Associated-risk determinants for anthroponotic cutaneous leishmaniasis treated with meglumine antimoniate: A cohort study in Iran

Abstract

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.

Fig 1. Screening profile and treatment outcome.

Fig 2. Representative images of patients with anthroponotic cutaneous leishmaniasis in endemic areas from southeastern Iran (A-F; localized cutaneous leishmaniasis lesions, G; leishmaniasis recidivans (lupoid leishmaniasis), H; a non-healing skin lesion.

Fig 3. Comparison of survival rate of intramuscular and intralesional prescription of meglumine antimoniate over time.

Fig 4. Identification of Leishmania species by nested PCR to amplify a variable minicircle region of kinetoplat DNA (kDNA) prepared on gel electrophoresis products.

Ladder: DNA size marker,100 bp; Negative: Negative control (distilled water); 6. Positive control (Leishmania tropica, 750 bp); 5. Positive control (Leishmania major, 560 bp); Representative isolates (1–5) obtained from the patients with anthroponotic cutaneous leishmaniasis, southeast Iran.