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B Zelman et al. Costs of Eliminating Malaria and the Impact of the Global Fund in 34 Countries. PLoS One

High Impact Journal from Malaria Portal - 31 December 2015 - 12:00am
International financing for malaria increased more than 18-fold between 2000 and 2011; the largest source came from The Global Fund to Fight AIDS, Tuberculosis and Malaria (Global Fund). . . .
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AJ Arik et al. Increased Akt signaling in the mosquito fat body increases adult survivorship. FASEB J

High Impact Journal from Malaria Portal - 31 December 2015 - 12:00am
Akt signaling regulates diverse physiologies in a wide range of organisms. . . .
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JJ Campo et al. RTS,S vaccination is associated with serologic evidence of decreased exposure to Plasmodium falciparum liver and blood stage parasites. Mol Cell Proteomics

High Impact Journal from Malaria Portal - 30 December 2015 - 12:00am
The leading malaria vaccine candidate, RTS,S, targets the sporozoite and liver stages of the Plasmodium falciparum life cycle, yet it provides partial protection against disease associated with subsequent blood-stage of infection. . . .
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C Waterman et al. Miniaturized Cultivation of Microbiota for Antimalarial Drug Discovery. Med Res Rev

High Impact Journal from Malaria Portal - 29 December 2015 - 12:00am
The ongoing search for effective antiplasmodial agents remains essential in the fight against malaria worldwide. . . .
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CV Hobbs et al. Neither the HIV Protease Inhibitor Lopinavir-Ritonavir nor the Antimicrobial Trimethoprim-Sulfamethoxazole Prevent Malaria Relapse in Plasmodium cynomolgi-Infected Non-Human Primates. PLoS One

High Impact Journal from Malaria Portal - 27 December 2015 - 12:00am
Plasmodium vivax malaria causes significant morbidity and mortality worldwide, and only one drug is in clinical use that can kill the hypnozoites that cause P. . . .
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K Schuldt et al. Endothelial protein C receptor gene variants not associated with severe malaria in ghanaian children. PLoS One

High Impact Journal from Malaria Portal - 27 December 2015 - 12:00am
Two recent reports have identified the Endothelial Protein C Receptor (EPCR) as a key molecule implicated in severe malaria pathology. . . .
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Implications for changes in <it>Anopheles darlingi</it> biting behaviour in three communities in the peri-Iquitos region of Amazonian Peru

Malaria Journal - 22 hours 57 min ago
Background: Malaria transmission in the peri-Iquitos region of Amazonian Peru has been designated as seasonal and hypo-endemic with recently described hyper-endemic hotspots. Despite relatively recent distribution of long-lasting insecticidal bed nets (LLINs), malaria in Amazonian Peru persists and increased substantially in 2014 compared to previous years. Anopheles darlingi, identified as the main malaria vector, is known for its variable behaviour depending on locality and environment. Methods: To evaluate vector biology metrics in relation to seasonality and malaria transmission, mosquito collections were carried out in three localities in the peri-Iquitos region, Loreto, Peru in 2011–2012. Human landing catch (HLC) collection method, Shannon (SHA) and CDC trap types were compared for effectiveness in a neotropical setting. Abundance, human biting rate and entomological inoculation rate (EIR) were measured to provide an updated view of transmission patterns post-LLIN distribution. Results: HLC collected significantly more anopheline mosquitoes than SHA and CDC light traps. Anopheles darlingi was the most prevalent species in all three villages (84% overall). Biting patterns varied depending on trap type, season and village. EIR varied temporally (monthly) and spatially and the highest (2.52) occurred during the 2012 malaria outbreak in Cahuide. Unexpectedly there was a high infection rate (1.47 and 1.75) outside the normal malaria transmission season, coincident with a second local outbreak in Cahuide. The first identification of Anopheles dunhami and Anopheles oswaldoi C in Peru, using molecular markers, is also reported in this study. Conclusion: These data underscore the importance of HLC as the most meaningful collection method for measuring vector biology indices in this region. The highest monthly EIR provides additional evidence of seasonal transmission in riverine localities correlated with high river levels, and An. darlingi as the only contributor to transmission. The trend of an increase in outdoor-biting together with early-evening infected mosquitoes may undermine the effectiveness of LLINs as a primary malaria intervention.
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The influence of host genetics on erythrocytes and malaria infection: is there therapeutic potential?

