Intermittent Preventive Treatment for Malaria in Papua New Guinean Infants Exposed to Plasmodium falciparum and P. vivax: A Randomized Controlled Trial

Background

Intermittent preventive treatment in infants (IPTi) has been shown in randomized trials to reduce malaria-related morbidity in African infants living in areas of high Plasmodium falciparum (Pf) transmission. It remains unclear whether IPTi is an appropriate prevention strategy in non-African settings or those co-endemic for P. vivax (Pv).

Methods and Findings

In this study, 1,121 Papua New Guinean infants were enrolled into a three-arm placebo-controlled randomized trial and assigned to sulfadoxine-pyrimethamine (SP) (25 mg/kg and 1.25 mg/kg) plus amodiaquine (AQ) (10 mg/kg, 3 d, n = 374), SP plus artesunate (AS) (4 mg/kg, 3 d, n = 374), or placebo (n = 373), given at 3, 6, 9 and 12 mo. Both participants and study teams were blinded to treatment allocation. The primary end point was protective efficacy (PE) against all episodes of clinical malaria from 3 to 15 mo of age. Analysis was by modified intention to treat. The PE (compared to placebo) against clinical malaria episodes (caused by all species) was 29% (95% CI, 10–43, p≤0.001) in children receiving SP-AQ and 12% (95% CI, −11 to 30, p = 0.12) in those receiving SP-AS. Efficacy was higher against Pf than Pv. In the SP-AQ group, Pf incidence was 35% (95% CI, 9–54, p = 0.012) and Pv incidence was 23% (95% CI, 0–41, p = 0.048) lower than in the placebo group. IPTi with SP-AS protected only against Pf episodes (PE = 31%, 95% CI, 4–51, p = 0.027), not against Pv episodes (PE = 6%, 95% CI, −24 to 26, p = 0.759). Number of observed adverse events/serious adverse events did not differ between treatment arms (p>0.55). None of the serious adverse events were thought to be treatment-related, and the vomiting rate was low in both treatment groups (1.4%–2.0%). No rebound in malaria morbidity was observed for 6 mo following the intervention.

Conclusions

IPTi using a long half-life drug combination is efficacious for the prevention of malaria and anemia in infants living in a region highly endemic for both Pf and Pv.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00285662","term_id":"NCT00285662"}}NCT00285662 Please see later in the article for the Editors'' Summary     

Production and subsequent second-order decomposition of protein disulfide anions: Lengthy collisions between proteins

By a technique of radiation chemistry, one can convert small groups on a protein (surface disulfide bonds) into reactive centers (disulfide anion radicals) in less than 100 μs. The reactive centers on different molecules then proceed to react with each other and are destroyed. The anion radical is formed by electron transfer from transient CO₂^? generated by pulse radiolysis (Adams et al., 1972). The formation and decay of the disulfide anion radical were studied by monitoring its absorption at 410 nm. The transient disulfide anion absorption is a reliable qualitative but not quantitative test for the presence of surface disulfide groups.The area of this reactive center is very small compared to the total surface area of the protein. Nevertheless the rate of this reaction for 13 proteins ranges from 2% to 50% of the diffusion controlled rate of 3 × 10⁹m^?1 s^?1. Billiard ball type collisions during which the protein molecules briefly touch each other do not account for these fast rates. We conclude that the collision has substantial duration. A radially symmetric potential holds the molecules together but allows them to roll on each others' surfaces. The model of Sole & Stockmayer (1973) can be applied to this reaction, showing that the collision duration is typically 10 to 100 μs. This conclusion, valid for 12 of 13 proteins studied, seems to be very general. Whenever two proteins approach each other, attractive forces hold them together long enough for mutual rotation to bring the reactive groups into contact, a necessary but sometimes not sufficient condition for their reaction.     

