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https://www.readbyqxmd.com/read/27907215/cd8-t-cells-induce-fatal-brainstem-pathology-during-cerebral-malaria-via-luminal-antigen-specific-engagement-of-brain-vasculature
#1
Phillip A Swanson, Geoffrey T Hart, Matthew V Russo, Debasis Nayak, Takele Yazew, Mirna Peña, Shahid M Khan, Chris J Janse, Susan K Pierce, Dorian B McGavern
Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection that results in thousands of deaths each year, mostly in African children. The in vivo mechanisms underlying this fatal condition are not entirely understood. Using the animal model of experimental cerebral malaria (ECM), we sought mechanistic insights into the pathogenesis of CM. Fatal disease was associated with alterations in tight junction proteins, vascular breakdown in the meninges / parenchyma, edema, and ultimately neuronal cell death in the brainstem, which is consistent with cerebral herniation as a cause of death...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27907019/the-effects-of-transdermally-delivered-oleanolic-acid-on-malaria-parasites-and-blood-glucose-homeostasis-in-p-berghei-infected-male-sprague-dawley-rats
#2
Happiness P Sibiya, Musa V Mabandla, Cephas T Musabayane
The present study investigated the effects of transdermally delivered oleanolic acid (OA) monotherapy and in combination with chloroquine (CHQ) on malaria parasites and glucose homeostasis of P. berghei-infected male Sprague-Dawley rats. Oral glucose test (OGT) responses to OA-pectin patch and CHQ-OA combination matrix patch were monitored in non-infected and infected rats. To evaluate the short-term effects of treatment, percentage parasitaemia, blood glucose, glycogen and plasma insulin were monitored in separate groups of animals treated with either OA-patch monotherapy or CHQ-OA combination pectin patch over a 21-days period...
2016: PloS One
https://www.readbyqxmd.com/read/27905921/systematic-review-of-the-role-of-angiopoietin-1-and-angiopoietin-2-in-plasmodium-species-infections-biomarkers-or-therapeutic-targets
#3
Gerdie M de Jong, Jasper J Slager, Annelies Verbon, Jaap J van Hellemond, Perry J J van Genderen
BACKGROUND: Levels of both angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) correlate with malaria disease severity and are proposed as biomarkers and possible therapeutic targets. To establish their role in malaria, a systematic review was performed of the literature on Ang-1 and Ang-2 with regard to their potential as biomarkers in malaria and discuss their possible place in adjuvant treatment regimens. METHODS: Ten electronic databases were systematically searched to identify studies investigating Ang-1 and Ang-2 in human and murine malaria in both clinical and experimental settings...
December 1, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27895526/development-of-a-simple-and-specific-direct-competitive-elisa-for-the-determination-of-artesunate-using-an-anti-artesunate-polyclonal-antiserum
#4
Yoshinori Mitsui
BACKGROUND: Since artesunate (ART) became a vital component of artemisinin (ARM)-based combination therapies for the treatment for malaria, counterfeit ART drugs have spread in regions of Southeast Asia and Africa. The consumption of counterfeit ART drugs has resulted in the death of many patients. Thus, evaluating the quality of ART drugs is needed. There are several methods for quantitating the ART content in tablets, the most common being a high-performance liquid chromatography. However, that method is hampered by the need for expensive equipment and a rather time-consuming process of extraction...
2016: Tropical Medicine and Health
https://www.readbyqxmd.com/read/27887614/insight-into-k13-propeller-gene-polymorphism-and-ex-vivo-dha-response-profiles-from-cameroonian-isolates
#5
Sandie Menard, Joëlle Njila Tchoufack, Christelle Ngou Maffo, Sandrine E Nsango, Xavier Iriart, Luc Abate, Majoline Tchioffo Tsapi, Parfait H Awono-Ambéné, Francis A Abega Mekongo, Isabelle Morlais, Antoine Berry
BACKGROUND: The spread of Plasmodium falciparum resistance to artemisinin derivatives in Southeast Asia is a major source of concern and the emergence of resistance in Africa would have dramatic consequences, by increasing malaria mortality and morbidity. It is therefore urgent to implement regular monitoring in sentinel sites in sub-Saharan Africa using robust and easy-to-implement tools. The prevalence of k13-propeller mutations and the phenotypic profiles are poorly known in sub-Saharan Africa...
