Skip directly to site content Skip directly to page options Skip directly to A-Z link Skip directly to A-Z link Skip directly to A-Z link
Volume 27, Number 6—June 2021

Precision Tracing of Household Dengue Spread Using Inter- and Intra-Host Viral Variation Data, Kamphaeng Phet, Thailand

Irina Maljkovic Berry1Comments to Author , Melanie C. Melendrez1, Simon Pollett, Katherine Figueroa, Darunee Buddhari, Chonticha Klungthong, Ananda Nisalak2, Michael Panciera, Butsaya Thaisomboonsuk, Tao Li, Tyghe G. Vallard, Louis Macareo, In-Kyu Yoon, Stephen J. Thomas, Timothy Endy, and Richard G. Jarman
Author affiliations: Walter Reed Army Institute of Research Viral Diseases Branch, Silver Spring, Maryland, USA (I. Maljkovic Berry, M.C. Melendrez, S. Pollett, K. Figueroa, M. Panciera, T. Li, T.G. Vallard, R.G. Jarman); Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand (D. Buddhari, C. Klungthong, A. Nisalak, B. Thaisomboonsuk, L. Macareo); International Vaccine Institute, Seoul, South Korea (I.-K. Yoon); Upstate Medical University of New York Department of Medicine, Syracuse, New York, USA (S.J. Thomas, T. Endy)

Main Article

Table 2

Dengue virus serotype 1 transmission clusters revealed by minor variant sharing, Kamphaeng Phet, Thailand, 2009–2012*

Sublineage Transmission cluster Household† No. persons Sampling dates Approximate distance, m
LD02H056 1 2011 Jun 2 800
2011 Jun 16
2011 Nov 28–29
7 3 TN18H023 3 2012 Oct 10 0–80
TN18H019 1 2012 Oct 10
TN18H021‡ 2 2012 Oct 10
TN18H014‡ 1 2012 Oct 9

*LD, Lan Dokmai; ST, Song Tham; TN, Thep Nakhon.
†Households are described by their subdistrict, cluster, and house numbers, such that the first 2 letters denote subdistrict, the next 2-digit number denotes cluster, and an H followed by a 3-digit number denotes house number.
‡House or individual involvement with the transmission cluster also confirmed by BEAST analyses (38).

