Cryptococcal meningitis associated HIV infection in the Donka national hospital in Conakry (Guinea)

Background Cryptococcal meningitis (CM) is an infection of the brain parenchyma and subarachnoid space by the encapsulated saprophyte yeast organisms such as Cryptococcus neoformans. Over the last twenty years, HIV has created a large and severely immune compromisized population in whom C. neoformans is a dangerous opportunistic infection. In Guinea, the prevalence of CM is unknown. We hypothesized that the occurrence of CM correlates with AIDS/ HIV prevalence.Method This retrospective observational study was carried out at the national Hospital of Conakry (Guinea) between 2001 and 2002. We describe here the epidemiological and clinical and biological characteristics of CM disease in our national hospital.Results Our data show that, 28.6 % of HIV patients with neurological symptoms had Cryptococcus neoformans in their CSF by using Indian ink staining. The median age was 36±3 years and sex ratio (M/F) was 1.8. The major complaints were fever and cephalgia, giddiness while the major complications were altered consciousness and hemiplegia. CSF was clear with low level of glucose and higher level of albumin. The means of lymphocytes in CSF was 8±2/mm3.Conclusion This data therefore becomes relevant in not only focusing of neurological symptoms associated with HIV to be toxoplasmosis but the possibility of C neoformans in these patients; particularly when they present symptoms such as headaches, giddiness and sniff neck etc. This can easily be carried out with Indian ink staining technique

Efflux pump inhibitors (EPIs) as new antimicrobial agents against Pseudomonas aeruginosa

Pseudomonas aeruginosa is an opportunistic human pathogen and one of the leading causes of nosocomial infections worldwide. The difficulty in treatment of pseudomonas infections arises from being multidrug resistant (MDR) and exhibits resistance to most antimicrobial agents due to the expression of different mechanisms overcoming their effects. Of these resistance mechanisms, the active efflux pumps in Pseudomonas aeruginosa that belong to the resistance nodulation division (RND) plays a very important role in extruding the antibiotics outside the bacterial cells providing a protective means against their antibacterial activity. Beside its role against the antimicrobial agents, these pumps can extrude biocides, detergents, and other metabolic inhibitors. It is clear that efflux pumps can be targets for new antimicrobial agents. Peptidomimetic compounds such as phenylalanine arginyl β-naphthylamide (PAβN) have been introduced as efflux pump inhibitors (EPIs); their mechanism of action is through competitive inhibition with antibiotics on the efflux pump resulting in increased intracellular concentration of antibiotic, hence, restoring its antibacterial activity. The advantage of EPIs is the difficulty to develop bacterial resistance against them, but the disadvantage is their toxic property hindering their clinical application. The structure activity relationship of these compounds showed other derivatives from PAβN that are higher in their activity with higher solubility in biological fluids and decreased toxicity level. This raises further questions on how can we compact Pseudomonas infections. Of particular importance, the recent resurgence in the use of older antibiotics such as polymyxins and probably applying stricter control measures in order to prevent their spread in clinical sittings

Efflux Pump, the Masked Side of ß-Lactam Resistance in Klebsiella pneumoniae Clinical Isolates

International audienceBACKGROUND: Beta-lactamase production and porin decrease are the well-recognized mechanisms of acquired beta-lactam resistance in Klebsiella pneumoniae isolates. However, such mechanisms proved to be absent in K. pneumoniae isolates that are non susceptible to cefoxitin (FOX) and susceptible to amoxicillin+clavulanic acid in our hospital. Assessing the role of efflux pumps in this beta-lactam phenotype was the aim of this study. METHODOLOGY/FINDINGS: MICs of 9 beta-lactams, including cloxacillin (CLX), and other antibiotic families were tested alone and with an efflux pump inhibitor (EPI), then with both CLX (subinhibitory concentrations) and EPI against 11 unique bacteremia K. pneumoniae isolates displaying the unusual phenotype, and 2 ATCC strains. CLX and EPI-dose dependent effects were studied on 4 representatives strains. CLX MICs significantly decreased when tested with EPI. A similar phenomenon was observed with piperacillin+tazobactam whereas MICs of the other beta-lactams significantly decreased only in the presence of both EPI and CLX. Thus, FOX MICs decreased 128 fold in the K. pneumoniae isolates but also 16 fold in ATCC strain. Restoration of FOX activity was CLX dose-dependent suggesting a competitive relationship between CLX and the other beta-lactams with regard to their efflux. For chloramphenicol, erythromycin and nalidixic acid whose resistance was also due to efflux, adding CLX to EPI did not increase their activity suggesting differences between the efflux process of these molecules and that of beta-lactams. CONCLUSION: This is the first study demonstrating that efflux mechanism plays a key role in the beta-lactam susceptibility of clinical isolates of K. pneumoniae. Such data clearly evidence that the involvement of efflux pumps in beta-lactam resistance is specially underestimated in clinical isolates

The Lake CHAd Deep DRILLing project (CHADRILL) - targeting ~ 10 million years of environmental and climate change in Africa

At present, Lake Chad ( ~13°0 N, ~14° E) is a shallow freshwater lake located in the Sahel/Sahara region of central northern Africa. The lake is primarily fed by the Chari-Logone river system draining a ~600 000 km2 watershed in tropical Africa. Discharge is strongly controlled by the annual passage of the intertropical convergence zone (ITCZ) and monsoon circulation leading to a peak in rainfall during boreal summer. During recent decades, a large number of studies have been carried out in the Lake Chad Basin (LCB). They have mostly focused on a patchwork of exposed lake sediments and outcrops once inhabited by early hominids. A dataset generated from a 673m long geotechnical borehole drilled in 1973, along with outcrop and seismic reflection studies, reveal several hundred metres of Miocene-Pleistocene lacustrine deposits. CHADRILL aims to recover a sedimentary core spanning the Miocene-Pleistocene sediment succession of Lake Chad through deep drilling. This record will provide significant insights into the modulation of orbitally forced changes in northern African hydroclimate under different climate boundary conditions such as high CO2 and absence of Northern Hemisphere ice sheets. These investigations will also help unravel both the age and the origin of the lake and its current desert surrounding. The LCB is very rich in early hominid fossils (Australopithecus bahrelghazali; Sahelanthropus tchadensis) of Late Miocene age. Thus, retrieving a sediment core from this basin will provide the most continuous climatic and environmental record with which to compare hominid migrations across northern Africa and has major implications for understanding human evolution. Furthermore, due to its dramatic and episodically changing water levels and associated depositional modes, Lake Chad's sediments resemble maybe an analogue for lake systems that were once present on Mars. Consequently, the study of the subsurface biosphere contained in these sediments has the potential to shed light on microbial biodiversity present in this type of depositional environment. We propose to drill a total of ~1800m of poorly to semi-consolidated lacustrine, fluvial, and eolian sediments down to bedrock at a single on-shore site close to the shoreline of present-day Lake Chad. We propose to locate our drilling operations on-shore close to the site where the geotechnical Bol borehole (13°280 N, 14°440 E) was drilled in 1973. This is for two main reasons: (1) nowhere else in the Chad Basin do we have such detailed information about the lithologies to be drilled; and (2) the Bol site is close to the depocentre of the Chad Basin and therefore likely to provide the stratigraphically most continuous sequence