Treatment for human visceral leishmaniasis: a cost-effectiveness analysis for Brazil.

OBJECTIVE: To estimate the cost-effectiveness of strategies for the treatment of VL in Brazil. METHODS: Cost-effectiveness study comparing three therapeutic options: meglumine antimoniate (MA), liposomal amphotericin B (LAMB) and a combination of LAMB plus MA (LAMB plus MA), from public health system and societal perspectives. An analytical decision-making model was used to compare strategies for the following outcomes: early therapeutic failure avoided at 30 days, days of hospitalisation avoided and VL cure at 180 days. The efficacy and safety parameters of the drugs came from a randomised, open-label trial and the cost data came from a cost-of-illness study, both carried out in Brazil. RESULTS: For all outcomes analysed, the LAMB strategy was more effective. The MA strategy was inferior to the LAMB plus MA strategy for the outcomes early therapeutic failure avoided and cure. When only LAMB and MA were compared from a societal perspective, a cost of US$ 278.56 was estimated for each additional early therapeutic failure avoided, a cost of US$ 26.88 for each additional day of hospitalisation avoided and a cost of US$ 89.88 for each additional case of cured VL, for the LAMB strategy vs. MA. CONCLUSION: In Brazil, the LAMB strategy proved to be cost-effective for treating VL, considering a GDP per capita as the willingness-to-pay threshold, for all of the outcomes analysed in comparison to MA.

OBJECTIF: Estimer la rentabilité des stratégies de traitement de la leishmaniose viscérale (LV) au Brésil. MÉTHODES: Etude coût-efficacité comparant trois options thérapeutiques: l'antimoniate de méglumine (AM), amphotéricine B liposomale (LAMB) et une combinaison de LAMB et MA (LAMB plus AM), du point de vue du système de santé publique et sociétal. Un modèle décisionnel analytique a été utilisé pour comparer les stratégies pour les résultats suivants: échec thérapeutique précoce évité à 30 jours, jours d'hospitalisation évités et guérison de la LV à 180 jours. Les paramètres d'efficacité et de sécurité des médicaments provenaient d'un essai randomisé ouvert et les données relatives aux coûts, d'une étude sur le coût de la maladie, toutes deux menées au Brésil. RÉSULTATS: Pour tous les résultats analysés, la stratégie LAMB était plus efficace. La stratégie AM était inférieure à la stratégie LAMB plus AM pour les résultats: échec thérapeutique précoce évité et guérison. Lorsque seules les stratégies LAMB et AM ont été comparées d'un point de vue sociétal, un coût de 278,56 USD a été estimé pour chaque échec thérapeutique précoce additionnel évité, un coût de 26,88 USD pour chaque jour d'hospitalisation additionnel évité et un coût de 89,88 USD pour chaque cas additionnel de LV guéri, pour la stratégie LAMB par rapport à AM. CONCLUSION: Au Brésil, la stratégie LAMB s'est avérée rentable pour traiter la LV, considérant un PIB par habitant comme seuil de volonté de payer, pour tous les résultats analysés par rapport à l'AM.

Leishmaniasis and various immunotherapeutic approaches.

Leishmaniasis is a vector-borne infectious disease caused by multiple Leishmania (L.) species with diverse clinical manifestations. There is currently no vaccine against any form of the disease approved in humans, and chemotherapy is the sole approach for treatment. Unfortunately, treatment options are limited to a small number of drugs, partly due to high cost and significant adverse effects. The other obstacle in leishmaniasis treatment is the potential for drug resistance, which has been observed in multiple endemic countries. Immunotherapy maybe another important avenue for controlling leishmaniasis and could help patients control the disease. There are different approaches for immunotherapy in different infectious diseases, generally with low-cost, limited side-effects and no possibility to developing resistance. In this paper, different immunotherapy approaches as alternatives to routine drug treatment will be reviewed against leishmaniasis.

