Antimalarial Transmission-Blocking Interventions: Past, Present, and Future

Delves, Michael J.; Angrisano, Fiona; Blagborough, Andrew M.

doi:10.1016/j.pt.2018.07.001

Cited by 68 publications

(65 citation statements)

References 123 publications

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“…Molecules/pathways involved in these crucial steps of the parasite life cycle may represent novel promising targets for effective transmission-blocking interventions (11).…”

Section: Introductionmentioning

confidence: 99%

A Comprehensive Gender-related Secretome of Plasmodium berghei Sexual Stages

Grasso

Mochi

Fratini

et al. 2020

Molecular & Cellular Proteomics

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Plasmodium, the malaria parasite, undergoes a complex life cycle alternating between a vertebrate host and a mosquito vector of the genus Anopheles. In red blood cells of the vertebrate host, Plasmodium multiplies asexually or differentiates into gamete precursors, the male and female gametocytes, responsible for parasite transmission. Sexual stage maturation occurs in the midgut of the mosquito vector, where male and female gametes egress from the host erythrocytes to fuse and form a zygote. Gamete egress entails the successive rupture of two membranes surrounding the parasite, the parasitophorous vacuole membrane and the erythrocyte plasma membrane. In this study, we used the rodent model parasite Plasmodium berghei to design a label-free quantitative proteomic approach aimed at identifying gender-related proteins differentially released/secreted by purified mature gametocytes when activated to form gametes. We compared the abundance of molecules secreted by wild type gametocytes of both genders with that of a transgenic line defective in male gamete maturation and egress. This enabled us to provide a comprehensive dataset of egress-related molecules and their gender specificity. Using specific antibodies, we validated eleven candidate molecules, predicted as either gender-specific or common to both male and female gametocytes. All of them localize to punctuate, vesicle-like structures that relocate to cell periphery upon activation, but only three of them localize to the gametocyte-specific secretory vesicles named osmiophilic bodies. Our results confirm that the egress process involves a tightly coordinated secretory apparatus that includes different types of vesicles and may put the basis for functional studies aimed at designing novel transmission-blocking molecules.

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“…Molecules/pathways involved in these crucial steps of the parasite life cycle may represent novel promising targets for effective transmission-blocking interventions (11).…”

Section: Introductionmentioning

confidence: 99%

A Comprehensive Gender-related Secretome of Plasmodium berghei Sexual Stages

Grasso

Mochi

Fratini

et al. 2020

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

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“…With the move towards malaria elimination and eradication, new tools and strategies to reduce onward transmission of Plasmodium infections, including transmission-blocking interventions (TBI), are considered highly beneficial [1,2]. An increasing number of drugand vaccine-based TBI are in the pipeline [3] and will require monitoring tools for efficacy. Additionally, it is considered highly beneficial to characterize the human infectious reservoir for malaria in low endemic settings approaching elimination, to better target and monitor TBI [4,5].…”

Section: Introductionmentioning

confidence: 99%

Comparison of infectivity of Plasmodium vivax to wild-caught and laboratory-adapted (colonized) Anopheles arabiensis mosquitoes in Ethiopia

et al. 2020

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Background: Mosquito-feeding assays that assess transmission of Plasmodium from man-to-mosquito typically use laboratory mosquito colonies. The microbiome and genetic background of local mosquitoes may be different and influence Plasmodium transmission efficiency. In order to interpret transmission studies to the local epidemiology, it is therefore crucial to understand the relationship between infectivity in laboratory-adapted and local mosquitoes. Methods: We assessed infectivity of Plasmodium vivax-infected patients from Adama, Ethiopia, using laboratoryadapted (colony) and wild-caught (wild) mosquitoes raised from larval collections in paired feeding experiments. Feeding assays used 4-6 day-old female Anopheles arabiensis mosquitoes after starvation for 12 h (colony) and 18 h (wild). Oocyst development was assessed microscopically 7 days post-feeding. Wild mosquitoes were identified morphologically and confirmed by genotyping. Asexual parasites and gametocytes were quantified in donor blood by microscopy. Results: In 36 paired experiments (25 P. vivax infections and 11 co-infections with P. falciparum), feeding efficiency was higher in colony (median: 62.5%; interquartile range, IQR: 47.0-79.0%) compared to wild mosquitoes (median: 27.8%; IQR: 17.0-38.0%; Z = 5.02; P < 0.001). Plasmodium vivax from infectious individuals (51.6%, 16/31) infected a median of 55.0% (IQR: 6.7-85.7%; range: 5.5-96.7%; n = 14) of the colony and 52.7% (IQR: 20.0-80.0%; range: 3.2-95.0%; n = 14) of the wild mosquitoes. A strong association (ρ (16) = 0.819; P < 0.001) was observed between the proportion of infected wild and colony mosquitoes. A positive association was detected between microscopically detected gametocytes and the proportion of infected colony (ρ (31) = 0.452; P = 0.011) and wild (ρ (31) = 0.386; P = 0.032) mosquitoes.

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“…Unfortunately, the two drugs are beset by toxicity concerns in patients with Glucose-6-phosphate dehydrogenase (G6PD) enzyme deficiency. 18 The above described scenarios, therefore, warrant sustained efforts in the discovery and development of new antimalarial drugs as suitable alternatives to currently existing ones and having transmission-blocking potential.…”

Section: Introductionmentioning

confidence: 99%