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B Zelman et al. Costs of Eliminating Malaria and the Impact of the Global Fund in 34 Countries. PLoS One
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). . . .
AJ Arik et al. Increased Akt signaling in the mosquito fat body increases adult survivorship. FASEB J
Akt signaling regulates diverse physiologies in a wide range of organisms. . . .
G Carissimo et al. Antiviral immunity of Anopheles gambiae is highly compartmentalized, with distinct roles for RNA interference and gut microbiota. Proc Natl Acad Sci U S A
Arboviruses are transmitted by mosquitoes and other arthropods to humans and animals. . . .
Z Chen et al. Elimination of malaria due to Plasmodium vivax in central part of the People's Republic of China: analysis and prediction based on modelling. Geospat Health
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AG Fonseca et al. Imported malaria in portugal 2000-2009: a role for hospital statistics for better estimates and surveillance. Malar Res Treat
Background. . . .
H Bouharoun-Tayoun et al. Mechanisms underlying the monocyte-mediated antibody-dependent killing of Plasmodium falciparum asexual blood stages. J Exp Med
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
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. . . .
KA épin et al. China¿s role as a global health donor in Africa: what can we learn from studying under reported resource flows? Global Health
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SJ Naine et al. Larvicidal and repellent properties of Streptomyces sp. VITJS4 crude extract against Anopheles stephensi, Aedes aegypti and Culex quinquefasciatus (Diptera: Culicidae). Pol J Microbiol
The aim of the present study was to assess the larvicidal and repellent properties of marine Streptomyces sp. . . .
C Waterman et al. Miniaturized Cultivation of Microbiota for Antimalarial Drug Discovery. Med Res Rev
The ongoing search for effective antiplasmodial agents remains essential in the fight against malaria worldwide. . . .
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
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. . . .
K Schuldt et al. Endothelial protein C receptor gene variants not associated with severe malaria in ghanaian children. PLoS One
Two recent reports have identified the Endothelial Protein C Receptor (EPCR) as a key molecule implicated in severe malaria pathology. . . .
P Awor et al. Increased access to care and appropriateness of treatment at private sector drug shops with integrated management of malaria, pneumonia and diarrhoea: a quasi-experimental study in Uganda. PLoS One
Drug shops are a major source of care for children in low income countries but they provide sub-standard care. . . .
A Roca-Feltrer et al. Field Trial Evaluation of the Performances of Point-of-Care Tests for Screening G6PD Deficiency in Cambodia. PLoS One
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Journal of the Royal Society of Medicine, Vol. 74, No. 7. (July 1981), pp. 531-536
Monitoring of efficacy and safety of artemisinin-based anti-malarials for treatment of uncomplicated malaria: a review of evidence of implementation of anti-malarial therapeutic efficacy trials in Tanzania
Background: Prompt diagnosis and effective treatment are considered the cornerstones of malaria control and artemisinin-based combination therapy (ACT) is currently the main anti-malarial drugs used for case management. After deployment of ACT due to widespread parasite resistance to the cheap and widely used anti-malarial drugs, chloroquine and sulphadoxine/pyrimethamine, the World Health Organization recommends regular surveillance to monitor the efficacy of the new drugs. The present paper assessed the implementation of anti-malarial efficacy testing for monitoring the therapeutic efficacy of ACT for treatment of uncomplicated malaria in Tanzania before and after policy changes in 2006. Methods: A literature search was performed for published clinical trials conducted in Tanzania from 2001 to 2014. It focused on studies which assessed at least one form of ACT for treatment of uncomplicated falciparum malaria in children less than 10 years and reported efficacy and safety of the tested anti-malarials. References were imported into the Endnote library and duplicates removed. An electronic matrix was developed in Microsoft Excel followed by full text review with predetermined criteria. Studies were independently assessed and information related to ACT efficacy and safety extracted. Results: Nine papers were selected from 125 papers screened. The efficacy of both artemether-lumefantrine (AL) and artesunate-amodiaquine (AS + AQ) against uncomplicated P. falciparum infections in Tanzania was high with PCR-corrected cure rates on day 28 of 91-100% and 88-93.8%, respectively. The highest day-3 parasite positivity rate was 1.4%. Adverse events ranged from mild to serious but were not directly attributed to the drugs. Conclusion: ACT is efficacious and safe for treatment of uncomplicated malaria in Tanzania. However, few trials were conducted in Tanzania before and after policy changes in 2006 and thus more surveillance should be urgently undertaken to detect future changes in parasite sensitivity to ACT.
