Anemia Offers Stronger Protection Than Sickle Cell Trait Against the Erythrocytic Stage of Falciparum Malaria and This Protection Is Reversed by Iron Supplementation.

BACKGROUND: Iron deficiency causes long-term adverse consequences for children and is the most common nutritional deficiency worldwide. Observational studies suggest that iron deficiency anemia protects against Plasmodium falciparum malaria and several intervention trials have indicated that iron supplementation increases malaria risk through unknown mechanism(s). This poses a major challenge for health policy. We investigated how anemia inhibits blood stage malaria infection and how iron supplementation abrogates this protection. METHODS: This observational cohort study occurred in a malaria-endemic region where sickle-cell trait is also common. We studied fresh RBCs from anemic children (135 children; age 6-24months; hemoglobin <11g/dl) participating in an iron supplementation trial (ISRCTN registry, number ISRCTN07210906) in which they received iron (12mg/day) as part of a micronutrient powder for 84days. Children donated RBCs at baseline, Day 49, and Day 84 for use in flow cytometry-based in vitro growth and invasion assays with P. falciparum laboratory and field strains. In vitro parasite growth in subject RBCs was the primary endpoint. FINDINGS: Anemia substantially reduced the invasion and growth of both laboratory and field strains of P. falciparum in vitro (~10% growth reduction per standard deviation shift in hemoglobin). The population level impact against erythrocytic stage malaria was 15.9% from anemia compared to 3.5% for sickle-cell trait. Parasite growth was 2.4 fold higher after 49days of iron supplementation relative to baseline (p<0.001), paralleling increases in erythropoiesis. INTERPRETATION: These results confirm and quantify a plausible mechanism by which anemia protects African children against falciparum malaria, an effect that is substantially greater than the protection offered by sickle-cell trait. Iron supplementation completely reversed the observed protection and hence should be accompanied by malaria prophylaxis. Lower hemoglobin levels typically seen in populations of African descent may reflect past genetic selection by malaria. FUNDING: National Institute of Child Health and Development, Bill and Melinda Gates Foundation, UK Medical Research Council (MRC) and Department for International Development (DFID) under the MRC/DFID Concordat

First Report of Phytophthora occultans Causing Root and Collar Rot on Ceanothus, Boxwood, Rhododendron, and Other Hosts in Horticultural Nurseries in Oregon, USA

Dead and dying Ceanothus sanguineus, C. velutinus, and C. integerrimus plants grown in a native plant nursery in Oregon for landscape restoration were reported in 2011. Plants were wilted with stem lesions above necrotic roots. Using selective media (Hansen et al. 2012), twelve similar Phytophthora isolates were obtained. DNA sequences of the cox 1, β tubulin, and the rDNA ITS regions were generated (Hansen et al. 2012). All isolates had identical ITS sequences (GenBank KP742989), and were identical to Phytophthora occultans (Man in’t Veld et al. 2014) (JX978155) and 99% similar to P. himalsilva (HM752784) in a BLAST analysis. They were also identical to P. occultans in cox 1 and β tubulin (KR028484 and KR028483). Isolates were homothallic, with smooth 30-µm-diameter oogonia, and slightly aplerotic oospores. Antheridia were mostly paragynous. Colonies were stellate on carrot agar, growing 6 to 7 mm/d at optimum temperature (25°C). Sporangia were ovoid to irregular and papillate. Morphology and growth were consistent with P. occultans. Collections of unidentified Phytophthora spp. from the OSU Plant Clinic and from other Oregon nurseries (J. Parke et al. 2014) revealed additional isolates with similar morphology and identical DNA sequences. P. occultans was identified from boxwood (Buxus spp.), rhododendron, Gaultheria shallon, Arctostaphylos uva-ursi, and Mahonia nervosa in addition to Ceanothus spp. Two inoculation trials were conducted: (i) Healthy 1-year-old plants of C. sanguineus and C. velutinus were stem wound inoculated with two isolates of P. occultans from Ceanothus, or with sterile agar. There were 3 to 5 replications for each host and the control. The test was repeated with addition of two isolates from boxwood. (ii) Boxwood (B. sempervirens) and rhododendron (R. catawbiense Alba) were stem wound inoculated with two isolates each of P. occultans from Ceanothus and boxwood. There were four replications of each host for each isolate. All plants were incubated at 20 to 22°C. In test 1, all isolates induced stem lesions and wilting on all inoculated plants of both Ceanothus species. Wilting began in 14 days and lesions, measured at 19 days, averaged about 150 mm. There were no symptoms on control plants. In test 2, lesions developed on rhododendron stems, often girdling the stem within 12 days. Most boxwood showed no foliar symptoms or only mild yellowing, although stem lesions averaging 3.5 cm in 7 weeks were present on all plants. P. occultans was reisolated from all hosts in both tests. P. occultans was recently described from Buxus nursery stock in The Netherlands (Man in’t Veld et al. 2014), and isolates with identical DNA sequences were reported from Germany and Romania (Nechwatal et al. 2014). This is the first report from North America. It appears that a single clone of P. occultans recently has been spread widely in the nursery trade. P. occultans is similar to P. himalsilva (Vettraino et al. 2011) and to other members of the poorly defined P. citrophthora clade. Phylogenetic analysis may revise species definitions. Nursery plants grown for wildland restoration are at high risk to carry exotic Phytophthora species into vulnerable landscapes. Forest restoration specialists must demand healthy stock from nurseries

