Raimunda Nonata Ribeiro Sampaio

Estudo comparativo da eficácia de isotionato de pentamidina administrada em três doses durante uma semana e de N-metil-glucamina 20mgSbV/kg/dia durante 20 dias para o tratamento da forma cutânea da leishmaniose tegumentar americana

Seventy-nine patients with cutaneous leishmaniasis were included in this study. The experimental group (n = 38) was treated with pentamidine isothionate in a dose of 4mg/kg/day on alternate days, for one week. The control group (n = 41) was treated with N-methylglucamine in a dose of 20mgSbV/kg/day for 20 days. Twenty-one isolates were identified using monoclonal antibody technique. We characterized Leishmania (Viannia) braziliensis, most frequently. There was a cure rate of 71.05% of the patients in the experimental group and 73.17% in the control group (p = 0.47). We found a statistical significance regarding frequency of ECG alterations between the experimental and control group (p<0.05). In our study pentamidine was as effective as antimonial for the treatment of american cutaneous leishmaniasis. It proved to be a safer drug considering heart toxicity. Moreover, it requires less time to complete the treatment.

Tratamento da forma mucosa de leishmaniose sem resposta a glucantime, com anfotericina B liposomal

We treated six patients with mucosal leishmaniasis who failed to respond to glucantime (20 mg/kg/day) with ambisome (2-5 grams total dose). The daily dose was 2-3 mg/kg/day given for a minimum of 20 days. After 26-38 months of follow up, five patients were clinically cured. One relapsed after six months. No side effects of therapy were observed apart from headache after infection. Ambisome is a therapeutic option for patients with mucosal leishmaniasis unresponsive to antimonials.

Tratamento da Leishmaniose Tegumentar Americana

American cutaneous leishmaniasis is an infectious disease of the skin and mucosa caused by a protozoon of the genus Leishmania. Its treatment is a challenge since the drugs available are highly toxic and none is completely effective. Recurrence, therapeutic failure in immunosuppressed patients and treatment resistance are some factors that encourage searching an ideal drug.

Antiplasmodial and antileishmanial activities of phylloseptin-1, an antimicrobial peptide from the skin secretion of Phyllomedusa azurea (Amphibia).

The development of drug resistance by infectious agents represents a major hindrance for controlling parasitic diseases and has stimulated the search for new compounds. We have previously shown that phylloseptin-1 (PS-1), a cationic peptide from the skin secretion of Phyllomedusa azurea, exhibited potent antimicrobial activity. Now we evaluate the effect of PS-1 on Leishmania amazonensis and Plasmodium falciparum. Concentrations as low as 0.5 microg/mL of PS-1 exhibited antileishmanial activity comparable to that of antimoniate of N-metilglucamine, while the antiplasmodial effect of PS-1 was evident at the concentration of 16 microg/mL, and reached an activity comparable to that of artesunate, at the concentration of 64 microg/mL. The high antiparasitic activity of PS-1, together with the unrelatedness of its chemical structure to any present antimicrobial drug, which prevents the development of cross-resistance, together with its non-toxicity to mammalian cells make this peptide a promising candidate for the treatment of malaria and leishmaniasis.

Nifurtimox in the treatment of South American leishmaniasis

A trial of Nifurtimox (Lampit) in 26 patients with mucocutaneous leishmaniasis is reported. 13 patients with cutaneous lesions and 13 patients with mucosal disease were treated with a daily oral divided dose of 10 mg/kg body-weight for 30 days. 46% of the cutaneous cases and only 15% of the mucosal cases apparently responded to this regimen during at least one year of follow up. The difficulties of assessing cure in this disease are briefly discussed. We consider that Nifurtimox remains an investigational drug. While possibly exhibiting some anti-leishmanial activity it cannot be recommended for routine use in either form of the disease.

Estudo clínico, epidemiológico e terapêutico de 402 pacientes com leishmaniose tegumentar americana atendidos no Hospital Universitário de Brasília, DF, Brasil

BACKGROUND: American cutaneous leishmaniasis is a disease with high prevalence and incidence in Brazil. The Brazilian Central-Western Region currently holds the third largest incidence and the first growth rate of this disease in the country. OBJECTIVES: To evaluate clinical, epidemiological and treatment features of patients with American cutaneous leishmaniasis seen at the University Hospital of Brasilia. METHOD: A case series study with 402 patients was carried out, spanning the period between January 1st, 1994 and February 28th, 2003. The following variables were studied: sex, age, occupation, state of origin, clinical features, diagnostic techniques, treatment with pentavalent antimony and side effects. Follow-up was one year after the end of treatment. RESULTS: The predominant group of patients was composed by male rural laborers who presented mainly the cutaneous form of the illness. The greatest efficacy of the antimony was observed in patients presenting the cutaneous form treated up to six months after the onset of symptoms, and in females in general (both differences were statistically significant in multivariate analysis). The early treatment of the mucocutaneous form also presented better results, although not statistically significant. Electrocardiographical alterations were more frequent in the group of patients receiving a 20mg SbV/Kg/day for a 30-day schedule than those with the same dosage for 20 days. Eosinophilia was found in 17.5%. CONCLUSIONS: Early treatment, female gender and cutaneous form presented higher levels of cure. Electrocardiographic changes rose as time of treatment was increased. The remarkable report of eosinophilia as a side effect of N-methylglucamine deserves further investigation.

