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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
Dieudonné Tshitenge Tshitenge, Doris Feineis, Virima Mudogo, Marcel Kaiser, Reto Brun, Ean-Jeong Seo, Thomas Efferth, Gerhard Bringmann
Four new dimeric naphthylisoquinoline alkaloids, michellamine A5 (2) and mbandakamines C-E (4-6), were isolated from the Congolese plant Ancistrocladus ealaensis, along with the known dimer mbandakamine A (3). They represent constitutionally unsymmetric dimers, each consisting of two 5,8'-coupled naphthylisoquinoline monomers. While the molecular halves of michellamine A5 (2) are linked via C-6' of both of the naphthalene moieties, i.e., via the least-hindered positions, so that the central biaryl axis is configurationally unstable and not an additional element of chirality, the mbandakamines 3-6 possess three consecutive stereogenic axes...
March 21, 2018: Journal of Natural Products
Richard Bwanika, Charles D Kato, Johnson Welishe, Daniel C Mwandah
Background: Malaria and helminths share the same geographical distribution in tropical Africa. Studies of the interaction of helminth and malaria co-infection in humans have been few and are mainly epidemiological, with little information on cellular immune responses. This study aimed to determine Cytokine profiles among patients co-infected with Plasmodium falciparum malaria and soil borne helminth attending Kampala International University Teaching Hospital (KIU). Methods: A case control study of 240 patients were recruited at KIU teaching hospital...
2018: Allergy, Asthma, and Clinical Immunology
Marilia N N Lima, Cleber C Melo-Filho, Gustavo C Cassiano, Bruno J Neves, Vinicius M Alves, Rodolpho C Braga, Pedro V L Cravo, Eugene N Muratov, Juliana Calit, Daniel Y Bargieri, Fabio T M Costa, Carolina H Andrade
Malaria is a life-threatening infectious disease caused by parasites of the genus Plasmodium , affecting more than 200 million people worldwide every year and leading to about a half million deaths. Malaria parasites of humans have evolved resistance to all current antimalarial drugs, urging for the discovery of new effective compounds. Given that the inhibition of deoxyuridine triphosphatase of Plasmodium falciparum ( Pf dUTPase) induces wrong insertions in plasmodial DNA and consequently leading the parasite to death, this enzyme is considered an attractive antimalarial drug target...
2018: Frontiers in Pharmacology
Opute M Yvette, Sarel F Malan, Dale Taylor, Erika Kapp, Jacques Joubert
Previously we have shown that pentacycloundecylamine-chloroquinoline (PCU-CQ) conjugates possess significant chemosensitizing abilities and can circumvent the resistance associated with chloroquine (CQ) resistant plasmodia. In order to further explore structurally related polycyclic compounds as reversed CQ agents we synthesized a series of eight aza-adamantanol (1-4) and adamantane-imine (5-8) CQ conjugates. All conjugates showed limited cytotoxicity against CHO cells (IC50  > 37 µM). Compounds 1, 2 and 5 were highly active (K1 IC50  < 100 nM) exhibiting a 3-4-fold increase in antiplasmodial activity against CQ resistant strain K1 compared to CQ...
March 12, 2018: Bioorganic & Medicinal Chemistry Letters
Anne C G Almeida, Andrea Kuehn, Arthur J M Castro, Sheila Vitor-Silva, Erick F G Figueiredo, Larissa W Brasil, Marcelo A M Brito, Vanderson S Sampaio, Quique Bassat, Ingrid Felger, Wanderli P Tadei, Wuelton M Monteiro, Ivo Mueller, Marcus V G Lacerda
BACKGROUND: Population-based studies conducted in Latin America have shown a high proportion of asymptomatic and submicroscopic malarial infections. Considering efforts aiming at regional elimination, it is important to investigate the role of this asymptomatic reservoir in malaria transmission in peri-urban areas. This study aimed to estimate the prevalence of Plasmodium spp. and gametocyte burden on symptomatic and asymptomatic infections in the Brazilian Amazon. RESULTS: Two cross-sectional household surveys (CS) were conducted including all inhabitants in a peri-urban area of Manaus, western Amazonas State, Brazil...
