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Teun Bousema - One of the best experts on this subject based on the ideXlab platform.
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Assays for quantification of male and female Gametocytes in human blood by qRT-PCR in the absence of pure sex-specific Gametocyte standards
Malaria Journal, 2020Co-Authors: Claire Yt Wang, Teun Bousema, James S. Mccarthy, Emma Ballard, Stacey Llewellyn, Louise Marquart, Katharine A CollinsAbstract:Malaria transmission from humans to Anopheles mosquitoes requires the presence of Gametocytes in human peripheral circulation, and the dynamics of transmission are determined largely by the density and sex ratio of the Gametocytes. Molecular methods are thus employed to measure Gametocyte densities, particularly when assessing transmission epidemiology and the efficacy of transmission-blocking interventions. However, accurate quantification of male and female Gametocytes with molecular methods requires pure male and female Gametocytes as reference standards, which are not widely available. qRT-PCR assays were used to quantify levels of sex-specific mRNA transcripts in Plasmodium falciparum female and male Gametocytes (pfs25 and pfMGET, respectively) using synthetic complimentary RNA standards and in vitro cultured Gametocytes. Assays were validated and assay performance was investigated in blood samples of clinical trial participants using these standards and compared to absolute quantification by droplet digital PCR (ddPCR). The number of transcript copies per Gametocyte were determined to be 279.3 (95% CI 253.5–307.6) for the female-specific transcript pfs25, and 12.5 (95% CI 10.6–14.9) for the male-specific transcript pfMGET. These numbers can be used to convert from transcript copies/mL to Gametocyte/mL. The reportable range was determined to be 5.71 × 106 to 5.71 female Gametocytes/mL for pfs25, and 1.73 × 107 to 1.73 × 101 male Gametocytes/mL for pfMGET. The limit of detection was 3.9 (95% CI 2.5–8.2) female Gametocytes/mL for pfs25, and 26.9 (95% CI 19.3–51.7) male Gametocytes/mL for PfMGET. Both assays showed minimal intra-assay and inter-assay variability with coefficient of variation
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An assay for quantification of male and female Gametocytes in human blood by qRT-PCR in the absence of pure Gametocyte standards
2020Co-Authors: Claire Yt Wang, Teun Bousema, James S. Mccarthy, Emma Ballard, Stacey Llewellyn, Louise Marquart, Katharine A CollinsAbstract:Abstract Background Malaria transmission from humans to mosquitoes requires the presence of Gametocytes in human peripheral circulation, and the dynamics of transmission are determined largely by the density and sex ratio of the Gametocytes. Molecular methods are thus employed to measure Gametocyte densities, particularly when assessing transmission epidemiology and the efficacy of transmission-blocking interventions. However accurate quantification of Gametocytes with molecular methods requires pure male and female Gametocytes as reference standards, which are not widely available. Methods qRT-PCR assays were used to quantify levels of sex-specific mRNA transcripts in Plasmodium falciparum female and male Gametocytes ( pfs25 and pfMGET respectively) using synthetic cRNA standards and in-vitro cultured Gametocytes. Assay were validated and assay performance was investigated using blood samples of clinical trial participants (ClinicalTrials.gov reference number NCT02431637 and NCT02431650) using these standards and compared to absolute quantification by droplet digital PCR (ddPCR). Results The number of transcript copies per Gametocyte were determined to be 279.3 (95% CI 253.5 - 307.6) for the female-specific transcript pfs25, and 12.5 (95% CI 10.6 - 14.9) for the male-specific transcript pfMGET . These numbers can be used to convert from transcript copies/mL to Gametocyte/mL. The reportable range was determined to be 5.71x10 6 to 5.71 Gametocytes/mL for pfs25, and 1.73x10 7 to 5.59 for pfMGET. The limit of detection was 3.9 (95% CI 2.5-8.2) Gametocytes/mL for pfs25, and 26.9 (95% CI 19.3 - 51.7) Gametocytes/mL for PfMGET . Both assays showed minimal intra-assay and inter-assay variability with coefficient of variation < 3%. No cross-reactivity was observed in both assays in uninfected human blood samples. Comparison of results from ddPCR to qRT-PCR assays on clinical blood samples indicated high level agreement (ICC=0.998 for pfs25 and 0.995 for pfMGET ). Conclusions We developed and validated qRT-PCR assays that are able to accurately quantify levels of female and male P. falciparum Gametocytes at submicroscopic densities. The assays showed excellent reproducibility, sensitivity, precision, specificity and accuracy. The methodology will enable the estimation of Gametocyte density in the absence of pure female and male Gametocyte standards, and will facilitate clinical trials and epidemiological studies.