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

OBJECTIVE: To compare the cost-effectiveness of L-AmB with that of SbV and AmB-D, for the treatment of mucocutaneous leishmaniasis in a hospital in north-east 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 L-AmB had completed it after 2 months, vs. 22.0% for the SbV and 19.9% for the AmB-D groups. After 12 months of follow-up, these proportions were 100% in the L-AmB, 77.4% in the AmB-D and 72.2% in the SbV group. Markov chain analyses showed that the group that started therapy with SbV had the lowest mean total cost (US$ 3782.38), followed by AmB-D (US$ 5211.27) and L-AmB (US$ 11 337.44). The incremental cost-effectiveness ratio for L-AmB was US$ 18 816.23 against SbV and US$ 24 504.65 against AmB-D. In the sensitivity analysis, the drug acquisition cost of L-AmB significantly influenced the results. CONCLUSIONS: In the treatment of mucocutaneous leishmaniasis, L-AmB is a cost-effective alternative to SbV and AmB-D owing to its higher effectiveness, safety and shorter course.

Cheminformatic models based on machine learning for pyruvate kinase inhibitors of Leishmania mexicana.

BACKGROUND: Leishmaniasis is a neglected tropical disease which affects approx. 12 million individuals worldwide and caused by parasite Leishmania. The current drugs used in the treatment of Leishmaniasis are highly toxic and has seen widespread emergence of drug resistant strains which necessitates the need for the development of new therapeutic options. The high throughput screen data available has made it possible to generate computational predictive models which have the ability to assess the active scaffolds in a chemical library followed by its ADME/toxicity properties in the biological trials. RESULTS: In the present study, we have used publicly available, high-throughput screen datasets of chemical moieties which have been adjudged to target the pyruvate kinase enzyme of L. mexicana (LmPK). The machine learning approach was used to create computational models capable of predicting the biological activity of novel antileishmanial compounds. Further, we evaluated the molecules using the substructure based approach to identify the common substructures contributing to their activity. CONCLUSION: We generated computational models based on machine learning methods and evaluated the performance of these models based on various statistical figures of merit. Random forest based approach was determined to be the most sensitive, better accuracy as well as ROC. We further added a substructure based approach to analyze the molecules to identify potentially enriched substructures in the active dataset. We believe that the models developed in the present study would lead to reduction in cost and length of clinical studies and hence newer drugs would appear faster in the market providing better healthcare options to the patients.

Single-dose liposomal amphotericin B for visceral leishmaniasis in India.

BACKGROUND: Some 50% of patients with visceral leishmaniasis (kala-azar) worldwide live in the Indian state of Bihar. Liposomal amphotericin B is an effective treatment when administered in short courses. We wanted to determine whether the efficacy of a single infusion of liposomal amphotericin B was inferior to conventional parenteral therapy, consisting of 15 alternate-day infusions of amphotericin B deoxycholate. METHODS: In this open-label study, we randomly assigned 412 patients in a 3:1 ratio to receive either liposomal amphotericin B (liposomal-therapy group) or amphotericin B deoxycholate (conventional-therapy group). Liposomal amphotericin B (at a dose of 10 mg per kilogram of body weight) was given once, and patients were discharged home 24 hours later. Amphotericin B deoxycholate, which was administered in 15 infusions of 1 mg per kilogram, was given every other day during a 29-day hospitalization. We determined the cure rate 6 months after treatment. RESULTS: A total of 410 patients--304 of 304 patients (100%) in the liposomal-therapy group and 106 of 108 patients (98%) in the conventional-therapy group--had apparent cure responses at day 30. Cure rates at 6 months were similar in the two groups: 95.7% (95% confidence interval [CI], 93.4 to 97.9) in the liposomal-therapy group and 96.3% (95% CI, 92.6 to 99.9) in the conventional-therapy group. Adverse events in the liposomal-therapy group were infusion-related fever or rigors (in 40%) and increased anemia or thrombocytopenia (in 2%); such events in the conventional-therapy group were fever or rigors (in 64%), increased anemia (in 19%), and hypokalemia (in 2%). Nephrotoxicity or hepatotoxicity developed in no more than 1% of patients in each group. CONCLUSIONS: A single infusion of liposomal amphotericin B was not inferior to and was less expensive than conventional therapy with amphotericin B deoxycholate. (ClinicalTrials.gov number, NCT00628719.)

Importance of the horse and financial impact of equine trypanosomiasis on cattle raising in Venezuela.

