The impact of malaria parasitism: from corpuscles to communities

Wellems, Thomas E.; Hayton, Karen; Fairhurst, Rick M.

doi:10.1172/jci38307

Cited by 64 publications

(58 citation statements)

References 123 publications

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“…1 The recent evidence of emerging resistance to artemisinin derivatives, including ACTs, in southeast Asia raises serious concern that such parasite populations may spread toward Africa, mirroring parasite resistance to chloroquine, 2 sulfadoxine, and pyrimethamine. 3 Recently, mutations in the PF3D7_1343700 kelch propeller (K13-propeller) domain were shown to be useful markers of delayed parasite clearance in surveillance for artemisinin resistance in southeast Asia.…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms in the K13-Propeller Gene in Artemisinin-Susceptible Plasmodium falciparum Parasites from Bougoula-Hameau and Bandiagara, Mali

Ouattara¹,

Koné²,

Adams³

et al. 2015

The American Society of Tropical Medicine and Hygiene

100

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Abstract. Artemisinin-resistant Plasmodium falciparum malaria has been documented in southeast Asia and may already be spreading in that region. Molecular markers are important tools for monitoring the spread of antimalarial drug resistance. Recently, single-nucleotide polymorphisms (SNPs) in the PF3D7_1343700 kelch propeller (K13-propeller) domain were shown to be associated with artemisinin resistance in vivo and in vitro. The prevalence and role of K13-propeller mutations are poorly known in sub-Saharan Africa. K13-propeller mutations were genotyped by direct sequencing of nested polymerase chain reaction (PCR) amplicons from dried blood spots of pre-treatment falciparum malaria infections collected before and after the use of artemisinin-based combination therapy (ACT) as first-line therapy in Mali. Although K13-propeller mutations previously associated with delayed parasite clearance in Cambodia were not identified, 26 K13-propeller mutations were identified in both recent samples and pre-ACT infections. Parasite clearance time was comparable between infections with non-synonymous K13-propeller mutations and infections with the reference allele. These findings suggest that K13-propeller mutations are present in artemisinin-sensitive parasites and that they preceded the wide use of ACTs in Mali.

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Section: Introductionmentioning

confidence: 99%

Polymorphisms in the K13-Propeller Gene in Artemisinin-Susceptible Plasmodium falciparum Parasites from Bougoula-Hameau and Bandiagara, Mali

Ouattara¹,

Koné²,

Adams³

et al. 2015

The American Society of Tropical Medicine and Hygiene

100

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“…Molecular-epidemiological studies have identified at least six independent origins of CQR in different regions of the world (23). These origins are distinguished by codon mutations and flanking polymorphisms of pfcrt, the transporter-encoding gene responsible for CQR (24,25).…”

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confidence: 99%

Geographic patterns of Plasmodium falciparum drug resistance distinguished by differential responses to amodiaquine and chloroquine

Sá

Twu

Hayton

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

242

230

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Chloroquine (CQ) resistance (CQR) in Plasmodium falciparum originated from at least six foci in South America, Asia, and Oceania. Malaria parasites from these locations exhibit contrasting resistance phenotypes that are distinguished by point mutations and microsatellite polymorphisms in and near the CQR transporter gene, pfcrt, and the multidrug resistance transporter gene, pfmdr1. Amodiaquine (AQ), a 4-aminoquinoline related to CQ, is recommended and often used successfully against CQ-resistant P. falciparum in Africa, but it is largely ineffective across large regions of South America. The relationship of different pfcrt and pfmdr1 combinations to these drug-resistant phenotypes has been unclear. In two P. falciparum genetic crosses, particular pfcrt and pfmdr1 alleles from South America interact to yield greater levels of resistance to monodesethylamodiaquine (MDAQ; the active metabolite of AQ) than to CQ, whereas a pfcrt allele from Southeast Asia and Africa is linked to greater CQ than MDAQ resistance with all partner pfmdr1 alleles. These results, together with (i) available haplotype data from other parasites; (ii) evidence for an emerging focus of AQ resistance in Tanzania; and (iii) the persistence of 4-aminoquinoline-resistant parasites in South America, where CQ and AQ use is largely discontinued, suggest that different histories of drug use on the two continents have driven the selection of distinct suites of pfcrt and pfmdr1 mutations. Increasing use of AQ in Africa poses the threat of a selective sweep of highly AQ-resistant, CQ-resistant parasites with pfcrt and pfmdr1 mutations that are as advantaged and persistent as in South America.

