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EY Lukianova-Hleb et al. Hemozoin-generated vapor nanobubbles for transdermal reagent- and needle-free detection of malaria. Proc Natl Acad Sci U S A

High Impact Journal from Malaria Portal - 31 December 2014 - 12:00am
Successful diagnosis, screening, and elimination of malaria critically depend on rapid and sensitive detection of this dangerous infection, preferably transdermally and without sophisticated reagents or blood drawing. . . .
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KJ Vogel et al. Phylogenetic investigation of Peptide hormone and growth factor receptors in five dipteran genomes. Front Endocrinol (Lausanne)

High Impact Journal from Malaria Portal - 31 December 2014 - 12:00am
Peptide hormones and growth factors bind to membrane receptors and regulate a myriad of processes in insects and other metazoans. . . .
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J Rydzak et al. Human erythrocyte glycophorin C as the receptor for EBA-140 Plasmodium falciparum merozoite ligand. Postepy Hig Med Dosw (Online)

High Impact Journal from Malaria Portal - 31 December 2014 - 12:00am
Erythrocyte invasion by the blood-stage Plasmodium falciparum parasites is a multistep process involving specific interactions between parasites and red blood cells. . . .
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R Sundararajan et al. Barriers to Malaria Control among Marginalized Tribal Communities: A Qualitative Study. PLoS One

High Impact Journal from Malaria Portal - 30 December 2014 - 12:00am
Malaria infection accounts for over one million deaths worldwide annually. . . .
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DV Canyon et al. Insights in public health: systems thinking: basic constructs, application challenges, misuse in health, and how public health leaders can pave the way forward. Hawaii J Med Public Health

High Impact Journal from Malaria Portal - 30 December 2014 - 12:00am
The strengthening of health systems is fundamental to improving health outcomes, crisis preparedness, and our capacity to meet global challenges, such as accelerating progress towards the Millennium Development Goals, reducing maternal and child mortality, combating HIV, malaria and other diseases, limiting the effects of a new influenza pandemic, and responding appropriately to climate change. . . .
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In vitro and in vivo anti-malarial activity of tigecycline, a glycylcycline antibiotic, in combination with chloroquine

Malaria Journal - 21 October 2014 - 12:00am
Background: Several antibiotics have shown promising anti-malarial effects and have been useful for malarial chemotherapy, particularly in combination with standard anti-malarial drugs. Tigecycline, a semi-synthetic derivative of minocycline with a unique and novel mechanism of action, is the first clinically available drug in a new class of glycylcycline antibiotics. Methods: Tigecycline was tested in vitro against chloroquine (CQ)-sensitive (D6) and resistant strains (W2) of Plasmodium falciparum alone and in combination with CQ. Tigecycline was also tested in vivo in combination with CQ in Plasmodium berghei-mouse malaria model for parasitaemia suppression, survival and cure of the malaria infection. Results: Tigecycline was significantly more active against CQ-resistant (W2) than CQ-susceptible (D6) strain of P. falciparum. Tigecycline potentiated the anti-malarial action of CQ against the CQ-resistant strain of P. falciparum by more than seven-fold. Further, treatment of mice infected with P. berghei with tigecycline (ip) produced significant suppression in parasitaemia development and also prolonged the mean survival time. Treatment with as low as 3.7 mg/kg dose of tigecycline, once daily for four days, produced 77-91% suppression in parasitaemia. In vivo treatment with tigecycline in combination with subcurative doses of CQ produced complete cure in P. berghei-infected mice. Conclusion: Results indicate prominent anti-malarial action of tigecycline in vitro and in vivo in combination with CQ and support further evaluation of tigecycline as a potential combination candidate for treatment of drug-resistant cases of malaria.
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Malaria parasite detection increases during pregnancy in wild chimpanzees

