On the basis of the WHO classification for persistent anemia in a population (40%), our findings indicate that anemia among preschool aged children in Nyando District, Kenya was a severe public health problem that was associated with many known risk factors.2
This is one of the first studies to measure many factors thought to be associated with anemia including hemoglobinopathies among a single population in a developing country setting where malaria was highly prevalent. We found that malaria, iron deficiency, and homozygous α-thalassemia were the factors that were most strongly associated with having anemia, and that malaria, non-malarial inflammation, and stunting were most strongly associated with severe anemia. Non-modifiable characteristics including α-thalassemia, sex, and age < 24 months were also associated with anemia and commonly found in the population.
The fact that malaria and iron deficiency were the characteristics that were most strongly associated with anemia was plausible for rural, western Kenya. Recurrent malaria infections and a diet deficient in iron are common in this community. However, neither condition was associated with a majority of cases of anemia, which may challenge the estimation that 50% of cases of anemia in malaria-endemic areas is caused by iron deficiency.4
George and others27
recently examined the association of genetic disorders and other factors with anemia in Cambodia; however, the association of these disorders with severe anemia, a risk factor for mortality, was not examined. Furthermore, no estimate was made of the relative contribution of each of these factors to anemia in the population. In our Kenyan study, malaria was common, and as a result we were able to determine the strength of association between anemia and malaria, as well as the strength of association between anemia and iron deficiency and hemoglobinopathies, factors thought to be affected by the presence of malaria.
Severe anemia was most strongly associated with malaria, non-malarial inflammation, and stunting. Malaria is a known cause of severe anemia and as expected, was associated with a large percentage of cases.26
Non-malarial inflammation was also strongly associated with severe anemia, which may be caused by several characteristics commonly found in this population that are known causes of inflammation and anemia including tropical enteropathy, HIV, and resolving inflammation in those that have recently cleared malaria infection. After the resolution of malaria, levels of alpha-1-acid-glycoprotein (AGP) stay elevated for up to 3 weeks after clearance of parasitemia.28
Therefore, children who clear parasitemia can have continued removal of unparasitized red blood cells by activated macrophages in the spleen. This mechanism is thought to cause severe anemia in children with malaria and may explain, in part, the strong association we observed between non-malarial inflammation and severe anemia.26
Our results suggest that inflammation may be an intermediate in the causal pathway for malaria and anemia. When the variable “any inflammation” instead of “non-malarial inflammation” was used in the multivariable model, the association between both anemia and malaria and severe anemia and malaria decreased. Furthermore, the association between anemia and severe anemia and “any inflammation” was stronger in comparison to the association between anemia and severe anemia and “non-malarial inflammation.”
Another possible source of inflammation that could lead to anemia is tropical enteropathy, whereby elevated inflammatory markers and blunted intestinal villi impair absorption of nutrients and cause anemia of chronic inflammation.29
Nearly everyone living in developing countries may have signs of tropical enteropathy or intestinal dysfunction, thought to be as a result of poor hygiene and sanitation conditions.30
Furthermore, HIV prevalence among infants in western Kenya is estimated to be 10%,31
which could cause inflammation as well as anemia and severe anemia.32,33
Schistosomiasis, present in school-aged children in the region, can also cause anemia and inflammation.34,35
It is possible that children had multiple parasitic infections, resulting in inflammation and anemia that has been seen in other developing country settings.36
Stunting was also associated with a large fraction of the cases of anemia and severe anemia. Intestinal parasites can cause stunting, anemia, and severe anemia.32,37,38
Because we did not measure intestinal parasites, and intestinal parasites were present among school-aged children in the study community in 2007, stunting may be an indicator for intestinal parasite infection that could in part explain its association with anemia and severe anemia.12
Other studies have shown that helminthiasis may not be associated with inflammation, and its association with anemia was not likely captured within the non-malarial inflammation group.37,39
Stunting and wasting can be associated with HIV infection, and HIV is a known risk factor for anemia present in this region.31,40
This could be a possible explanation for the association between wasting and anemia and stunting and anemia. Wasting has also been shown to be associated with helminthiasis, and treating helminthiasis has also been shown to reduce both wasting and anemia.10
Even though we adjusted for some of the possible infectious and nutrition-related pathways, there may be other unmeasured factors that could explain the link between anthropometric measures and anemia.
Sickle cell hemoglobin and sickle cell disease were not associated with anemia. Because this was a cross-sectional study that did not follow a cohort from birth, it was unknown what happened to all children in this population that were born with sickle cell disease. There is a high mortality rate among children with sickle cell disease between 1 and 3 years of age, and low hemoglobin is a risk factor for death among these children.41
It was possible that in this population, children with sickle cell disease that were more likely to have anemia or severe anemia already died.42
There are limited studies with few subjects that have evaluated the prevalence of α-thalassemia in eastern Africa and its association with anemia.20,43
Our study found that α-thalassemia is an important genetic characteristic that is associated with anemia. Although it is thought that heterozygous α-thalassemia is not associated with anemia, and those with homozygous α-thalassemia will have a mild anemia, we found that both homozygous and heterozygous α-thalassemia were associated with anemia.44
Vitamin A deficiency was not associated with anemia or severe anemia in this survey, which is inconsistent with other published findings.32
It is possible that the other studies did not adjust their retinol or RBP values for inflammation, which could have biased the association between vitamin A deficiency and anemia and severe anemia.32,45
The study had several limitations. First, the study was carried out in Nyando District, Kenya, and the findings are likely not representative of Kenya or sub-Saharan Africa. Second, this was a cross-sectional study, therefore causality cannot be determined. In addition, PRs, not risk ratios were measured. As a result, we were not able to calculate population attributable fractions. However, prevalence fractions are still helpful for measuring population-level associations by helping one understand both the strength of the association and how common the factor is in the population.25
Third, the correction factor method has never been validated against bone marrow biopsy or liver biopsy, the gold standard tests of iron deficiency and vitamin A deficiency in the presence of inflammation.46,47
Fourth, the cause of the high prevalence of inflammation was unknown. We did not collect data on additional characteristics that can cause inflammation such as HIV, tropical enteropathy, or schistosomiasis that also were potentially associated with anemia. Finally, we could not examine the effect of polyparasitic infections on anemia, which was shown to be important in other populations where malaria, schistosomiasis, and intestinal parasites were likely present.36
In conclusion, anemia is a severe public health problem in Nyando District, Kenya. Malaria and iron deficiency were most strongly associated with anemia, and non-malarial inflammation, malaria, and stunting were most strongly associated with severe anemia. Alpha-thalassemia was an important non-modifiable genetic factor that was associated with anemia and common in this population. There was no single characteristic that was associated with the majority of the cases of anemia. To implement effective public health interventions to prevent anemia in this population, one must take an integrated approach that addresses iron deficiency, as well as infections including malaria, schistosomiasis, HIV, and intestinal parasites.