Anemia is a global public health problem, at any stage of life [1, 2]. A recent systematic analysis using national and subnational anemia survey data estimated a worldwide prevalence of 32.9% in all ages combined, contributing more years lived with disability than either depression or chronic respiratory diseases [3]. The bulk of the global anemia burden was driven by under-5 children and women [3].

Sub-Saharan Africa (SSA) has the highest regional prevalence of anemia with a slower decline over time than in other regions [1, 3]. Using WHO definitions, anemia is a severe public health problem among non-pregnant and pregnant women in SSA. Variations occur within the region, however, with highest prevalence and least improvement for subgroups in West and Central Africa [2]. A combination of population growth, aging population, infectious diseases and iron deficiency are driving the anemia burden in SSA [3]. The majority of published studies on anemia in SSA focus on children and pregnant women [4–9]. Men and elderly populations have received relatively little attention [10, 11].

Anemia has diverse consequences and different subgroups of the population have varying vulnerabilities to its complications, such as fatigue and congestive cardiac failure; the rate and severity increasing with the severity of anemia [12–14]. Conditions resulting in anemia act largely through either reduced red cell production or increased red cell loss, but the former is more often implicated in the etiology of severe anemia [15–17]. Although different risk factors influence anemia independently, they commonly exist concomitantly, making it challenging to single out a definitive cause especially in resource-poor settings where access to advanced diagnostic tools is limited [18, 19]. Important causes of anemia in developing countries include micronutrient deficiencies, infectious diseases, hemoglobinopathies, and maternal blood loss. In terms of presentation, iron deficiency anemia is typically microcytic hypochromic, and anemia from chronic diseases is normocytic normochromic, whereas macrocytic anemia is commonly associated with B12 and folate deficiencies, or drug and alcohol toxicities, though overlap is common [20–22]. Intricate relationships between economic, political, demographic, sociocultural and biological factors influence the patterns of underlying causes, vulnerability to, and distribution of anemia severity and consequences [8, 16, 19].

Distinction between different severity levels of anemia has been recommended for the appropriate monitoring of anemia in populations, especially as countries have intensified control efforts, shifting the burden to the lower end of the hemoglobin distribution [3, 16, 23]. For instance, a recent analysis of global anemia burden from 1990 to 2010 showed that although overall prevalence has declined for all severities, among men, prevalence of severe anemia appears to be increasing [3].

Prevalence of anemia in Malawi has been estimated from Demographic and Health Surveys (DHS) for under-5 children, pregnant women, and women of reproductive age. Men and women outside reproductive age are not included and study sample sites are scattered. According to the 2010 Malawi DHS, prevalence levels of mild, moderate, and severe anemia were 21.7, 5.8 and 0.6% for non-pregnant and 19.5, 17.8 and 0.2% for pregnant women [24].

In order to describe the prevalence and distribution of different severities and types of anemia, and to examine the risk factors for different severities of anemia, we analysed data from a large cross-sectional population study of cardio-metabolic risk factors in rural and urban adults in Malawi.

A large population-wide cross-sectional survey was conducted in two sites by the Malawi Epidemiology and Intervention Research Unit (MEIRU) from 2013 to 2015. One site was rural – Chilumba, in southern Karonga district, northern Malawi. The rural study was nested within a demographic surveillance site (DSS) established by MEIRU’s forerunner, the Karonga Prevention Study, in 2002 [25–27]. The other site was an enumerated urban population, in Area 25 within Lilongwe city in central Malawi [25, 27].

Anemia is of moderate public health importance among women, and of mild public health importance in men, in these Malawian rural and urban populations, based on the WHO prevalence-based classification [28]. Multivariable analyses indicate that for men, increasing age and HIV infection were independent risk factors for both mild and moderate-to-severe anemia. Being underweight was also associated with mild anemia. Among women, being between 35 and 54 years of age, pregnancy, nulliparity, and HIV infection were risk factors for any anemia severity. Additionally, women with secondary or tertiary education and those with six or more previous pregnancies had higher odds of having mild anemia.

