This study suggests that, among pregnant women in Entebbe, Uganda, malaria and HIV are more important infectious causes of anaemia than helminths. No association was observed between mild-to-moderate anaemia and any species of helminth, and a weak association between anaemia and increasing intensity of hookworm infection was reduced after adjusting for confounding factors. Anaemia was slightly more common among women heavily infected with S. mansoni, but the number of such women was small.
In keeping with the exclusion of women with Hb < 8 g/dl, excluded women were more likely to be anaemic than enrolled women, but this had minimal impact on the overall estimate of prevalence of anaemia (40.5%). Given the recognised ability of hookworm to cause anaemia (Bondevik et al., 2000; Hotez et al., 2004; Shulman et al., 1996
), we conducted a sensitivity analysis to estimate the effect of hookworm if all women with Hb < 8 g/dl and no stool result had hookworm. The result was in keeping with a possible effect of hookworm, but after adjusting for confounding factors the effect was small. Associations between anaemia and malaria and between anaemia and HIV infection were similar in enrolled and excluded women.
Our investigations for intestinal helminths used only one stool sample from each woman, meaning that a proportion of women with low-intensity infections will have been misclassified as uninfected and that estimates of intensity will have been imprecise (Hall, 1981; Utzinger et al., 2001
). Recent comparable studies have the same limitation (Ajanga et al., 2006; Bondevik et al., 2000; Dreyfuss et al., 2000; Larocque et al., 2005
). In our study this may, again, be important for hookworm, where there was a small increase in anaemia with infection intensity, but may not explain the lack of association for schistosomiasis where there was no suggestion of an effect of light-to-moderate infections. Our method of investigation for Mansonella
and intensity does not suffer from this limitation: repeat examinations among 1971 women showed 96% agreement for the binary variable (infected/uninfected), with an ICC for mf/ml of 0.87 (95% CI 0.85–0.88) (unpublished data).
Not all pregnant women in Entebbe attend the district hospital antenatal clinic, but a community survey undertaken in the study area showed an increase in the proportion choosing this clinic during the recruitment period, to approximately 80%, and most of the personal and socioeconomic characteristics of women choosing, or not choosing, to attend the district hospital clinic were similar (unpublished data). Thus, our results are likely to be reasonably representative of pregnant women in this area.
Recent studies from different settings give similar results in relation to the effects of hookworm and S. mansoni
on anaemia in pregnancy. In Peru (where hookworm and Trichuris
are predominant), in Tanzania (S. mansoni
and hookworm), in the Democratic Republic of Congo (Ascaris
and hookworm) and in Java (Trichuris
and hookworm), no association was observed between anaemia and infection with any single species (Ajanga et al., 2006; Kalenga et al., 2003; Larocque et al., 2005; Nurdia et al., 2001
). In Peru there was an association between anaemia and higher hookworm intensities, and in Java there was a negative association between serum ferritin and hookworm, suggesting an effect of hookworm on iron status but not anaemia; in Tanzania, in an area of higher S. mansoni
prevalence and intensity, a strong association between anaemia and heavy S. mansoni
infection was observed. Infection intensity thus appears to be important, with light-to-moderate hookworm or S. mansoni
infections having relatively weak effects on Hb levels. However, a second important factor is the underlying nutritional status of the women. In two studies in Nepal, among populations perhaps poorer and less well nourished than ours (as indicated by items owned, anthropometry and vitamin A status (Dreyfuss et al., 2000
) and with a traditionally vegetarian diet (Bondevik et al., 2000
)), anaemia showed a significant association with hookworm infection (Bondevik et al., 2000; Dreyfuss et al., 2000
). The effects of hookworm infection are partially mediated by iron deficiency (Bondevik et al., 2000; Olsen et al., 1998
) and in the trial conducted in Sierra Leone iron-folate supplements had a greater benefit for anaemia in pregnancy than treatment with albendazole (Torlesse and Hodges, 2001
We found no suggestion of an association between anaemia and any other helminth species that was common in our environment (Mansonella
). This again is in agreement with other studies (Dreyfuss et al., 2000; Larocque et al., 2005; Nurdia et al., 2001
). Larocque et al. (2005)
noted a stronger effect of moderate-to-heavy hookworm infection when combined with moderate-to-heavy Trichuris
infection. Although there was broad overlap between the confidence intervals for these effects in their analysis, such an effect is plausible, given evidence in children that heavy Trichuris
infections (>10 000 epg) can be associated with anaemia (Ramdath et al., 1995
). In our study, as in that reported by Nurdia et al. (2001)
, no such heavy Trichuris
infections were observed.
The strong effects of malaria and HIV contrast with the weak effect of hookworm and the lack of effects of other helminths in this study.
Of note, women were screened for this study when they were apparently healthy, thus both malaria and HIV infection were largely asymptomatic. The effects of these infections are not mediated by iron deficiency and may override any benefit of good nutrition. The importance of malaria as a cause of anaemia in pregnancy is well established (Shulman and Dorman, 2003
). HIV infection is also a recognised cause of anaemia (Belperio and Rhew, 2004
), and anaemia may be one mechanism by which it causes adverse birth outcomes (Dairo et al., 2005; McIntyre, 2003
There are compelling reasons for preventing and treating malaria and HIV during pregnancy (Shulman and Dorman, 2003; ter Kuile et al., 2004
). Our results highlight that anaemia is among them. On the other hand, our results as well as recent literature suggest that associations between helminth infections and anaemia in pregnancy are weaker, with regional variations that may be based on nutrition and intensity of helminth infection. These findings are relevant when estimating the relative disease burden of helminths and other infections and the relative value of possible interventions in pregnancy. Globally, the majority of helminth infections are of low intensity so, in some settings, the benefit of routine deworming during pregnancy in relation to anaemia may be modest. The effects of deworming during pregnancy on other parameters, including birth outcome, birth weight and long-term effects on health in infancy and childhood, also need to be considered (Christian et al., 2004
). The forthcoming results of our ongoing trial of deworming in pregnancy are expected to contribute further to this debate.