The polymorphism of cutaneous leishmaniasis (CL) complicates diagnosis in health care services because lesions may be confused with other dermatoses such as sporotrichosis, paracocidiocomycosis, and venous insufficiency. Automated identification of skin diseases based on deep learning (DL) has been applied to assist diagnosis. In this study, we evaluated the performance of AlexNet, a DL algorithm, to identify pictures of CL lesions in patients from Midwest Brazil. We used a set of 2458 pictures (up to 10 of each lesion) obtained from patients treated between 2015 and 2022 in the Leishmaniasis Clinic at the University Hospital of Brasilia. We divided the picture database into training (80%), internal validation (10%), and testing sets (10%), and trained and tested AlexNet to identify pictures of CL lesions. We performed three simulations and trained AlexNet to differentiate CL from 26 other dermatoses (e.g., chromomycosis, ecthyma, venous insufficiency). We obtained an average accuracy of 95.04% (Confidence Interval 95%: 93.81–96.04), indicating an excellent performance of AlexNet in identifying pictures of CL lesions. We conclude that automated CL identification using AlexNet has the potential to assist clinicians in diagnosing skin lesions. These results contribute to the development of a mobile application to assist in the diagnosis of CL in health care services.
Protective effects of Bacillus Calmette–Guérin (BCG) vaccination and clofazimine and dapsone treatment against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported. Patients at risk for leprosy represent an interesting model for assessing the effects of these therapies on the occurrence and severity of coronavirus disease 2019 (COVID-19). We assessed the influence of leprosy-related variables in the occurrence and severity of COVID-19. We performed a 14-month prospective real-world cohort study in which the main risk factor was 2 previous vaccinations with BCG and the main outcome was COVID-19 detection by reverse transcription polymerase chain reaction (RT-PCR). A Cox proportional hazards model was used. Among the 406 included patients, 113 were diagnosed with leprosy. During follow-up, 69 (16.99%) patients contracted COVID-19. Survival analysis showed that leprosy was associated with COVID-19 (p<0.001), but multivariate analysis showed that only COVID-19-positive household contacts (hazard ratio (HR) = 8.04; 95% CI = 4.93–13.11) and diabetes mellitus (HR = 2.06; 95% CI = 1.04–4.06) were significant risk factors for COVID-19. Leprosy patients are vulnerable to COVID-19 because they have more frequent contact with SARS-CoV-2-infected patients, possibly due to social and economic limitations. Our model showed that the use of corticosteroids, thalidomide, pentoxifylline, clofazimine, or dapsone or BCG vaccination did not affect the occurrence or severity of COVID-19. Leprosy is a chronic infectious disease caused by Mycobacterium leprae and Mycobacterium lepromatosis. Coronavirus disease 2019 (COVID-19) results in an intense inflammatory response that is dependent on several immune mediators. Since the beginning of the COVID-19 pandemic, an interaction of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and M. leprae infection has been considered a possibility. Protective effects of Bacillus Calmette–Guérin (BCG) vaccination and clofazimine and dapsone treatment against SARS-CoV-2 infection have been reported. Patients at risk for leprosy represent an interesting model for assessing the effects of these therapies on the occurrence and severity of COVID-19. We assessed the influence of leprosy-related variables in the occurrence and severity of COVID-19. We performed a 14-month study. Among the 406 included patients, 113 were diagnosed with leprosy. During follow-up, 69 (16.99%) patients contracted COVID-19. Our analysis showed that only COVID-19-positive household contacts and diabetes mellitus were significant risk factors for COVID-19. Leprosy patients are vulnerable to COVID-19 because they have more frequent contact with SARS-CoV-2-infected patients, possibly due to social and economic limitations. Our model showed that the use of clofazimine or dapsone or BCG vaccination did not affect the occurrence or severity of COVID-19.
1 July 2021 in Frontiers in Cellular and Infection Microbiology
Introduction: American tegumentary leishmaniasis (ATL), which can present as either cutaneous (CL) or mucosal leishmaniasis (ML), is endemic in South America, and first-line antimonial treatments are known for their wide range of adverse effects (AEs). Growing reports of drug resistance increase the urgency of the need for better treatment options. The objective of this pilot clinical trial was to assess the efficacy of and AEs associated with the oral combination of miltefosine and pentoxifylline based on a post hoc analysis.Methods: A pilot, randomized, open-label clinical trial was performed. The experimental group (M+P) received 50 mg twice a day (BID) miltefosine and 400 mg three times a day (TID) pentoxifylline, and the control group (A+P) received 20 mg Sb+V/kg/day intravenously and 400 mg TID pentoxifylline. Patients with ML received treatment for 28 days, and patients with CL received treatment for 20 days.Results: Forty-three patients were included: 25 with ML and 18 with CL caused by L.(V.) braziliensis. AEs were more frequent in the A+P group (p=0.322), and there was a need for treatment interruption due to severe AEs (p=0.027). Patients with CL had a higher chance of achieving a cure (p=0.042) and a higher risk of AEs (p=0.033). There was no difference in the chance of a cure based on the treatment (p=0.058).Conclusion: In this pilot randomized clinical trial, M+P treatment and A+P treatment yielded similar cure rates, and the former was associated with a lower risk of AEs. Future studies with more patients and longer follow-up are recommended.
