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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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<it>Plasmodium falciparum</it> in the southeastern Atlantic forest: a challenge to the bromeliad-malaria paradigm?

Malaria Journal - 25 April 2015 - 12:00pm
Background: Recently an unexpectedly high prevalence of Plasmodium falciparum was found in asymptomatic blood donors living in the southeastern Brazilian Atlantic forest. The bromeliad-malaria paradigm assumes that transmission of Plasmodium vivax and Plasmodium malariae involves species of the subgenus Kerteszia of Anopheles and only a few cases of P. vivax malaria are reported annually in this region. The expectations of this paradigm are a low prevalence of P. vivax and a null prevalence of P. falciparum. Therefore, the aim of this study was to verify if P. falciparum is actively circulating in the southeastern Brazilian Atlantic forest remains. Methods: In this study, anophelines were collected with Shannon and CDC-light traps in seven distinct Atlantic forest landscapes over a 4-month period. Field-collected Anopheles mosquitoes were tested by real-time PCR assay in pools of ten, and then each mosquito from every positive pool, separately for P. falciparum and P. vivax. Genomic DNA of P. falciparum or P. vivax from positive anophelines was then amplified by traditional PCR for sequencing of the 18S ribosomal DNA to confirm Plasmodium species. Binomial probabilities were calculated to identify non-random results of the P. falciparum-infected anopheline findings. Results: The overall proportion of anophelines naturally infected with P. falciparum was 4.4% (21/480) and only 0.8% (4/480) with P. vivax. All of the infected mosquitoes were found in intermixed natural and human-modified environments and most were Anopheles cruzii (22/25 = 88%, 18 P. falciparum plus 4 P. vivax). Plasmodium falciparum was confirmed by sequencing in 76% (16/21) of positive mosquitoes, whereas P. vivax was confirmed in only 25% (1/4). Binomial probabilities suggest that P. falciparum actively circulates throughout the region and that there may be a threshold of the forested over human-modified environment ratio upon which the proportion of P. falciparum-infected anophelines increases significantly. Conclusions: These results show that P. falciparum actively circulates, in higher proportion than P. vivax, among Anopheles mosquitoes of fragments of the southeastern Brazilian Atlantic forest. This finding challenges the classical bromeliad-malaria paradigm, which considers P. vivax circulation as the driver for the dynamics of residual malaria transmission in this region.
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The influence of nevirapine and efavirenz-based anti-retroviral therapy on the pharmacokinetics of lumefantrine and anti-malarial dose recommendation in HIV-malaria co-treatment

Malaria Journal - 25 April 2015 - 12:00am
Background: HIV-malaria co-infected patients in most parts of sub-Saharan Africa are treated with both artemether-lumefantrine (AL) and efavirenz (EFV) or nevirapine (NVP)-based antiretroviral therapy (ART). EFV, NVP, artemether and lumefantrine are substrate, inhibitor or inducer of CYP3A4 and CYP2B6, which creates a potential for drug-drug interactions. The effect of EFV and/or NVP on lumefantrine pharmacokinetic profile among HIV-malaria co-infected patients on ART and treated with AL was investigated. Optimal lumefantrine dosage regimen for patients on EFV-based ART was determined by population pharmacokinetics and simulation. Methods: This was a non-randomized, open label, parallel, prospective cohort study in which 128, 66 and 75 HIV-malaria co-infected patients on NVP-based ART (NVP-arm), EFV-based ART (EFV-arm) and ART naïve (control-am) were enrolled, respectively. Patients were treated with AL and contributed sparse venous plasma samples. Pharmacokinetic analysis of lumefantrine was done using non-linear mixed effect modelling. Results: Of the evaluated models, a two-compartment pharmacokinetic model with first order absorption and lag-time well described lumefantrine plasma concentrations. Patients in the EFV-arm but not in the NVP-arm had significantly lower lumefantrine bioavailability compared to that in the control-arm. Equally, 32% of patients in the EFV-arm had day-7 lumefantrine plasma concentrations below 280 ng/ml compared to only 4% in the control-arm and 3% in the NVP-arm. Upon post hoc simulation of lumefantrine exposure, patients in the EFV-arm had lower exposure (median (IQR)) compared to that in the control-arm; AUC 0-inf; was 303,130 (211,080–431,962) versus 784,830 (547,405–1,116,250); day-7 lumefantrine plasma concentrations was: 335.5 (215.8-519.5) versus 858.7 (562.3-1,333.8), respectively. The predictive model through simulation of lumefantrine exposure at different dosage regimen scenarios for patients on EFV-based ART, suggest that AL taken twice daily for five days using the current dose could improve lumefantrine exposure and consequently malaria treatment outcomes. Conclusions: Co-treatment of AL with EFV-based ART but not NVP-based ART significantly reduces lumefantrine bioavailability and consequently total exposure. To ensure adequate lumefantrine exposure and malaria treatment success in HIV-malaria co-infected patients on EFV-based ART, an extension of the duration of AL treatment to five days using the current dose is proposed.
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Re-imagining malaria &#8211; a platform for reflections to widen horizons in malaria control

