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Anaemia as a challenge to world health 

Anaemia as a challenge to world health
Anaemia as a challenge to world health

D.J. Roberts

and D.J. Weatherall



Updated section on the role of hepcidin in chronic anaemia associated with infection.

Updated on 30 May 2013. The previous version of this content can be found here.
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Anaemia is a very common problem in the developing world: 47% of women aged 15 to 49 years have haemoglobin less than 12 g/dl; 59% of pregnant women have haemoglobin less than 11 g/dl; 26% of men aged 15 to 49 years have haemoglobin less than 13 g/dl. About 20% of perinatal mortality and 10% of maternal mortality in developing countries is attributable to iron deficiency.

Causes of anaemia in developing countries—this is often multifactorial, with causes including (1) nutritional deficiencies—iron, folate, vitamin B12; (2) chronic infection—including malaria, tuberculosis, AIDS; (3) blood loss—hookworm, schistosomiasis; (4) protein–energy malnutrition; (5) malabsorption—e.g. tropical sprue; (6) hereditary—e.g. thalassaemias, haemoglobin variants, glucose-6-phosphate dehydrogenase deficiency.

A series of vicious cycles in the developing world—maternal anaemia due to iron or folate deficiency and chronic malaria is associated with the birth of underweight infants who frequently have low iron stores, may also be folate deplete, and are usually anaemic from about 6 months of age. Such infants are prone to infection, particularly gastrointestinal, and may be further depleted of iron or folate by inappropriately prolonged breastfeeding or weaning onto an inadequate diet. They are exposed to hookworm infection as soon as they start to crawl, malaria becomes an important problem after 6 months, and in many populations the increasingly common haemoglobinopathies are a further cause of anaemia after the first few months of life.


Despite improvements in nutrition and hygiene, which have reduced childhood mortality in many developing countries, anaemia continues to be an important problem in the health of the world’s population. It is not, of course, a disease in its own right but simply a by-product of a wide variety of different disorders, most of which are described in detail elsewhere. However, because of its importance as a source of chronic ill health in many populations, the global aspects of the aetiology and manifestations of anaemia are summarized briefly in this chapter. Readers who wish to learn more of the complex literature on this important topic are referred to the extensive reviews cited at the end of the chapter.

Definition and prevalence

It has been very difficult to produce an adequate definition of anaemia. ‘Normal’ haematological values vary with age, between sexes, at different altitudes, and, possibly, between races. On the other hand, it is helpful to have a standard set of haemoglobin levels at different ages below which ‘anaemia’ is defined. The World Health Organization (WHO) have attempted to set out criteria of these kind, summarized in Table Despite their many shortcomings, including methodological vagaries, they at least provide a way of obtaining an approximate comparison of the distribution and frequency of anaemia among the different countries of the world.

Table Definition of haemoglobin levels below which anaemia is said to exist in populations at sea level (WHO 1968)

Haemoglobin (g/dl) below

Children, 6 months–6 years


Children, 6–14 years


Adult males


Adult females (nonpregnant)


Adult females (pregnant)


The global prevalence of anaemia, based on WHO criteria, was estimated in the 1980s. A review of the epidemiological data available at this time suggested that about 1.3 billion people were affected by anaemia, particularly in the developing countries. Infants, young children, menstruating, and, especially, pregnant women were the most severely affected groups (Table More recent estimations of the prevalence of anaemia suggest that there has been little improvement. For example it is now estimated that some 2 billion people worldwide are affected by iron-deficiency anaemia. About one-fifth of perinatal mortality and one-tenth of maternal mortality in developing countries is attributable to iron deficiency. In total, 0.8 million deaths worldwide are now attributable to iron deficiency, i.e. about 1.3% of all male deaths and 1.8% of all female deaths. Attributable disability-adjusted life years (DALYs) are even greater, accounting for the loss of about 35 million healthy life years, again the bulk of which are in the developing countries.

Table Estimated prevalence of anaemia by region and sex


Percentage anaemic


Women 15–49 years


0–4 years

5–12 years



15–59 years



















Data from DeMaeyer EM, Adiels-Tegman M (1985). The prevalence of anemia in the world. World Health Statist Quart, 38, 302–16.

