Changes in neutrophil-to-lymphocyte and monocyte-to-lymphocyte ratios after multidrug therapy in multibacillary leprosy

To the Editor, Multibacillary leprosy is characterized by a high bacillary load and complex immune responses, with systemic inflammation playing a central role in disease progression and the development of reactional states.[1,2] Simple hematological indices derived from routine blood counts, such as the neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR),[3,4] are increasingly used as surrogate markers of inflammatory burden in various infectious and immune-mediated diseases, including leprosy.[3,5] While previous studies have primarily focused on the role of these ratios in predicting leprosy reactions,[5,6] data regarding their longitudinal behaviour following multidrug therapy (MDT) remain limited. In this correspondence, we report exploratory observations regarding the changes in the NLR and MLR before and after MDT in patients with multibacillary leprosy. This study was approved by the Health Research Ethics Committee of the Faculty of Medicine and Health Sciences, Universitas Muhammadiyah Makassar (519/UM.PKE/II/45/2024) and was conducted in accordance with the Declaration of Helsinki. The requirement for individual informed consent was waived by the ethics committee due to the retrospective design of the study and the use of anonymised medical record data. This retrospective cohort study involved 40 adult patients with newly diagnosed multibacillary leprosy treated at a referral dermatology center in South Sulawesi, Indonesia, between February and October 2024. All participants were free of acute leprosy reactions at baseline and were re-evaluated at release from treatment (RFT). Baseline hematological parameters were obtained from medical records prior to MDT initiation, and follow-up blood samples were collected 2–3 weeks after RFT. Neutrophil, lymphocyte, and monocyte counts were measured using an automated hematology analyzer to calculate the NLR and MLR. During follow-up, patients were categorized descriptively into three groups: those without a reaction, those who developed a type 1 reaction (reversal reaction, T1R), and those who developed a type 2 reaction (erythema nodosum leprosum, ENL). Overall, both NLR and MLR consistently decreased following MDT completion across all patient subgroups. For example, in patients without reaction, the median NLR declined from approximately 14 at baseline to about 2, with a similarly marked reduction observed in the MLR (Table 1). Comparable downward trends were observed among patients who developed T1R or ENL during follow-up. These findings indicate a general reduction in systemic inflammation following MDT, regardless of reactional status. Given the correspondence format, the results are presented descriptively to highlight observed longitudinal patterns rather than to infer diagnostic or predictive performance. Table 1 - Changes in neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) before and after multidrug therapy (MDT) Variable Without reaction group (n = 18) Type 1 reaction group (n = 7) Type 2 reaction group (n = 15) NLR Before MDT 14.52 (12.64–15.67) 16.00 (13.06–17.33) 15.10 (12.54–23.55) After MDT 1.98 (1.72–3.38) 3.64 (2.84–5.56) 3.13 (2.09–3.56) P <0.001 0.016 <0.001 MLR Before MDT 1.41 (1.10–1.52) 1.28 (1.21–1.40) 1.34 (1.11–1.76) After MDT 0.25 (0.18–0.35) 0.41 (0.36–0.45) 0.35 (0.24–0.50) P <0.001 0.016 <0.001 Data are presented as median (interquartile range). Comparisons before and after MDT were performed using the Wilcoxon signed-rank test. The observed reductions in NLR and MLR are biologically plausible as neutrophils and monocytes constitute the primary innate immune responses to Mycobacterium leprae, while lymphocytes govern the subsequent adaptive immunity response.[3,4] These longitudinal shifts reflect a modulation of the host immune response following effective antimicrobial therapy. MDT is known to reduce bacillary burden and modulate host immune responses, which may contribute to the observed normalization of these hematological ratios.[4] Although a sustained downward trend was observed, patients experiencing reactional episodes exhibited relatively higher post-treatment values than non-reactional counterparts, likely due to persistent but diminished immune activation. This study has several limitations that should be acknowledged. First, it was conducted at a single center with a relatively small sample size. Second, hematological measurements were obtained only at baseline and shortly after RFT, lacking intermediate longitudinal data. Finally, the use of non-standardized corticosteroid and inflammatory treatments to manage reactional episodes may have influenced the inflammatory indices. Consequently, these findings should be considered preliminary and hypothesis-generating rather than definitive evidence of clinical utility. In summary, this correspondence highlights exploratory observations indicating that NLR and MLR decrease following MDT in patients with multibacillary leprosy, reflecting a broad reduction in systemic inflammation. As accessible, widely available indices, they hold potential for tracking inflammatory trends in clinical practice. Further prospective studies with larger cohorts and standardized follow-ups are warranted to validate their role in leprosy management. Notably, this analysis presents descriptive, pre-post changes following MDT. Due to the small sample size, statistical inferences are limited, and results should be interpreted with caution. Further validation is warranted in larger cohorts. Funding This study is supported by an internal research grant from Universitas Muhammadiyah Makassar. Author Contributions Sitti Musafirah Arif was involved in the conception and design of the study, data analysis and interpretation, and drafting the manuscript. Andi Tenri Padad contributed to data acquisition and data interpretation and critically revised the manuscript for important intellectual content. Tri Ariguntar Wikaningtyas and Nurul Mujahidah A Agus contributed to data analysis and acquisition, interpretation of results, and manuscript revision. All authors approved the final version of the manuscript for publication. Conflicts of Interest None. Data Availability Statement The datasets generated and/or analysed during the current study are available from the corresponding author on reasonable request.