In vivo compartmental kinetics of Plasmodium falciparum histidine-rich protein II in the blood of humans and in BALB/c mice infected with a transgenic Plasmodium berghei parasite expressing histidine-rich protein II

Hemozoin (Hz) is released into the blood stream after rupture of infected red blood cells (iRBCs) at the end of each parasite replication cycle. This free Hz is ingested by circulating and resident phagocytes. The presence of Hz in tissues after clearance of infection has been previously reported. Still, little is known about the kinetics of Hz in vivo, during and after Plasmodium infection. It is particularly important to understand Hz kinetics after malaria infections as it has been reported that Hz is associated with impairment of immune functions, including possible consequences for coinfections. Indeed, if Hz remains biologically active for prolonged periods of time inside immunocompetent cells, the potential consequences of such accumulation and presence to the immune system should be clarified. Here, using several independent methods to assess the presence of Hz, we report the long-term in vivo kinetics of Hz in diverse organs in a murine model of malaria infection.

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Modelling the population dynamics of Plasmodium falciparum gametocytes in humans during malaria infection

10.1101/641472 ◽

2019 ◽

Author(s):

Pengxing Cao ◽

Katharine A. Collins ◽

Sophie Zaloumis ◽

Thanaporn Wattanakul ◽

Joel Tarning ◽

...

Keyword(s):

Mathematical Model ◽

Plasmodium Falciparum ◽

Population Dynamics ◽

Malaria Infection ◽

Credible Interval ◽

The Novel ◽

Reliable Prediction ◽

Bayesian Hierarchical ◽

Kinetics Of

AbstractEvery year over two hundred million people are infected with the malaria parasite. Renewed efforts to eliminate malaria has highlighted the potential to interrupt transmission from humans to mosquitoes which is mediated through the gametocytes. Reliable prediction of transmission requires an improved understanding of in vivo kinetics of gametocytes. Here we study the population dynamics of Plasmodium falciparum gametocytes in human hosts by establishing a framework which incorporates improved measurements of parasitaemia in humans, a novel mathematical model of gametocyte dynamics, and model validation using a Bayesian hierarchical inference method. We found that the novel mathematical model provides an excellent fit to the available clinical data from 17 volunteers infected with P. falciparum, and reliably predicts observed gametocyte levels. We estimated the P. falciparum’s sexual commitment rate and gametocyte sequestration time in humans to be 0.54% (95% credible interval: 0.30-1.00) per life cycle and 8.39 (6.54-10.59) days respectively. Furthermore, we used the data-calibrated model to predict the effects of those gametocyte dynamics parameters on human-to-mosquito transmissibility, providing a method to link within-human host kinetics of malaria infection to epidemiological-scale infection and transmission patterns.

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The Development of Novel Compounds Against Malaria: Quinolines, Triazolpyridines, Pyrazolopyridines and Pyrazolopyrimidines

Molecules ◽

10.3390/molecules24224095 ◽

2019 ◽

Vol 24 (22) ◽

pp. 4095 ◽

Cited By ~ 11

Author(s):

Luiz C. S. Pinheiro ◽

Lívia M. Feitosa ◽

Marilia O. Gandi ◽

Flávia F. Silveira ◽

Nubia Boechat

Keyword(s):

Plasmodium Falciparum ◽

Mouse Model ◽

Infected Mouse ◽

Plasmodium Berghei ◽

Medicinal Chemistry ◽

Quinoline Derivatives ◽

Dihydroorotate Dehydrogenase ◽

New Compounds

Based on medicinal chemistry tools, new compounds for malaria treatment were designed. The scaffolds of the drugs used to treat malaria, such as chloroquine, primaquine, amodiaquine, mefloquine and sulfadoxine, were used as inspiration. We demonstrated the importance of quinoline and non-quinoline derivatives in vitro with activity against the W2 chloroquine-resistant (CQR) Plasmodium falciparum clone strain and in vivo against Plasmodium berghei-infected mouse model. Among the quinoline derivatives, new hybrids between chloroquine and sulfadoxine were designed, which gave rise to an important prototype that was more active than both chloroquine and sulfadoxine. Hybrids between chloroquine–atorvastatin and primaquine–atorvastatin were also synthesized and shown to be more potent than the parent drugs alone. Additionally, among the quinoline derivatives, new mefloquine derivatives were synthesized. Among the non-quinoline derivatives, we obtained excellent results with the triazolopyrimidine nucleus, which gave us prototype I that inspired the synthesis of new heterocycles. The pyrazolopyrimidine derivatives stood out as non-quinoline derivatives that are potent inhibitors of the P. falciparum dihydroorotate dehydrogenase (PfDHODH) enzyme. We also examined the pyrazolopyridine and pyrazolopyrimidine nuclei.

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Andrographolide: A Novel Antimalarial Diterpene Lactone Compound fromAndrographis paniculataand Its Interaction with Curcumin and Artesunate

Journal of Tropical Medicine ◽

10.1155/2011/579518 ◽

2011 ◽

Vol 2011 ◽

pp. 1-6 ◽

Cited By ~ 27

Author(s):

Kirti Mishra ◽

Aditya P. Dash ◽

Nrisingha Dey

Keyword(s):

Plasmodium Falciparum ◽

Life Span ◽

Plasmodium Berghei ◽

Antimalarial Activity ◽

Andrographis Paniculata ◽

Antiplasmodial Activity ◽

Template Molecule

Andrographolide (AND), the diterpene lactone compound, was purified by HPLC from the methanolic fraction of the plantAndrographis paniculata. The compound was found to have potent antiplasmodial activity when tested in isolation and in combination with curcumin and artesunate against the erythrocytic stages ofPlasmodium falciparum in vitroandPlasmodium bergheiANKAin vivo. IC50s for artesunate (AS), andrographolide (AND), and curcumin (CUR) were found to be 0.05, 9.1 and 17.4 μM, respectively. The compound (AND) was found synergistic with curcumin (CUR) and addictively interactive with artesunate (AS).In vivo, andrographolide-curcumin exhibited better antimalarial activity, not only by reducing parasitemia (29%), compared to the control (81%), but also by extending the life span by 2-3 folds. Being nontoxic to thein vivosystem this agent can be used as template molecule for designing new derivatives with improved antimalarial properties.

