Epidemiological, virological and clinical characterization of a Dengue/Zika outbreak in the Caribbean region of Costa Rica 2017-2018.

Claudio Soto-Garita, Tatiana Murillo, Ileana Chávez-Peraza, Josué Campos-Ávila, Grace Prado-Hidalgo, Jan Felix Drexler, Andres Moreira-Soto, Eugenia Corrales-Aguilar
Author Information
  1. Claudio Soto-Garita: Research Center for Tropical Diseases (CIET) and Faculty of Microbiology, University of Costa Rica, San José, Costa Rica.
  2. Tatiana Murillo: Research Center for Tropical Diseases (CIET) and Faculty of Microbiology, University of Costa Rica, San José, Costa Rica.
  3. Ileana Chávez-Peraza: Siquirres Integral Healthcare Center (CAIS), Costa Rican Social Security Fund (CCSS), Limón, Costa Rica.
  4. Josué Campos-Ávila: Siquirres Integral Healthcare Center (CAIS), Costa Rican Social Security Fund (CCSS), Limón, Costa Rica.
  5. Grace Prado-Hidalgo: Talamanca Healthcare Center, Costa Rican Social Security Fund (CCSS), Limón, Costa Rica.
  6. Jan Felix Drexler: Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Institute of Virology, Berlin, Germany.
  7. Andres Moreira-Soto: Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Institute of Virology, Berlin, Germany.
  8. Eugenia Corrales-Aguilar: Research Center for Tropical Diseases (CIET) and Faculty of Microbiology, University of Costa Rica, San José, Costa Rica.

Abstract

The increase in incidence and geographical expansion of viruses transmitted by the mosquitoes, such as dengue (DENV) and zika (ZIKV) in the Americas, represents a burden for healthcare systems in tropical and subtropical regions. These and other under-detected arboviruses co-circulate in Costa Rica, adding additional complexity to their management due to their shared epidemiological behavior and similarity of symptoms in early stages. Since diagnostics of febrile illness is mostly based on clinical symptoms alone, we gathered acute-phase serum and urine from 399 samples of acute dengue-like cases from two healthcare facilities of Costa Rica, during an outbreak of arboviruses from July 2017 to May 2018, and tested them using molecular and serological methods. The analyses showed that of the clinically presumptive arbovirus cases that were reported, only 39.4% (n=153) of the samples were confirmed positive by RT-PCR to be DENV (DENV (10.3%), CHIKV (0.2%), ZIKV (27.3%), or mixed infections (1.5%). RT-PCR for other alphaviruses and flaviviruses, and PCR for sp were negative. Furthermore, to assess flavivirus positivity in post-acute patients, the negative sera were tested against Dengue-IgM. 20% of sera were found positive, confounding even more the definitive number of cases, and emphasizing the need of several distinct diagnostic tools for accurate diagnostics. Molecular characterization of the and genes from isolated viruses revealed that the American/Asian genotype of DENV-2 and the Asian lineage of ZIKV were circulating during this outbreak. Two different clades of DENV-2 American/Asian genotype were identified to co-circulate in the same region and a difference in the platelet and leukocyte count was noted between people infected with each clade, suggesting a putative distinct virulence. Our study sheds light on the necessity for healthcare strategies in managing arbovirus outbreaks, emphasizing the importance of comprehensive molecular and serological diagnostic approaches, as well as molecular characterization. This approach aids in enhancing our understanding of the clinical and epidemiological aspects of arboviral diseases during outbreaks. Our research highlights the need to strengthen training programs for health professionals and the need to increase research-based on laboratory evidence for diagnostic accuracy, guidance, development and implementation of public health interventions and epidemiological surveillance.