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transmission blocking effects of primaquine and methylene blue suggest plasmodium falciparum Gametocyte sterilization rather than effects on sex ratio
Clinical Infectious Diseases, 2019Co-Authors: John S Bradley, Chris Drakeley, Almahamoudou Mahamar, Michael J. Delves, Alassane Dicko, Harouna M Soumare, Halimatou Diawara, Thomas S Churcher, Roly Gosling, Teun BousemaAbstract:Gametocyte density and sex ratio can predict the proportion of mosquitoes that will become infected after feeding on blood of patients receiving nongametocytocidal drugs. Because primaquine and methylene blue sterilize Gametocytes before affecting their density and sex ratio, mosquito feeding experiments are required to demonstrate their early transmission-blocking effects.
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Gametocyte sex ratio the key to understanding plasmodium falciparum transmission
Trends in Parasitology, 2019Co-Authors: Fitsum G Tadesse, Chris Drakeley, Lisette Meersteinkessel, Teun Bousema, Bronner P Goncalves, Lisa C RanfordcartwrightAbstract:A mosquito needs to ingest at least one male and one female Gametocyte to become infected with malaria. The sex of Plasmodium falciparum Gametocytes can be determined microscopically but recent transcriptomics studies paved the way for the development of molecular methods that allow sex-ratio assessments at much lower Gametocyte densities. These sex-specific Gametocyte diagnostics were recently used to examine Gametocyte dynamics in controlled and natural infections as well as the impact of different antimalarial drugs. It is currently unclear to what extent sex-specific Gametocyte diagnostics obviate the need for mosquito feeding assays to formally assess transmission potential. Here, we review recent and historic assessments of Gametocyte sex ratio in relation to host and parasite characteristics, treatment, and transmission potential.
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plasmodium falciparum Gametocyte enrichment in peripheral blood samples by magnetic fractionation Gametocyte yields and possibilities to reuse columns
American Journal of Tropical Medicine and Hygiene, 2019Co-Authors: Wouter Graumans, Kjerstin Lanke, Teun Bousema, Shehu S Awandu, Chiara Andolina, Lynn GrignardAbstract:: Gametocytes are sexual stage malaria parasites responsible for transmission to mosquitoes. Multiple Gametocyte-producing clones may be present in natural infections, but the molecular characterization of Gametocytes is challenging. Because of their magnetic properties, Gametocyte enrichment can be achieved by magnetic fractionation. This increases detection sensitivity and allows specific genotyping of clones that contribute to malaria transmission. Here, we determined the percentage of Plasmodium falciparum Gametocytes successfully bound to magnetic activated cell sorting (MACS) LS columns during magnetic fractionation and assessed whether columns can be reused without risking contamination or affecting column binding efficiency. Bound column fractions were quantified using multiplex quantitative reverse transcription polymerase chain reaction (qRT-PCR) for male (pfMGET) and female (CCp4) Gametocytes and ring-stage asexual parasites (SBP1). To investigate cross contamination between columns, parasite strain identity was determined by merozoite surface protein 2 genotyping followed by capillary electrophoresis fragment sizing. A reproducible high percentage of Gametocytes was bound to MACS LS columns with 94%) of Gametocyte enrichment was achieved when columns were used up to five times with lower binding success after eight times (79%). We observed no evidence for cross contamination between columns.
Robert W. Sauerwein - One of the best experts on this subject based on the ideXlab platform.
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Erythrocyte remodeling by Plasmodium falciparum Gametocytes in the human host interplay
Trends in Parasitology, 2015Co-Authors: Marta Tibúrcio, Robert W. Sauerwein, Catherine Lavazec, Pietro AlanoAbstract:The spread of malaria critically relies on the presence of Plasmodium transmission stages – the Gametocytes – circulating in the blood of an infected individual, which are taken up by Anopheles mosquitoes. A striking feature of Plasmodium falciparum Gametocytes is their long development inside the erythrocytes while sequestered in the internal organs of the human host. Recent studies of the molecular and cellular remodeling of the host erythrocyte induced by P. falciparum during Gametocyte maturation are shedding light on how these may affect the establishment and maintenance of sequestration of the immature transmission stages and the subsequent release and circulation of mature Gametocytes in the peripheral bloodstream.