Malaria Journal - 24 April 2015 - 12:00am
Ongoing political-economic discussions that take stock of social and societal determinants of health present an opportunity for productive dialogue on why current approaches to malaria control and elimination need to be broadened, and how this may be accomplished. They invite us, for example, to look beyond malaria as a disease, to appreciate the experiences of malaria-afflicted populations, to transcend techno-centric approaches, to investigate social conflicts around malaria, to give voice to the communities engaged in bottom-up approaches, and to revisit lessons learned in the past.While contributions from all disciplines are invited to this discussion, social scientists are particularly encouraged to participate. They have struggled in the past to find an appropriate platform within the malaria community that provides them the opportunity to address researchers from other disciplines, malaria practitioners, and policy makers. The Malaria Journal’s new thematic series on ‘re-imagining malaria’ offers them this opportunity. The goal of the series is to encourage transdisciplinary thinking, to stimulate discussion, to promote constructive criticism, and to gather overlooked experiences that help to reflect on implicit assumptions. Overall it aims at widening horizons in malaria control.
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Re-imagining the control of malaria in tropical Africa during the early years of the World Health Organization

Malaria Journal - 24 April 2015 - 12:00am
This paper grew out of a meeting organized in October 2014 in London on ‘Re-imagining malaria’. The focus of that meeting was on malaria today; only afterwards did the idea emerge that re-imagining the past might serve as a useful way for guiding present re-thinking. Sub-Saharan Africa is the logical place for such a re-examination for, as argued in this paper, the approaches that emerged following the collapse of the global eradication campaign were available to WHO in the 1950s, but these were not pursued as Africa was not encouraged to seek solutions outside those being advocated for eradication elsewhere.
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Characterization of imported malaria, the largest threat to sustained malaria elimination from Sri Lanka

Malaria Journal - 24 April 2015 - 12:00am
Sri Lanka has reached zero indigenous malaria cases in November 2012, two years before its targeted deadline for elimination. Currently, the biggest threat to the elimination efforts are the risk of resurgence of malaria due to imported cases. This paper describes two clusters of imported malaria infections reported in 2013 and 2014, one among a group of Pakistani asylum-seekers resident in Sri Lanka, and the other amongst local fishermen who returned from Sierra Leone. The two clusters studied reveal the potential impact of imported malaria on the risk of reintroducing the disease, as importation is the only source of malaria in the country at present. In the event of a case occurring, detection is a major challenge both amongst individuals returning from malaria endemic countries and the local population, as malaria is fast becoming a “forgotten” disease amongst health care providers. In spite of a very good coverage of diagnostic services (microscopy and rapid diagnostic tests) throughout the country, malaria is being repeatedly overlooked by health care providers even when individuals present with fever and a recent history of travel to a malaria endemic country. Given the high receptivity to malaria in previously endemic areas of the country due to the prevalence of the vector mosquito, such cases pose a significant threat for the reintroduction of malaria to Sri Lanka. The challenges faced by the Anti Malaria Campaign and measures taken to prevent the resurgence of malaria are discussed here.
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<it>Plasmodium vivax</it> malaria at households: spatial clustering and risk factors in a low endemicity urban area of the northwestern Peruvian coast

Malaria Journal - 24 April 2015 - 12:00am
Background: Peru has presented a decreasing malaria trend during the last decade, particularly in areas on northwestern coast; however, a limited number of cases continues to be reported yearly mainly in malaria hotspots. Methods: A two-phase study was conducted to identify spatial and temporal clusters of incident Plasmodium vivax malaria, as well as to determine risk factors associated with households (HH) presenting P. vivax malaria episodes in an urban area of the northwestern Peruvian Coast from June 2008 to May 2010. In the first stage, a full census of the study population was conducted, including geo-referencing of reported P. vivax episodes. In the second stage, a population-based case–control study allowed the identification of risk factors associated with HHs reporting episodes. A total of 117 case HHs with reported P. vivax and 117 control HHs without malaria episodes were assessed. A semi-structured questionnaire was used to interview the head of households and to collect data on HH location and structure, availability of public services, preventive malaria measures, family member with outdoor occupation (farmer, moto-taxi driver), and other HH characteristics. Univariate and multivariate logistic regression analyses were performed to determine case-HH risk factors. SaTScan was used to detect spatial and temporal P. vivax malaria clusters. Results: The most likely spatial cluster of malaria incidence included 1,040 people (22.4% of total population) in 245 HHs (24.6% of total HHs) accounting for 283 malaria episodes (40.1% of total episodes) during the study period (LLR = 55.8, RR = 2.3, p < 0.001). A temporal cluster was also identified from April 12, 2009 to July 4, 2009 accounting for 355 malaria episodes (50.4% of total episodes) (LLR = 299.2, RR = 7.2, p = 0.001). Factors significantly associated with case HHs compared with control HHs were: proximity to water drain < 200 metres (OR = 2.3, 95% CI: 1.3, 4.0); HH size >5 individuals (OR = 1.8, 95% CI: 1.0, 3.2); lack of potable water (OR = 1.8, 95% CI: 1.1, 3.2); and having domestic and peridomestic animals (OR = 3.6, 95% CI: 1.3, 9.5). Conclusion: Plasmodium vivax malaria incidence is highly heterogeneous in space and time in the urban study area with important geographical and housing risk factors associated with symptomatic episodes.
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