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“…Anemia continues to exert tremendous burdens to human health. [1][2][3][4] Thus, a considerable effort has been made to develop new therapies for the treatment of anemia. Although the focus in the treatment of anemia has been on growth factors (eg, erythropoietin [EPO]), derivation of hematopoietic cells from human embryonic stem cells and induced pluripotent stem cells are considered a worthwhile endeavor in the areas of transfusion therapies.…”

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confidence: 99%

Macrophages prevent human red blood cell reconstitution in immunodeficient mice

Rooijen

Yang

2011

Blood

130

138

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IntroductionRed blood cells (RBCs) are part of nonimmune blood-lineage cells derived from hematopoietic stem cells. Anemia continues to exert tremendous burdens to human health. [1][2][3][4] Thus, a considerable effort has been made to develop new therapies for the treatment of anemia. Although the focus in the treatment of anemia has been on growth factors (eg, erythropoietin [EPO]), derivation of hematopoietic cells from human embryonic stem cells and induced pluripotent stem cells are considered a worthwhile endeavor in the areas of transfusion therapies. 5 It has been reported that enucleated RBCs can be differentiated from human embryonic stem cells with functional oxygen-carrying ability on large scale. 6 However, these studies have been limited to in vitro assays because of the lack of a suitable animal model. Immunodeficient mice provide a very useful in vivo model for the study of human lymphohematopoietic cell function. Human hematopoietic stem cell engraftment and differentiation can now be reproducibly established in NOD/SCID mice or their derivatives. 7 However, it remains unclear whether immunodeficient mice are suitable for the study of human RBC differentiation and function. Although a previous report showed detectable human RBCs in NOD/SCID/IL2r null (NSG) mice receiving human cord blood CD34 ϩ cell transplantation via the facial vein at the newborn stage, 8 the ability of immunodeficient mice to support human erythropoiesis and/or survival of human RBCs has not been confirmed by other studies. 9 Recently, hydrodynamic injection of pcDNA-encoding EPO and IL-3 was found to improve human RBC reconstitution in NSG mice receiving CD34 ϩ cells, but the levels of human RBCs in these mice were extremely low compared with the levels of human PBMCs. 10 We have previously developed a humanized mouse model, in which cotransplantation of human fetal thymic tissue (under renal capsule) and CD34 ϩ fetal liver cells (FLCs; intravenously) resulted in sustained repopulation with multilineages of human lymphohematopoietic cells, including T, B, and dendritic cells, and the formation of secondary lymphoid organs in NOD/SCID mice. [11][12][13] In this study, we assessed human RBC reconstitution in these humanized mice. We observed that human RBCs were undetectable in blood circulation, despite that large numbers of human normoblasts were detected in the bone marrow. Furthermore, the lack of human RBCs in blood circulation was largely accounted for by the extremely high susceptibility of human RBCs to rejection by recipient mouse macrophages. Methods Animals and human tissues and cellsNOD.CB17-Prkdc scid /J (NOD/SCID), NOD.Cg-Prkdc scid Il2rg tm1Wjl /SzJ (NOD/SCID/␥c Ϫ/Ϫ or NSG), and B6.129-Itgp tm1Fpl (CD47 KO B6) mice were purchased from The Jackson Laboratory and were housed in a specific pathogen-free microisolator environment and used in experiments at 6 to 10 weeks of age. GFP-transgenic CD47 KO mice were generated by Submitted November 24, 2010; accepted September 5, 2011. Prepublished online as Blood First E...

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The impact of malaria parasitism: from corpuscles to communities

Cited by 64 publications

References 123 publications

Polymorphisms in the K13-Propeller Gene in Artemisinin-Susceptible Plasmodium falciparum Parasites from Bougoula-Hameau and Bandiagara, Mali

Polymorphisms in the K13-Propeller Gene in Artemisinin-Susceptible Plasmodium falciparum Parasites from Bougoula-Hameau and Bandiagara, Mali

Geographic patterns of Plasmodium falciparum drug resistance distinguished by differential responses to amodiaquine and chloroquine

Macrophages prevent human red blood cell reconstitution in immunodeficient mice

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