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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. . . .
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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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Identification of sibling species status of <it>Anopheles culicifacies</it> breeding in polluted water bodies in Trincomalee district of Sri Lanka

Malaria Journal - 8 hours 36 min ago
Background: Anopheles culicifacies s.l., the major vector of malaria in Sri Lanka, is known to breed in clean and clear water. However, recent findings have confirmed breeding from waste water bodies in urban and semi-urban areas. No study has been conducted to identify whether it is vector or non-vector siblings. The objective of the study was to identify the sibling species status of An. culicifacies s.l. Methods: Anopheles culicifacies s.l. adult samples (reared from larvae) were obtained from the Padavisiripura Entomological team attached to Tropical and Environmental Diseases and Health Associates (TEDHA) Malaria Elimination Programme in Trincomalee District. The collected mosquito specimens were processed for the extraction of genomic DNA individually. The PCR amplifications were carried out using different primer combinations for differentiating species A from D, species B from C, species B from E, and species B, C, and E from each other. The results obtained from the gel electrophoresis were compared with the marker and band sizes of 359 bp, 248 bp, 95 + 248 bp, 166 + 359 bp and 178 + 248 bp were used to compare the sibling species A, B, C, D and E, respectively. Results: The molecular biological identification of the field caught An. culicifacies s.l. samples observed that only 13.34 % (4/30) was represented sibling species B. About 86.66 % (26/30) of the samples were An. culicifacies sibling species E. This study also provided evidence that An. culicifacies E was able to breed in a wide range of breeding habitats. This is the first time that An. culicifacies E breeding in waste water was confirmed by a molecular method. Malaria control programmes in most parts of the country focus on rural communities as a result of bio-ecology of mosquitoes. Therefore, unusual breeding habitats, such as waste water collections, may mislead the current vector controlling programmes. Conclusions: These results reconfirm that An. culicifacies s.l. has adapted to breed in a wide range of water bodies, including waste water collections. Since the majority of mosquitoes sampled belong to sibling species E, this may adversely affect the current malaria elimination programme and new strategies should be adopted to control malaria vectors breeding in these unusual breeding habitats in Sri Lanka.
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Nowhere to hide: interrogating different metabolic parameters of <it>Plasmodium falciparum</it> gametocytes in a transmission blocking drug discovery pipeline towards malaria elimination

Malaria Journal - 20 hours 36 min ago
Background: The discovery of malaria transmission-blocking compounds is seen as key to malaria elimination strategies and gametocyte-screening platforms are critical filters to identify active molecules. However, unlike asexual parasite assays measuring parasite proliferation, greater variability in end-point readout exists between different gametocytocidal assays. This is compounded by difficulties in routinely producing viable, functional and stage-specific gametocyte populations. Here, a parallel evaluation of four assay platforms on the same gametocyte populations was performed for the first time. This allowed the direct comparison of the ability of different assay platforms to detect compounds with gametocytocidal activity and revealed caveats in some assay readouts that interrogate different parasite biological functions. Methods: Gametocytogenesis from Plasmodium falciparum (NF54) was optimized with a robust and standardized protocol. ATP, pLDH, luciferase reporter and PrestoBlue® assays were compared in context of a set of 10 reference compounds. The assays were performed in parallel on the same gametocyte preparation (except for luciferase reporter lines) using the same drug preparations (48 h). The remaining parameters for each assay were all comparable. Results: A highly robust method for generating viable and functional gametocytes was developed and comprehensively validated resulting in an average gametocytaemia of 4 %. Subsequent parallel assays for gametocytocidal activity indicated that different assay platforms were not able to screen compounds with variant chemical scaffolds similarly. Luciferase reporter assays revealed that synchronized stage-specific gametocyte production is essential for drug discovery, as differential susceptibility in various gametocyte developmental populations is evident. Conclusions: With this study, the key parameters for assays aiming at testing the gametocytocidal activity of potential transmission blocking molecules against Plasmodium gametocytes were accurately dissected. This first and uniquely comparative study emphasizes differential effects seen with the use of different assay platforms interrogating variant biological systems. Whilst this data is informative from a biological perspective and may provide indications of the drug mode of action, it does highlight the care that must be taken when screening broad-diversity chemotypes with a single assay platform against gametocytes for which the biology is not clearly understood.
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Coverage, use and maintenance of bed nets and related influence factors in Kachin Special Region II, northeastern Myanmar

