Modeling the dynamics of Plasmodium falciparum gametocytes in humans during malaria infection.
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ABSTRACT:
SUBMITTER: Cao P
PROVIDER: S-EPMC6819085 | biostudies-literature | 2019 Oct
REPOSITORIES: biostudies-literature
Publications
Modeling the dynamics of <i>Plasmodium falciparum</i> gametocytes in humans during malaria infection.
Cao Pengxing P Collins Katharine A KA Zaloumis Sophie S Wattanakul Thanaporn T Tarning Joel J Simpson Julie A JA McCarthy James J McCaw James M JM
eLife 20191029
Renewed efforts to eliminate malaria have highlighted the potential to interrupt human-to-mosquito transmission - a process mediated by gametocyte kinetics in human hosts. Here we study the in vivo dynamics of <i>Plasmodium falciparum</i> gametocytes by establishing a framework which incorporates improved measurements of parasitemia, a novel gametocyte dynamics model and model fitting using Bayesian hierarchical inference. We found that the model provides an excellent fit to the clinical data fr ...[more]
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Project description:The sexual stages are vital phases in malaria parasite transmission and are the targets of various interventions such as transmission blocking vaccines. The molecular mechanisms underlying sexual development, however, remain poorly understood. We report mappping of a determinant previously linked to a male gametocyte development defect in the P. falciparum Dd2 parasite to an 82 kb region on chromosome 12. In order to find a critical gene in this region, we compared gene expression pattern in sexual stage of the parasite between Dd2 and its normal gametocyte-producing ancestor W2 clones. The region contains a sexual stage specific gene (pfmdv 1) that is expressed substantially at a lower level in the Dd2 than in W2 parasite. Disruption of pfmdv 1 results in a dramatic reduction in mature gametocytes, especially male gametocytes, with the majority of sexually committed parasites arrested at stage-I. The pfmdv-1 knockout parasites show an enlarged nucleus, often with separation of the inner and outer nuclear membranes and presence of multi-membrane vesicles in red blood cell cytoplasm. Mosquito infectivity of the knockout parasites is also greatly reduced, but not completely lost, suggesting presence of compensatory mechanisms in the sexual development pathways. Data include Day 8 gametocytes of male defective Dd2 and parental W2 clones of Plasmodium falciparum. The series includes three biological repeats. Keywords: repeat sample
2010-06-10 | E-GEOD-2265 | biostudies-arrayexpress
Project description:BackgroundThe sexual stages (gametocytes) of Plasmodium falciparum do not directly contribute to the pathology of malaria but are essential for transmission of the parasite from the human host to the mosquito. Mature gametocytes circulate in infected human blood for several days and their circulation time has been modelled mathematically from data of previous in vivo studies. This is the first time that longevity of gametocytes is studied experimentally in vitro.MethodsThe in vitro longevity of P. falciparum gametocytes of 1 clinical isolate and 2 laboratory strains was assessed by three different methods: microscopy, flow cytometry and reverse transcription quantitative real-time PCR (RT-qPCR). Additionally, the rate of gametocytogenesis of the used P. falciparum strains was compared.ResultsThe maximum in vitro lifespan of P. falciparum gametocytes reached almost 2 months (49 days by flow cytometry, 46 days by microscopy, and at least 52 days by RT-qPCR) from the starting day of gametocyte culture to death of last parasite in the tested strains with an average 50% survival rate of 6.5, 2.6 and 3.5 days, respectively. Peak gametocytaemia was observed on average 19 days after initiation of gametocyte culture followed by a steady decline due to natural decay of the parasites. The rate of gametocytogenesis was highest in the NF54 strain.ConclusionsPlasmodium falciparum mature gametocytes can survive up to 16-32 days (at least 14 days for mature male gametocytes) in vitro in absence of the influence of host factors. This confirms experimentally a previous modelling estimate that used molecular tools for gametocyte detection in treated patients. The survival time might reflect the time the parasite can be transmitted to the mosquito after clearance of asexual parasites. These results underline the importance of efficient transmission blocking agents in the fight against malaria.
| S-EPMC5553604 | biostudies-literature