Unraveling the Impact of Malaria Exposure Before Birth

Lars Hviid discusses a research article in PLoS Medicine that explores whether prenatal exposure to malaria is associated with increased susceptibility to malarial infection and anemia in infancy

Shape modeling technique KOALA validated by ESA Rosetta at (21) Lutetia

We present a comparison of our results from ground-based observations of asteroid (21) Lutetia with imaging data acquired during the flyby of the asteroid by the ESA Rosetta mission. This flyby provided a unique opportunity to evaluate and calibrate our method of determination of size, 3-D shape, and spin of an asteroid from ground-based observations. We present our 3-D shape-modeling technique KOALA which is based on multi-dataset inversion. We compare the results we obtained with KOALA, prior to the flyby, on asteroid (21) Lutetia with the high-spatial resolution images of the asteroid taken with the OSIRIS camera on-board the ESA Rosetta spacecraft, during its encounter with Lutetia. The spin axis determined with KOALA was found to be accurate to within two degrees, while the KOALA diameter determinations were within 2% of the Rosetta-derived values. The 3-D shape of the KOALA model is also confirmed by the spectacular visual agreement between both 3-D shape models (KOALA pre- and OSIRIS post-flyby). We found a typical deviation of only 2 km at local scales between the profiles from KOALA predictions and OSIRIS images, resulting in a volume uncertainty provided by KOALA better than 10%. Radiometric techniques for the interpretation of thermal infrared data also benefit greatly from the KOALA shape model: the absolute size and geometric albedo can be derived with high accuracy, and thermal properties, for example the thermal inertia, can be determined unambiguously. We consider this to be a validation of the KOALA method. Because space exploration will remain limited to only a few objects, KOALA stands as a powerful technique to study a much larger set of small bodies using Earth-based observations.Comment: 15 pages, 8 figures, 2 tables, accepted for publication in P&S

Cost-Effectiveness Study of Three Antimalarial Drug Combinations in Tanzania

BACKGROUND: As a result of rising levels of drug resistance to conventional monotherapy, the World Health Organization (WHO) and other international organisations have recommended that malaria endemic countries move to combination therapy, ideally with artemisinin-based combinations (ACTs). Cost is a major barrier to deployment. There is little evidence from field trials on the cost-effectiveness of these new combinations. METHODS AND FINDINGS: An economic evaluation of drug combinations was designed around a randomised effectiveness trial of combinations recommended by the WHO, used to treat Tanzanian children with non-severe slide-proven malaria. Drug combinations were: amodiaquine (AQ), AQ with sulfadoxine-pyrimethamine (AQ+SP), AQ with artesunate (AQ+AS), and artemether-lumefantrine (AL) in a six-dose regimen. Effectiveness was measured in terms of resource savings and cases of malaria averted (based on parasitological failure rates at days 14 and 28). All costs to providers and to patients and their families were estimated and uncertain variables were subjected to univariate sensitivity analysis. Incremental analysis comparing each combination to monotherapy (AQ) revealed that from a societal perspective AL was most cost-effective at day 14. At day 28 the difference between AL and AQ+AS was negligible; both resulted in a gross savings of approximately US$1.70 or a net saving of US$22.40 per case averted. Varying the accuracy of diagnosis and the subsistence wage rate used to value unpaid work had a significant effect on the number of cases averted and on programme costs, respectively, but this did not change the finding that AL and AQ+AS dominate monotherapy. CONCLUSIONS: In an area of high drug resistance, there is evidence that AL and AQ+AS are the most cost-effective drugs despite being the most expensive, because they are significantly more effective than other options and therefore reduce the need for further treatment. This is not necessarily the case in parts of Africa where recrudescence following SP and AQ treatment (and their combination) is lower so that the relative advantage of ACTs is smaller, or where diagnostic services are not accurate and as a result much of the drug goes to those who do not have malaria

Clinical and laboratory characteristics of children with sickle cell disease on hydroxyurea treated with artemether-lumefantrine for acute uncomplicated malaria