Anti-malarial activity and toxicity assessment of <it>Himatanthus articulatus</it>, a plant used to treat malaria in the Brazilian Amazon
Background: Plasmodium falciparum has become resistant to some of the available drugs. Several plant species are used for the treatment of malaria, such as Himatanthus articulatus in parts of Brazil. The present paper reports the phyto-chemistry, the anti-plasmodial and anti-malarial activity, as well as the toxicity of H. articulatus. Methods: Ethanol and dichloromethane extracts were obtained from the powder of stem barks of H. articulatus and later fractionated and analysed. The anti-plasmodial activity was assessed against a chloroquine resistant strain P. falciparum (W2) in vitro, whilst in vivo anti-malarial activity against Plasmodium berghei (ANKA strain) was tested in mice, evaluating the role of oxidative stress (total antioxidant capacity - TEAC; lipid peroxidation – TBARS, and nitrites and nitrates - NN). In addition, cytotoxicity was evaluated using the HepG2 A16 cell-line. The acute oral and sub-chronic toxicity of the ethanol extract were evaluated in both male and female mice. Results: Plumieride was isolated from the ethyl acetate fraction of ethanol extract, Only the dichloromethane extract was active against clone W2. Nevertheless, both extracts reduced parasitaemia in P. berghei-infected mice. Besides, a significant reduction in pulmonary and cerebral levels of NN (nitrites and nitrates) was found, as well as in pulmonary TBARS, indicating a reduced oxidative damage to these organs. The ethanol extract showed low cytotoxicity to HepG2 A16 cells in the concentrations used. No significant changes were observed in the in vivo toxicity studies. Conclusions: The ethanol extract of H. articulatus proved to be promising as anti-malarial medicine and showed low toxicity.
Do frontline health care providers know enough about artemisinin–based combination therapy to rationally treat malaria? A cross-sectional survey in Gezira State, Sudan
Background: In 2004, artemisinin-based combination therapy (ACT) was introduced in Sudan for the treatment of malaria. The role of health care providers working in first-level health care facilities is central for the effective implementation of this revised malaria treatment policy. However, information about their level of ACT knowledge is inadequate. This study sought to describe frontline health care providers’ knowledge about the formulations and dose regimens of nationally recommended ACT in Sudan. Methods: This cross-sectional study took place in Gezira State, Sudan. Data were gathered from five localities comprising forty primary health care facilities. A total of 119 health care providers participated in the study (72 prescribers and 47 dispensers). The primary outcome was the proportion of health care providers who were ACT knowledgeable, a composite indicator of health care providers’ ability to (1) define what combination therapy is; (2) identify the recommended first- and second-line treatments; and (3) correctly state the dose regimens for each. Results: All prescribers and 95.7% (46/47) of dispensers were aware of the new national malaria treatment policy. However, 93.1% (67/72) of prescribers compared to 87.2% (41/47) of dispensers recognized artesunate-sulphadoxine/pyrimethamine as the recommended first-line treatment in Sudan. Only a small number of prescribers and dispensers (9.4% and 13.6%, respectively) were able to correctly define the meaning of a combination therapy. Overall, only 22% (26/119, 95% CI 14.6-29.4) of health care providers were found to be ACT knowledgeable with no statistically significant difference between prescribers and dispensers. Conclusion: Overall, ACT knowledge among frontline health care providers is very poor. This finding suggests that efforts are needed to improve knowledge of prescribers and dispensers working in first-level health care facilities, perhaps through implementing focused, provider-oriented training programmes. Additionally, a system for regularly monitoring and evaluating the quality of in-service training may be beneficial to ensure its responsiveness to the needs of the target health care providers.
