Nutrition and infection, health and disease

The interaction or synergism of malnutrition and infection is the leading cause of morbidity and mortality in children in most countries in Africa, Asia and Latin America. Viral, bacterial and parasitic infections tend to be prevalent, and all can have a negative impact on the nutritional status of children and adults. The situation was similar in North America and Europe from about 1900 to 1925; common infectious diseases had an impact on nutrition and produced high case fatality rates.

The synergistic relationship between malnutrition and infectious diseases is now well accepted and has been conclusively demonstrated in animal experiments. The simultaneous presence of both malnutrition and infection results in an interaction that has more serious consequences for the host than the additive effect would be if the two worked independently. Infections make malnutrition worse and poor nutrition increases the severity of infectious diseases.
Effects of malnutrition on infection

The immune system

The human body has the ability to resist almost all types of organisms or toxins that tend to damage the tissues and organs. This capacity is called immunity. Much of the immunity is caused by a special immune system that forms antibodies and sensitized lymphocytes which attack and destroy the specific organisms or toxins. This type of immunity is called acquired immunity. An additional portion of the immunity results from the general processes of the body; this is called innate immunity

Innate immunity is due to:

resistance of the skin to invasion by organisms;

phagocytosis of bacteria and other invaders by white blood cells and cells of the tissue macrophage system;

destruction by the acid secretions of the stomach and by the digestive enzymes of organisms swallowed into the stomach;

the presence in the blood of certain chemical compounds that attach to the foreign organisms or toxins and destroy them.

There are two basic but closely allied types of acquired immunity. In one of these the body develops circulating antibodies, which are globulin molecules that are capable of attacking the invading agents and destroying them. This type of immunity is called humoral immunity. Antibodies circulate in the blood and may remain there for a long time, so that a second infection with the same organism is immediately controlled. This is the basis for some forms of immunization, which are designed to stimulate antibody production.


The second type of acquired immunity is achieved through the formation of large numbers of highly specialized lymphocytes which are specifically sensitized against the invading foreign agents. These sensitized lymphocytes have the ability to attach to the foreign agents and to destroy them. This type of immunity is called cellular immunity. It is a highly complex system involving many different body organs (such as the spleen, thymus, lymph system and bone marrow) and also body fluids, particularly blood and its constituents and lymph.

The study of the complex system of immunity is termed immunology.

Effects of malnutrition on resistance to infection

A considerable amount of literature, documenting studies both in experimental animals and in people, demonstrates that dietary deficiency diseases may reduce the body's resistance to infections and adversely affect the immune system.

Some of the normal defence mechanisms of the body are impaired and do not function properly in the malnourished subject. For example, children with kwashiorkor were shown to be unable to form antibodies to either typhoid vaccine or diphtheria toxoid; their capacity to do so was restored after protein therapy. Similarly, children with protein malnutrition have an impaired antibody response to inoculation with yellow fever vaccine. An inhibition of the agglutinating response to cholera antigen has been reported in children with kwashiorkor and nutritional marasmus. These studies provide a fairly clear indication that the malnourished body has a reduced ability to defend itself against infection.

Another defence mechanism that has been studied in relation to nutrition is that of leucocytosis (increased production of white blood cells) and phagocytic activity (destruction of bacteria by white corpuscles). Children with kwashiorkor show a lower than normal leucocyte response in the presence of an infection. Perhaps of greater importance is the reduced phagocytic efficiency in malnourished subjects of the polymorphonuclear leucocytes that are part of the fight against invading bacteria. When malnutrition is present, these cells appear to have a defect in their intracellular bactericidal (bacteria-destroying) capacity.

Although malnourished children frequently have increased immunoglobulin levels (presumably related to concurrent infections), they also may have depressed cell-mediated immunity. In a recent study, the extent of this depression was directly related to the severity of the protein-energy malnutrition (PEM). Serum transferrin levels are also low in those with severe PEM, and they often take considerable time to return to normal even after proper dietary treatment.

