Institute of Tropical Medicine Antwerp

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    6320 research outputs found

    Efficacy of miltefosine in the treatment of visceral leishmaniasis after a decade of use in India

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    Background: Miltefosine is the only oral drug available for treatment of Indian Visceral Leishmaniasis (VL) which was shown to have an efficacy of 94% in a phase 3 trial in Indian subcontinent. Its unrestricted use has raised concern about its continued effectiveness. This study evaluates the efficacy and safety of miltefosine for the treatment of VL after a decade of use in India.MethodsIt was an open-label non-comparative study, in which 567 patients received oral Miltefosine (50 mg for those weighing /=25 kg, and 2.5 mg per kg for children < 12years, daily for 28 days) in a directly observed manner. Patients were followed up for six months to see the response to therapy.ResultAt the end of treatment the initial cure rate was 97.5% (intention to treat) and at six month the final cure rate was 90.3%. Overall death rate was 0.9% (5/567) and two deaths were drug-toxicity related. Gastrointestinal intolerance was frequent (64.5%). The drug was interrupted in 9 (1.5%) patients due to the adverse events of the drug.ConclusionAs compared to the phase 3 trial which led to registration of the drug a decade ago, there is a substantial increase in the failure rate of oral miltefosine for treatment of VL in India

    Presence of extended-spectrum beta-lactamase-producing Enterobacteriaceae in waste waters, Kinshasa, the Democratic Republic of the Congo

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    Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae are a major public health concern. We previously demonstrated the presence of ESBL-producing Enterobacteriaceae in sachet-packaged water bags sold in Kinshasa, the Democratic Republic of the Congo. In complement to the previous study, we aimed to assess the presence of ESBL-producing Enterobacteriaceae in waste waters in Kinshasa.Enterobacteriaceae isolates recovered from environmental water samples were screened and phenotypically confirmed as ESBL-producers by disk diffusion according to Clinical and Laboratory Standards Institute (CLSI) guidelines (CLSI M100-S21). Final identification to the species level and further antimicrobial susceptibility testing were carried out with MicroScan(R) NBC42 panels and the identification of bla (ESBL) coding genes was performed by a commercial multiplex ligation polymerase chain reaction (PCR) microarray (Check-Points CT 101, Wageningen, the Netherlands). Overall, 194 non-duplicate Enterobacteriaceae were recovered from several sewer and river sites in nine out of 24 municipalities of Kinshasa. Fourteen isolates (7.4 %) were confirmed as ESBL-producers, the main species being Enterobacter cloacae (46.6 %) and Klebsiella pneumoniae (40.0 %). Associated resistance to both aminoglycoside and fluoroquinolone antibiotics was observed in ten isolates; the remaining isolates showed co-resistance to either fluoroquinolone (n = 3) or to aminoglycoside (n = 1) alone. All but one isolate carried bla (CTX-M) genes belonging to the CTX-M-1 group. ESBL-producing Enterobacteriaceae are increasingly being reported from various sources in the community. The present results suggest that ESBL-producing Enterobacteriaceae are widespread in the environment in the community of Kinshasa. Cities in Central Africa should be added to the map of potentially ESBL-contaminated environments and highlight the need to reinforce safe water supply and public sanitation

    Genetic diversity and population structure of Mycobacterium marinum: new insights into host and environmental specificities

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    Mycobacterium marinum causes a systemic tuberculosis-like disease in fish, and skin infections in humans that might spread to deeper structures, resulting in tenosynovitis, arthritis and ostemomyelitis. However, little information is available concerning: (i) the intraspecific genetic diversity of M. marinum isolated from humans and animals; (ii) the M. marinum genotype circulation in the different ecosystems and (iii) the link between M. marinum genetic diversity and hosts (humans and fish). Here, we conducted a genetic study on 89 M. marinum isolates from humans (n = 68) and fish (n = 21) by using Mycobacterial Interspersed Repetitive Units-Variable Number of Tandem Repeats (MIRU-VNTR) typing. The results show that the M. marinum population is genetically structured not only according to the host, but also to the ecosystem as well as to tissue tropism in humans. This suggests the existence of different genetic pools in function of the biological and ecological compartments. Moreover, the presence of only certain M. marinum genotypes in humans suggests a different zoonotic potential of the M. marinum genotypes. Considering, the infection linked to the aquarium activity, a significant genetic difference was also detected when the human tissue tropism of M. marinum was taken into consideration, with a higher genetic polymorphism in strains isolated from patients with cutaneous forms than from individuals with deeper-structure infection. It appears that only few genotypes can produce deeper infections in humans, suggesting that the immune system might play a filtering role