Malaria Journal - 20 October 2014 - 12:00am
Background: The diversity of malaria parasites (Plasmodium sp.) infecting chimpanzees (Pan troglodytes) and their close relatedness with those infecting humans is well documented. However, their biology is still largely unexplored and there is a need for baseline epidemiological data. Here, the effect of pregnancy, a well-known risk factor for malaria in humans, on the susceptibility of female chimpanzees to malaria infection was investigated. Methods: A series of 384 faecal samples collected during 40 pregnancies and 36 post-pregnancies from three habituated groups of wild chimpanzees in the Tai National Park, Cote d'Ivoire, were tested. Samples were tested for malaria parasites by polymerase chain reaction (PCR) and sequencing. Data were analysed using a generalized linear mixed model. Results: Probability of malaria parasite detection significantly increased towards the end of pregnancy and decreased with the age of the mother. Conclusions: This study provides evidence that susceptibility to malaria parasite infection increases during pregnancy, and, as shown before, in younger individuals, which points towards similar dynamics of malaria parasite infection in human and chimpanzee populations and raises questions about the effects of such infections on pregnancy outcome and offspring morbidity/mortality.
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High-throughput tri-colour flow cytometry technique to assess Plasmodium falciparum parasitaemia in bioassays

Malaria Journal - 20 October 2014 - 12:00am
Background: Unbiased flow cytometry-based methods have become the technique of choice in many laboratories for high-throughput, accurate assessments of malaria parasites in bioassays. A method to quantify live parasites based on mitotracker red CMXRos was recently described but consistent distinction of early ring stages of Plasmodium falciparum from uninfected red blood cells (uRBC) remains a challenge. Methods: Here, a high-throughput, three-parameter (tri-colour) flow cytometry technique based on mitotracker red dye, the nucleic acid dye coriphosphine O (CPO) and the leucocyte marker CD45 for enumerating live parasites in bioassays was developed. The technique was applied to estimate the specific growth inhibition index (SGI) in the antibody-dependent cellular inhibition (ADCI) assay and compared to parasite quantification by microscopy and mitotracker red staining. The Bland-Altman analysis was used to compare biases between SGI estimated by the tri-colour staining technique, mitotracker red and by microscopy. Results: CPO allowed a better separation between early rings and uRBCs compared to mitotracker red resulting in a more accurate estimate of total parasitaemia. The tri-colour technique is rapid, cost effective and robust with comparable sensitivity to microscopy and capable of discriminating between live and dead and/or compromised parasites. Staining for CD45 improved parasitaemia estimates in ADCI assay since high numbers of leucocytes interfered with the accurate identification of parasitized RBC. The least bias (-1.60) in SGI was observed between the tri-colour and microscopy. Conclusion: An improved methodology for high-throughput assessment of P. falciparum parasitaemia under culture conditions that could be useful in different bioassays, including ADCI and growth inhibition assays has been developed.
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X Zhou et al. Divergent and conserved elements comprise the chemoreceptive repertoire of the non-blood feeding mosquito Toxorhynchites amboinensis. Genome Biol Evol

High Impact Journal from Malaria Portal - 18 October 2014 - 12:00am
Many mosquito species serve as vectors of diseases such as malaria and yellow fever, wherein pathogen transmission is tightly associated with the reproductive requirement of taking vertebrate blood meals. . . .
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Detection of mixed infection level of Plasmodium falciparum and Plasmodium vivax by SYBR Green I-based real-time PCR in North Gondar, north-west Ethiopia