The complex and multiple aetiology of anaemia in developing countries

The main causes of anaemia in developing countries are summarized in Box It is very difficult to determine their relative importance, particularly in tropical countries. Most surveys have focused on one particular mechanism, e.g. iron or folate deficiency. To obtain a true picture of the cause of anaemia in a particular population it is essential to obtain consecutive data over a long period. For example, work in the Gambia has shown that the haemoglobin levels in children vary significantly at different times of the year; anaemia is much more common in the wet season when malaria transmission is at its highest. To complicate matters, this is also the time when diarrhoea and malnutrition are most common. Heavy rains after many dry months have profound effects on the community; sanitation measures are disrupted and food stores are at the lowest level in the annual cycle (Fig.

Fig. Admissions to the children’s ward in a hospital in the Gambia over dry and rainy seasons.

Admissions to the children’s ward in a hospital in the Gambia over dry and rainy seasons.

(Data from Brewster DR, Greenwood BM (1993). Season variation of paediatric disease in The Gambia, West Africa. Ann Trop Paediatr, 13, 133.)

These observations underline the multifactorial aetiology of anaemia in the developing world. Nonetheless it is clear that iron deficiency, which probably affects at least 20% of the world’s population, is the most important factor; the many other diseases that can exacerbate anaemia are often operating in the background of low body-iron stores.

Iron deficiency

The causes of iron-deficiency anaemia are extremely complex and vary widely among different populations. The absorption of nonhaem iron, except from breast milk, is comparatively restricted, and the content of iron in breast milk is very low. Iron deficiency is particularly common in communities in which food is predominantly of vegetable origin. The three great staples in these populations are rice, wheat, and maize. Sorghum and millet are also important in parts of Africa and Asia. Soy and similar legumes are an important source of protein in many countries. The iron content of these diets is generally low, and, furthermore, absorption is inhibited by fibre, phytates, phosphates, and polyphenols, all of which occur in high levels in vegetarian diets. Populations who have remained as hunter-gatherers, and pastoralists who eat blood and meat, appear to have a lower frequency of iron-deficiency anaemia.

Anaemia as a challenge to world healthThe body’s response to infection may also reduce iron stores and iron utilization. Hepcidin is regulated by pro-inflammatory mediators, such as tumour necrosis factor and IL-6, which are elevated in a wide variety of infections. High hepcidin levels stimulated by malaria infection or bacterial infections reduce absorption of iron from the gut and also reduce incorporation of iron into red cells. Iron may act as a growth factor for malaria parasites, and so raised hepcidin and reduction in available iron may form part of a protective innate response to malaria infection. However, this protective response may contribute to functional iron deficiency and anaemia in endemic areas.

Against this background of deficient or borderline dietary iron intake, there are several other factors which may exacerbate iron deficiency. Iron requirements are greatly increased during pregnancy because of the expansion of the maternal red-cell mass (c.500 mg), iron transport to the fetus (c.300 mg), and the constitution of the placenta (c.25 mg), together with any blood loss at birth. Although there is some compensation by the cessation of iron loss due to menstruation (c.200 mg), the total requirements for a single pregnancy are more than 1 g. Iron is also excreted in breast milk and although the concentration is low this loss, particularly with prolonged breastfeeding, places a further burden on maternal iron stores.

In many tropical countries, there are important sources of pathological iron loss due to parasitic infection. Hookworm infestation affects millions of people worldwide. These parasites attach themselves to the mucosa of the intestinal tract. With a worm load of 1000 eggs/g faeces, the intestinal blood loss averages about 2.5 ml/day, representing 1 mg of iron. Although some of this is reabsorbed, perhaps up to 40%, hookworm infestation is an important source of iron imbalance. Infection with Schistosoma mansoni results in intestinal blood loss, while S. haematobium results in chronic haematuria. In Kenyan children, for example, mean iron losses in those infected with S. haematobium varied from 149 to 652 μ‎g/day, according to the magnitude of the egg counts.

Finally, it should be remembered that chronic ill health due to protein–calorie malnutrition or chronic infection may, by its effect on a patient’s appetite, result in further depletion of iron intake.

It must be emphasized that many surveys for assessing body iron stores have used methods which are confounded by associated inflammatory disease or other disorders. These problems are particularly germane to surveys which have been based on serum iron or ferritin levels. More recently, screening methods based on estimation of transferrin receptor levels have been developed but their application to large populations is, as yet, limited.

