Efficacy of aminosidine administered alone or in combination with meglumine antimoniate for the treatment of experimental visceral leishmaniasis caused by Leishmania infantum

ABSTRACT In a murine model of Leishmania infantum visceral leishmaniasis, metronidazole, ketoconazole, fluconazole, itraconazole, and terbinafine were less effective than antimonial agents in reducing hepatic parasite load. Ketoconazole potentiated the effect of meglumine antimoniate reference therapy through its marked activity against spleen infection.

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Quantification of Leishmania infantum Kinetoplast DNA for Monitoring the Response to Meglumine Antimoniate Therapy in Visceral Leishmaniasis

American Journal of Tropical Medicine and Hygiene ◽

10.4269/ajtmh.12-0440 ◽

2013 ◽

Vol 88 (5) ◽

pp. 868-871 ◽

Cited By ~ 15

Author(s):

Bahman Pourabbas ◽

Zahra Rezaee ◽

Abdolkarim Ghadimi Moghadam ◽

Abdolvahab Alborzi ◽

Gholamreza Pouladfar

Keyword(s):

Visceral Leishmaniasis ◽

Leishmania Infantum ◽

Kinetoplast Dna ◽

Meglumine Antimoniate

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Treatment of canine visceral leishmaniasis with Milteforan™ induces Leishmania infantum resistance to miltefosine and amphotericin B

10.1101/2021.04.08.438938 ◽

2021 ◽

Author(s):

Gustavo Gonçalves ◽

Monique Paiva Campos ◽

Alessandra Silva Gonçalves ◽

Lia Carolina Soares Medeiros ◽

Fabiano Borges Figueiredo

Keyword(s):

Visceral Leishmaniasis ◽

Amphotericin B ◽

Leishmania Infantum ◽

Cross Resistance ◽

Canine Visceral Leishmaniasis ◽

In Vitro Susceptibility ◽

Meglumine Antimoniate ◽

Parasite Fitness ◽

The Impact

Visceral leishmaniasis (VL) is the most severe form of leishmaniasis and is caused by Leishmania infantum in the Americas. Since the use of Milteforam™ was authorized to treat canine visceral leishmaniasis (CVL) in Brazil in 2017, there has also been fear of the emergence of parasites resistant to this drug and, through cross-resistance mechanisms, to meglumine antimoniate and amphotericin B. Additionally, the literature shows that acquisition of resistance is followed by increased parasite fitness, with higher rates of proliferation, infectivity and metacyclogenesis, which are determining factors for parasite virulence. In this context, this study aims to analyze the impact of treating a dog with Milteforan™ on the generation of parasites resistant to miltefosine, meglumine antimoniate, and amphotericin B. To this end, in vitro susceptibility tests were conducted against these drugs with T0 (parasites isolated from the dog before treatment with Milteforan™), T1 (after one course of treatment), and T2 (after two courses of treatment) isolates. The rates of cell proliferation, infectivity, and metacyclogenesis of the isolates were also evaluated. The results indicate a gradual increase in parasite resistance to miltefosine and amphotericin B with increasing the number of treatment courses. A trend increase in the metacyclogenesis rate of the parasites was also observed as drug resistance increased. Therefore, treatment of CVL with Milteforan™ induces resistance to miltefosine and amphotericin B as well as changes in parasite fitness, and may have an impact on animal and human public health.

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Cutaneous Leishmaniasis in Algeria; Highlight on the Focus of M’Sila

Microorganisms ◽

10.3390/microorganisms9050962 ◽

2021 ◽

Vol 9 (5) ◽

pp. 962

Author(s):

Razika Beniklef ◽

Karim Aoun ◽

Karim Boudrissa ◽

Meriem Ben Abid ◽

Kamel Cherif ◽

...

Keyword(s):

Risk Factors ◽

Visceral Leishmaniasis ◽

Cutaneous Leishmaniasis ◽

Leishmania Infantum ◽

Psammomys Obesus ◽

Phlebotomus Papatasi ◽

Wild Rodents ◽

High Incidence ◽

Medical Importance ◽

Underlying Risk

Algeria ranks second after Afghanistan for the incidence of cutaneous leishmaniasis (CL) worldwide. Here, we report a 34-years retrospective analysis of CL in Algeria and focused on the most affected region, the M’Sila province. All 66 cutaneous isolates corresponded to Leishmania (L.) major. Our study of the sandfly and rodent fauna further highlighted the high density of Phlebotomus papatasi and additional phlebotomine species of medical importance, not previously identified in M’Sila. Wild rodents belonging to nine species were trapped in M’Sila, and Psammomys obesus and Meriones shawi were found infected by L. major. In addition, Leishmania infantum was isolated from two visceral leishmaniasis cases, one dog and its proven vectors (P. perniciosus, P. longicuspis, and P. perfiliewi) inventoried during the survey. The high incidence of CL in the M’Sila province is likely a consequence of the increase in minimum temperatures recorded that constitutes suitable conditions for establishing a high endemicity and leads to an explosive rise in leishmaniases cases in this region. A thorough investigation of the underlying risk factors is urgently needed to detect new cases earlier. All these would improve the preparedness to fight the disease.