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a plasmodium falciparum screening assay for anti Gametocyte drugs based on parasite lactate dehydrogenase detection
Journal of Antimicrobial Chemotherapy, 2013Co-Authors: Sarah Dalessandro, Robert W. Sauerwein, Francesco Silvestrini, Yolanda Corbett, Silvia Parapini, Koen J Dechering, Martijn Timmerman, Laura Galastri, Nicoletta Basilico, Pietro AlanoAbstract:OBJECTIVES: Plasmodium Gametocytes, responsible for malaria parasite transmission from humans to mosquitoes, represent a crucial target for new antimalarial drugs to achieve malaria elimination/eradication. We developed a novel colorimetric screening method for anti-Gametocyte compounds based on the parasite lactate dehydrogenase (pLDH) assay, already standardized for asexual stages, to measure Gametocyte viability and drug susceptibility. METHODS: Gametocytogenesis of 3D7 and NF54 Plasmodium falciparum strains was induced in vitro and asexual parasites were depleted with N-acetylglucosamine. Gametocytes were treated with dihydroartemisinin, epoxomicin, methylene blue, primaquine, puromycin or chloroquine in 96-well plates and the pLDH activity was evaluated using a modified Makler protocol. Mosquito infectivity was measured by the standard membrane feeding assay (SMFA). RESULTS: A linear correlation was found between gametocytaemia determined by Giemsa staining and pLDH activity. A concentration-dependent reduction in pLDH activity was observed after 72 h of drug treatment, whereas an additional 72 h of incubation without drugs was required to obtain complete inhibition of Gametocyte viability. SMFA on treated and control Gametocytes confirmed that a reduction in pLDH activity translates into reduced oocyst development in the mosquito vector. CONCLUSIONS: The Gametocyte pLDH assay is fast, easy to perform, cheap and reproducible and is suitable for screening novel transmission-blocking compounds, which does not require parasite transgenic lines.
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sulfadoxine pyrimethamine impairs plasmodium falciparum Gametocyte infectivity and anopheles mosquito survival
International Journal for Parasitology, 2010Co-Authors: Aminatou Kone, Robert W. Sauerwein, Marga Van De Vegtebolmer, Adrian J F Luty, Ogobara K Doumbo, Rianne Siebelinkstoter, Geertjan Van Gemert, Antoine Dara, Hamidou Niangaly, Abdoulaye A DjimdeAbstract:Sulfadoxine-pyrimethamine (SP) is currently the drug of choice for intermittent preventive treatment of Plasmodium falciparum both in pregnancy and infancy. A prolonged parasite clearance time conferred by dhfr and dhps mutations is believed to be responsible for increased Gametocyte prevalence in SP treated individuals. However, using a direct feeding assay in Mali, we showed that Gametocytes present in peripheral venous blood post-SP treatment had reduced infectivity for Anopheles gambiae sensu stricto (ss) mosquitoes. We investigated the potential mechanisms involved in the dhfr and dhps quintuple mutant NF-135 and the single dhps 437 mutant NF-54. Concentrations of sulfadoxine (S) and pyrimethamine (P) equivalent to the serum levels of the respective drugs on day 3 (S = 61 μg/ml, P = 154.7 ng/ml) day 7 (S = 33.8 μg/ml, P = 66.6 ng/ml) and day 14 (S = 14.2 μg/ml, P = 15.7 ng/ml) post-SP treatment were used to study the effect on gametocytogenesis, Gametocyte maturation and infectivity to Anopheles stephensi mosquitoes fed through an artificial membrane. The drugs readily induced gametocytogenesis in the mutant NF-135 strain but effectively killed the wild-type NF-54. However, both drugs impaired Gametocyte maturation yielding odd-shaped non-exflagellating mature Gametocytes. The concomitant ingestion of both S and P together with Gametocytemic blood-meal significantly reduced the prevalence of oocyst positivity as well as oocyst density when compared to controls (P < 0.001). In addition, day 3 concentrations of SP decreased mosquito survival by up to 65% (P < 0.001). This study demonstrates that SP is deleterious in vitro for Gametocyte infectivity as well as mosquito survival.
