RESUMO
The aim of this study was to describe a case of a patient with ocular toxoplasmosis, which has resulted in Kyrieleis plaques formation (segmental periarteritis associated with severe inflammation) and later follow-up and alternative treatment due to documented allergy to sulfonamide. A 33-year-old Brazilian woman diagnosed with acute toxoplasmosis, initially treated with sulfonamide, developed a critical cutaneous rash. Cotrimoxazole was changed to clindamycin and pyrimethamine, and prednisone was started. The medication was maintained for 45 days. Four months later, she developed retinal lesions suggestive of toxoplasmosis with Kyrieleis plaques in the upper temporal vessels. Pyrimethamine, clindamycin, and prednisone were initiated until healing. She presented reactivation months later, and a suppressive treatment with pyrimethamine was instituted for one year. This is the first report to use the combination of clindamycin with pyrimethamine in the treatment and recurrence prophylaxis for OT in a documented allergy to sulfonamide.
Assuntos
Clindamicina , Pirimetamina , Sulfonamidas , Toxoplasmose Ocular , Humanos , Feminino , Adulto , Pirimetamina/uso terapêutico , Pirimetamina/efeitos adversos , Toxoplasmose Ocular/tratamento farmacológico , Sulfonamidas/uso terapêutico , Sulfonamidas/efeitos adversos , Clindamicina/uso terapêutico , Recidiva , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Hipersensibilidade a Drogas/etiologia , Brasil , Antiprotozoários/uso terapêutico , Antiprotozoários/efeitos adversos , Resultado do Tratamento , Prednisona/uso terapêuticoRESUMO
In situ and systemic evaluations of the immune responses of HIV-infected patients to mucosal leishmaniasis have been poorly described. We describe a recently diagnosed HIV-infected patient with mucosal leishmaniasis who was characterized by a CD4 count of 85 cells/mm3 and nasal septum destruction resulting from pruritic and ulcerated nasal mucosa with crust formation and progression over 2 years. In situ and systemic immune evaluations of T cell activation, memory, and exhaustion were conducted using cytofluorometric assays, and sequencing of the Leishmania species was performed. The immune profile of HIV-infected patient with mucosal leishmaniasis shows a mixed Th1/Th2 pattern and an activated and exhausted status.
Assuntos
Infecções por HIV , Leishmania , Leishmaniose Mucocutânea , Humanos , Leishmaniose Mucocutânea/diagnóstico , Leishmaniose Mucocutânea/tratamento farmacológico , Contagem de Linfócito CD4 , Imunidade , Infecções por HIV/complicaçõesRESUMO
BACKGROUND: Meglumine antimoniate (MA) remains the main treatment for cutaneous leishmaniasis (CL). Uncontrolled studies suggest that intralesional MA (IL-MA) may be noninferior and safer than systemic MA (S-MA). METHODS: Multicenter, randomized, controlled, open-label, phase 3 clinical trial to evaluate the efficacy and toxicity of IL-MA in 3 infiltrations at 14-day intervals compared with S-MA (10-20 mg Sb5+/kg/day, 20 days) for CL, with noninferiority margin of 20%. Primary and secondary outcomes were definitive cure at day 180 and epithelialization rate at day 90 of treatment, respectively. A 2-year follow-up was performed to assess relapses and emergence of mucosal lesions. Adverse events (AEs) were monitored according to the Division of AIDS AE grading system. RESULTS: We evaluated 135 patients. The cure rates (95% confidence interval) for IL-MA and S-MA treatment were, respectively, 82.8% (70.5-91.4) and 67.8% (53.3-78.3) per protocol (PP) and 70.6% (58.3-81.0) and 59.7% (47.0-71.5) per intention to treat (ITT). The epithelialization rates of the IL-MA and S-MA treatment were, respectively, 79.3% (66.6-88 + 8) and 71.2% (57.9-82.2) PP and 69.1% (55.2-78.5) and 64.2% (50.0-74.2) ITT. AEs in the IL-MA and S-MA groups were, respectively, clinical, 45.6% and 80.6%; laboratory, 26.5% and 73.1%; and electrocardiogram, 8.8% and 25.4%. Ten participants in the S-MA group and 1 in the IL-MA group were discontinued due to severe or persistent AEs. CONCLUSIONS: IL-MA provides a similar cure rate and results in less toxicity compared with S-MA and may be used as first-line therapy for CL patients. CLINICAL TRIALS REGISTRATION: REBEC: RBR-6mk5n4.
