Discussion
anaemia, HbAS, haemolyse, anxiety, illness, toxicity, malaria, infections, blood disorders, splenomegaly, bone marrow dyserythropoiesis, falciparum-infected, haemolysis, parasitaemias
ANAEMIA, MALARIA, DISEASE, INFECTIONS, BLOOD DISORDERS, MALNUTRITION
MCPs with residual anxiety regarding the safety of SLDPQ should be reassured by the substantial evidence from our earlier randomised, placebo-controlled trial, which showed that the toxicity of age-dosed SLDPQ was similar to that of placebo and significantly reduced gametocyte carriage [In this analysis, we detail the factors influencing Hb dynamics to guide clinicians and MCPs on identifying particular patients who may be at increased risk of developing clinically significant and, possibly, life-threatening anaemia and those who may not recover their Hb by 6 weeks.At baseline, children with a lower Hb concentration were younger, had longer illness durations, lower MUACs, an increased prevalence of splenomegaly, and were more frequently affected by either homozygous α-thalassaemia, HbSS, or G6PDd (either as heterozygous females or hemizygous males/homozygous females). Consistent with previous clinical descriptions [Some of our findings, notably age, length of illness, and splenomegaly, were also significant factors for baseline Hb or anaemia in African patients, especially in children < 5 years [The majority of patients with uncomplicated falciparum infections experience an initial fall in Hb and reach their nadir concentration on day 2 [We found that a lower nadir Hb was associated with a lower baseline Hb in younger children with longer illnesses and higher baseline parasite counts; these factors were also associated with greater fractional falls in Hb except that a higher baseline Hb was associated with a greater fractional fall. Importantly, SLDPQ, G6PDd, and α-thalassaemia genotypes were not explanatory factors for both parameters. HbAS was associated with a slightly higher nadir Hb and lower fractional fall compared to those with normal Hbs that may be related to greater pretreatment haemolysis and, therefore, fewer red cells are available to haemolyse after treatment is given. Our findings concur with previous work showing that younger age, higher baseline Hbs and parasitaemias, and length of illness are significantly associated with a greater mean fractional fall in Hb [Few studies have examined the effects of inherited blood disorders on malaria dynamics. Genotypically defined G6PDd and CYP2D6 genotypes were not factors in the initial absolute fall in falciparum-infected Tanzanian patients (median age 6.4 years), who were treated with SLDPQ [Posttreatment Hb recovery occurs as the malaria-induced bone marrow dyserythropoiesis and suppression are reversed and the haemolysis of parasitised and non-parasitised red cells ceases [Although we observed a rapid median time to Hb recovery (14 days), ~ 25% of children did not recover their Hb. A higher baseline Hb resulted in a longer time to Hb recovery (Fig. Despite the apparent disadvantage of a lower baseline Hb, the D42 Hb concentration was not affected, in contrast to a small study of adults from Papua [Our study had several limitations. The number of children with moderate anaemia was quite low (~ 7%); there were only three children with HbSS (cautioning interpretation of significant findings), and the majority of children had good nutritional status. As a result, we cannot generalise our findings to children in the community with Hb concentrations of 4–6 g/dL and uncomplicated disease, those with HbSS, or those with moderate or severe acute malnutrition. We dosed SLDPQ by age, which is typically associated with broader mg/kg doses compared to weight-based dosing [