Characterization of ubiquitin-activating (E1) and ubiquitinconjugating (E2) genes over-expressed in the infective stage of Leishmania infantum (original) (raw)

Cost-effectiveness of liposomal amphotericin B in hospitalised patients with mucocutaneous leishmaniasis

Tropical Medicine & International Health, 2017

objective To compare the cost-effectiveness of LAmB with that of Sb V and AmB-D, for the treatment of mucocutaneous leishmaniasis in a hospital in northeast Brazil. methods We developed an economic model based on retrospective data of 73 hospitalised patients in 2006-2012, from hospital and public health system perspectives. results In the economic model, 82.2% of patients who started treatment with LAmB had completed it after 2 months, vs. 22.0% for the Sb V and 19.9% for the AmB-D groups. After 12 months of follow-up, these proportions were 100% in the LAmB , 77.4% in the AmB-D and 72.2% in the Sb V group. Markov chain analyses showed that the group that started therapy with Sb V had the lowest mean total cost

The direct costs of treating human visceral leishmaniasis in Brazil

Revista da Sociedade Brasileira de Medicina Tropical

Introduction: The drugs available for visceral leishmaniasis (VL) treatment in Brazil have specific characteristics in terms of operability, effectiveness, toxicity, and cost. The aim of this study was to estimate the direct costs of therapies recommended by the Ministry of Health (MH) for VL treatment in Brazil. Methods: The analytical perspective used was that adopted by the Brazilian Public Health System. Three drugs and four regimens were included: 1) N-methyl glucamine antimoniate intramuscularly at 20mg per kg per day for 30 days; 2) N-methyl glucamine antimoniate intravenously at 20mg per kg per day for 30 days; 3) amphotericin B deoxycholate at 1mg per kg per day for 21 days; and 4) liposomal amphotericin B at 3mg per kg per day for a 7 days treatment. Results: The estimated direct costs of treatment for an adult patient using N-methylglucamine antimoniate administered via the intramuscular and intravenous routes were USD 418.52 and USD 669.40, respectively. The estimated cost of treatment with amphotericin B deoxycholate was USD 1,522.70. Finally, the estimated costs of treatment with liposomal amphotericin B were USD 659.79, and USD 11,559.15 using the price adopted by the WHO and the Drug Regulation Board, respectively. Conclusions: This analysis indicates the economic feasibility of replacing N-methyl glucamine antimoniate with liposomal amphotericin B, which allows a shorter treatment period with less toxicity compared with other treatments, provided that the purchase value used by the WHO and transferred to the MH is maintained.

Drug policy for visceral leishmaniasis: a cost-effectiveness analysis

OBJECTIVE: To facilitate the choice of the best visceral leishmaniasis (VL) treatment strategy for first-line health services in (VL)-endemic areas, we compared in a formal decision analysis the cost and the cost-effectiveness of the different available options. METHODS: We selected four drug regimens for VL on the basis of frequency of use, feasibility and reported efficacy studies. The point estimates and the range of plausible values of effectiveness and cost were retrieved from a literature review. A decision tree was constructed and the strategy minimizing the cost per death averted was selected. RESULTS: Treatment with amphotericin B deoxycholate was the most effective approach in the baseline analysis and averted 87.2% of all deaths attributable to VL. The least expensive and the most cost-effective treatment was the miltefosine regimen, and the most expensive and the least cost-effective was AmBisome treatment. The cost of drug and medical care are the main determinants of the cost-effectiveness ranking of the alternative schemes. Sensitivity analysis showed that antimonial was competitive with miltefosine in the low-resistance regions. CONCLUSION: In areas with >94% response rates to antimonials, generic sodium stibogluconate remains the most cost-effective option for VL treatment, mainly due to low drug cost. In other regions, miltefosine is the most cost-effective option of treatment, but its use as a first-line drug is limited by its teratogenicity and rapid resistance development. AmBisome in mono- or combination therapy is too expensive to compete in cost-effectiveness with the other regimens.

