title: Risk factors for Plasmodium falciparum and Plasmodium vivax gametocyte carriage in Papua New Guinean children with uncomplicated malaria.
abstract: There are limited data on gametocytaemia risk factors before/after treatment with artemisinin combination therapy in children from areas with transmission of multiple Plasmodium species. We utilised data from a randomised trial comparing artemether-lumefantrine (AL) and artemisinin-naphthoquine (AN) in 230 Papua New Guinean children aged 0.5-5 years with uncomplicated malaria in whom determinants of gametocytaemia by light microscopy were assessed at baseline using logistic regression and during follow-up using multilevel mixed effects modelling. Seventy-four (32%) and 18 (8%) children presented with P. falciparum and P. vivax gametocytaemia, respectively. Baseline P. falciparum gametocytaemia was associated with Hackett spleen grade 1 (odds ratio (95% CI) 4.01 (1.60-10.05) vs grade 0; P<0.001) and haemoglobin (0.95 (0.92-0.97) per 1g/L increase; P<0.001), and P. falciparum asexual parasitaemia in slide-positive cases (0.36 (0.19-0.68) for a 10-fold increase; P=0.002). Baseline P. vivax gametocytaemia was associated with Hackett grade 2 (12.66 (1.31-122.56); P=0.028), mixed P. falciparum/vivax infection (0.16 (0.03-1.00); P=0.050), P. vivax asexual parasitaemia (5.68 (0.98-33.04); P=0.053) and haemoglobin (0.94 (0.88-1.00); P=0.056). For post-treatment P. falciparum gametocytaemia, independent predictors were AN vs AL treatment (4.09 (1.43-11.65)), haemoglobin (0.95 (0.93-0.97)), presence/absence of P. falciparum asexual forms (3.40 (1.66-0.68)) and day post-treatment (0.086 (0.82-0.90)) (P<0.001). Post-treatment P. vivax gametocytaemia was predicted by presence of P. vivax asexual forms (596 (12-28,433); P<0.001). Consistent with slow P. falciparum gametocyte maturation, low haemoglobin, low asexual parasite density and higher spleen grading, markers of increased prior infection exposure/immunity, were strong associates of pre-treatment gametocyte positivity. The persistent inverse association between P. falciparum gametocytaemia and haemoglobin during follow-up suggests an important role for bone marrow modulation of gametocytogenesis. In P. vivax infections, baseline and post-treatment gametocyte carriage was positively related to the acute parasite burden, reflecting the close association between the development of asexual and sexual forms.
authors.affiliation: Population Health and Immunity Division, Walter and Eliza Hall Institute, Parkville, Victoria, Australia; Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Stephan
authors.initials: S
authors.lastname: Karl
authors.affiliation: Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea.
authors.forename: Moses
authors.initials: M
authors.lastname: Laman
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Brioni R
authors.initials: BR
authors.lastname: Moore
authors.affiliation: Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea.
authors.forename: John M
authors.initials: JM
authors.lastname: Benjamin
authors.affiliation: Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea.
authors.forename: Mary
authors.initials: M
authors.lastname: Salib
authors.affiliation: Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea.
authors.forename: Lina
authors.initials: L
authors.lastname: Lorry
authors.affiliation: Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea.
authors.forename: Samuel
authors.initials: S
authors.lastname: Maripal
authors.affiliation: Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea.
authors.forename: Peter
authors.initials: P
authors.lastname: Siba
authors.affiliation: Population Health and Immunity Division, Walter and Eliza Hall Institute, Parkville, Victoria, Australia; Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia; Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea.
authors.forename: Leanne J
authors.initials: LJ
authors.lastname: Robinson
authors.affiliation: Population Health and Immunity Division, Walter and Eliza Hall Institute, Parkville, Victoria, Australia; Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Ivo
authors.initials: I
authors.lastname: Mueller
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia. Electronic address: tim.davis@uwa.edu.au.
authors.forename: Timothy M E
authors.initials: TM
authors.lastname: Davis
mesh_terms: D000962:Antimalarials / Q000627:therapeutic use; D002353:Carrier State; D002648:Child; D002662:Child Health Services; D005260:Female; D006790:Host-Parasite Interactions; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000469:parasitology / Q000635:transmission*; D016780:Malaria, Vivax / Q000188:drug therapy / Q000469:parasitology / Q000635:transmission*; D008297:Male; D010219:Papua New Guinea / Q000453:epidemiology; D010963:Plasmodium falciparum; D010966:Plasmodium vivax; D012307:Risk Factors
chemical_list: D000962:Antimalarials
keywords: Artemisinin combination therapy; Children; Gametocytes; Plasmodium falciparum; Plasmodium vivax; Risk factors