Leishmaniasis in HIV-infected patients: difficulties in diagnostics and treatment

В статье представлены клинические случаи лейшманиоза, которые проанализированы в контексте течения ВИЧ-инфекции, при которой лейшманиоз выступает в роли оппортунистического заболевания. Дана общая характеристика лейшманиоза, а также отмечены особенности течения этой инфекции на фоне приобретенного иммунодефицита. Рассмотрены вопросы диагностики и лечения лейшманиоза, смертность при котором остается достаточно высокой. Значительная распространенность ВИЧ-инфекции в мире, ежегодно увеличивающийся туристический поток в эндемичные страны, а также увеличение эндемичных очагов на территории РФ в связи с присоединением Республики Крым требуют от врачей всех специальностей пристального внимания и настороженности в отношении лейшманиоза. Особое внимание заслуживают больные ВИЧ-инфекцией, уже имеет место ряд сообщений о том, что у инфицированных ВИЧ диагностируется висцеральный лейшманиоз, и они подвергаются бóльшему риску инфицирования, чем общая популяция. Проявления висцерального лейшманиоза среди пациентов с иммунодефицитом, как правило, не отличаются от классического течения, однако в зависимости от степени угнетения иммунитета болезнь может принимать атипичные формы, что затрудняет своевременную диагностику и назначение адекватной терапии. При наличии у больного ВИЧ-инфекции, длительной лихорадки неправильного типа, увеличения лимфоузлов, селезенки, печени, потери веса > 10%, прогрессирующей анемии, нейтропении, тромбоцитопении, гипоальбуминемии и данных о пребывании в регионах, эндемичных по лейшманиозу, целесообразно обследование на висцеральный лейшманиоз – пункция костного мозга с окраской мазков по Романовскому – Гимзе, постановкой ПЦР-пунктата с использованием тест-системы на лейшманиоз, а при получении положительных результатов – назначение препаратов пятивалентной сурьмы, препаратов второго ряда – амфотерицина В, липосомального амфотерицина В или паромомицина. In this article, leishmaniasis is considered in the context of HIV infection, in which this disease appears to be an opportunistic. A general characteristic of leishmaniasis is given, and the features of the course of infection in immunodeficiency are also presented. In the example of clinical cases, issues featuring diagnostics and treatment of leishmaniasis are reviewed, the mortality rate of which remains quite high. The accession of Crimea to Russia, the high prevalence of HIV infection in the world, as well as the annually increasing tourist flow to endemic countries, require physicians of all specialties to be aware of this disease. HIV patients deserve special attention, there are already a number of reports that people with HIV are diagnosed with visceral leishmaniasis and are at greater risk of infection than the general population. The manifestations of visceral leishmaniasis among patients with immunodeficiency, as a rule, do not differ from the classical course, however, depending on the degree of suppression of immunity, the disease can take on atypical forms, which complicates timely diagnosis and the appointment of adequate therapy. If the patient has HIV infection, prolonged fever of the wrong type, enlarged lymph nodes, spleen, liver, weight loss > 10%, progressive anemia, neutropenia, thrombocytopenia, hypoalbuminemia and data on stay in regions endemic for leishmaniasis, it is advisable to be tested for visceral leishmaniasis – puncture of bone marrow with staining of smears according to Romanovsky – Giemsa, staging of PCR punctate using a test system for leishmaniasis, and if positive results are obtained, the appointment of pentavalent antimony drugs, second-line drugs – amphotericin B, liposomal amphotericin B or paromomycin.

A Promising Cutaneous Leishmaniasis Treatment with a Nanoemulsion-Based Cream with a Generic Pentavalent Antimony (Ulamina) as the Active Ingredient

Leishmania parasites are the etiological agents of Leishmaniasis, a tropical disease that affects around 15 million people in about 90 countries. The chosen therapy for this disease is based on antimony V compounds, such as meglumine antimoniate. It can be administered as a parenteral, subcutaneous or perilesional form as successive infiltrations with pre-established doses localized in the border of the granuloma that characterizes the wound of Cutaneous Leishmaniasis (CL). Herein, a topical pharmaceutical recipe, such as an emulsion, is proposed to eliminate the trauma caused by administering the medicine in parenteral form to the face or other difficult access zones. The evaluation of this vehicle was performed by analyzing parameters such as pH, viscosity, homogeneity and droplet size distribution. Furthermore, the effectiveness of the emulsion was proved by in vitro experiments using Strat-M synthetic membranes, showing that the transdermal passage of the antimonial complex is guaranteed. Moreover, complete healing of the wound has been attained in patients with CL, as shown with two clinical cases in this article.