Health Economic Evaluations of Visceral Leishmaniasis Treatments: A Systematic Review

PLOS Neglected Tropical Diseases, 2015

Visceral leishmaniasis (VL) is a severe form of the leishmaniasis-disease complex. Its importance to public health relies on its high fatality rate in non-treated cases, the socioeconomic impact related to its morbidity, and its endemicity on different continents. The estimated burden of disease of VL varies from 1,969,000 to 2,357,000 Disability Adjusted Life Years (DALYs). VL is classified as a Neglected Tropical Disease (NTD), and is strongly related to poverty and its consequences. Visceral leishmaniasis calls for the development of cost-effective technologies for diagnosis and treatment. Objective The main objective of this study was to identify, describe, classify and analyze the scientific health economic evidence of VL-related technologies. Methods A web search of combinations of free text and Mesh terms related to the economic evaluation of visceral leishmaniasis was conducted on scientific publication databases (Web of Science, Scopus, Medline via the Pubmed and Lilacs). A manual search of references lists of articles previously identified by the authors was also included. Articles written in English, Portuguese, Spanish or French were considered suitable for inclusion. Articles that matched the inclusion criteria were screened by at least two researchers, who extracted information regarding the epidemiologic scenario and methodological issues on a standardized form. Results The initial search retrieved 107 articles, whose abstracts were inspected according to the inclusion criteria leading to a first selection of 49 (46%) articles. After the elimination of duplicates, the list was reduced to 21 (20%) articles. After careful reading and application of exclusion criteria, 14 papers were eligible according to the description, classification and analysis process proposed by the study. When classified by type of economic evaluation, articles were 7 (50%) cost-effectiveness, 5 (36%) cost-minimization, 1(7%) cost-benefit, and 1(7%) budget impact. When classified by methodology, studies were mainly nested to clinical-trials (“piggy back”) 8(57%). Discount rates for outcomes and costs were present in 3 (43%) of the cost-effectiveness studies, and according to WHO's recommendations, the discount rate of 3% was used in all studies. Conclusions This article showed that health economic evaluations on visceral leishmaniasis used a wide range of technologies and methods. Nevertheless it is important to point out the geographic concentration of studies, which makes their transferability uncertain to different epidemiological scenarios, especially those concerning visceral leishmaniasis caused by Leishmania infantum.

Single-dose liposomal amphotericin B (AmBisome®) for the treatment of Visceral Leishmaniasis in East Africa: study protocol for a randomized controlled trial

Trials, 2011

Background AmBisome® is an efficacious, safe anti-leishmanial treatment. There is growing interest in its use, either as a single dose or in combination treatments. In East Africa, the minimum optimal single-dosage has not been identified. Methods/Design An open-label, 2-arm, non-inferiority, multi-centre randomised controlled trial is being conducted to determine the optimal single-dose treatment with AmBisome®. Patients in the single-dose arm will receive one infusion on day 1, at a dose depending on body weight. For the first group of patients entered to the trial, the dose will be 7.5 mg/kg, but if this dose is found to be ineffective then in subsequent patient series the dose will be escalated progressively to 10, 12.5 and 15 mg/kg. Patients in the reference arm will receive a multi-dose regimen of AmBisome® (3 mg/kg/day on days 1-5, 14 and 21: total dose 21 mg/kg). Patients will be hospitalised for approximately one month after the start of treatment and then followed up at th...

Cost-effectiveness of competing diagnostic- therapeutic strategies for visceral leishmaniasis

Reported are the results of a formal decision analysis which facilitated the choice of the most appropriate testtreatment strategy for visceral leishmaniasis in areas where the disease is endemic. The following strategies were compared: treatment of all suspects (strategy A); testing by means of parasitological investigation followed by treatment of positives (strategy B); two-step testing by means of the direct agglutination test (DAT) followed by treatment of patients with high titres as well as those with parasitologically confirmed borderline titres (strategy C); and DAT followed by treatment of positives (strategy D).

Cost of Pediatric Visceral Leishmaniasis Care in Morocco

PLOS ONE, 2016

Background Visceral leishmaniasis (VL) is a neglected parasitic disease that is fatal if left untreated. VL is endemic in Morocco and other countries in North Africa were it mainly affects children from rural areas. In Morocco, the direct observation of Leishmania parasites in bone marrow aspirates and serological tests are used to diagnose VL. Glucantime is the first line of treatment. The objective of this study was to report the costs associated to standard clinical management of pediatric VL from the provider perspective in Morocco. As a secondary objective we described the current clinical practices and the epidemiological characteristics of pediatric VL patients.