March 20, 2018: Parasites & Vectors
Ottavia Romoli, Mathilde Gendrin
The microbiota of Anopheles mosquitoes interferes with mosquito infection by Plasmodium and influences mosquito fitness, therefore affecting vectorial capacity. This natural barrier to malaria transmission has been regarded with growing interest in the last 20 years, as it may be a source of new transmission-blocking strategies. The last decade has seen tremendous progress in the functional characterisation of the tripartite interactions between the mosquito, its microbiota and Plasmodium parasites. In this review, we provide insights into the effects of the mosquito microbiota on Plasmodium infection and on mosquito physiology, and on how these aspects together influence vectorial capacity...
March 20, 2018: Parasites & Vectors
Shehu S Awandu, Jaishree Raman, Takalani I Makhanthisa, Philip Kruger, John Frean, Teun Bousema, Jandeli Niemand, Lyn-Marie Birkholtz
BACKGROUND: Primaquine (PQ) is recommended as an addition to standard malaria treatments in pre-elimination settings due to its pronounced activity against mature Plasmodium falciparum gametocytes, the parasite stage responsible for onward transmission to mosquitoes. However, PQ may trigger haemolysis in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals. Additional human genetic factors, including polymorphisms in the human cytochrome P450 2D6 (CYP2D6) complex, may negatively influence the efficacy of PQ...
March 20, 2018: Malaria Journal
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
Christine F Markwalter, Lauren E Gibson, Lwiindi Mudenda, Danielle W Kimmel, Saidon Mbambara, Philip E Thuma, David W Wright
A rapid, on-bead ELISA for Plasmodium lactate dehydrogenase ( p LDH) and Plasmodium falciparum histidine-rich protein 2 (HRP2) was adapted for use with dried blood spot (DBS) samples. This assay detected both biomarkers from a single DBS sample with only 45 minutes of total incubation time and detection limits of 600 ± 500 pM ( p LDH) and 69 ± 30 pM (HRP2), corresponding to 150 and 24 parasites/μL, respectively. This sensitive and reproducible on-bead detection method was used to quantify p LDH and HRP2 in patient DBS samples from rural Zambia collected at multiple time points after treatment...
March 19, 2018: American Journal of Tropical Medicine and Hygiene
Nigani Willie, Rajeev K Mehlotra, Rosalind E Howes, Tovonahary A Rakotomanga, Stephanie Ramboarina, Arsène C Ratsimbasoa, Peter A Zimmerman
Plasmodium falciparum histidine-rich protein 2 (PfHRP2) forms the basis of many current malaria rapid diagnostic tests (RDTs). However, the parasites lacking part or all of the pfhrp2 gene do not express the PfHRP2 protein and are, therefore, not identifiable by PfHRP2-detecting RDTs. We evaluated the performance of the SD Bioline Malaria Ag P.f/Pan RDT together with pfhrp2 variation in Madagascar. Genomic DNA isolated from 260 patient blood samples were polymerase chain reaction (PCR)-amplified for the parasite 18S rRNA and pfhrp2 genes...
March 19, 2018: American Journal of Tropical Medicine and Hygiene
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
Luciana Pereira de Sousa, Roberto Farina de Almeida, Flávia Lima Ribeiro-Gomes, Leonardo José de Moura Carvalho, Tadeu Mello E Souza, Diogo Onofre Gomes de Souza, Cláudio Tadeu Daniel-Ribeiro
BACKGROUND: Cerebral malaria, the main complication of Plasmodium falciparum infection in humans, is associated with persistent neurocognitive sequels both in human disease and the murine experimental model. In recent years, cognitive deficits related to uncomplicated (non-cerebral) malaria have also been reported in chronically exposed residents of endemic areas, but not in some murine experimental models of non-cerebral malaria. This study aimed at evaluating the influence of uncomplicated malaria on different behavioural paradigms associated with memory and anxiety-like parameters in a murine model that has the ability to develop cerebral malaria...
