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Imipramine is an orally active drug against both antimony sensitive and resistant Leishmania donovani clinical isolates in experimental infection
No full textBACKGROUND: In an endeavor to find an orally active and affordable antileishmanial drug, we tested the efficacy of a cationic amphiphilic drug, imipramine, commonly used for the treatment of depression in humans. The only available orally active antileishmanial drug is miltefosine with long half life and teratogenic potential limits patient compliance. Thus there is a genuine need for an orally active antileishmanial drug. Previously it was shown that imipramine, a tricyclic antidepressant alters the protonmotive force in promastigotes, but its in vivo efficacy was not reported. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that the drug is highly active against antimony sensitive and resistant Leishmania donovani in both promastigotes and intracellular amastigotes and in LD infected hamster model. The drug was found to decrease the mitochondrial transmembrane potential of Leishmania donovani (LD) promastigotes and purified amastigotes after 8 h of treatment, whereas miltefosine effected only a marginal change even after 24 h. The drug restores defective antigen presenting ability of the parasitized macrophages. The status of the host protective factors TNF alpha, IFN gamma and iNOS activity increased with the concomitant decrease in IL 10 and TGF beta level in imipramine treated infected hamsters and evolution of matured sterile hepatic granuloma. The 10-day therapeutic window as a monotherapy, showing about 90% clearance of organ parasites in infected hamsters regardless of their SSG sensitivity. CONCLUSIONS: This study showed that imipramine possibly qualifies for a new use of an old drug and can be used as an effective orally active drug for the treatment of Kala-azar
Azithromycin and ciprofloxacin resistance in Salmonella bloodstream infections in Cambodian adults
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Residual activity and integrity of PermaNet((R)) 2.0 after 24 months of household use in a community randomised trial of long lasting insecticidal nets against visceral leishmaniasis in India and Nepal
No full textThe World Health Organization (WHO) recommends several brands of long lasting insecticidal net (LN) for protection against insect vectors but also advises national programmes to monitor and evaluate performance under local conditions to help them select the most suitable LN for their setting. During the course of a community randomised trial of LNs against visceral leishmaniasis in northern India and Nepal, opportunity arose to assess the efficacy of PermaNet 2.0 (Vestergaard-Frandsen, Denmark) after two years of use against sandfly vectors. Between 63% (India) and 78% (Nepal) of LNs became holed over the course of two years, deltamethrin residues fell from 55mg/m(2) to an average of 11.6mg/m(2) (India) and 27.9mg/m(2) (Nepal), but on the basis of bioassay criteria all LNs tested still met the WHO Pesticide Evaluation Scheme standard for LN effectiveness. Nets had on average only been washed 2.5 times (India) and 0.6 times (Nepal) by householders over the course of two years. The loss of insecticide was attributed to factors which had little or nothing to do with washing, such as handling, friction and torsion during daily use. Under conditions pertaining in this region of south Asia, and for two years at least, this brand of net continues to meet the criteria established by WHO for LNs
Tuberculosis and HIV/AIDS: burden, community perception and its effect on mental health and quality of life in Ethiopia
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Glucose-6-phosphate dehydrogenase deficiency, chlorproguanil-dapsone with artesunate and post-treatment haemolysis in African children treated for uncomplicated malaria
No full textBACKGROUND: Malaria is a leading cause of mortality, particularly in sub-Saharan African children. Prompt and efficacious treatment is important as patients may progress within a few hours to severe and possibly fatal disease. Chlorproguanil-dapsone-artesunate (CDA) was a promising artemisinin-based combination therapy (ACT), but its development was prematurely stopped because of safety concerns secondary to its associated risk of haemolytic anaemia in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals. The objective of the study was to assess whether CDA treatment and G6PD deficiency are risk factors for a post-treatment haemoglobin drop in African children <5 years of age with uncomplicated malaria. METHODS: This case-control study was performed in the context of a larger multicentre randomized clinical trial comparing safety and efficacy of four different ACT in children with uncomplicated malaria. Children, who after treatment experienced a haemoglobin drop [greater than or equal to]2 g/dl (cases) within the first four days (days 0, 1, 2, and 3), were compared with those without an Hb drop (controls). Cases and controls were matched for study site, sex, age and baseline haemoglobin measurements. Data were analysed using a conditional logistic regression model. RESULTS: G6PD deficiency prevalence, homo- or hemizygous, was 8.5% (10/117) in cases and 6.8% (16/234) in controls (p = 0.56). The risk of a Hb drop [greater than or equal to]2 g/dl was not associated with either G6PD deficiency (adjusted odds ratio (AOR): 0.81; p = 0.76) or CDA treatment (AOR: 1.28; p = 0.37) alone. However, patients having both risk factors tended to have higher odds (AOR: 11.13; p = 0.25) of experiencing a Hb drop [greater than or equal to]2 g/dl within the first four days after treatment, however this finding was not statistically significant, mainly because G6PD deficient patients treated with CDA were very few. In non-G6PD deficient individuals, the proportion of cases was similar between treatment groups while in G6PD-deficient individuals, haemolytic anaemia occurred more frequently in children treated with CDA (56%) than in those treated with other ACT (29%), though the difference was not significant (p = 0.49). CONCLUSION: The use of CDA for treating uncomplicated malaria may increase the risk of haemolytic anaemia in G6PD-deficient children
Field detection of resistance to isometamidium chloride and diminazene aceturate in Trypanosoma vivax from the region of the Boucle du Mouhoun in Burkina Faso
No full textA longitudinal study assessed the chemoresistance to isometamidium chloride (ISM) and diminazene aceturate (DA) in the region of the Boucle du Mouhoun in Burkina Faso. A preliminary cross-sectional survey allowed the identification of the 10 villages with the highest parasitological prevalences (from 2.1% to 16.1%). In each of these 10 villages, two herds of approximately 50 bovines were selected, one being treated with ISM (1mg/kg b.w.) and the other remaining untreated as control group. All animals (treated and untreated herds) becoming infected were treated with DA (3.5mg/kg b.w.). In total, 978 head of cattle were followed up. Fortnightly controls of the parasitaemia and PCV were carried out during 8 weeks. The main trypanosome species was Trypanosoma vivax (83.6%) followed by Trypanosoma congolense (16.4%). In two villages, less than 25% of the control untreated cattle became positive indicating no need to use prophylactic treatment. These two villages were not further studied. Resistance to ISM was observed in 5 of the remaining 8 villages (Debe, Bendougou, Kangotenga, Mou and Laro) where the relative risk (control/treated hazard ratios) of becoming infected was lower than 2 i.e. between 0.89 (95% CI: 0.43-2.74) and 1.75 (95% CI: 0.57-5.37). In contrast, this study did not show evidence of resistance to DA in the surveyed villages with only 8.6% (n=93) of the cattle relapsing after treatment. Our results suggest that because of the low prevalence of multiple resistances in the area a meticulous use of the sanative pair system would constitute the best option to delay as much as possible the spread of chemoresistance till complete eradication of the disease by vector control operations