In Venezuela, horses are indispensable for extensive cattle raising, and extensive cattle raising prevails in all regions. This determines the numerical relationship between horses and cattle (r = 0.93) to be relatively constant nationwide. At regional level, the average extension of cattle ranches varies greatly. However, in relation to the area covered by pastures, the numbers of horses (r = 0.95) and cattle (r = 0.93) are relatively uniform nationwide. Water buffalo occupy small fractions of the territory; therefore, their numbers are related to the area of pastures less strongly (r = 0.56). There is no information on the numerical relationship between the numbers of horses and water buffalo. In the Llanos region of the country, equine trypanosomiasis is responsible for a high mortality in horses, causing considerable financial losses to cattle ranches. So far, such losses have not been assessed. For this region, in 2008, it can be calculated that: (1) with no treatment, losses owing to horse mortality caused by this hemoparasitosis would have amounted to US$7,486,000; (2) the diagnosis and treatment of affected horses would have required an investment of US$805,000; and (3) in terms of horses saved, this investment would have resulted in benefit of US$6,232,000. Therefore, for every monetary unit invested, there would be a benefit 7.75 times greater, this ratio being applicable to any year and all regions of the country. It follows that the profitability of investing in the diagnosis and treatment of equine trypanosomiasis is guaranteed.

Economic burden of bovine trypanosomosis in three villages of Metekel zone, northwest Ethiopia.

The study was carried out to assess the economic burden of trypanosomosis in three villages of the Metekel zone in 2009. The disease was found to cause substantial economic losses through cattle mortality, drug purchase, and draft power loss of infected oxen. The farmers in the area were spending a significantly (p < 0.05) higher amount of money for the treatment of trypanosomosis than all other diseases combined. The overall mortality rate of cattle due to trypanosomosis was 4.4%. The mortality was significantly higher (p < 0.05) in an area where trypanosomosis prevalence was also higher. Many of the farmers prioritized losses of draft power as the most important impact of the disease. The overall prevalence of the disease was 12.1%. The disease burden was significantly (p < 0.05) higher in the rainy season than at other times of the year. In general, farmers had good knowledge on the signs and seasonality of trypanosomosis. Thus, tsetse suppression activities that involve the local community can be an important tool towards minimizing the economic burden of the disease in the area.

Effect of distillation waste water and plant hormones on spearmint growth and composition.

BACKGROUND: Distillation waste water (DWW) is a by-product from steam distillation of essential-oil crops; and currently, it is discharged into streams and rivers. The effects of DWW from 13 essential-oil crops, extracts from two alkaloid-containing species, and three plant hormones (methyl jasmonate, MJ; gibberellic acid, GA3; and salicylic acid, SA) were evaluated on productivity, essential-oil content and composition of spearmint (Mentha spicata L.) cv. 'Native'. RESULTS: Spearmint plant height was increased by the application of GA3 and Melissa officinalis DWW but suppressed by the application of Rosmarinus officinalis and Tagetes lucida DWW. Generally, MJ, GA3 and M. officinalis and Mentha arvensis DWW increased dry yields. The concentration of L-carvone in the oil ranged from 550 g kg(-1) (with Monarda citriodora DWW) to 670 g kg(-1) (with T. lucida DWW). M. citriodora DWW reduced the concentration of L-carvone in the oil by 23% relative to the control. CONCLUSION: Results suggest that DWW from essential-oil crops may affect monoterpene synthesis in M. spicata and, hence, may have a direct effect on the essential oil composition. DWW from essential-oil crops may be used as a growth promoter and modifier of the essential oil composition of spearmint.

Drug combinations for visceral leishmaniasis.

PURPOSE OF REVIEW: Several attempts have been made to combine drugs for treating visceral leishmaniasis, but only recently have effective drugs become available and combinations been tested systematically. RECENT FINDINGS: Sequential treatments with liposomal amphotericin B followed by miltefosine or paromomycin (as short as 7 days), as well as the concomitant administration of miltefosine and paromomycin (for 10 days) are very effective in India (>95%). Sodium stibogluconate plus paromomycin for 17 days is more than 90% effective in East Africa. The shortened combination regimens are cost-effective in India. No combination has been tested so far in Brazil, Nepal and Bangladesh, although studies may be expected in the near future. No cost-effectiveness analysis has been done as yet outside India. SUMMARY: There is evidence of high efficacy and benefits with sequential and co-administration treatments in India. More studies are needed in other endemic areas. Introducing combinations and scaling up their use will be challenging. Experience acquired with malaria may be useful. Proper monitoring of use and effects (efficacy and safety) will be required. Currently there are no options for fixed-dose combination treatments for leishmaniasis.

Amphotericin B therapy in children with visceral leishmaniasis: daily vs. alternate day, a randomized trial.

