Clinical and Parasite Species Risk Factors for Pentavalent Antimonial Treatment Failure in Cutaneous Leishmaniasis in Peru

Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru.
Clinical Infectious Diseases (Impact Factor: 8.89). 01/2008; 46(2):223-31. DOI: 10.1086/524042
Source: PubMed


Treatment for cutaneous leishmaniasis (CL) with standard pentavalent antimonial therapy is hampered by cumbersome administration, toxicity, and potential failure. Knowledge of factors influencing treatment outcome is essential for successful management.
A case-control study of incident cases was performed with patients experiencing their first CL episode. The standard treatment for CL for these patients was 20 mg/kg/day of sodium stibogluconate for 20 days. Clinical and epidemiological data were recorded, and parasite isolates were species typed. Patients were followed up for 6 months to assess treatment outcome. Clinical cure was defined as complete wound closure and re-epithelization without inflammation or infiltration; new lesions, wound reopening, or signs of activity were classified as treatment failure. Descriptive, bivariate, and logistic regression analyses were performed.
One hundred twenty-seven patients were recruited; 63 (49.6%) were infected with Leishmania (Viannia) peruviana, 29 (22.8%) were infected with Leishmania (Viannia) braziliensis, 27 (21.3%) were infected with Leishmania (Viannia) guyanensis, and 8 (6.3%) were infected with other species. Only patients infected with the 3 most common species were selected for risk-factor analysis (n=119). Final failure rate at 6 months was 24.4% (95% confidence interval [CI], 16.5%-32.1%), with 96% of failures occurring within the first 3 months of follow-up assessment. Risk factors for treatment failure identified in the final multivariate model were age (per year, odds ratio [OR], 0.95; 95% CI, 0.92-0.99; P=.017), stay of <72 months in area of disease acquisition (OR, 30.45; 95% CI, 2.38-389.25; P=.009), duration of disease <5 weeks (OR, 4.39; 95% CI, 1.12-17.23; P=.034), additional lesion (per lesion, OR, 2.06; 95% CI, 1.3-3.28; P=.002), infection with L. (V.) peruviana (OR, 9.85; 95% CI, 1.01-95.65; P=.049), and infection with L. (V.) braziliensis (OR, 22.36; 95% CI, 1.89-263.96; P=.014).
The identification of parasite species and clinical risk factors for antimonial treatment failure should lead to an improved management of CL in patients in Peru.

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    • "It displays a wide range of adverse effects affecting the heart, liver, pancreas, and kidney. Moreover, parasite resistance to the drug and therapeutic failure is increasing (Llanos-Cuentas et al., 2008), and there exist a number of contra indications for its administration. Other second line treatments are available, including amphotericin B. This drug has low efficacy, needs intravenous administration, and has well documented adverse effects, mainly affecting kidney function. "
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    ABSTRACT: Leishmaniasis, a disease caused by parasites of the Leishmania genus, constitutes a significant health and social problem in many countries and is increasing worldwide. The conventional treatment, meglumine antimoniate (MA), presents numerous disadvantages, including invasiveness, toxicity and frequent therapeutic failure, justifying the attempts at finding alternatives to the first-line therapy. We have studied the comparative long-term efficacy of MA against miltefosine (MF) in Leishmania infection in experimental mice. The criteria for efficacy evaluation were: footpad lesion size, anti-Leishmania antibodies level, histopathology of the site of inoculation (right footpad, RFP), splenic index (SI) and the presence of parasites in RFP, spleen and liver, determined by Polymerase Chain Reaction (PCR). Swiss mice, infected with L. (L.) amazonensis were treated, at different time points (5 and 40 days after infection) with either MA or MF. The efficacy of MF was better than that of MA for inhibiting lesions and for reducing tissue damage and presence/load of amastigotes in spleen and liver. Moreover, early administration of MF, produced a clear reduction in splenomegaly, and was equal in reducing antibody titles in comparison to MA. Our results demonstrated that MF is an effective and safe therapeutic alternative for leishmaniasis by L. (L.) amazonensis and is more efficacious than MA.
    Full-text · Article · Dec 2014 · Journal of Parasitology
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    • "Pentavalent antimonials (SbV) are currently the first-line treatment for LCL, but because 24.4% of the treated patients do not achieve cure with a single cycle of SbV, ≥2 cycles are indicated to heal the lesions [5]. DCL is characterized by multiple nonulcerative nodules with an extremely high parasite burden, as well as a nonhealing or relapsing phenotype [1, 3, 4, 5]. DCL is typically refractory to SbV and second-line treatment. "
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    ABSTRACT: We show that increased plasma superoxide dismutase 1 (SOD1) levels are statistically significant predictors of the failure of pentavalent antimony treatment for cutaneous leishmaniasis caused by Leishmania braziliensis. In Leishmania amazonensis–infected patients, host SOD1 levels can be used to discriminate between localized and drug-resistant diffuse cutaneous leishmaniasis. Using in situ transcriptomics (nCounter), we demonstrate a significant positive correlation between host SOD1 and interferon α/β messenger RNA (mRNA) levels, as well as interkingdom correlation between host SOD1 and parasite SOD2/4 mRNA levels. In human macrophages, in vitro treatment with SOD1 increases the parasite burden and induces a diffuse cutaneous leishmaniasis–like morphology. Thus, SOD1 is a clinically relevant biomarker and a therapeutic target in both localized and diffuse cutaneous leishmaniasis.
    Full-text · Article · Feb 2014 · The Journal of Infectious Diseases
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    • "Therapeutic failure during antimony treatment remains a well know problem, but antimony resistance is not the only factor responsible to therapeutic failure. Indeed, factors that are linked to the host (e.g., immunosuppression or malnutrition), the drug itself (e.g., drug batch or counterfeit drugs), the Leishmania species, or the practitioner (e.g., incomplete treatment followups ) will also play a role in parasite drug resistance and treatment failure [1] [8] [9]. In most parts of the world, the frequency of parasite antimony resistance linked to treatment failure is unknown. "
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    ABSTRACT: Leishmania are the causative protozoal agents of leishmaniasis, that is a significant cause of morbidity and mortality in more than 88 countries. In the absence of any effective vaccines, the only feasible way to treat leishmaniasis is through the use of medications. The first line drugs is composed of molecules developed in the 1950s, like pentavalent antimony (i.e., Pentostam®, Glucantime®). Currently Leishmania antimony resistance still continues to emerge in various part of the world. In Algeria, as early as 1986, a high rate of treatment failure (48.5%) was recorded during the treatment of cutaneous leishmaniasis caused by Leishmania major. In addition, lower sensitivity to meglumine antimoniate was observed in L. major isolated from Psammomys obesus, a reservoir host. More recently decrease antimony susceptibility was reported in L. infantum strains. The current studies engaged in Algeria on the susceptibility of Leishmania parasites will shed light not only on the occurrence of antimony resistance in this area but also on factors that are involved in the selection of antimony resistance in natural Leishmania populations.
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