Malaria Journal - 29 July 2015 - 12:00am
As parasites, Plasmodium species depend upon their host for survival. During the blood stage of their life-cycle parasites invade and reside within erythrocytes, commandeering host proteins and resources towards their own ends, and dramatically transforming the host cell. Parasites aptly avoid immune detection by minimizing the exposure of parasite proteins and removing themselves from circulation through cytoadherence. Erythrocytic disorders brought on by host genetic mutations can interfere with one or more of these processes, thereby providing a measure of protection against malaria to the host. This review summarizes recent findings regarding the mechanistic aspects of this protection, as mediated through the parasites interaction with abnormal erythrocytes. These novel findings include the reliance of the parasite on the host enzyme ferrochelatase, and the discovery of basigin and CD55 as obligate erythrocyte receptors for parasite invasion. The elucidation of these naturally occurring malaria resistance mechanisms is increasing the understanding of the host-parasite interaction, and as discussed below, is providing new insights into the development of therapies to prevent this disease.
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Extensive introgression in a malaria vector species complex revealed by phylogenomics

CiteULike malaria tags - 28 July 2015 - 4:44pm
Science, Vol. 347, No. 6217. (02 January 2015), 1258524, doi:10.1126/science.1258524

The notion that species boundaries can be porous to introgression is increasingly accepted. Yet the broader role of introgression in evolution remains contentious and poorly documented, partly because of the challenges involved in accurately identifying introgression in the very groups where it is most likely to occur. Recently diverged species often have incomplete reproductive barriers and may hybridize where they overlap. However, because of retention and stochastic sorting of ancestral polymorphisms, inference of the correct species branching order is notoriously challenging for recent speciation events, especially those closely spaced in time. Without knowledge of species relationships, it is impossible to identify instances of introgression.
Michael Fontaine, James Pease, Aaron Steele, Robert Waterhouse, Daniel Neafsey, Igor Sharakhov, Xiaofang Jiang, Andrew Hall, Flaminia Catteruccia, Evdoxia Kakani, Sara Mitchell, Yi-Chieh Wu, Hilary Smith, Rebecca Love, Mara Lawniczak, Michel Slotman, Scott Emrich, Matthew Hahn, Nora Besansky
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<it>Plasmodium</it> transmission blocking activities of <it>Vernonia amygdalina</it> extracts and isolated compounds

Malaria Journal - 25 July 2015 - 12:00am
Background: Medicinal plants are a validated source for discovery of new leads and standardized herbal medicines. The aim of this study was to assess the activity of Vernonia amygdalina leaf extracts and isolated compounds against gametocytes and sporogonic stages of Plasmodium berghei and to validate the findings on field isolates of Plasmodium falciparum. Methods: Aqueous (Ver-H 2 O) and ethanolic (Ver-EtOH) leaf extracts were tested in vivo for activity against sexual and asexual blood stage P. berghei parasites. In vivo transmission blocking effects of Ver-EtOH and Ver-H 2 O were estimated by assessing P. berghei oocyst prevalence and density in Anopheles stephensi mosquitoes. Activity targeting early sporogonic stages (ESS), namely gametes, zygotes and ookinetes was assessed in vitro using P. berghei CTRP p .GFP strain. Bioassay guided fractionation was performed to characterize V. amygdalina fractions and molecules for anti-ESS activity. Fractions active against ESS of the murine parasite were tested for ex vivo transmission blocking activity on P. falciparum field isolates. Cytotoxic effects of extracts and isolated compounds vernolide and vernodalol were evaluated on the human cell lines HCT116 and EA.hy926. Results: Ver-H 2 O reduced the P. berghei macrogametocyte density in mice by about 50% and Ver-EtOH reduced P. berghei oocyst prevalence and density by 27 and 90%, respectively, in An. stephensi mosquitoes. Ver-EtOH inhibited almost completely (>90%) ESS development in vitro at 50 μg/mL. At this concentration, four fractions obtained from the ethylacetate phase of the methanol extract displayed inhibitory activity >90% against ESS. Three tested fractions were also found active against field isolates of the human parasite P. falciparum, reducing oocyst prevalence in Anopheles coluzzii mosquitoes to one-half and oocyst density to one-fourth of controls. The molecules and fractions displayed considerable cytotoxicity on the two tested cell-lines. Conclusions: Vernonia amygdalina leaves contain molecules affecting multiple stages of Plasmodium, evidencing its potential for drug discovery. Chemical modification of the identified hit molecules, in particular vernodalol, could generate a library of druggable sesquiterpene lactones. The development of a multistage phytomedicine designed as preventive treatment to complement existing malaria control tools appears a challenging but feasible goal.
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Age-shifting in malaria incidence as a result of induced immunological deficit: a simulation study

