Cutaneous leishmaniasis (CL) is a serious health challenge at the global level due to Leishmania tropica. This study was conducted to evaluate the risk factors associated with anthroponotic CL (ACL) in unresponsive (patient who does not heal and remains with an active lesion, despite receiving two courses of intra-lesional Glucantime along with cryotherapy and one cycle of systemic Glucantime) and responsive patients in a major focus in southeastern Iran. A case-control study was conducted from April 2015 to October 2016 in the southeast of Iran. Patients were recruited in a major ACL focus from unresponsive and responsive cases. These patients were compared for environmental, clinical, and demographic characteristic factors. Twenty-five risk related factors were analyzed using multivariate logistic regression and backward elimination stepwise models. P<0.05 was defined to be statistically significant. In general, 340 patients with ACL comprising 72 (21.2%) unresponsive cases and 268 (78.8%) responsive cases with active lesions or scars were analyzed by estimating odds ratio (OR). All isolates from 15 responsive and 15 unresponsive patients were characterized as Leishmania tropica based on the BLAST and phylogenic analyses by PCR sequences of the Hsp70 and ITS1 loci. Among the 25 variables, 4 major risk factors including poor interior housing conditions (OR = 1.99, confidence interval (CI) = 1–3.93, P<0.04), history of chronic diseases (OR = 6.22, CI = 2.51–15.44, P≤0.001), duration of lesion in the patients referred ≥13 months (OR = 74.99, CI = 17.24–326.17, P≤0.001), and 5–12 months (OR = 7.42, CI = 3.07–17.92, P≤0.001) than lesions with ≤4 months of age and age groups ≥51 years (OR = 3.85, CI = 1.04–14.22, P<0.04) than those ≤7 years, were significantly associated with unresponsive forms. Improving interior house construction protecting high risk individuals and those with debilitating diseases from being bitten by sand flies, together with the early detection and effective treatment of older age groups with history of chronic diseases are highly important measures for preventing unresponsive forms in patients with ACL in southeastern Iran.
Background
The control of cutaneous leishmaniasis (CL) is facilitated by knowledge of factors associated with the treatment failures in endemic countries. The aim of this evaluation was to identify the potential risk determinants which might affect the significance of demographic and clinical characteristics for the patients with anthroponotic CL (ACL) and the outcome of meglumine antimoniate (MA) (Glucantime) treatment.
Methodology/Principal findings
This current was executed as a cohort spanning over a period of 5 years which centered in southeastern part of Iran. Altogether, 2,422 participants were evaluated and 1,391 eligible volunteer patients with ACL caused by
Leishmania tropica
were included. Overall, 1,116 (80.2%) patients received MA intraleisionally (IL), once a week for 12 weeks along with biweekly cryotherapy, while 275 (19.8%) patients received MA alone (20 mg/kg/day for 3 weeks) (intramuscular, IM). The treatment failure rate in ACL patients was 11% using IL combined with cryotherapy plus IM alone, whilst 9% and 18.5% by IL along with cryotherapy or IM alone, respectively. Multivariate logistic regression model predicted 5 major associated-risk determinants including male (odds ratio (OR) = 1.54, confidence interval (CI) = 1.079–2.22, p = 0.018), lesion on face (OR = 1.574, CI = 1.075–2.303, p = 0.02), multiple lesions (OR = 1.446, CI = 1.008–2.075, p = 0.045), poor treatment adherence (OR = 2.041, CI = 1.204–3.46, p = 0.008) and disease duration > 4 months (OR = 2.739, CI = 1.906–3.936, p≤0.001).
Conclusions/Significance
The present study is the original and largest cohort of ACL patients who treated with MA. A comprehensive intervention and coordinated action by the health authorities and policy-makers are crucial to make sure that patients strictly follow medical instructions. Early detection and effective therapy < 4 months following the onset of the lesion is critical for successful treatment of the patients. Since a significant number of patients are still refractory to MA, reducing man-vector exposure and development of new effective alternative drugs are essential measures against ACL due to
L
.
tropica
.
In cases of inconclusive outcomes of resistance tests in clinical isolates, expression analysis of a set of influential genes can be beneficial to identify distinctive biomarkers between antimony-unresponsive and responsive parasites.
This study aimed to explore geographic distribution and molecular characterization of cutaneous leishmaniasis (CL) species by amplifying two popular markers in kinetoplast DNA and internal transcribed spacer 1 loci by nested-PCR, and characterized by sequencing and phylogenetic analyses. Findings demonstrated that two species co-existed in the province: L. tropica (88.5%) and L. major (11.5%). All gender and age groups were equally infected, although males, 21-30 years old, exhibited a significantly higher infection. Sequencing and phylogenetic analyses of 34 randomly selected samples showed that L. tropica isolates exhibited some degree of heterogeneity. Both anthroponotic CL and zoonotic CL are present in south-eastern Iran with predominance of L. tropica species. Some level of heterogeneity was observed in L. tropica isolates which possibly reflects different colonies in the area. Implementation of diagnostic tools directly from clinical samples could be an important strategic approach for exploration of spatial distribution, molecular characterization and phylogenetic analyses.
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