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Sexual and vertical transmission of visceral leishmaniasis

The Journal of Infection in Developing Countries ◽

10.3855/jidc.4108 ◽

2014 ◽

Vol 8 (04) ◽

pp. 403-407 ◽

Cited By ~ 17

Author(s):

Andreia P Turchetti ◽

Tayse D Souza ◽

Tatiane A Paixão ◽

Renato L. Santos

Keyword(s):

Visceral Leishmaniasis ◽

Vertical Transmission ◽

Leishmania Infantum ◽

Vertebrate Host ◽

Domestic Dog ◽

Sand Flies ◽

Phlebotomine Sand Flies

Visceral leishmaniasis (VL) is an important zoonosis caused by Leishmania infantum, which has in the domestic dog its principal vertebrate host. VL is usually transmitted by phlebotomine sand flies, however atypical routes of transmission have been described. In this review we discuss the the role of sexual and vertical transmissions, and their role in the maintenance of VL in canine populations.

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Effectiveness of Short-Course Meglumine Antimoniate (Glucantime ® ) for Treatment of Visceral Leishmaniasis: A 13-Year, Multistage, Non-Inferiority Study in Iran

American Journal of Tropical Medicine and Hygiene ◽

10.4269/ajtmh.16-0345 ◽

2016 ◽

Vol 96 (1) ◽

pp. 182-189 ◽

Cited By ~ 2

Author(s):

Abdolvahab Alborzi ◽

Gholamreza Pouladfar ◽

Armin Attar ◽

Fatemeh Falahi ◽

Zahra Jafarpour ◽

...

Keyword(s):

Visceral Leishmaniasis ◽

Meglumine Antimoniate ◽

Short Course

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In vitro and in vivo resistance of Leishmania infantum to meglumine antimoniate: a study of 37 strains collected from patients with visceral leishmaniasis.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.41.4.827 ◽

1997 ◽

Vol 41 (4) ◽

pp. 827-830 ◽

Cited By ~ 140

Author(s):

F Faraut-Gambarelli ◽

R Piarroux ◽

M Deniau ◽

B Giusiano ◽

P Marty ◽

...

Keyword(s):

Visceral Leishmaniasis ◽

Leishmania Infantum ◽

Strongly Correlated ◽

Duration Of Treatment ◽

In Vitro Sensitivity ◽

Sensitivity Tests ◽

Leishmania Parasites ◽

Immunocompetent Patients

Primary and secondary unresponsiveness to meglumine has long been described in human visceral leishmaniasis. However, no studies have been performed to elucidate if these therapeutic failures were due to strain variability in meglumine sensitivity or were related to host factors. We have studied the in vitro sensitivity of 37 strains of Leishmania infantum isolated from 23 patients (11 human immunodeficiency virus-infected and 12 immunocompetent patients) with visceral leishmaniasis. Sensitivity tests were performed by infecting murine macrophages with Leishmania parasites and culturing them in medium containing different concentrations of meglumine. For each test we calculated a 50% effective dose (ED50) corresponding to the meglumine concentration at which 50% of the Leishmania parasites survived. In vitro results were strongly correlated to immediate clinical outcome. All strains requiring an ED50 of >70 microg/ml were related to therapeutic failures, whereas all strains requiring an ED50 of <40 microg/ml corresponded to an initial efficiency of meglumine. Among those patients who were initially improved, relapses occurred in all immunocompromised patients and in most immunocompetent patients who had a short duration of treatment (15 days). Finally, we found that in vitro sensitivity of strains decreased progressively in relapsing patients treated with meglumine. Consequently, the physician may be encouraged to alternate meglumine with other treatments such as amphotericin B or pentamidine, especially in the case of relapsing patients.

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Ecology of Lutzomyia longipalpis and Lutzomyia migonei in an endemic area for visceral leishmaniasis

Revista Brasileira de Parasitologia Veterinária ◽

10.1590/s1984-29612014068 ◽

2014 ◽

Vol 23 (3) ◽

pp. 320-327 ◽

Cited By ~ 11

Author(s):

Rafaella Albuquerque Silva ◽

Fabricio Kassio Moura Santos ◽

Lindemberg Caranha de Sousa ◽

Elizabeth Ferreira Rangel ◽

Claudia Maria Leal Bevilaqua

Keyword(s):

Visceral Leishmaniasis ◽

Leishmania Infantum ◽

Indoor Environment ◽

Endemic Area ◽

Natural Infection ◽

Sampling Site ◽

Lutzomyia Longipalpis ◽

Sand Flies ◽

Sampling Points ◽

Lutzomyia Migonei

The main vector for visceral leishmaniasis (VL) in Brazil is Lutzomyia longipalpis. However, the absence of L. longipalpis in a region of autochthonous VL demonstrates the participation of other species in the transmission of the parasite. Studies conducted in La Banda, Argentina, and São Vicente Férrer, Pernambuco State, Brazil, have correlated the absence of L. longipalpisand the presence of L. migonei with autochthonous cases of VL. In São Vicente Férrer, Pernambuco, there was evidence for the natural infection of L. migonei with Leishmania infantum chagasi. Thus, the objective of this work was to assess the ecology of the sand flies L. longipalpis and L. migonei in Fortaleza, an endemic area for VL. Insect capture was conducted at 22 sampling points distributed across four regions of Fortaleza. In total, 32,403 sand flies were captured; of these, 18,166 (56%) were identified as L. longipalpis and 14,237 (44%) as L. migonei. There were significant density differences found between the vectors at each sampling site (indoors and outdoors) (p <0.0001). These findings confirm that L. migonei and L. longipalpis are distributed throughout Fortaleza, where they have adapted to an indoor environment, and suggest that L. migonei may share the role as a vector with L. longipalpis in the transmission of VL in Fortaleza.

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