Communication Occurrence of measles genotype D8 during a 2014 outbreak in Banjarmasin, South Kalimantan, Indonesia

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Edi Hartoyo1, 2, Ageng Wiyatno3, Ungke Anton Jaya3, 4, Chairin Nisa Ma’roef 3, Corina

Ulin General Hospital, Banjarmasin, South Kalimantan, Indonesia; 2Faculty of Medicine,

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Monagin5, Khin Saw Myint3, Dodi Safari3*

Lambung Mangkurat University, Banjarmasin, South Kalimantan, Indonesia; 3Eijkman Institute

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Indonesia; 5Metabiota, San Francisco, CA USA

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for Molecular Biology, Jakarta, Indonesia; 4Eijkman-Oxford Clinical Research Unit, Jakarta,

Corresponding Author: *Dodi Safari

Eijkman Institute for Molecular Biology Jakarta, Indonesia

Email: [email protected]

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Summary Objectives: We investigate an outbreak with measles symptoms occurred in children in Banjarmasin, South Kalimantan, Indonesia in 2014.

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Methods: Nasal swabs were collected from 23 hospitalized (median age of 41 months) with fever and other measles symptoms in Ulin General Hospital and Islamic Hospital, Banjarmasin, South

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using paramyxovirus family consensus- and -N-gene primers.

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Kalimantan. Viral RNA was extracted for cDNA synthesis followed by PCR and Sequencing

Result: We identified sixteen measles-positive patients (70%) and that the 15 virus strains

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belonged to genotype D8 and one strain was confirmed as a genotype D9.

Conclusion: We detected measles virus genotype D8 in an outbreak of measles in South

measles; genotype D8; Indonesia

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Key words :

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Kalimantan, Indonesia, in 2014.

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 An outbreak with measles symptoms occurred in children in Banjarmasin, South Kalimantan, Indonesia in 2014.  16 measles-positive patients (70%) and that the fifteen virus belonged to genotype D8

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and one strain was confirmed as a genotype D9.

 These strains were similar to other D8 strains circulating in the region.

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vaccination coverage is below the national standard

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 Evaluation of vaccination program might needed especially for population which

Measles is an acute, highly contagious illness caused by an enveloped virus in the family

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Paramyxovirus, genus Morbillivirus. Measles is a vaccine preventable disease and the currently available vaccine is expected to provide protection against all circulating strains. Three genotypes of measles have been previously reported to circulate in Indonesia: Genotype G2, G3 and D91. The Ministry of Health (MoH), Republic of Indonesia reported that measles vaccination had a coverage of 94.7 % of children in Indonesia, and 69.5% in South Kalimantan province in particular in 20142. Despite vaccination efforts in Indonesia, a total of 12,943 measles cases were reported in 2014, which is increased from 11,521 in 2013, with an incidence rate (IR) of 5,13/100.000 and 4,64/100.000 for both years, respectively2. We report on an investigation of the

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virus responsible for an outbreak involving children with measles symptoms in Banjarmasin, South Kalimantan. Nasal swabs were collected in viral transport medium (VTM) from children presenting

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with fever and other measles symptoms. Samples were taken <5 days after illness of onset from patients who were hospitalized at pediatric wards in Ulin General Hospital and Islamic Hospital,

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Banjarmasin, South Kalimantan, from October to November 2014. Travel history or any contact

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of the patients with travelers could not be recalled. The testing of outbreak specimens was approved by the Eijkman Institute Research Ethics Commission (number 66, November 18th,

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2013).

