Faculty Opinions recommendation of Drug resistance. Population transcriptomics of human malaria parasites reveals the mechanism of artemisinin resistance.

2016 ◽  
Author(s):  
Frank Seeber
Keyword(s):  
Drug Resistance ◽  
Artemisinin Resistance ◽  
Malaria Parasites ◽  
Human Malaria

scholarly journals Plasmodium Species and Drug Resistance

2021 ◽  
Author(s):  
Sintayehu Tsegaye Tseha
Keyword(s):  
Drug Resistance ◽  
Artemisinin Resistance ◽  
Plasmodium Species ◽  
Public Health Problem ◽  
Antimalarial Drugs ◽  
Chloroquine Resistance ◽  
Resistance Pattern ◽  
Malaria Parasites ◽  
Human Malaria ◽  
The World

Malaria is a leading public health problem in tropical and subtropical countries of the world. In 2019, there were an estimated 229 million malaria cases and 409, 000 deaths due malaria in the world. The objective of this chapter is to discuss about the different Plasmodium parasites that cause human malaria. In addition, the chapter discusses about antimalarial drugs resistance. Human malaria is caused by five Plasmodium species, namely P. falciparum, P. malariae, P. vivax, P. ovale and P. knowlesi. In addition to these parasites, malaria in humans may also arise from zoonotic malaria parasites, which includes P. inui and P. cynomolgi. The plasmodium life cycle involves vertebrate host and a mosquito vector. The malaria parasites differ in their epidemiology, virulence and drug resistance pattern. P. falciparum is the deadliest malaria parasite that causes human malaria. P. falciparum accounted for nearly all malarial deaths in 2018. One of the major challenges to control malaria is the emergence and spread of antimalarial drug-resistant Plasmodium parasites. The P. vivax and P. falciparum have already developed resistance against convectional antimalarial drugs such as chloroquine, sulfadoxine-pyrimethamine, and atovaquone. Chloroquine-resistance is connected with mutations in pfcr. Resistance to Sulfadoxine and pyrimethamine is associated with multiple mutations in pfdhps and pfdhfr genes. In response to the evolution of drug resistance Plasmodium parasites, artemisinin-based combination therapies (ACTs) have been used for the treatment of uncomplicated falciparum malaria since the beginning of 21th century. However, artemisinin resistant P. falciparum strains have been recently observed in different parts of the world, which indicates the possibility of the spread of artemisinin resistance to all over the world. Therefore, novel antimalarial drugs have to be searched so as to replace the ACTs if Plasmodium parasites develop resistance to ACTs in the future.

scholarly journals Replication of Plasmodium in reticulocytes can occur without hemozoin formation, resulting in chloroquine resistance

2015 ◽  
Vol 212 (6) ◽  
pp. 893-903 ◽  
Author(s):  
Jing-wen Lin ◽  
Roberta Spaccapelo ◽  
Evelin Schwarzer ◽  
Mohammed Sajid ◽  
Takeshi Annoura ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Drug Development ◽  
Antimalarial Drug ◽  
Malaria Parasite ◽  
Chloroquine Resistance ◽  
Malaria Parasites ◽  
Human Malaria ◽  
Complete Development

Most studies on malaria-parasite digestion of hemoglobin (Hb) have been performed using P. falciparum maintained in mature erythrocytes, in vitro. In this study, we examine Plasmodium Hb degradation in vivo in mice, using the parasite P. berghei, and show that it is possible to create mutant parasites lacking enzymes involved in the initial steps of Hb proteolysis. These mutants only complete development in reticulocytes and mature into both schizonts and gametocytes. Hb degradation is severely impaired and large amounts of undigested Hb remains in the reticulocyte cytoplasm and in vesicles in the parasite. The mutants produce little or no hemozoin (Hz), the detoxification by-product of Hb degradation. Further, they are resistant to chloroquine, an antimalarial drug that interferes with Hz formation, but their sensitivity to artesunate, also thought to be dependent on Hb degradation, is retained. Survival in reticulocytes with reduced or absent Hb digestion may imply a novel mechanism of drug resistance. These findings have implications for drug development against human-malaria parasites, such as P. vivax and P. ovale, which develop inside reticulocytes.