Malaria Journal - 18 October 2014 - 12:00am
Background: Malaria is caused by five Plasmodium species and transmitted by anopheline mosquitoes. It occurs in single and mixed infections. Mixed infection easily leads to misdiagnosis. Accurate detection of malaria species is vital. Therefore, the study was conducted to determine the level of mixed infection and misdiagnosis of malaria species in the study area using SYBR Green I-based real time PCR. Methods: The study was conducted in seven health centres from North Gondar, north-west Ethiopia. The data of all febrile patients, who attended the outpatient department for malaria diagnosis, from October to December 2013, was recorded. Dried blood spots were prepared from 168 positive samples for molecular re-evaluation. Parasite DNA was extracted using a commercial kit and Plasmodium species were re-evaluated with SYBR Green I-based real time PCR to detect mixed infections and misdiagnosed mono-infections. Results: Among 7343 patients who were diagnosed for malaria in six study sites within the second quarter of the Ethiopian fiscal year (2013) 1802(24.54%) were positive for malaria parasite. Out of this, 1,216 (67.48%) Plasmodium falciparum, 553 (30.68%) Plasmodium vivax and 33 (1.8%) mixed infections of both species were recorded. The result showed high prevalence of P. falciparum and P. vivax, but very low prevalence of mixed infections. Among 168 samples collected on dried blood spot 7 (4.17%) were P. vivax, 158 (94.05%) were P. falciparum and 3 (1.80%) were mixed infections of both species. After re-evaluation 10 (5.95%) P. vivax, 112 (66.67%) P. falciparum, 21 (12.50%) P. falciparum + P. vivax mixed infection, and 17 (10.12%) Plasmodium ovale positive rate was recorded. The re-evaluation showed high level of mixed infection, and misdiagnosis of P. ovale and P. vivax. Conclusions: The result shows that P. falciparum prevalence is higher than P. vivax in the study area. The results, obtained from SYBR Green I-based real time PCR, indicated that the diagnosis efficiency of microscopy is very low for species-specific and mixed infection detection. Therefore, real time PCR-based species diagnosis should be applied for clinical diagnosis and quality control purposes in order to prevent the advent of drug resistant strains due to misdiagnosis and mistreatment.
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RT Gazzinelli et al. Innate sensing of malaria parasites. Nat Rev Immunol

High Impact Journal from Malaria Portal - 17 October 2014 - 12:00am
Innate immune receptors have a key role in immune surveillance by sensing microorganisms and initiating protective immune responses. . . .
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M Svensson-Coelho et al. Reciprocal Specialization in Multihost Malaria Parasite Communities of Birds: A Temperate-Tropical Comparison. Am Nat

High Impact Journal from Malaria Portal - 17 October 2014 - 12:00am
Abstract How specialization of consumers with respect to resources varies with respect to latitude is poorly understood. . . .
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Comparative analysis of IgG responses to Plasmodium falciparum MSP1p19 and PF13-DBL1alpha1 using ELISA and a magnetic bead-based duplex assay (MAGPIX(R)-Luminex) in a Senegalese meso-endemic community

Malaria Journal - 17 October 2014 - 12:00am
Background: Numerous Plasmodium falciparum antigens elicit humoral responses in humans living in endemic areas. Use of multiplex assays is a convenient approach to monitor the antibody response against multiple antigens, but to integrate multiplex assay-derived data with datasets, generated previously using ELISA, comparative studies are needed. This work compares antibody responses to two P. falciparum antigens monitored using both technologies. Methods: The IgG response against the merozoite surface protein-1 PfMSP1p19 and the PF13-DBL1alpha1 domain of the P. falciparum Erythrocyte Membrane Protein1, expressed by the rosette-forming parasite 3D7/PF13 (PF13), was investigated using ELISA and a MAGPIX(R)-Luminex duplex assay. Archived plasma samples collected before the rainy season from 217 villagers living in Ndiop, a Senegalese meso-endemic setting, were studied. ROC analysis was used to define the optimal antibody measure readout. Association of antibody levels with protection against clinical malaria was analysed using Poisson regression in a retrospective study from active case detection records performed during the 5.5-month transmission season that followed blood sampling. Results: There was a strong positive correlation (P <10-3) between ELISA and MAGPIX(R)-Luminex-MFI (median fluorescence intensity) values for antibody to PfMSP1p19 (rho = 0.78) and PF13-DBL1alpha1 (rho = 0.89), with a similar degree of concordance in all age groups. Antibody levels to both antigens were high but displayed a different age-associated pattern. Independent age-adjusted Poisson regression analysis showed a significant association with protection only for IgG responses to MSP1p19 (P <0.01 RR = 0.71 [0.53-0.93]) measured by ELISA. Conclusion: The individual ELISA and duplex-MAGPIX assays provide a concordant evaluation of age-associated antibody responses to MSP1p19 and PF13-DBL1alpha1, irrespective of the formulation of antibody levels (values, ratios or ROC-adjusted figures) but do diverge with regard to the association of antibody levels with clinical protection in age-adjusted models. This may reflect incomplete overlap of the epitopes presented in the two formats. Further development for multiplex assessment of antibody responses to a larger panel of antigens with the robust and cost effective MAGPIX(R)-Luminex technology is warranted.
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Anti-relapse activity of mirincamycin in the Plasmodium cynomolgi sporozoite-infected Rhesus monkey model

