In-vitro sensitivity of Pakistani Leishmania tropica field isolate against buparvaquone in comparison to standard anti-leishmanial drugs

Jamal, Qaisar; Khan, Nazma Habib; Wahid, Sobia; Awan, M. M.; Sutherland, Colin J.; Shah, Anwar‐ul‐Haq Ali

doi:10.1016/j.exppara.2015.04.017

Cited by 12 publications

(7 citation statements)

References 42 publications

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“…A related hydroxynaphthoquinone compound, buparvaquone (Table 3 ), is used for the treatment of theileriosis in cattle (McHardy et al, 1985 ; Minami et al, 1985 ; Muraguri et al, 1999 ; Mhadhbi et al, 2010 ), and horses (Zaugg and Lane, 1989 ). Anti-leishmanial activity was evaluated in vitro for L. donovani, Leishmania aethiopica, L. major, Leishmania amazonensis, Leishmania mexicana, Leishmania panamensis, L. infantum, Leishmania chagasi, L. braziliensis , and L. tropica promastigotes and amastigotes resulting in IC 50 -values of 0.001–5.495 μM (Mäntylä et al, 2004a , b ; Reimão et al, 2012 ; Jamal et al, 2015 ). Animal models showed that the in vivo efficiency was higher when prodrugs of buparvaquone were applied (Croft et al, 1992 ; Garnier et al, 2007 ) or when a nanoliposomal drug preparation was used (da Costa-Silva et al, 2017 ).…”

Section: Targeting Transport Processes Of Parasites At Different Levementioning

confidence: 99%

Targeting Channels and Transporters in Protozoan Parasite Infections

2018

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Infectious diseases caused by pathogenic protozoa are among the most significant causes of death in humans. Therapeutic options are scarce and massively challenged by the emergence of resistant parasite strains. Many of the current anti-parasite drugs target soluble enzymes, generate unspecific oxidative stress, or act by an unresolved mechanism within the parasite. In recent years, collections of drug-like compounds derived from large-scale phenotypic screenings, such as the malaria or pathogen box, have been made available to researchers free of charge boosting the identification of novel promising targets. Remarkably, several of the compound hits have been found to inhibit membrane proteins at the periphery of the parasites, i.e., channels and transporters for ions and metabolites. In this review, we will focus on the progress made on targeting channels and transporters at different levels and the potential for use against infections with apicomplexan parasites mainly Plasmodium spp. (malaria) and Toxoplasma gondii (toxoplasmosis), with kinetoplastids Trypanosoma brucei (sleeping sickness), Trypanosoma cruzi (Chagas disease), and Leishmania ssp. (leishmaniasis), and the amoeba Entamoeba histolytica (amoebiasis).

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Section: Targeting Transport Processes Of Parasites At Different Levementioning

confidence: 99%

Targeting Channels and Transporters in Protozoan Parasite Infections

2018

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“…70 Several studies back the widespread drug resistance to traditional antimonial treatments in South Asia and the study area in particular. 71,72 However, heterozygosity observed in the Pak-Afghan cluster may be explained either by heterozygosity at individual loci or by the presence of mixtures of strains because isolates in the present study were not cloned. 28,34 It would, therefore, be interesting to analyze clones of Pakistani strains that were allocated to different populations, subpopulations, or clusters although studies suggest that, in nature, complex infections with mixed parasite genotypes in mammalian hosts are probably rare especially in hypoendemic foci.…”

Section: Discussionmentioning

confidence: 68%

Variability of Cutaneous Leishmaniasis Lesions Is Not Associated with Genetic Diversity of Leishmania tropica in Khyber Pakhtunkhwa Province of Pakistan