A randomized study was carried out to compare the efficacy and adverse reactions of daily vs. alternate day regimens of amphotericin B in children with visceral leishmaniasis (VL). Six hundred and five children of VL below 14 years of age were randomized into two groups; Group A (302), who received amphotericin B at a dose of 1 mg kg(-1) day(-1) for 15 days and Group B (303); same doses but on alternate days. All patients in both groups were cured, who had completed course of amphotericin B therapy. None had relapsed at 1 and 6 months of follow-up. Adverse reactions in both groups were non-significant. The duration of stay and cost of therapy was significantly lower in Group A children who left the hospital against medical advice, which was also significantly more in Group B. Thus, daily regimen of amphotericin B is equally effective, well tolerated, not more toxic and cost-effective than alternate day regimen, which is currently practiced.

Barriers to treatment for visceral leishmaniasis in hyperendemic areas: India, Bangladesh, Nepal, Brazil and Sudan.

CONTEXT: Visceral leishmaniasis (VL) is a severe and potentially fatal infection caused by the trypanosome parasite Leishmania sp. Over 90% of reported cases occur in India, Bangladesh, Nepal, Sudan, and Brazil, affecting mainly impoverished individuals and creating a significant economic burden through direct and indirect costs of treatment. OBJECTIVES: To identify the direct and indirect costs of VL treatment, compare these costs to household income, and identify the barriers to treatment in each of the five VL-endemic countries. METHODS: Articles obtained through PubMed (US National Library of Medicine), EMBASE, and Cochrane Library were selected for relevance to VL treatment, costs for all forms of amphotericin B, miltefosine, paromomycin, and antimony compounds, and healthcare costs in India, Bangladesh, Nepal, Brazil, and Sudan. Healthcare statistics were obtained from the World Health Organization Statistical Information System, Médecins Sans Frontieres, and each country's national health ministry. RESULTS: Per capita GDP, per capita GNI, cost of drugs, and hospitalization expenses differ by up to 10-fold in each of the five countries where VL is hyperendemic, resulting in unequal barriers to treatment. We found that the cost of specific drugs influences the choice of therapy. CONCLUSIONS: Poverty and VL treatment-related costs cause potential limitations in the provision of full and efficacious treatment, which may result in further dissemination of the disease. Effective nonparenteral antileishmania drugs would provide a significant advantage in reducing the barriers to VL treatment.

Cost-effectiveness projections of single and combination therapies for visceral leishmaniasis in Bihar, India.

OBJECTIVES: To assess the cost-effectiveness of current monotherapies and prospective combinations for treating visceral leishmaniasis (VL) in Bihar, India in terms of years of life lost (YLL) averted as well as deaths averted. METHODS: We employed two methods to estimate the number of avertable deaths in our analysis: one using estimated mortality, the other using direct incidence estimates for VL. Costs of care are based on an average private hospital in Bihar, and data on drug costs were obtained both locally and from the World Health Organization. RESULTS: The cost of monotherapies per averted YLL ranged from US$2 for paromomycin in an outpatient setting to US$20-22 for AmBisome at 20 mg/kg. The corresponding costs per death averted ranged from US$53-54 to US$523-527. Combinations ranged US$5-8 per YLL averted and US$124-213 per death averted. CONCLUSION: The available treatments for VL are cost-effective, and our mortality and incidence-based methods produce consistent estimates. The combinations considered here were more cost-effective than most monotherapies. Having multiple treatment options and combining drugs are also likely to reduce drug pressure and prolong the drugs' life-span of effective use.

Anthropometrically derived dosing and drug costing calculations for treating visceral leishmaniasis in Bihar, India.

OBJECTIVE AND METHOD: To estimate drug costs of treating visceral leishmaniasis (VL) based on data on the VL population structure from the high-burden, antimony-resistant area of Northern Bihar, India. RESULTS: Paromomycin is the cheapest option ($7450 to treat 1000 patients). Treating 1000 patients with oral miltefosine would cost $119,250 at the current private market price or $64,383-$75,129 at preferential public sector price depending on the size of the order. With AmBisome it would be $163,600 or $229,500 depending on the dose (10 or 15 mg/kg total). These costs are without considering other direct costs (daily intramuscular injections for 3 weeks for paromomycin; intravenous devices and hospitalization for AmBisome; directly observed treatment if applied for miltefosine) and indirect costs. CONCLUSION: These calculations provide useful basic information for projections.