Main Article

  1. Bhatt  S, Gething  PW, Brady  OJ, Messina  JP, Farlow  AW, Moyes  CL, et al. The global distribution and burden of dengue. Nature. 2013;496:5047. DOIPubMedGoogle Scholar
  2. Brady  OJ, Gething  PW, Bhatt  S, Messina  JP, Brownstein  JS, Hoen  AG, et al. Refining the global spatial limits of dengue virus transmission by evidence-based consensus. PLoS Negl Trop Dis. 2012;6:e1760. DOIPubMedGoogle Scholar
  3. Yoon  IK. Focal dengue virus transmission in Kamphaeng Phet, Thailand and implications for management. Southeast Asian J Trop Med Public Health. 2015;46(Suppl 1):1725.PubMedGoogle Scholar
  4. Alera  MT, Srikiatkhachorn  A, Velasco  JM, Tac-An  IA, Lago  CB, Clapham  HE, et al. Incidence of dengue virus infection in adults and children in a prospective longitudinal cohort in the Philippines. PLoS Negl Trop Dis. 2016;10:e0004337. DOIPubMedGoogle Scholar
  5. Nisalak  A, Clapham  HE, Kalayanarooj  S, Klungthong  C, Thaisomboonsuk  B, Fernandez  S, et al. Forty years of dengue surveillance at a tertiary pediatric hospital in Bangkok, Thailand, 1973–2012. Am J Trop Med Hyg. 2016;94:13427. DOIPubMedGoogle Scholar
  6. Cucunawangsih, Lugito NPH. Trends of Dengue Disease Epidemiology. Virology (Auckl). 2017;8:1178122X17695836.
  7. Messina  JP, Brady  OJ, Scott  TW, Zou  C, Pigott  DM, Duda  KA, et al. Global spread of dengue virus types: mapping the 70 year history. Trends Microbiol. 2014;22:13846. DOIPubMedGoogle Scholar
  8. Hoang Quoc  C, Henrik  S, Isabel  RB, In-Kyu  Y, Chau  NV, Hung  NT, et al. Synchrony of dengue incidence in Ho Chi Minh City and Bangkok. PLoS Negl Trop Dis. 2016;10:e0005188. DOIPubMedGoogle Scholar
  9. Bhoomiboonchoo  P, Gibbons  RV, Huang  A, Yoon  IK, Buddhari  D, Nisalak  A, et al. The spatial dynamics of dengue virus in Kamphaeng Phet, Thailand. PLoS Negl Trop Dis. 2014;8:e3138. DOIPubMedGoogle Scholar
  10. Bhoomiboonchoo  P, Nisalak  A, Chansatiporn  N, Yoon  IK, Kalayanarooj  S, Thipayamongkolgul  M, et al. Sequential dengue virus infections detected in active and passive surveillance programs in Thailand, 1994-2010. BMC Public Health. 2015;15:250. DOIPubMedGoogle Scholar
  11. Pollett  S, Melendrez  MC, Maljkovic Berry  I, Duchêne  S, Salje  H, Cummings  DAT, et al. Understanding dengue virus evolution to support epidemic surveillance and counter-measure development. Infect Genet Evol. 2018;62:27995. DOIPubMedGoogle Scholar
  12. Salje  H, Lessler  J, Maljkovic Berry  I, Melendrez  MC, Endy  T, Kalayanarooj  S, et al. Dengue diversity across spatial and temporal scales: Local structure and the effect of host population size. Science. 2017;355:13026. DOIPubMedGoogle Scholar
  13. Tian  H, Sun  Z, Faria  NR, Yang  J, Cazelles  B, Huang  S, et al. Increasing airline travel may facilitate co-circulation of multiple dengue virus serotypes in Asia. PLoS Negl Trop Dis. 2017;11:e0005694. DOIPubMedGoogle Scholar
  14. Normile  D. Tropical medicine. Surprising new dengue virus throws a spanner in disease control efforts. Science. 2013;342:415. DOIPubMedGoogle Scholar
  15. Vasilakis  N, Cardosa  J, Hanley  KA, Holmes  EC, Weaver  SC. Fever from the forest: prospects for the continued emergence of sylvatic dengue virus and its impact on public health. Nat Rev Microbiol. 2011;9:53241. DOIPubMedGoogle Scholar
  16. Myat Thu  H, Lowry  K, Jiang  L, Hlaing  T, Holmes  EC, Aaskov  J. Lineage extinction and replacement in dengue type 1 virus populations are due to stochastic events rather than to natural selection. Virology. 2005;336:16372. DOIPubMedGoogle Scholar
  17. Rico-Hesse  R, Harrison  LM, Salas  RA, Tovar  D, Nisalak  A, Ramos  C, et al. Origins of dengue type 2 viruses associated with increased pathogenicity in the Americas. Virology. 1997;230:24451. DOIPubMedGoogle Scholar
  18. Rabaa  MA, Klungthong  C, Yoon  IK, Holmes  EC, Chinnawirotpisan  P, Thaisomboonsuk  B, et al. Frequent in-migration and highly focal transmission of dengue viruses among children in Kamphaeng Phet, Thailand. PLoS Negl Trop Dis. 2013;7:e1990. DOIPubMedGoogle Scholar
  19. Rabaa  MA, Ty Hang  VT, Wills  B, Farrar  J, Simmons  CP, Holmes  EC. Phylogeography of recently emerged DENV-2 in southern Viet Nam. PLoS Negl Trop Dis. 2010;4:e766. DOIPubMedGoogle Scholar
  20. Jarman  RG, Holmes  EC, Rodpradit  P, Klungthong  C, Gibbons  RV, Nisalak  A, et al. Microevolution of Dengue viruses circulating among primary school children in Kamphaeng Phet, Thailand. J Virol. 2008;82:5494500. DOIPubMedGoogle Scholar
  21. Schreiber  MJ, Holmes  EC, Ong  SH, Soh  HS, Liu  W, Tanner  L, et al. Genomic epidemiology of a dengue virus epidemic in urban Singapore. J Virol. 2009;83:416373. DOIPubMedGoogle Scholar
  22. Pybus  OG, Tatem  AJ, Lemey  P. Virus evolution and transmission in an ever more connected world. Proc Biol Sci. 2015;282:20142878. DOIPubMedGoogle Scholar
  23. Gire  SK, Goba  A, Andersen  KG, Sealfon  RS, Park  DJ, Kanneh  L, et al. Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak. Science. 2014;345:136972. DOIPubMedGoogle Scholar