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revisiting the circulation time of plasmodium falciparum Gametocytes molecular detection methods to estimate the duration of Gametocyte carriage and the effect of gametocytocidal drugs
Malaria Journal, 2010Co-Authors: Teun J Bousema, Colin J Sutherland, Lucy C Okell, Seif Shekalaghe, Jamie T Griffin, Sabah A Omar, Patrick Sawa, Robert W. SauerweinAbstract:Background: There is renewed acknowledgement that targeting Gametocytes is essential for malaria control and elimination efforts. Simple mathematical models were fitted to data from clinical trials in order to determine the mean Gametocyte circulation time and duration of Gametocyte carriage in treated malaria patients. Methods: Data were used from clinical trials from East Africa. The first trial compared non-artemisinin combination therapy (non-ACT: sulphadoxine-pyrimethamine (SP) plus amodiaquine) and artemisinin-based combination therapy (ACT: SP plus artesunate (AS) or artemether-lumefantrine). The second trial compared ACT (SP+AS) with ACT in combination with a single dose of primaquine (ACT-PQ: SP+AS+PQ). Mature Gametocytes were quantified in peripheral blood samples by nucleic acid sequence based amplification. A simple deterministic compartmental model was fitted to Gametocyte densities to estimate the circulation time per Gametocyte; a similar model was fitted to Gametocyte prevalences to estimate the duration of Gametocyte carriage after efficacious treatment. Results: The mean circulation time of Gametocytes was 4.6-6.5 days. After non-ACT treatment, patients were estimated to carry Gametocytes for an average of 55 days (95% CI 28.7 - 107.7). ACT reduced the duration of Gametocyte carriage fourfold to 13.4 days (95% CI 10.2-17.5). Addition of PQ to ACT resulted in a further fourfold reduction of the duration of Gametocyte carriage. Conclusions: These findings confirm previous estimates of the circulation time of Gametocytes, but indicate a much longer duration of (low density) Gametocyte carriage after apparently successful clearance of asexual parasites. ACT shortened the period of Gametocyte carriage considerably, and had the most pronounced effect on mature Gametocytes when combined with PQ.
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revisiting the circulation time of plasmodium falciparum Gametocytes molecular detection methods to estimate the duration of Gametocyte carriage and the effect of gametocytocidal drugs
Malaria Journal, 2010Co-Authors: Colin J Sutherland, Lucy C Okell, Seif Shekalaghe, Jamie T Griffin, Sabah A Omar, Patrick Sawa, Teun Bousema, Robert W. SauerweinAbstract:Background There is renewed acknowledgement that targeting Gametocytes is essential for malaria control and elimination efforts. Simple mathematical models were fitted to data from clinical trials in order to determine the mean Gametocyte circulation time and duration of Gametocyte carriage in treated malaria patients.
Chris Drakeley - One of the best experts on this subject based on the ideXlab platform.
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transmission blocking effects of primaquine and methylene blue suggest plasmodium falciparum Gametocyte sterilization rather than effects on sex ratio
Clinical Infectious Diseases, 2019Co-Authors: John S Bradley, Chris Drakeley, Almahamoudou Mahamar, Michael J. Delves, Alassane Dicko, Harouna M Soumare, Halimatou Diawara, Thomas S Churcher, Roly Gosling, Teun BousemaAbstract:Gametocyte density and sex ratio can predict the proportion of mosquitoes that will become infected after feeding on blood of patients receiving nongametocytocidal drugs. Because primaquine and methylene blue sterilize Gametocytes before affecting their density and sex ratio, mosquito feeding experiments are required to demonstrate their early transmission-blocking effects.
