RESUMO
Group-specific component (Gc) variants of vitamin D binding protein differ in their affinity for vitamin D metabolites that modulate antimycobacterial immunity. We conducted studies to determine whether Gc genotype associates with susceptibility to tuberculosis (TB). The following subjects were recruited into case-control studies: in the UK, 123 adult TB patients and 140 controls, all of Gujarati Asian ethnic origin; in Brazil, 130 adult TB patients and 78 controls; and in South Africa, 281 children with TB and 182 controls. Gc genotypes were determined and their frequency was compared between cases versus controls. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were obtained retrospectively for 139 Gujarati Asians, and case-control analysis was stratified by vitamin D status. Interferon (IFN)-gamma release assays were also performed on 36 Gujarati Asian TB contacts. The Gc2/2 genotype was strongly associated with susceptibility to active TB in Gujarati Asians, compared with Gc1/1 genotype (OR 2.81, 95% CI 1.19-6.66; p = 0.009). This association was preserved if serum 25(OH)D was <20 nmol.L(-1) (p = 0.01) but not if serum 25(OH)D was > or =20 nmol.L(-1) (p = 0.36). Carriage of the Gc2 allele was associated with increased PPD of tuberculin-stimulated IFN-gamma release in Gujarati Asian TB contacts (p = 0.02). No association between Gc genotype and susceptibility to TB was observed in other ethnic groups studied.
Assuntos
Tuberculose/genética , Proteína de Ligação a Vitamina D/sangue , Proteína de Ligação a Vitamina D/genética , Vitamina D/sangue , Adulto , Alelos , Ásia/etnologia , Brasil , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Pré-Escolar , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , Interferon gama/sangue , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , África do Sul , Tuberculose/etnologia , Reino UnidoRESUMO
Existing systemic treatments for New World cutaneous leishmaniasis (CL) caused by Leishmania (vianna) braziliensis are unsatisfactory. Liposomal amphotericin B has been used extensively for the treatment of visceral leishmaniasis, but in few cases of CL, and an appropriate regimen for CL has not been described. We successfully treated a patient with multiple L. braziliensis CL lesions acquired in Belize. Liposomal amphotericin B (AmBisome) was given to our patient as an inpatient for seven daily doses of 3 mg kg(-1) day(-1) and then as an outpatient at 3 mg kg(-1) twice weekly for a further three weeks, a total of 40 mg kg(-1). Liposomal amphotericin offers a well-tolerated alternative to pentavalent antimony or amphotericin B deoxycholate for the systemic treatment of New World CL.
Assuntos
Anfotericina B/administração & dosagem , Antiprotozoários/administração & dosagem , Leishmania braziliensis , Leishmaniose Cutânea/tratamento farmacológico , Adulto , Animais , Humanos , Dermatoses da Perna/tratamento farmacológico , Dermatoses da Perna/patologia , Leishmaniose Cutânea/patologia , Lipossomos , MasculinoRESUMO
We used liposomal amphotericin B as first-choice treatment of visceral leishmaniasis in 106 immunocompetent children who acquired the infection in a temperate region of southern Europe (Italy) where Leishmania infantum visceral leishmaniasis is endemic. The aim of the study was to identify the minimum total dose of liposomal amphotericin B needed to cure the infection in children and reduce the period of hospitalization. We conclude that the optimal regimen in immunocompetent children with L. infantum visceral leishmaniasis to be a total dose of 18 mg/kg of liposomal amphotericin B (3 mg/kg per day for 5 days, followed by 3 mg/kg administered as an outpatient regimen on day 10).
Assuntos
Anfotericina B/administração & dosagem , Antiprotozoários/administração & dosagem , Leishmaniose Visceral/tratamento farmacológico , Adolescente , Assistência Ambulatorial , Animais , Medula Óssea/parasitologia , Criança , Pré-Escolar , Esquema de Medicação , Portadores de Fármacos , Eletroforese , Doenças Endêmicas , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Seguimentos , Hospitalização , Humanos , Imunocompetência , Lactente , Isoenzimas/análise , Itália , Leishmania infantum/efeitos dos fármacos , Leishmania infantum/enzimologia , Tempo de Internação , Lipossomos , MasculinoRESUMO
Thirteen dogs naturally infected with Leishmania infantum showing viscerocutaneous signs of disease were treated with different dosages of liposomal amphotericin B (AmBisome) 3-3.3 kg showed rapid clinical improvement, with regression of lymphadenomegaly and splenomegaly, and cure of skin lesions. The clinical response was similar to that obtained with 14-21 doses of conventional antileishmanial drugs. However, follow-up lymph node aspirates remained positive for Leishmania in all dogs except one, which was treated with the total dose ofAmBisome 15 mg kg. The failure in parasitological cure may be due to inadequate drug targeting to parasitized cells, or to T-cell immune depression characteristic of patent cases of canine leishmaniasis, or to both