The Role of Neutrophil to Lymphocyte Ratio in Dengue Hemorrhagic Fever and Dengue Shock Syndrome: A Narrative Systematic Review

Authors

  • Dyah Deviyanti
  • Yetti Hernaningsih
  • Puspa Wardhani

Keywords:

Biomarkers (MeSH), Blood Cell Count (MeSH), Disease Progression (MeSH), Hemorrhage (MeSH), Humans (MeSH), Immunity (MeSH), Lymphocytes (MeSH), Neutrophils (MeSH), Prognosis (MeSH), Risk Asessment (MeSH), Severe Dengue (MeSH)

Abstract

This systematic review aimed to evaluate the diagnostic and prognostic utility of the neutrophil-to-lymphocyte ratio (NLR) in distinguishing disease severity among patients with dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). The review emphasizes the biomarker’s role in early detection and risk stratification. Literature searches were conducted in PubMed, Scopus, ScienceDirect, Cochrane Library, and manual searching from inception to May 2025. Only articles published in English and involving human subjects were considered. Studies were included if they reported NLR values among patients with DHF or DSS and assessed the relationship between NLR and clinical severity. The initial database search yielded 1.794 records. After removing duplicates and screening titles, abstracts, and full texts, 15 eligible studies were selected. Quality appraisal was performed using the Joanna Briggs Institute (JBI) and Newcastle–Ottawa Scale (NOS) checklists. Two independent reviewers extracted data on study design, sample size, NLR measurement, severity classification, and key statistical outcomes. Disagreements were resolved by consensus. The majority of studies reported a significant association between higher NLR and increased dengue severity, particularly in patients with DSS. However, there was notable heterogeneity in cut-off values, timing of NLR measurement, and reference standards used. A few studies suggested that lower NLR may occur at critical or late stages. NLR demonstrates potential as a simple, cost-effective biomarker for identifying severe dengue, including DHF and DSS. Nonetheless, variation in methodologies and inconsistent cut-offs limit its generalizability. Further standardized, prospective studies are warranted to establish its diagnostic thresholds and timing of use.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

References

Agrawal, S., Kumar, S., Talwar, D., Patel, M., & Reddy, H. (2023). Significance of Neutrophil-lymphocyte Ratio , Neutrophil-platelet Ratio , and Neutrophil-to- lymphocyte and Platelet Ratio in Predicting Outcomes in Dengue Patients on Admission in Wardha , Maharashtra , India : A Retrospective Cohort Study. 17(11), 001–004. https://doi.org/10.7860/JCDR/2023/65292.18658

Amri, I., Rahma, R., Hutasoit, G. A., Putri, A. S. D., Harun, H., & Rasyid, R. (2025). Comparison of Neutrophile-to-Lymphocyte Ratio Between Dengue Haemorrhagic Fever and Dengue Shock Syndrome in Pediatric Patients at Anutapura Hospital. Journal of Health and Nutrition Research, 4(1), 162–171. https://doi.org/10.56303/jhnresearch.v4i1.360

Ashma, A. N., Susilo, S. B., Marwanta, S., & Harioputro, D. R. (2023). Neutrophil-lymphocyte Ratio and Platelet-lymphocyte Ratio as Early Sign Plasma Leakage Process in Dengue Infection. JURNAL INFO KESEHATAN, 21(4), 749–757. https://doi.org/10.31965/infokes.Vol21.Iss4.1382

Biswas, M., Suvarna, R., Krishnan S, V., Devasia, T., Shenoy Belle, V., & Prabhu, K. (2022). The mechanistic role of neutrophil lymphocyte ratio perturbations in the leading non communicable lifestyle diseases. F1000Research, 11, 960. https://doi.org/10.12688/f1000research.123245.1

Buonacera, A., Stancanelli, B., Colaci, M., & Malatino, L. (2022). Neutrophil to Lymphocyte Ratio: An Emerging Marker of the Relationships between the Immune System and Diseases. In International Journal of Molecular Sciences (Vol. 23, Issue 7). https://doi.org/10.3390/ijms23073636

Calderón-Peláez, M.-A., Coronel-Ruiz, C., Castellanos, J. E., & Velandia-Romero, M. L. (2022). Endothelial Dysfunction, HMGB1, and Dengue: An Enigma to Solve. Viruses, 14(8). https://doi.org/10.3390/v14081765

Chan, L., Morovati, S., Karimi, N., Alizadeh, K., Vanderkamp, S., Kakish, J. E., Bridle, B. W., & Karimi, K. (2022). Neutrophil Functional Heterogeneity and Implications for Viral Infections and Treatments. In Cells (Vol. 11, Issue 8). https://doi.org/10.3390/cells11081322

