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

Abstract

Abstract. The World Health Organization's (WHO) recommendation is 28-day course of meglumine antimoniate (Glucantime ® , Sanofi Aventis, France) for the treatment of visceral leishmaniasis (VL). The aim of this study was to evaluate the effectiveness of a shorter duration of treatment in regions with low level of resistance to Glucantime. During 13 years, this study was conducted in three phases on 392 patients. In the pilot first phase, we performed splenic punctures in seven patients to assess the correlation between the changes in the parasite load during treatment with Glucantime and defervescence. With defervescence, parasite density was dramatically dropped (P = 0.014), propounding defervescence as a marker of parasitological response. On the basis of the results, we conducted a randomized trial on 75 patients, comparing the efficacy of continuation of Glucantime therapy for 1, 2, or 3 weeks after defervescence. The treatment course of 1 week after defervescence (mean = 11.7 days) was non-inferior to that of 3 weeks (final cure rate, 96% versus 100%; P = 0.023). The third phase was a retrospective cohort study of 302 patients treated either with the WHO's regimen or for 7 days after defervescence (intervention group). Relapse was detected in 8.3% patients of the intervention group and in 5% patients following the WHO's regimen (P = 0.006 for non-inferiority). The final duration of treatment in intervention group was significantly shorter than standard course (13.3 ± 2.6 versus 28 days; P < 0.001). In summary, treatment of VL with Glucantime for 1 week after defervescence was non-inferior to and appears to be an acceptable alternative to the standard 28-day course for patients in Iran who show a response to antimonial therapy.

Treatment effects on IL‐9+CD4+ T cells and the cytokines influencing IL‐9 production in paediatric visceral leishmaniasis

“…Comparing the demographic data (gender and age) revealed no significant differences between VL patients and controls ( P > .05). The patients were treated with two protocols, as previously described 17,27,28 . Since there were no statistically significant differences in the amounts of IL‐9+CD4+ T cells and the corresponding cytokines, the cumulative data of both therapeutic protocols were included in the analysis.…”

“…Furthermore, the disease was confirmed by the laboratory findings such as anaemia, the presence of amastigote form of Leishmania (Leishman body) in bone marrow aspirates and/or positive serological tests including positive indirect fluorescent antibody (IFA) ≥1/128 against Leishmania parasites or detection of antibody against kinesin related protein K39 (rK39) and also the detection of L infantum DNA in the peripheral blood using real‐time PCR. Based on the guidelines of WHO expert committee, all the patients were treated with 20 mg/kg/day Glucontime up to a maximum of 850 mg for 4 weeks, 17 or treated until one week after defervescence as a short course therapy, previously described by Alborzi et al 27,28 The study was approved by the ethics committee of the Clinical Microbiology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran (IR.SUMS.REC.1398.703). The demographic, laboratory and clinical data are shown in Table 1.…”

“…The study was carried out on 18 paediatric patients with VL (56% female, age range; 20 ± 17 months) who were referred to Nemazee 17 or treated until one week after defervescence as a short course therapy, previously described by Alborzi et al 27,28 The study was approved by the ethics committee of the…”

“…The patients were treated with two protocols, as previously described. 17,27,28 Since there were no statistically significant differences in the amounts of IL-9 + CD4+T cells and the corresponding cytokines, the cumulative data of both therapeutic protocols were included in the analysis. The clinical and laboratory data of the VL patients are summarized in Table 1 and Figure 3.…”

Treatment failure of pentavalent antimonial therapy for human visceral leishmaniasis: a meta-analysis

“…Nevertheless, shorter courses of up to 21 days have been shown to be efficacious with low levels of treatment failure. 44 , 45 -46 Moreover, this likely explains why no studies from South America were identified, despite ongoing research there.…”