Hepcidin-guided screen-and-treat interventions against iron-deficiency anaemia in pregnancy: a randomised controlled trial in The Gambia.

BACKGROUND: WHO recommends daily iron supplementation for pregnant women, but adherence is poor because of side-effects, effectiveness is low, and there are concerns about possible harm. The iron-regulatory hormone hepcidin can signal when an individual is ready-and-safe to receive iron. We tested whether a hepcidin-guided screen-and-treat approach to combat iron-deficiency anaemia could achieve equivalent efficacy to universal administration, but with lower exposure to iron. METHODS: We did a three-arm, randomised, double-blind, non-inferiority trial in 19 rural communities in the Jarra West and Kiang East districts of The Gambia. Eligible participants were pregnant women aged 18-45 years at between 14 weeks and 22 weeks of gestation. We randomly allocated women to either WHO's recommended regimen (ie, a daily UN University, UNICEF, and WHO international multiple-micronutrient preparation [UNIMMAP] containing 60 mg iron), a 60 mg screen-and-treat approach (ie, daily UNIMMAP containing 60 mg iron for 7 days if weekly hepcidin was <2·5 μg/L or UNIMMAP without iron if hepcidin was ≥2·5 μg/L), or a 30 mg screen-and-treat approach (ie, daily UNIMMAP containing 30 mg iron for 7 days if weekly hepcidin was <2·5 μg/L or UNIMMAP without iron if hepcidin was ≥2·5 μg/L). We used a block design stratified by amount of haemoglobin at enrolment (above and below the median amount of haemoglobin on every enrolment day) and stage of gestation (14-18 weeks vs 19-22 weeks). Participants and investigators were unaware of the random allocation. The primary outcome was the amount of haemoglobin at day 84 and was measured as the difference in haemoglobin in each screen-and-treat group compared with WHO's recommended regimen; the non-inferiority margin was set at -5·0 g/L. The primary outcome was assessed in the per-protocol population, which comprised all women who completed the study. This trial is registered with the ISRCTN registry, number ISRCTN21955180. FINDINGS: Between June 16, 2014, and March 3, 2016, 498 participants were randomised, of whom 167 were allocated to WHO's recommended regimen, 166 were allocated to the 60 mg per day screen-and-treat approach, and 165 were allocated to the 30 mg per day screen-and-treat approach. 78 participants were withdrawn or lost to follow-up during the study; thus, the per-protocol population comprised 140 women assigned to WHO's recommended regimen, 133 allocated to the 60 mg screen-and-treat approach, and 147 allocated to the 30 mg screen-and-treat approach. The screen-and-treat approaches did not exceed the non-inferiority margin. Compared with WHO's recommended regimen, the difference in the amount of haemoglobin at day 84 was -2·2 g/L (95% CI -4·6 to 0·1) with the 60 mg screen-and-treat approach and -2·7 g/L (-5·0 to -0·5) with the 30 mg screen-and-treat approach. Adherence, reported side-effects, and adverse events were similar between the three groups. The most frequent side-effect was stomachache, which was similar in the 60 mg screen-and-treat group (82 cases per 1906 person-weeks) and with WHO's recommended regimen (81 cases per 1974 person-weeks; effect 1·0, 95% CI 0·7 to 1·6); in the 30 mg screen-and-treat group the frequency of stomachache was slightly lower than with WHO's recommended regimen (58 cases per 2009 person-weeks; effect 0·7, 95% CI 0·5 to 1·1). No participants died during the study. INTERPRETATION: The hepcidin-guided screen-and-treat approaches had no advantages over WHO's recommended regimen in terms of adherence, side-effects, or safety outcomes. Our results suggest that the current WHO policy for iron administration to pregnant women should remain unchanged while more effective approaches continue to be sought. FUNDING: Bill & Melinda Gates Foundation and the UK Medical Research Council