Chapman, N. M., & Chi, H. (2022). Metabolic adaptation of lymphocytes in immunity and disease. Immunity, 55(1), 14–30. https://doi.org/10.1016/j.immuni.2021.12.012

Chen, T., Tu, S., Ding, L., Jin, M., Chen, H., & Zhou, H. (2023). The role of autophagy in viral infections. Journal of Biomedical Science, 30(1), 5. https://doi.org/10.1186/s12929-023-00899-2

de Almeida, M. T., Merighi, D. G., Visnardi, A. B., Boneto Gonçalves, C. A., Amorim, V. M., Ferrari, A. S., de Souza, A. S., & Guzzo, C. R. (2025). Latin America’s Dengue Outbreak Poses a Global Health Threat. In Viruses (Vol. 17, Issue 1). https://doi.org/10.3390/v17010057

Deshapande, D. V. B., Dinakara, D. N., Somashekar, D., Mg, D. K., Revanna, D. R., & Meda, D. P. (2024). Absolute neutrophil counts and neutrophil to lymphocyte ratio as predictive markers of dengue severity among children. Int J Pediatr Neonatology, 6(2), 74–76.

Fontoura, M. A., Rocha, R. F., & Marques, R. E. (2021). Neutrophil Recruitment and Participation in Severe Diseases Caused by Flavivirus Infection. In Life (Vol. 11, Issue 7). https://doi.org/10.3390/life11070717

Gauri, L. A., Bhatnagar, K., Sameja, P., Nehara, H. R., Saini, K., Dutt, R., Bhatnagar, B., Khokhar, M. S., Kumar, V., & Garg, A. (2022). Hematological indices as predictors of mortality in dengue shock syndrome: A retrospective study. Journal of Acute Disease, 11(4).

Hasanah, A. N., Esa, T., & Bahrun, U. (2023). Comparison of Neutrophil-Lymphocyte Ratio in Patients with COVID-19 and Dengue Hemorrhagic Fever. INDONESIAN JOURNAL OF CLINICAL PATHOLOGY AND MEDICAL LABORATORY, 30(1), 60–65. https://doi.org/10.24293/ijcpml.v30i1.2056

Irmayanti, I., Nurulita, A., & Sennang, N. (2017). Neutrophil/lymphocyte count ratio on dengue hemorrhagic fever. Indonesian Journal Of Clinical Pathology And Medical Laboratory, 23(3), 234–239.

Ishaque, N., Siddique, M. U., Imran, A., & Malik, N. A. (2022). Utilization of Neutrophil to Lymphocyte Ratio to Assess Recovery in Patients with Dengue. Journal of Haematology and Stem Cell Research, 2(2), 77–80.

Koundinya, M. A., Dasari, D., Kumar, S. A., Manjula, B. S., & Vinaya, D. (2021). Neutrophil to lymphocyte ratio as prognostic and predictor factor for severity of dengue fever-A retrospective observational study in a tertiary care centre. IAIM, 8(12), 46–52.

Leliefeld, P. H. C., Wessels, C. M., Leenen, L. P. H., Koenderman, L., & Pillay, J. (2016). The role of neutrophils in immune dysfunction during severe inflammation. Critical Care (London, England), 20, 73. https://doi.org/10.1186/s13054-016-1250-4

Ma, Y., Zhang, Y., & Zhu, L. (2021). Role of neutrophils in acute viral infection. Immunity, Inflammation and Disease, 9(4), 1186–1196. https://doi.org/10.1002/iid3.500

mahayanti, kadek seri, & Suardamana, K. (2024). THE RELATION BETWEEN THE NEUTROFIL LYMPHOCYTE RATIO (NLR) AND THE DEGREE OF DENGUE HEMORRHAGIC FEVER IN THE INPATIENT INSTALLATION OF ARI CANTI HOSPITAL FOR THE PERIOD OF APRIL 2022 – MAY 2023. E-Jurnal Medika Udayana; Vol 13 No 1 (2024): E-Jurnal Medika Udayana. https://doi.org/10.24843/MU.2024.V13.i01.P02

Maulida, Y. R., Amelia, R., & Sari, E. M. (2023). Correlation Between Neutrophil Lymfocyte Ratio (Nlr) And Platelets Values in Dengue Hemorrhagic Fever Patients at Private Hospital Jatiasih Bekasi Period 2019-2021. Proceedings The International Allied Health Students Conference (IAHSC), 222–226.

