Blocking malaria transmission with genetically engineered symbiotic bacteria from vector mosquitoes

2016 ◽  
Author(s):  
Sibao Wang
Keyword(s):  
Malaria Transmission ◽  
Genetically Engineered ◽  
Symbiotic Bacteria ◽  
Blocking Malaria Transmission

scholarly journals PlasmodiumOokinete-secreted Proteins Secreted through a Common Micronemal Pathway Are Targets of Blocking Malaria Transmission

2004 ◽  
Vol 279 (25) ◽  
pp. 26635-26644 ◽  
Author(s):  
Fengwu Li ◽  
Thomas J. Templeton ◽  
Vsevolod Popov ◽  
Jason E. Comer ◽  
Takafumi Tsuboi ◽  
...  
Keyword(s):  
Malaria Transmission ◽  
Secreted Proteins ◽  
Blocking Malaria Transmission

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 Gametocyte clearance in children, from western Kenya, with uncomplicated Plasmodium falciparum malaria after artemether–lumefantrine or dihydroartemisinin–piperaquine treatment

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Protus Omondi ◽  
Marion Burugu ◽  
Damaris Matoke-Muhia ◽  
Edwin Too ◽  
Eva A. Nambati ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Transmission ◽  
Plasmodium Falciparum Malaria ◽  
Western Kenya ◽  
Transmission Season ◽  
Gametocyte Carriage ◽  
Qrt Pcr ◽  
Malaria Transmission Season ◽  
Significant Difference ◽  
Blocking Malaria Transmission

Abstract Background The efficacy and safety of artemether–lumefantrine (AL) and dihydroartemisinin–piperaquine (DP) against asexual parasites population has been documented. However, the effect of these anti-malarials on sexual parasites is still less clear. Gametocyte clearance following treatment is essential for malaria control and elimination efforts; therefore, the study sought to determine trends in gametocyte clearance after AL or DP treatment in children from a malaria-endemic site in Kenya. Methods Children aged between 0.5 and 12 years from Busia, western Kenya with uncomplicated Plasmodium falciparum malaria were assigned randomly to AL or DP treatment. A total of 334 children were enrolled, and dried blood spot samples were collected for up to 6 weeks after treatment during the peak malaria transmission season in 2016 and preserved. Plasmodium falciparum gametocytes were detected by qRT-PCR and gametocyte prevalence, density and mean duration of gametocyte carriage were determined. Results At baseline, all the 334 children had positive asexual parasites by microscopy, 12% (40/334) had detectable gametocyte by microscopy, and 83.7% (253/302) children had gametocytes by RT-qPCR. Gametocyte prevalence by RT-qPCR decreased from 85.1% (126/148) at day 0 to 7.04% (5/71) at day 42 in AL group and from 82.4% (127/154) at day 0 to 14.5% (11/74) at day 42 in DP group. The average duration of gametocyte carriage as estimated by qRT-PCR was slightly shorter in the AL group (4.5 days) than in the DP group (5.1 days) but not significantly different (p = 0.301). Conclusion The study identifies no significant difference between AL and DP in gametocyte clearance. Gametocytes persisted up to 42 days post treatment in minority of individuals in both treatment arms. A gametocytocidal drug, in combination with artemisinin-based combination therapy, will be useful in blocking malaria transmission more efficiently.

scholarly journals Blocking malaria transmission

2017 ◽  
Vol 16 (10) ◽  
pp. 680-680
Author(s):  
Sarah Crunkhorn
Keyword(s):  
Malaria Transmission ◽  
Blocking Malaria Transmission

scholarly journals Identification of Novel Plasmodium gallinaceum Zygote- and Ookinete-Expressed Proteins as Targets for Blocking Malaria Transmission

2002 ◽  
Vol 70 (1) ◽  
pp. 102-106 ◽  
Author(s):  
Rebecca C. Langer ◽  
Fengwu Li ◽  
Joseph M. Vinetz
Keyword(s):  
Malaria Transmission ◽  
Time Course ◽  
Antigen Expression ◽  
Protein Band ◽  
Secreted Proteins ◽  
Valuable Insight ◽  
Plasmodium Gallinaceum ◽  
Western Immunoblot ◽  
Mosquito Midgut ◽  
Blocking Malaria Transmission

ABSTRACT The development of transmission-blocking vaccines is one approach to malaria control. To identify novel Plasmodium zygote- and ookinete-secreted proteins as targets of blocking malaria transmission, monoclonal antibodies (MAbs) were produced against parasite-secreted proteins found in Plasmodium gallinaceum ookinete culture supernatants. Four MAbs—1A6, 2A5, 2B5, and 4B6—were identified that bound to P. gallinaceum zygotes and ookinetes in diverse patterns in terms of spatial localization on parasites, time course of antigen expression, and Western immunoblot patterns. MAbs 2A5 and 4B6 recognized more than one protein band as detected by Western immunoblot of P. gallinaceum ookinete supernatants. Beginning at 0 h postfertilization, MAb 2A5 recognized a diverse set of antigens; at 10 h postfertilization, MAb 4B6 recognized several antigens as well. MAb 1A6 recognized a single ∼17-kDa protein, and 2B5 recognized a single ∼32-kDa protein at 15 h postfertilization. In membrane feeding assays to assess the effect of these MAbs on P. gallinaceum infectivity for Aedes aegypti mosquitoes, the addition of MAbs 1A6 and 2B5 to infectious blood meals significantly inhibited oocyst development in the mosquito midgut. In contrast, MAb 2A5 seemed to enhance infectivity. These results demonstrate that Plasmodium ookinetes secrete proteins (in addition to previously characterized chitinases) that may be targets for blocking malaria transmission. Future investigation of ookinete-secreted neutralization-sensitive molecules should provide valuable insight into mechanisms by which ookinetes exit the blood meal, penetrate and transverse the peritrophic matrix, and invade the mosquito midgut epithelium.

scholarly journals On a mission to block transmission

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Amanda Ross ◽  
Nicolas MB Brancucci
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Transmission ◽  
New Drugs ◽  
Block Transmission ◽  
Blocking Malaria Transmission

The controlled infection of volunteers with Plasmodium falciparum parasites could provide a platform to evaluate new drugs and vaccines aimed at blocking malaria transmission.

Driving mosquito refractoriness to Plasmodium falciparum with engineered symbiotic bacteria

Science ◽  
2017 ◽  
Vol 357 (6358) ◽  
pp. 1399-1402 ◽  
Author(s):  
Sibao Wang ◽  
André L. A. Dos-Santos ◽  
Wei Huang ◽  
Kun Connie Liu ◽  
Mohammad Ali Oshaghi ◽  
...  
Keyword(s):  
Developing Countries ◽  
Plasmodium Falciparum ◽  
Genetically Engineered ◽  
Effector Proteins ◽  
Symbiotic Bacteria ◽  
Male Accessory Glands ◽  
Accessory Glands ◽  
Bacterium Strain ◽  
Novel Approaches ◽  
Deadly Disease

The huge burden of malaria in developing countries urgently demands the development of novel approaches to fight this deadly disease. Although engineered symbiotic bacteria have been shown to render mosquitoes resistant to the parasite, the challenge remains to effectively introduce such bacteria into mosquito populations. We describe a Serratia bacterium strain (AS1) isolated from Anopheles ovaries that stably colonizes the mosquito midgut, female ovaries, and male accessory glands and spreads rapidly throughout mosquito populations. Serratia AS1 was genetically engineered for secretion of anti-Plasmodium effector proteins, and the recombinant strains inhibit development of Plasmodium falciparum in mosquitoes.

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