Keywords

References

  1. Am J Trop Med Hyg. 2015 Apr;92(4):875-878 [PMID: 25667056]
  2. J Virol Methods. 2001 Jun;95(1-2):153-61 [PMID: 11377722]
  3. BMC Infect Dis. 2020 Jan 30;20(1):89 [PMID: 32000695]
  4. J Clin Microbiol. 1992 Mar;30(3):545-51 [PMID: 1372617]
  5. Trop Med Infect Dis. 2020 Oct 03;5(4): [PMID: 33022908]
  6. Emerg Infect Dis. 2021 Feb;27(2): [PMID: 33496653]
  7. MethodsX. 2022 Sep 17;9:101859 [PMID: 36187156]
  8. Viruses. 2021 Mar 31;13(4): [PMID: 33807442]
  9. Annu Rev Med. 2018 Jan 29;69:395-408 [PMID: 28846489]
  10. Viruses. 2019 Aug 20;11(8): [PMID: 31434193]
  11. Pathog Glob Health. 2024 Jun;118(4):358-359 [PMID: 38421348]
  12. Lancet. 2016 Apr 2;387(10026):1482 [PMID: 27115821]
  13. PLoS One. 2017 Jan 17;12(1):e0169256 [PMID: 28095443]
  14. Trends Microbiol. 2020 Apr;28(4):276-292 [PMID: 31864844]
  15. Am J Trop Med Hyg. 2016 Jul 6;95(1):201-5 [PMID: 27139442]
  16. PLoS Negl Trop Dis. 2021 Jun 3;15(6):e0009418 [PMID: 34081717]
  17. Diagnostics (Basel). 2021 Jun 25;11(7): [PMID: 34202195]
  18. Pathogens. 2021 Jul 10;10(7): [PMID: 34358022]
  19. Am J Trop Med Hyg. 2022 Jul 05;107(2):397-400 [PMID: 35895409]
  20. Trop Doct. 2010 Apr;40(2):92-4 [PMID: 20305103]
  21. Cell Host Microbe. 2018 Jun 13;23(6):855-864.e7 [PMID: 29805095]
  22. Mol Biol Evol. 2013 Apr;30(4):772-80 [PMID: 23329690]
  23. Trans R Soc Trop Med Hyg. 2019 Nov 1;113(11):653-660 [PMID: 31365115]
  24. Am J Trop Med Hyg. 2019 Dec;101(6):1212-1218 [PMID: 31571566]
  25. Arch Med Res. 2006 Aug;37(6):760-73 [PMID: 16824937]
  26. Curr Opin Virol. 2016 Dec;21:146-150 [PMID: 27771517]
  27. Ann Glob Health. 2014 Nov-Dec;80(6):466-75 [PMID: 25960096]
  28. Emerg Infect Dis. 2019 Feb;25(2):311-315 [PMID: 30666934]
  29. Travel Med Infect Dis. 2022 Jan-Feb;45:102232 [PMID: 34896649]
  30. Lancet Infect Dis. 2017 Mar;17(3):e88-e100 [PMID: 28185868]
  31. Am J Trop Med Hyg. 2010 Jan;82(1):128-35 [PMID: 20065008]
  32. Nature. 2017 Jun 15;546(7658):411-415 [PMID: 28538734]
  33. Trends Immunol. 2016 Oct;37(10):635-636 [PMID: 27599407]
  34. Emerg Infect Dis. 2015 Jan;21(1):84-6 [PMID: 25530324]
  35. Acta Trop. 2014 Sep;137:80-7 [PMID: 24832009]
  36. Sci Rep. 2016 Mar 04;6:22592 [PMID: 26940650]
  37. Lancet. 2015 Jan 31;385(9966):453-65 [PMID: 25230594]
  38. PLoS Negl Trop Dis. 2017 Jan 9;11(1):e0005224 [PMID: 28068335]
  39. PLoS Negl Trop Dis. 2023 Sep 6;17(9):e0011169 [PMID: 37672514]
  40. BMC Infect Dis. 2023 Jun 1;23(1):371 [PMID: 37264307]
  41. Nat Rev Microbiol. 2010 Dec;8(12 Suppl):S30-8 [PMID: 21548185]
  42. Am J Trop Med Hyg. 2012 Oct;87(4):584-93 [PMID: 23042846]
  43. Am J Trop Med Hyg. 2011 Feb;84(2):218-23 [PMID: 21292887]
  44. PLoS Negl Trop Dis. 2013 Sep 26;7(9):e2462 [PMID: 24086788]
  45. Emerg Infect Dis. 2008 Aug;14(8):1232-9 [PMID: 18680646]
  46. PLoS One. 2021 Jul 30;16(7):e0255314 [PMID: 34329309]
  47. Front Cell Infect Microbiol. 2022 Sep 15;12:975398 [PMID: 36189346]
  48. Nature. 2017 Jun 15;546(7658):406-410 [PMID: 28538727]
  49. Annu Rev Microbiol. 2008;62:71-92 [PMID: 18429680]
  50. Emerg Infect Dis. 2015 Apr;21(4):557-61 [PMID: 25816211]
