Clinical and epidemiological characteristics of imported cases of dengue fever depending on the molecular genetic properties of the pathogen and the levels of endothelial dysfunction markers

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Abstract

Objective. Comprehensive analysis of the clinical and epidemiological characteristics of imported cases of dengue fever (DF) in patients residing in non-endemic areas and evaluation of the relationship between disease severity, virus (DENV) serotype, and markers of endothelial dysfunction.

Materials and methods. The study included 51 patients with DF hospitalized in infectious disease hospitals in Moscow in 2024–2025. Serotyping was performed by PCR; IgM, IgG, and cytokines (tumor necrosis factor α, interleukins (IL) 1β, 8, 10) were determined by ELISA; von Willebrand factor was determined by agglutination. DF severity was assessed according to the WHO classification (2009).

Results. The study group was dominated by women (62.7%), the average age was 33.9 years. The main countries of importation were the Maldives, Thailand and Indonesia. The dominant serotype was DENV-3 (43.1%), less common were DENV-2 (31.4%) and DENV-1 (25.5%); DENV-4 was not detected. DENV-2 was more often associated with the importation of DF from the Maldives, DENV-3 - with Thailand and Sri Lanka. In the structure of forms, DF without precursors (DF-P) was predominant (64.7%), DF with precursors (LD+P) accounted for 33.3%, severe DF - 2.0%. All patients with DF+P and severe DF had hemorrhagic syndrome. The main symptoms were fever, weakness, arthralgia, rash and diarrhea. Leukopenia, lymphopenia and thrombocytopenia are characteristic. DENV-2 infection was associated with more pronounced leukotropenia and neutropenia, while DENV-3 infection was associated with elevated alanine aminotransferase levels. DF+P was more common in women and was associated with more pronounced hematological and coagulation abnormalities, as well as elevated IL-10 (p = 0.01) and von Willebrand factor (p = 0.024) levels.

Conclusion. The data obtained confirm the feasibility of using immunological, endothelial, and biochemical markers in combination with virus serotyping to improve epidemiological surveillance and assess the severity of imported cases of DF.

About the authors

Alexandra A. Luzhetskayа

Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being; Infectious Diseases Clinical Hospital № 1, Moscow Healthcare Department

Author for correspondence.
Email: luzhetskaya.98@mail.ru
ORCID iD: 0009-0004-6748-6786

Postgraduate Student; Physician, 7th Infectious Diseases Department

Russian Federation, Moscow; Moscow

Natalia Yu. Pshenichnaya

Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being; Russian Medical Academy of Continuous Professional Education, Ministry of Health of the Russia; M.F. Vladimirsky Moscow Regional Research Clinical Institute

Email: pshenichnaya@cmd.su
ORCID iD: 0000-0003-2570-711X

MD, Professor, Deputy Director for Clinical and Analytical Work; Head, Department of Infectious Diseases; Professor, Department of Infectious Diseases

Russian Federation, Moscow; Moscow; Moscow

Galina V. Gopatsa

Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being; Infectious Diseases Clinical Hospital № 1, Moscow Healthcare Department; Russian Medical Academy of Continuous Professional Education, Ministry of Health of the Russia

Email: galentinabk@mail.ru
ORCID iD: 0000-0001-8703-7671

Cand. Med, Sci., Senior Researcher, Clinical Department of Infectious Pathology; Head, 7th Infectious Diseases Department; Assistant Professor, Department of Infectious Diseases

Russian Federation, Moscow; Moscow; Moscow

Evgeny S. Morozkin

Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being

Email: morozkin@cmd.su
ORCID iD: 0000-0001-8407-2623

Cand. Chem. Sci., Head, Research Group for Developing New Methods for Diagnosing Natural Focal Diseases