"Cheaper and better": Societal cost savings and budget impact of changing from systemic to intralesional pentavalent antimonials as the first-line treatment for cutaneous leishmaniasis in Bolivia.

INTRODUCTION: Cutaneous leishmaniasis (CL), endemic in Bolivia, mostly affects poor people in rainforest areas. The current first-line treatment consists of systemic pentavalent antimonials (SPA) for 20 days and is paid for by the Ministry of Health (MoH). Long periods of drug shortages and a lack of safe conditions to deliver treatment are challenges to implementation. Intralesional pentavalent antimonials (ILPA) are an alternative to SPA. This study aims to compare the cost of ILPA and SPA, and to estimate the health and economic impacts of changing the first-line treatment for CL in a Bolivian endemic area. METHODS: The cost-per-patient treated was estimated for SPA and ILPA from the perspectives of the MoH and society. The quantity and unit costs of medications, staff time, transportation and loss of production were obtained through a health facility survey (N = 12), official documents and key informants. A one-way sensitivity analysis was conducted on key parameters to evaluate the robustness of the results. The annual number of patients treated and the budget impact of switching to ILPA as the first-line treatment were estimated under different scenarios of increasing treatment utilization. Costs were reported in 2017 international dollars (1 INT$ = 3.10 BOB). RESULTS: Treating CL using ILPA was associated with a cost-saving of $248 per-patient-treated from the MoH perspective, and $688 per-patient-treated from the societal perspective. Switching first-line treatment to ILPA while maintaining the current budget would allow two-and-a-half times the current number of patients to be treated. ILPA remained cost-saving compared to SPA in the sensitivity analysis. CONCLUSIONS: The results of this study support a shift to ILPA as the first-line treatment for CL in Bolivia and possibly in other South American countries.

Cost-effectiveness analysis of diagnostic-therapeutic strategies for visceral leishmaniasis in Brazil.

INTRODUCTION: Visceral leishmaniasis (VL) is fatal if not diagnosed and treated. This study aimed to estimate the cost-effectiveness of diagnostic-therapeutic alternatives for VL in Brazil. METHODS: A decision model estimated the life expectancy and costs of six diagnostic-therapeutic strategies. RESULTS: IT LEISH + liposomal amphotericin B emerged the best option, presenting lower costs and higher effectiveness. DAT-LPC + liposomal amphotericin B showed an incremental cost-effectiveness ratio of US$ 326.31 per life year. CONCLUSIONS: These findings indicate the feasibility of incorporating DAT and designating liposomal amphotericin B as the first-line drug for VL in Brazil.

Drug regimens for visceral leishmaniasis in Mediterranean countries.

Until the early 1990s, pentavalent antimony was the only documented first-line drug employed for the treatment of zoonotic visceral leishmaniasis (VL) in the Mediterranean, with reported cure rates exceeding 95% in immunocompetent patients. The emergence of antimony resistance in other endemic settings and the increase in drug options have stimulated re-evaluation of the current therapeutic approaches and outcomes in Mediterranean countries. A scientific consortium ('LeishMed' network) collected updated information from collaborating clinical health centres of 11 endemic countries of Southern Europe, Northern Africa and the Middle East. In contrast with the previous situation, VL is now treated differently in the region, basically through three approaches: (1) In Northern Africa and in part of the Middle East, pentavalent antimony is still the mainstay for therapy, with no alternative drug options for treating relapses; (2) In some European countries and Israel, both pentavalent antimony and lipid-associated amphotericin B (AmB) formulations are used as first-line drugs, although in different patients' categories; (3) In other countries of Europe, mainly liposomal AmB is employed. Importantly, cure rates exhibited by different drugs, including antimonials in areas where they are still in routine use, are similarly high (>/=95%) in immunocompetent patients. Our findings show that antimony resistance is not an emerging problem in the Mediterranean. A country's wealth affects the treatment choice, which represents a balance between drug efficacy, toxicity and cost, and costs associated with patient's care.

The economic value of identifying and treating Chagas disease patients earlier and the impact on Trypanosoma cruzi transmission.

