Targeting Gametocytes of the Malaria Parasite Plasmodium falciparum in a Functional Genomics Era: Next Steps

Chawla, Jyotsna; Oberstaller, Jenna; Adams, John

doi:10.3390/pathogens10030346

Cited by 20 publications

(21 citation statements)

References 235 publications

(169 reference statements)

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“…Indeed, the enormous complexity of this overall system has led to new efforts utilizing mathematical and computational modelling strategies to study the problems and trajectories [ 172 – 174 ]. Top goals to achieve malaria eradication include treatment of infected individuals, whether they are symptomatic or not [ 175 ], with the goal of getting rid of all parasite subpopulations (circulating or not), including gametocytes [ 176 ] that transmit the disease to Anopheles mosquitoes where fertilization occurs and a new brood of parasites forms.…”

Section: Twenty-first Century—turning Point In Malaria Researchmentioning

confidence: 99%

Systems biology of malaria explored with nonhuman primates

Galinski

2022

Malar J

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Abstract“The Primate Malarias” book has been a uniquely important resource for multiple generations of scientists, since its debut in 1971, and remains pertinent to the present day. Indeed, nonhuman primates (NHPs) have been instrumental for major breakthroughs in basic and pre-clinical research on malaria for over 50 years. Research involving NHPs have provided critical insights and data that have been essential for malaria research on many parasite species, drugs, vaccines, pathogenesis, and transmission, leading to improved clinical care and advancing research goals for malaria control, elimination, and eradication. Whilst most malaria scientists over the decades have been studying Plasmodium falciparum, with NHP infections, in clinical studies with humans, or using in vitro culture or rodent model systems, others have been dedicated to advancing research on Plasmodium vivax, as well as on phylogenetically related simian species, including Plasmodium cynomolgi, Plasmodium coatneyi, and Plasmodium knowlesi. In-depth study of these four phylogenetically related species over the years has spawned the design of NHP longitudinal infection strategies for gathering information about ongoing infections, which can be related to human infections. These Plasmodium-NHP infection model systems are reviewed here, with emphasis on modern systems biological approaches to studying longitudinal infections, pathogenesis, immunity, and vaccines. Recent discoveries capitalizing on NHP longitudinal infections include an advanced understanding of chronic infections, relapses, anaemia, and immune memory. With quickly emerging new technological advances, more in-depth research and mechanistic discoveries can be anticipated on these and additional critical topics, including hypnozoite biology, antigenic variation, gametocyte transmission, bone marrow dysfunction, and loss of uninfected RBCs. New strategies and insights published by the Malaria Host–Pathogen Interaction Center (MaHPIC) are recapped here along with a vision that stresses the importance of educating future experts well trained in utilizing NHP infection model systems for the pursuit of innovative, effective interventions against malaria.

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Section: Twenty-first Century—turning Point In Malaria Researchmentioning

confidence: 99%

Systems biology of malaria explored with nonhuman primates

Galinski

2022

Malar J

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“…Previous studies have shown that a majority of asexual parasites have AP2-G silenced [47] and this gene silencing may be induced by histone deacetylase (Hda2) [57]. Depletion of HP1 through GDV1, another gene that regulates gametocyte production, was shown to increase schizont development into gametocytes by 50% [47,58]. Further, the presence of Stabilization ligand Shield 1 (Shld1) may also increase transcription of AP2-G by stabilizing the protein complex for transcription and enhance gametocyte production.…”

Section: Gametocyte Commitment and Developmentmentioning

confidence: 99%

From Genes to Biomarkers: Understanding the Biology of Malaria Gametocytes and Their Detection

Kepple¹,

Ford²,

Little³

et al. 2022

Genetic Polymorphisms - New Insights

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Each year, approximately 230 million malaria cases and 400,00 malaria deaths are reported worldwide. Malaria is a life-threatening disease caused by Plasmodium parasites that are transmitted from one individual to another through the bites of infected female Anopheles mosquitoes. Malaria parasites replicate asexually in the human host, and, in each replication cycle, a portion of the asexual stages develops into sexual gametocytes that permit transmission. The proportion of infections that carries gametocytes and the infectivity of gametocytes are indicators of human-to-mosquito transmission potential. In P. falciparum, gametocytes appear 10–14 days after infection, whereas in P. vivax gametocytes appear simultaneously with asexual schizonts. Such difference in development not only increases the length of time that an individual is infectious, but also increases the likelihood of transmission before treatment. The conversion from asexual parasites to gametocytes is also highly variable between infections. Differences in age, host immune response, parasite genetic composition, density of red blood cells, presence of co-infecting parasite strains, and antimalarial drug use could affect gametocytes production. In P. vivax, the unique ability to produce hypnozoites, a dormant liver stage of the parasite, may allow gametocytes to be produced periodically from relapse and contribute to transmission. In this chapter, we will provide an overview of the biology of Plasmodium gametocytes, existing tools for gametocyte detection, and features of gametocyte genes. The biological insights and genetic findings are essential to developing better detection biomarkers and effective strategies to reduce transmission in malaria-endemic countries.

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“…Additional gametocyte-specific gene discovery efforts have been published ( Ikadai et al, 2013 ; Chawla et al, 2021 ; Muthui et al, 2021 ); although antigen expression, immunization, and TRA assessment of the antibodies are not completed.…”

Section: Novel Tbv Candidate Discovery Directly Using Human Malaria Parasitesmentioning

confidence: 99%

Identification of Novel Malaria Transmission-Blocking Vaccine Candidates

Takashima

Tachibana

Morita

et al. 2021

Front. Cell. Infect. Microbiol.

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Control measures have significantly reduced malaria morbidity and mortality in the last two decades; however, the downward trends have stalled and have become complicated by the emergence of COVID-19. Significant efforts have been made to develop malaria vaccines, but currently only the RTS,S/AS01 vaccine against Plasmodium falciparum has been recommended by the WHO, for widespread use among children in sub-Saharan Africa. The efficacy of RTS,S/AS01 is modest, and therefore the development of more efficacious vaccines is still needed. In addition, the development of transmission-blocking vaccines (TBVs) to reduce the parasite transmission from humans to mosquitoes is required toward the goal of malaria elimination. Few TBVs have reached clinical development, and challenges include low immunogenicity or high reactogenicity in humans. Therefore, novel approaches to accelerate TBV research and development are urgently needed, especially novel TBV candidate discovery. In this mini review we summarize the progress in TBV research and development, novel TBV candidate discovery, and discuss how to accelerate novel TBV candidate discovery.

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Targeting Gametocytes of the Malaria Parasite Plasmodium falciparum in a Functional Genomics Era: Next Steps

Cited by 20 publications

References 235 publications

Systems biology of malaria explored with nonhuman primates

Systems biology of malaria explored with nonhuman primates

From Genes to Biomarkers: Understanding the Biology of Malaria Gametocytes and Their Detection

Identification of Novel Malaria Transmission-Blocking Vaccine Candidates

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