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Gametocyte sex ratio the key to understanding plasmodium falciparum transmission
Trends in Parasitology, 2019Co-Authors: Fitsum G Tadesse, Chris Drakeley, Lisette Meersteinkessel, Teun Bousema, Bronner P Goncalves, Lisa C RanfordcartwrightAbstract:A mosquito needs to ingest at least one male and one female Gametocyte to become infected with malaria. The sex of Plasmodium falciparum Gametocytes can be determined microscopically but recent transcriptomics studies paved the way for the development of molecular methods that allow sex-ratio assessments at much lower Gametocyte densities. These sex-specific Gametocyte diagnostics were recently used to examine Gametocyte dynamics in controlled and natural infections as well as the impact of different antimalarial drugs. It is currently unclear to what extent sex-specific Gametocyte diagnostics obviate the need for mosquito feeding assays to formally assess transmission potential. Here, we review recent and historic assessments of Gametocyte sex ratio in relation to host and parasite characteristics, treatment, and transmission potential.
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plasmodium falciparum antigens on the surface of the Gametocyte infected erythrocyte
PLOS ONE, 2008Co-Authors: Maha Saeed, Chris Drakeley, Geoffrey A T Targett, Will Roeffen, Neal Alexander, Colin J SutherlandAbstract:BACKGROUND: The asexual blood stages of the human malaria parasite Plasmodium falciparum produce highly immunogenic polymorphic antigens that are expressed on the surface of the host cell. In contrast, few studies have examined the surface of the Gametocyte-infected erythrocyte. METHODOLOGY/PRINCIPAL FINDINGS: We used flow cytometry to detect antibodies recognising the surface of live cultured erythrocytes infected with Gametocytes of P. falciparum strain 3D7 in the plasma of 200 Gambian children. The majority of children had been identified as carrying Gametocytes after treatment for malaria, and each donated blood for mosquito-feeding experiments. None of the plasma recognised the surface of erythrocytes infected with developmental stages of Gametocytes (I-IV), but 66 of 194 (34.0%) plasma contained IgG that recognised the surface of erythrocytes infected with mature (stage V) Gametocytes. Thirty-four (17.0%) of 200 plasma tested recognised erythrocytes infected with trophozoites and schizonts, but there was no association with recognition of the surface of Gametocyte-infected erythrocytes (odds ratio 1.08, 95% C.I. 0.434-2.57; P = 0.851). Plasma antibodies with the ability to recognise Gametocyte surface antigens (GSA) were associated with the presence of antibodies that recognise the gamete antigen Pfs 230, but not Pfs48/45. Antibodies recognising GSA were associated with donors having lower Gametocyte densities 4 weeks after antimalarial treatment. CONCLUSIONS/SIGNIFICANCE: We provide evidence that GSA are distinct from antigens detected on the surface of asexual 3D7 parasites. Our findings suggest a novel strategy for the development of transmission-blocking vaccines.
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increased plasmodium falciparum Gametocyte production in mixed infections with p malariae
American Journal of Tropical Medicine and Hygiene, 2008Co-Authors: Teun J Bousema, Chris Drakeley, Sabah A Omar, Louis C Gouagna, Henk D F H Schallig, Petra F Mens, Theo Arens, Rein M G J Houben, Robert W. SauerweinAbstract:Plasmodium falciparum and P. malariae occur endemically in many parts of Africa. Observations from malariotherapy patients suggest that co-infection with P. malariae may increase P. falciparum Gametocyte production. We determined P. falciparum Gametocyte prevalence and density by quantitative nucleic acid sequence-based amplifi- cation (QT-NASBA) after antimalarial treatment of Kenyan children with either P. falciparum mono-infection or P. falciparum and P. malariae mixed infection. In addition, we analyzed the relationship between mixed species infections and microscopic P. falciparum Gametocyte prevalence in three datasets from previously published studies. In Kenyan children, QT-NASBA Gametocyte density was increased in mixed species infections (P 0.03). We also observed higher microscopic prevalences of P. falciparum Gametocytes in mixed species infections in studies from Tanzania and Kenya (odds ratio 2.15, 95% confidence interval 0.99-4.65 and 2.39, 1.58-3.63) but not in a study from Nigeria. These data suggest that co-infection with P. malariae is correlated with increased P. falciparum Gametocytemia.