A quite different kind of interaction of nutrition and infection is seen in the effect of some deficiency diseases on the integrity of the tissues. Reduction in the integrity of certain epithelial surfaces, notably the skin and mucous membranes, decreases resistance to invasion and makes an easy avenue of entry for pathogenic organisms. Examples of this effect are cheilosis and angular stomatitis in riboflavin deficiency, bleeding gums and capillary fragility in vitamin C deficiency, flaky-paint dermatosis and atrophic intestinal changes in severe protein deficiency and serious eye lesions in vitamin A deficiency.
Effects of infection on nutritional status

Infection affects nutritional status in several ways. Perhaps the most important of these is that bacterial and some other infections lead to an increased loss of nitrogen from the body. This repercussion was first demonstrated in serious infections such as typhoid fever, but it has subsequently been shown in much milder infections such as otitis media, tonsillitis, chicken pox and abscesses.

Nitrogen is lost by several mechanisms. The principal one is probably increased breakdown of tissue protein and mobilization of amino acids, especially from the muscles. The nitrogen is excreted in the urine and is evidence of a depletion of body protein from muscles.

Full recovery is dependent upon the restoration of these amino acids to the tissues once the infection is overcome. This requires increased intake of protein, above maintenance levels, in the post-infection period. In children whose diet is marginal in protein content, or those who are already protein depleted, growth will be retarded during and after infections. In developing countries, children from poor families suffer from many infections in quick succession during the post-weaning period, and they often have multiple infections.

Anorexia or loss of appetite is another factor in the relationship between infection and nutrition. Infections, especially if accompanied by a fever, often lead to loss of appetite and therefore to reduced food intake. Some infectious diseases commonly cause vomiting, with the same result. In many societies mothers and often medical attendants as well consider it desirable to withhold food or to place the child with an infection on a liquid diet. Such a diet may consist of rice water, very dilute soups, water alone or some other fluid with a low calorie density and usually deficient in protein and other essential nutrients. The old adage of "starve a fever" is of doubtful validity, and this practice may have serious consequences for the child whose nutritional status is already precarious.

The traditional treatment of diarrhoea in some communities is to prescribe a purgative or enema. The gastro-enteritis may already have resulted in reduced absorption of nutrients from food, and the treatment may further aggravate this situation.

These are all examples of how illnesses such as measles, upper respiratory infections and gastro-intestinal infections may contribute to the development of malnutrition. The relationship of intestinal parasites, diarrhoea and measles to nutrition is discussed below.

Parasitic infections

Parasitic infections, particularly intestinal helminthic infections, are extremely prevalent and are increasingly being shown to have an adverse effect on nutritional status, especially in those heavily infected. Hookworms (Ancylostoma duodenale and Necator americanus) infect over 00 million people, mainly the poor in tropical and subtropical countries. They used to cause a prevalent debilitating disease in the southern United States. Hookworms cause intestinal blood loss, and although it appears that most of the protein in the lost blood is absorbed lower down in the intestinal tract, there is considerable loss of iron.

Hookworm disease is a major cause of iron deficiency anaemia in many countries. The extent of the loss of blood and iron in hookworm infections has been studied (Layrisse and Roche, 1966): daily faecal blood loss per hookworm (N. americanus) was reported to be 0.031 0.015 ml. It was estimated that about 350 hookworms in the intestine cause a daily loss of 10 ml of blood, or 2 mg of iron. Infection densities much higher than this are not uncommon. In Venezuela, where much of this work was done, iron losses greater than 3 mg per day often resulted in anaemia in adult males, and losses of half this amount frequently produced anaemia in women of child-bearing age and in young children.

Worldwide, roundworm (Ascaris lumbricoides) is among the most prevalent of intestinal parasites. It is estimated that 1 200 million people in the world (one-quarter of the world's population) harbour roundworms. The roundworm is large (15 to 30 cm long), so its own metabolic needs must be considerable. High parasite densities, particularly in children, are common in environments where sanitation is poor. Complications of ascariasis can develop, including intestinal obstruction or the presence of worms in aberrant sites such as the common bile duct. In some countries ascarids are a cause of surgical emergencies in children, and many with obstruction die. In the majority of children, however, when malnutrition is prevalent, deworming improves child growth.