Malaria Journal - 21 May 2015 - 12:00am
Background: Myanmar is one of the 31 highest burden malaria countries worldwide. Scaling up the appropriate use of insecticide-treated nets (ITNs) is a national policy for malaria prevention and control. However, the data on use, influencing factors and maintenance of bed nets is still lack among the population in Kachin Special Region II, Northeastern Myanmar. Methods: The study combined a quantitative household questionnaire survey and qualitative direct observation of households. A Chi-squared test was used to compare the percentages of ownership, coverage, and rates of use of bed nets. Additionally, multivariate logistic regression analysis (MVLRA) was used to analyse factors that influence the use of bed nets. Finally, covariance compared the mean calibrated hole indexes (MCHI) across potential influence variables. Results: The bed net to person ratio was 1:1.96 (i.e., more than one net for every two people). The long-lasting insecticidal net (LLIN) to person ratio was 1: 2.52. Also, the percentage of households that owned at least one bed net was 99.7 % (666/688). Some 3262 (97.3 %) residents slept under bed nets the prior night, 2551 (76.1 %) of which slept under ITNs/LLINs the prior night (SUITNPN). The poorest families, those with thatched roofing, those who use agriculture as their main source of family income, household heads who knew that mosquitoes transmit malaria and those who used bed nets to prevent malaria, were significantly more likely to be in the SUITNPN group. However, residents in lowlands, and foothills were significantly less likely to be SUITNPNs. Finally, head of household attitude towards fixing bed nets influenced MCHI (F = 8.09, P = 0.0046). Conclusions: The coverage and usage rates of bed nets were high, especially among children, and pregnant women. Family wealth index, geographical zones, household roofing, source of family income, household head’s knowledge of malaria transmission and of using bed nets as tools for malaria prevention are all independent factors which influence use of ITNs/LLINs in KR2. Maintaining high coverage, and use rate of bed nets should be a priority for the war-torn population of KR2 to ensure equity and human rights.
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Costs and cost-effectiveness of a large-scale mass testing and treatment intervention for malaria in Southern Province, Zambia

Malaria Journal - 20 May 2015 - 12:00pm
Background: A cluster, randomized, control trial of three dry-season rounds of a mass testing and treatment intervention (MTAT) using rapid diagnostic tests (RDTs) and artemether-lumefantrine (AL) was conducted in four districts in Southern Province, Zambia. Methods: Data were collected on the costs and logistics of the intervention and paired with effectiveness estimated from a community randomized control trial for the purpose of conducting a provider perspective cost-effectiveness analysis of MTAT vs no MTAT (Standard of Care). Results: Dry-season MTAT in this setting did not reduce malaria transmission sufficiently to permit transition to a case-investigation strategy to then pursue malaria elimination, however, the intervention did substantially reduce malaria illness and was a highly cost-effective intervention for malaria burden reduction in this moderate transmission area. The cost per RDT administered was estimated to be USD4.39 (range: USD1.62-13.96) while the cost per AL treatment administered was estimated to be USD34.74 (range: USD3.87-3,835). The net cost per disability adjusted life year averted (incremental cost-effectiveness ratio) was estimated to be USD804. Conclusions: The intervention appears to be highly cost-effective relative to World Health Organization thresholds for malaria burden reduction in Zambia as compared to no MTAT. However, it was estimated that population-wide mass drug administration is likely to be more cost-effective for burden reduction and for transmission reduction compared to MTAT.
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Mechanisms of Stage-Transcending Protection Following Immunization of Mice with Late Liver Stage-Arresting Genetically Attenuated Malaria Parasites

CiteULike malaria tags - 20 May 2015 - 9:08am
PLoS Pathog, Vol. 11, No. 5. (14 May 2015), e1004855, doi:10.1371/journal.ppat.1004855