Anti-leishmanial activity of 29 daily sessions of intralesional-pentavalent antimony administration on Leishmania (Viannia)-infected BALB/c mice

Introduction: Intralesional-pentavalent antimonials (IL-SbV) are recommended for simple cutaneous leishmaniasis (CL). Few treatment sessions (1-5) and drug volumes (1-5 ml each), relative to lesion size (LS), are recommended. There is not a validated IL-SbV protocol using doses calculated as mg/kg body weight and administered over a large number of IL-sessions, with small injection volumes. Objective: The study aim was to determine the efficacy of different concentrations of IL-SbV administered in 29 daily sessions of 100 μL each, on CL infected mice. Methods: Leishmania (Viannia) panamensis and L. (V.) braziliensis-infected mice (N = 6) were treated with 150, 50, and 16.6 mgSbV/kg/day x 29 days. Percentage of lesion area reduction, aesthetic and final (no lesions, no parasites) efficacy and effective dose (ED)50 were determined. In vitro-SbV activity against parasites was evaluated for both species. Results: The ED50 values were 72.2 and 66.3 (at the end of treatment), 54.3 and 37.7 (15-days pt.), and 145.3 and 148.6 (60-days pt.) for each species, respectively. Differences were observed between Leishmania species at 15-days pt., but not later. At 60-day pt., IL-SbV-150 mg showed final cure rates of 66.6 % for L. (V.) panamensis and 33.3 % for L. (V.) braziliensis-infected mice. After 15 days pt., lesion reactivation was observed in some “aesthetically cured” mice. Glucantime was not active in in vitro assays. Conclusions: The IL-SbV use with a dose calculated as mg/kg body weight and administered over a large number of IL-sessions, with small injection volumes each day could be effective against L. (V.) panamensis and L. (V.) braziliensis-CL infection. An appropriate SbV-dose (higher than 150 mg/kg/day x less than 29 days) must be evaluated.

Application of Fe-Impregnated Biochar from Cattle Manure for Removing Pentavalent Antimony from Aqueous Solution

This study assessed the applicability of Fe-impregnated biochar derived from cattle manure (Fe-CMB) as an adsorbent for removing Sb(V) from aqueous solutions and investigated the Sb(V) adsorption mechanism. Fe-CMB was mainly composed of C, O, Cl, Fe, Ca, and P, and the adsorption of Sb(V) onto Fe-CMB was identified using an energy dispersive spectrometer and Fourier transform infrared spectroscopy. Sb(V) adsorption reached equilibrium within 6 h, and the Sb(V) adsorption data as a function of time were well described by the pseudo-second-order model. The Langmuir isotherm model fit the equilibrium data better than the Freundlich model. The maximum adsorption capacity of Fe-CMB for Sb(V) obtained from the Langmuir model was 58.3 mg/g. Thermodynamic analysis of Sb(V) adsorption by Fe-CMB indicated that the adsorption process was exothermic and spontaneous. The Sb(V) removal percentage increased with the Fe-CMB dose, which achieved a removal of 98.5% at 10.0 g/L Fe-CMB. Increasing the solution pH from 3 to 11 slightly reduced Sb(V) adsorption by 6.5%. The inhibitory effect of anions on Sb(V) adsorption followed the order: Cl− ≈ NO3− < SO42− < HCO3− < PO43−.

Highly efficient removal of Sb(V) from water by franklinite-containing nano-FeZn composites