Detection of the virus causing this outbreak was conducted as part of ongoing fever study

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algorithm which is designed for the surveillance of viruses of pandemic potential (USAID

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PREDICT Project). Viral RNA was extracted from all nasal swab specimens for cDNA synthesis

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followed by PCR amplification using Paramyxovirus family consensus primers3. Positive amplicons were sequenced using the Sanger method and a BLAST search was performed in the

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GenBank database. All positive samples, as identified by sequencing, went through further amplification and sequencing of 450 nucleotides on the N-gene region recommended for measles virus genotyping, following the procedure described by Chibo, 20004. All positive samples were sent to PT Bio Farma, the World Health Organization (WHO) reference laboratory located in West Java, Indonesia for sequence confirmation. During the outbreak, 23 swabs were collected from as many patients, ranging in age from 6 months to 11 years (median age of 41 months), with 11 males and 12 females. Clinical presentations included fever (n=23, 100%), severe rash typical of measles (n=21, 91%), cough (n=23, 100%), vomiting and nausea (n=15, 65%), sore throat (n=16, 70%); stomach ache (n=4,

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17%), and seizures (n=2, 9%). All patients recovered without further complications and were discharged in an average of 2.8 days after hospitalization. Patients’ vaccination status, as determined by review of records and parental report, revealed 14 as vaccinated, 7 as

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unvaccinated, and 2 as inconclusive.

Among the 16 measles-positive patients, 15 virus strains were confirmed by PT Bio Farma

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as genotype D8 and one strain was confirmed as a genotype D9. The sequence of D8 strains were

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99% similar to other D8 strains circulating in the region (Figure 1). All sequence data of genotype D8 reported in this study were deposited into GenBank (Accession number KT964105-

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KT964119).

Until 2009, measles outbreaks in Indonesia were associated with genotypes G2, G3, and

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D91. Measles genotype D8 (MV-D8) has already been reported to be circulating and is

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associated with sporadic cases in many countries in the South East Asia region including

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Thailand, Vietnam, Nepal, India, and Bangladesh1. Recently, MV-D8 was reported in two Taiwanese travelers visiting Indonesia5. According to the WHO Report 6 and personal

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communication with Indonesian Ministry of Health representative and PT. Bio Farma, MV-D8 has been detected in Sumatera and Jakarta, Indonesia co-circulating with genotype D9 and B3 in 2013 and 2014. It is possible that MV-D8 has been circulating within Indonesia in areas of low vaccination coverage, but the origin of the strain is difficult to specify. Measles vaccination coverage for children in South Kalimantan has reached 69.5 %, with 2 doses at months 9 and 24 as part of the national immunization program. This is lower than a minimum vaccination coverage to protect population from large outbreak, which is >93-95% of the population immunized7. This coverage can be achieved through more active, routine and/ or campaign of two doses vaccination8. Failure to maintain this high coverage of vaccination will lead to

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resurgence of measles 8. Moreover, the interval between the first and second dose vaccination will leave several birth cohorts protected by only 1 dose which only protect about 85% efficacy 9

. According to RISKESDAS, a health survey by Indonesian MoH which were done in 2007,

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2010, 2013 and 2014, measles vaccination coverage for baby 12-23 month of age in South

Kalimantan is decreasing from 81.7, 75.2, 74.1, and 69.5 % respectively2,10–12. Decrease of

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vaccination coverage might impact on occurrence of measles outbreak. This study has some

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limitations; sera samples were not available from any of the patients to assess their immunity status and the breakthrough infection in the 11 cases could be due to children only received one

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dose of vaccination and variability of immune response to measles vaccine13. We report the recovery of MV-D8 from an outbreak in Banjarmasin, South Kalimantan.

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This information might be beneficial for directing public health action in Indonesia and

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informing strategies to increase vaccine coverage. The results should alert the responsible health

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authorities to increase measles surveillance as well as to determine immunity status among

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vaccinated children to evaluate the measles vaccine effectiveness and elimination program.

Acknowledgement

This study was supported by the United States Agency for International Development (USAID) Emerging Pandemic Threats PREDICT. We thank the patient, physicians and the management of Ulin General Hospital and Islamic Hospital, Banjarmasin, South Kalimantan, U.S. Centers for Disease Control and Prevention for their supports during this investigation and PT Bio Farma, Bandung, West Java for measles confirmation testing. References