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Plants as Sources of Antimalarial Drugs, Part 4: Activity of Brucea javanica Fruits Against Chloroquine-Resistant Plasmodium falciparum in vitro and Against Plasmodium berghei in vivo

Journal of Natural Products ◽

10.1021/np50049a007 ◽

1987 ◽

Vol 50 (1) ◽

pp. 41-48 ◽

Cited By ~ 69

Author(s):

Melanie J. O'Neill ◽

Dorothy H. Bray ◽

Peter Boardman ◽

Kit L. Chan ◽

J. David Phillipson ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Plasmodium Berghei ◽

Antimalarial Drugs ◽

Brucea Javanica

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Antimalarial potential of quinones isolated from plants: an integrative review

Research Society and Development ◽

10.33448/rsd-v10i2.12507 ◽

2021 ◽

Vol 10 (2) ◽

pp. e38210212507

Author(s):

Antonio Rafael Quadros Gomes ◽

Heliton Patrick Cordovil Brígido ◽

Valdicley Vieira Vale ◽

Juliana Correa-Barbosa ◽

Sandro Percário ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Natural Products ◽

Plasmodium Berghei ◽

Structural Changes ◽

In Vivo Studies ◽

Inclusion Criteria ◽

Antimalarial Treatment ◽

Exclusion Criteria ◽

Therapeutic Alternatives

Antimalarial treatment is often associated with the resistance developed by Plasmodium which generate ineffective drug treatment. Based on this, the search for therapeutic alternatives is necessary and urgent. This review intends to assess the antimalarial potential of quinones isolated from plants. The search for scientific articles was carried out on the CAPES Journal Portal (PPC), Virtual Health Library (VHL), PUBMED, NCBI and SCIELO, using the following descriptors: quinones and antimalarials. Inclusion criteria were adopted based on studies about quinones isolated from plants and tested against Plasmodium falciparum and Plasmodium berghei. The exclusion criteria were based mainly on articles that tested extracts, fractions and synthesis of quinones obtained from plants and other natural products. A total of 1344 publications were collected for screening (PPC = 5, VHL = 248, PUBMED = 525, NCBI = 462 and SCIELO = 94). From this total, 1280 articles were excluded, with only 64 articles selected for full reading. All benzoquinones were active against P. falciparum. Naphthoquinones were active, inactive and moderately active against the P. falciparum e P berghei. Anthraquinones and anthrones were active and moderately active against P. falciparum. The naphthoquinone 2-acetylnaphtho- [2,3b] -furan-4,9-dione was the most active of all the molecules tested against Plasmodium. Whereas lapachol was the most studied naphthoquinone and structural changes do not seem to contribute to the activity. In summary, quinones are promising as antimalarials, however, need in vivo studies.

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New quinoline derivatives demonstrate a promising antimalarial activity against Plasmodium falciparum in vitro and Plasmodium berghei in vivo

Bioorganic & Medicinal Chemistry Letters ◽

10.1016/j.bmcl.2015.04.014 ◽

2015 ◽

Vol 25 (11) ◽

pp. 2308-2313 ◽

Cited By ~ 24

Author(s):

Roberta Reis Soares ◽

José Marcio Fernandes da Silva ◽

Bianca Cecheto Carlos ◽

Camila Campos da Fonseca ◽

Laila Salomé Araújo de Souza ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Plasmodium Berghei ◽

Antimalarial Activity ◽

Quinoline Derivatives

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Chemical Attenuation of Plasmodium berghei Sporozoites Induces Sterile Immunity in Mice

Infection and Immunity ◽

10.1128/iai.01399-07 ◽

2008 ◽

Vol 76 (3) ◽

pp. 1193-1199 ◽

Cited By ~ 42

Author(s):

Lisa A. Purcell ◽

Stephanie K. Yanow ◽

Moses Lee ◽

Terry W. Spithill ◽

Ana Rodriguez

Keyword(s):

Plasmodium Falciparum ◽

Plasmodium Berghei ◽

Alkylating Agent ◽

Blood Stage ◽

Wild Type ◽

Vaccine Strategy ◽

Liver Stage ◽

Stage Development

ABSTRACT Radiation and genetic attenuation of Plasmodium sporozoites are two approaches for whole-organism vaccines that protect against malaria. We evaluated chemical attenuation of sporozoites as an alternative vaccine strategy. Sporozoites were treated with the DNA sequence-specific alkylating agent centanamycin, a compound that significantly affects blood stage parasitemia and transmission of murine malaria and also inhibits Plasmodium falciparum growth in vitro. Here we show that treatment of Plasmodium berghei sporozoites with centanamycin impaired parasite function both in vitro and in vivo. The infection of hepatocytes by sporozoites in vitro was significantly reduced, and treated parasites showed arrested liver stage development. Inoculation of mice with sporozoites that were treated in vitro with centanamycin failed to produce blood stage infections. Furthermore, BALB/c and C57BL/6 mice vaccinated with treated sporozoites were protected against subsequent challenge with wild-type sporozoites. Our findings demonstrate that chemically attenuated sporozoites could be a viable alternative for the production of an effective liver stage vaccine for malaria.

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