Short‐Course of Oral Miltefosine for Treatment of Visceral Leishmaniasis

Sundar, Shyam; Makharia, Anand; More, Deepak K.; Agrawal, Gaurav; Voß, Andreas; Fischer, Christina; Bachmann, Peter; Murray, Henry W.

doi:10.1086/318122

Cited by 124 publications

(78 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Novas drogas de uso oral e vacinas para a LV vêm sendo desenvolvidas, com resultados animadores, mas, enquanto não dispomos destes avanços, devemos estar atentos para o diagnóstico da LV e utilizarmos as formas habituais de diagnóstico e tratamento, altamente eficientes no controle desta endemia 28,29 .…”

Section: Resultsunclassified

Visceral leishmaniasis: clinical and laboratorial aspects

Pastorino¹,

Jacob²,

Oselka³

et al. 2002

J Pediatr (Rio J)

View full text Add to dashboard Cite

Objective: to compare the clinical and laboratorial data before and after the treatment of patients with visceral leishmaniasis admitted to a pediatric hospital in a nonendemic area, highlighting the importance of recognizing visceral leishmaniasis in pediatric patients.Methods: clinical, laboratorial and treatment data of 78 patients with visceral leishmaniasis were evaluated from 1981 to 1992. We analyzed the average level of hemoglobin, leukocyte, neutrophil, platelet, albumin, gammaglobulin, class and subclass of immunoglobulin, size of the liver and spleen during the pre-and posttreatment using the paired t test.Results: we included 78 patients with visceral leishmaniasis, 44 males, with age ranging from 8 months to 13.5 years. Sixty-one patients were from Bahia. Fever and splenomegaly were present in 96.1% and 100% of the cases, respectively. The parasitological diagnosis was obtained in 74/78 patients: 67 patients through smear and/or culture of bone marrow (85.7%), five through liver biopsy and two through spleen puncture. The hematological findings and serum albumin presented significant improvement at the end of treatment (P<0.001), differently from serum gammaglobulin levels (P=0.087). There was predominance of IgG1 subclass, with two patients presenting low levels of IgG2. Initial treatment used antimoniate in 67 cases and amphotericin B in five. Eleven patients (15.7%) needed a second treatment, and were considered cured after it. There was significant improvement in the liver and spleen size at the end of the treatment (P<0.001). One patient presented spontaneous remission and five died due to bleeding.Conclusions: in order to obtain accurate diagnosis and treatment, especially regarding health services of areas with low-incidence of visceral leishmaniasis, the diagnosis of patients with fever and visceromegaly, who come from endemic areas, should include visceral leishmaniasis.J Pediatr (Rio J) 2002; 78 (2): 120-7: visceral leishmaniasis, kala-azar, infancy, diagnosis, treatment. ResumoObjetivo: comparar os dados clínicos e laboratoriais no pré e pós-tratamento de pacientes portadores de leishmaniose visceral (LV), admitidos em hospital pediátrico localizado em área não-endêmica, destacando a importância do reconhecimento da LV na faixa etária pediátrica.Métodos: avaliação dos dados clínicos, laboratoriais e de tratamento de pacientes portadores de LV no período compreendido entre 1981 e 1992, comparando-se os valores médios de hemoglobina, leucócitos, neutrófilos, plaquetas, albumina, gamaglobulina, classes e subclasses de imunoglobulinas, tamanho do fígado e baço antes e após o tratamento, utilizando-se o teste "t" para amostras pareadas.Resultados: foram incluídos 78 pacientes, com idade variando entre 8 meses e 13,5 anos, sendo 44 casos do sexo masculino e 61 provenientes da Bahia. Febre e esplenomegalia estavam presentes em 96,1% e 100% dos casos, respectivamente. O diagnóstico parasitológico foi obtido em 74/78 pacientes, com positividade pelo mielograma e/ou mielocultura em 67 casos...

show abstract

Section: Resultsunclassified

Visceral leishmaniasis: clinical and laboratorial aspects

Pastorino¹,

Jacob²,

Oselka³

et al. 2002

J Pediatr (Rio J)

