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P. falciparum

P Chellapandi, R Prathiviraj, A Prisilla
Malaria, caused by Plasmodium falciparum, continues to be one of the leading parasitic diseases to humans. It is urgent to discover novel targets for the development of antimalarial drugs. The 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase (IspD) in 2-C-methyl-D-erythritol-4-phosphate pathway has been considered as a second in vivo off-target to discover novel antimalarial drugs for its essentiality in malarial parasites and devoid in mammals. Our aim is to rationalize the basis of its functional parts by studying molecular diversity, origin and evolution across malarial parasites...
August 14, 2018: Infection, Genetics and Evolution
Erin V McConnell, Igor Bruzual, Sovitj Pou, Rolf W Winter, Rozalia A Dodean, Martin J Smilkstein, Alina Krollenbrock, Aaron Nilsen, Lev N Zakharov, Michael K Riscoe, J Stone Doggett
Cytochrome bc1 inhibitors have been broadly studied as human and veterinary medicines, and agricultural fungicides. For the most part, cytochrome bc1 inhibitors compete with ubiquinol at the ubiquinol oxidation (Qo) site or with ubiquinone at the quinone reduction (Qi ) site. 4(1H)-quinolones with 3-position substituents may inhibit either site based on quinolone ring substituents. 4(1 H)-quinolones that inhibit the Qi site are highly effective against toxoplasmosis, malaria and babesiosis and do not inhibit human cytochrome bc1 ...
August 17, 2018: ACS Infectious Diseases
Kennedy Makola Mbanzulu, Josué Kikana Zanga, Jean Pierre Kambala Mukendi, Felly Mbaya Ntita, Junior Rika Matangila, Hypolite Mavoko Muhindo, Sylvain Mpoyi Wa Mpoyi, Michel Ntetani Aloni, Roger Wumba
Background: Malaria and schistosomiasis remain life-threatening public health problems in sub-Saharan Africa. The infection pattern related to age indicates that preschool and school-age children are at the highest risk of malaria and schistosomiasis. Both parasitic infections, separately or combined, may have negative impacts on the haemoglobin concentration levels. The existing data revealed that artemisinin derivatives commonly used to cure malaria present also in antischistosomal activities...
2018: BioMed Research International
Heloisa B Gabriel, Mauro F Azevedo, Emília A Kimura, Alejandro M Katzin
Farnesyl diphosphate synthase/geranylgeranyl diphosphate synthase (FPPS/GGPPS) is a key enzyme in the synthesis of isoprenic chains. Risedronate, a bisphosphonate containing nitrogen (N-BP), is a potent inhibitor of blood stage Plasmodium. Here, we show that P. falciparum parasites overexpressing FPPS/GGPPS are more resistant to risedronate, suggesting that this enzyme is an important target, and bisphosphonate analogues can be used as potential antimalarial drugs.
2018: Memórias do Instituto Oswaldo Cruz
Yitayih Wondimeneh, Teklay Gebrecherkos, Dagnachew Muluye, Demekech Damtie, Getachew Ferede
OBJECTIVE: Malaria and human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) are the major medical challenges of priority faced by the sub-Saharan African countries in general and Ethiopia in particular. Thus, the aim of this study was to determine the prevalence and associated risk factors of HIV and malaria infections among febrile illness patients. METHODS: A cross-sectional study was conducted from November 1, 2014 to May 30, 2015 at Kolla-Diba Health Center, Northwest Ethiopia...
August 15, 2018: Türkiye Parazitolojii Dergisi
Amarjeet Kumar, Suman Kumar Dhar, Naidu Subbarao
In erythrocytes, actively multiplying Plasmodium falciparum parasites exhibit a unique signature of virulence associated histone modifications, thereby epigenetically regulating the expression of the majority of genes. Histone acetylation is one such modification, effectuated and maintained by the dynamic interplay of two functionally antagonist enzymes, histone acetyltransferases (HATs) and histone deacetylases (HDACs). Their inhibition leads to hypo/hyperacetylation and is known to be deleterious for P. falciparum, and hence they have become attractive molecular targets to design novel antimalarials...
August 14, 2018: Journal of Molecular Modeling
Kartikey Singh, Prince Joshi, Rohit Mahar, Pragati Baranwal, Sanjeev K Shukla, Renu Tripathi, Rama Pati Tripathi
A series of homologous C -nucleoside mimics have been synthesized via an efficient and facile synthetic protocol involving the conjugate addition of purine to sugar derived olefinic ester in good yields. The synthesized compounds were evaluated for their antiplasmodial activity in vitro against both the CQ-sensitive and resistant strains of P. falciparum . Interestingly, all the synthesized nucleoside analogs exhibited an IC50 of <5 μM, while compounds 22a , 23a , and 23b showed promising antiplasmodial activity with an IC50 of 1...