23 September 2022 in Frontiers in Cellular and Infection Microbiology
Background: Pentavalent antimonials (PAs) are the primary therapeutic option for American tegumentary leishmaniasis (ATL). However, the use of these drugs is complicated by adverse events (AEs), resistance and contraindications. Alternative therapies relative effectiveness is not well established.Objective: This study compared the effectiveness of liposomal amphotericin B (LAB) with intravenous meglumine antimoniate (NMG) in the treatment of ATL. We also analysed and compared associated AEs and treatment interruption rates.Methods: This was a retrospective cohort study from Brazil. The potential risk factors for the primary outcome were age, sex, total cutaneous lesion area, presence of mucosal lesions, AEs and treatment interruption. The primary outcome was lesion healing within 6 months of treatment. AEs and treatment interruption were also analysed. Multiple analytic strategies were employed to evaluate the reliability of the results.Results: Before propensity score (PS) matching, patients in the LAB group were older and had a higher frequency of mucosal lesions. The NMG group had a higher cure rate than the LAB group (cure rate 88% versus 55% respectively) in the adjusted analysis (relative risk (RR)=1.55 95% CI: 1.19 - 2.02) and after PS matching (RR=1.63 95% CI: 1.20 - 2.21). NMG group had a higher AE rate (event rate 52% versus 44%) in the adjusted analysis (RR= 1.61, 95% CI: 1.06 - 2.43, p=0.02), but this result was not observed after PS matching (RR= 0.87, 95% CI: 0.49 -1.52, p= 0.61).Conclusions: We observed that the NMG group had a higher cure rate than the LAB group, with an equivocally higher EV rate in the adjusted analysis.
1 December 2020 in International Journal for Parasitology: Drugs and Drug Resistance
The standard therapy for American cutaneous leishmaniasis (ACL) is intravenous meglumine antimoniate (IV-MA). However, treatment interruptions due to adverse events (AEs) and non-adherence are frequent. Consequently, intralesional MA (IL-MA) was proposed. This study examined the effectiveness of and AEs associated with IL-MA. We performed a retrospective cohort study of 240 patients with ACL. We excluded patients with mucous lesions and disseminated leishmaniasis and those who received treatment in the previous 6 months. We considered protocol treatments as the main risk factors. IL-MA was performed using a subcutaneous injection of MA in a volume sufficient to elevate the lesion base (approximately 1 mL/cm2 of lesion area) once weekly for 1-8 weeks. IV-MA was performed via intravenous injections of MA at a dosage of 10-20 mg Sb5+/kg/day for 20 days. The primary outcome was defined as a lesion cure 3 months after treatment, and AEs were secondary outcomes. Seventy-three patients were included. The IL-MA group consisted of 21 patients, and the IV-MA group consisted of 52 patients. The IL-MA group was older, had more comorbidities and more previous unsuccessful treatment of ACL. The antimonial dose was significantly lower in this group. The cure rate for IL-MA was 66.7%, which was lower than that in the IV-MA group (relative risk (RR) = 0.68, 95% CI: 0.50-0.92, p < 0.001), while the rate of AEs was similar. Female sex (RR = 1.16, 95% CI: 1.02-1.33), lesion diameter ≤1 cm (RR = 1.25, 95% CI: 1.00-1.56) and treatment with IV-MA (RR = 1.43, 95% CI: 1.06-1.93) were independently associated with achieving a cure. Comorbidities (RR = 1.7, 95% CI: 1.06-2.98) were independently associated with AEs. Patients of IL-MA group were older, had more comorbidities and more previous unsuccessful treatment of ACL. Nevertheless, IL-MA had a cure rate of 66.7%, and it was useful in this context. A prospective randomized trial is recommended.
Background: Recently developed immunosuppressive drugs, especially TNF antagonists, may enhance the risk of granulomatous infections, including leprosy. We aimed to evaluate the leprosy detection rate in patients under immunosuppression due to rheumatological, dermatological and gastroenterological diseases. Methods: We performed a systematic review of the literature by searching the PubMed, EMBASE, LILACS, Web of Science and Scielo databases through 2018. No date or language restrictions were applied. We included all articles that reported the occurrence of leprosy in patients under medication-induced immunosuppression. Results: The search strategy resulted in 15,103 articles; finally, 20 articles were included, with 4 reporting longitudinal designs. The detection rate of leprosy ranged from 0.13 to 116.18 per 100,000 patients/year in the USA and Brazil, respectively. In the meta-analysis, the detection rate of cases of leprosy per 100,000 immunosuppressed patients with rheumatic diseases was 84 (detection rate = 0.00084; 95% CI = 0.0000–0.00266; I2 = 0%, p = 0.55). Conclusion: Our analysis showed that leprosy was relatively frequently detected in medication-induced immunosuppressed patients suffering from rheumatological diseases, and further studies are needed. The lack of an active search for leprosy in the included articles precluded more precise conclusions. Trial registration: This review is registered in PROSPERO with the registry number CRD42018116275.