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submicroscopic plasmodium falciparum Gametocyte carriage is common in an area of low and seasonal transmission in tanzania
Tropical Medicine & International Health, 2007Co-Authors: Seif Shekalaghe, Robert W. Sauerwein, J T Bousema, K K Kunei, P Lushino, Alutu Masokoto, L R Wolters, Steve Mwakalinga, Franklin W Mosha, Chris DrakeleyAbstract:OBJECTIVE: Recently developed molecular Gametocyte detection techniques have shown that submicroscopic Plasmodium falciparum Gametocytes are common in symptomatic patients and can infect mosquitoes. The relevance for the infectious reservoir of malaria in the general population remains unknown. In this study, we investigated submicroscopic asexual parasitaemia and gametocytaemia in inhabitants of an area of hypoendemic and seasonal malaria in Tanzania. METHODS: Two cross-sectional malariometric surveys were conducted in the dry and wet seasons of 2005 in villages in lower Moshi, Tanzania. Finger prick blood samples were taken to determine the prevalence of P. falciparum parasites by microscopy, rapid diagnostic test and real-time nucleic acid sequence-based amplification (QT-NASBA). RESULTS: 2752 individuals participated in the surveys, of whom 1.9% (51/2721) had microscopically confirmed asexual parasites and 0.4% (10/2721) had Gametocytes. In contrast, QT-NASBA revealed that 32.5% (147/453) of the individuals harboured asexual parasites and 15.0% (68/453) had Gametocytes. No age dependency or seasonality was observed in submicroscopic parasite carriage. DISCUSSION: Molecular detection techniques reveal that carriage of submicroscopic asexual parasite and Gametocyte densities is relatively common in this low transmission area. Submicroscopic gametocytaemia is likely to be responsible for maintaining malarial transmission in the study area.
Teun J Bousema - One of the best experts on this subject based on the ideXlab platform.
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revisiting the circulation time of plasmodium falciparum Gametocytes molecular detection methods to estimate the duration of Gametocyte carriage and the effect of gametocytocidal drugs
Malaria Journal, 2010Co-Authors: Teun J Bousema, Colin J Sutherland, Lucy C Okell, Seif Shekalaghe, Jamie T Griffin, Sabah A Omar, Patrick Sawa, Robert W. SauerweinAbstract:Background: There is renewed acknowledgement that targeting Gametocytes is essential for malaria control and elimination efforts. Simple mathematical models were fitted to data from clinical trials in order to determine the mean Gametocyte circulation time and duration of Gametocyte carriage in treated malaria patients. Methods: Data were used from clinical trials from East Africa. The first trial compared non-artemisinin combination therapy (non-ACT: sulphadoxine-pyrimethamine (SP) plus amodiaquine) and artemisinin-based combination therapy (ACT: SP plus artesunate (AS) or artemether-lumefantrine). The second trial compared ACT (SP+AS) with ACT in combination with a single dose of primaquine (ACT-PQ: SP+AS+PQ). Mature Gametocytes were quantified in peripheral blood samples by nucleic acid sequence based amplification. A simple deterministic compartmental model was fitted to Gametocyte densities to estimate the circulation time per Gametocyte; a similar model was fitted to Gametocyte prevalences to estimate the duration of Gametocyte carriage after efficacious treatment. Results: The mean circulation time of Gametocytes was 4.6-6.5 days. After non-ACT treatment, patients were estimated to carry Gametocytes for an average of 55 days (95% CI 28.7 - 107.7). ACT reduced the duration of Gametocyte carriage fourfold to 13.4 days (95% CI 10.2-17.5). Addition of PQ to ACT resulted in a further fourfold reduction of the duration of Gametocyte carriage. Conclusions: These findings confirm previous estimates of the circulation time of Gametocytes, but indicate a much longer duration of (low density) Gametocyte carriage after apparently successful clearance of asexual parasites. ACT shortened the period of Gametocyte carriage considerably, and had the most pronounced effect on mature Gametocytes when combined with PQ.
