scholarly journals In vitro Multistage Malaria Transmission Blocking Activity of Selected Malaria Box Compounds

2020 ◽  
Vol Volume 14 ◽  
pp. 1593-1607
Author(s):  
Hamisi M Malebo ◽  
Sarah D'Alessandro ◽  
Yehenew A Ebstie ◽  
Harouna Sorè ◽  
Alain R Tenoh Guedoung ◽  
...  
Keyword(s):  
Malaria Transmission ◽  
Transmission Blocking ◽  
Blocking Activity ◽  
Malaria Box

In vitro antimalarial interaction and transmission-blocking activity of cryptolepine

Planta Medica ◽  
2016 ◽  
Vol 81 (S 01) ◽  
pp. S1-S381
Author(s):  
A Donkor Forkuo ◽  
C Ansah ◽  
B Gyan ◽  
D Mancama ◽  
A Theron
Keyword(s):  
Transmission Blocking ◽  
Blocking Activity

scholarly journals Comparison and Optimization of Different Methods for theIn VitroProduction ofPlasmodium falciparumGametocytes

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
María Roncalés ◽  
Jaume Vidal-Mas ◽  
Didier Leroy ◽  
Esperanza Herreros
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Transmission ◽  
Improved Method ◽  
Transmission Blocking ◽  
Blocking Malaria Transmission

The generation of sexually committed parasites (gametocytogenesis) is poorly understood in malaria. If the mechanisms regulating this process were elucidated, new opportunities for blocking malaria transmission could be revealed. Here we compare several methods described previously for thein vitroproduction ofPlasmodium falciparumgametocytes. Our approach relies on the combination of several factors that we demonstrated as impacting on or being critical to gametocytogenesis. An improved method has been developed for thein vitroproduction ofP. falciparumgametocytes as the first step toward obtaining adequate numbers of pure gametocytes forin vitrostudies, such as, for example, the identification of transmission blocking drugs.

scholarly journals Salinomycin and Other Ionophores as a New Class of Antimalarial Drugs with Transmission-Blocking Activity

2015 ◽  
Vol 59 (9) ◽  
pp. 5135-5144 ◽  
Author(s):  
Sarah D'Alessandro ◽  
Yolanda Corbett ◽  
Denise P. Ilboudo ◽  
Paola Misiano ◽  
Nisha Dahiya ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Drug Target ◽  
Stage Iv ◽  
Stage Ii ◽  
Transmission Blocking ◽  
Content Type ◽  
New Class ◽  
Blocking Activity ◽  
Sexual Stages

ABSTRACTThe drug target profile proposed by the Medicines for Malaria Venture for a malaria elimination/eradication policy focuses on molecules active on both asexual and sexual stages ofPlasmodium, thus with both curative and transmission-blocking activities. The aim of the present work was to investigate whether the class of monovalent ionophores, which includes drugs used in veterinary medicine and that were recently proposed as human anticancer agents, meets these requirements. The activity of salinomycin, monensin, and nigericin onPlasmodium falciparumasexual and sexual erythrocytic stages and on the development of thePlasmodium bergheiandP. falciparummosquito stages is reported here. Gametocytogenesis of theP. falciparumstrain 3D7 was inducedin vitro, and gametocytes at stage II and III or stage IV and V of development were treated for different lengths of time with the ionophores and their viability measured with the parasite lactate dehydrogenase (pLDH) assay. The monovalent ionophores efficiently killed both asexual parasites and gametocytes with a nanomolar 50% inhibitory concentration (IC50). Salinomycin showed a fast speed of kill compared to that of standard drugs, and the potency was higher on stage IV and V than on stage II and III gametocytes. The ionophores inhibited ookinete development and subsequent oocyst formation in the mosquito midgut, confirming their transmission-blocking activity. Potential toxicity due to hemolysis was excluded, since only infected and not normal erythrocytes were damaged by ionophores. Our data strongly support the downstream exploration of monovalent ionophores for repositioning as new antimalarial and transmission-blocking leads.

scholarly journals N-Terminal Prodomain of Pfs230 Synthesized Using a Cell-Free System Is Sufficient To Induce Complement-Dependent Malaria Transmission-Blocking Activity

2011 ◽  
Vol 18 (8) ◽  
pp. 1343-1350 ◽  
Author(s):  
Mayumi Tachibana ◽  
Yimin Wu ◽  
Hideyuki Iriko ◽  
Olga Muratova ◽  
Nicholas J. MacDonald ◽  
...  
Keyword(s):  
Malaria Transmission ◽  
Expression System ◽  
Surface Protein ◽  
Western Blot Assay ◽  
Free System ◽  
Transmission Blocking ◽  
Content Type ◽  
Membrane Feeding ◽  
Blocking Activity ◽  
Transmission Blocking Vaccine

ABSTRACTThe aim of a malaria transmission-blocking vaccine is to block the development of malaria parasites in the mosquito and thus prevent subsequent infection of the human host. Previous studies have demonstrated that the gametocyte/gamete surface protein Pfs230 can induce transmission-blocking immunity and have evaluatedEscherichia coli-produced Pfs230 as a transmission-blocking vaccine candidate. In this study, we used the wheat germ cell-free expression system to produce N-terminal fragments of Pfs230 and evaluated the transmission-blocking activity of antisera raised against the recombinant Pfs230 protein. The rabbit antisera reacted to the surface of cultured gametocytes and gametes of thePlasmodium falciparumNF54 line, recognized the 360-kDa form of parasite-produced Pfs230 by Western blot assay, and reduced the infectivity of NF54 parasites toAnopheles stefensimosquitoes in the presence of complement in a standard membrane feeding assay. Thus, our data demonstrate that the N-terminal pro domain of Pfs230 is sufficient to induce complement-dependent transmission-blocking activity againstP. falciparum.