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1Rota Paul A, Brown Kevin, Mankertz Annette, Santibanez Sabine, Shulga Sergey, Muller Claude P, et al. Global Distribution of Measles Genotypes and Measles Molecular Epidemiology. J Infect Dis 2011;204(suppl 1):S514–23. Doi: 10.1093/infdis/jir118. 2Oscar Primadi, Zulfi, Supriyono Pangribowo, Marlina Indah Susanti, Athi Susilowati Rois, Budi Prihantoro, et al. Profil Kesehatan Indonesia Tahun 2014. Jakarta: Kementerian Kesehatan Republik Indonesia; 2015. 3Tong Suxiang, Chern Shur-Wern Wang, Li Yan, Pallansch Mark A, Anderson Larry J. Sensitive and Broadly Reactive Reverse Transcription-PCR Assays To Detect Novel Paramyxoviruses. J Clin Microbiol 2008;46(8):2652–8. Doi: 10.1128/JCM.00192-08. 4Chibo D, Birch CJ, Rota PA, Catton MG. Molecular characterization of measles viruses isolated in Victoria, Australia, between 1973 and 1998. J Gen Virol 2000;81(Pt 10):2511–8. Doi: 10.1099/0022-1317-81-10-2511. 5Cheng Wen-Yueh, Wang Hsiao-Chi, Wu Ho-Sheng, Liu Ming-Tsan. Measles surveillance in Taiwan, 2012–2014: Changing epidemiology, immune response, and circulating genotypes. J Med Virol 2016;88(5):746–53. Doi: 10.1002/jmv.24392. 6Featherstone David. Report on The 12th WHO Global Measles and Rubella Laboratory Network Meeting. 2014. Istanbul : http://www.who.int/immunization/monitoring_surveillance/burden/laboratory/MR_labnet_Rep ort_2014.pdf 7Kaiser Reinhard, Shibeshi Messeret E, Chakauya Jethro M, Dzeka Emelda, Masresha Balcha G, Daniel Fussum, et al. Surveys of measles vaccination coverage in eastern and southern Africa: a review of quality and methods used. Bull World Health Organ 2015;93(5):314–9. Doi: 10.2471/BLT.14.146050. 8World Health Organization. Weekly Epidemiological Report. 2009. Switzerland. http://www.who.int/wer/2009/wer8435.pdf?ua=1 9Acharya Arnab, Diaz-Ortega Jose Luis, Tambini Gina, de Quadros Ciro, Arita Isao. Costeffectiveness of measles elimination in Latin America and the Caribbean: a prospective analysis. Vaccine 2002;20(27-28):3332–41. 10Badan Penelitian dan Pengembangan Kesehatan Kementerian RI 2008. Laporan Hasil Riset Kesehatan Dasar 2007. Jakarta: https://www.k4health.org/sites/default/files/laporanNasional%20Riskesdas%202007.pdf; 2008. 11Badan Penelitian dan Pengembangan Kesehatan Kementerian RI 2010. Laporan Nasional Riset Kesehatan Dasar 2010. Jakarta: http://www.diskes.baliprov.go.id/files/subdomain/diskes/Januari%202015/RISKESDAS%2020 10.pdf; 2010. 12Badan Penelitian dan Pengembangan Kesehatan Kementerian RI 2013. Riset Kesehatan Dasar 2013. Jakarta: http://www.depkes.go.id/resources/download/general/Hasil%20Riskesdas%202013.pdf; 2013. 13 Haralambieva Iana H, Kennedy Richard B, Ovsyannikova Inna G, Whitaker Jennifer A, Poland Gregory A. Variability in Humoral Immunity to Measles Vaccine: New Developments. Trends Mol Med 2015;21(12):789–801. Doi: 10.1016/j.molmed.2015.10.005.

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Figure 1. Phylogenetic tree of measles virus sequences from outbreak in Banjarmasin and other genotype D8 strains circulating in the region. Total 19 reference strains obtained from GenBank database and WHO reference strain, accession numbers are given on the phylogenetic tree.

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Sequences cover 450- nucleotides encoding C-terminal hypervariable region on N-gene

recommended for measles genotyping. Phylogenetic tree was constructed using Geneious

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software version 8.1.5 applying the neighbor-joining model and the Kimura 2-parameter method

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with 1,000 bootstrap replicates

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