Khan

Llewellyn

Schönian

et al. 2017

The American Journal of Tropical Medicine and Hygiene

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is the causative agent of cutaneous leishmaniasis in Pakistan. Here, intraspecific diversity of from northern Pakistan was investigated using multilocus microsatellite typing. Fourteen polymorphic microsatellite markers were typed in 34 recently collected isolates from Pakistan along with 158 archival strains of diverse Afro-Eurasian origins. Previously published profiles for 145 strains of originating from different regions of Africa, Central Asia, Iran, and Middle East were included for comparison. Six consistently well-supported genetic groups were resolved: 1) Asia, 2) Morroco A, 3) Namibia and Kenya A, 4) Kenya B/Tunisia and Galilee, 5) Morocco B, and 6) Middle East. Strains from northern Pakistan were assigned to Asian cluster except for three that were placed in a geographically distant genetic group; Morocco A. Lesion variability among these Pakistani strains was not associated with specific genetic profile. Pakistani strains showed little genetic differentiation from strains of Iraq, Afghanistan, and Syria (F = 0.00-0.06); displayed evidence of modest genetic flow with India (F = 0.14). Furthermore, genetic structuring within these isolates was not geographically defined. Pak-Afghan cluster was in significant linkage disequilibrium (I = 1.43), had low genetic diversity, and displayed comparatively higher heterozygosity (F = -0.62). Patterns of genetic diversity observed suggest dominance of a minimally diverse clonal lineage within northern Pakistan. This is surprising as a wide clinical spectrum was observed in patients, suggesting the importance of host and other factors. Further genotyping studies of isolates displaying different clinical phenotypes are required to validate this potentially important observation.

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“…Buparvaquone has also shown activity against other protozoan parasites such Plasmodium spp . [19], Leishmania spp. [20] or Neospora spp.…”

Section: Introductionmentioning

confidence: 99%

“…Although the mechanism of action of this drug has not been fully elucidated, there are indications of its selective toxicity through inhibition of parasite respiratory systems as postulated for Theileria spp., Plasmodium spp., and Eimeria spp. [19]. Today, buparvaquone is commercially available for use against theileriosis in cattle in some African countries.…”

Section: Introductionmentioning

confidence: 99%

Efficacy, safety and tolerance of imidocarb dipropionate versus atovaquone or buparvaquone plus azithromycin used to treat sick dogs naturally infected with the Babesia microti-like piroplasm

et al. 2017

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BackgroundPiroplasmosis caused by the Babesia microti-like piroplasm (Bml) is increasingly being detected in dogs in Europe. Sick dogs show acute disease with severe anaemia associated with thrombocytopenia with a poor response to current available drugs. This study assesses the safety and tolerance of three treatments and compares their efficacy over a full year of follow up in dogs naturally infected with Bml.MethodsFifty-nine dogs naturally infected with Bml were randomly assigned to a treatment group: imidocarb dipropionate (5 mg/kg SC, 2 doses 14 d apart) (IMI); atovaquone (13.3 mg/kg PO q 8 h, 10 d)/azithromycin (10 mg/kg PO q 24 h, 10 d) (ATO); or buparvaquone (5 mg/kg IM, 2 d apart)/azithromycin (same dosage) (BUP). Before and after treatment (days 15, 45, 90 and 360), all dogs underwent a physical exam, blood tests and parasite detection (blood cytology and PCR). Clinical efficacy was assessed by grading 24 clinical and 8 clinicopathological signs from low to high severity.ResultsBefore treatment, most dogs had severe regenerative anaemia (88.13%) and thrombocytopenia (71.4%). On treatment Day 45, clinical signs were mostly reduced in all dogs, and by Day 90, practically all dogs under the ATO or BUP regimen were clinically healthy (76.4 and 88%, respectively). Highest percentage reductions in laboratory abnormalities (82.04%) were detected in animals treated with ATO. Over the year, clinical relapse of Bml was observed in 8 dogs (8/17) treated with IMI. However, on Day 360, these animals had recovered clinically, though clinicopathological abnormalities were still present in some of them. Parasitaemia was PCR-confirmed on Days 90 and 360 in 47.05 and 50% of dogs treated with ATO, 68 and 60.08% with BUP, and 94.1 and 73.3% with IMI, respectively. Even after 360 days, 13.3% of the dogs treated with IMI returned a positive blood cytology result.ConclusionsIMI showed the worse clinical and parasitological, efficacy such that its use to treat Bml infection in dogs is not recommended. The treatments ATO and BUP showed better efficacy, though they were still incapable to completely eliminate PCR-proven infection at the recommended dose. All three treatments showed good tolerance and safety with scarce adverse events observed.

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In-vitro sensitivity of Pakistani Leishmania tropica field isolate against buparvaquone in comparison to standard anti-leishmanial drugs

Cited by 12 publications

References 42 publications

Targeting Channels and Transporters in Protozoan Parasite Infections

Targeting Channels and Transporters in Protozoan Parasite Infections

Variability of Cutaneous Leishmaniasis Lesions Is Not Associated with Genetic Diversity of Leishmania tropica in Khyber Pakhtunkhwa Province of Pakistan

Efficacy, safety and tolerance of imidocarb dipropionate versus atovaquone or buparvaquone plus azithromycin used to treat sick dogs naturally infected with the Babesia microti-like piroplasm

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