An Attentional Effect of Musical Metrical Structure

Theories of metrical structure postulate the existence of several degrees of beat strength. While previous work has clearly established that humans are sensitive to the distinction between strong beats and weak ones, there is little evidence for a more fine grained distinction between intermediate levels. Here, we present experimental data showing that attention can be allocated to an intermediate level of beat strength. Comparing the effects of short exposures to 6/8 and 3/4 metrical structures on a tone detection task, we observe that subjects respond differently to beats of intermediate strength than to weak beats.     

Contact Matters: Local People’s Perceptions of <Emphasis Type="Italic">Hapalemur alaotrensis</Emphasis> and Implications for Conservation

Understanding factors that influence local community support for conservation projects is critical to their success. Perceptions of wildlife are particularly important in countries where people rely heavily on natural resources for their survival, as is the case in Madagascar. Renowned as one of the “hottest” regions for global biodiversity, Madagascar hosts an exceptional assemblage of lemurs. Yet little is known concerning the knowledge and perceptions of local people toward lemurs. The Lake Alaotra gentle lemur (Hapalemur alaotrensis) is classified as Critically Endangered on the IUCN Red List and restricted to marsh habitat in the Lake Alaotra New Protected Area. Habitat destruction and hunting have brought the lemur to the brink of extinction. In this study we characterize local people’s knowledge, awareness, and perceptions of Hapalemur alaotrensis. We conducted an initial survey with 180 participants in 6 villages with varying distance to Park Bandro, a high-priority conservation zone. During a second survey, we interviewed 50 people in the village adjacent to the park. Our findings demonstrate that fishers are the most knowledgeable local resource users despite having the lowest education levels, and they also are the most concerned with the endemic lemur’s decline. There is a link between environmental awareness and distance in both a literal and figurative sense; the more often people encounter Hapalemur alaotrensis, the more they know about it, and the more likely they are to be concerned about its future. Our study further shows that despite this concern, subsistence is prioritized over conservation in the Alaotra region. Ecological knowledge in the fishers’ communities is a valuable resource that can benefit the conservation of Hapalemur alaotrensis and its marshland habitat if conservation planning and management can align the resource users’ concerns and livelihood needs with biodiversity values.     

Recent Emergence of a Chytrid Fungal Pathogen in California Cascades Frogs (<Emphasis Type="Italic">Rana cascadae</Emphasis>)

The pathogenic fungus Batrachochytrium dendrobatidis (Bd) has been associated with global amphibian declines, but it is often difficult to discern the relative importance of Bd as a causal agent in declines that have already occurred. Retrospective analyses of museum specimens have allowed researchers to associate the timing of Bd arrival with the timing of past amphibian declines. Cascades frogs (Rana cascadae) have experienced dramatic declines in northern California, but it is not clear whether the onset of these declines corresponds to the arrival of Bd. We used quantitative real-time PCR assays of samples collected from museum specimens to determine historical Bd prevalence in the northern California range of Cascades frogs. We detected Bd in 13 of 364 (3.5%) Cascades frog specimens collected between 1907 and 2003, with the first positive result from 1978. A Bayesian analysis suggested that Bd arrived in the region between 1973 and 1978, which corresponds well with the first observations of declines in the 1980s.     

Relative Selection Strength: Quantifying effect size in habitat‐ and step‐selection inference

Habitat‐selection analysis lacks an appropriate measure of the ecological significance of the statistical estimates—a practical interpretation of the magnitude of the selection coefficients. There is a need for a standard approach that allows relating the strength of selection to a change in habitat conditions across space, a quantification of the estimated effect size that can be compared both within and across studies. We offer a solution, based on the epidemiological risk ratio, which we term the relative selection strength (RSS ). For a “used‐available” design with an exponential selection function, the RSS provides an appropriate interpretation of the magnitude of the estimated selection coefficients, conditional on all other covariates being fixed. This is similar to the interpretation of the regression coefficients in any multivariable regression analysis. Although technically correct, the conditional interpretation may be inappropriate when attempting to predict habitat use across a given landscape. Hence, we also provide a simple graphical tool that communicates both the conditional and average effect of the change in one covariate. The average‐effect plot answers the question: What is the average change in the space use probability as we change the covariate of interest, while averaging over possible values of other covariates? We illustrate an application of the average‐effect plot for the average effect of distance to road on space use for elk (Cervus elaphus ) during the hunting season. We provide a list of potentially useful RSS expressions and discuss the utility of the RSS in the context of common ecological applications.     