Russian Federation, Moscow

Vasiliy G. Аkimkin

Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being

Email: crie@pcr.ru
ORCID iD: 0000-0003-4228-9044

Academician of the Russian Academy, МD, Professor, Director

Russian Federation, Moscow

References

  1. Osman S., Preet R. Dengue, chikungunya and Zika in GeoSentinel surveillance of international travellers: a literature review from 1995 to 2020. J. Travel Med. 2020; 27(8): taaa222. doi: 10.1093/jtm/taaa222
  2. Dengue: guidelines for diagnosis, treatment, prevention and control. Geneva: World Health Organization, 2009, 149 р.
  3. Namirimu T., Kim S. Dengue fever: epidemiology, clinical manifestations, diagnosis, and therapeutic strategies. Ann. Clin. Microbiol. 2024; 27(2): 131–141. doi: 10.5145/ACM.2024.27.2.7
  4. Tricou V., Minh N.N., Farrar J., Tran H.T., Simmons C.P. Kinetics of viremia and NS1 antigenemia are shaped by immune status and virus serotype in adults with dengue. PLoS Negl. Trop. Dis. 2011; 5(9): e1309. doi: 10.1371/journal.pntd.0001309
  5. Николаева Л.И., Ларичев В.Ф., Сайфуллин М.А., Дедова А.В., Гришечкин А.Е., Васильев А.В. и др. Анализ возможного влияния генетических факторов пациентов на течение инфекции, вызванной вирусом лихорадки денге. Инфекционные болезни: Новости. Мнения. Обучение 2022; 11(1): 8–14. [Nikolaeva L.I., Larichev V.F., Sayfullin M.A., Dedova A.V., Grishechkin A.E., Vasiliev A.V. et al. Analysis of the possible influence of patients’ genetic factors on the course of Dengue virus infectio. Infectious Diseases: News, Opinions, Training 2022; 11(1): 8–14. (In Russ.)]. doi: 10.33029/2305-3496-2022-11-1-8-14
  6. Sahu R., Verma R., Jain A., Garg R.K., Singh M.K., Malhotra H.S. et al. Neurologic complications in dengue virus infection: a prospective cohort study. Neurology 2014; 83(18): 1601–1609. doi: 10.1212/WNL.0000000000000935
  7. Malavige G.N., Ogg G.S. Pathogenesis of vascular leak in dengue virus infection. Immunology. 2017; 151(3): 261–269. doi: 10.1111/imm.12748
  8. Gómez-Barrera S., Moreno-Hortua J.M., Gallego-Gómez J.C., de Schroeder M.M., Castaño-Osorio J.C. Dengue and endothelium: a perspective on the pathophysiological implications of endothelial activation in dengue and its therapeutic possibilities. Infectio 2025; 29(4): 228–238. doi: 10.22354/24223794.1251
  9. Adikari T.N., Gomes L., Wickramasinghe N., Salimi M., Wijesiriwardana N., Kamaladasa A. et al. Dengue NS1 antigen contributes to disease severity by inducing interleukin (IL)-10 by monocytes. Clin. Exp. Immunol. 2016; 184(1): 90–100. doi: 10.1111/cei.12747
  10. Djamiatun K., van der Ven A.J., de Groot P.G., Faradz S.M., Hapsari D., Dolmans W.M. Severe dengue is associated with consumption of von Willebrand factor and its cleaving enzyme ADAMTS-13. PLoS Negl. Trop. Dis. 2012; 6(5): e1628. doi: 10.1371/journal.pntd.0001628
  11. Raghupathy R., Chaturvedi U.C., Al-Sayer H., Elbishbishi E.A., Agarwal R., Nagar R. et al. Elevated levels of IL-8 in dengue hemorrhagic fever. J. Med. Virol. 1998; 56(3): 280–285. doi: 10.1002/(sici)1096-9071(199811)56:3< 280:aid-jmv18>3.0.co;2-i
  12. Khanam A., Gutiérrez-Barbosa H., Lyke K.E., Chua J.V. Immune-Mediated Pathogenesis in Dengue Virus Infection. Viruses 2022; 14(11): 2575. doi: 10.3390/v14112575
  13. Alexander N., Balmaseda A., Coelho I.C., Dimaano E., Hien T.T., Hung N.T. et al. European Union, World Health Organization (WHO‐TDR) supported DENCO Study Group. Multicentre prospective study on dengue classification in four South-east Asian and three Latin American countries. Trop. Med. Int. Health 2011; 16(8): 936–948. doi: 10.1111/j.1365-3156.2011.02793.x
  14. Yuan K., Chen Y., Zhong M., Lin Y., Liu L. Risk and predictive factors for severe dengue infection: A systematic review and meta-analysis. PLoS One 2022; 17(4): e0267186. doi: 10.1371/journal.pone.0267186
  15. Tsheten T., Clements A.C.A., Gray D.J., Adhikary R.K., Furuya-Kanamori L., Wangdi K. Clinical predictors of severe dengue: a systematic review and meta-analysis. Infect. Dis. Poverty 2021; 10(1): 123–132. doi: 10.1186/s40249-021-00908-2
  16. Wilder-Smith A., Ooi E.E., Horstick O., Wills B. Dengue. Lancet 2019; 393(10169): 350–363. doi: 10.1016/S0140-6736(18)32560-1
  17. Campana V., Inizan C., Pommier J.D., Menudier L.Y., Vincent M., Lecuit M. Liver involvement in dengue: A systematic review. Rev. Med. Virol. 2024; 34(4): e2564. doi: 10.1002/rmv.2564
  18. Rodrigo C., Sigera C., Fernando D., Rajapakse S. Plasma leakage in dengue: a systematic review of prospective observational studies. BMC Infect. Dis. 2021; 21(1): 1082–1092. doi: 10.1186/s12879-021-06793-2
  19. Masyeni S., Wardhana I.M.W., Nainu F. Cytokine profiles in dengue fever and dengue hemorrhagic fever: A study from Indonesia. Narra J. 2024; 4(1): e309. doi: 10.52225/narra.v4i1.309
  20. Gomatheswari S.N., Poornakala R., Jeyamurugan J.T., Devi C.S. Assessment of Serum Interleukin-10 as a Marker of Severity in Dengue Virus Infection: A Cross-sectional Study. J. Clin. Diagn. Res. 2026; 20(3): DC24–DC27. doi: 10.7860/JCDR/2026/78001.22563
  21. Balmaseda A., Hammond S.N., Pérez L., Tellez Y., Saborío S.I., Mercado J.C. et al. Serotype-specific differences in clinical manifestations of dengue. Am. J. Trop. Med. Hyg. 2006; 74(3): 449–456.
  22. Soo K.M., Khalid B., Ching S.M., Chee H.Y. Meta-Analysis of Dengue Severity during Infection by Different Dengue Virus Serotypes in Primary and Secondary Infections. PLoS One 2016; 11(5): e0154760. doi: 10.1371/journal.pone.0154760
  23. Halstead S.B. Dengue Antibody-Dependent Enhancement: Knowns and Unknowns. Microbiol. Spectr. 2014; 2(6). doi: 10.1128/microbiolspec.AID-0022-2014
  24. Katzelnick L.C., Gresh L., Halloran M.E., Mercado J.C., Kuan G., Gordon A. et al. Antibody-dependent enhancement of severe dengue disease in humans. Science 2017; 358(6365): 929–932. doi: 10.1126/science.aan6836
  25. Bhatt P., Jayaram A., Varma M., Mukhopadhyay C. Kinetics of dengue viremia and its association with disease severity: an ambispective study. Virusdisease 2024; 35(2): 250–259. doi: 10.1007/s13337-024-00872-z

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