Randomized Single-Blinded Non-inferiority Trial Of 7 mg/kg Pentamidine Isethionate Versus 4 mg/kg Pentamidine Isethionate for Cutaneous Leishmaniaisis in Suriname

Abstract

BackgroundStandard treatment of cutaneous leishmaniasis (CL) in Suriname entails three injections of pentamidine isethionate (PI) 4 mg/kg per injection in 7 days (7 day regimen). Compliance to treatment is low and may contribute to increasing therapy failure. A 3 day regimen, including 2 injections of 7 mg/kg in 3 days may increase compliance.MethodsIn a randomized, single-blinded non-inferiority trial conducted in Suriname, 84 CL patients received the 7 day regimen and 79 CL patients received the 3 day regimen. Primary objective was the proportion of patients clinically cured at 6 weeks follow-up. Secondary objectives were clinical cure at 12 weeks follow-up; parasitological cure at 6 and 12 weeks; adverse and drug related toxicity events recorded one week after the end of treatment and health related quality of life. The non-inferiority margin was set at 15%, 1 sided test, α = 0.1.ResultsAt 6 weeks follow-up 31 (39%) patients in the 3 day regimen and 41 (49%) patients in the 7 day regimen were clinically cured. Intention to treat (ITT) analyses showed that the difference in proportion clinically cured was -9.6% (90% Confidence Interval (CI): -22.3% to 3.2%). Per protocol (PP) analysis showed that the difference in proportion clinically cured was 0.2% (90% CI: -14.6% to 15.2%). ITT analysis showed that the difference in proportion parasitological cured at 6 weeks was -15.2% (90% CI:-28.0% to -2.5%). PP analyses showed similar results. Non-inferiority could not be concluded for all adverse and toxicological events.ConclusionWe cannot conclude that the 3 day regimen is non-inferior to the 7 day regimen regarding proportion clinically and parasitological cured. Therefore there is no evidence to change the current standard practice of the 7 day regimen for the treatment of CL in Suriname.

Epidemiological, Biological and Clinical Aspects of Leishmaniasis with Special Emphasis on Busi Yasi in Suriname

“…However, in the past decades, a number of patients presented with clinical forms of the disease that behaved differently from that associated with this parasite species. The presumption that there were other Leishmania species present in Suriname was confirmed by PCR-based methods identifying a few cases of leishmaniasis caused by L. (V.) lainsoni [159], L. (V.) naiffi [164], L. (V.) braziliensis [165], and L. (L.) amazonensis [159,166]. At the same time, sand fly species associated with the transmission of CL by all the above-mentioned Leishmania species were detected in high-transmission areas of CL in Suriname [167,168].…”

“…The infection responds in general favorably to pentamidine isethionate [109,110] if not resolving spontaneously [54,83,84], but, as mentioned above, accomplishes cures in only about 75% of patients [112,165]. This suggests that some of the infections may be caused by Leishmania species other than L. (V.) guyanensis which do not respond to pentamidine isethionate [159,[164][165][166]. It is also possible that the infections are caused by distinct populations of L. (V.) guyanensis which behave differently from each other with respect to severity and dissemination of cutaneous lesions as well as response to pentamidine isethionate.…”

“…The first cases of CL caused by L. (V.) naiffi in Suriname -three Dutch male military who had been infected during jungle training in the country -were reported in 2010 [164]. The infecting Leishmania species was identified in patient biopsies by microscopy of Giemsastained smears, culture, and mini-exon repeat PCR [164].…”

“…The infecting Leishmania species was identified in patient biopsies by microscopy of Giemsastained smears, culture, and mini-exon repeat PCR [164]. The identification in Suriname of a confirmed reservoir host (the ninebanded armadillo Dasypus novemcinctus) as well as sand fly vectors implicated in the transmission of L. (V.) naiffi (Lu.…”

“Nature, green in leaf and stem”. Research on plants with medicinal properties in Suriname

“…Pentamidine isethionate given intramuscularly at the dose of three injections of 4 mg/kg on days 1, 4, and 7 is the first-line drug and the only treatment option for cutaneous leishmaniasis caused by L. (V.) guyanensis in Suriname [89]. However, many patients with cutaneous leishmaniasis in Suriname's interior cannot afford the costs of treatment and transportation to health centers in Paramaribo, and instead use traditional herbal substances [80].…”