The prevalence of anemia in non-pregnant and pregnant women reported here is lower than that reported by the Malawi DHS. The DHS may exclude relatively healthier participants not found at home or the population may differ [24]. The differences in anemia prevalence between men and women was minimal after 55 years of age, and after 65 years prevalence was higher in men. This possibly indicates greater biological and social vulnerability during the reproductive years in women and among elderly men [31–33]. It is also plausible that interventions targeted at women during the reproductive years may protect them from anemia at later ages. This is also supported by the higher risk of anemia found among women who have never been pregnant although this may be related to fitness for reproduction.

Higher anemia prevalence in rural regions has been attributed to disparities in health service provision and access, disease risk, fertility preferences, and genetic conditions such as sickle cell anemia [16, 34–36]. Although urban/rural residence was not found to be an independent risk factor for anemia of any severity in men or women, crude rates of anemia were higher in urban than rural women but higher in rural than urban men. There were also urban/rural differences in types of anemia. Microcytic anemia was more prevalent among urban residents. Iron deficiency may be less prevalent in rural areas as rural residents have better access to diverse and more nutritious food sources; foods rich in iron such as eggs, leafy green vegetables and in our lake-shore population, fish; and fruits containing Vitamin C, enhancing iron absorption. Rural women may be more likely to access the mineral-rich clay pellets traditionally consumed during pregnancy [37].

Anemia is related inversely to economic development at country/regional level, to wealth at household level and to income and education at individual level [16, 24, 38]. Though studies have shown associations between low socioeconomic status and all anemia levels, our findings indicate that women with higher educational levels had higher odds of mild anemia [32, 34, 39]. We observed gender-specific variations in prevalence of anemia among different occupation groups. Amongst men, farmers/fishermen had the highest prevalence and amongst women, salaried workers. This indicates that the difference in drivers of anemia in men and relate to factors that affect production as well as breakdown or loss of red blood cells. Prevalence of microcytic anemia increased with increasing levels of education and was lowest among farmers. It is plausible that diets of more educated women from wealthier homes, as with urban residents, may have moved away from traditional diets and supplements, thereby increasing their risk of nutrition-related anemia. Conversely, farming/fishing can increase the risk of other anemia-inducing infectious diseases such as schistosomiasis and hookworm, and such exposures may be more common in men.

Repeated pregnancies and short birth intervals deplete iron stores, resulting in anemia, explaining the association of higher parity with mild anemia [7, 40, 41]. In contrast, higher parity was not associated with moderate-to-severe anemia. Interventions for anemia control are usually targeted at pregnant women, so multiparous women repeatedly access anemia-control interventions such as iron/folate supplement, insecticide-treated nets (ITN), malaria chemoprophylaxis, deworming, HIV testing, and subsequent treatment. This may buffer the effect of parity on anemia and maintain hemoglobin levels at mild anemia stage. High risks of mild and moderate-to-severe anemia among nulliparous women could be related to their physical fitness to reproduce and to associated co-morbidities. Although HIV infection and treatment status have been adjusted for, residual confounding is still possible from severity/stage of HIV which is unaccounted for in this analysis.

Low BMI (<18.5 kg/m²) was associated with mild anemia in men. Many studies have shown inverse relationships between BMI and anemia [31, 32, 34, 42]. A multi-country, multi-level analysis of hemoglobin levels of African women showed stronger associations of anemia with socioeconomic and contextual factors than with BMI [11]. Micronutrient deficiencies have been shown to have different roles in etiology of varying severities of anemia [17]. Iron and folate deficiency have been associated with mild anemia, while vitamins A and B12 deficiency have been shown to be important in the etiology of severe anemia [6, 17]. Although high BMI may not necessarily imply better micronutrient intake, underweight persons are more likely to have other associated comorbid illnesses and hence poorer nutrition.

Our results show that reported alcohol use strongly lowered the odds of moderate-to-severe anemia among men, even after adjustment for age, education, residence, occupation, BMI, smoking, and HIV status. There is some evidence that traditionally brewed beers in SSA have a high enough iron content to be protective against iron deficiency [43, 44]. However, due to the social nature of alcohol use, the role of reverse causality cannot be ruled out.