Studying the effect of chloroquine on sporozoite-induced protection and immune responses in <it>Plasmodium berghei</it> malaria
Background: Sporozoite immunization of animals and humans under a chemo-prophylactic cover of chloroquine (CPS-CQ) efficiently induces sterile protection against malaria. In humans, CPS-CQ is strikingly more efficient than immunization with radiated attenuated sporozoites (RAS), raising the hypothesis that this might be partially due to CQ. Chloroquine, an established anti-malarial drug, is also well known for its immune modulating properties including improvement of cross-presentation. The aim of this study was to investigate whether co-administration of CQ during sporozoite immunization improves cellular responses and protective efficacy in Plasmodium berghei models. Methods: A number of experiments in selected complimentary P. berghei murine models in Balb/cByJ and C57BL/6j mice was performed. First, the effect of CQ administration on the induction of protection and immune responses by RAS immunization was studied. Next, the effect of CQ on the induction of circumsporozoite (CS) protein-specific CD8+ T cells by immunization with P. berghei parasites expressing a mutant CS protein was investigated. Finally, a direct comparison of CPS-CQ to CPS with mefloquine (MQ), an anti-malarial with little known immune modulating effects, was performed. Results: When CQ was co-administered during immunization with graded numbers of RAS, this did not lead to an increase in frequencies of total memory CD8+ T cells or CS protein-specific CD8+ T cells. Also parasite-specific cytokine production and protection remained unaltered. Replacement of CQ by MQ for CPS immunization resulted in significantly reduced percentages of IFNγ producing memory T cells in the liver (p = 0.01), but similar protection. Conclusions: This study does not provide evidence for a direct beneficial effect of CQ on the induction of sporozoite-induced immune responses and protection in P. berghei malaria models. Alternatively, the higher efficiency of CPS compared to RAS might be explained by an indirect effect of CQ through limiting blood-stage exposure after immunization or to increased antigen exposure and, therefore, improved breadth of the immune response.
Prevalence of <it>Plasmodium falciparum</it> anti-malarial resistance-associated polymorphisms in <it>pfcrt</it>, <it>pfmdr1</it> and <it>pfnhe1</it> in Muheza, Tanzania, prior to introduction of artemisinin combination therapy
Background: A report of the chloroquine and amodiaquine resistance pfcrt-SVMNT haplotype in Tanzania raises concern about high-level resistance to the artesunate-amodiaquine combination treatment widely employed in Africa. Mutations in the pfmdr1 multi-drug resistance gene may also be associated with resistance, and a highly polymorphic microsatellite (ms-4760) of the pfnhe1 gene involved in quinine susceptibility has not been surveyed in Tanzania. Methods: A total of 234 samples collected between 2003 – 2006 from an observational birth cohort of young children in Muheza, Tanzania were analysed. In these children, 141 cases of P. falciparum infections were treated with AQ and 93 episodes were treated with QN. Haplotypes of pfcrt and pfmdr1 were determined by a Taqman assay, and ms-4760 repeats in pfnhe1 were assessed by nested PCR amplification and direct sequencing. Parasite population diversity was evaluated using microsatellite markers on five different chromosomes. Results: The pfcrt-CVIET haplotype was present alone in 93.6% (219/234) of the samples over the study period; the wild-type chloroquine- and amodiaquine-sensitive haplotype pfcrt-CVMNK was present in 4.3% (10/234) of the samples; and both haplotypes were present in 2.1% (5/234) of the samples. No significant change in wild-type pfcrt-CVMNK prevalence was evident over the 4-year period of the study. The pfcrt-SVMNT haplotype associated with high-level amodiaquine resistance was not detected in this study. The pfmdr1 locus was genotyped in 178 of these samples. The pfmdr1-YYNY haplotype predominated in 67.4% (120/178) of infections and was significantly associated with the pfcrt-CVIET haplotype. All samples carried the wild-type pfmdr1-N1042 codon. The ms-4760 repeat on pfnhe1 locus displayed 12 distinct haplotypes with ms-4760-1 predominating in the population. Analysis of these haplotypes showed no association of a particular haplotype with quinine treatment outcome. Conclusion: The pfcrt-CVIET chloroquine resistance haplotype dominated in the collection of P. falciparum samples from Muheza. The pfcrt-SVMNT haplotype, which threatens the efficacy of amodiaquine and was reported in the same time period from Korogwe, Tanzania, 40 Km from Muheza, was not detected. Relative low prevalence of pfcrt-SVMNT in Africa may result from genetic or other factors rendering P. falciparum less supportive of this haplotype than in South America or other regions.Trial registrationTrial Protocol Number: 08-I-N064.