Association Between Nonstructural Protein 1 Antigenemia and Leukopenia in Dengue Infection

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Background: Dengue is a widespread mosquito-borne illness across tropical and subtropical areas. Leukopenia is a common hematological abnormality in dengue infection; however, the association between dengue serological markers and white blood cell (WBC) count has not been well characterized. Objective: To evaluate the association between dengue nonstructural protein 1 (NS1) antigen positivity, dengue immunoglobulin M (IgM) antibody positivity, and WBC count categories among serologically confirmed dengue patients. Materials and Methods: A retrospective observational study was conducted among 457 serologically confirmed dengue patients attending a tertiary care teaching hospital between October and December 2025. Demographic characteristics, dengue NS1 antigen status, dengue IgM antibody status, and WBC counts were obtained from laboratory records. WBC counts were categorized as leukopenia (<4000 cells/mm 3 ), normal (4000 to 11,000 cells/mm 3 ), or leukocytosis (>11,000 cells/mm 3 ). Associations between serological markers and WBC count categories were analyzed using Pearson’s chi-square test. Odds ratios (ORs) with 95% CIs were calculated where appropriate. Results: Among the 457 patients, leukopenia was observed in 145 (31.7%), while 305 (66.7%) had normal counts and 7 (1.5%) had leukocytosis. NS1 antigen was positive in 288 patients (63.0%) and dengue IgM antibody in 264 (57.8%). Leukopenia was present in 128 of 288 NS1 antigen-positive patients (44.4%) compared with 17 of 169 NS1 antigen-negative patients (10.1%) (Fisher exact test, P < 0.001; OR: 7.15; 95% CI: 4.12-12.43). As a marker of NS1 antigen positivity, leukopenia showed a specificity of 89.9% (95% CI: 84.5-93.6) and a positive predictive value of 88.3% (95% CI: 82.0-92.5), but a sensitivity of only 44.4% (95% CI: 38.8-50.2). Dengue IgM antibody positivity showed the opposite relationship: leukopenia was present in 63 of 264 IgM-positive patients (23.9%) compared with 69 of 177 IgM-negative patients (39.0%) (Fisher exact test, P < 0.001; OR: 0.49; 95% CI: 0.32-0.74). Leukopenia was most frequent in the small group with equivocal IgM results (13/16, 81.2%). Conclusions: Leukopenia was markedly more frequent among NS1 antigen-positive patients and markedly less frequent among IgM antibody-positive patients, indicating that leukopenia clusters in the early viremic phase of dengue infection and resolves as the antibody response develops. Leukopenia was specific but insensitive as a marker of the NS1 antigen-positive phase, so its principal practical value may lie in informing the choice and timing of serological testing rather than in confirming a diagnosis already established by NS1 antigen detection. Prospective multicenter studies recording the day of illness at presentation, serial hematological measurements, quantitative NS1 antigen levels, and clinical outcomes are warranted to validate these findings.