scholarly journals A Comparison of Transmission-Blocking Activity with Reactivity in a Plasmodium falciparum 48/45-kD Molecule-Specific Competition Enzyme-Linked Immunosorbent Assay

1995 ◽  
Vol 52 (1) ◽  
pp. 60-65 ◽  
Author(s):  
W. Roeffen ◽  
R. Sauerwein ◽  
T. Lensen ◽  
J. Van Druten ◽  
B. Mulder ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Immunosorbent Assay ◽  
Enzyme Linked Immunosorbent Assay ◽  
Transmission Blocking ◽  
Blocking Activity

scholarly journals DSM265 at 400 Milligrams Clears Asexual Stage Parasites but Not Mature Gametocytes from the Blood of Healthy Subjects Experimentally Infected with Plasmodium falciparum

2019 ◽  
Vol 63 (4) ◽  
Author(s):  
Katharine A. Collins ◽  
Thomas Rückle ◽  
Suzanne Elliott ◽  
Louise Marquart ◽  
Emma Ballard ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Pharmacodynamic Modeling ◽  
Dihydroorotate Dehydrogenase ◽  
Transmission Blocking ◽  
Content Type ◽  
Blocking Activity ◽  
Cutaneous Rash ◽  
Phase 1B ◽  
Study Support ◽  
Previous Phase

ABSTRACT DSM265 is a novel antimalarial drug in clinical development that acts as a selective inhibitor of Plasmodium dihydroorotate dehydrogenase. In a previous phase 1b study, a single 150-mg dose of DSM265 showed partial efficacy against experimentally induced blood-stage Plasmodium falciparum malaria (IBSM). Pharmacokinetic/pharmacodynamic modeling predicted a human efficacious dose of 340 mg. The primary objectives of the current study were to determine the safety and efficacy of a single oral 400-mg dose of DSM265 against P. falciparum in the IBSM model. Eight healthy participants were inoculated intravenously with 2,800 parasites and treated with DSM265 7 days later. Unexpectedly, one participant did not develop parasitemia during the study. All other participants developed parasitemia, with the complete clearance of asexual parasites occurring following DSM265 treatment. All seven subjects also became gametocytemic. The secondary objectives were to investigate the gametocytocidal and transmission-blocking activity of a second 400-mg dose of DSM265, which was administered 23 days after inoculation. Gametocytes were not cleared by the second dose of DSM265, and transmission-blocking activity could not be determined due to low gametocyte densities. Three DSM265-related adverse events occurred, including a cutaneous rash in one subject on the day of the second DSM265 dose. The results obtained in this study support the prediction of the efficacious dose of DSM265 and provide further evidence that DSM265 is generally safe and well tolerated. In addition, this study confirms preclinical data indicating that DSM265 permits the development and maturation of gametocytes and does not clear mature circulating gametocytes. (This study has been registered at ClinicalTrials.gov under identifier NCT02573857.)

scholarly journals Enzyme-Linked Immunosorbent Assay for Detection of Plasmodium falciparum Histidine-Rich Protein 2 in Blood, Plasma, and Serum

2008 ◽  
Vol 15 (6) ◽  
pp. 1012-1018 ◽  
Author(s):  
Carolyne M. Kifude ◽  
Halli G. Rajasekariah ◽  
David J. Sullivan ◽  
V. Ann Stewart ◽  
Evelina Angov ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Immunosorbent Assay ◽  
Whole Blood ◽  
Linear Range ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Samples ◽  
Target Concentration ◽  
Intervention Trials ◽  
Lower Limits ◽  
Asexual Cycle

