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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). . . .
Categories: malaria news feeds

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. . . .
Categories: malaria news feeds

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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Revealing the Sequence and Resulting Cellular Morphology of Receptor-Ligand Interactions during Plasmodium falciparum Invasion of Erythrocytes

CiteULike malaria tags - 3 hours 7 min ago
PLoS Pathog, Vol. 11, No. 2. (27 February 2015), e1004670, doi:10.1371/journal.ppat.1004670

During blood stage Plasmodium falciparum infection, merozoites invade uninfected erythrocytes via a complex, multistep process involving a series of distinct receptor-ligand binding events. Understanding each element in this process increases the potential to block the parasite’s life cycle via drugs or vaccines. To investigate specific receptor-ligand interactions, they were systematically blocked using a combination of genetic deletion, enzymatic receptor cleavage and inhibition of binding via antibodies, peptides and small molecules, and the resulting temporal changes in invasion and morphological effects on erythrocytes were filmed using live cell imaging. Analysis of the videos have shown receptor-ligand interactions occur in the following sequence with the following cellular morphologies; 1) an early heparin-blockable interaction which weakly deforms the erythrocyte, 2) EBA and PfRh ligands which strongly deform the erythrocyte, a process dependant on the merozoite’s actin-myosin motor, 3) a PfRh5-basigin binding step which results in a pore or opening between parasite and host through which it appears small molecules and possibly invasion components can flow and 4) an AMA1–RON2 interaction that mediates tight junction formation, which acts as an anchor point for internalization. In addition to enhancing general knowledge of apicomplexan biology, this work provides a rational basis to combine sequentially acting merozoite vaccine candidates in a single multi-receptor-blocking vaccine. The development of an effective malaria vaccine is a world health priority and would be a critical step toward the control and eventual elimination of this disease. In addition, new pharmacological solutions are necessary as Plasmodium falciparum, the deadliest of the malaria-causing parasites, has developed resistance to every drug currently approved for treatment. Understanding the interactions required for the parasite to invade its erythrocyte host, as well as being valuable to our basic knowledge of parasite biology, is important for the development of drug-based therapies and vaccines. In this study we have, for the first time, filmed P. falciparum parasites invading erythrocytes while systematically blocking several specific interactions between the parasite and the erythrocyte. We have shown there is a sequential progression of specific interactions that occur in at least four distinct steps leading up to invasion. Previous vaccine attempts have targeted one or two of these steps, however, if a single vaccine were designed to block interactions at all four steps, the combined effect might so reduce invasion that parasite growth and disease progression would be arrested. A better understanding of each interaction during invasion, their role and order, can also inform the development of new anti-malarial drugs.
Greta Weiss, Paul Gilson, Tana Taechalertpaisarn, Wai-Hong Tham, Nienke de Jong, Katherine Harvey, Freya Fowkes, Paul Barlow, Julian Rayner, Gavin Wright, Alan Cowman, Brendan Crabb
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Improving uptake and use of malaria rapid diagnostic tests in the context of artemisinin drug resistance containment in eastern Myanmar: an evaluation of incentive schemes among informal private healthcare providers

Malaria Journal - 12 hours 33 min ago
Background: As efforts to contain artemisinin resistance and eliminate Plasmodium falciparum intensify, the accurate diagnosis and prompt effective treatment of malaria are increasingly needed in Myanmar and the Greater Mekong Sub-region (GMS). Rapid diagnostic tests (RDTs) have been shown to be safe, feasible, and effective at promoting appropriate treatment for suspected malaria, which are of particular importance to drug resistance containment. The informal private sector is often the first point of care for fever cases in malaria endemic areas across Myanmar and the GMS, but there is little published information about informal private provider practices, quality of service provision, or potential to contribute to malaria control and elimination efforts. This study tested different incentives to increase RDT use and improve the quality of care among informal private healthcare providers in Myanmar. Methods: The study randomized six townships in the Mon and Shan states of rural Myanmar into three intervention arms: 1) RDT price subsidies, 2) price subsidies with product-related financial incentives, and 3) price subsidies with intensified information, education and counselling (IEC). The study assessed the uptake of RDT use in the communities by cross-sectional surveys of 3,150 households at baseline and six months post-intervention (6,400 households total, 832 fever cases). The study also used mystery clients among 171 providers to assess quality of service provision across intervention arms. Results: The pilot intervention trained over 600 informal private healthcare providers. The study found a price subsidy with intensified IEC, resulted in the highest uptake of RDTs in the community, as compared to subsidies alone or merchandise-related financial incentives. Moreover, intensified IEC led to improvements in the quality of care, with mystery client surveys showing almost double the number of correct treatment following diagnostic test results as compared to a simple subsidy. Conclusions: Results show that training and quality supervision of informal private healthcare providers can result in improved demand for, and appropriate use of RDTs in drug resistance containment areas in eastern Myanmar. Future studies should assess the sustainability of such interventions and the scale and level of intensity required over time as public sector service provision expands.
Categories: malaria news feeds

Sibling species of the Anopheles funestus group, and their infection with malaria and lymphatic filarial parasites, in archived and newly collected specimens from northeastern Tanzania