The existence of toxic and carcinogenic pentavalent antimony in water is a great safety problem. In order to remove antimony(V) from water, the purpose of this study was to prepare a novel graphene nano iron zinc (rGO/NZV-FeZn) photocatalyst via hydrothermal method followed by ultrasonication. Herein, weakly magnetic nano-Fe–Zn materials (NZV-FeZn, GACSP/NZV-FeZn, and rGO/NZV-FeZn) capable of rapid and efficient Sb(V) adsorption from water were prepared and characterised. In particular, rGO/NZV-FeZn was shown to comprise franklinite, Fe0, and graphite. Adsorption data were fitted by a quasi-second-order kinetic equation and Langmuir model, revealing that among these materials, NZV-FeZn exhibited the best Sb removal performance (543.9 mgSb gNZV-FeZn−1, R2 = 0.951). In a practical decontamination test, Sb removal efficiency of 99.38% was obtained for a reaction column filled with 3.5 g of rGO/NZV-FeZn. Column regenerability was tested at an initial concentration of 0.8111 mgSb L−1, and the treated water obtained after five consecutive runs complied with the GB5749-2006 requirement for Sb. rGO/NZV-FeZn was suggested to remove Sb(V) through adsorption-photocatalytic reduction and flocculation sedimentation mechanisms and, in view of its high cost performance, stability, and upscalable synthesis, was concluded to hold great promise for source water and wastewater treatment.

Apoptosis-Like Cell Death in Leishmania major Treated with HESA-A: An Herbal Marine Compound

Background: The first drug for the treatment of leishmaniasis is pentavalent antimony compounds which have great side effects. Objectives: This study aimed to assess apoptosis induction by HESA-A, an herbal marine compound in Leishmania major promastigotes. Methods: Leishmania major promastigotes were treated with HESA-A in different increasing concentrations ranged 1.625 - 120 µg/mL, and amphotericin B and the phenomenon of apoptosis in the parasite were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, and DNA fragmentation tests. Results: The IC50 value of the compound and amphotericin B at 72 h were estimated at 2.81 µg/mL and 40 µg/mL, respectively. After 72 h of the adjacency of Leishmania major promastigotes with IC50 dose (2.81 µg/mL), the percentage of promastigotes in early and late apoptosis phases in the treated group was 5.4% and 60.4%, respectively. DNA fragmentation of Leishmania major promastigotes treated with 2.81 µg/mL for 72 h was observed. Conclusions: HESA-A, with significant induction of apoptosis in Leishmania major promastigotes, can be plausible in the treatment of cutaneous Leishmaniasis.

Three decades of clinical trials on immunotherapy for human leishmaniases: a systematic review and meta-analysis

Aim: Current treatments for leishmaniases are not satisfactory, thus alternatives are needed. We searched for clinical trials with immunotherapeutic approaches for patients with leishmaniasis. Materials & methods: Out of 205 articles, 24 clinical trials were selected, and eight submitted to meta-analysis. Results: A reduction in healing time was observed in patients with tegumentary leishmaniasis treated with pentavalent antimony plus granulocyte-macrophage colony-stimulating factor, and therapeutic vaccines. Overall meta-analysis indicated that immunotherapy associated with the standard chemotherapy generated a significantly reduced risk of treatment failure than the pentavalent antimony alone (p = 0.03). Conclusion: Our review confirmed the efficacy of immunotherapies for the treatment of cutaneous and visceral leishmaniasis and highlighted the importance of clinical trials using immunotherapies for leishmaniases.

A Case of Cutaneous Leishmaniasis Responding to Systemic Liposomal Amphotericin B Treatment

Leishmania is a vector-induced endemic tropical disease caused by protozoans. The most common cutaneous, mucosal and visceral forms are the cutaneous form. The main drugs in treatment are pentavalent antimony compounds, but their side effects create limitation of use. Local antimony compounds are used primarily in the treatment of cutaneous leishmaniasis. In some cases, alternative treatment modalities are required due to insufficient response to local treatment. Systemic amphotericin B treatment is one of the alternative treatments. In a patient who developed cutaneous Leishmania at 21 months and who did not respond with local meglumine antimoniate therapy, a total of 21 mg/kg dose of systemic amphotericin B was given intermittently and successful results were obtained.

A Case of Cutaneous Leishmaniasis Responding to Systemic Liposomal Amphotericin B Treatment

Leishmania is a vector-induced endemic tropical disease caused by protozoans. The most common cutaneous, mucosal and visceral forms are the cutaneous form. The main drugs in treatment are pentavalent antimony compounds, but their side effects create limitation of use. Local antimony compounds are used primarily in the treatment of cutaneous leishmaniasis. In some cases, alternative treatment modalities are required due to insufficient response to local treatment. Systemic amphotericin B treatment is one of the alternative treatments. In a patient who developed cutaneous leishmania at 21 months and who did not respond with local meglumine antimoniate therapy, a total of 21 mg / kg dose of systemic amphotericin B was given intermittently and successful results were obtained.