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Efflux as mechanism for drug resistance in Mycobacterium tuberculosis
No full textTuberculosis (TB) remains an important global public health problem with an estimated prevalence of 14 million people with TB worldwide in 2007. Since antibiotic treatment is one of the main tools for TB control, knowledge of Mycobacterium tuberculosis drug resistance is an important component for the disease control strategy. Although several gene mutations in specific loci of the M. tuberculosis genome have been reported as the basis for drug resistance, additional resistance mechanisms are now believed to exist. Efflux is a ubiquitous mechanism responsible for intrinsic and acquired drug resistance in prokaryotic and eukaryotic cells. M. tuberculosis presents one of the largest numbers of putative drug efflux pumps compared to its genome size. Bioinformatics, as well as direct and indirect evidence have established relationships among drug efflux with intrinsic or acquired resistance in M. tuberculosis. This mini-review describes the current knowledge on drug efflux in M. tuberculosis
Intracellular detection of differential APOBEC3G, TRIM5alpha, and LEDGF/p75 protein expression in peripheral blood by flow cytometry
No full textExpression studies on specific host proteins predominantly use quantitative PCR and western blotting assays. In this study, we optimized a flow cytometry-based assay to study intracellular expression levels of three important host proteins involved in HIV-1 replication: apolipoprotein B mRNA-editing catalytic polypeptide-like 3G (APOBEC3G), tripartite motif 5alpha (TRIM5alpha), and lens epithelium-derived growth factor (LEDGF/p75). An indirect intracellular staining (ICS) method was optimized using antibodies designed for other applications like enzyme-linked immunosorbent assay (ELISA), confocal imaging, and western blotting. The median fluorescence intensity (MFI) value - a measure for the protein expression level - increased upon higher antibody concentration and longer incubation time, and was reduced following preincubation with recombinant proteins. Staining of stably transfected or knock-down cell lines supported the method's specificity. Moreover, confocal microscopy analysis of peripheral blood mononuclear cells (PBMC), when stained according to the ICS method, confirmed the localization of APOBEC3G and TRIM5alpha in the cytoplasm, and of LEDGF/p75 in the nucleus. Also, stimulation with mitogen, interferon-alpha, or interferon-beta resulted in detectable, albeit weak, increases in intracellular expression of APOBEC3G and TRIM5alpha. After optimization, the method was applied to healthy control and HIV-1 infected subjects. For all subjects studied, the memory subset of CD4+ T cells showed significantly higher expression levels of APOBEC3G, TRIM5alpha, and LEDGF/p75, while the CD16+ subset of monocytes was characterized by higher expression levels of LEDGF/p75. In addition, we observed that therapy-naive HIV-1 patients tended to have lower expression levels of APOBEC3G and TRIM5alpha than HIV-1 negative controls. In summary, our data provide proof-of-principle for the detection of specific host factors at the level of a single cell, which may prove useful for our further understanding of their role in virus-host interactions
User fee removal in low-income countries: sharing knowledge to support managed implementation
No full textAntimicrobial resistance and virulence genes of non-typhoidal Salmonella isolates in The Gambia and Senegal
No full textINTRODUCTION: The prevalence of virulence genes in non-typhoidal Salmonella (NTS) and its association with commonly used antibiotics in West Africa is unknown. METHODOLOGY: We tested 185 NTS isolates from children, animals, and food products for the presence of twelve virulence genes by PCR. Ten of the virulence genes tested belonged to the five Salmonella pathogenicity islands implicated in its pathogenesis. RESULTS: Ten of twelve virulence genes except sopE and pefA were present in at least 70% of the isolates tested; sopE and pefA were observed in 33% and 44% of the isolates, respectively. The most prevalent gene was invA (99.5%), which is an invasion gene conserved within the Salmonella enterica. pipD and sopB genes, which were associated with serovar Enteritidis, were detected in 92.4% and 94.1% of isolates respectively. S. Istanbul and S. Javiana, which were isolated from chicken-serving restaurants, carried all the virulence genes of the five pathogenicity islands. There was significant association between sopB, sitC, orfLC, pipD and pefA virulence genes and resistance to commonly used antibiotics in Senegal and The Gambia, namely amoxicillin, ticarcillin, trimethoprim plus sulfamethoxazole, tetracycline, trimethoprim, spectinomycin, streptomycin, sulfonamides and nitrofurantoin. CONCLUSIONS: This study shows that virulence genes are present in NTS strains isolated from various sources. The significant association between some virulence genes and antibiotic resistance may have important implications with regard to the spread and persistence of resistance and virulence genes in Salmonella and to the prudent use of antimicrobial agents in humans and animals in West Africa
