Article

Leishmania donovani: genetic diversity of isolates from Sudan characterized by PCR-based RAPD.

Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.
Experimental Parasitology (impact factor: 2.12). 03/2010; 125(4):389-93. DOI:10.1016/j.exppara.2010.03.008 pp.389-93
Source: PubMed

ABSTRACT Drug unresponsiveness in patients with visceral leishmaniasis (VL) is a problem in many endemic areas. This study aimed to determine genetic diversity of Leishmania donovani isolates from a VL endemic area in Sudan as a possible explanation for drug unresponsiveness in some patients. Thirty clinically stibogluconate (SSG)-sensitive isolates were made SSG-unresponsive in vitro by gradually increasing SSG concentrations. The sensitive isolates and their SSG-unresponsive counterparts were typed using mini-circle kDNA and categorized using PCR-RAPD. All the isolates were typed as L. donovani, the resulting PCR-RAPD characterization of the SSG-sensitive isolates gave three distinct primary genotypes while, the SSG-unresponsive isolates showed only a single band. L. donovani isolates from eastern Sudan are diverse; this probably resulted from emergence of new L. donovani strains during epidemics due to the pressure of widespread use of antimonials. In this communication the possible role of isolates diversity in antimonial unresponsiveness and the in vitro changing PCR-RAPD band pattern in SSG-unresponsive strains were discussed.

0 0
 · 
0 Bookmarks
 · 
27 Views
  • Source
    Article: Sodium stibogluconate (SSG) & paromomycin combination compared to SSG for visceral leishmaniasis in East Africa: a randomised controlled trial.
    Ahmed Musa, Eltahir Khalil, Asrat Hailu, Joseph Olobo, Manica Balasegaram, Raymond Omollo, Tansy Edwards, Juma Rashid, Jane Mbui, Brima Musa, [......], Hailemariam Tafes, Yalemtsehay Mekonnen, Eyasu Makonnen, Serah Ndegwa, Patrick Sagaki, Robert Kimutai, Josephine Kesusu, Rhoda Owiti, Sally Ellis, Monique Wasunna
    [show abstract] [hide abstract]
    ABSTRACT: Alternative treatments for visceral leishmaniasis (VL) are required in East Africa. Paromomycin sulphate (PM) has been shown to be efficacious for VL treatment in India. A multi-centre randomized-controlled trial (RCT) to compare efficacy and safety of PM (20 mg/kg/day for 21 days) and PM plus sodium stibogluconate (SSG) combination (PM, 15 mg/kg/day and SSG, 20 mg/kg/day for 17 days) with SSG (20 mg/kg/day for 30 days) for treatment of VL in East Africa. Patients aged 4-60 years with parasitologically confirmed VL were enrolled, excluding patients with contraindications. Primary and secondary efficacy outcomes were parasite clearance at 6-months follow-up and end of treatment, respectively. Safety was assessed mainly using adverse event (AE) data. The PM versus SSG comparison enrolled 205 patients per arm with primary efficacy data available for 198 and 200 patients respectively. The SSG & PM versus SSG comparison enrolled 381 and 386 patients per arm respectively, with primary efficacy data available for 359 patients per arm. In Intention-to-Treat complete-case analyses, the efficacy of PM was significantly lower than SSG (84.3% versus 94.1%, difference = 9.7%, 95% confidence interval, CI: 3.6 to 15.7%, p = 0.002). The efficacy of SSG & PM was comparable to SSG (91.4% versus 93.9%, difference = 2.5%, 95% CI: -1.3 to 6.3%, p = 0.198). End of treatment efficacy results were very similar. There were no apparent differences in the safety profile of the three treatment regimens. The 17 day SSG & PM combination treatment had a good safety profile and was similar in efficacy to the standard 30 day SSG treatment, suggesting suitability for VL treatment in East Africa. www.clinicaltrials.govNCT00255567.
    PLoS Neglected Tropical Diseases 06/2012; 6(6):e1674. · 4.69 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

antimonial unresponsiveness
 
clinically stibogluconate
 
distinct primary genotypes
 
Drug unresponsiveness
 
eastern Sudan
 
endemic areas
 
genetic diversity
 
Leishmania donovani
 
mini-circle kDNA
 
new L. donovani strains
 
PCR-RAPD band pattern
 
possible explanation
 
possible role
 
resulting PCR-RAPD characterization
 
SSG concentrations
 
SSG-unresponsive counterparts
 
SSG-unresponsive strains
 
visceral leishmaniasis
 
VL endemic area
 
widespread use
 

Sh Hamad