BACKGROUND: The World Health Organization's 2020 Goals for Chagas disease include access to antiparasitic treatment and care of all infected/ill patients. Policy makers need to know the economic value of identifying and treating patients earlier. However, the economic value of earlier treatment to cure and prevent the Chagas' spread remains unknown. METHODS: We expanded our existing Chagas disease transmission model to include identification and treatment of Chagas disease patients. We linked this to a clinical and economic model that translated chronic Chagas disease cases into health and economic outcomes. We evaluated the impact and economic outcomes (costs, cost-effectiveness, cost-benefit) of identifying and treating different percentages of patients in the acute and indeterminate disease states in a 2,000-person village in Yucatan, Mexico. RESULTS: In the absence of early treatment, 50 acute and 22 new chronic cases occurred over 50 years. Identifying and treating patients in the acute stage averted 0.5-5.4 acute cases, 0.6-5.5 chronic cases, and 0.6-10.8 disability-adjusted life years (DALYs), saving $694-$7,419 and $6,976-$79,950 from the third-party payer and societal perspectives, respectively. Treating in the indeterminate stage averted 2.2-4.9 acute cases, 6.1-12.8 chronic cases, and 11.7-31.1 DALYs, saving $7,666-$21,938 from the third-party payer perspective and $90,530-$243,068 from the societal perspective. Treating patients in both stages averted ≤9 acute cases and ≤15 chronic cases. Identifying and treating patients early was always economically dominant compared to no treatment. Identifying and treating patients earlier resulted in a cumulative cost-benefit of $7,273-$224,981 at the current cost of identification and treatment. CONCLUSIONS: Even when identifying and treating as little as 5% of cases annually, treating Chagas cases in the acute and indeterminate stages reduces transmission and provides economic and health benefits. This supports the need for improved diagnostics and access to safe and effective treatment.

Health economic evaluation of moist wound care in chronic cutaneous leishmaniasis ulcers in Afghanistan.

BACKGROUND: The present health economic evaluation in Afghanistan aims to support public health decision makers and health care managers to allocate resources efficiently to appropriate treatments for cutaneous leishmaniasis (CL) elicited by Leishmania tropica or Leishmania major. METHODS: A decision tree was used to analyse the cost and the effectiveness of two wound care regimens versus intra-lesional antimony in CL patients in Afghanistan. Costs were collected from a societal perspective. Effectiveness was measured in wound free days. The incremental cost-effectiveness ratio (ICER) and incremental net monetary benefit (NMB) were calculated. The model was parameterized with baseline parameters, sensitivity ranges, and parameter distributions. Finally, the model was simulated and results were evaluated with deterministic and probability sensitivity analyses. Final outcomes were the efficiency of the regimens and a budget impact analysis in the context of Afghanistan. RESULTS: Average costs per patients were US$ 11 (SE = 0.016) (Group I: Intra-dermal Sodium Stibogluconate [IL SSG]), US$ 16 (SE = 7.58) (Group II: Electro-thermo-debridement [ETD] + Moist wound treatment [MWT]) and US$ 25 (SE = 0.48) (Group III: MWT) in patients with a single chronic CL ulcer. From a societal perspective the budget impact analysis shows that the regimens' drug costs are lower than indirect disease cost. Average effectiveness in wound free days are 177 (SE = 0.36) in Group II, 147 (SE = 0.33) in Group III, and 129 (SE = 0.27) in Group I. The ICER of Group II versus Group I was US$ 0.09 and Group III versus Group I US$ 0.77, which is very cost-effective with a willingness-to-pay threshold of US$ 2 per wound free day. Within a Monte-Carlo probabilistic sensitivity analysis Group II was cost-effective in 80% of the cases starting at a willingness-to-pay of 80 cent per wound free day. CONCLUSIONS: Group II provided the most cost-effective treatment. The non-treatment alternative is not an option in the management of chronic CL ulcers. MWT of Group III should at least be practiced. The cost-effectiveness of Group III depends on the number of dressings necessary until complete wound closure.

Miltefosine Combined with Intralesional Pentamidine for Leishmania braziliensis Cutaneous Leishmaniasis in Bolivia.

Bolivian cutaneous leishmaniasis due to Leishmania braziliensis was treated with the combination of miltefosine (150 mg/day for 28 days) plus intralesional pentamidine (120 µg/mm2 lesion area on days 1, 3, and 5). Ninety-two per cent of 50 patients cured. Comparison to historic controls at our site suggests that the efficacy of the two drugs was additive. Adverse effects and cost were also additive. This combination may be attractive when a prime consideration is efficacy (e.g., in rescue therapy), avoidance of parenteral therapy, or the desire to treat locally and also provide systemic protection against parasite dissemination.