Assuntos
Antiprotozoários , Leishmaniose Cutânea , Compostos Organometálicos , Humanos , Antimoniato de Meglumina/uso terapêutico , Antimoniato de Meglumina/efeitos adversos , Antiprotozoários/efeitos adversos , Meglumina/efeitos adversos , Brasil , Resultado do Tratamento , Compostos Organometálicos/efeitos adversos , Leishmaniose Cutânea/tratamento farmacológicoRESUMO
The immunosuppressive effect of methotrexate has rarely been associated with reactivation of cutaneous leishmaniasis. Here we present a case of a cutaneous leishmaniasis patient with atypical clinical symptoms without splenomegaly but with cutaneous manifestations after treatment of rheumatoid arthritis with methotrexate and blood recovery of the parasite. Next-generation sequencing was used to identify Leishmania infantum chagasi in the patient's blood sample.
Assuntos
Artrite Reumatoide , Leishmania infantum , Leishmaniose Cutânea , Leishmaniose Visceral , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Humanos , Leishmaniose Cutânea/diagnóstico , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/parasitologia , Leishmaniose Visceral/tratamento farmacológico , Metotrexato/efeitos adversosRESUMO
Human le ishmaniasis is a vector-borne, neglected infectious disease that is widely distributed in America, Africa, Europe, and Asia. Current therapy is based on old and toxic drugs, including antimonials, aminoglycosides, and amphotericin. As a neglected disease, investment in the development of new therapeutic molecules is scarce. Considering these aspects, the optimization of treatment through novel delivery systems for current therapeutic agents is an attractive alternative. The encapsulation into liposomes of drugs used in treating leishmaniasis increases the concentration of these molecules in macrophages, which may not only increase the chance of cure but also expand their therapeutic spectrum to include resistant Leishmania, as well as reducing toxicity since the drug is less exposed to healthy cells. The classical example is the liposomal formulation of amphotericin B, a well-established therapeutic option that uses liposomes to decrease the progression of renal failure in patients. However, loading other leishmanicidal drugs into liposomes, such as pentavalent antimonials, presents an opportunity for innovative and cheaper therapeutic options for the treatment of human leishmaniasis. This review aims to discuss liposomes as a drug delivery system for leishmanicidal drugs.
Assuntos
Antiprotozoários , Leishmaniose , Aminoglicosídeos/uso terapêutico , Anfotericina B/uso terapêutico , Antiprotozoários/uso terapêutico , Sistemas de Liberação de Medicamentos , Humanos , Leishmaniose/tratamento farmacológico , LipossomosRESUMO
Human leishmaniasis is a neglected tropical disease (NTD) with high morbidity and is endemic in low- to middle-income countries. Its diagnosis, treatment and epidemiological control methods are outdated and obsolete, which has become a challenge for health practitioners in controlling the disease. Computational methods have proven to be beneficial and have become popular in many fields of medicine, especially in affluent countries. However, they have not been widely used for NTDs. To date, few computational technologies have been employed for leishmaniasis. Although new technologies in leishmaniasis are theorized, they have only been minimally applied and have not been updated, even in other infections. Research and development on NTDs suffers from the inherent difficulties of the demographic regions the diseases afflict. In this narrative review we described the e-tools available in managing leishmaniasis, ranging from drug discovery to treatment.
