Multidrug Therapy for Leprosy Can Cure Patients with Lobomycosis in Acre State, Brazil: A Proof of Therapy Study

Abstract

Lobomycosis, also referred to as lacaziosis, is an endemic cutaneous and subcutaneous fungal disease that mainly affects Amazonian forest dwellers in Brazil. There is no disease control program in place in Brazil, and antifungal therapy failures are common, and the therapy is inaccessible to most patients. We performed a randomized, unblinded clinical trial testing the cure rate of multiple drug therapy (MDT) for leprosy with surgical excision, with or without itraconazole. A control arm consisted of patients who did not adhere to either therapeutic regimens but continued to be followed up. Multiple drug therapy consisted of monthly supervised doses of 600 mg rifampicin, 300 mg clofazimine, and 100 mg dapsone, in addition to daily doses of 50 mg clofazimine and 100 mg dapsone. The patients in the MDT plus itraconazole arm also received itraconazole 100 mg twice daily. We followed up 54 patients from the MDT group and 26 patients from the MDT plus itraconazole group for an average of 4 years and 9 months. The 23 controls were followed up for 6 months on average. The following endpoints were observed: 1) unchanged (no apparent improvement), 2) improved (reduction in lesion size and/or pruritus), and 3) cured (complete remission of the lesions, no viable fungi, and no relapse for 2 years after the end of the drug treatment). The results indicated a significantly greater likelihood of cure associated with the use of multidrug therapy for leprosy with or without itraconazole when compared with the control group. The addition of itraconazole to MDT was not associated with improved outcomes, suggesting that MDT alone is effective.

Lobomycosis Epidemiology and Management: The Quest for a Cure for the Most Neglected of Neglected Tropical Diseases

“…Notably, combination therapy with itraconazole clofazimine, rifampin, dapsone, and surgical excision resulted in a clinical cure in both localized and disseminated forms of the disease [ 46 , 63 , 71 ]. To date, the most promising approach to lobomycosis was found by chance while treating leprosy patients co-infected with lobomycosis in the Leprosy Elimination Program carried out by SDPA in Acre state, Brazil.…”

“…All lesions showing atrophy were then surgically excised, with no further disease recurrence, resulting in 10 of 10 patients cured [ 10 ]. Recently, SDPA reported a randomized clinical trial with multibacillary multidrug therapy (MDT/MB/WHO) and surgery resulting in a likelihood ratio of 2.5 (CI 95% 1.4–4.4) of cure compared with untreated or incompletely treated patients (controls) [ 71 ] ( Table 1 ). In this trial, out of 80 patients treated with MDT/MB/WHO, 72 (90%) showed improvement, and 20 (25%) were considered cured [ 71 ].…”

“…Recently, SDPA reported a randomized clinical trial with multibacillary multidrug therapy (MDT/MB/WHO) and surgery resulting in a likelihood ratio of 2.5 (CI 95% 1.4–4.4) of cure compared with untreated or incompletely treated patients (controls) [ 71 ] ( Table 1 ). In this trial, out of 80 patients treated with MDT/MB/WHO, 72 (90%) showed improvement, and 20 (25%) were considered cured [ 71 ]. MDT/MB/WHO alone is effective in most lobomycosis cases ( Figure 1 A,B).…”

“…The WHO/MDT/MB therapy (clofazimine, rifampin, dapsone) in Gonçalves et al [ 71 ] was associated with less than $100 in medical expenditure per patient. Thus, this triple drug therapy in combination with surgery not only leads to remission of skin lesions, but also does so at reduced cost ( Figure 1 ).…”

“… WHO/MDT/MB standard protocol for lobomycosis treatment, SDPA, Acre state, 2020 [ 71 ]. ( A ) localized lobomycosis before and ( B ) after WHO/MDT/MB treatment for four years.…”