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Background: Anti-leishmanial drug regimens that include a single dose AmBisome® could be suitable for eastern African patients with symptomatic visceral leishmaniasis (VL) but the appropriate single dose is unknown. Methodology: A multi-centre, open-label, non-inferiority, randomized controlled trial with an adaptive design, was conducted to compare the efficacy and safety of a single dose and multiple doses of AmBisome® for the treatment of VL in eastern Africa. The primary efficacy endpoint was definitive cure (DC) at 6 months. Symptomatic patients with parasitologically-confirmed, non-severe VL, received a single dose of AmBisome® 7.5 mg/kg body weight or multiple doses, 7 times 3 mg/kg on days 1–5, 14, and 21. If interim analyses, evaluated 30 days after the start of treatment following 40 or 80 patients, showed the single dose gave significantly poorer parasite clearance than multiple doses at the 5% significance level, the single dose was increased by 2·5 mg/kg. In a sub-set of patients, parasite clearance was measured by quantitative reverse transcriptase (qRT) PCR. Principal Findings: The trial was terminated after the third interim analysis because of low efficacy of both regimens. Based on the intention-to-treat population, DC was 85% (95%CI 73–93%), 40% (95%CI 19–64%), and 58% (95%CI 41–73%) in patients treated with multiple doses (n = 63), and single doses of 7·5 (n = 21) or 10 mg/kg (n = 40), respectively. qRT-PCR suggested superior parasite clearance with multiple doses as early as day 3. Safety data accorded with the drug label. Conclusions: The tested AmBisome® regimens would not be suitable for VL treatment across eastern Africa. An optimal single dose regimen was not identified. Trials Registration: www.clinicaltrials.gov NCT00832208 [ABSTRACT FROM AUTHOR]

Background: The Leishmania OligoC-TesT and NASBA-Oligochromatography (OC) were recently developed for simplified and standardised molecular detection of Leishmania parasites in clinical specimens. We here present the phase II evaluation of both tests for diagnosis of visceral leishmaniasis (VL), cutaneous leishmaniasis (CL) and post kala-azar dermal leishmaniasis (PKDL) in Sudan. Methodology: The diagnostic accuracy of the tests was evaluated on 90 confirmed and 90 suspected VL cases, 7 confirmed and 8 suspected CL cases, 2 confirmed PKDL cases and 50 healthy endemic controls from Gedarif state and Khartoum state in Sudan. Principal Findings: The OligoC-TesT as well as the NASBA-OC showed a sensitivity of 96.8% (95% CI: 83.8%–99.4%) on lymph node aspirates and of 96.2% (95% CI: 89.4%–98.7%) on blood from the confirmed VL cases. The sensitivity on bone marrow was 96.9% (95% CI: 89.3%–99.1%) and 95.3% (95% CI: 87.1%–98.4%) for the OligoC-TesT and NASBA-OC, respectively. All confirmed CL and PKDL cases were positive with both tests. On the suspected VL cases, we observed a positive OligoC-TesT and NASBA-OC result in 37.1% (95% CI: 23.2%–53.7%) and 34.3% (95% CI: 20.8%–50.9%) on lymph, in 72.7% (95% CI: 55.8%–84.9%) and 63.6% (95% CI: 46.6%–77.8%) on bone marrow and in 76.9% (95% CI: 49.7%–91.8%) and 69.2% (95% CI: 42.4%–87.3%) on blood. Seven out of 8 CL suspected cases were positive with both tests. The specificity on the healthy endemic controls was 90% (95% CI: 78.6%–95.7%) for the OligoC-TesT and 100% (95% CI: 92.9%–100.0%) for the NASBA-OC test. Conclusions: Both tests showed high sensitivity on lymph, blood and tissue scrapings for diagnosis of VL, CL and PKDL in Sudan, but the specificity for clinical VL was significantly higher with NASBA-OC. Author Summary: The leishmaniases are a group of vector-borne diseases caused by protozoan parasites of the genus Leishmania. The parasites are transmitted by phlebotomine sand flies and can cause, depending on the infecting species, three clinical manifestations of leishmaniasis: visceral leishmaniasis (VL), post kala-azar dermal leishmaniasis (PKDL) and cutaneous leishmaniasis (CL) including the mucocutaneous form. VL, PKDL as well as CL are endemic in several parts of Sudan, and VL especially represents a major health problem in this country. Molecular tests such as the polymerase chain reaction (PCR) or nucleic acid sequence based assay (NASBA) are powerful techniques for accurate detection of the parasite in clinical specimens, but broad use is hampered by their complexity and lack of standardisation. Recently, the Leishmania OligoC-TesT and NASBA-Oligochromatography were developed as simplified and standardised PCR and NASBA formats. In this study, both tests were phase II evaluated for diagnosis of VL, PKDL and CL in Sudan. [ABSTRACT FROM AUTHOR]

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