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increased plasmodium falciparum Gametocyte production in mixed infections with p malariae
American Journal of Tropical Medicine and Hygiene, 2008Co-Authors: Teun J Bousema, Chris Drakeley, Sabah A Omar, Louis C Gouagna, Henk D F H Schallig, Petra F Mens, Theo Arens, Rein M G J Houben, Robert W. SauerweinAbstract:Plasmodium falciparum and P. malariae occur endemically in many parts of Africa. Observations from malariotherapy patients suggest that co-infection with P. malariae may increase P. falciparum Gametocyte production. We determined P. falciparum Gametocyte prevalence and density by quantitative nucleic acid sequence-based amplifi- cation (QT-NASBA) after antimalarial treatment of Kenyan children with either P. falciparum mono-infection or P. falciparum and P. malariae mixed infection. In addition, we analyzed the relationship between mixed species infections and microscopic P. falciparum Gametocyte prevalence in three datasets from previously published studies. In Kenyan children, QT-NASBA Gametocyte density was increased in mixed species infections (P 0.03). We also observed higher microscopic prevalences of P. falciparum Gametocytes in mixed species infections in studies from Tanzania and Kenya (odds ratio 2.15, 95% confidence interval 0.99-4.65 and 2.39, 1.58-3.63) but not in a study from Nigeria. These data suggest that co-infection with P. malariae is correlated with increased P. falciparum Gametocytemia.
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seasonal patterns of plasmodium falciparum Gametocyte prevalence and density in a rural population of burkina faso
Acta Tropica, 2008Co-Authors: Andre Lin Ouedraogo, Teun J Bousema, Sake J De Vlas, Edith Ilboudosanogo, N Cuzinouattara, Issa Nebie, J P Verhave, Aboubakar S Ouattara, Robert W. SauerweinAbstract:Gametocytes are the malaria parasite stages that secure the transmission from the human host to the mosquito. The identification of natural parameters that influence Gametocyte carriage can contribute to a better understanding of the dynamics of the sexual stage parasites for transmission reducing strategies. A total of 3400 blood slide readings were done during four cross-sectional surveys (2002-2003) including all age groups to determine the effect of season on Plasmodium falciparum Gametocytes in a seasonal malaria transmission area of Burkina Faso. Entomological data were collected to determine the malaria transmission intensity in relation to seasons. Transmission intensity was estimated by monthly EIRs, averaging 28 and 32 infective bites/person/month in the wet seasons of 2002 and 2003, respectively. The EIR in the dry seasons was below one infective bite/person/month. The Gametocyte prevalence was significantly higher at the start and peak of the wet season compared to the dry season when corrected for asexual parasite density and age. Gametocyte density significantly increased during the wet season after correction for asexual parasite density and age. In this study, season appears to be an independent parameter that determines Gametocyte prevalence and density and should be considered to be included in epidemiological studies on malaria transmission.
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submicroscopic plasmodium falciparum Gametocyte densities frequently result in mosquito infection
American Journal of Tropical Medicine and Hygiene, 2007Co-Authors: Petra Schneider, Teun J Bousema, Marga Van De Vegtebolmer, Sabah A Omar, Louis C Gouagna, Silas Otieno, Robert W. SauerweinAbstract:Submicroscopic Plasmodium falciparum Gametocytemia (<5,000 Gametocytes/mL) is common and may result in mosquito infection. We assessed the relation between Gametocyte density and mosquito infection under experimental and field conditions using real-time quantitative nucleic acid sequence-based amplification (QT-NASBA) for Gametocyte quantification. Serial dilutions of NF54 P. falciparum Gametocytes showed a positive association between Gametocyte density and the proportion of infected mosquitoes (beta=6.1; 95% confidence interval [CI], 2.7-9.6; P=0.001). Successful infection became unlikely below an estimated density of 250-300 Gametocytes/mL. In the field, blood samples of 100 naturally infected children showed a positive association between Gametocyte density and oocyst counts in mosquitoes (beta=0.38; 95% CI, 0.14-0.61; P=0.002). The relative contribution to malaria transmission was similar for carriers with submicroscopic and microscopic Gametocytemia. Our results show that transmission occurs efficiently at submicroscopic Gametocyte densities and that carriers harboring submicroscopic Gametocytemia constitute a considerable proportion of the human infectious reservoir.
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the epidemiology of plasmodium falciparum Gametocytes weapons of mass dispersion
Trends in Parasitology, 2006Co-Authors: Chris Drakeley, Teun J Bousema, Robert W. Sauerwein, Colin J Sutherland, Geoffrey A T TargettAbstract:Much of the epidemiology of Plasmodium falciparum in Sub-Saharan Africa focuses on the prevalence patterns of asexual parasites in people of different ages, whereas the Gametocytes that propagate the disease are often neglected. One expected benefit of the widespread introduction of artemisinin-based combination therapy for malaria is a reduction in Gametocyte carriage. However, the factors that affect the transmission of parasites from humans to mosquitoes show complex dynamics in relation to the intensity and seasonality of malaria transmission, and thus such benefits might not be automatic. Here, we review data on Gametocyte carriage in the context of the development of naturally acquired immunity and population infectivity.