‘Black’ and ‘white’ death: burials in a time of Ebola in Freetown,Sierra Leone

The article examines experiences of the 2014‐15 Ebola crisis in Freetown, Sierra Leone, through an analysis of the performance of burials. While most of the city's residents had no contact with the virus, ‘Ebola’ was inescapable, owing to the onerous state of emergency regulations imposed by national and international authorities. All burials, regardless of the cause of death, were to be performed by newly established official teams operating according to unfamiliar biomedical and bureaucratic protocols. Burials became emblematic of the crisis through presenting a conflict between local practices and novel procedures, which was coded locally in a complex racial language of ‘black’ and ‘white’, recalling a long regional history of violent integration into the Atlantic World. Building on long‐standing anthropological discussion on the relationship between ‘good’ death and social order, the article explores how burials became sites around which opposing ‘orders’ were experienced, negotiated, and reconciled in locally meaningful ways.     

Lemur Diversity in Madagascar

A basic understanding of the taxonomy, diversity, and distributions of primates is essential for their conservation. This review of the status of the taxonomy of lemurs is based on a 5-d workshop entitled “Primate Taxonomy for the New Millennium,” held at the Disney Institute, Orlando, Florida, in February 2000. The aim is not to present a taxonomic revision, but to review our current understanding of the diversity and current and past ranges of lemurs and indicate where there is controversy, discrepancy, or lack of knowledge. Our goal therefore is to provide a baseline for future taxonomic investigation, as well as a clearer focus for research and conservation priorities. We here focus on the lemurs of Madagascar and recognize 5 families, 15 genera, and 99 species and subspecies. We list 39 species of lemurs described since 2000: 2 dwarf lemurs, Cheirogaleus; 11 mouse lemurs, Microcebus; a giant mouse lemur, Mirza; a bamboo lemur, Hapalemur; 17 sportive lemurs, Lepilemur; and 7 woolly lemurs, Avahi. Taxonomic revisions have resulted in the resurrection of a further 9 taxa. However, the figures do not represent the total diversity of Malagasy lemurs because more new species are being identified via new field studies and accompanying genetic research, and should be described in the near future.     

Characterization of Caenorhabditis elegans homologs of the Down syndrome candidate gene DYRK1A

The pathology of trisomy 21/Down syndrome includes cognitive and memory deficits. Increased expression of the dual-specificity protein kinase DYRK1A kinase (DYRK1A) appears to play a significant role in the neuropathology of Down syndrome. To shed light on the cellular role of DYRK1A and related genes we identified three DYRK/minibrain-like genes in the genome sequence of Caenorhabditis elegans, termed mbk-1, mbk-2, and hpk-1. We found these genes to be widely expressed and to localize to distinct subcellular compartments. We isolated deletion alleles in all three genes and show that loss of mbk-1, the gene most closely related to DYRK1A, causes no obvious defects, while another gene, mbk-2, is essential for viability. The overexpression of DYRK1A in Down syndrome led us to examine the effects of overexpression of its C. elegans ortholog mbk-1. We found that animals containing additional copies of the mbk-1 gene display behavioral defects in chemotaxis toward volatile chemoattractants and that the extent of these defects correlates with mbk-1 gene dosage. Using tissue-specific and inducible promoters, we show that additional copies of mbk-1 can impair olfaction cell-autonomously in mature, fully differentiated neurons and that this impairment is reversible. Our results suggest that increased gene dosage of human DYRK1A in trisomy 21 may disrupt the function of fully differentiated neurons and that this disruption is reversible.