March 20, 2018: Parasites & Vectors
Melanie Bannister-Tyrrell, Nguyen Xuan Xa, Johanna Helena Kattenberg, Nguyen Van Van, Vu Khac Anh Dung, Truong Minh Hieu, Nguyen Van Hong, Eduard Rovira-Vallbona, Nguyen Thanh Thao, Tran Thanh Duong, Anna Rosanas-Urgell, Koen Peeters Grietens, Annette Erhart
BACKGROUND: In Vietnam, malaria persists in remote forested regions where infections are spatially heterogeneous, mostly asymptomatic and with low parasite density. Previous studies in Vietnam have investigated broad behavioural concepts such as 'engaging in forest activities' as risk factors for malaria infection, which may not explain heterogeneity in malaria risk, especially in malaria elimination settings. METHODS: A mixed methods study combining ethnographic research and a cross-sectional survey was embedded in a 1-year malariometric cohort study in three ethnic minority villages in South Tra My district, Quang Nam Province in Central Vietnam...
March 19, 2018: Malaria Journal
Yair Fastman, Shany Assaraf, Miriam Rose, Elad Milrot, Katherine Basore, B Sivanandam Arasu, Sanjay A Desai, Michael Elbaum, Ron Dzikowski
Plasmodium falciparum, the causative agent of the deadliest form of human malaria, alternates expression of variable antigens, encoded by members of a multi-copy gene family named var. In var2csa, the var gene implicated in pregnancy-associated malaria, translational repression is regulated by a unique upstream open reading frame (uORF) found only in its 5' UTR. Here, we report that this translated uORF significantly alters both transcription and posttranslational protein trafficking. The parasite can alter a protein's destination without any modifications to the protein itself, but instead by an element within the 5' UTR of the transcript...
March 15, 2018: Nucleic Acids Research
Seda Yerlikaya, Ana Campillo, Iveth J Gonzalez
Despite the increased use and worldwide distribution of malaria rapid diagnostic tests (RDTs) which distinguish between Plasmodium falciparum and non-falciparum species, little is known about their performance for detecting Plasmodium knowlesi (Pk), Plasmodium malariae (Pm), and Plasmodium ovale (Po). The objective of this review is to analyze results of published studies evaluating the diagnostic accuracy of malaria RDTs in detecting Pk, Pm and Po mono-infections.MEDLINE, EMBASE, Web of Science and CENTRAL databases were systematically searched to identify studies which reported on the performance of RDTs in detecting Pk, Pm,Po mono-infections...
March 15, 2018: Journal of Infectious Diseases
Joshua Tan, Brandon K Sack, David Oyen, Isabelle Zenklusen, Luca Piccoli, Sonia Barbieri, Mathilde Foglierini, Chiara Silacci Fregni, Jessica Marcandalli, Said Jongo, Salim Abdulla, Laurent Perez, Giampietro Corradin, Luca Varani, Federica Sallusto, Betty Kim Lee Sim, Stephen L Hoffman, Stefan H I Kappe, Claudia Daubenberger, Ian A Wilson, Antonio Lanzavecchia
Immunization with attenuated Plasmodium falciparum sporozoites (PfSPZs) has been shown to be protective against malaria, but the features of the antibody response induced by this treatment remain unclear. To investigate this response in detail, we isolated IgM and IgG monoclonal antibodies from Tanzanian volunteers who were immunized with repeated injection of Sanaria PfSPZ Vaccine and who were found to be protected from controlled human malaria infection with infectious homologous PfSPZs. All isolated IgG monoclonal antibodies bound to P...
March 19, 2018: Nature Medicine
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
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