18 research outputs found
Visceral Leishmaniasis Relapse in Southern Sudan (1999–2007): A Retrospective Study of Risk Factors and Trends
Visceral leishmaniasis (kala-azar) caused by Leishmania donovani is spread from person to person by Phlebotomus sandflies. Major epidemics of visceral leishmaniasis have occurred in Southern Sudan during the 20th century. The worst of these killed 100,000 people in the western Upper Nile area of Southern Sudan from 1984–1994, a loss of one-third of the population. Médecins Sans Frontières has treated 40,000 kala-azar patients in Southern Sudan since the late 1980's. In this study we used routinely collected clinical data to investigate why some patients relapse after treatment. We found that patients with severely enlarged spleens (splenomegaly) are more likely to relapse. Patients treated for 17 days with a combination of two drugs (sodium stibogluconate and paromomycin) were more likely to relapse (but less likely to die) than patients treated for 30 days with a single drug (sodium stibogluconate). However, the transition from sodium stibogluconate to the sodium stibogluconate/paromomycin combination as standard treatment between 2001–2003 has not led to a significant increase in visceral leishmaniasis relapse
Sodium Stibogluconate (SSG) & Paromomycin Combination Compared to SSG for Visceral Leishmaniasis in East Africa: A Randomised Controlled Trial
Visceral leishmaniasis (VL) is a parasitic disease with about 500,000 new cases each year and is fatal if untreated. The current standard therapy involves long courses, has toxicity and there is evidence of increasing resistance. New and better treatment options are urgently needed. Recently, the antibiotic paromomycin (PM) was tested and registered in India to treat this disease, but the same dose of PM monotherapy evaluated and registered in India was not efficacious in Sudan. This article reports the results of a clinical trial to test the effectiveness of injectable PM either alone (in a higher dose) or in combination with sodium stibogluconate (SSG) against the standard SSG monotherapy treatment in four East African countries—Sudan, Kenya, Ethiopia and Uganda. The study showed that the combination of SSG &PM was as efficacious and safe as the standard SSG treatment, with the advantages of being cheaper and requiring only 17 days rather than 30 days of treatment. In March 2010, a WHO Expert Committee recommended the use of the SSG & PM combination as a first line treatment for VL in East Africa
Geographical Variation in the Response of Visceral Leishmaniasis to Paromomycin in East Africa: A Multicentre, Open-Label, Randomized Trial
Visceral leishmaniasis (VL) is a fatal parasitic disease with 500,000 new cases each year according to WHO estimates. New and better treatment options are urgently needed in disease endemic areas due to the long courses, toxicity and development of resistance to current treatments. Recently, the antibiotic paromomycin was tested and registered in India to treat this disease. The current study describes a clinical trial to test the effectiveness of injectable paromomycin, either alone or in combination with the standard drug sodium stibogluconate in three East African countries—Sudan, Kenya and Ethiopia. The study showed that at the same paromomycin dose that was successfully used and registered in India, a far poorer outcome was obtained, particularly in Sudan, suggesting that there are either differences in the patients ability to respond to the drug or in the susceptibility of parasites in East Africa compared with those in India. However, no major safety concerns were noted with the treatment. Further research was initiated to see if a higher dose of paromomycin would perform better, especially in Sudan. The results of this and the performance of the combination arm will be reported later. Our study highlights the importance of considering geographical differences to treatment responses
Estudo terapêutico aberto com sulfato de aminosidine na leishmaniose mucosa causada for Leishmania (viannia) braziliensis
A policy for leishmaniasis with respect to the prevention and control of drug resistance.
At the moment no country has a policy designed to control or prevent drug resistance in leishmaniasis. The risk of resistance is high in areas of anthroponotic visceral leishmaniasis, for example North Bihar, India, where the rate in some areas is 60%. Post-epidemic Sudan is also at risk. Zoonotic areas in which HIV co-infection is common could also be at risk as sandflies can become infected from co-infected individuals. Many factors determine the choice of drug for the treatment of visceral leishmaniasis, and drug resistance may not be the over-riding priority. In anthroponotic areas reduction in transmission through public health measures will be important, but the use of two drugs in combination should be seriously considered. Pharmacokinetic and other features of the drugs available, relevant to their use in combination are discussed and tentative suggestions made concerning trials of possible combinations. These include miltefosine plus paromomycin and allopurinol plus an azole. Lessons may be learnt from the experiences of similar problems in malaria, leprosy and tuberculosis. Guidelines are offered for the introduction of policies to use drugs in combination, which differ between anthroponotic and zoonotic areas of transmission
A Comparison of the Effectiveness of Sodium Stibogluconate Monotherapy to Sodium Stibogluconate and Paromomycin Combination for the Treatment of Severe Post Kala Azar Dermal Leishmaniasis in South Sudan – A Retrospective Cohort Study
Therapy with Sodium Stibogluconate in Stearylamine- Bearing Liposomes Confers Cure against SSG-Resistant Leishmania Donovani in BALB/c Mice
Background: Resistance of Leishmania donovani to pentavalent antimonials, the first-line treatment of visceral leishmaniasis
(VL), has become a critical issue worldwide. Second-line and new drugs are also not devoid of limitations. Suitable drugdelivery
systems can improve the mode of administration and action of the existing antimonials, thus increasing their
clinical life.
Methodology/Principal Findings: We investigated the efficacy of sodium stibogluconate (SSG) in phosphatidylcholine (PC)–
stearylamine-bearing liposomes (PC-SA-SSG), PC-cholesterol liposomes (PC-Chol-SSG) and free amphotericin B (AmB)
against SSG-resistant L. donovani strains in 8-wk infected BALB/c mice. Animals were sacrificed and parasites in liver, spleen
and bone marrow were estimated 4-wk post-treatment by microscopic examination of stamp smears and limiting dilution
assay. A set of PC-SA-SSG and AmB treated mice were further studied for protection against reinfection. Serum antibodies
and cytokine profiles of ex-vivo cultured splenocytes were determined by ELISA. Uptake of free and liposomal SSG in
intracellular amastigotes was determined by atomic absorption spectroscopy. Rhodamine 123 and 5-carboxyfluorescein,
known substrates of Pgp and MRP transporter proteins, respectively, were used in free and liposomal forms for efflux
studies to estimate intracellular drug retention. Unlike free and PC-Chol-SSG, PC-SA-SSG was effective in curing mice
infected with two differentially originated SSG-unresponsive parasite strains at significantly higher levels than AmB.
Successful therapy correlated with complete suppression of disease-promoting IL-10 and TGF-b, upregulation of Th1
cytokines and expression of macrophage microbicidal NO. Cure due to elevated accumulation of SSG in intracellular
parasites, irrespective of SSG-resistance, occurs as a result of increased drug retention and improved therapy when
administered as PC-SA-SSG versus free SSG.
Conclusions/Significance: The design of this single-dose combination therapy with PC-SA-SSG for VL, having reduced
toxicity and long-term efficacy, irrespective of SSG-sensitivity may prove promising, not only to overcome SSG-resistance in
Leishmania, but also for drugs with similar resistance-related problems in other diseases