Effectiveness of intralesional sodium stibogluconate for the treatment of localized cutaneous leishmaniasis at Boru Meda general hospital, Amhara, Ethiopia: Pragmatic trial

Abstract

Background Cutaneous leishmaniasis (CL) is generally caused by Leishmania aethiopica in Ethiopia, and is relatively hard to treat. Sodium stibogluconate (SSG) is the only routinely and widely available antileishmanial treatment, and can be used systemically for severe lesions and locally for smaller lesions. There is limited data on the effectiveness of intralesional (IL) SSG for localized CL in Ethiopia and therefore good data is necessary to improve our understanding of the effectiveness of the treatment. Methodology/Principal findings A pragmatic (before and after Quazi experimental) study was done to assess the effectiveness of intralesional SSG among localized CL patients at Boru Meda general hospital, Northeast Ethiopia. Patients who were assigned to intralesional SSG by the treating physician were eligible for this study. Study subjects were recruited between January and August 2021. Infiltration of intralesional SSG was given weekly to a maximum of six doses. However, when a patient’s lesions were already cured before getting 6 doses, treatment was not conintued, and patient were only asked to come for lesion assessment. Skin slit smears (SSS) were taken each week until they became negative. Outcomes were assessed at day 90, with patients who had 100% reepithelization (for ulcerative lesions) and/or flattening (for indurated lesions) defined as cured. Multi-level logistic regression was done to assess factors associated with cure. A total of 83 patients were enrolled, and final outcomes were available for 72 (86.75%). From these 72, 43 (59.7%, 95% confidence interval 0.44–0.69) were cured at day 90. Adverse effects were common with 69/72 patients (95.8%) reporting injection site pain. Factors associated with cure were age (OR 1.07 95% CI: 1.07–1.27), being male (OR 1.79, 95% CI: 1.10–2.25), size of the lesion (OR 0.79, 95% CI: 0.078–0.94) and skin slit smear (SSS) result +1 grading (OR 1.53, 95% CI: 1.24–1.73) and +2 grading (OR 1.51, 95% CI: 1.41–3.89) compared to the SSS grade +6. Conclusion Our findings revealed that intralesional sodium stibogluconate resulted in a cure rate of around 60%, with almost all patients experiencing injection site pain. This emphasizes the need for local treatment options which are more patient-friendly and have better cure rates.

Histological findings associated with treatment response in cutaneous leishmaniasis: a clinicopathological correlation study

“…Our study has provided evidence that heavy parasite loads observed during histological examinations predict a poor response to SSG and longer healing times. Similar observations have been reported in localized CL due to L. aethiopica , where SSS with lower parasite numbers were associated with a higher chance of cure 25 . The response to effective treatment is typically expected to be higher and faster during the early stages of infection, when parasites are abundant and easier for the drug to reach, in contrast to chronic and relapsing forms of CL, which are usually associated with low parasite loads and fibrotic tissue reactions.…”

“…Oliveira et al., conducting a study in a similar setting, reported that the size of the ulcer at the first medical visit correlated with healing time, 29 while treatment failure was more likely when referred 5 months after the onset of lesions due to L. tropica 30 . The addition of other treatment modalities, such as cryotherapy, as we and others have reported, is often a clinical decision based on features such as the type of lesion 25 . Further comprehensive studies are required to investigate if such combination therapies, which apparently improve the efficacy of treatment, have similar clinicopathological associations.…”

“…Similar observations have been reported in localized CL due to L. aethiopica, where SSS with lower parasite numbers were associated with a higher chance of cure. 25 The response to effective treatment is typically expected to be higher and faster during the early stages of infection, when parasites are abundant and easier for the drug to reach, in contrast to chronic and relapsing forms of CL, which are usually associated with low parasite loads and fibrotic tissue reactions. Taken together with our findings of higher parasite loads being associated with inflammation involving the entire dermis, we believe that the prolonged healing time is also a reflection of the exacerbated inflammatory response by the host in such instances.…”

“…30 The addition of other treatment modalities, such as cryotherapy, as we and others have reported, is often a clinical decision based on features such as the type of lesion. 25 Further comprehensive studies are required to investigate if such combination therapies, which apparently improve the efficacy of treatment, have similar clinicopathological associations.…”

Treatment outcomes of cutaneous leishmaniasis due to Leishmania aethiopica: A systematic review and meta-analysis

“…aethiopica [ 17 , 18 ]. Among LCL cases treated with six cycles of intralesional-SSG v (IL-SSG v ), a higher chance of cure was positively associated with being male, increasing age and SSS grade +1 and +2 [ 18 ]. With 28 days of oral miltefosine treatment, MCL cases showed lower odds of relapse on day 180 [ 17 ].…”