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.

Evaluation of Two Sexual-stage Antigens as Bivalent Transmission-blocking Vaccines in Rodent Malaria

2021 ◽  
Author(s):  
Fan Yang ◽  
Fei Liu ◽  
Xinxin Yu ◽  
Wenqi Zheng ◽  
Yudi Wu ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Chimeric Protein ◽  
Transmission Blocking ◽  
Native Proteins ◽  
Blocking Activity ◽  
Antibody Titers ◽  
Sexual Stages ◽  
Transmission Blocking Vaccines

Abstract Background: Transmission-blocking vaccine (TBV) is a promising strategy for malaria elimination. It is hypothesized that mixing or fusing two antigens targeting different stages of sexual development may provide higher transmission-blocking activity than these antigens are used individually.Methods: We designed a chimeric protein composed of fragments of Pbg37 and PSOP25 and expressed the recombinant protein in Escherichia coli Rosetta-gami B (DE3). After immunizing mice with mixing or fusing recombinant proteins, the antibody titers of sera were analyzed by ELISA. IFA and Western blot were performed to test the reactivity of the antisera with the native proteins of the parasite. The transmission blocking activity were assessed in vitro and in vivo assay. Results: When Pbg37 and PSOP25 were co-administered in a mixture or as a fusion protein, they elicited similar antibody responses in mice as single antigens without causing immunological interference with each other. Antibodies against the mixed or fused antigens recognized the target proteins in the gametocyte, gamete, zygote and ookinete stages. The two bivalent vaccines (mixed proteins or a fusion protein) produced the superior TBA compared to that of the antibodies against individual antigens.Conclusions: There was no immunological interference between the two antigens of bivalent vaccines. And the bivalent vaccines produced significantly stronger transmission-blocking activities than single antigens. Altogether, these data provide the theoretical basis for the development of combination TBVs targeting different sexual stages.

scholarly journals Characterization of Plasmodium vivax Transmission-Blocking Activity in Low to Moderate Malaria Transmission Settings of the Colombian Pacific Coast

2011 ◽  
Vol 84 (2_Suppl) ◽  
pp. 71-77 ◽  
Author(s):  
Myriam Arévalo-Herrera ◽  
Yezid Solarte ◽  
Sócrates Herrera ◽  
John C. Beier ◽  
Diego Álvarez ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Malaria Transmission ◽  
Pacific Coast ◽  
Transmission Blocking ◽  
Blocking Activity ◽  
Colombian Pacific

scholarly journals Evaluation of two sexual-stage antigens as bivalent transmission-blocking vaccines in rodent malaria

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Fan Yang ◽  
Fei Liu ◽  
Xinxin Yu ◽  
Wenqi Zheng ◽  
Yudi Wu ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Sexual Development ◽  
Chimeric Protein ◽  
Transmission Blocking ◽  
Native Proteins ◽  
Blocking Activity ◽  
Antibody Titers ◽  
Blocking Antibodies

Abstract Background Transmission-blocking vaccine (TBV) is a promising strategy for malaria elimination. It is hypothesized that mixing or fusing two antigens targeting different stages of sexual development may provide higher transmission-blocking activity than these antigens used individually. Methods A chimeric protein composed of fragments of Pbg37 and PSOP25 was designed and expressed the recombinant protein in Escherichia coli Rosetta-gami B (DE3). After immunizing mice with individual recombinant proteins Pbg37 and PSOP25, mixed proteins (Pbg37+PSOP25), or the fusion protein (Pbg37-PSOP25), the antibody titers of individual sera were analyzed by ELISA. IFA and Western blot were performed to test the reactivity of the antisera with the native proteins in the parasite. The transmission-blocking activity of the different immunization schemes was assessed using in vitro and in vivo assays. Results When Pbg37 and PSOP25 were co-administered in a mixture or as a fusion protein, they elicited similar antibody responses in mice as single antigens without causing immunological interference with each other. Antibodies against the mixed or fused antigens recognized the target proteins in the gametocyte, gamete, zygote, and ookinete stages. The mixed proteins or the fusion protein induced antibodies with significantly stronger transmission-reducing activities in vitro and in vivo than individual antigens. Conclusions There was no immunological interference between Pbg37 and PSOP25. The bivalent vaccines, which expand the portion of the sexual development during which the transmission-blocking antibodies act, produced significantly stronger transmission-reducing activities than single antigens. Altogether, these data provide the theoretical basis for the development of combination TBVs targeting different sexual stages. Graphic Abstract

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