Interleukin-8 Predicts Fatal Kala-Azar: A Case–Control Study
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Design and Setting
2.2. Inclusion Criteria and Follow-Up
2.3. Serum Cytokines
2.4. Clinical and Laboratory Variables
2.5. Statistical Analysis
2.6. Ethical Approval
3. Results
3.1. Study Population
3.2. Serum Cytokine Levels in Survivors and Non-Survivors with Kala-Azar
3.3. Diagnostic Performance of Serum Cytokines in Predicting Fatal Kala-Azar
3.4. Serum Cytokine Profiles by HIV Coinfection Status
3.5. Diagnostic Performance of Dichotomized IL-8 in Predicting Fatal Kala-Azar
3.6. Influence of HIV Coinfection on IL-8 Discriminatory Power
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
AUC | Area under the curve |
CI | Confidence interval |
CNPq | Conselho Nacional de Desenvolvimento Científico e Tecnológico |
HIV | Human immunodeficiency virus |
IFN-γ | Interferon-gamma |
IL | Interleukin |
IL-1β | Interleukin-1 beta |
ROC | Receiver operating characteristic curve |
TNF-α | Tumor necrosis factor-alpha |
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Variables | Survivors (n = 42) n (%) | Deceased (n = 48) n (%) | Total (n = 90) n (%) | p-Value |
---|---|---|---|---|
Sex | 0.924 a | |||
Male | 31 (73.8) | 35 (72.9) | 66 (73.3) | |
Female | 11 (26.2) | 13 (27.1) | 24 (26.7) | |
Age groups | ||||
Child (age < 18 years) | 23 (54.8) | 9 (18.7) | 32 (35.6) | <0.0001 a |
Adult (18–59 years) | 18 (42.8) | 30 (62.5) | 48 (53.3) | 0.06 a |
Elderly (≥60 years) | 1 (2.4) | 9 (18.8) | 10 (11.1) | 0.014 a |
Comorbidities | ||||
HIV coinfection | 3 (7.1) | 16 (33.3) | 19 (21.1) | 0.002 b |
Complications during hospitalization c | ||||
Bacterial infection | 12 (28.6) | 27 (56.2) | 39 (43.3) | 0.008 a |
Hemorrhage | 1 (2.4) | 22 (45.8) | 23 (25.6) | <0.0001 b |
Cytokine | Survivors (n = 42) | Deceased (n = 48) | Total (n = 90) | p-Value * | Reference 1 | |||
---|---|---|---|---|---|---|---|---|
Mean | Median (IQR) | Mean | Median (IQR) | Mean | Median (IQR) | Median (IQR) | ||
IL-1β | 22.7 | 2.5 (1.0–6.6) | 3.6 | 0.0 (0.0–4.0) | 12.5 | 1.7 (0.0 –6.0) | 0.001 | 0.2 (0.0–3.7) |
IL-6 | 161.3 | 26.7 (11.2–54.7) | 334.0 | 49.9 (13.1–125.1) | 253.4 | 30.1 (11.4–77.1) | 0.100 | 0.0 (0.0–0.0) |
IL-8 | 176.5 | 26.4 (15.1–47.7) | 267.0 | 76.5 (35.2–242.4) | 224.8 | 46.6 (21.9–120.5) | <0.0001 | 0.0 (0.0–0.0) |
IL-10 | 21.4 | 15.9 (8.0–30.6) | 27.4 | 13.1 (4.8–29.5) | 24.6 | 13.8 (5.6–30.6) | 0.571 | 0.0 (0.0–0.0) |
IL-12 | 1.8 | 0.9 (0.0–2.0) | 1.5 | 0.0 (0.0–0.0) | 1.6 | 0.0 (0.0–1.1) | <0.0001 | 0.0 (0.0–0.0) |
TNF-α | 6.1 | 1.7 (0.3–6.5) | 2.5 | 0.0 (0.0–2.4) | 4.2 | 0.8 (0.0–3.9) | <0.001 | 0.0 (0.0–0.0) |
