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.