The ratio of monocytes to lymphocytes in peripheral blood correlates with increased susceptibility to clinical malaria in Kenyan children.

BACKGROUND: Plasmodium falciparum malaria remains a major cause of illness and death in sub-Saharan Africa. Young children bear the brunt of the disease and though older children and adults suffer relatively fewer clinical attacks, they remain susceptible to asymptomatic P. falciparum infection. A better understanding of the host factors associated with immunity to clinical malaria and the ability to sustain asymptomatic P. falciparum infection will aid the development of improved strategies for disease prevention. METHODS AND FINDINGS: Here we investigate whether full differential blood counts can predict susceptibility to clinical malaria among Kenyan children sampled at five annual cross-sectional surveys. We find that the ratio of monocytes to lymphocytes, measured in peripheral blood at the time of survey, directly correlates with risk of clinical malaria during follow-up. This association is evident among children with asymptomatic P. falciparum infection at the time the cell counts are measured (Hazard ratio (HR)  =  2.7 (95% CI 1.42, 5.01, P  =  0.002) but not in those without detectable parasitaemia (HR  =  1.0 (95% CI 0.74, 1.42, P  =  0.9). CONCLUSIONS: We propose that the monocyte to lymphocyte ratio, which is easily derived from routine full differential blood counts, reflects an individual's capacity to mount an effective immune response to P. falciparum infection

High-Utilisation Nanoplatinum Catalyst (Pt@cPIM) Obtained via Vacuum Carbonisation in a Molecularly Rigid Polymer of Intrinsic Microporosity

Polymers of intrinsic microporosity (PIM or here PIM-EA-TB) offer a highly rigid host environment into which hexachloroplatinate(IV) anions are readily adsorbed and vacuum carbonised (at 500 °C) to form active embedded platinum nanoparticles. This process is characterised by electron and optical microscopy, atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS) and electrochemical methods, which reveal that the PIM microporosity facilitates the assembly of nanoparticles of typically 1.0 to 2.5-nm diameter. It is demonstrated that the resulting carbonised “Pt@cPIM” from drop-cast films of ca. 550-nm average thickness, when prepared on tin-doped indium oxide (ITO), contain not only fully encapsulated but also fully active platinum nanoparticles in an electrically conducting hetero-carbon host. Alternatively, for thinner films (50–250 nm) prepared by spin coating, the particles become more exposed due to additional loss of the carbon host. In contrast to catalyst materials prepared by vacuum-thermolysed hexachloroplatinate(IV) precursor, the platinum nanoparticles within Pt@cPIM retain high surface area, electrochemical activity and high catalyst efficiency due to the molecular rigidity of the host. Data are presented for oxygen reduction, methanol oxidation and glucose oxidation, and in all cases, the high catalyst surface area is linked to excellent catalyst utilisation. Robust transparent platinum-coated electrodes are obtained with reactivity equivalent to bare platinum but with only 1 μg Pt cm−2 (i.e. ~100% active Pt nanoparticle surface is maintained in the carbonised microporous host). [Figure not available: see fulltext.

Using serological measures to monitor changes in malaria transmission in Vanuatu

BACKGROUND: With renewed interest in malaria elimination, island environments present unique opportunities to achieve this goal. However, as transmission decreases, monitoring and evaluation programmes need increasingly sensitive tools to assess Plasmodium falciparum and Plasmodium vivax exposure. In 2009, to assess the role of serological markers in evaluating malaria transmission, a cross-sectional seroprevalence study was carried out in Tanna and Aneityum, two of the southernmost islands of the Vanuatu archipelago, areas where malaria transmission has been variably reduced over the past few decades. METHODS: Malaria transmission was assessed using serological markers for exposure to P. falciparum and P. vivax. Filter blood spot papers were collected from 1,249 people from Tanna, and 517 people from Aneityum to assess the prevalence of antibodies to two P. falciparum antigens (MSP-119 and AMA-1) and two P. vivax antigens (MSP-119 and AMA-1). Age-specific prevalence was modelled using a simple catalytic conversion model based on maximum likelihood to generate a community seroconversion rate (SCR). RESULTS: Overall seropositivity in Tanna was 9.4%, 12.4% and 16.6% to P. falciparum MSP-119, AMA-1 and Schizont Extract respectively and 12.6% and 15.0% to P. vivax MSP-119 and AMA-1 respectively. Serological results distinguished between areas of differential dominance of either P. vivax or P. falciparum and analysis of age-stratified results showed a step in seroprevalence occurring approximately 30 years ago on both islands, indicative of a change in transmission intensity at this time. Results from Aneityum suggest that several children may have been exposed to malaria since the 2002 P. vivax epidemic. CONCLUSION: Seroepidemiology can provide key information on malaria transmission for control programmes, when parasite rates are low. As Vanuatu moves closer to malaria elimination, monitoring changes in transmission intensity and identification of residual malaria foci is paramount in order to concentrate intervention efforts