Malaria Journal - 17 October 2014 - 12:00am
Background: Mirincamycin is a close analog of the drug clindamycin used to treat Plasmodium falciparum blood stages. The clinical need to treat Plasmodium vivax dormant liver stages and prevent relapse with a drug other than primaquine led to the evaluation of mirinicamycin against liver stages in animals. Methods: cis-mirinicamycin and trans-mirinicamycin were evaluated as prophylaxis against early liver stages of Plasmodium berghei in mice and as antirelapse hypnozoiticides against Plasmodium cynomolgi in the Rhesus monkey (Macaca mulatta). Results: Mirincamycin was very effective against early liver stages of P. berghei in mice: both cis and trans enantiomers were 90-100% causally prophylactic at 3.3 mg/kg/day for 3 days orally. Both cis and trans mirincamycin, however, failed to kill dormant liver stages (hypnozoites) in the P. cynomolgi infected Rhesus monkey, the only preclinical hypnozoite model. Mirincamycin enantiomers at 80 mg/kg/day for 7 days orally, a dose that generated exposures comparable to that seen clinically, did not prevent relapse in any of four monkeys. Conclusions: Although efficacy against early liver stages of P. berghei was thought to correlate with anti-hypnozoite activity in primates, for mirincamycin, at least, there was no correlation. The negative P. cynomolgi hypnozoite data from Rhesus monkeys indicates that mirincamycin is unlikely to have potential as a clinical anti-relapse agent.
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Nationwide assessment of insecticide susceptibility in Anopheles gambiae populations from Zimbabwe

Malaria Journal - 17 October 2014 - 12:00am
Background: The scale-up of malaria interventions in sub-Saharan Africa has been accompanied by a dramatic increase in insecticide resistance in Anopheles spp. In Zimbabwe resistance to pyrethroid insecticides was reported in Gokwe District in 2008. This study reports results of the first nation-wide assessment of insecticide susceptibility in wild populations of Anopheles gambiae sensu lato (s.l.) in Zimbabwe, and provides a comprehensive review of the insecticide resistance status of An. gambiae s.l. in southern African countries. Methods: World Health Organization (WHO) insecticide susceptibility tests were performed on 2,568 field collected mosquitoes originating from 13 sentinel sites covering all endemic regions in Zimbabwe in 2011-2012. At each site, 24-hour mortality and knock-down values for 50% and 90% of exposed mosquitoes (KD50 and KD90, respectively) were calculated for pools of 20-84 (mean, 54) mosquitoes exposed to 4% DDT, 0.1% bendiocarb, 0.05% lamda-cyhalothrin or 5% malathion. Susceptibility results from Zimbabwe were compiled with results published during 2002-2012 for all southern African countries to investigate the resistance status of An. gambiae s.l. in the region. Results: Using WHO criteria, insecticide resistance was not detected at any site sampled and for any of the insecticide formulations tested during the malaria transmission season in 2012. Knock-down within 1 hr post-insecticide exposure ranged from 95% to 100%; mortality 24 hours post-insecticide exposure ranged from 98% to 100%. Despite the lack of insecticide resistance, high variability was found across sites in KD50 and KD90 values. A total of 24 out of 64 (37.5%) sites in southern Africa with reported data had evidence of phenotypic insecticide resistance in An. gambiae s.l. to at least one insecticide. Conclusion: Despite a long history of indoor residual spraying of households with insecticide, up to 2012 there was no evidence of phenotypic resistance to any of the four insecticide classes in An. gambiae s.l. collected across different eco-epidemiological areas in Zimbabwe. Results reinforce the need for careful monitoring over time in sentinel sites in order to detect the potential emergence and propagation of insecticide resistance as insecticidal vector control interventions in Zimbabwe continue to be implemented.
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Genetic determinants of glucose-6-phosphate dehydrogenase activity in Kenya.