IntroductionLimited information exists on any interactions between hydroxyurea (HU) and antimalarials in sickle cell disease (SCD). We evaluated changes in clinical and laboratory parameters among children with SCD on HU therapy treated with artemether-lumefantrine (AL) for acute uncomplicated malaria (UM).MethodsA prospective, non-randomized, pilot study of 127 children with SCD (23, UM; 104, steady state) were recruited from three hospitals in Accra. UM participants were treated with standard doses of AL and followed up, on days 1, 2, 3, 7, 14, and 28. Venous blood was collected at baseline and follow-up days in participants with UM for determination of malaria parasitaemia, full blood count, reticulocytes, and clinical chemistry. Further, Plasmodium falciparum identification of rapid diagnostic test (RDT) positive samples was done using nested polymerase chain reaction (PCR).ResultsAmong SCD participants with UM, admission temperature, neutrophils, alanine-aminotransferase, gamma-glutamyl-transferase, and haemoglobin significantly differed between HU recipients (HU+) and steady state, while white blood cell, neutrophils, reticulocytes, bilirubin, urea, and temperature differed significantly between non-HU recipients (no-HU), and steady state. Mean parasitaemia (HU+, 2930.3 vs. no-HU, 1,060, p = 0.74) and adverse events (HU+, 13.9% vs. no-HU, 14.3%), were comparable (p = 0.94). Day 28 reticulocyte count was higher in the HU+ (0.24) (0.17 to 0.37) vs. no-HU, [0.15 (0.09 to 0.27), p = 0.022]. Significant differences in lymphocyte [HU+ 2.74 95% CI (−5.38 to 58.57) vs. no-HU −0.34 (−3.19 to 4.44), p = 0.024]; bilirubin [HU+, −4.44 (−16.36 to 20.74) vs. no-HU −18.37 (−108.79 to −7.16)]; and alanine aminotransferase, [HU+, −4.00 (−48.55 to 6.00) vs. no-HU, 7.00 (−22.00 to 22.00)] were observed during follow up.ConclusionParasite clearance and adverse event occurrence were comparable between SCD children treated with AL irrespective of HU status. However, distinct patterns of changes in laboratory indices suggest the need for larger, more focused studies

Can we enhance the ability to return to work among workers with stress-related disorders?

<p>Abstract</p> <p>Background</p> <p>Stress-related disorders are widespread and responsible for high societal costs e.g. sick leave payment and reduced productivity. The aim of this study was to evaluate the effect of an intervention program on return to work or labour market.</p> <p>Methods</p> <p>In a controlled interventional study design we compared 72 emotionally distressed patients, who received support during 2006, with 89 control individuals who had also been sick listed for emotional distress. Intervention was provided by trained psychologists and social workers who were in continuous dialog with the patients, providing counselling e.g. on decisions concerning resumption of work, support to families, participation in meetings with the workplace. Basically, the controls and the intervention group share the same access to welfare benefits. The main outcome was time to return to labour market (TTR).</p> <p>Results</p> <p>The baseline characteristics were similar in the two groups. There were no differences in the rate of resuming work between the two groups. About 80% in both groups had returned to the labour market after one year.</p> <p>Conclusion</p> <p>An intervention program with psychological stress management and case management did not improve work capability compared to usual care. Work resumption as a single outcome probably is an insensitive parameter of intervention management quality, and should be supplemented by other data on different aspects of treatment.</p

Microscopic Views of Martian Soils and Evidence for Incipient Diagenesis

Mars landed missions returned im-ages at increasingly higher spatial resolution (Table 1). These images help to constrain the microstructure of Martian soils, i.e. the grain-by-grain association of chemistry and mineralogy with secondary properties, such as albedo, color, magnetic properties, and mor-phology (size, shape, texture). The secondary charac-teristics are controlled by mineralogical composition as well as the geo-setting (transport and weathering modes, e.g. water supply, pH, atmospheric properties, exposure to radiation, etc.). As of today this association is poorly constrained. However, it is important to un-derstand soil-forming processes on the surface of Mars. Here we analyze high-resolution images of soils re-turned by different landed missions. Eventually these images must be combined with other types of data (chemistry and mineralogy at small spatial scale) to nail down the microstructure of Martian soils

Lectin-like bacteriocins from pseudomonas spp. utilise D-rhamnose containing lipopolysaccharide as a cellular receptor

Lectin-like bacteriocins consist of tandem monocot mannose-binding domains and display a genus-specific killing activity. Here we show that pyocin L1, a novel member of this family from Pseudomonas aeruginosa, targets susceptible strains of this species through recognition of the common polysaccharide antigen (CPA) of P. aeruginosa lipopolysaccharide that is predominantly a homopolymer of d-rhamnose. Structural and biophysical analyses show that recognition of CPA occurs through the C-terminal carbohydrate-binding domain of pyocin L1 and that this interaction is a prerequisite for bactericidal activity. Further to this, we show that the previously described lectin-like bacteriocin putidacin L1 shows a similar carbohydrate-binding specificity, indicating that oligosaccharides containing d-rhamnose and not d-mannose, as was previously thought, are the physiologically relevant ligands for this group of bacteriocins. The widespread inclusion of d-rhamnose in the lipopolysaccharide of members of the genus Pseudomonas explains the unusual genus-specific activity of the lectin-like bacteriocins