A live-attenuated chlamydial vaccine protects against trachoma in nonhuman primates

In cynomolgus macaques, ocular infection with a live trachoma strain lacking the conserved 7.5-kb plasmid induced no ocular pathology but facilitated solid or partial protection from subsequent infection with a virulent strain of trachoma

Lessons Learned from a Decade of Sudden Oak Death in California: Evaluating Local Management

Sudden Oak Death has been impacting California’s coastal forests for more than a decade. In that time, and in the absence of a centrally organized and coordinated set of mandatory management actions for this disease in California’s wildlands and open spaces, many local communities have initiated their own management programs. We present five case studies to explore how local-level management has attempted to control this disease. From these case studies, we glean three lessons: connections count, scale matters, and building capacity is crucial. These lessons may help management, research, and education planning for future pest and disease outbreaks

Thrombocytogenesis by megakaryocyte; Interpretation by protoplatelet hypothesis

Serial transmission electron microscopy of human megakaryocytes (MKs) revealed their polyploidization and gradual maturation through consecutive transition in characteristics of various organelles and others. At the beginning of differentiation, MK with ploidy 32N, e.g., has 16 centrosomes in the cell center surrounded by 32N nucleus. Each bundle of microtubules (MTs) emanated from the respective centrosome supports and organizes 16 equally volumed cytoplasmic compartments which together compose one single 32N MK. During the differentiation, single centriole separated from the centriole pair, i.e., centrosome, migrates to the most periphery of the cell through MT bundle, corresponding to a half of the interphase array originated from one centrosome, supporting one “putative cytoplasmic compartment” (PCC). Platelet demarcation membrane (DM) is constructed on the boundary surface between neighbouring PCCs. Matured PCC, composing of a tandem array of platelet territories covered by a sheet of DM is designated as protoplatelet. Eventually, the rupture of MK results in release of platelets from protoplatelets

Effects of body size on estimation of mammalian area requirements.

Accurately quantifying species' area requirements is a prerequisite for effective area-based conservation. This typically involves collecting tracking data on species of interest and then conducting home range analyses. Problematically, autocorrelation in tracking data can result in space needs being severely underestimated. Based on the previous work, we hypothesized the magnitude of underestimation varies with body mass, a relationship that could have serious conservation implications. To evaluate this hypothesis for terrestrial mammals, we estimated home-range areas with global positioning system (GPS) locations from 757 individuals across 61 globally distributed mammalian species with body masses ranging from 0.4 to 4000 kg. We then applied blockcross validation to quantify bias in empirical home range estimates. Area requirements of mammals 1, meaning the scaling of the relationship changedsubstantially at the upper end of the mass spectrum