Assuntos
Leishmaniose , Medicina Tropical , Humanos , Doenças Negligenciadas/tratamento farmacológico , Doenças Negligenciadas/epidemiologia , Doenças Negligenciadas/diagnóstico , Leishmaniose/diagnóstico , Leishmaniose/tratamento farmacológico , Renda , MorbidadeRESUMO
Leishmaniasis is a major public health problem worldwide. Although next generation sequencing technology has been widely used in the diagnosis of infectious diseases, it has been scarcely applied in identification of Leishmania species. The aim of this study was to compare the efficiency of MinION™ nanopore sequencing and polymerase chain reaction restriction fragment length polymorphism in identifying Leishmania species. Our results showed that the MinION™ sequencer was able to discriminate reference strains and clinical samples with high sensitivity in a cost and time effective manner without the prior need for culture.
Assuntos
Leishmania , Leishmaniose Cutânea , DNA de Protozoário , Proteínas de Choque Térmico HSP70/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Leishmania/genética , Leishmaniose Cutânea/diagnóstico , Reação em Cadeia da Polimerase/métodos , Polimorfismo de Fragmento de RestriçãoRESUMO
Asymptomatic VL is a concern, considering the risk of transmission in highly endemic areas due to human-to-human transmission. The aim of this study was to report the sero-epidemiological prevalence in Bihar, India, a highly endemic area of VL, using the leishmanin skin test (LST) and the direct agglutination test (DAT). This was a cross-sectional study performed in Muzaffarpur, Bihar, India. Relatives of patients with VL were tested by LST and DAT. Other epidemiological data were evaluated and correlated with tests results. Forty individuals (either previous or current patients), and 109 household contacts were studied. There were 36% of male visceral leishmaniasis family members versus 17.57% of females visceral leishmaniasis family members, thus showing more males with symptomatic disease than females (p< 0.01). All visceral leishmaniasis cases had positive DAT tests, but only 37% of past cases were positive on the skin testing. Amongst healthy household contacts, 34% were DAT-positive, whilst 21% were LST-positive. The overall positivity for both assays combined was 44.8% and 23.8% were DAT-positive alone. The finding of high infection prevalence amongst asymptomatic individuals, and the estimation of those at greater risk for overt disease (DAT-positive alone) are important in the development of future disease control policies.
Assuntos
Leishmania/classificação , Leishmania/isolamento & purificação , Leishmaniose Visceral/diagnóstico , Testes Cutâneos/métodos , Teste de Coombs , Estudos Transversais , Feminino , Humanos , Índia , Leishmania/imunologia , Leishmaniose Visceral/imunologia , MasculinoRESUMO
Tegumentary leishmaniasis (TL) diagnosis is challenging due to the lack of a gold standard diagnostic tool. The diagnosis is significantly harder in regions where visceral leishmaniasis (VL) is also prevalent since immunological tests may present cross-reactivity. A cirrhotic patient from an endemic Brazilian region for TL and VL presented with atypical cutaneous lesions, a usual clinico-laboratory feature of VL (including a positive rk39 test result), but he was diagnosed with TL histopathologically; VL was ruled out by necropsy. Physicians working in co-prevalent areas should be aware of atypical features, unusual clinical course, and unexpected laboratory findings of leishmaniasis.
Assuntos
Leishmaniose Cutânea/patologia , Leishmaniose Visceral/diagnóstico , Cirrose Hepática/complicações , Diagnóstico Diferencial , Evolução Fatal , Humanos , Leishmaniose Cutânea/complicações , Leishmaniose Cutânea/diagnóstico , Masculino , Pessoa de Meia-IdadeRESUMO
Leishmaniasis occurs in the five continents and represents a serious public health challenge, but is still a neglected disease, and the current pharmacological weaponry is far from satisfactory. Triglyceride-rich nanoparticles mimicking chylomicrons (TGNP) behave metabolically like native chylomicrons when injected into the bloodstream. Previously we have shown that TGNP as vehicle to amphothericin B (AB) for treatment of fungi infection showed reduced renal toxicity and lower animal death rates compared to conventional AB. The aim of the current study was to test the tolerability and effectiveness of the TGNP-AB preparation in a murine model of Leishmania amazonensis infection. The in vitro assays determined the cytotoxicity of TGNP-AB, AB, and TGNP in macrophages and promastigote forms and the leishmanicidal activity in infected macrophages. The in vivo toxicity tests were performed in healthy mice with increasing doses of TGPN-AB and AB. Then, animals were treated with 2.5 mg/kg/day of AB, 17.5 mg/kg/day of TGNP-AB, or TGNP three times a week for 4 weeks. TGNP-AB formulation was less cytotoxic for macrophages than AB. TGNP-AB was more effective than AB against the promastigotes forms of the parasite and more effective in reducing the number of infected macrophages and the number of amastigotes forms per cell. TGNP-AB-treated animals showed lower hepatotoxicity. In addition, TGNP-AB group showed a marked reduction in lesion size on the paws and parasitic load. The TGNP-AB preparation attained excellent leishmanicidal activity with remarkable lower drug toxicity at very high doses that, due to the toxicity-buffering properties of the nanocarrier, become fully tolerable.