Implementing ideal health policy in a fragile health system: the example of expanding the use of malaria rapid diagnostic tests in mainland Tanzania [comment]
No full textMalaria confirmation before treatment provides an opportunity for improving the quality of malaria case management in endemic regions. However, increased coverage of this strategy is facing many organizational, logistical and technical challenges that threaten its success. Introducing an intervention with system-wide effect, such as the use of malaria rapid diagnostic tests in areas where malaria is still a public health problem, should be accompanied by system strengthening measures to better attain the goal of improving quality of care
"Ten Commandments" for the appropriate use of antibiotics by the practicing physician in an outpatient setting
No full textA multi-national working group on antibiotic stewardship, from the International Society of Chemotherapy, put together ten recommendations to physicians prescribing antibiotics to outpatients. These recommendations are: (1) use antibiotics only when needed; teach the patient how to manage symptoms of non-bacterial infections; (2) select the adequate ATB; precise targeting is better than shotgun therapy; (3) consider pharmacokinetics and pharmacodynamics when selecting an ATB; use the shortest ATB course that has proven clinical efficacy; (4) encourage patients' compliance; (5) use antibiotic combinations only in specific situations; (6) avoid low quality and sub-standard drugs; prevent prescription changes at the drugstore; (7) discourage self-prescription; (8) follow only evidence-based guidelines; beware those sponsored by drug companies; (9) rely (rationally) upon the clinical microbiology lab; and (10) prescribe ATB empirically - but intelligently; know local susceptibility trends, and also surveillance limitations
Effect of a control project on clinical profiles and outcomes in buruli ulcer: a before/after study in Bas-Congo, Democratic Republic of Congo
No full textBACKGROUND: Buruli ulcer (BU) is a necrotizing bacterial infection of skin, subcutaneous tissue and bone caused by Mycobacterium ulcerans. Although the functional impairment caused by BU results in severe suffering and in socio-economic problems, the disease remains largely neglected in Africa. The province of Bas-Congo in Democratic Republic of Congo contains one of the most important BU foci of the country, i.e. the Songololo Territory in the District of Cataractes. This study aims to assess the impact of a BU control project launched in 2004 in the Songololo Territory. METHODS: We used a comparative non-randomized study design, comparing clinical profiles and outcomes of the group of patients admitted at the General Reference Hospital (GRH) of the "Institut Medical Evangelique" (IME) of Kimpese 3 years before the start of the project (2002-2004) with those admitted during the 3 years after the start of the project (2005-2007). RESULTS: The BU control project was associated with a strong increase in the number of admitted BU cases at the GRH of IME/Kimpese and a fundamental change in the profile of those patients; more female patients presented with BU, the proportion of relapse cases amongst all admissions reduced, the proportion of early lesions and simple ulcerative forms increased, more patients healed without complications and the case fatality rate decreased substantially. The median duration since the onset of first symptoms however remained high, as well as the proportion of patients with osteomyelitis or limitations of joint movement, suggesting that the diagnostic delay remains substantial. CONCLUSION: Implementing a specialized program for BU may be effective in improving clinical profiles and outcomes in BU. Despite these encouraging results, our study highlights the need of considering new strategies to better improve BU control in a low resources setting