The kinetics of antibody binding to Plasmodium falciparum VAR2CSA PfEMP1 antigen and modelling of PfEMP1 antigen packing on the membrane knobs

<p>Abstract</p> <p>Background</p> <p>Infected humans make protective antibody responses to the PfEMP1 adhesion antigens exported by <it>Plasmodium falciparum </it>parasites to the erythrocyte membrane, but little is known about the kinetics of this antibody-receptor binding reaction or how the topology of PfEMP1 on the parasitized erythrocyte membrane influences antibody association with, and dissociation from, its antigenic target.</p> <p>Methods</p> <p>A Quartz Crystal Microbalance biosensor was used to measure the association and dissociation kinetics of VAR2CSA PfEMP1 binding to human monoclonal antibodies. Immuno-fluorescence microscopy was used to visualize antibody-mediated adhesion between the surfaces of live infected erythrocytes and atomic force microscopy was used to obtain higher resolution images of the membrane knobs on the infected erythrocyte to estimate knob surface areas and model VAR2CSA packing density on the knob.</p> <p>Results</p> <p>Kinetic analysis indicates that antibody dissociation from the VAR2CSA PfEMP1 antigen is extremely slow when there is a high avidity interaction. High avidity binding to PfEMP1 antigens on the surface of <it>P. falciparum</it>-infected erythrocytes in turn requires bivalent cross-linking of epitopes positioned within the distance that can be bridged by antibody. Calculations of the surface area of the knobs and the possible densities of PfEMP1 packing on the knobs indicate that high-avidity cross-linking antibody reactions are constrained by the architecture of the knobs and the large size of PfEMP1 molecules.</p> <p>Conclusions</p> <p>High avidity is required to achieve the strongest binding to VAR2CSA PfEMP1, but the structures that display PfEMP1 also tend to inhibit cross-linking between PfEMP1 antigens, by holding many binding epitopes at distances beyond the 15-18 nm sweep radius of an antibody. The large size of PfEMP1 will also constrain intra-knob cross-linking interactions. This analysis indicates that effective vaccines targeting the parasite's vulnerable adhesion receptors should primarily induce strongly adhering, high avidity antibodies whose association rate constant is less important than their dissociation rate constant.</p

Expanded geographic distribution and dietary strategies of the earliest Oldowan hominins and Paranthropus

The oldest Oldowan tool sites, ca. 2.6 million years ago (Ma), have previously been confined to Ethiopia’s Afar Triangle. We describe sites at Nyayanga, Kenya, dated to 3.032-2.581 Ma, and expand this distribution by over 1300 km. Furthermore, we found two hippopotamid butchery sites associated with mosaic vegetation and a C4 grazer-dominated fauna. Tool flaking proficiency was comparable to younger Oldowan assemblages, but pounding activities were more common. Tool use-wear and bone damage indicate plant and animal tissue processing. Paranthropus sp. teeth, the first from southwestern Kenya, possessed carbon isotopic values indicative of a diet rich in C4 foods. We argue that the earliest Oldowan was more widespread than previously known, used to process diverse foods including megafauna, and associated with Paranthropus from its onset

Fauna and Paleoenvironments of the Homa Peninsula, Western Kenya

The Homa Peninsula has been known to science since 1911, and fossil specimens from the area comprise many type specimens for common African mammalian paleospecies. Here we discuss the fauna and the paleoenvironmental information from the Homa Peninsula. The Homa Peninsula is a 200 km2 area in Homa Bay County, situated on the southern margin of the Winam Gulf of Lake Victoria in Kenya (Figure 29.1). Lake Victoria is estimated to be the third largest lake in the world, with a surface area of 68,900 km2 and a maximum length of approximately 616 km. Although its catchment is extensive, it is relatively shallow compared to any other lake of similar size, with a maximum depth of 84 m. Lake Victoria is located in a depression formed by the western and eastern branches of the East African Rift System (EARS), and is at an average elevation of 1135 m a.s.l. (Database for Hydrological Time Series of Inland Waters, 2017)