July 1, 2018: MedChemComm
Johanna M Roth, Patrick Sawa, George Omweri, Nicodemus Makio, Victor Osoti, Menno D de Jong, Henk D F H Schallig, Pètra F Mens
Artemisinin resistance is rapidly rising in Southeast Asia and may spread to African countries, where efficacy estimates are currently still excellent. Extensive monitoring of parasite clearance dynamics after treatment is needed to determine whether responsiveness to artemisinin-based combination therapies (ACT) is changing in Africa. In this study, Kenyan children with uncomplicated falciparum malaria were randomly assigned to pyronaridine-artesunate (PA) or artemether-lumefantrine (AL) treatment. Parasite clearance was evaluated over 7 days following the start of treatment by qPCR and direct-on-blood PCR nucleic acid lateral flow immunoassay (db-PCR-NALFIA), a simplified molecular malaria diagnostic...
August 13, 2018: American Journal of Tropical Medicine and Hygiene
Manickam Yogavel, Joanne E Nettleship, Akansha Sharma, Karl Harlos, Abhishek Jamwal, Rini Chaturvedi, Manmohan Sharma, Vitul Jain, Jyoti Chhibber-Goel, Amit Sharma
The genomes of the malaria-causing Plasmodium parasites encode a protein fused of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) and dihydropteroate synthase (DHPS) domains that catalyze sequential reactions in the folate biosynthetic pathway. Whereas higher organisms derive folate from their diet and lack the enzymes for its synthesis, most eubacteria and a number of lower eukaryotes including malaria parasites synthesize tetrahydrofolate via DHPS. Plasmodium falciparum ( Pf ) and Plasmodium vivax ( Pv ) HPPK-DHPSs are currently targets of drugs like sulfadoxine (SDX)...
August 13, 2018: Journal of Biological Chemistry
Alfred B Tiono, Alphonse Ouédraogo, Daouda Ouattara, Edith C Bougouma, Sam Coulibaly, Amidou Diarra, Brian Faragher, Moussa W Guelbeogo, Nelson Grisales, Issa N Ouédraogo, Zininwindé Amidou Ouédraogo, Margaret Pinder, Souleymane Sanon, Tom Smith, Fiona Vanobberghen, N'Fale Sagnon, Hilary Ranson, Steve W Lindsay
BACKGROUND: Substantial reductions in malaria incidence in sub-Saharan Africa have been achieved with massive deployment of long-lasting insecticidal nets (LLINs), but pyrethroid resistance threatens control. Burkina Faso is an area with intense malaria transmission and highly pyrethroid-resistant vectors. We assessed the effectiveness of bednets containing permethrin, a pyrethroid, and pyriproxyfen, an insect growth regulator, versus permethrin-only (standard) LLINs against clinical malaria in children younger than 5 years in Banfora, Burkina Faso...
August 10, 2018: Lancet
Pichamon Sittikul, Napat Songtawee, Ngampong Kongkathip, Nonlawat Boonyalai
Plasmodium proteases play both regulatory and effector roles in essential biological processes in this important pathogen and have long been investigated as drug targets. Plasmepsin V from P. falciparum (PfPMV) is an essential protease that processes proteins for export into the host erythrocyte and is a focus of ongoing drug development efforts. In the present study, recombinant protein production, inhibition assays, binding studies as well as molecular docking and molecular dynamics simulation studies were used to investigate the mode of binding of a PEXEL-based peptidomimetic and naphthoquinone compounds to PfPMV...
September 2018: Biochimie
Kolapo Muyiwa Oyebola, Oluwagbemiga Olanrewaju Aina, Emmanuel Taiwo Idowu, Yetunde Adeola Olukosi, Olusola Sunday Ajibaye, Olubunmi Adetoro Otubanjo, Taiwo Samson Awolola, Gordon Akanzuwine Awandare, Alfred Amambua-Ngwa
BACKGROUND: The decline in the efficacy of artemisinin-based combination treatment (ACT) in some endemic regions threatens the progress towards global elimination of malaria. Molecular surveillance of drug resistance in malaria-endemic regions is vital to detect the emergence and spread of mutant strains. METHODS: We observed 89 malaria patients for the efficacy of artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum infections in Lagos, Nigeria and determined the prevalence of drug resistant strains in the population...
August 13, 2018: BMC Infectious Diseases
Mandar Patgaonkar, Fabien Herbert, Krushali Powale, Prajakta Gandhe, Nithya Gogtay, Urmila Thatte, Sylviane Pied, Shobhona Sharma, Sulabha Pathak
B cell-mediated humoral responses are essential for controlling malarial infection. Studies have addressed the effects of Plasmodium falciparum infection on peripheral B cell subsets but not much is known for P. vivax infection. Furthermore, majority of the studies investigate changes during acute infection, but not after parasite clearance. In this prospective study we analyzed peripheral B cell profiles and antibody responses during acute P. vivax infection and upon recovery (30 days post-treatment) in a low-transmission area in India...