ABSTRACT Microscopy, the gold standard for the detection and quantification of malaria parasites in blood, is in many aspects deficient for this purpose. The method is poorly reproducible and can be inaccurate because Plasmodium falciparum parasites sequester for a portion of each asexual cycle. Due to these deficiencies, biomarkers such as P. falciparum histidine-rich protein 2 (PfHRP2) are increasingly being used. In this study, we evaluated the use of a commercial PfHRP2 enzyme-linked immunosorbent assay (ELISA) kit with some procedural modifications. We determined the linear range of the assay, including the lower limits of detection and quantitation, using recombinant PfHRP2 (rPfHRP2). In 10 repeat experiments, the linear range of optical densities (ODs) at 450 to 650 nm was from 0.05 ± 0.002 to 2.28 ± 0.042, corresponding to 3.91 to 250 ng/ml of rPfHRP2. The coefficient of variation (CV) at each target concentration ranged from 1.93 to 8.07%. Using cultured parasites, we confirmed the linear range of ODs as well as the association between the PfHRP2 ELISA results and the microscopic parasite densities. For whole-blood samples spiked with cultured, washed, ring-stage-infected red blood cells (iRBCs), the linear range was 11.7 to 750 iRBCs/μl, with CVs of 0.29 to 7.56%. The same spiked samples evaluated by microscopists had similar sensitivities, but the CVs were unacceptably high (20.7 to 161.6%). Stock rPfHRP2 was stable through four freeze-thaw cycles (P < 0.05; paired t test). When different patient sample types at different concentrations within the linear range of the assay are compared, the recoveries of PfHRP2 from blood and serum were within ±20%, whereas the recoveries from plasma ranged between +35 and −41%. We conclude that PfHRP2 ELISA using whole-blood and serum samples is a suitable adjunct to microscopy and could ultimately benefit malaria intervention trials.

scholarly journals Transmission-Blocking Activities of Quinine, Primaquine, and Artesunate

2006 ◽  
Vol 50 (6) ◽  
pp. 1927-1930 ◽  
Author(s):  
Kesinee Chotivanich ◽  
Jetsumon Sattabongkot ◽  
Rachanee Udomsangpetch ◽  
Sornchai Looareesuwan ◽  
Nicholas P. J. Day ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Standard Deviation ◽  
Anopheles Dirus ◽  
Transmission Blocking ◽  
Transmission Potential ◽  
Membrane Feeding ◽  
Blocking Activity ◽  
The Mean ◽  
High Concentrations

ABSTRACT The infectivity of Plasmodium falciparum gametocytes after exposure in vitro to quinine, artesunate, and primaquine was assessed in Anopheles dirus, a major vector of malaria in Southeast Asia. Mature gametocytes (stage 5) of a Thai isolate of P. falciparum were exposed to the drugs for 24 h in vitro before membrane feeding to A. dirus. After 10 days, the mosquito midguts were dissected and the oocysts were counted. In this system, artesunate showed the most potent transmission-blocking activity; the mean (standard deviation [SD]) 50% and 90% effective concentrations (EC50, and EC90, respectively, in nanograms per milliliter) were 0.1 (0.02) and 0.4 (0.15), respectively. Transmission-blocking activity of quinine and primaquine was observed at relatively high concentrations (SDs): EC50 of quinine, 642 (111) ng/ml; EC50 of primaquine, 181 (23) ng/ml; EC90 of quinine, 816 (96) ng/ml; EC90 of primaquine, 543 (43) ng/ml. Artesunate both prevents the maturation of immature P. falciparum gametocytes and reduces the transmission potential of mature gametocytes. Both of these effects may contribute to reducing malaria transmission.

Detection of Plasmodium falciparum malaria in 1 h using a simplified enzyme-linked immunosorbent assay

2021 ◽  
Vol 1152 ◽  
pp. 338254
Author(s):  
Erica de la Serna ◽  
Kevin Arias-Alpízar ◽  
Livia Neves Borgheti-Cardoso ◽  
Ana Sanchez-Cano ◽  
Elena Sulleiro ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Falciparum Malaria ◽  
Immunosorbent Assay ◽  
Plasmodium Falciparum Malaria ◽  
Enzyme Linked Immunosorbent Assay
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