Malaria Journal - 12 hours 33 min ago
Background: Studies on the East African coast have shown a recent dramatic decline in malaria vector density and change in composition of sibling species of the Anopheles gambiae complex, paralleled by a major decline in malaria incidence. In order to better understand the ongoing changes in vector-parasite dynamics in the area, and to allow for appropriate adjustment of control activities, the present study examined the composition, and malaria and lymphatic filarial infection, of sibling species of the Anopheles funestus group. Similar to the An. gambiae complex, the An. funestus group contains important vectors of both malaria and lymphatic filariasis. Methods: Archived (from 2005–2012) and newly collected (from 2014) specimens of the An. funestus group collected indoors using CDC light traps in villages in northeastern Tanzania were analysed. They were identified to sibling species by PCR based on amplification of a species-specific nucleotide sequence in the ITS2 region on the rDNA genes. The specimens were furthermore examined for infection with Plasmodium falciparum and Wuchereria bancrofti by PCR. Results: The identified sibling species were An. funestus s.s., Anopheles parensis, Anopheles rivulorum, and Anopheles leesoni, with the first being by far the most common (overall 94.4%). When comparing archived specimens from 2005–2007 to those from 2008–2012, a small but statistically significant decrease in proportion of An. funestus s.s. was noted, but otherwise observed temporal changes in sibling species composition were minor. No P. falciparum was detected in archived specimens, while 8.3% of the newly collected An. funestus s.s. were positive for this parasite. The overall W. bancrofti infection rate decreased from 14.8% in the 2005–2007 archived specimens to only 0.5% in the newly collected specimens, and with overall 93.3% of infections being in An. funestus s.s. Conclusion: The study indicated that the sibling species composition of the An. funestus group had remained rather stable during the study period, with An. funestus s.s. being the most predominant. The study also showed increasing P. falciparum infection and decreasing W. bancrofti infection in An. funestus s.s. in the study period, most likely reflecting infection levels with these parasites in the human population in the area.
Categories: malaria news feeds

Malaria genomics: tracking a diverse and evolving parasite population

CiteULike malaria tags - 5 March 2015 - 1:46pm
International Health, Vol. 7, No. 2. (1 March 2015), pp. 82-84, doi:10.1093/inthealth/ihv007

Malaria parasites are continually evolving to evade the immune system and human attempts to control the disease. To eliminate malaria from regions where it is deeply entrenched we need ways of monitoring what is going on in the parasite population, detecting problematic changes as soon as they arise, and executing a prompt and effective response based on a deep understanding of this natural evolutionary process. Powerful new tools to address this problem are emerging from the fast-growing field of genomic epidemiology, driven by new sequencing technologies and computational methods that allow parasite genome variation to be studied in much greater detail and in many more samples than was previously considered possible. These new tools will provide a deep understanding of what is going on in the parasite population, generating actionable knowledge for strategic planning of control interventions, for monitoring their effects and steering them for greatest impact, and for raising the alert if things start to go wrong.
Dominic Kwiatkowski
Categories: malaria news feeds

A Genome-Scale Vector Resource Enables High-Throughput Reverse Genetic Screening in a Malaria Parasite

CiteULike malaria tags - 5 March 2015 - 1:05pm
Cell Host & Microbe (February 2015), doi:10.1016/j.chom.2015.01.014
Ana Gomes, Ellen Bushell, Frank Schwach, Gareth Girling, Burcu Anar, Michael Quail, Colin Herd, Claudia Pfander, Katarzyna Modrzynska, Julian Rayner, Oliver Billker
Categories: malaria news feeds

Comparison of rapid diagnostic test Plasmotec Malaria-3, microscopy, and quantitative real-time PCR for diagnoses of Plasmodium falciparum and Plasmodium vivax infections in Mimika Regency, Papua, Indonesia

Malaria Journal - 5 March 2015 - 12:00am
Background: The World Health Organization recommends malaria be diagnosed by standard microscopy or rapid diagnostic test (RDT) before treatment. RDTs have been used with greater frequency in the absence of matching blood slide confirmation in the majority of RDT reported cases in Mimika Regency, Papua Province, Indonesia. Given the importance of RDT in current health system as point-of-care tool, careful validation of RDT product performance for providing accurate malaria diagnosis is critical. Methods: Plasmotec Malaria-3 (XW-P07) performance was evaluated by comparing it with paired blood film microscopy and quantitative real-time PCR (qPCR). Consecutive whole blood samples were derived from one clinic in Mimika as part of routine passive malaria case detection. RDT results were read by two trained technicians and interpreted by consensus. Expert microscopic examination of blood slides was cross-checked by observer-blinded second reader and a third examiner if discordant between examinations. qPCR was used as the ‘gold standard’, followed by microscopy for the outcome/disease variable. Comparison analysis included sensitivity (Sn), specificity (Sp), positive and negative predictive values (PPV & NPV), and other diagnostic screening performance measures for detecting Plasmodium falciparum and Plasmodium vivax infections. Results: Overall malaria positive samples from qPCR was 42.2% (175/415 samples); and from matching blood slides 40.5% (168/415) of which those infections with relatively low parasite densities ≤100/μl blood was 5.7% of P. falciparum and 16.5% of P. vivax samples examined. Overall RDT performance when compared with microscopy for detecting P. falciparum was Sn:92%, Sp:96.6%, PPV:88%, NPV:97.8%, Kappa:0.87; and for P. vivax Sn:72.9%, Sp:99.1%, PPV:95.4%, NPV:93.4%, Kappa:0.79. Overall RDT performance when compared with qPCR for detecting P. falciparum was Sn:92%, Sp:96.6%, PPV:88%, NPV:97.8%, Kappa:0.87; and for P. vivax Sn:66%, Sp:99.1%, PPV:95.4%, NPV:90.9%, Kappa:0.73. Conclusions: Plasmotec Malaria-3 test showed good overall performance scores in precision for detecting P. falciparum, but lower values regarding sensitivity and negative likelihood ratio for detecting P. vivax, a finding partly associated with greater frequency of lower density P. vivax infections compared to P. falciparum in this study. In particular, the negative likelihood ratio (>0.1) for P. vivax detection indicates RDT lacked sufficient discriminating exclusion power falling below general acceptance criteria.
Categories: malaria news feeds

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