  51. PLoS Negl Trop Dis. 2020 May 11;14(5):e0008320 [PMID: 32392224]
  52. Am J Trop Med Hyg. 2016 Feb;94(2):400-3 [PMID: 26643533]
  53. Lancet Infect Dis. 2024 Jul;24(7):e439-e452 [PMID: 38281494]
  54. Sci Transl Med. 2024 May 29;16(749):eadn2199 [PMID: 38809964]
  55. Parasit Vectors. 2023 Jan 26;16(1):34 [PMID: 36703148]
  56. J Infect Dis. 2016 Dec 15;214(suppl 5):S441-S445 [PMID: 27920170]
  57. Lancet Infect Dis. 2017 Mar;17(3):e101-e106 [PMID: 28011234]
  58. Front Epidemiol. 2024 Jan 15;4:1342723 [PMID: 38456075]
  59. Diagnostics (Basel). 2020 May 14;10(5): [PMID: 32423058]
  60. Acta Trop. 2017 Feb;166:155-163 [PMID: 27876643]
  61. Front Cell Infect Microbiol. 2023 Nov 15;13:1279147 [PMID: 38035335]
  62. Viruses. 2022 Jan 06;14(1): [PMID: 35062297]
  63. J Wildl Dis. 2014 Jul;50(3):651-4 [PMID: 24807182]
  64. PLoS Negl Trop Dis. 2024 Jan 31;18(1):e0011408 [PMID: 38295108]
  65. PLoS Med. 2019 Jan 22;16(1):e1002726 [PMID: 30668565]
  66. Mol Biol Evol. 2020 May 1;37(5):1530-1534 [PMID: 32011700]
  67. Clin Infect Dis. 2000 May;30(5):819 [PMID: 10816152]
  68. Lancet Glob Health. 2023 Mar;11(3):e306-e307 [PMID: 36796966]
  69. Mol Biol Evol. 2018 Feb 1;35(2):518-522 [PMID: 29077904]
  70. Lancet. 2000 Mar 25;355(9209):1053-9 [PMID: 10744091]
  71. J Clin Virol. 2016 Apr;77:69-70 [PMID: 26921737]
  72. Nat Rev Microbiol. 2024 Mar 14;: [PMID: 38486116]
  73. Am J Trop Med Hyg. 2014 Mar;90(3):410-417 [PMID: 24493674]
  74. Virol J. 2008 May 21;5:63 [PMID: 18495043]
  75. Euro Surveill. 2023 Dec;28(49): [PMID: 38062947]
  76. PLoS Negl Trop Dis. 2022 Aug 4;16(8):e0010586 [PMID: 35925876]
  77. Clin Diagn Virol. 1998 May 1;10(1):75-81 [PMID: 9646004]
  78. Curr Opin Pediatr. 2023 Apr 1;35(2):155-165 [PMID: 36801979]
  79. Int J Environ Res Public Health. 2021 Jun 02;18(11): [PMID: 34199508]
  80. Clin Infect Dis. 2016 Dec 15;63(12):1584-1590 [PMID: 27578819]
  81. Nat Methods. 2017 Jun;14(6):587-589 [PMID: 28481363]
  82. Nat Microbiol. 2019 Sep;4(9):1508-1515 [PMID: 31182801]
  83. Pathogens. 2022 Dec 21;12(1): [PMID: 36678356]
  84. Emerg Infect Dis. 2016 Aug;22(8):1515-7 [PMID: 27139219]
  85. J Virol. 1998 Jan;72(1):73-83 [PMID: 9420202]
  86. PLoS One. 2015 Sep 28;10(9):e0138900 [PMID: 26414178]
  87. Sci Transl Med. 2017 Sep 27;9(409): [PMID: 28954927]
  88. PLoS Negl Trop Dis. 2023 Sep 14;17(9):e0011610 [PMID: 37708121]
  89. Diagnostics (Basel). 2021 Apr 30;11(5): [PMID: 33946597]
  90. PLoS Negl Trop Dis. 2021 Apr 26;15(4):e0008879 [PMID: 33901185]
  91. Am J Trop Med Hyg. 2022 Nov 21;108(1):107-114 [PMID: 36410319]
  92. J Infect Public Health. 2020 Feb;13(2):173-176 [PMID: 31399372]
  93. Lancet Infect Dis. 2016 Jun;16(6):641-642 [PMID: 27184420]

MeSH Term

Humans
Disease Outbreaks
Costa Rica
Dengue
Zika Virus Infection
Zika Virus
Dengue Virus
Female
Male
Adult
Adolescent
Middle Aged
Young Adult
Child
Child, Preschool
Aged
Caribbean Region
Phylogeny
Infant
Animals
Coinfection
Aged, 80 and over
Antibodies, Viral

Chemicals

Antibodies, Viral

Word Cloud

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