scholarly journals Population transcriptomics of human malaria parasites reveals the mechanism of artemisinin resistance

Science ◽  
2014 ◽  
Vol 347 (6220) ◽  
pp. 431-435 ◽  
Author(s):  
S. Mok ◽  
E. A. Ashley ◽  
P. E. Ferreira ◽  
L. Zhu ◽  
Z. Lin ◽  
...  
Keyword(s):  
Artemisinin Resistance ◽  
Malaria Parasites ◽  
Human Malaria

C-terminal aromatic residue of Plasmodium ferredoxin important for the interaction with ferredoxin: NADP(H) oxidoreductase: possible involvement for artemisinin resistance of human malaria parasites

2020 ◽  
Vol 168 (4) ◽  
pp. 427-434
Author(s):  
Yoko Kimata-Ariga ◽  
Asako Sakamoto ◽  
Miho Kamatani ◽  
Takashi Saitoh ◽  
Toshiharu Hase
Keyword(s):  
Electron Transfer ◽  
Artemisinin Resistance ◽  
Reducing Power ◽  
Redox System ◽  
Site Directed Mutagenesis ◽  
Structural Basis ◽  
Malaria Parasites ◽  
Aromatic Residue ◽  
Human Malaria ◽  
Protein Protein Interaction

Abstract The malaria parasite (Plasmodium sp.) contains a plastid-derived organelle called the apicoplast, which is essential for the growth of the parasite. In this organelle, a redox system comprising plant-type ferredoxin (Fd) and Fd: NADP(H) oxidoreductase (FNR) supplies reducing power for the crucial metabolic pathways. Electron transfer between Plasmodium falciparum Fd (PfFd) and FNR (PfFNR) is performed with higher affinity and specificity than those of plant Fd and FNR. We investigated the structural basis for such superior protein–protein interaction by focussing on the Plasumodium-specific regions of PfFd. Significant contribution of the C-terminal region of PfFd for the electron transfer with PfFNR was revealed by exchanging the C-terminal three residues between plant Fd and PfFd. Further site-directed mutagenesis of the PfFd C-terminal residues indicated that the presence of aromatic residue at Positions 96 and 97 contributes to the lower Km for PfFNR. Physical binding analyses using fluorescence and calorimetric measurements supported the results. A mutation from Asp to Tyr at position 97 of PfFd was recently reported to be strongly associated with P. falciparum resistance to artemisinin, the front line anti-malarial drug. Thus, the enhanced interaction of PfFd D97Y protein with PfFNR could be involved in artemisinin resistance of human malaria parasites.

scholarly journals Non-human primate and human malaria: past, present and future

2021 ◽  
Author(s):  
Spinello Antinori ◽  
Cecilia Bonazzetti ◽  
Andrea Giacomelli ◽  
Mario Corbellino ◽  
Massimo Galli ◽  
...  
Keyword(s):  
Plasmodium Knowlesi ◽  
Plasmodium Species ◽  
Molecular Techniques ◽  
Malaria Parasites ◽  
Human Malaria ◽  
Complex Interactions ◽  
Zoonotic Malaria ◽  
The Impact ◽  
Human Plasmodium ◽  
Human Primate

Abstract Background Studies of the malaria parasites infecting various non-human primates (NHPs) have increased our understanding of the origin, biology and pathogenesis of human Plasmodium parasites. This review considers the major discoveries concerning NHP malaria parasites, highlights their relationships with human malaria and considers the impact that this may have on attempts to eradicate the disease. Results The first description of NHP malaria parasites dates back to the early 20th century. Subsequently, experimental and fortuitous findings indicating that some NHP malaria parasites can be transmitted to humans have raised concerns about the possible impact of a zoonotic malaria reservoir on efforts to control human malaria. Advances in molecular techniques over the last 15 years have contributed greatly to our knowledge of the existence and geographical distribution of numerous Plasmodium species infecting NHPs, and extended our understanding of their close phylogenetic relationships with human malaria parasites. The clinical application of such techniques has also made it possible to document ongoing spillovers of NHP malaria parasites (Plasmodium knowlesi, P. cynomolgi, P. simium, P. brasilianum) in humans living in or near the forests of Asia and South America, thus confirming that zoonotic malaria can undermine efforts to eradicate human malaria. Conclusions Increasing molecular research supports the prophetic intuition of the pioneers of modern malariology who saw zoonotic malaria as a potential obstacle to the full success of malaria eradication programmes. It is, therefore, important to continue surveillance and research based on one-health approaches in order to improve our understanding of the complex interactions between NHPs, mosquito vectors and humans during a period of ongoing changes in the climate and the use of land, monitor the evolution of zoonotic malaria, identify the populations most at risk and implement appropriate preventive strategies.