Assuntos
Anfotericina B/administração & dosagem , Antiprotozoários/administração & dosagem , Quilomícrons/química , Leishmaniose Cutânea/tratamento farmacológico , Triglicerídeos/química , Anfotericina B/química , Anfotericina B/farmacologia , Animais , Antiprotozoários/química , Antiprotozoários/farmacologia , Linhagem Celular , Modelos Animais de Doenças , Composição de Medicamentos , Feminino , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Mimetismo Molecular , Nanopartículas , Carga ParasitáriaRESUMO
Abstract Tegumentary leishmaniasis (TL) diagnosis is challenging due to the lack of a gold standard diagnostic tool. The diagnosis is significantly harder in regions where visceral leishmaniasis (VL) is also prevalent since immunological tests may present cross-reactivity. A cirrhotic patient from an endemic Brazilian region for TL and VL presented with atypical cutaneous lesions, a usual clinico-laboratory feature of VL (including a positive rk39 test result), but he was diagnosed with TL histopathologically; VL was ruled out by necropsy. Physicians working in co-prevalent areas should be aware of atypical features, unusual clinical course, and unexpected laboratory findings of leishmaniasis.
Assuntos
Humanos , Masculino , Leishmaniose Cutânea/patologia , Leishmaniose Visceral/diagnóstico , Cirrose Hepática/complicações , Leishmaniose Cutânea/complicações , Leishmaniose Cutânea/diagnóstico , Evolução Fatal , Diagnóstico Diferencial , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Liposomal amphotericin B (L-AMB) has been used for mucosal leishmaniasis (ML), but comparative studies on L-AMB and other drugs used for the treatment of ML have not been conducted. The present study aimed to evaluate the outcome of patients with ML who were treated with L-AMB. METHODS: This is a 15-year retrospective study of Brazilian patients with a confirmed diagnosis of ML. The therapeutic options for the treatment of ML consisted of L-AMB, amphotericin B lipid complex (ABLC), deoxycholate amphotericin B (d-AMB), itraconazole, antimonial pentavalent, or pentamidine. Healing, cure rate and adverse effects (AEs) associated with the drugs used to treat this condition were analyzed. RESULTS: In 71 patients, a total of 105 treatments were evaluated. The outcome of the treatment with each drug was compared, and results showed that L-AMB was superior to other therapeutic regimens (P = 0.001; odds ratio [OR] = 4.84; 95% confidence interval [CI] = 1.78-13.17). d-AMB had worse AEs than other treatment regimens (P = 0.001, OR = 0.09; 95% CI = 0.09-0.43). Approximately 66% of the patients presented with AEs during ML treatment. Although L-AMB was less nephrotoxic than d-AMB, it was associated with acute kidney injury compared with other drugs (P <0.05). CONCLUSION: L-AMB was more effective than other therapies for the treatment of ML. However, a high incidence of toxicity was associated with its use. Therapeutic choices should be reassessed, and the development of new drugs is necessary for the treatment of ML.