CiteULike malaria tags - 16 October 2014 - 12:13pm
BMC medical genetics, Vol. 15, No. 1. (9 September 2014)

BackgroundThe relationship between glucose-6-phosphate dehydrogenase (G6PD) deficiency and clinical phenomena such as primaquine-sensitivity and protection from severe malaria remains poorly defined, with past association studies yielding inconsistent and conflicting results. One possibility is that examination of a single genetic variant might underestimate the presence of true effects in the presence of unrecognized functional allelic diversity.MethodsWe systematically examined this possibility in Kenya, conducting a fine-mapping association study of erythrocyte G6PD activity in 1828 Kenyan children across 30 polymorphisms at or around the G6PD locus.ResultsWe demonstrate a strong functional role for c.202G>A (rs1050828), which accounts for the majority of variance in enzyme activity observed (P=1.5×10¿200, additive model). Additionally, we identify other common variants that exert smaller, intercorrelated effects independent of c.202G>A, and haplotype analyses suggest that each variant tags one of two haplotype motifs that are opposite in sequence identity and effect direction. We posit that these effects are of biological and possible clinical significance, specifically noting that c.376A>G (rs1050829) augments 202AG heterozygote risk for deficiency trait by two-fold (OR = 2.11 [1.12 - 3.84], P=0.014).ConclusionsOur results suggest that c.202G>A is responsible for the majority of the observed prevalence of G6PD deficiency trait in Kenya, but also identify a novel role for c.376A>G as a genetic modifier which marks a common haplotype that augments the risk conferred to 202AG heterozygotes, suggesting that variation at both loci merits consideration in genetic association studies probing G6PD deficiency-associated clinical phenotypes.
Shivang Shah, Alex Macharia, Johnstone Makale, Sophie Uyoga, Katja Kivinen, Rachel Craik, Christina Hubbart, Thomas Wellems, Kirk Rockett, Dominic Kwiatkowski, Thomas Williams
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Large, rapidly evolving gene families are at the forefront of host–parasite interactions in Apicomplexa

CiteULike malaria tags - 16 October 2014 - 12:04pm
Parasitology, Vol. FirstView (September 2014), pp. 1-14, doi:10.1017/s0031182014001528

The Apicomplexa is a phylum of parasitic protozoa, which includes the malaria parasite Plasmodium, amongst other species that can devastate human and animal health. The past decade has seen the release of genome sequences for many of the most important apicomplexan species, providing an excellent basis for improving our understanding of their biology. One of the key features of each genome is a unique set of large, variant gene families. Although closely related species share the same families, even different types of malaria parasite have distinct families. In some species they tend to be found at the ends of chromosomes, which may facilitate aspects of gene expression regulation and generation of sequence diversity. In others they are scattered apparently randomly across chromosomes. For some families there is evidence they are involved in antigenic variation, immune regulation and immune evasion. For others there are no known functions. Even where function is unknown these families are most often predicted to be exposed to the host, contain much sequence diversity and evolve rapidly. Based on these properties it is clear that they are at the forefront of host–parasite interactions. In this review I compare and contrast the genomic context, gene structure, gene expression, protein localization and function of these families across different species.
Adam Reid
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EL Flannery et al. Mutations in the P-type cation-transporter ATPase 4, PfATP4, mediate resistance to both aminopyrazole and spiroindolone antimalarials. ACS Chem Biol

High Impact Journal from Malaria Portal - 16 October 2014 - 12:00am
Aminopyrazoles are a new class of antimalarial compounds identified in a cellular antiparasitic screen with potent activity against Plasmodium falciparum asexual and sexual stage parasites. . . .
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