View full text Add to dashboard Cite

show abstract

“…Combinations of SSG and paromomycin have shown to be efficient and safe in India , Sudan (Seaman et al, 1993), and Kenya (Chunge et al, 1990) but paramomycin has yet to be registered for VL treatment and its future production and cost remain unclear. Other possible combinations could include in future trials conventional or liposomal amphotericin B as well as miltefosine, an oral drug showed to be very efficient in India when used alone for 4 weeks (Jha et al, 1999;Sundar et al, 2000b). Miltefosine was registered for the treatment of VL in India in 2002 and a phase IV trial will take place in India and Nepal in the coming year.…”

Section: Discussionmentioning

confidence: 99%

Treatment of visceral leishmaniasis in south-eastern Nepal: decreasing efficacy of sodium stibogluconate and need for a policy to limit further decline

Rijal

Chappuis

Singh

et al. 2003

Transactions of the Royal Society of Tropical Medicine and Hygi

117

View full text Add to dashboard Cite

Sodium stibogluconate (SSG) is the first-line therapy for visceral leishmaniasis (VL) in south-eastern Nepal. Recent studies from the neighbouring state of Bihar, India, have shown a dramatic fall in cure rates with treatment failure occurring in up to 65% of VL patients treated with SSG. A prospective study was conducted at a tertiary-level hospital located in south-eastern Nepal from July 1999 to January 2001. Parasitologically proven kala-azar patients with no previous history of treatment for VL were treated with SSG 20 mg/kg/d for 30 d which was extended to 40 d in those with persistent positive parasitology. Of the 110 patients who completed SSG therapy and were assessed at 1 and 6 months, definite cure was achieved in 99 patients (90%) and SSG failure occurred in 11 patients (10%). Except for the presence of hepatomegaly and a lower platelet count there was no clinical or laboratory baseline characteristic associated with treatment failure. A significantly lower cure rate (76%, P= 0.03) was observed in patients from the district of Saptari, which borders the antimony-resistant VL areas of Bihar. The efficacy of SSG as a first-line treatment for VL in south-eastern Nepal was still satisfactory, except for the patients living closer to the antimony-resistant VL areas of India. These findings indicate that the spread of resistance to antimonials is already taking place in Nepal and that a policy to control further spread should be urgently implemented.

show abstract

“…Traditional antileishmanial therapies include the use of pentavalent antimonial compounds, amphotericin B, and pentamidine. More recently, miltefosine (hexadecylphosphocholine) has demonstrated efficacy against visceral leishmaniasis when administered orally (Sundar et al, 2000). However, current treatment strategies all suffer from drawbacks which include toxicity, developing resistance, administration by injection, and expense (Ouellette et al, 2004;Singh and Sivakumar, 2004).…”

Section: Introductionmentioning

confidence: 99%

Leishmania tarentolae: Purification and characterization of tubulin and its suitability for antileishmanial drug screening

Yakovich

Ragone

Alfonzo

et al. 2006

Experimental Parasitology

View full text Add to dashboard Cite

Previously, tubulin has been purified from Leishmania amazonensis and used to identify novel molecules with selective antimitotic activity. However, Leishmania amazonensis is pathogenic and requires a relatively expensive medium for large-scale cultivation. Herein, the purification and characterization of tubulin from the non-pathogenic Leishmania tarentolae is reported, together with the sequence of α-and β-tubulin from this organism. This protein was purified by sonication, diethylaminoethyl-Sepharose chromatography, and one assembly-disassembly cycle in 1% overall recovery based on total cellular protein. L. tarentolae tubulin was indistinguishable from the corresponding L. amazonensis protein in terms of binding affinity for dinitroaniline sulfanilamides and sensitivity to assembly inhibition by these compounds. The amino acid sequences derived from the L. tarentolae α-and β-tubulin genes were 99.6% and 99.4% identical to the corresponding amino acid sequences from the L. major Friedlin strain. These results indicate that tubulin from L. tarentolae is suitable for use in drug screening.

show abstract

Short‐Course of Oral Miltefosine for Treatment of Visceral Leishmaniasis

Cited by 124 publications

References 12 publications

Visceral leishmaniasis: clinical and laboratorial aspects

Visceral leishmaniasis: clinical and laboratorial aspects

Treatment of visceral leishmaniasis in south-eastern Nepal: decreasing efficacy of sodium stibogluconate and need for a policy to limit further decline

Leishmania tarentolae: Purification and characterization of tubulin and its suitability for antileishmanial drug screening

Contact Info

Product

Resources

About