Folate deficiency

Folate deficiency is thought to be the second most frequent cause of nutritional anaemia in the world population. The mechanisms are complex and differ widely between different populations depending in the way in which food is prepared, in particular the temperature at which it is cooked. It is also clear that dietary folate deficiency is not the whole story. Research in Africa suggests that the continuous anorexia which accompanies recurrent infections such as malaria or tuberculosis is a major cause of folate deficiency in children. Postinfective malabsorption and the tropical sprue syndrome are also important causes of folate deficiency, particularly in the Indian subcontinent. Folate requirements may be increased in patients with erythroid hyperplasia secondary to chronic haemolytic anaemia, e.g. sickle cell anaemia, or chronic malarial infection. They also increase markedly during pregnancy. In women with low baseline folate stores, megaloblastic anaemia in pregnancy or the puerperium is particularly common.

Vitamin B12 deficiency

Nutritional vitamin B12 deficiency is uncommon, although it is observed in true vegans, particularly in the Indian subcontinent. Infants born of mothers with sprue or postinfective malabsorption who are fed on breast milk or goat’s milk containing insufficient vitamin B12 may develop megaloblastic anaemia with locomotor complications during the early months of life.


Almost any chronic infection may produce anaemia. Globally, the most important are the parasitic disorders, malaria, visceral leishmaniasis (kala-azar), schistosomiasis, and some forms of trypanosomiasis. The anaemias due to chronic hookworm infestation are considered in Chapter 22.5.2.

Malaria is still the most important parasitic illness of humans. Currently it is estimated that it has a global incidence of about 200 million cases per year, with over 1 million deaths. Its transmission and clinical manifestations are considered in Section 7. Profound anaemia is a major cause of mortality and morbidity during acute attacks of P. falciparum malaria in nonimmune individuals, but, from the perspective of health in the developing world, chronic infection with this organism in childhood is an extremely common cause of anaemia. This is most commonly seen in areas of high malarial transmission and is also a growing problem in regions of lower transmission because the rise in antimalarial drug resistance prolongs the average duration of infection. The anaemia of chronic malaria has a complex basis involving haemolysis, hypersplenism, and a suboptimal bone marrow response, often set against a background of iron or folate deficiency. In some populations, notably those of Africa, India, and parts of South-East Asia, chronic malarial infection may be complicated by the hyper-reactive malarial splenomegaly syndrome, in which hypersplenism plays a major role in the generation of chronic anaemia.

The haematological manifestations of the other common parasitic illnesses in the tropics are considered elsewhere.


Many people in tropical climates, both indigenous populations and expatriates who have worked in rural areas, have abnormalities of the intestinal mucosa, often associated with impairment of absorption. These structural and functional alterations of the gut have been called ‘tropical enteropathies’ (see Chapter 15.10.8). It is likely that they result from adaptation to life in the contaminated environment of the tropics, with frequent gastrointestinal infections and differences of diet.

More severe malabsorption syndromes, called sprue and postinfective malabsorption, are associated with chronic diarrhoea, wasting, and a variable degree of anaemia. The pathophysiology and world distribution of these syndromes are considered in Section 15. They are nearly all associated with anaemia, which has a complex aetiology including folate deficiency and, in some cases, iron deficiency.

It should also be remembered that in a tropical setting malabsorption can also result from colonization of the small bowel by specific parasites, including Giardia lamblia, Strongyloides stercralais, cryptosporidium, and others. Abdominal tuberculosis with malabsorption is also common. In Africa, HIV infection is now an important cause of malabsorption and bone marrow suppression.

Inherited anaemias

The inherited haemoglobin disorders are becoming an increasingly common cause of anaemia, particularly in tropical countries. They are described in detail in Chapter 22.5.7.