November 26, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27881136/community-health-workers-adherence-to-referral-guidelines-evidence-from-studies-introducing-rdts-in-two-malaria-transmission-settings-in-uganda
#6
Sham Lal, Richard Ndyomugenyi, Lucy Paintain, Neal D Alexander, Kristian S Hansen, Pascal Magnussen, Daniel Chandramohan, Siân E Clarke
BACKGROUND: Many malaria-endemic countries have implemented national community health worker (CHW) programmes to serve remote populations that have poor access to malaria diagnosis and treatment. Despite mounting evidence of CHWs' ability to adhere to malaria rapid diagnostic tests (RDTs) and treatment guidelines, there is limited evidence whether CHWs adhere to the referral guidelines and refer severely ill children for further management. In southwest Uganda, this study examined whether CHWs referred children according to training guidelines and described factors associated with adherence to the referral guideline...
November 24, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27879554/measles-and-rubella-seroprevalence-among-hiv-infected-and-uninfected-zambian-youth
#7
Catherine G Sutcliffe, Kelly Searle, Hellen K Matakala, Dip Biomed, Michelle Greenman, Kaitlin Rainwater-Lovett, Philip E Thuma, William J Moss
BACKGROUND: Measles and congenital rubella syndrome remain significant causes of morbidity and mortality despite available vaccines. HIV-infected youth may be at increased risk of measles because of greater waning immunity following vaccination. At a population level, they constitute a potentially large pool of susceptibles to measles and rubella. More data among HIV-infected youth in sub-Saharan Africa are needed to guide vaccination policy and control strategies. METHODS: This cross-sectional study was nested within two ongoing studies of malaria and HIV in Zambia...
November 22, 2016: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/27872816/evidence-of-triple-mutant-pfdhps-isgnga-haplotype-in-plasmodium-falciparum-isolates-from-north-east-india-an-analysis-of-sulfadoxine-resistant-haplotype-selection
#8
Manuj K Das, Sumi Chetry, Mohan C Kalita, Prafulla Dutta
BACKGROUND: North-east region of India has consistent role in the spread of multi drug resistant Plasmodium (P.) falciparum to other parts of Southeast Asia. After rapid clinical treatment failure of Artemisinin based combination therapy-Sulphadoxine/Pyrimethamine (ACT-SP) chemoprophylaxis, Artemether-Lumefantrine (ACT-AL) combination therapy was introduced in the year 2012 in this region for the treatment of uncomplicated P. falciparum malaria. In a DNA sequencing based polymorphism analysis, seven codons of P...
December 2016: Genomics Data
https://www.readbyqxmd.com/read/27872070/estimation-of-the-in-vivo-minimum-inhibitory-concentration-of-cipargamin-in-uncomplicated-plasmodium-falciparum-malaria
#9
Hien Tinh Tran, Nicholas J White, Thuy-Nhien Thanh Nguyen, Hoa Thi Nhu, Thuan Duc Phung, Joel Tarning, François Nosten, Baldur Magnusson, Jay Prakash Jain, Kamal Hamed
The minimum inhibitory concentration (MIC) of an antimalarial drug for a particular infection is the drug level associated with a net parasite multiplication rate of one per asexual cycle. To ensure cure of malaria the MIC must be exceeded until all parasites have been eliminated. The development of highly sensitive and accurate polymerase chain reaction quantitation of low-density malaria parasitemia enables prospective pharmacokinetic-pharmacodynamic (PK-PD) characterization of antimalarial drug effects, and now allows identification of the in-vivo MIC...
November 21, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27871303/geographically-weighted-regression-of-knowledge-and-behaviour-determinants-to-anti-malarial-recommending-and-dispensing-practice-among-medicine-retailers-in-western-kenya-capacitating-targeted-interventions
#10
Andria Rusk, Linda Highfield, J Michael Wilkerson, Melissa Harrell, Andrew Obala, Benjamin Amick
BACKGROUND: Most patients with malaria seek treatment first in retail drug shops. Myriad studies have examined retailer behaviours and characteristics to understand the determinants to these behaviours. Geospatial methods are helpful in discovering if geographic location plays a role in the relationship between determinants and outcomes. This study aimed to discover if spatial autocorrelation exists in the relationship between determinants and retailer behaviours, and to provide specific geographic locations and target behaviours for tailoring future interventions...