Trichuris trichiura or whipworm inhabits the large intestine and infects about 600 million people worldwide. The worms are small and, in heavily infected children, may cause diarrhoea and abdominal pain.

Many children living in poor sanitary conditions are infected with several parasitic infections at the same time. In areas where infection with these three parasites is common and where malnutrition is prevalent, deworming of children leads to an improvement in growth, a reduction in the extent of malnutrition and an increase in appetite. It also positively influences physical fitness and perhaps psychological development.

Bilharzia or schistosomiasis infections are prevalent in some countries. They also contribute to poor nutrition, poor appetite and poor growth. The three organisms that cause schistosomiasis (Schistosoma haematobium, Schistosoma mansoni and Schistosoma japonicum) are flukes, rather than ordinary worms.

Somewhat less is known about the relationship between intestinal protozoa! diseases and nutrition, but amoebas, causing serious dysentery and liver abscess, are highly pathogenic organisms, and infection with Giardia lamblia may cause malabsorption and abdominal pain.

The fish tapeworm (Diphyllobothrium latum) has an avidity for vitamin B12 and can deprive its host of this vitamin, with megaloblastic anaemia resulting. The fish tapeworm is common in people in only limited geographic areas, mainly in temperate areas and where undercooked fish is frequently consumed.

In many northern industrialized countries, farm animals and domestic pets such as dogs and cats are dewormed routinely. Much evidence suggests that pigs grow better when they regularly receive anthelmintics. Now that highly effective, relatively inexpensive and safe broad-spectrum anthelmintics such as albendazole and mebendazole are available, routine mass deworming should be introduced where parasitic infections are prevalent in humans and where PEM and anaemia are common. Similarly, routine efforts to treat children with schistosomiasis using metrifonate or praziquantel seem highly desirable both to rid children of potential serious pathology and to improve their nutritional status. More attention needs to be given to population-based chemotherapy for these infections along with intensification of public health and other measures to reduce their transmission, including improved sanitation and water supplies. Such efforts would improve the health and nutritional status of millions of the world's children.

Effects of diarrhoea

Many studies have indicated that gastrointestinal infections, and especially diarrhoea, are very important in precipitating serious PEM. Diarrhoea is common in, and often lethal to, the young child. In breastfed infants there is often some protection during the first months of life, so diarrhoea is often a feature of the weaning process. Weanling diarrhoea is extraordinarily prevalent in poor communities throughout the world, both in tropical and temperate zones. The organism responsible varies and often cannot be identified. Diarrhoea was a major cause of mortality in children in industrialized countries up to the beginning of the twentieth century.

Several studies have shown that admissions of cases of malnutrition are greatly increased during the season when diarrhoea is most common. For example, in a report from the Islamic Republic of Iran, more than twice as many cases of PEM were admitted in the warm summer than in the cold winter. The incidence of diarrhoeal disease followed the same pattern.

Hospital and community studies indicate that cases of xerophthalmia and keratomalacia are frequently precipitated by gastro-enteritis, as well as by other infectious diseases such as measles and chicken pox. Xerophthalmia is the major cause of blindness in several Asian countries; it is also prevalent in certain parts of Africa, Latin America and the Near East.

Intestinal parasites may contribute to diarrhoea and to poor vitamin A status. The exact mechanism of this relationship has not been proved, but it is likely that many infections reduce vitamin A absorption and that some result in decreased consumption of foods containing vitamin A and carotene.

Diarrhoea can be fatal, usually because it can lead to severe dehydration (see Chapter 37). Diarrhoea, and the complication of dehydration, may be said to be a form of malnutrition. Dehydration is a "deficiency" in the body of water and mineral electrolytes, and providing adequate quantities of these cures the deficiency. The term "fluid electrolyte malnutrition" (FEM) has been coined for this condition. Provision of water and adequate minerals in home-prepared food, breastfeeding or administration of oral rehydration fluids is now the accepted treatment. Although these are forms of therapy or treatment, they are really refeeding and replenishment. However, prevention requires measures and interventions to reduce infections, poverty and malnutrition. These are essential if countries are to reduce the incidence of diarrhoea.