August 13, 2018: Parasite Immunology
Arne Hillebrand, Joachim M Matz, Martin Almendinger, Katja Müller, Kai Matuschewski, Christian Schmitz-Linneweber
Gene expression in mitochondria of Plasmodium falciparum is essential for parasite survival. The molecular mechanisms of Plasmodium organellar gene expression remain poorly understood. This includes the enigmatic assembly of the mitochondrial ribosome from highly fragmented rRNAs. Here, we present the identification of clustered organellar short RNA fragments (cosRNAs) that are possible footprints of RNA-binding proteins (RBPs) in Plasmodium organelles. In plants, RBPs of the pentatricopeptide repeat (PPR) class produce footprints as a consequence of their function in processing organellar RNAs...
August 8, 2018: Nucleic Acids Research
Hadi Mirahmadi, Azam Shahrakipour, Ahmad Mehravaran, Alireza Salami Khorashad, Mansour Rahmati-Balaghaleh, Mehdi Zarean
BACKGROUND: Malaria is still a major public health problem in subtropical and tropical regions. The rapid and accurate diagnosis of malaria remains a challenge in most of the endemic areas. The primary objective of the present study was to evaluate the performance of multiplex/nested PCR in detecting Plasmodium falciparum at low parasite densities and mixed infection. METHODS: The study was performed in the Sistan-Baluchestan province of the southeastern Iran, from May 2015 to July 2016...
August 7, 2018: Infection, Genetics and Evolution
Paula C Hernández, Moisés Wasserman, Jacqueline Chaparro-Olaya
Apicomplexan parasites, including Plasmodium falciparum, are obligate intracellular organisms that utilize a strategy termed "gliding" to move and invade host cells, causing disease. Gliding is carried out by a protein complex known as the glideosome, which includes an actin-myosin motor. To date, six myosins have been identified in P. falciparum (PfMyoA, B, C, D, E, and F), but only the role of PfMyoA, the myosin of the glideosome that is involved in the process of red blood cell and mosquito cell invasion, has been established...
August 9, 2018: Parasitology Research
Catherin Marin-Mogollon, Fiona J A van Pul, Shinya Miyazaki, Takashi Imai, Jai Ramesar, Ahmed M Salman, Beatrice M F Winkel, Ahmad Syibli Othman, Hans Kroeze, Severine Chevalley-Maurel, Arturo Reyes-Sandoval, Meta Roestenberg, Blandine Franke-Fayard, Chris J Janse, Shahid M Khan
BACKGROUND: Rodent malaria parasites where the gene encoding circumsporozoite protein (CSP) has been replaced with csp genes from the human malaria parasites, Plasmodium falciparum or Plasmodium vivax, are used as pre-clinical tools to evaluate CSP vaccines in vivo. These chimeric rodent parasites produce sporozoites in Anopheles stephensi mosquitoes that are capable of infecting rodent and human hepatocytes. The availability of chimeric P. falciparum parasites where the pfcsp gene has been replaced by the pvcsp would open up possibilities to test P...
August 9, 2018: Malaria Journal
Amir Alelign, Zinaye Tekeste, Beyene Petros
BACKGROUND: Data on trends in malaria prevalence is significant to assist efforts in the control and prevention of the disease. This retrospective study was, therefore, aimed to determine the prevalence of malaria in Woreta town, northwestern Ethiopia over 8 years. METHODS: A retrospective study was conducted in Woreta town, northwestern Ethiopia, from November to January 2013. Eight years (2005 to 2012) health center record of malaria cases was reviewed. Odds ratio (OR) was used to determine trend in malaria prevalence with respect to age, sex and Plasmodium species...
August 8, 2018: BMC Public Health
Anna E van Beek, Isatou Sarr, Simon Correa, Davis Nwakanma, Mieke C Brouwer, Diana Wouters, Fatou Secka, Suzanne T B Anderson, David J Conway, Michael Walther, Michael Levin, Taco W Kuijpers, Aubrey J Cunnington
Background: Plasmodium falciparum may evade complement-mediated host defense by hijacking complement Factor H (FH), a negative regulator of the alternative complement pathway. Plasma levels of FH vary between individuals and may therefore influence malaria susceptibility and severity. Methods: We measured convalescent FH plasma levels in 149 Gambian children who had recovered from uncomplicated or severe P. falciparum malaria and in 173 healthy control children...
July 2018: Open Forum Infectious Diseases
Rasha Hassan Soliman, Patricia Garcia-Aranda, Sherine Mohamed Elzagawy, Boshra El-Sayed Hussein, Wael Wahid Mayah, Alexandra Martin Ramirez, Thuy-Huong Ta-Tang, José Miguel Rubio
BACKGROUND: The Kingdom of Saudi Arabia is seeking malaria eradication. Malaria transmission has been very low over the last few years. Discovered cases of Plasmodium falciparum infection are assigned a treatment protocol of artemisinin-based combination therapy, which consists of artesunate in addition to sulfadoxine-pyrimethamine rather than the traditional chloroquine, which has high resistance rates worldwide. This study aims to investigate the presence of different gene mutations concerning anti-malarial drug resistance (pfdhfr, pfdhps, pfmdr1, pfcrt, pfcytb, pfketch13) to identify whether drug-resistant alleles are present in this area of the Kingdom and whether the country's treatment protocol is still suitable for Plasmodium bearing a resistance mutation...
August 7, 2018: Malaria Journal
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