November 21, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27866919/in-vitro-sensitivity-of-antimalarial-drugs-and-correlation-with-clinico-parasitological-response-following-treatment-with-a-3-day-artesunate-mefloquine-combination-in-patients-with-falciparum-malaria-along-the-thai-myanmar-border
#11
Phunuch Muhamad, Artitaya Thiengsusuk, Papichaya Phompradit, Kesara Na-Bangchang
A 3-day artesunate-mefloquine combination therapy has been using as first-line treatment for acute uncomplicated Plasmodium falciparum malaria in Thailand since 1995 on the background of mefloquine resistance. The aim of the present study was to assess sensitivity of P. falciparum isolates (n=44) in an area along the Thai-Myanmar border (year 2009) to artesunate, mefloquine, chloroquine and quinine, including their correlation with clinico-parasitological response. Twenty, 19, and 5 isolates were collected from patients with 'Adequate Clinical and Parasitological Response (ACPR)', 'Late Parasitological Failure (LPF)' and 're-infection', respectively...
November 17, 2016: Acta Tropica
https://www.readbyqxmd.com/read/27865890/safety-tolerability-and-efficacy-of-repeated-doses-of-dihydroartemisinin-piperaquine-for-prevention-and-treatment-of-malaria-a-systematic-review-and-meta-analysis
#12
Julie Gutman, Stephanie Kovacs, Grant Dorsey, Andy Stergachis, Feiko O Ter Kuile
BACKGROUND: Intermittent preventive treatment (IPT) for malaria is used in infants, children, adults, and pregnant women. Dihydroartemisinin-piperaquine (DP) is an effective, well tolerated artemisinin-based combination therapy. The long half-life of piperaquine makes it attractive for IPT. We conducted a systematic review and meta-analysis to establish the efficacy and safety of repeated treatment with DP. METHODS: Following PRISMA guidelines, we searched multiple databases on Sept 1, 2016, with the terms: "human" AND "dihydroartemisinin-piperaquine" OR "DHA-PPQ"...
November 16, 2016: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/27857147/molecular-mechanism-of-action-of-antimalarial-benzoisothiazolones-species-selective-inhibitors-of-the-plasmodium-spp-mep-pathway-enzyme-ispd
#13
Kathryn E Price, Christopher M Armstrong, Leah S Imlay, Dana M Hodge, C Pidathala, Natalie J Roberts, Jooyoung Park, Marwa Mikati, Raman Sharma, Alexandre S Lawrenson, Niraj H Tolia, Neil G Berry, Paul M O'Neill, Audrey R Odom John
The methylerythritol phosphate (MEP) pathway is an essential metabolic pathway found in malaria parasites, but absent in mammals, making it a highly attractive target for the discovery of novel and selective antimalarial therapies. Using high-throughput screening, we have identified 2-phenyl benzo[d]isothiazol-3(2H)-ones as species-selective inhibitors of Plasmodium spp. 2-C-methyl-D-erythritol-4-phosphate cytidyltransferase (IspD), the third catalytic enzyme of the MEP pathway. 2-Phenyl benzo[d]isothiazol-3(2H)-ones display nanomolar inhibitory activity against P...
November 18, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27856948/impact-of-introducing-subsidized-combination-treatment-with-artemether-lumefantrine-on-sales-of-anti-malarial-monotherapies-a-survey-of-private-sector-pharmacies-in-huambo-angola
#14
Cristina Lussiana, Marco Floridia, Joana Martinho do Rosário, Filomeno Fortes, Richard Allan
BACKGROUND: Artemisinin-based combination therapies (ACTs) against malaria are subsidized in many African countries, but the impact of subsidy programs in reducing the sales of concomitantly available antimalarial monotherapies is poorly defined. METHODS: Data from The MENTOR initiative, that introduced subsidized artemether-lumefantrine (sAL) in the private sector of Huambo province, Angola, were used. The main response variable was represented by sales of sAL and of monotherapies, measured as number of treatment courses...
November 17, 2016: Transactions of the Royal Society of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/27853090/steroid-pulse-therapy-may-mitigate-prolonged-neurological-manifestations-after-eradication-of-severe-plasmodium-falciparum-parasitemia
#15
Chihiro Hasegawa, Akiko Inagaki, Gohei Yamada, Koji Morita, Isamu Kitamura, Koya Ariyoshi
A 58-year-old Japanese man with a high parasitemia of Plasmodium falciparum, returning from Uganda, was admitted to our hospital since his consciousness level rapidly deteriorated after the initial dose of mefloquine. Despite the parasitemia was cleared by quinine by day 7, the coma remained unchanged and diffuse leukoencephalopathy was detected on magnetic resonance image. Steroid pulse therapy was initiated on day 8. Subsequently, the neurological manifestations improved and he was discharged on day 73 without any sequelae...
