Decreased Hemoglobin Concentrations, Hyperparasitemia, and Severe Malaria Are Associated With Increased Plasmodium Falciparum Gametocyte Carriage

Abstract

To determine factors influencing gametocyte carriage, a cross-sectional study was conducted among 512 patients admitted for Plasmodium falciparum malaria. After adjustments for potential confounders, hemoglobin concentrations were lower in gametocyte carriers 10.5 (+/-2.5) than in patients without gametocytes 12.5 (+/-2.3) (P < 0.0001). Hemoglobin concentrations were negatively correlated with peak gametocyte counts (Spearman's p = -0.37, P < 0.0001) and gametocyte carriage durations (Spearman's p = -(0.30, P < 0.0001). Adjustments for the duration of the malaria episode and other potential confounders did not alter the association (P < 0.0001). After adjustment for potential confounders, the median asexual parasitemia was higher in patients with gametocytes than in patients without gametocytes (P = 0.003). Severe malaria cases were more likely to have gametocytes (65%) than malaria with hyperparasitemia (38%) or mild malaria (31%) (P = 0.0001). These findings suggest that events surrounding anemia and tissue hypoxia stimulate Plasmodium falciparum gametocytogenesis.

Assessment of submicroscopic infections and gametocyte carriage of Plasmodium falciparum during peak malaria transmission season in a community-based cross-sectional survey in western Kenya, 2012

“…It remains unclear to what extent which mechanisms are involved in the relationship between anaemia and gametocytogenesis. A high proportion of anaemic gametocytaemic individuals could be due to a longer duration of malarial infection [69, 70] or due to reticulocytes [71] and erythropoietin [72] triggering the pathway of gametocytogenesis. In addition, this study showed that high density of parasitaemia and presence of gametocytes measured by sensitive molecular tools were associated with fever.…”

Associations between Season and Gametocyte Dynamics in Chronic Plasmodium falciparum Infections

“…Variation in gametocyte density during infections has been linked to many in-host environmental and parasite genetic factors, including anti-malarial drug treatment [32,49,50], anaemia [25,27,28], and the presence of multiple genotypes within an infection [26]. Seasonal variation in these factors is likely to occur and could obscure or confound parasite responses to transmission opportunities.…”

“…Several factors modulate gametocyte investment in P . falciparum including parasite density [14,24,25], multiplicity of infection [26], anaemia [25,27,28], duration of infection [29], host immunity [30], and anti-malarial drugs [31–33]. …”

Transmission stage investment of malaria parasites in response to in-host competition

“…Phenotypic plasticity in the rate of conversion of asexual parasites into gametocytes can be pronounced (Drakeley et al 2006). For example, gametocyte investment often increases in response to environmental changes indicative of deteriorating in-host conditions, such as drug pressure and anaemia (Buckling et al 1999 a , b ; Nacher et al 2002; Paul et al 2004; Reece et al 2005; Ali et al 2006). …”