Fatality rates for measles and other infectious diseases

A dramatic illustration of the effect of malnutrition on infection is seen in the fatality rates for common childhood diseases such as measles. Measles is a severe disease with a case fatality rate of about 15 percent in many poor countries because the young children who develop it have poor nutritional status, lowered resistance and poor health. In Mexico the fatality rate for measles has been reported to be 180 times higher than that in the United States; in Guatemala, 268 times higher; and in Ecuador, 480 times higher. The decline in case fatality rates of measles in North America, Europe and other industrialized countries has been dramatic over the last century.

Differences in the clinical severity and the fatality rates of measles in developed and developing countries are due not to differences in virus virulence but to differences in the hosts' nutritional status. For example, during a measles epidemic in the United Republic of Tanzania that was causing considerable mortality among the children of poorer families, it was observed that fatalities from the disease were extremely uncommon in the children of families of moderate income, such as those of hospital employees. Measles is also related to vitamin A deficiency. It has been shown that providing vitamin A supplements to children with measles who have poor vitamin A status greatly reduces case fatality rates.

Immunization against measles is proving very effective, and in many countries measles incidence has been markedly reduced.

Other common infectious diseases such as whooping cough, diarrhoea and upper respiratory infections also have much more serious consequences in malnourished children than in those who are well nourished. Mortality statistics from most developing countries show that such communicable diseases are the major causes of death. It was observed in several African countries at the end of the Sahel famine that very few children were dying of starvation or malnutrition, but that deaths from measles, respiratory infections and other infectious diseases were still very much above pre-famine levels. It is clear that many, perhaps the majority, of these deaths were due to malnutrition. This may seem a moot point for a grieving parent, but for the policy planner and the public health official it is important to know to what extent morbidity and mortality rates are due to or related to undernutrition.

An inter-American investigation of mortality in childhood showed that of 35 000 deaths of children under five years of age in ten countries, in 57 percent of the cases malnutrition was either the underlying or an associated cause of death. Nutritional deficiency was the most serious health problem uncovered, and it was frequently associated with common infectious diseases.

HIV infection and AIDS

Perhaps no disease has a more dramatic and obvious effect on nutritional status than acquired immunodeficiency syndrome (AIDS), the disease caused by the human immunodeficiency virus (HIV). In Uganda for many years the disease was called "slim disease" because extreme thinness was the main visible manifestation of the disease. Although the mechanisms by which AIDS leads to severe malnutrition have not been proven, there is no doubt that the disease and its associated opportunistic infections cause marked anorexia, diarrhoea and malabsorption as well as increased nitrogen losses. Some of the infections and conditions that are part of the AIDS complex of diseases were known to affect nutritional status long before the HIV virus was identified: tuberculosis has for many decades been associated with cachexia and weight loss, and malignancies such as sarcoma have long been known to result in wasting as they advance.

For a discussion of the relationship of AIDS to breastfeeding, see Chapter 7.
Chronic diseases and old age

There is a relationship between certain chronic diseases and immune response. It has also been clearly shown that in old age immunologic response is reduced, and undernutrition worsens this decline. The association of diabetes with infections is well known, and it is clear that in diabetes there is often impaired cellular response. Other diseases, for example several cancers, may also be related to lowered immune response (see Chapter 23).
Intervention studies

There have been relatively few well-controlled intervention studies to demonstrate either the effects of improved diets on infection or the nutritional effects of control of infectious diseases. Research in the village of Candelaria in Colombia showed that diarrhoea declined sharply as a result of supplementary feeding of children. A similar study in a Guatemalan village illustrated a significant decline in morbidity and mortality from certain common illnesses following the introduction of a nutritious daily supplement for preschool children.

