Nonlinear mixed effects modeling of gametocyte carriage in patients with uncomplicated malaria

Simple item page
dc.contributor.authorDistiller, Gregen_ZA
dc.contributor.authorLittle, Francescaen_ZA
dc.contributor.authorBarnes, Karenen_ZA
dc.date.accessioned2015-10-30T09:32:53Z
dc.date.available2015-10-30T09:32:53Z
dc.date.issued2010en_ZA
dc.description.abstractBACKGROUND:Gametocytes are the sexual form of the malaria parasite and the main agents of transmission. While there are several factors that influence host infectivity, the density of gametocytes appears to be the best single measure that is related to the human host's infectivity to mosquitoes. Despite the obviously important role that gametocytes play in the transmission of malaria and spread of anti-malarial resistance, it is common to estimate gametocyte carriage indirectly based on asexual parasite measurements. The objective of this research was to directly model observed gametocyte densities over time, during the primary infection. METHODS: Of 447 patients enrolled in sulphadoxine-pyrimethamine therapeutic efficacy studies in South Africa and Mozambique, a subset of 103 patients who had no gametocytes pre-treatment and who had at least three non-zero gametocyte densities over the 42-day follow up period were included in this analysis. RESULTS: A variety of different functions were examined. A modified version of the critical exponential function was selected for the final model given its robustness across different datasets and its flexibility in assuming a variety of different shapes. Age, site, initial asexual parasite density (logged to the base 10), and an empirical patient category were the co-variates that were found to improve the model. CONCLUSIONS: A population nonlinear modeling approach seems promising and produced a flexible function whose estimates were stable across various different datasets. Surprisingly, dihydrofolate reductase and dihydropteroate synthetase mutation prevalence did not enter the model. This is probably related to a lack of power (quintuple mutations n = 12), and informative censoring; treatment failures were withdrawn from the study and given rescue treatment, usually prior to completion of follow up.en_ZA
dc.identifier.apacitationDistiller, G., Little, F., & Barnes, K. (2010). Nonlinear mixed effects modeling of gametocyte carriage in patients with uncomplicated malaria. <i>Malaria Journal</i>, http://hdl.handle.net/11427/14521en_ZA
dc.identifier.chicagocitationDistiller, Greg, Francesca Little, and Karen Barnes "Nonlinear mixed effects modeling of gametocyte carriage in patients with uncomplicated malaria." <i>Malaria Journal</i> (2010) http://hdl.handle.net/11427/14521en_ZA
dc.identifier.citationDistiller, G. B., Little, F., & Barnes, K. I. (2007). Nonlinear mixed effects modeling of gametocyte carriage in patients with uncomplicated malaria (Doctoral dissertation, University of Cape Town).en_ZA
dc.identifier.ris TY - Journal Article AU - Distiller, Greg AU - Little, Francesca AU - Barnes, Karen AB - BACKGROUND:Gametocytes are the sexual form of the malaria parasite and the main agents of transmission. While there are several factors that influence host infectivity, the density of gametocytes appears to be the best single measure that is related to the human host's infectivity to mosquitoes. Despite the obviously important role that gametocytes play in the transmission of malaria and spread of anti-malarial resistance, it is common to estimate gametocyte carriage indirectly based on asexual parasite measurements. The objective of this research was to directly model observed gametocyte densities over time, during the primary infection. METHODS: Of 447 patients enrolled in sulphadoxine-pyrimethamine therapeutic efficacy studies in South Africa and Mozambique, a subset of 103 patients who had no gametocytes pre-treatment and who had at least three non-zero gametocyte densities over the 42-day follow up period were included in this analysis. RESULTS: A variety of different functions were examined. A modified version of the critical exponential function was selected for the final model given its robustness across different datasets and its flexibility in assuming a variety of different shapes. Age, site, initial asexual parasite density (logged to the base 10), and an empirical patient category were the co-variates that were found to improve the model. CONCLUSIONS: A population nonlinear modeling approach seems promising and produced a flexible function whose estimates were stable across various different datasets. Surprisingly, dihydrofolate reductase and dihydropteroate synthetase mutation prevalence did not enter the model. This is probably related to a lack of power (quintuple mutations n = 12), and informative censoring; treatment failures were withdrawn from the study and given rescue treatment, usually prior to completion of follow up. DA - 2010 DB - OpenUCT DO - 10.1186/1475-2875-9-60 DP - University of Cape Town J1 - Malaria Journal LK - https://open.uct.ac.za PB - University of Cape Town PY - 2010 T1 - Nonlinear mixed effects modeling of gametocyte carriage in patients with uncomplicated malaria TI - Nonlinear mixed effects modeling of gametocyte carriage in patients with uncomplicated malaria UR - http://hdl.handle.net/11427/14521 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/14521
dc.identifier.urihttp://dx.doi.org/10.1186/1475-2875-9-60
dc.identifier.vancouvercitationDistiller G, Little F, Barnes K. Nonlinear mixed effects modeling of gametocyte carriage in patients with uncomplicated malaria. Malaria Journal. 2010; http://hdl.handle.net/11427/14521.en_ZA
dc.language.isoengen_ZA
dc.publisherBioMed Central Ltden_ZA
dc.publisher.departmentDepartment of Statistical Sciencesen_ZA
dc.publisher.facultyFaculty of Scienceen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution Licenseen_ZA
dc.rights.holder2010 Distiller et al; licensee BioMed Central Ltd.en_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/2.0en_ZA
dc.sourceMalaria Journalen_ZA
dc.source.urihttp://www.malariajournal.com/en_ZA
dc.subject.otherMalaria, Falciparumen_ZA
dc.subject.otherHost-Parasite Interactionsen_ZA
dc.subject.otherModels, Biologicalen_ZA
dc.subject.otherPlasmodium falciparumen_ZA
dc.titleNonlinear mixed effects modeling of gametocyte carriage in patients with uncomplicated malariaen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Distiller_Nonlinear_mixed_effects_2010.pdf
Size:
1.11 MB
Format:
Adobe Portable Document Format
Description:
Download
Collections
Journal Articles