Efficacy and Safety of AmBisome in Combination with Sodium Stibogluconate or Miltefosine and Miltefosine Monotherapy for African Visceral Leishmaniasis: Phase II Randomized Trial

Wasunna, Monique; Njenga, Simon; Balasegaram, Manica; Nast, Alexander; Omollo, Raymond; Edwards, Tansy; Dorlo, Thomas P. C.; Musa, Brima; Ali, Mohammed Hassan; Elamin, Mohammed Yasein; Kirigi, George; Rashid, Juma; Kip, Anke E; Schoone, Gerard J.; Hailu, Asrat; Olobo, Joseph; Ellis, Sally; Kimutai, Robert; Wells, Susan; Khalil, E. A. G.; Wourgaft, Nathalie Strub; Alves, Fabiana; Musa, Ahmed

doi:10.1371/journal.pntd.0004880

Cited by 68 publications

(85 citation statements)

References 22 publications

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“…Multicenter studies and systematic reviews with subgroup analyses may substantially increase our knowledge of those predictors in the overall VL and HIV-seronegative subjects. Certainly, subjects who are prone to relapses are eligible for a closer follow-up, and possibly for novel therapeutic options, such as a combination of drugs (Patole et al, 2014;Wasunna et al, 2016;Mastroianni et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Predictors of relapse of visceral leishmaniasis in inner São Paulo State, Brazil

Simão

Victória

Fortaleza

2020

International Journal of Infectious Diseases

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Objectives: Visceral leishmaniasis (VL) is a public health threat for several tropical countries, including Brazil. Therapy failures and relapses aggravate VL morbidity and mortality. Our study aimed at identifying predictors of relapse and thus contributes to directing therapeutic options and patient followup. Methods: A nonconcurrent cohort of 571 subjects who completed successful therapy for VL in the city of Bauru, São Paulo State, Brazil, was followed for 24 months in order to identify the incidence and predictors of relapse. Extensive review of medical charts and laboratory files was conducted. Univariate and multivariable Cox regression models were used to identify predictors for the outcome of interest. A hierarchical strategy was used for variable selection in multivariable models. Results: Relapses occurred in 6.8% of treated subjects, after a median of 6 months (interquartile range, 4-9). In a comprehensive multivariable model, relapse was associated with: HIV-coinfection (hazard ratio [HR], 7.47; 95% confidence interval [CI], 2.58-21.55); the presence of lower limb edema (HR, 6.06; 95%CI, 1.38-26.77) and low platelet count upon admission (HR for platelet count Â 1000, 0.99; 95%CI, 0.98-0.99) ; and secondary pneumonia (HR, 5.49; 95%CI, 1.49-20.18). On the other hand, therapy with Liposomal Amphotericin (as opposed to Antimoniate) was not independently associated with relapse (HR, 5.97; 95% CI, 0.63-56.29). Conclusion: Besides reinforcing the impact of HIV coinfection on the outcome of VL, our study points to clinical and laboratory findings that characterize patients who were more likely to relapse. Those groups should be more closely followed, and possibly could benefit from novel therapeutic options.

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Section: Discussionmentioning

confidence: 99%

Predictors of relapse of visceral leishmaniasis in inner São Paulo State, Brazil

Simão

Victória

Fortaleza

2020

International Journal of Infectious Diseases

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“…From Lonchocarpus xuul roots was isolated 2′,4′-dihydroxy-3′-(3methyl-but-2-enyl) chalcone or isocordoin (11), this compound was active against promastigotes of the same Leishmania strains (L. brazilensis, L. donovani, and L. amazonensis), showing an IC 50 values of 10, 40, and 26.7 μg/mL, respectively, also, this compound was active against the P-388 cell line with IC 50 = 34-57 μM [52]. Isocordoin (11) and 2′,4′-dihydroxy-3′-(γ,γ-dimethylallyl)dihydrochalcone or dihydroisocordoin (12), isolated from Lonchocarpus xuul roots were tested against L. mexicana promastigotes. These compounds showed an IC 50 = 7.7-66.5 μM, respectively.…”

Section: Leishmaniases As Re-emerging Diseases 168mentioning

confidence: 91%

“…On the other hand, 24% of the new synthetic drugs have as a base molecule or are derived from, active molecules obtained from medicinal plants [8][9][10][11][12][13][14][15][16][17]. Another report states that between the years 2000-2005, 23 new natural-origin drugs were introduced into the market, all of which exhibited structural and biological diversity.…”

Section: An Overview Of the Leishmanicidal Potential Of Medicinal Plamentioning

confidence: 99%

“…Currently, treatment of leishmaniasis employs first-line drugs such as sodium stibogluconate (commercially known as Pentostam) and meglumine antimoniate (commercially known as Glucantime), and other options (second-line drugs) are pentamidine isothionate (commercially known as Pentamidine), amphotericin B, (Fungizone or Ambisome), miltefosine, and paramomycin sulfate (Aminosidine), although this latter option is not widely utilized in Mexico and is not effective when administered orally [11]. Even when administered in combination, the effectiveness of the drugs is less than optimal [12,13].…”