  24. Stack  JC, Murcia  PR, Grenfell  BT, Wood  JL, Holmes  EC. Inferring the inter-host transmission of influenza A virus using patterns of intra-host genetic variation. Proc Biol Sci. 2013;280:20122173. DOIPubMedGoogle Scholar
  25. Zanini  F, Brodin  J, Thebo  L, Lanz  C, Bratt  G, Albert  J, et al. Population genomics of intrapatient HIV-1 evolution. eLife. 2015;4:4. DOIPubMedGoogle Scholar
  26. Fischer  GE, Schaefer  MK, Labus  BJ, Sands  L, Rowley  P, Azzam  IA, et al. Hepatitis C virus infections from unsafe injection practices at an endoscopy clinic in Las Vegas, Nevada, 2007-2008. Clin Infect Dis. 2010;51:26773. DOIPubMedGoogle Scholar
  27. Worby  CJ, Lipsitch  M, Hanage  WP. Shared genomic variants: identification of transmission routes using pathogen deep-sequence data. Am J Epidemiol. 2017;186:120916. DOIPubMedGoogle Scholar
  28. Wymant  C, Hall  M, Ratmann  O, Bonsall  D, Golubchik  T, de Cesare  M, et al. PHYLOSCANNER: inferring transmission from within- and between-host pathogen genetic diversity. Mol Biol Evol. 2017.PubMedGoogle Scholar
  29. Skums  P, Zelikovsky  A, Singh  R, Gussler  W, Dimitrova  Z, Knyazev  S, et al. QUENTIN: reconstruction of disease transmissions from viral quasispecies genomic data. Bioinformatics. 2018;34:16370. DOIPubMedGoogle Scholar
  30. Thomas  SJ, Aldstadt  J, Jarman  RG, Buddhari  D, Yoon  IK, Richardson  JH, et al. Improving dengue virus capture rates in humans and vectors in Kamphaeng Phet Province, Thailand, using an enhanced spatiotemporal surveillance strategy. Am J Trop Med Hyg. 2015;93:2432. DOIPubMedGoogle Scholar
  31. Vallard  T, Melendrez  M, Panciera  M. ngs_mapper v1.4.2: apipeline for viral and microbial genome construction. 2014 [cited 2016 Mar 25].
  32. Wilm  A, Aw  PP, Bertrand  D, Yeo  GH, Ong  SH, Wong  CH, et al. LoFreq: a sequence-quality aware, ultra-sensitive variant caller for uncovering cell-population heterogeneity from high-throughput sequencing datasets. Nucleic Acids Res. 2012;40:11189201. DOIPubMedGoogle Scholar
  33. McCrone  JT, Lauring  AS. Measurements of intrahost viral diversity are extremely sensitive to systematic errors in variant calling. J Virol. 2016;90:688495. DOIPubMedGoogle Scholar
  34. Edgar  RC. MUSCLE: a multiple sequence alignment method with reduced time and space complexity. BMC Bioinformatics. 2004;5:113. DOIPubMedGoogle Scholar
  35. Darriba  D, Taboada  GL, Doallo  R, Posada  D. jModelTest 2: more models, new heuristics and parallel computing. Nat Methods. 2012;9:772. DOIPubMedGoogle Scholar
  36. Guindon  S, Delsuc  F, Dufayard  JF, Gascuel  O. Estimating maximum likelihood phylogenies with PhyML. Methods Mol Biol. 2009;537:11337. DOIPubMedGoogle Scholar
  37. Rambaut  A, Lam  TT, Max Carvalho  L, Pybus  OG. Exploring the temporal structure of heterochronous sequences using TempEst (formerly Path-O-Gen). Virus Evol. 2016;2:vew007. DOIPubMedGoogle Scholar
  38. Drummond  AJ, Rambaut  A. BEAST: Bayesian evolutionary analysis by sampling trees. BMC Evol Biol. 2007;7:214. DOIPubMedGoogle Scholar
  39. Sim  S, Aw  PP, Wilm  A, Teoh  G, Hue  KD, Nguyen  NM, et al. Tracking dengue virus intra-host genetic diversity during human-to-mosquito transmission. PLoS Negl Trop Dis. 2015;9:e0004052. DOIPubMedGoogle Scholar
  40. De Maio  N, Worby  CJ, Wilson  DJ, Stoesser  N. Bayesian reconstruction of transmission within outbreaks using genomic variants. PLOS Comput Biol. 2018;14:e1006117. DOIPubMedGoogle Scholar
  41. Alamil  M, Hughes  J, Berthier  K, Desbiez  C, Thébaud  G, Soubeyrand  S. Inferring epidemiological links from deep sequencing data: a statistical learning approach for human, animal and plant diseases. Philos Trans R Soc Lond B Biol Sci. 2019;374:20180258. DOIPubMedGoogle Scholar
  42. Didelot  X, Fraser  C, Gardy  J, Colijn  C. Genomic infectious disease epidemiology in partially sampled and ongoing outbreaks. Mol Biol Evol. 2017;34:9971007. DOIPubMedGoogle Scholar
  43. Lequime  S, Fontaine  A, Ar Gouilh  M, Moltini-Conclois  I, Lambrechts  L. Genetic drift, purifying selection and vector genotype shape dengue virus intra-host genetic diversity in mosquitoes. PLoS Genet. 2016;12:e1006111. DOIPubMedGoogle Scholar
  44. Fung  CK, Li  T, Pollett  S, Alera  MT, Yoon  IK, Hang  J, et al. Effect of low-passage number on dengue consensus genomes and intra-host variant frequencies. J Gen Virol. 2021;102:102. DOIPubMedGoogle Scholar
  45. Grubaugh  ND, Gangavarapu  K, Quick  J, Matteson  NL, De Jesus  JG, Main  BJ, et al. An amplicon-based sequencing framework for accurately measuring intrahost virus diversity using PrimalSeq and iVar. Genome Biol. 2019;20:8. DOIPubMedGoogle Scholar
  46. Karst  SM, Ziels  RM, Kirkegaard  RH, Sørensen  EA, McDonald  D, Zhu  Q, et al. High-accuracy long-read amplicon sequences using unique molecular identifiers with Nanopore or PacBio sequencing. Nat Methods. 2021;18:1659. DOIPubMedGoogle Scholar

Main Article

1These authors contributed equally to this article.


Page created: April 01, 2021
Page updated: May 18, 2021
Page reviewed: May 18, 2021
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.