A strong association was observed with all severities of anemia and HIV. Anemia is a frequent complication in HIV infection and it has been shown to increase with disease progression [45, 46]. Use of ART has been shown to reduce anemia prevalence among HIV-infected, [47, 48] but our findings indicate that in this setting where anemia may not be actively managed in ART clinic attenders, this benefit may only be seen after several years of treatment. Conversely, use of certain ART medications (Zidovudine) may be associated with increased risk of anemia, through myelosuppression [47, 49]. Despite the moderate HIV prevalence in this study, almost 20% of severe anemia in the population was attributable to HIV.

The burden and distribution of anemia in this population has several implications. As anemia has been shown to negatively affect physical capacity and reduce individual productive capability, decrease in household income and food security is a likely consequence, especially in populations such as ours, that rely primarily on subsistence farming/fishing and other often-seasonal sources of income [16, 50]. Anemia can contribute to poor pregnancy and birth outcomes in women of reproductive age and these can worsen already poor maternal and perinatal indices [16] and may counteract the improved outcomes otherwise seen in educated urban women. Anemia among HIV-infected persons is associated with poorer quality of life, disease progression, and increased mortality; and therefore, can worsen prognosis, [45, 51] but may not be routinely screened for in all HIV services.

Our research findings should be considered in light of several limitations. The cross-sectional nature of the survey makes it difficult to explore temporal relationships. Though misclassification of exposure variables is likely to be minimal, exposure measured at time of survey may not reflect past exposure that may be important for a chronic condition such as anemia. Previous research has shown that place of long-term childhood residence may influence anemia risk more than place of current residence and the complete effect of SES on health may not be captured by measuring SES at a single point in time [32, 52, 53]. Finally, the large number of missing HIV and anemia observations may have introduced bias in to the sampling. The response rates in urban men were poor, which might introduce selection bias as employed men were challenging to recruit [27]. To minimize missing HIV data, we assessed HIV status from different sources – testing from current or prior study and self-report. Though it is unlikely that subjects will falsely report being HIV-positive, it is possible that participants that did not consent to HIV testing are more likely be HIV-positive. Thus, we may have underestimated the prevalence of anemia and the effect of HIV. Additionally, we may have overestimated the prevalence of anemia if healthier participants with lower risk of anemia had missing values because they were at work, and thus were unavailable for HIV testing. It is also likely that some of the women self-reporting as not pregnant may in fact have been in early pregnancy and this may have led to overestimation of anemia prevalence among non-pregnant women and underestimated the effect of pregnancy. The main limitation of our study is the absence of data on other anemia-inducing comorbidities. Underlying presence of infectious (malaria, schistosomiasis, and hookworm) and non-infectious (chronic kidney disease, menorrhagia, gastritis, peptic ulcer disease) diseases which are important in anemia etiology in SSA populations may have resulted in some residual confounding. For instance, because pregnant women are at particular risk of malaria, some of the observed effect of pregnancy may be confounded by malaria. The burden of some anemia-inducing chronic diseases such as chronic kidney disease and peptic ulcer disease may be higher in urban populations, and may contribute to the observed higher risk of anemia among urban women.

This study provides several insights into the population burden of anemia among less well-studied groups and indicates that there may be risks associated with higher socioeconomic status and urban living. Biological (age, parity, pregnancy, and HIV infection) and social (urban residence, education, occupation, and wealth) factors are associated with anemia and this understanding can inform intervention strategies both in identification and management of high-risk groups as well as in the nature of the intervention. To effectively control anemia, a comprehensive and multi-sectoral approach will have far-reaching consequences. Supporting women farmers/fisherwomen will not only improve their nutritional status and reduce their nutrition-related anemia risk, but will improve the overall household income and promote empowerment of women and gender equality. Among urban women and women with higher socioeconomic status, food-based interventions such as dietary diversification and fortification of staple foods would reduce nutrition-related anemia as well as other micro-nutrient deficiencies. Consistent findings are the implications of HIV infection for higher risk of any severity of anemia, which may be contributing to poorer HIV outcomes. Wider access to ART and improved detection is important to control anemia among HIV-infected persons.