Because of heterozygote advantage against P. falciparum malaria, the important inherited haemoglobin disorders, notably sickle cell anaemia and the thalassaemias, have a high frequency throughout tropical populations of the Old World. Sickle cell anaemia and its variants are particularly common in Africa, some Mediterranean populations, and throughout the Middle East and parts of India. They also occur at a high frequency in the Caribbean and in other regions with large African populations. The thalassaemias occur at a high frequency in parts of Africa, the Mediterranean, the Middle East, the Indian subcontinent, and throughout South-East Asia. There is now clear evidence that these conditions will produce a major public health problem in these countries in the future. Children with sickle cell anaemia are highly susceptible to systemic bacterial infection and without neonatal screening for this disease and delivery of vaccination, prophylaxis, and good medical care up to half of children born with HbSS may die within the first three 3 years of life. As poorer countries go through the demographic transition, resulting from better hygiene and control of infectious illness, infants with these genetic anaemias are now surviving long enough to present for diagnosis and treatment. The high frequency of consanguineous marriages in many developing countries also plays an important role in maintaining the high frequency of these recessively-inherited diseases. Some estimated figures for the annual numbers of births of babies with sickle cell anaemia or β‎-thalassaemia are shown in Table

The effect that a high frequency of a disease such as thalassaemia can have on the health economy of an emerging country was shown graphically in the case of Cyprus after it passed through the demographic transition in the 1950s. It was estimated that if every patient with this disease was treated with regular blood transfusion and appropriate medication, within 15 years the management of this one condition would consume up to 40% of the island’s health budget. Recent studies in Indonesia indicate that, at a minimum estimate, approximately 1.25 million units of blood will be required each year to treat a proportion of the thalassaemic population in future years.

In many populations, there are hundreds of thousands of carriers for β‎-thalassaemia or the more common severe forms of α‎-thalassaemia. Although they are asymptomatic they have haemoglobin values which are, on average, 1 to 1.5 g/dl below normal. During pregnancy they retain this difference so that in the midtrimester they have haemoglobin values of approximately 8 g/dl or less. They have increased folate requirements and, in some populations, there appears to be an increased frequency of folate deficiency in pregnancy.

It should be remembered that the inherited anaemias may be exacerbated by other illnesses which are widespread in tropical countries. Folate requirements are increased in all these conditions and secondary folate deficiency is extremely common. They may also be exacerbated by malaria; children may develop malarial infection from infected blood donors. There is also a high frequency of other blood-borne infections, particularly hepatitis C and, in some populations, HIV. Furthermore, there is clear evidence that sickle cell anaemia and thalassaemia can render children more prone to infection. In short, like all forms of anaemia in the tropical world, the inherited disorders of haemoglobin may present with a complex series of complications due to a background of nutritional deficiency and a wide variety of infections.

These complex interactions have a dominant effect on the prognosis for the important inherited haemoglobin disorders. Early studies in Africa reported a marked paucity of patients with sickle cell anaemia despite a very high carrier frequency, indicating that very few patients with this disorder were surviving beyond early childhood. This may still be the case in parts of rural Africa. On the other hand, in more developed countries, and with a high quality of medical care, patients with this disease are regularly surviving into adult life; the mean survival time in the United States of America is now approximately 42 years, with many patients surviving to old age. A similar situation exists for β‎-thalassaemia. In poorer countries, supplies of blood may be limited, there may be difficulties in screening blood for agents such as hepatitis C and HIV, and the prohibitive cost of iron-chelating agents means that even children who receive transfusion die from iron loading before they reach the age of 20 years.

Table Annual births of severe disorders of haemoglobin

Sickle cell anaemia

Sub-Saharan Africa

240 932


92 997

HbSC disease

54 736


β‎thalassaemia major

23 329


20 588

HbH disease

14 504


12 321

Hb Bart’s hydrops

5 183

These recently collated data have to be viewed with caution because in many cases they are based on small surveys from a small number of centres in individual countries; there is recent evidence that the distribution of these conditions in different countries is extremely heterogeneous. The data are based on Modell and Darlinson (2008), Pielet et al. (2010), and Weatherall (2011), together with a variety of personal communications to the author.

There are other inherited anaemias which are particularly common on tropical countries due to heterozygote advantage against malaria. Glucose-6-phosphate dehydrogenase deficiency is estimated to occur in some 100 million individuals world-wide. Its clinical and haematological manifestations are discussed in Chapter 22.5.12. They include haemolytic reactions to a wide variety of drugs, and, of particular public health significance, to certain foods (favism). There is a form of ovalocytosis, particularly common in Melanesia, which is associated with a mild and well compensated haemolytic anaemia. Recent studies have shown that carriers of Melanesian ovalocytosis are completely protected against cerebral malaria.