Malaria, caused by Plasmodium parasite infection, continues to be one of the leading causes of worldwide morbidity and mortality. Development of an effective vaccine has been encumbered by the complex life cycle of the parasite that has distinct pre-erythrocytic and erythrocytic stages of infection in the mammalian host. Historically, malaria vaccine development efforts have targeted each stage in isolation. An ideal vaccine, however, would target multiple life cycle stages with multiple arms of the immune system and be capable of eliminating initial infection in the liver, the subsequent blood stage infection, and would prevent further parasite transmission. We have previously shown that immunization of mice with Plasmodium yoelii genetically attenuated parasites (GAP) that arrest late in liver stage development elicits stage-transcending protection against both a sporozoite challenge and a direct blood stage challenge. Here, we show that this immunization strategy engenders both T- and B-cell responses that are essential for stage-transcending protection, but the relative importance of each is determined by the host genetic background. Furthermore, potent anti-blood stage antibodies elicited after GAP immunization rely heavily on FC-mediated functions including complement fixation and FC receptor binding. These protective antibodies recognize the merozoite surface but do not appear to recognize the immunodominant merozoite surface protein-1. The antigen(s) targeted by stage-transcending immunity are present in both the late liver stages and blood stage parasites. The data clearly show that GAP-engendered protective immune responses can target shared antigens of pre-erythrocytic and erythrocytic parasite life cycle stages. As such, this model constitutes a powerful tool to identify novel, protective and stage-transcending T and B cell targets for incorporation into a multi-stage subunit vaccine. Malaria is arguably one of the deadliest infectious diseases in human history. Today, it infects nearly 300 million people each year and kills up to 1 million of those—mostly women and children under the age of 5—and no effective malaria vaccine has been developed. Traditional subunit vaccines for pathogens work by training the immune system to recognize a single pathogen target. Attempts at developing a subunit malaria vaccine have, however, been stymied by the complexity of the parasite genome which encodes a complex life cycle with specific stages in the mosquito, as well as in the liver and blood of the mammalian host. Only the blood stage parasites cause malaria symptoms and mortality. Previously, it was assumed that immunity to malaria is stage-specific, either targeting parasites in the liver or in blood, but not both. The herein described vaccination approach uses genetically engineered, attenuated rodent malaria parasites that are able to infect the mouse liver and replicate, but die shortly before red blood-infectious parasite stages are formed and released. Immunization with these attenuated parasites induces the immune system to build defenses against both parasite stages in the liver and blood. Protection is mediated by multiple arms of the immune system. The antibody arm recognizes parasite targets shared between liver stages and blood stages. This not only demonstrates the optimal potency of this live-attenuated vaccination strategy, but also provides a potential source of new malaria subunit vaccine targets.
Brandon Sack, Gladys Keitany, Ashley Vaughan, Jessica Miller, Ruobing Wang, Stefan Kappe
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When a discriminating dose assay is not enough: measuring the intensity of insecticide resistance in malaria vectors

Malaria Journal - 20 May 2015 - 12:00am
Background: Guidelines from the World Health Organization for monitoring insecticide resistance in disease vectors recommend exposing insects to a predetermined discriminating dose of insecticide and recording the percentage mortality in the population. This standardized methodology has been widely adopted for malaria vectors and has provided valuable data on the spread and prevalence of resistance. However, understanding the potential impact of this resistance on malaria control requires a more quantitative measure of the strength or intensity of this resistance. Methods: Bioassays were adapted to quantify the level of resistance to permethrin in laboratory colonies and field populations of Anopheles gambiae sensu lato. WHO susceptibility tube assays were used to produce data on mortality versus exposure time and CDC bottle bioassays were used to generate dose response data sets. A modified version of the CDC bottle bioassay, known as the Resistance Intensity Rapid Diagnostic Test (I-RDT), was also used to measure the knockdown and mortality after exposure to different multipliers of the diagnostic dose. Finally cone bioassays were used to assess mortality after exposure to insecticide treated nets. Results: The time response assays were simple to perform but not suitable for highly resistant populations. After initial problems with stability of insecticide and bottle washing were resolved, the CDC bottle bioassay provided a reproducible, quantitative measure of resistance but there were challenges performing this under field conditions. The I-RDT was simple to perform and interpret although the end point selected (immediate knockdown versus 24 h mortality) could dramatically affect the interpretation of the data. The utility of the cone bioassays was dependent on net type and thus appropriate controls are needed to interpret the operational significance of these data sets. Conclusions: Incorporating quantitative measures of resistance strength, and utilizing bioassays with field doses of insecticides, will help interpret the possible impact of resistance on vector control activities. Each method tested had different benefits and challenges and agreement on a common methodology would be beneficial so that data are generated in a standardized format. This type of quantitative data are an important prerequisite to linking resistance strength to epidemiological outcomes.
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