Short-course Regimens of Liposomal Amphotericin B for the Treatment of Mediterranean Visceral Leishmaniasis in Children

Krepis, Panagiotis; Argyri, Ioanna; Krepi, Adamantia; Syrmou, Areti; Spyridis, Νikos; Τσολιά, Μαρία

doi:10.1097/inf.0000000000001602

Cited by 13 publications

(19 citation statements)

References 30 publications

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“…The treatment continued for up to 40 weeks unless hematopoietic stem cell transplantation from a matched donor was available. Most of the patients with leishmaniasis-associated HLH (94.7%) were only treated with liposomal amphotericin B (total cumulative dose: 20 mg/kg divided into 4 or 5 doses administered in 4 or 5 days, respectively with no need to start HLH-specific therapy [ 15 ].. A minority were treated with dexamethasone (0.15 mg/kg/dose three times a day) for 3–5 days to control the cytokine storm.…”

Section: Methodsmentioning

confidence: 99%

Comparison of the clinical features and outcome of children with hemophagocytic lymphohistiocytosis (HLH) secondary to visceral leishmaniasis and primary HLH: a single-center study

et al. 2021

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Background Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of excessive inflammation. We aimed to describe the clinical and laboratory findings of HLH patients secondary to Visceral leishmaniasis (VL) and their treatment outcome during a 4-year follow-up period compared to primary HLH. Method Forty children with primary HLH confirmed by genetic study and 20 children with HLH secondary to VL confirmed by a blood or bone marrow polymerase chain reaction from 2014 to 2018 in Shiraz, Fars province, Southern Iran, were enrolled. Results The median age at diagnosis was 11.5 months (range 1–170), and 56.7% were male. Fever and splenomegaly were the most frequent clinical presentations. 93.3% of the subjects had an HScore > 169, which had a good correlation with HLH-2004 criteria (r = 0.371, P = 0.004). Patients with primary HLH experienced more thrombocytopenia (P = 0.012) and higher alanine transaminase (P = 0.016), while patients with VL-associated HLH had higher ferritin (P = 0.034) and erythrocyte sedimentation rate (P = 0.011). Central nervous system (CNS) involvement occurred in 38.3% of patients. The mortality rate was higher in patients with CNS disease (61% vs. 35%, P = 0.051). The 3-yr overall survival rate was 35.9%. (24% in primary HLH and 100% in VL-associated HLH, P < 0.001). In Cox regression analysis, platelet count < 100,000/ μ l (hazard ratio 4.472, 95% confidence interval 1.324–15.107, P = 0.016) correlated with increased mortality in patients with primary HLH. Conclusion VL is a potential source of secondary HLH in regions with high endemicity. Treatment of the underlying disease in VL-associated HLH is sufficient in most cases, with no need to start etoposide-based chemotherapy.

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Section: Methodsmentioning

confidence: 99%

Comparison of the clinical features and outcome of children with hemophagocytic lymphohistiocytosis (HLH) secondary to visceral leishmaniasis and primary HLH: a single-center study

et al. 2021

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“…In 2003, Syriopoulou et al tested the validity of two doses of 10 mg/kg/day in children administered on two consecutive days, compared to longer-lasting regimens with LAMB and antimonial therapy: they found faster resolution of signs and symptoms in patients undergoing the shorter LAMB regimen, with better cost-effectiveness [ 79 ]. The same two-day LAMB regimen was analysed by Krepis et al in a retrospective pediatric trial in 2017 and proved to be successful [ 83 ]. To date, however, there are no studies investigating the effectiveness of a single administration of LAMB for the treatment of VL caused by L. infantum in the Mediterranean basin.…”

Section: Therapymentioning

confidence: 99%

Visceral Leishmaniasis: Epidemiology, Diagnosis, and Treatment Regimens in Different Geographical Areas with a Focus on Pediatrics

et al. 2022

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Visceral Leishmaniasis (VL) is a vector-borne disease caused by an intracellular protozoa of the genus Leishmania that can be lethal if not treated. VL is caused by Leishmania donovani in Asia and in Eastern Africa, where the pathogens’ reservoir is represented by humans, and by Leishmania infantum in Latin America and in the Mediterranean area, where VL is a zoonotic disease and dog is the main reservoir. A part of the infected individuals become symptomatic, with irregular fever, splenomegaly, anemia or pancytopenia, and weakness, whereas others are asymptomatic. VL treatment has made progress in the last decades with the use of new drugs such as liposomal amphotericin B, and with new therapeutic regimens including monotherapy or a combination of drugs, aiming at shorter treatment duration and avoiding the development of resistance. However, the same treatment protocol may not be effective all over the world, due to differences in the infecting Leishmania species, so depending on the geographical area. This narrative review presents a comprehensive description of the clinical picture of VL, especially in children, the diagnostic approach, and some insight into the most used pharmacological therapies available worldwide.

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“…A study in Greece using a total dose of 20 mg/kg LAB demonstrated an efficacy of 97.6% when administered over 2 days versus 90.4% when given over 5 days (79). The current recommendation in the Mediterranean region for LAB is 3 to 5 mg/kg daily, given over 3 to 6 days (total dose of 18 to 21 mg/kg) (80).…”

Section: Zoonotic Visceral Leishmaniasismentioning

confidence: 99%

Recent Development of Visceral Leishmaniasis Treatments: Successes, Pitfalls, and Perspectives

et al. 2018

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SUMMARYResearch in visceral leishmaniasis in the last decade has been focused on how better to use the existing medicines as monotherapy or in combination. Systematic research by geographical regions has shown that a universal treatment is far from today's reality. Substantial progress has been made in the elimination of kala-azar in South Asia, with a clear strategy on first- and second-line therapy options of single-dose liposomal amphotericin B and a combination of paromomycin and miltefosine, respectively, among other interventions. In Eastern Africa, sodium stibogluconate (SSG) and paromomycin in combination offer an advantage compared to the previous SSG monotherapy, although not exempted of limitations, as this therapy requires 17 days of painful double injections and bears the risk of SSG-related cardiotoxicity. In this region, attempts to improve the combination therapy have been unsuccessful. However, pharmacokinetic studies have led to a better understanding of underlying mechanisms, like the underexposure of children to miltefosine treatment, and an improved regimen using an allometric dosage. Given this global scenario of progress and pitfalls, we here review what steps need to be taken with existing medicines and highlight the urgent need for oral drugs. Furthermore, it should be noted that six candidates belonging to five new chemical classes are reaching phase I, ensuring an optimistic near future.

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Short-course Regimens of Liposomal Amphotericin B for the Treatment of Mediterranean Visceral Leishmaniasis in Children

Abstract: Short-course L-AmB regimens are effective and safe for the treatment of childhood VL in our area. Our findings suggest that large L-AmB doses can possibly account for a higher rate of adverse events including nephrotoxicity.

Cited by 13 publications

References 30 publications

Comparison of the clinical features and outcome of children with hemophagocytic lymphohistiocytosis (HLH) secondary to visceral leishmaniasis and primary HLH: a single-center study

Comparison of the clinical features and outcome of children with hemophagocytic lymphohistiocytosis (HLH) secondary to visceral leishmaniasis and primary HLH: a single-center study

Visceral Leishmaniasis: Epidemiology, Diagnosis, and Treatment Regimens in Different Geographical Areas with a Focus on Pediatrics

Recent Development of Visceral Leishmaniasis Treatments: Successes, Pitfalls, and Perspectives

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