Malaria Journal - 25 July 2015 - 12:00am
Effective population-level interventions against Plasmodium falciparum malaria lead to age-shifts, delayed morbidity or rebounds in morbidity and mortality whenever they are deployed in ways that do not permanently interrupt transmission. When long-term intervention programmes target specific age-groups of human hosts, the age-specific morbidity rates ultimately adjust to new steady-states, but it is very difficult to study these rates and the temporal dynamics leading up to them empirically because the changes occur over very long time periods. This study investigates the age and magnitude of age- and time- shifting of incidence induced by either pre-erythrocytic vaccination (PEV) programmes or seasonal malaria chemo-prevention (SMC), using an ensemble of individual-based stochastic simulation models of P. falciparum dynamics. The models made various assumptions about immunity decay, transmission heterogeneity and were parameterized with data on both age-specific infection and disease incidence at different levels of exposure, on the durations of different stages of the parasite life-cycle and on human demography. Effects of transmission intensity, and of levels of access to malaria treatment were considered. While both PEV and SMC programmes are predicted to have overall strongly positive health effects, a shift of morbidity into older children is predicted to be induced by either programme if transmission levels remain static and not reduced by other interventions. Predicted shifting of burden continue into the second decade of the programme. Even if long-term surveillance is maintained it will be difficult to avoid mis-attribution of such long-term changes in age-specific morbidity patterns to other factors. Conversely, short-lived transient changes in incidence measured soon after introduction of a new intervention may give over-positive views of future impacts. Complementary intervention strategies could be designed to specifically protect those age-groups at risk from burden shift.
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Absence of correlation between ex vivo susceptibility to doxycycline and <it>pfteQ</it>&#8211;<it>pfmdt</it> gene polymorphism in French Guiana

Malaria Journal - 25 July 2015 - 12:00am
Background: In French Guiana, doxycycline is used for both chemoprophylaxis and the treatment of malaria. The presence of isolates with reduced ex vivo susceptibility to doxycycline in French Guiana makes it critical to identify any genetic determinants contributing to the chemosusceptibility level of Plasmodium falciparum to doxycycline, such as pfmdt and pftetQ, which were recently identified as potential molecular markers in African isolates. Methods: A Bayesian statistical approach was used to define different ex vivo doxycycline phenotypes. The pfmdt and pftetQ gene copy numbers were quantified by quantitative real-time polymerase chain reaction in 129 P. falciparum isolates collected between 2000 and 2010, and pftetQ, pfrps7, pfssurRNA, and pflsurRNA sequences were analysed after amplification by polymerase chain reaction. Results: PftetQ and pfmdt copy numbers were not associated with reduced susceptibility to doxycycline in P. falciparum within French Guiana. Sequence analysis of the genes revealed five known single nucleotide polymorphisms. Three new SNPs were identified in the apicoplast ribosomal RNA long sub-unit (pflsurRNA): C740T, A1875C and A1875T. These polymorphisms were not associated with reduced chemosusceptibility to doxycycline. Conclusions: The present study does not validate pfmdt and pftetQ genes as molecular markers of decreased susceptibility to doxycycline in P. falciparum isolates in French Guiana.
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