Consequences of anaemia

The results of many studies directed at determining the functional consequences of anaemia are still controversial. It is often difficult to distinguish between the effects of anaemia per se and the consequences of iron or folate deficiency on other physiological functions. Whatever the mechanism, chronic anaemia is associated with diminished function.

Many studies have suggested that even mild anaemia may reduce near-maximal work capacity. WHO has recently stressed the increasing evidence that iron deficiency in children may reduce learning ability, intelligence and, in extreme cases, may lead to intellectual disability. There is no doubt that anaemia increases maternal mortality and morbidity. There is a very large literature on the effect of iron deficiency on resistance to infection, as mediated through either immune function or the bacteriostatic and bacteriocidal roles of iron-containing proteins such as transferrin and lactoferrin. The complex relationship between iron status and susceptibility of infection requires further work. It is clear that folate deficiency is associated with an increased prevalence of obstetric complications and fetal malformation, although its effect on intellectual and immune function is less clear.

In short, because of the remarkable ability of otherwise healthy individuals to adapt to moderate anaemia it seems likely that many of the associated manifestations which have been observed result from the effects of different deficiency states on other physiological functions rather than the anaemia per se. On the other hand, chronic severe anaemia, particularly in childhood, results in a wide variety of complications including failure of growth and development and, possibly, proneness to infection.


It is beyond the scope of this brief review to discuss the protean aspects of the prevention of anaemia, particularly in poorer countries. Its high prevalence is a reflection of gross poverty, particularly as manifested by nutritional deficiency, infection, and malabsorption. Its control requires action on many different fronts, including improvements in diet, fortification of commonly eaten foods with iron, the use of modified milk formulae for infants, malaria and hookworm control, iron and folate supplementation in pregnancy, and all-round improvements in hygiene. The problem of the population control of sickle cell anaemia and thalassaemia is discussed in Chapter 22.5.7. Good antenatal care helps to prevent anaemia in childhood by reducing prematurity, increasing average birth weight, and improving the nutritional status of the newborn.

Further reading

Beales PF (1997). Anaemia in malaria control: a practical approach. Ann Trop Med Parasitol, 91, 713–18.Find this resource:

    DeMaeyer EM, Adiels-Tegman M (1985). The prevalence of anemia in the world. World Health Statist Quart, 38, 302–16.Find this resource:

      DeMaeyer EM, et al. (1989). Preventing and controlling iron-deficiency anaemia through primary health care. World Health Organization, Geneva.Find this resource:

        Drakesmith H, Prentice AM (2012). Hepcidin and the iron-infection axis. Science, 338, 768–72.Find this resource:

          Fleming AF (1989). Tropical obstetrics and gynaecology. 1. Anaemia in pregnancy in tropical Africa. Trans R Soc Trop Med Hyg, 83, 441–8.Find this resource:

            Gallacher PG, Ehrenkranz RA (1995). Nutritional anaemias in infancy. Clin Perinatol, 22, 671–92.Find this resource:

              Hercberg S, Galan P (1992). Nutritional anaemias. Clin Haematol, 5, 143–68.Find this resource:

                Khusun H, et al. (1999). World Health Organization hemoglobin cut-off points for the detection of anemia are valid for an Indonesian population. J Nutr, 129, 1669–74.Find this resource:

                  Modell B, Darlison M (2008). Global epidemiology of haemoglobin disorders and derived service indicators. Bull World Health Organ, 86, 480–7.Find this resource:

                    Piel FB, et al. (2010) Global distribution of the sickle cell gene and geographical confirmation of the malaria hypothesis. Nat Commun, 1, 104.Find this resource:

                      Weatherall DJ, Kwiatkowski D, Roberts D (2009). Hematologic manifestations of systemic diseases in children of the developing world. In: Orkin, S.H. et al. (eds) Nathan & Oski’s Hematology of Infancy and Childhood, 7th ed, pp. 1741–1768, W.B. Saunders, Philadelphia.Find this resource:

                        Weatherall DJ (2011). The challenge of haemoglobinopathies in resource-poor countries. Br J Haematol, In press.Find this resource:

                          WHO (1968). Nutritional anaemias. Technical Report Series No. 405. World Health Organization, Geneva.Find this resource:

                            WHO (2002). The world health report 2002—reducing risks, promoting healthy life. World Health Organization, Geneva.Find this resource: