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severe malaria

Claire M Keene, Arjen Dondorp, Jane Crawley, Eric O Ohuma, Mavuto Mukaka
Background: Malaria burdens global health systems, and management with limited resources requires robust treatment guidelines and comprehensive planning. Expected length of stay (LOS) is useful in health-system planning, and factors influencing it can be targeted to reduce admission time and optimise service delivery. Methods: A secondary survival analysis of 1217 adult severe malaria patients from the South-East Asia Quinine Artesunate Malaria Trial, using a competing-risk approach...
March 19, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
K Szewczyk-Golec, R Wesołowski, I Hołyńska-Iwan
Malaria belongs to the most dangerous infectious diseases globally. Every effort to understand the mechanisms involved in Plasmodium spp. malaria infection and the antimalarial action cannot be overestimated. We have read with great interest the recently published article by Muhammad et al. entitled "Alteration of redox status by commonly used antimalarial drugs in the north-western region of Nigeria." Several questions have arisen about the conducted study that we would like to comment on.
January 1, 2018: Human & Experimental Toxicology
Maëlle Duffey, Cecilia P Sanchez, Michael Lanzer
BACKGROUND: The increased resistance of the human malaria parasite Plasmodium falciparum to currently employed drugs creates an urgent call for novel anti-malarial drugs. Particularly, efforts should be devoted to developing fast-acting anti-malarial compounds in case clinical resistance increases to the first-line artemisinin-based combination therapy. SC83288, an amicarbalide derivative, is a clinical development candidate for the treatment of severe malaria. SC83288 is fast-acting and able to clear P...
March 20, 2018: Malaria Journal
Hargobinder Kaur, Rakesh Sehgal, Devendra Bansal, Ali A Sultan, Ashish Bhalla, Sunit C Singhi
More than 80% of the global burden of the Plasmodium vivax is contributed by mainly three countries (India, Indonesia, and Pakistan). Reports from last decades have highlighted the occurrence of severe P. vivax malaria which was earlier considered to be benign. The recent trends of increasing P. vivax -associated morbidity and mortality emphasizes the need for early and accurate diagnosis of P. vivax malaria for the timely management of patients. Microscopy is considered a gold standard but needs experienced laboratory technologists...
March 19, 2018: American Journal of Tropical Medicine and Hygiene
Annemieke Abel, Christiane Steeg, Francis Aminkiah, Otchere Addai-Mensah, Marylyn Addo, Nicola Gagliani, Christian Casar, Denis Dekugmen Yar, Ellis Owusu-Dabo, Thomas Jacobs, Maria Sophia Mackroth
The immune response of malaria patients is a main factor influencing the clinical severity of malaria. A tight regulation of the CD4+ T cell response or the induction of tolerance have been proposed to contribute to protection from severe or clinical disease. We therefore compared the CD4+ T cell phenotypes of Ghanaian children with complicated malaria, uncomplicated malaria, asymptomatic Plasmodium falciparum (Pf) infection or no infection. Using flow cytometric analysis and automated multivariate clustering, we characterized the expression of the co-inhibitory molecules CTLA-4, PD-1, Tim-3, and LAG-3 and other molecules implicated in regulatory function on CD4+ T cells...
March 19, 2018: Scientific Reports
Adelaide S M Dennis, Adele M Lehane, Melanie C Ridgway, John P Holleran, Kiaran Kirk
For an increasing number of antimalarial agents identified in high throughput phenotypic screens there is evidence that they target PfATP4, a putative Na+ efflux transporter on the plasma membrane of the human malaria parasite, Plasmodium falciparum For several such 'PfATP4-associated' compounds it has been noted that their addition to parasitised erythrocytes results in cell swelling. Here we show that six structurally diverse PfATP4-associated compounds, including the clinical candidate KAE609 (cipargamin), induce swelling both of isolated blood-stage parasites and of intact parasitised erythrocytes...
March 19, 2018: Antimicrobial Agents and Chemotherapy
Neville K Kisalu, Azza H Idris, Connor Weidle, Yevel Flores-Garcia, Barbara J Flynn, Brandon K Sack, Sean Murphy, Arne Scho N, Ernesto Freire, Joseph R Francica, Alex B Miller, Jason Gregory, Sandra March, Hua-Xin Liao, Barton F Haynes, Kevin Wiehe, Ashley M Trama, Kevin O Saunders, Morgan A Gladden, Anthony Monroe, Mattia Bonsignori, Masaru Kanekiyo, Adam K Wheatley, Adrian B McDermott, S Katie Farney, Gwo-Yu Chuang, Baoshan Zhang, Natasha Kc, Sumana Chakravarty, Peter D Kwong, Photini Sinnis, Sangeeta N Bhatia, Stefan H I Kappe, B Kim Lee Sim, Stephen L Hoffman, Fidel Zavala, Marie Pancera, Robert A Seder
Development of a highly effective vaccine or antibodies for the prevention and ultimately elimination of malaria is urgently needed. Here we report the isolation of a number of human monoclonal antibodies directed against the Plasmodium falciparum (Pf) circumsporozoite protein (PfCSP) from several subjects immunized with an attenuated Pf whole-sporozoite (SPZ) vaccine (Sanaria PfSPZ Vaccine). Passive transfer of one of these antibodies, monoclonal antibody CIS43, conferred high-level, sterile protection in two different mouse models of malaria infection...
March 19, 2018: Nature Medicine
María Andrea Hernández-Castañeda, Smart Mbagwu, Kehinde Adebayo Babatunde, Michael Walch, Luis Filgueira, Pierre-Yves Mantel
Malaria is a life-threatening disease caused by Plasmodium parasites, with P. falciparum being the most prevalent on the African continent and responsible for most malaria-related deaths globally. Several factors including parasite sequestration in tissues, vascular dysfunction, and inflammatory responses influence the evolution of the disease in malaria-infected people. P. falciparum-infected red blood cells (iRBCs) release small extracellular vesicles (EVs) containing different kinds of cargo molecules that mediate pathogenesis and cellular communication between parasites and host...
February 14, 2018: Journal of Visualized Experiments: JoVE
Laurence Thielemans, Gornpan Gornsawun, Borimas Hanboonkunupakarn, Moo Kho Paw, Pen Porn, Paw Khu Moo, Bart Van Overmeire, Stephane Proux, François Nosten, Rose McGready, Verena I Carrara, Germana Bancone
Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an inherited enzymatic disorder associated with severe neonatal hyperbilirubinemia and acute haemolysis after exposure to certain drugs or infections. The disorder can be diagnosed phenotypically with a fluorescent spot test (FST), which is a simple test that requires training and basic laboratory equipment. This study aimed to assess the diagnostic performances of the FST used on umbilical cord blood by locally-trained staff and to compare test results of the neonates at birth with the results after one month of age...
2018: Wellcome Open Research
Babak Ebrahimi, Bryan T Jackson, Julie L Guseman, Colin M Przybylowicz, Christopher M Stone, Woodbridge A Foster
Knowledge of the link between a vector population's pathogen-transmission potential and its biotic environment can generate more realistic forecasts of disease risk due to environmental change. It also can promote more effective vector control by both conventional and novel means.This study assessed the effect of particular plant species assemblages differing in nectar production on components of the vectorial capacity of the mosquito Anopheles gambiae s.s. , an important vector of African malaria.We followed cohorts of mosquitoes for three weeks in greenhouse mesocosms holding nectar-poor and nectar-rich plant species by tracking daily mortalities and estimating daily biting rates and fecundities...
March 2018: Journal of Applied Ecology
Valeria Messina, Mauro Valtieri, Mercedes Rubio, Mario Falchi, Francesca Mancini, Alfredo Mayor, Pietro Alano, Francesco Silvestrini
The gametocytes of Plasmodium falciparum , responsible for the transmission of this malaria parasite from humans to mosquitoes, accumulate and mature preferentially in the human bone marrow. In the 10 day long sexual development of P. falciparum , the immature gametocytes reach and localize in the extravascular compartment of this organ, in contact with several bone marrow stroma cell types, prior to traversing the endothelial lining and re-entering in circulation at maturity. To investigate the host parasite interplay underlying this still obscure process, we developed an in vitro tridimensional co-culture system in a Matrigel scaffold with P...
2018: Frontiers in Cellular and Infection Microbiology
Soyoung Park, Ah-Young Oh, Jung-Hyun Cho, Min-Ho Yoon, Tae-Guen Woo, Somi Kang, Ho-Young Lee, Yunjin Jung, Bum-Joon Park
Quinacrine (QNC), anti-protozoan drug commonly used against Malaria and Giardiasis, has been recently tried for rheumatics and prion diseases via drug repositioning. In addition, several reports suggest anti-tumor effects of QNC through suppression of NF-κB and activation of p53. This study, demonstrates the anti-cancer effect of QNC via a novel pathway through the elimination of check point kinase 1/2 (Chk1/2) under p53 inactivated conditions. Inhibition of p53, by PFT-α or siRNA, promotes QNC-induced apoptosis in normal fibroblast and p53-intact cancer cells...
March 15, 2018: Molecular Cancer Research: MCR
Katherine Plewes, Hugh W F Kingston, Aniruddha Ghose, Thanaporn Wattanakul, Md Mahtab Uddin Hassan, Md Shafiul Haider, Prodip K Dutta, Md Akhterul Islam, Shamsul Alam, Selim Md Jahangir, A S M Zahed, Md Abdus Sattar, M A Hassan Chowdhury, M Trent Herdman, Stije J Leopold, Haruhiko Ishioka, Kim A Piera, Prakaykaew Charunwatthana, Kamolrat Silamut, Tsin W Yeo, Sue J Lee, Mavuto Mukaka, Richard J Maude, Gareth D H Turner, Md Abul Faiz, Joel Tarning, John A Oates, Nicholas M Anstey, Nicholas J White, Nicholas P J Day, Md Amir Hossain, L Jackson Roberts, Arjen M Dondorp
Background: Acute kidney injury independently predicts mortality in falciparum malaria. It is not known whether acetaminophen's capacity to inhibit plasma hemoglobin-mediated oxidation is renoprotective in severe malaria. Methods: A phase 2, open-label, randomized controlled trial at two hospitals in Bangladesh was conducted to assess effects on renal function, safety, pharmacokinetic properties and pharmacodynamic effects of acetaminophen. Febrile patients ( >12 years) with severe and moderately severe falciparum malaria were randomly assigned to receive acetaminophen (1g 6-hourly for 72 hours) or no acetaminophen, as an adjunct to intravenous artesunate...
March 12, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Ishag Adam, Yassin Ibrahim, Gasim I Gasim
BACKGROUND: Malaria is a major public health problem in endemic countries including Sudan, where about 75% of populations are at risk. Due to widespread of chloroquine-resistant strains of Plasmodium falciparum, artemisinin-based combination therapy (ACT) is currently treatment of choice for malaria in the vast majority of malaria-endemic countries. This systematic review and meta-analysis is performed to obtain an overall stronger evidence of the outcomes of ACT in the treatment of uncomplicated falciparum malaria from the existing literature in Sudan...
March 13, 2018: Malaria Journal
Bin Yang, Jingxia Huang, Xuefeng Zhou, Xiuping Lin, Juan Liu, Shengrong Liao, Junfeng Wang, Feng-An Liu, Huaming Tao, Yonghong Liu
Malaria caused by Plasmodium parasites is amongst many prevalent public health concerns in several tropical regions of the world. Nowadays, the parasite resistance patterns to most currently used drugs in therapy and insecticides have created an urgent need for new chemical entities exhibiting new modes of action and management strategies. Fungus have been proven to be excellent sources of biologically active compounds, which have been screened for antiplasmodial activity as potential sources of new antimalarial drugs...
March 12, 2018: Current Medicinal Chemistry
Yasmin A Williams, Lucy S Tusting, Sophia Hocini, Patricia M Graves, Gerry F Killeen, Immo Kleinschmidt, Fredros O Okumu, Richard G A Feachem, Allison Tatarsky, Roly D Gosling
BACKGROUND: Additional vector control tools (VCTs) are needed to supplement insecticide-treated nets (ITNs) and indoor residual spraying (IRS) to achieve malaria elimination in many settings. To identify options for expanding the malaria vector control toolbox, we conducted a systematic review of the availability and quality of the evidence for 21 malaria VCTs, excluding ITNs and IRS. METHODS: Six electronic databases and grey literature sources were searched from January 1, 1980 to September 28, 2015 to identify systematic reviews, Phase I-IV studies, and observational studies that measured the effect of malaria VCTs on epidemiological or entomological outcomes across any age groups in all malaria-endemic settings...
2018: Advances in Parasitology
Gerry Q Tonkin-Hill, Leily Trianty, Rintis Noviyanti, Hanh H T Nguyen, Boni F Sebayang, Daniel A Lampah, Jutta Marfurt, Simon A Cobbold, Janavi S Rambhatla, Malcolm J McConville, Stephen J Rogerson, Graham V Brown, Karen P Day, Ric N Price, Nicholas M Anstey, Anthony T Papenfuss, Michael F Duffy
Within the human host, the malaria parasite Plasmodium falciparum is exposed to multiple selection pressures. The host environment changes dramatically in severe malaria, but the extent to which the parasite responds to-or is selected by-this environment remains unclear. From previous studies, the parasites that cause severe malaria appear to increase expression of a restricted but poorly defined subset of the PfEMP1 variant, surface antigens. PfEMP1s are major targets of protective immunity. Here, we used RNA sequencing (RNAseq) to analyse gene expression in 44 parasite isolates that caused severe and uncomplicated malaria in Papuan patients...
March 12, 2018: PLoS Biology
Bouchra Trari, Mohamed Dakki
The Anopheles maculipennis complex has been implicated in the transmission of malaria, which was endemic in Morocco until 2010. Climate change, intensification of international travel and the permanent presence of the vector increase the risk of malaria re-emergence. Using polymerase chain reaction assay (PCR), this study attempts to identify the possible presence of the Maculipennis complex in several areas of Morocco, based on the concept of risk. Eighty-six mosquito specimens were analyzed using PCR amplification of the ITS2 (Internal Transcribed Spacer 2) sequence of ribosomal DNA...
March 5, 2018: Eastern Mediterranean Health Journal, la Revue de Santé de la Méditerranée Orientale
Cheryl L Maier, Phillip J Gross, Christina L Dean, Satheesh Chonat, Andrew Ip, Morgan McLemore, Fuad El Rassi, Sean R Stowell, Cassandra D Josephson, Ross M Fasano
BACKGROUND: Fever accompanying vaso-occlusive crisis is a common presentation in patients with sickle cell disease (SCD) and carries a broad differential diagnosis. Here, we report a case of transfusion-transmitted malaria in a patient with SCD presenting with acute vaso-occlusive crisis and rapidly decompensating to multisystem organ failure (MSOF). CASE REPORT: An 18-year-old African American male with SCD was admitted after multiple days of fever and severe generalized body pain...
March 9, 2018: Transfusion
Michael J Boivin, Noeline Nakasujja, Alla Sikorskii, Horacio Ruiseñor-Escudero, Itziar Familiar-Lopez, Kimberley Walhof, Esther M van der Lugt, Robert O Opoka, Bruno Giordani
BACKGROUND: Computerized cognitive rehabilitation training (CCRT) may be beneficial for alleviating persisting neurocognitive deficits in Ugandan severe malaria survivors. We completed a randomized controlled trial of CCRT for both severe malaria and non-malaria cohorts of children. METHODS: 150 school-age severe malaria and 150 non-malaria children were randomized to three treatment arms: 24 sessions of Captain's Log CCRT for attention, working memory and nonverbal reasoning, in which training on each of 9 tasks difficulty increased with proficiency; a limited CCRT arm that did not titrate to proficiency but randomly cycled across the simplest to moderate level of training; and a passive control arm...
March 6, 2018: Brain Research Bulletin
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