Monteiro BÖER, L., Cinquini JUNQUEIRA, I., Cardoso do NASCIMENTO, T., Oliveira GUILARDE, A., de Rezende FÉRES, V. C., & Correia de ALCÂNTARA, K. (2024). MONOCYTE-LYMPHOCYTE, NEUTROPHIL-LYMPHOCYTE, AND PLATELET-LYMPHOCYTE RATIOS AS INFLAMMATORY BIOMARKERS OF CLINICAL DENGUE SEVERITY. Bioscience Journal, 40, 1–8. https://doi.org/10.14393/BJ-v40n0a2024-67413

NAVYA, P. T., BEGUM, R., THAJUDEEN, A. S., HUSSAIN, M. A., & VIJAYASHREE, R. (2024). Navigating the Haematological Maze: Unraveling the Role of NLR and PLR as Predictors of Dengue Severity-A Cross-sectional Study from Southern India. Journal of Clinical & Diagnostic Research, 18(3).

Prajapati, A. K. (2024). Significance of neutrophil to lymphocyte ratio evaluation as a prognostic indicator in dengue patients . 18(03), 9–17.

Pribadi, M. I., Umma, H. A., & Siregar, R. (2025). Neutrophil-lymphocyte ratio as an indicator of recovery phase in children with dengue fever. Trends in Pediatrics, 6(1), 25–32.

Raadsen, M., Du Toit, J., Langerak, T., van Bussel, B., van Gorp, E., & Goeijenbier, M. (2021). Thrombocytopenia in Virus Infections. In Journal of Clinical Medicine (Vol. 10, Issue 4). https://doi.org/10.3390/jcm10040877

Rawat, S., Vrati, S., & Banerjee, A. (2021). Neutrophils at the crossroads of acute viral infections and severity. Molecular Aspects of Medicine, 81, 100996. https://doi.org/10.1016/j.mam.2021.100996

Sadgir, A., Durge, K., & Masavkar, S. (2023). Neutrophil-lymphocyte ratio as a prognostic indicator in dengue fever patients at tertiary care hospital in northwest Maharashtra. Int J Ad Res, 11, 1198–1202.

Sajjad, Z., Tashfeen, S., Shahid, S., Bibi, A., Irfan, R., Naeem, U., & Butt, M. N. (2025). Correlation of Total Leucocyte Count, Neutrophil to Lymphocyte Ratio and Platelet Count with Duration of Hospital Stay in Dengue Fever. Life and Science, 6(1), 6.

Song, M., Graubard, B. I., Rabkin, C. S., & Engels, E. A. (2021). Neutrophil-to-lymphocyte ratio and mortality in the United States general population. Scientific Reports, 11(1), 464. https://doi.org/10.1038/s41598-020-79431-7

Wazib, A., Rahman, S., Al Mamun, K. A., Ahmed, M. R., Aman, S., Babu, M. A., Tahmid, A., Nishat, T. H., & Ira, I. J. (2025). Predicting the Risk of Dengue Shock Syndrome with Neutrophil-Lymphocyte Ratio on the Third Day of Dengue Infection. East West Medical College Journal, 13(1), 50–53.

Witte, P., Venturini, S., Meyer, H., Zeller, A., & Christ, M. (2024). Dengue Fever—Diagnosis, Risk Stratification, and Treatment. Deutsches Arzteblatt International, 121(23), 773–778. https://doi.org/10.3238/arztebl.m2024.0175

Yuditya, D. C., & Sudirgo, I. (2020). The Relation between Neutrophil Lymphocyte Count Ratio (NLCR) and Dengue Infection Grade of Severity in Adult Patients in RS Muhammadiyah Ahmad Dahlan Kediri in January 2019. STRADA : Jurnal Ilmiah Kesehatan, 9(1), 20–25. https://doi.org/10.30994/sjik.v9i1.265

Zahorec, R. (2021). Neutrophil-to-lymphocyte ratio, past, present and future perspectives. Bratislavske Lekarske Listy, 122(7), 474–488. https://doi.org/10.4149/BLL_2021_078

Downloads

Published

2025-07-09

How to Cite

1.
Deviyanti D, Hernaningsih Y, Wardhani P. The Role of Neutrophil to Lymphocyte Ratio in Dengue Hemorrhagic Fever and Dengue Shock Syndrome: A Narrative Systematic Review. J Neonatal Surg [Internet]. 2025Jul.9 [cited 2025Sep.10];14(32S):4468-77. Available from: https://www.jneonatalsurg.com/index.php/jns/article/view/8139