Leishmanicidal activity of amphotericin B encapsulated in PLGA–DMSA nanoparticles to treat cutaneous leishmaniasis in C57BL/6 mice

The major goal of this work was to design a new nanoparticle drug delivery system for desoxycholate amphotericin B (D-AMB), based on controlled particle size, looking for the most successful release of the active agents in order to achieve the best site-specific action of the drug at the therapeutically optimal rate and dose regimen. For this, AMB nanoencapsulated in poly(lactic-co-glycolic acid) (PLGA) and dimercaptosuccinic acid (DMSA) nanoparticles (Nano-D-AMB) has been developed, and its efficacy was evaluated in the treatment of experimental cutaneous leishmaniasis in C57BL/6 mice, to test if our nano-drug delivery system could favor the reduction of the dose frequency required to achieve the same therapeutic level of free D-AMB, and so, an extended dosing interval. Magnetic citrate-coated maghemite nanoparticles were added to this nanosystem (Nano-D-AMB-MG) aiming to increase controlled release of AMB by magnetohyperthermia. Female mice (N=6/group) were infected intradermally in the right footpad with promastigotes of Leishmania amazonensis in the metacyclic phase, receiving the following intraperitoneal treatments: 1% PBS for 10 consecutive days; D-AMB at 2 mg/kg/day for 10 days (totalizing 20 mg/kg/animal); Nano-D-AMB and Nano-D-AMB-MG at 6 mg/kg on the 1st, 4th and 7th days and at 2 mg/kg on the 10th day, also totalizing 20 mg/kg/animal by treatment end. The Nano-D-AMB-MG group was submitted to an AC magnetic field, allowing the induction of magnetohyperthermia. The evaluations were through paw diameter measurements; parasite number and cell viability were investigated by limiting dilution assay. D-AMB-coated PLGA-DMSA nanoparticles showed the same efficacy as free D-AMB to reduce paw diameter; however, the Nano-D-AMB treatment also promoted a significantly greater reduction in parasite number and cell viability compared with free D-AMB. The nano-drug AMB delivery system appeared more effective than free D-AMB therapy to reduce the dose frequency required to achieve the same therapeutic level. It thus favors a longer interval between doses, as expected with development of a new nano drug delivery system, and may be useful in the treatment of many different pathologies, from cancer to neurodegenerative diseases.

Sensitivity of a Vacuum Aspiratory Culture Technique for Diagnosis of Localized Cutaneous Leishmaniasis in an Endemic Area of Leishmania (Viannia) braziliensis Transmission

Sixty eight patients with localized cutaneous leishmaniasis from an area with Leishmania (Viannia) braziliensis transmission had cultures performed with a modified Marzochís vacuum aspiratory puncture technique to establish sensitivity and contamination rate with this new method. Overall sensitivity of three aspirates was 47.1%; (CI95% 39.4; 59.4) significantly greater than the sensitivity of a single one aspirate. Fungal contamination was observed in 6/204 (2.9%) inoculated culture tubes. We recommend that this useful technique should be adopted as routine for primary isolation of L. (V.) braziliensis from localized cutaneous ulcers.

Leishmaniose tegumentar americana associada à AIDS: relato de quatro casos

The co-infection American cutaneous leishmaniasis and AIDS has recently been described in the literature, observing differences between the clinical and immunological behavior of these patients. Four cases are reported here, attended at the Brasilia University Hospital, with diagnoses of infection by Leishmania species and immunodeficiency virus, with a view to illustrating the clinical presentations, course and therapeutic responses.

Avaliação da tolerância e nefrotoxicidade do antimonial pentavalente administrado na dose de 40mg Sb v/kg/dia, de 12/12h, por 30 dias na forma cutaneo-mucosa de leishmaniose

The renal function of eleven patients with mucocutaneous leishmaniasis was analyzed in a prospective study realized at the School Hospital of University of Brasília. The patients were treated with doses of 40 mg/kg/day of pentavalent antimony (Sb V), in a continuous scheme during thirty days. In this study three patients were excluded, one patient with reversible renal failure and two patients with hepatic and cardiac malfunctions. In the other eight patients, severe nephrotoxic effects were observed, like reduction of glomerular filtration rate, reduction of the urinary concentration capacity, evaluated by a sixteen hours hydric fasting and an increase of sodium fractional excretion. An increase in the number of leucocytes and cylinders were observed at the urinary sediment exam. Finally, the results shows that the treatment with pentavalent antimony in doses of 40 mg Sb/kg/day was less tolerated on account of its renal toxic effects. This scheme seems not be superior than the currently preconized scheme of 20 mg of Sb V/kg/day during 30 days.