2016: Internal Medicine
https://www.readbyqxmd.com/read/27846898/antibiotics-in-malaria-therapy-which-antibiotics-except-tetracyclines-and-macrolides-may-be-used-against-malaria
#16
REVIEW
Tiphaine Gaillard, Marylin Madamet, Francis Foguim Tsombeng, Jérôme Dormoi, Bruno Pradines
Malaria, a parasite vector-borne disease, is one of the most significant health threats in tropical regions, despite the availability of individual chemoprophylaxis. Malaria chemoprophylaxis and chemotherapy remain a major area of research, and new drug molecules are constantly being developed before drug-resistant parasites strains emerge. The use of anti-malarial drugs is challenged by contra-indications, the level of resistance of Plasmodium falciparum in endemic areas, clinical tolerance and financial cost...
November 15, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27843300/the-aqueous-extract-of-brucea-javanica-suppresses-cell-growth-and-alleviates-tumorigenesis-of-human-lung-cancer-cells-by-targeting-mutated-epidermal-growth-factor-receptor
#17
Seung-Hun Kim, Chun-Yen Liu, Po-Wei Fan, Chang-Heng Hsieh, Hsuan-Yuan Lin, Ming-Chung Lee, Kang Fang
As a practical and safe herbal medicine, the seeds of Brucea javanica (L.) Merr., were used to cure patients suffering from infectious diseases such as malaria. Recent advances revealed that the herb could also be a useful cancer therapy agent. The study demonstrated that aqueous B. javanica (BJ) extract attenuated the growth of human non-small-lung cancer cells bearing mutant L858R/T790M epidermal growth factor receptor (EGFR). The reduced cell viability in H1975 cells was attributed to apoptosis. Transfection of EGFR small hairpin RNA reverted the sensitivities...
2016: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/27843298/endoperoxide-antimalarials-development-structural-diversity-and-pharmacodynamic-aspects-with-reference-to-1-2-4-trioxane-based-structural-scaffold
#18
REVIEW
Mithun Rudrapal, Dipak Chetia
Malaria disease continues to be a major health problem worldwide due to the emergence of multidrug-resistant strains of Plasmodium falciparum. In recent days, artemisinin (ART)-based drugs and combination therapies remain the drugs of choice for resistant P. falciparum malaria. However, resistance to ART-based drugs has begun to appear in some parts of the world. Endoperoxide compounds (natural/semisynthetic/synthetic) representing a huge number of antimalarial agents possess a wide structural diversity with a desired antimalarial effectiveness against resistant P...
2016: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/27842555/low-prevalence-of-laboratory-confirmed-malaria-in-clinically-diagnosed-adult-women-from-the-wakiso-district-of-uganda
#19
Sergey Yegorov, Ronald M Galiwango, Aloysious Ssemaganda, Moses Muwanga, Irene Wesonga, George Miiro, David A Drajole, Kevin C Kain, Noah Kiwanuka, Bernard S Bagaya, Rupert Kaul
BACKGROUND: The malaria burden in sub-Saharan Africa (SSA) has fallen substantially. Nevertheless, malaria remains a serious health concern, and Uganda ranks third in SSA in total malaria burden. Epidemiological studies of adult malaria in Uganda are scarce and little is known about rates of malaria in non-pregnant adult women. This pilot study assessed malaria prevalence among adult women from Wakiso district, historically a highly malaria endemic region. METHODS: Adult women using public health services were screened for malaria, HIV and pregnancy...
November 14, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27825738/the-gametocytocidal-efficacy-of-different-single-doses-of-primaquine-with-dihydroartemisinin-piperaquine-in-asymptomatic-parasite-carriers-in-the-gambia-a-randomized-controlled-trial
#20
Joseph Okebe, Teun Bousema, Muna Affara, Gian Luca Di Tanna, Edgard Dabira, Abdoulaye Gaye, Frank Sanya-Isijola, Henry Badji, Simon Correa, Davis Nwakanma, Jean-Pierre Van Geertruyden, Chris Drakeley, Umberto D'Alessandro
BACKGROUND: Asymptomatic low-density gametocyte carriers represent the majority of malaria-infected individuals. However, the impact of recommended treatment with single low dose of primaquine and an artemisinin-based combination therapy to reduce transmission in this group is unknown. METHODS: This was a four-arm, open label, randomized controlled trial comparing the effect of dihydroartemisinin-piperaquine (DHAP) alone or combined with single dose of primaquine (PQ) at 0...
October 23, 2016: EBioMedicine
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