A classic study conducted in Narangwal in the Punjab region of India demonstrated the value of combining nutritional care and health care in one programme. Children were divided into four groups. One group was given dietary supplements, one group was given health care, one group received both the supplements and the health care, and the fourth group served as control. As far as nutritional status and certain other health parameters were concerned, the combined treatment gave the best results. Nutritional supplementation alone also had a major impact. In comparison with the control group, there was no improvement in the nutritional status of the group that received only medical care but no dietary supplements.
Nutrition, infection and national development

Clearly, the effects of nutritional status on infections and of infections on malnutrition signify a very important relationship. The majority of children in most developing countries suffer from malnutrition at some time in their first five years of life. The problems of infection and malnutrition are closely interrelated, yet programmes to control communicable diseases and to improve nutrition tend to be introduced quite independently. It would be much more efficient and effective if the twin problems were attacked together.

Success in improving the health and reducing the mortality of children is dependent both on control of infectious diseases and on improvements in the children's food intake and care. There is increasing evidence to suggest that parents are more willing to control their family size when the chances are good that most children born will survive into adulthood. Consideration also needs to be given to providing a stimulating environment for the growing child.

The situation in the major industrial cities of Europe and North America a century ago was comparable to that in the poorest developing countries today. In New York City in the summer months of 1892, the infant mortality rate was 340 per 1 000, and diarrhoea. accounted for half these deaths. Improvements in nutrition, through the use of milk stations, for example, and a reduction in infectious disease served to lower these mortality rates by half in a period of less than 25 years. In the United Kingdom at the beginning of the twentieth century, rickets, combined with infectious diseases, took a heavy toll in the insanitary, smoky slums of the industrial cities, and measles was very often fatal among children of poor families, presumably because of poor nutrition.

Malnutrition and infections combine to pose an enormous hazard to the health of the majority of the world's population who live in poverty. This ever-present hazard particularly threatens children under five years of age. Many of the children who suffer from both malnutrition and a series of infections succumb and die. They are continually replaced in answer to parents' strong desire and often real need to have surviving children. The children who live beyond five years of age are not mainly those who have escaped malnutrition or infectious diseases, but those who have survived. Seldom are they left without the permanent sequelae or scars of their early health experiences. They are often retarded in their physical, psychological or behavioural development, and they may have other abnormalities that contribute to a less than optimal ability to function as adults and possibly to a shortened life expectation. Other factors influencing the development of these children include a lack of environmental stimulation and a host of other deprivations related to poverty.

The challenge to health workers, development economists, governments and international agencies is how best to reduce the morbidity, mortality and permanent sequelae that result from the synergism of malnutrition and infection. The politicians must be persuaded that attention to these problems is not only highly desirable but politically advantageous.

The control of infectious diseases and projects aimed at providing more and better food for people are fully justified and important components of a development plan. By themselves they may contribute to increased productivity and better lives. An improved infant or toddler mortality rate, a lowered disease incidence and a better-nourished population are probably better indicators of development shall national averages of telephones or automobiles per 1 000 families, or even than dollars or pesos per caput. Efforts for the control of infectious diseases and the improvement of nutrition both deserve a high priority in development plans and in international or bilateral assistance to low-income countries. They should be undertaken together because they will be mutually reinforcing and more economical if provided in a coordinated manner rather than separately. An allied issue is the need to provide a stimulating environment for the growing child.

Historical and epidemiological evidence suggests that reductions in infant and child mortality and improvements in health and nutritional status may be prerequisites to successful family planning efforts. Birth spacing deserves a high priority, especially where women are already overworked and undernurtured. Parents in all countries should receive assistance to help them achieve their desired family size.

Alarming as the situation of children's malnutrition and infection is, there is a general tendency to overlook the significance of these conditions in adults. Weakness, lethargy, absenteeism, poor productivity and stress can all have social and economic costs for individuals, families and communities.

There seems to be unassailable logic in recommending coordinated programmes that have three objectives: to control infectious disease, to improve nutrition and to make family planning services widely available. These three types of endeavour may themselves be synergistic.