Cytokine | Optimal Cutoff (pg/mL) | Sensitivity (%) | Specificity (%) | AUC (95 % CI) |
---|---|---|---|---|
IL-1β | 0.6 | 56.3 | 88.1 | 0.31 (0.20–0.42) |
IL-6 | 49.5 | 52.1 | 73.8 | 0.60 (0.48–0.72) |
IL-8 | 49.3 | 70.8 | 76.2 | 0.75 (0.65–0.86) |
IL-10 | 45.3 | 16.7 | 92.9 | 0.47 (0.34–0.59) |
IL-12 | 0.3 | 83.3 | 69.0 | 0.30 (0.17–0.37) |
TNF-α | 0.0 | 62.5 | 85.7 | 0.29 (0.18–0.40) |
Cytokine | Kala-Azar without HIV (n = 71) | Kala-Azar with HIV (n = 19) | Total (n = 90) | p-Value * | |||
---|---|---|---|---|---|---|---|
Mean | Median (IQR) | Mean | Median (IQR) | Mean | Median (IQR) | ||
IL-1β | 15.6 | 2.3 (0.7–7.0) | 0.9 | 0.0 (0.0–0.7) | 12.5 | 1.7 (0.0–6.0) | 0.0002 |
IL-6 | 292.5 | 29.8 (11.7–77.1) | 107.2 | 34.7 (10.5–129.4) | 253.4 | 30.1 (11.4–77.1) | 0.9404 |
IL-8 | 247.6 | 45.5 (19.2–124.1) | 139.5 | 53.4 (25.8–104.5) | 224.8 | 46.6 (21.9–120.5) | 0.9606 |
IL-10 | 27.0 | 15.0 (8.1–30.6) | 15.5 | 5.6 (1.5–30.8) | 24.6 | 13.8 (5.6–30.6) | 0.0551 |
IL-12 | 2.0 | 0.0 (0.0–1.5) | 0.3 | 0.0 (0.0–0.0) | 1.6 | 0.0 (0.0–1.1) | 0.0123 |
TNF-α | 5.2 | 1.7 (0.0–6.9) | 0.2 | 0.0 (0.0–0.0) | 4.2 | 0.8 (0.0–3.9) | <0.0001 |
Parameter | n | AUC (95 % CI) | * p-Value (DeLong Test) |
---|---|---|---|
IL-8 in patients without HIV | 71 | 0.79 (0.67–0.89) | – |
IL-8 in patients with HIV | 19 | 0.77 (0.51–1.00) | 0.9216 |
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Lima, S.S.; Braz, D.C.; Silva, V.C.; de Jesus Cardoso Farias Pereira, T.; da Costa Araújo Alves Carvalho, L.K.; Costa, D.L.; Costa, C.H.N. Interleukin-8 Predicts Fatal Kala-Azar: A Case–Control Study. Trop. Med. Infect. Dis. 2025, 10, 250. https://doi.org/10.3390/tropicalmed10090250
Lima SS, Braz DC, Silva VC, de Jesus Cardoso Farias Pereira T, da Costa Araújo Alves Carvalho LK, Costa DL, Costa CHN. Interleukin-8 Predicts Fatal Kala-Azar: A Case–Control Study. Tropical Medicine and Infectious Disease. 2025; 10(9):250. https://doi.org/10.3390/tropicalmed10090250
Chicago/Turabian StyleLima, Simone Soares, Débora Cavalcante Braz, Vladimir Costa Silva, Teresinha de Jesus Cardoso Farias Pereira, Líndia Kalliana da Costa Araújo Alves Carvalho, Dorcas Lamounier Costa, and Carlos Henrique Nery Costa. 2025. "Interleukin-8 Predicts Fatal Kala-Azar: A Case–Control Study" Tropical Medicine and Infectious Disease 10, no. 9: 250. https://doi.org/10.3390/tropicalmed10090250
APA StyleLima, S. S., Braz, D. C., Silva, V. C., de Jesus Cardoso Farias Pereira, T., da Costa Araújo Alves Carvalho, L. K., Costa, D. L., & Costa, C. H. N. (2025). Interleukin-8 Predicts Fatal Kala-Azar: A Case–Control Study. Tropical Medicine and Infectious Disease, 10(9), 250. https://doi.org/10.3390/tropicalmed10090250