Michael J. Delves - One of the best experts on this subject based on the ideXlab platform.
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transmission blocking effects of primaquine and methylene blue suggest plasmodium falciparum Gametocyte sterilization rather than effects on sex ratio
Clinical Infectious Diseases, 2019Co-Authors: John S Bradley, Chris Drakeley, Almahamoudou Mahamar, Michael J. Delves, Alassane Dicko, Harouna M Soumare, Halimatou Diawara, Thomas S Churcher, Roly Gosling, Teun BousemaAbstract:Gametocyte density and sex ratio can predict the proportion of mosquitoes that will become infected after feeding on blood of patients receiving nongametocytocidal drugs. Because primaquine and methylene blue sterilize Gametocytes before affecting their density and sex ratio, mosquito feeding experiments are required to demonstrate their early transmission-blocking effects.
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hundreds of dual stage antimalarial molecules discovered by a functional Gametocyte screen
Nature Communications, 2017Co-Authors: Celia Miguelblanco, Irene Molina, Ana I Bardera, Beatriz Diaz, Laura De Las Heras, Sonia Lozano, Carolina Gonzalez, Janneth Rodrigues, Michael J. DelvesAbstract:Plasmodium falciparum stage V Gametocytes are responsible for parasite transmission, and drugs targeting this stage are needed to support malaria elimination. We here screen the Tres Cantos Antimalarial Set (TCAMS) using the previously developed P. falciparum female Gametocyte activation assay (Pf FGAA), which assesses stage V female Gametocyte viability and functionality using Pfs25 expression. We identify over 400 compounds with activities 10,000 compounds against stage V female Gametocytes, identify active compounds belonging to 57 chemotypes and confirm transmission blocking activity of four selected compounds in vitro.
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Changes in metabolic phenotypes of Plasmodium falciparum in vitro cultures during Gametocyte development
Malaria Journal, 2014Co-Authors: Sabrina D. Lamour, Ursula Straschil, Jasmina Saric, Michael J. DelvesAbstract:Background: Gametocytes are the Plasmodium life stage that is solely responsible for malaria transmission. Despite their important role in perpetuating malaria, Gametocyte differentiation and development is poorly understood. Methods: To shed light on the biochemical changes that occur during asexual and Gametocyte development, metabolic characterization of media from in vitro intra-erythrocytic Plasmodium falciparum cultures was performed throughout Gametocyte development by applying 1 H nuclear magnetic spectroscopy, and using sham erythrocyte cultures as controls. Spectral differences between parasite and sham cultures were assessed via principal component analyses and partial-least squares analyses, and univariate statistical methods. Results: Clear parasite-associated changes in metabolism were observed throughout the culture period, revealing differences between asexual parasites and Gametocyte stages. With culture progression and development of Gametocytes, parasitic release of the glycolytic end products lactate, pyruvate, alanine, and glycerol, were found to be dramatically reduced whilst acetate release was greatly increased. Also, uptake of lipid moieties CH2 ,C H3, and CH = CH-CH2-CH2 increased throughout Gametocyte development, peaking with maturity. Conclusions: This study uniquely presents an initial characterization of the metabolic exchange between parasite and culture medium during in vitro P. falciparum Gametocyte culture. Results suggest that energy metabolism and lipid utilization between the asexual stages and Gametocytes is different. This study provides new insights for Gametocyte-specific nutritional requirements to aid future optimization and standardization of in vitro Gametocyte cultivation, and highlights areas of novel Gametocyte cell biology that deserve to be studied in greater detail and may yield new targets for transmission-blocking drugs.
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changes in metabolic phenotypes of plasmodium falciparum in vitro cultures during Gametocyte development
Malaria Journal, 2014Co-Authors: Sabrina D. Lamour, Ursula Straschil, Jasmina Saric, Michael J. DelvesAbstract:Background Gametocytes are the Plasmodium life stage that is solely responsible for malaria transmission. Despite their important role in perpetuating malaria, Gametocyte differentiation and development is poorly understood.
