Anaemia was highly prevalent in this cohort of preschool Nigerian children, with a rate of 84%. This is significantly higher than prior studies [26, 28], and exceeds WHO’s estimate for anaemia among preschool-age children in Africa . Understanding the causal factors is crucial to developing an effective intervention. As has been shown previously, malaria infection was significantly associated with anaemia. Co-infection with Ascaris and malaria was common in this cohort of children and this study investigated whether the severity of malarial anaemia was altered in co-infected children.
The initial hypothesis was that Ascaris infection would be protective with respect to the severity of malarial anaemia. The rationale for this hypothesis was that the induction of an anti-Ascaris immunosuppressive response would dampen the anti-malarial inflammatory immune responses, thus reducing the contribution of the inflammatory immune response on malarial anaemia . However, it was found that concurrent infection with Ascaris did not have any effect on the severity of malarial anaemia, in agreement with a previous study carried out in Cameroon , and in partial agreement with a study looking at hookworm and malaria interaction in Zanzibar . In this study, there were slightly more anaemic children in the malaria-only infected group compared to the co-infected group (92% vs. 85%, respectively) but the odds ratio was not statistically significant and fell short of clinical significance.
Circulating levels of tumour necrosis factor (TNF) , macrophage migration inhibitory factor (MIF)  and interleukin-12 (IL-12)  correlate with the severity of malarial anaemia, and have been demonstrated to play a role in causing malarial anaemia in animal models [33, 35]. These pro-inflammatory cytokines lower the production of erythropoietin, the renal hormone responsible for RBC formation, thereby leading to anaemia [36–38]. Animal models of malaria suggest that erythroid suppression is further exacerbated by a reduced response of progenitor cells to erythropoietin [39, 40].
The immunoregulatory cytokine IL-10 is a powerful antagonist to the contributory effects of TNF on malarial anaemia. An elevated ratio of IL-10 to TNF in the serum is associated with a decreased severity of anaemia in Kenyan children . Immunoregulatory immune responses in malaria infection [42, 43] can down-regulate the production and action of pro-inflammatory cytokines [44–47]. Although in co-infected children there is potential for helminth-induced immunoregulatory cytokines to reduce the magnitude of the pro-inflammatory immune response induced by malaria infection, there may not be any visible effect if most pre-school children are already asymptomatic because of a prevailing malaria-induced immunoregulatory response. The majority of the children included in this study were otherwise asymptomatic from malaria infection . This phenomenon has previously been noted in older Nigerian school-age children by Ojurongbe et al. indicating that the immunoregulatory properties of malaria infection can develop quickly in preschool-age children.
The causes of anaemia in children living in resource poor settings are numerous. In this analysis, age and socio-economic status were significantly correlated with anaemia. Periods of rapid growth including early childhood (from the prenatal period to eight years of age), as in this cohort, and adolescence are notable for increased iron utilization which can lead to iron-deficiency and, in many cases, associated anaemia .
Other factors that were not analysed may also contribute to anaemia, masking the effect of co-infection on the severity of malarial anaemia. Nutritional factors such as vitamin and iron deficiencies play a significant role in the development of anaemia in resource poor regions of the world, like Nigeria. Additionally, sickle cell disease [50, 51] and other haemoglobinopathies  as well as HIV status [53, 54] may be contributing factors to the severity of anaemia.