Section: Introductionmentioning

confidence: 99%

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Natural Compounds and Extracts from Mexican Medicinal Plants with Anti-Leishmanial Activity: An Update

Jiménez-Arellanes¹,

León-Díaz²

2018

Leishmaniases as Re-Emerging Diseases

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Leishmaniasis is considered an emerging, uncontrolled disease, and is endemic in 98 countries. Annually, about 2 million cases of cutaneous and 500,000 cases of visceral type leishmaniasis are recorded, and 60,000 persons die from the disease. In Mexico, cutaneous leishmaniasis is known as chiclero's ulcer and is reported in 22 states; it is considered a health problem. For its treatment, pentavalent antimonial drugs are administered; these drugs cause severe side effects, are costly, and drug-resistant cases have been reported and have been developing for >70 years. One alternative to the drugs that are currently available is to find active molecules in medicinal plants; dihydrocorynantheine, corynantheine, and corynantheidine are active against Leishmania major, while harmane, pleiocarpin, buchtienin, luteolin, and quercetin are active against L. donovani. In Mexico, about 20 medicinal plants have been evaluated against L. mexicana, among which the most active are Tridax procumbens, Tridax procumbens, Pentalinon andrieuxii, Lantana camara, Schinus molle, and Prosopis laevigata. From some of these plants, active compounds with IC 50 ≤ 30 μg/mL or μM have been isolated, such as 3(S)-16,17-didehydrofalcarinol or Oxylipin, cholestra-4,20,24-trien-3-one or pentalinosterol, 24-methylcholest-4-24(28)-dien-3-one, cholest-4-en-3-one, 6,7-dihy-droneridie-none, neridienone, cholest-5,20,24-trien-3β-ol, and isocordoin. Today, the only pentalinonsterol has been synthesized and assayed in the visceral leishmaniasis experimental model using BALB/c mice infected with L. donovani. Liposome formulation of this compound administered by intravenous route at 2.5 mg/kg showed a significant reduction of parasite load in mouse liver and spleen.

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“…39,40 The combination of PM and antimonials produced a higher cure rate in VL patients in a trial in Bihar, than did antimonials alone, in which the lack of response was common. 41 Many other compounds are considered to be the secondline drugs for leishmaniasis, including pentamidine and the antifungal azole fluconazole, as well as fexinidazole and oleyl phosphocholine (OlPC), with approval status at different stages. The diguanidine-based compound pentamidine was initially developed as a synthetic analog of insulin.…”

mentioning

confidence: 99%

Nanostructured delivery systems with improved leishmanicidal activity: a critical review

Bruni¹,

Stella²,

Giraudo³

et al. 2017

IJN

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Leishmaniasis is a vector-borne zoonotic disease caused by protozoan parasites of the genus Leishmania , which are responsible for numerous clinical manifestations, such as cutaneous, visceral, and mucocutaneous leishmaniasis, depending on the site of infection for particular species. These complexities threaten 350 million people in 98 countries worldwide. Amastigotes living within macrophage phagolysosomes are the principal target of antileishmanial treatment, but these are not an easy target as drugs must overcome major structural barriers. Furthermore, limitations on current therapy are related to efficacy, toxicity, and cost, as well as the length of treatment, which can increase parasitic resistance. Nanotechnology has emerged as an attractive alternative as conventional drugs delivered by nanosized carriers have improved bioavailability and reduced toxicity, together with other characteristics that help to relieve the burden of this disease. The significance of using colloidal carriers loaded with active agents derives from the physiological uptake route of intravenous administered nanosystems (the phagocyte system). Nanosystems are thus able to promote a high drug concentration in intracellular mononuclear phagocyte system (MPS)-infected cells. Moreover, the versatility of nanometric drug delivery systems for the deliberate transport of a range of molecules plays a pivotal role in the design of therapeutic strategies against leishmaniasis. This review discusses studies on nanocarriers that have greatly contributed to improving the efficacy of antileishmaniasis drugs, presenting a critical review and some suggestions for improving drug delivery.

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Efficacy and Safety of AmBisome in Combination with Sodium Stibogluconate or Miltefosine and Miltefosine Monotherapy for African Visceral Leishmaniasis: Phase II Randomized Trial

Cited by 68 publications

References 22 publications

Predictors of relapse of visceral leishmaniasis in inner São Paulo State, Brazil

Predictors of relapse of visceral leishmaniasis in inner São Paulo State, Brazil

Natural Compounds and Extracts from Mexican Medicinal Plants with Anti-Leishmanial Activity: An Update

Nanostructured delivery systems with improved leishmanicidal activity: a critical review

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