ABSTRACT Introduction: Antimicrobial resistance in leprosy is an emerging problem, and the quantitative impact of low bacilloscopic indexes (BIs) on the sensitivity of molecular tests is unknown. We aimed to evaluate the sensitivity of gene sequencing for the detection of mutations related to antimicrobial resistance in Mycobacterium leprae in patients with low BIs using an analytical model. Methods: Patients with leprosy were included and divided into two groups depending on their BIs (≥ 2+ and < 2+). The sensitivities of the two DNA extraction methods were compared after amplifying and sequencing the repetitive element (RLEP), folP1, rpoB and gyrA in M. leprae. Results: We included 56 patients with leprosy: 35 had BIs less than 2+ (22 had negative slit-skin smear [SSS] results) and 21 patients had BIs greater than or equal to 2+. The sensitivity of the amplification of the RLEP target and the gene sequencing of folP1, rpoB and gyrA was 50 to 70% lower in patients with a BI less than 2+ and was significantly reduced in patients with lower BIs for all targets (p < 0.001). One patient had a mutation in the folP1 gene, and 14 patients had mutations in the gyrA gene, but no mutations related to antimicrobial resistance were found. Conclusions: We can conclude that the sensitivity of molecular tests is directly related to the BI, but these tests can still detect up to 20% of the targets in patients with BIs < 2+. New strategies to improve the sensitivity for detecting antimicrobial resistance in leprosy patients and reasonable clinical criteria for follow-up and the introduction of alternative treatments must be developed.

Abstract INTRODUCTION: Although supervised doses are essential for reducing leprosy treatment failure, the impact of specific drug interactions has rarely been assessed. This study aimed to estimate the risk of leprosy treatment suspension in patients receiving polypharmacy. METHODS We performed this case-control study in which the primary outcome was defined as the need to discontinue multibacillary leprosy treatment for at least one supervised dose, and the main risk factor was the detection of polypharmacy. Multivariate analysis by logistic regression was used for calculating odds ratio (OR). RESULTS: This study included 103 patients, of whom 43 needed to discontinue leprosy treatment (hemolysis = 26, hepatitis = 2, hemolysis associated with hepatitis = 6, and suspected treatment resistance = 9) and the rest did not. The severity of drug interactions had no effect on treatment discontinuation. Patients who used five or more drugs in addition to leprosy treatment had almost a 4-fold greater risk of treatment suspension (OR, 3.88; 95% confidence interval: 1.79-9.12; p < 0.001). The number of drugs used also positively influenced the occurrence of hemolysis (p < 0.001). No patient presented evidence of molecular resistance to rifampicin, dapsone, or ofloxacin treatment, as evidenced by genetic sequencing detection of rpoB, folp1, and gyrA mutations. CONCLUSIONS: Polypharmacy has deleterious effects on the already difficult-to-adhere-to treatment of leprosy and polypharmacy induces hemolysis. Additional measures must be taken to avoid the undesirable effects of inadequate polypharmacy.

ABSTRACT Immunosuppression is an important risk factor for leishmaniasis. We assessed the clinical profile, geographic distribution and prevalence of leishmaniasis in patients undergoing immunosuppressive therapy for dermatological, rheumatological or gastroenterological autoimmune diseases. We identified relevant studies in PubMed, EMBASE, Scopus, Web of Science and LILACS on July 3rd, 2018. We included articles that reported at least one case of leishmaniasis in patients undergoing immunosuppressive treatment for dermatological, rheumatological or gastroenterological diseases. Our protocol was registered in PROSPERO (CRD42018103050). We assessed the quality of the included studies with the Joanna Briggs Institute Critical Appraisal Tool. After the removal of duplicates, 5,431 articles were collected and screened. We included 138 articles; the prevalence of leishmaniasis in six methodologically similar studies varied from three to 1,282 cases per 100,000 patients using anti-TNFα drugs, but the results were significantly heterogeneous . Leishmaniasis in patients treated with immunosuppressive drugs is a health problem mostly reported in European countries bordering the Mediterranean Sea; sporadic activities, such as travelling, seem not to be associated with a significant risk of leishmaniasis, although effective control measures must always be observed.