Repeated four-monthly anthelminthic treatments for 14 months resulted in a significantly lower increase in the prevalence of Plasmodium infection in children aged 1 to 4 years which coincided with a reduction in both the prevalence and intensity of A. lumbricoides infections. This suggests that when children of this age group become infected with Plasmodium, infection with Ascaris could potentially influence the ability of the child's immune response to clear the Plasmodium infection. The immunological mechanism of action that underlines helminth/malaria interactions has been discussed and some authors suggest that helminths can contribute to the slow acquisition of immunity to malaria .
The greater increase in Plasmodium parasite density in the placebo group further supports the evidence that suggests that Ascaris can leave children aged 1 to 4 years less able to control Plasmodium infection although this was not statistically significant. This potential positive impact of anthelminthic treatment on Plasmodium infections in pre-school children contrasts with the results of other studies investigating the relationship between A. lumbricoides and malaria [5, 6, 8]. Two studies using an intervention have been undertaken in the Comoros islands  and Madagascar . Both studies have included subjects with a wide age range, 2-14 yrs and 0 - >15 yrs, respectively. In the Comoros study, children with heavy Ascaris infections demonstrated an increase in clinical malaria cases with anthelmintic treatment. In the present study, the significant effect of anthelmintic treatment on Plasmodium infections was demonstrated in a group of children where the majority (85.9%) had light Ascaris infections . The Comoro study had limitations and has been criticized for its small sample size (112), short follow-up (20 days) and severely malnourished study population .
In Madagascar, Brutus and colleagues revealed that while there was no effect of levamisole treatment on P. falciparum parasite density in children aged < 5 years, subjects more than five years of age had a significant increase in their P. falciparum parasitaemia compared with untreated controls. The small sample size (n = 67) in the six month to four year age group may not have been sufficient to detect an effect of anthelmintic treatment on P. falciparum parasitaemia. Furthermore, the prevalence of A. lumbricoides in this age group may have been very low in comparison to these Nigerian children considering that the prevalence in the treatment (26.2%) and placebo (27.4%) groups was moderate at entry into the study. Differences in acquired malaria immunity, owing to different transmission settings, in the Nigerian and Madagascan population may also have contributed to the contrasting results.
An observational field-based, case-control study in rural Senegal investigated the relationship between A. lumbricoides and severe malaria  demonstrating that children infected with A. lumbricoides had an increased risk of severe malaria. This is in line with the results of the present study which demonstrate that children infected with A. lumbricoides are apparently less able to control their malaria infections, albeit uncomplicated malaria infections. Other studies investigating the relationship between helminths and malaria, not differentiating between helminth species, have also shown comparable results to this study [11, 28].
In the present study, as expected haemoglobin levels increased over the study period as the children increased in age . However, There was a steeper increase in the change in haemoglobin level among children in the treatment group when compared to the placebo group. This trend corresponds with the lower increase in prevalence of malaria infections associated with the transmission season in the treatment group. Malaria infection is associated with a reduction in haemoglobin levels and can frequently lead to anaemia, especially in younger children and infants . Despite the fact that the trend in haemoglobin level was not statistically significant, the observations further support the evidence that Ascaris can leave these preschool children less able to control their Plasmodium infections.
The study may have some potential limitations that need to be considered when interpreting the findings. Plasmodium prevalence and parasite densities were significantly lower in the placebo group at baseline and thus it could be argued that that the placebo group had more potential for increasing Plasmodium prevalence and parasite densities than the treatment group. However, Plasmodium prevalence was comparable in the treatment and placebo groups at 8 months and while prevalence increased in the placebo group from the dry to the wet season, when malaria transmission was likely to be low, the prevalence reached a plateau in the treatment group. This trend does not support the theory that the faster increase in Plasmodium prevalence in the placebo group was due to differences in Plasmodium prevalence at baseline. Participants were not randomly selected from the community. Achieving a random sample of study participants in this field setting would prove very difficult owing to the widely dispersed nature of these semi-urban communities, and to the restricted age group being studied. Nevertheless, we believe that the moderate sample size, small age range and randomised design may compensate for the non-random selection of study participants. The majority of children (74%) were lost to follow-up. This high attrition rate may be attributed to the difficulty in retaining the participation of such young children particularly because they are not of school-going age. School-based studies provide a better infrastructure and can improve compliance considerably. Bias caused by such losses was probably minor because those lost were similar with respect to important characteristics to those that were analyzed, apart from village and weight. Akinlalu is less widely dispersed than the other villages and this may account for the higher compliance shown in Akinlalu and any potential bias owing to this was taken into account by adjusting for village in the analyses. We do not believe that the intake of Coartem had any effect on the results because few treatments (98) were given during the study period and there was no significant difference in the intake of Coartem between the two groups. Information on whether the children received treatment for malaria prior to the assessments was not recorded. The inhabitants of these semi-urban villages have poor access to healthcare. The Primary Health Care centres have inadequate medical supplies and the staff are often poorly trained. Although malaria is hyperendemic in Osun state, the authors believe that the children did not receive appropriate treatment for malaria outside of the study setting.