Assuntos
Anfotericina B/uso terapêutico , Antiprotozoários/uso terapêutico , Leishmania braziliensis , Leishmaniose Mucocutânea/tratamento farmacológico , Injúria Renal Aguda/induzido quimicamente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anfotericina B/efeitos adversos , Antimônio/efeitos adversos , Antimônio/uso terapêutico , Antiprotozoários/efeitos adversos , Brasil , Estudos de Coortes , Ácido Desoxicólico/efeitos adversos , Ácido Desoxicólico/uso terapêutico , Combinação de Medicamentos , Feminino , Humanos , Itraconazol/efeitos adversos , Itraconazol/uso terapêutico , Lipossomos , Masculino , Pessoa de Meia-Idade , Pentamidina/efeitos adversos , Pentamidina/uso terapêutico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Immunosuppressive treatments for rheumatic diseases present special problems in areas endemic for chronic infectious diseases because of the possibility of reactivation. Leishmaniasis is a significant neglected tropical disease caused by different species of protozoan parasites within the genus Leishmania. Amastigotes live as intracellular parasites in a variety of mammalian cells, most notably within phagocytes such as macrophages, and residual parasites can persist even after treatment and healing of the lesions. We herein report a case of relapsing mucosal leishmaniasis after aggressive immunotherapy for ankylosing spondylitis, with requirement for secondary prophylaxis with amphotericin B to prevent reactivation. This approach can be necessary for patients from endemic areas of tegumentary leishmaniasis, who will undergo aggressive immunotherapy.
Assuntos
Anfotericina B/administração & dosagem , Antiprotozoários/administração & dosagem , Leishmaniose Mucocutânea/tratamento farmacológico , Prevenção Secundária/métodos , Espondilite Anquilosante/imunologia , Espondilite Anquilosante/terapia , Adulto , Humanos , Imunossupressores/efeitos adversos , Imunoterapia , Masculino , Recidiva , Espondilite Anquilosante/complicaçõesAssuntos
Anfotericina B/administração & dosagem , Antiprotozoários/administração & dosagem , Leishmaniose Mucocutânea/tratamento farmacológico , Idoso , Anfotericina B/efeitos adversos , Antiprotozoários/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoAssuntos
Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Leishmaniose Mucocutânea/tratamento farmacológico , Linfoma de Células T/tratamento farmacológico , Fator de Necrose Tumoral alfa/imunologia , Adalimumab/efeitos adversos , Adalimumab/uso terapêutico , Adulto , Anfotericina B/uso terapêutico , Anti-Inflamatórios/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Antiprotozoários/uso terapêutico , Brasil/epidemiologia , Diagnóstico Diferencial , Granuloma/diagnóstico , Granuloma/parasitologia , Granuloma/patologia , Humanos , Infliximab/uso terapêutico , Leishmaniose Mucocutânea/patologia , Linfoma de Células T/patologia , MasculinoRESUMO
Rheumatoid arthritis (RA) is a chronic condition that is frequent in patients living in tropical areas exposed to leishmaniasis. RA therapy involves immunosuppressant drugs such as methotrexate (MTX), monoclonal antibodies (mAbs) and prednisone. We report an unusual presentation of cutaneous (CL) or mucocutaneous leishmaniasis (ML) in RA patients from an endemic area of leishmaniasis. A 51-year-old woman noted a cutaneous ulcer on her left ankle during MTX and prednisone RA therapy. Initially diagnosed as a venous stasis ulcer, the aspirate of the injury revealed the presence of Leishmania DNA. A 73-year-old woman presenting non-ulcerated, infiltrated and painful erythematous nodules inside her nostrils while receiving MTX, anti-TNF mAb, and prednisone for RA, had also the aspirate of injuries showing the presence of Leishmania DNA. Both patients healed after the therapy with liposomal amphotericin. The RA therapy has changed to low-dose prednisone, without further reactivation episodes. Both cases suggest that CL or ML can reactivate after administration of an immunosuppressant for RA treatment. Therefore, immunosuppressive treatments for RA should be carefully prescribed in patients from endemic areas or with a history of CL and ML.