scholarly journals A cornucopia of research resources for the fourth rodent malaria parasite species

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jane M. Carlton
Keyword(s):  
Malaria Parasite ◽  
Parasite Species ◽  
First Century ◽  
Model Systems ◽  
Rodent Malaria Parasite ◽  
Malaria Parasites ◽  
Rodent Malaria ◽  
Human Malaria ◽  
Plasmodium Vinckei ◽  
Research Resources

AbstractThe study of human malaria caused by species of Plasmodium has undoubtedly been enriched by the use of model systems, such as the rodent malaria parasites originally isolated from African thicket rats. A significant gap in the arsenal of resources of the species that make up the rodent malaria parasites has been the lack of any such tools for the fourth of the species, Plasmodium vinckei. This has recently been rectified by Abhinay Ramaprasad and colleagues, whose pivotal paper published in BMC Biology describes a cornucopia of new P. vinckei ‘omics datasets, mosquito transmission experiments, transfection protocols, and virulence phenotypes, to propel this species firmly into the twenty-first century.

scholarly journals Assessment of the Drug Susceptibility of Plasmodium falciparum Clinical Isolates from Africa by Using a Plasmodium Lactate Dehydrogenase Immunodetection Assay and an Inhibitory Maximum Effect Model for Precise Measurement of the 50-Percent Inhibitory Concentration

2006 ◽  
Vol 50 (10) ◽  
pp. 3343-3349 ◽  
Author(s):  
Halima Kaddouri ◽  
Serge Nakache ◽  
Sandrine Houzé ◽  
France Mentré ◽  
Jacques Le Bras
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Lactate Dehydrogenase ◽  
Active Metabolite ◽  
Inhibitory Concentration ◽  
Drug Susceptibility ◽  
Maximum Effect ◽  
Malaria Parasites ◽  
Effect Model

ABSTRACT The extension of drug resistance among malaria-causing Plasmodium falciparum parasites in Africa necessitates implementation of new combined therapeutic strategies. Drug susceptibility phenotyping requires precise measurements. Until recently, schizont maturation and isotopic in vitro assays were the only methods available, but their use was limited by technical constraints. This explains the revived interest in the development of replacement methods, such as the Plasmodium lactate dehydrogenase (pLDH) immunodetection assay. We evaluated a commercially controlled pLDH enzyme-linked immunosorbent assay (ELISA; the ELISA-Malaria antigen test; DiaMed AG, Cressier s/Morat, Switzerland) to assess drug susceptibility in a standard in vitro assay using fairly basic laboratory equipment to study the in vitro resistance of malaria parasites to major antimalarials. Five Plasmodium falciparum clones and 121 clinical African isolates collected during 2003 and 2004 were studied by the pLDH ELISA and the [8-3H]hypoxanthine isotopic assay as a reference with four antimalarials. Nonlinear regression with a maximum effect model was used to estimate the 50% inhibitory concentration (IC50) and its confidence intervals. The two methods were observed to have similar reproducibilities, but the pLDH ELISA demonstrated a higher sensitivity. The high correlation (r = 0.98) and the high phenotypic agreement (κ = 0.88) between the two methods allowed comparison by determination of the IC50s. Recently collected Plasmodium falciparum African isolates were tested by pLDH ELISA and showed drug resistance or decreased susceptibilities of 62% to chloroquine and 11.5% to the active metabolite of amodiaquine. No decreased susceptibility to lumefantrine or the active metabolite of artemisinin was detected. The availability of this simple and highly sensitive pLDH immunodetection assay will provide an easier method for drug susceptibility testing of malaria parasites.

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