Impact of Dapsone (MDT/WHO) on hematological tests of leprosy patients: A retrospective cohort study

BackgroundDapsone, a component of the WHO-recommended multidrug therapy (MDT/WHO) for leprosy, can induce oxidative hemolysis through its hydroxylamine metabolites. However, treatment guidelines lack objective laboratory thresholds to guide dapsone initiation. This study aimed to quantify the hematologic toxicity and evaluate potential liver effects of of dapsone and identify sex-specific cutoff values that predict anemia development. MethodologyWe conducted a retrospective cohort study using data from 258 patients treated for leprosy at a Brazilian tertiary hospital. Hematologic parameters were evaluated at diagnosis and 1, 3, 6, and 12 months of treatment. Patients were grouped by regimen: MDT/WHO (continuous dapsone use) and MDT/SUBSTITUTIVE (dapsone replaced after 1st month). ROC curve analyses were performed to identify optimal thresholds for predicting anemia by dapsone. Results/Principal FindingsAfter the first month, patients had a mean Hb value decline of 1.14g/dL for MDT/WHO, and 1.65g/dL for MDT/SUBSTITUTIVE. Anemia percentual decreased by 58.5% in the MDT/SUBSTITUTIVE while only 13.0% in the MDT/WHO on month 12. For males, ROC analysis identified Hb<14.15g/dL (AUC 0.710), HCT<43.05% (AUC 0.711), and RBC<4.88x10/mm3 (AUC 0.599) as optimal thresholds. For females, the cutoffs were Hb<13.65g/dL (AUC 0.767), HCT<38.85% (AUC 0.561), and RBC<4.455x10/mm3 (AUC 0.590). Aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase were also assessed; no clinically significant hepatotoxicity was found, nor correlation with Hb changes. ConclusionsDapsone induces early and sustained anemia during MDT/WHO. Our findings define sex-specific baseline thresholds for safer dapsone prescription. For males, absolute contraindication occurs with Hb<13.65g/dL (RR: 2.76[95%CI 1.92-3.98]), HCT<40.95%, or RBC<4.62x10/mm3; relative contraindication for Hb<14.15g/dL (RR: 2.53[1.68-3.80]), HCT<43.05%, or RBC<4.88x10/mm3. For females, absolute contraindication is with Hb<12.95g/dL (RR: 2.29[1.59-3.30]), HCT<36.5%, or RBC<4.2x10/mm3; relative contraindication for Hb<13.65g/dL (RR: 2.64[1.41-4.93]), HCT<38.85%, or RBC<4.455x10/mm3. These thresholds support individualized, laboratory-based eligibility criteria and early dapsone substitution in high-risk individuals. Author summaryLeprosy remains an important public health challenge, particularly in countries where it is still endemic, and its treatment depends on a combination of drugs that includes dapsone. While dapsone is a key part of therapy, it often causes anemia, a condition where the blood cannot carry enough oxygen to meet the bodys needs. This side effect not only weakens patients but can also reduce their ability to complete treatment successfully. Until now, there were no clear laboratory values to help doctors decide when dapsone could be used safely or when it should be replaced, leaving both patients and health professionals uncertain. In this study, we followed people with leprosy treated at a hospital in Brazil and reviewed their blood tests at several points during one year of treatment. We found that anemia appeared quickly after therapy began, especially among women, and in many patients, it persisted until the end of treatment. Those who stopped dapsone early showed faster recovery. By analyzing blood counts before treatment, we identified values that predicted who was most at risk. Our findings provide practical thresholds that can support safer, more personalized treatment of leprosy, particularly in resource-limited settings where close monitoring is difficult.