    Genetic markers for SSG resistance in Leishmania donovani and SSG treatment failure in visceral leishmaniasis patients of the Indian subcontinent

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    The current standard to assess pentavalent antimonial (SSG) susceptibility of Leishmania is a laborious in vitro assay of which the result has little clinical value because SSG-resistant parasites are also found in SSG-cured patients. Candidate genetic markers for clinically relevant SSG-resistant parasites identified by full genome sequencing were here validated on a larger set of clinical strains. We show that 3 genomic locations suffice to specifically detect the SSG-resistant parasites found only in patients experiencing SSG treatment failure. This finding allows the development of rapid assays to monitor the emergence and spread of clinically relevant SSG-resistant Leishmania parasites

    Internalisation of mRNA-lipoplexes by dendritic cells

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    Lipoplexes, composed of Lipofectamine and mRNA encoding HIV Gag protein, were shown to be internalised by dendritic cells (DCs) and promote antigen presentation to stimulate HIV-specific T cell responses. Using confocal microscopy, we showed that one third of fluorescently labelled mRNA containing lipoplexes are co-localised with late endosomes. We further investigated the effect of inhibitors, blocking phagocytosis, macropinocytosis, clathrin- and caveolae- mediated endocytosis, on both the internalisation of the lipoplexes by DCs and the transfection efficiency. We observed that chloropromazine had no effect on the cellular uptake or transfection efficiency, excluding the involvement of clathrin-mediated endocytosis. Cytochalasine D, inhibiting macropinocytosis and phagocystosis, strongly reduced internalisation (50%) of the lipoplexes as well as protein expression (70%). Amiloride, which should specifically block macropinocytosis, induced only a modest reduction of uptake and transfection. Genistein and dynasore induced a strong reduction of on the level of protein expression (>70%), but not the overall uptake. Our results indicate that transfection-effective mRNA lipoplex internalisation by DCs, i.e. uptake that results in protein expression, preferentially proceeds by macropinocytosis and/or phagocytosis

    Risk factors associated with bovine tuberculosis and molecular characterization of Mycobacterium bovis strains in urban settings in Niger

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    A retrospective and a longitudinal survey were carried out at the abattoir of Niamey. Results showed a highly significant difference in suspected tuberculosis (TB) gross lesions among different animal species (P < 0.0001). The proportion of carcasses with TB-like lesions was 0.19% among cattle, 0.11% among camels, 0.001% among sheep and 0.0006% among goats. In cattle, cows are significantly more affected than the other categories (P < 0.001). Also in cattle, TB-like lesions are mostly localized in the lungs (92.77%) followed by the lymph nodes (50.87%) and the liver (32.40%). The prevalence of gross lesions compatible with bovine TB (BTB) is strongly influenced by the season (P < 0.0001), is closely correlated with the origin of the animals (P < 0.001) and has a negative impact on the weight of affected animals (P < 0.0001). Sixty-two samples of suspected TB gross lesions were subject to microbiological analysis and molecular typing of strains. Mycobacterium bovis was identified in 18 animals showing five different spoligotypes, belonging to type 'African 1' previously identified in Central and West Africa. In addition, a profile (SB1982) not previously reported distinguished by the absence of spacers 3, 4, 9, 16, 22, 30 and 39-43 has been characterized in this study. To assess risk factors for BTB transmission, a questionnaire on animal husbandry practices, food habits, and clinical signs of TB in animals and humans was submitted to the heads of 1131 randomly selected households. The main risk factors identified are consumption of unpasteurized milk (91%) and lack of hygiene within households (32-74%). Clinical signs that could be attributed to TB were also reported both in humans and in animals of the households

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