1.3 Undernutrition, infectious morbidity and mortality

Question 1

Overview

Answer 1

Good nutrition fosters the growth of a strong and healthy population that is economically productive; and this holds true for both the individual and the population.Conversely, we have established that undernutrition in its varied forms leads to:Immuno-incompetence and a high burden of infectious disease; Increased severity of disease and higher mortality; and Reduced economic productivity.

Question 2

Overview

Answer 2

As such, undernutrition matters. Poverty and socio-economic deprivation may be linked to poor nutrition but the outcomes can differ: in high income countries obesity is often an outcome of poverty due to easy access to cheap, but high calorie convenience foods; in low-income settings undernourishment can be the result of poverty; and however, in low-income urban settings again the outcome is obesity. Undernutrition in children and adults increases the risk from infections and is a major contributor to the increased morbidity and mortality in populations in low-income countries.

Question 3

Overview Learning objectives

Answer 3

After working through this session, you will be better able to: understand the cycle between undernutrition and infection; describe the evidence base for the association between undernutrition and risk of morbidity, mortality from infections and effects on growth in children; and explain the role of key micronutrients and combined micronutrient deficiencies on the risk of infections.

Question 4

Key terms Catabolism

Answer 4

The metabolic breakdown of complex molecules into simpler ones, resulting in a release of energy.

Question 5

Key terms ‘Catch-up’ Growth

Answer 5

A period of rapid growth, above the normal growth rate for age, following a period of slow growth caused by acute malnutrition or severe illness.

Question 6

Key terms Kwashiorkor

Answer 6

Severe undernutrition in young children characterized by oedema.

Question 7

Key terms Latent infection

Answer 7

Pathogen remains dormant and the infection may not progress to active infection or disease unless re-activated.

Question 8

Key terms Marasmus

Answer 8

Severe undernutrition in young children characterized by severe muscle-wasting.

Question 9

Classification of undernutrition

Answer 9

The terms ‘malnutrition’ and ‘undernutrition’ are often used loosely and interchangeably but ‘malnutrition’ is the umbrella term referring to allforms of poor nutrition: undernutrition; overnutrition; and micronutrient imbalances. Micronutrient deficiencies are often called ‘hidden’ malnutrition and indeed they are rarely visually apparent.

Question 10

Classification of undernutrition

Answer 10

This sections focus is undernutrition as a result of insufficient quantity of food. It is important to bear in mind that energy is typically the most important inadequacy; without energy the body can’t digest food or launch an immune response.

Question 11

Classification of undernutrition

Answer 11

The effects of an inadequate dietary intake start with catabolism of body fat and is followed by catabolism of skeletal muscle to supply energy – it is this catabolism of lean body mass that underlies the process of wasting. The degree of wasting of different tissues varies with the type and duration of the disease. There is break down of the visceral organs, but the brain and nervous tissue will typically be protected. The catabolic response to poor food intake can be further understood in terms of type-1 and type 2 nutrients (Golden, 2009).

Question 12

Classification of undernutrition

Answer 12

Type-1nutrientsare stored in the body and have control mechanisms to regulate delivery to the tissues. Most micronutrients (vitamins A, calcium and iron) fall into this category. A dietary inadequacy of a type-1 nutrient causes a depletion of body reserves and the impairment of the specific nutrients function.

Question 13

Classification of undernutrition

Answer 13

Type-2 nutrientssuch as sodium, potassium, calcium and zinc don’t have body stores as such but are an integral part of our cells. After digestion they are used in the building of new cells and growth, so a dietary inadequacy leads to reduced growth, slow cell turnover and slow tissue repair. This immediately reduces the need for the specific nutrient. However, if more of a type-2 nutrient is needed then lean body mass with be catabolised to release it.

Question 14

Classification of undernutrition

Answer 14

The loss of body tissue compromises the ability of the individual to mount an immune response and combat infections; thus, a predisposition to periodic infections is established. Any loss of body strength will also lead to a drop in work capacity and a reduced ability to sustain economically productive work.

Question 15

Classification of undernutrition

Answer 15

The two classical syndromes of undernutrition in children (kwashiorkor and marasmus), have been recognized for many decades. Kwashiorkor is diagnosed by the presence of bilateral oedema whereas marasmus is severe loss of body weight as a result of severe wasting. The clinical features of kwashiorkor, see Photo 1, and marasmus, see Photo 2, are different but some children presenting with kwashiorkor will ‘recover’ and lose the oedema to reveal an emaciated marasmic child. Kwashiorkor and marasmus are both types of very severe undernutrition and it is not understood why some children develop kwashiorkor and other marasmus. The severity of weight deficit and the presence or absence of oedema constitute the two important criteria both for the diagnosis of undernutrition and for its classification.

Question 16

Classification of undernutrition Kwashiorkor

Answer 16

The term ‘kwashiorkor’ was first introduced by Cicely Williams in 1933. In the language of the Ga tribe who live in Ghana, kwashiorkor was the name for the ‘sickness of the older child when the next baby is born’. It is of note that this timing could also relate to when there is an increase in complementary foods and a concomitant reduction in breast milk intake. Features: Acute undernutrition with bilateral oedema, metabolic dysfunction, signs: moon face, flaky paint skin, hair changes, salt/water imbalance, poorer prognosis

Question 17

Classification of undernutrition Kwashiorkor

Answer 17

In the early 20thcentury, a low protein intake was thought to be a determinant of kwashiorkor but this is not current thinking; particularly as within twins one can be marasmic and the other have kwashiorkor. The metabolic dysfunction seen in kwashiorkor could be the result of an overload of free radicals which leads to extensive tissue damage by the resultant oxidative stress. However, undernutrition itself also prevents adequate cellular repair so could cause skin lesions, oedema, fatty liver. We still do not understand why some children develop kwashiorkor but similar children remain marasmic.

Question 18

Classification of undernutrition Kwashiorkor

Answer 18

Catabolism, free radicals and poor nutrition all impact the quality of the primary barriers such as skin, mucosal linings and the basic innate immune defences. This immunocompetence results in more infections, often by multiple pathogens which further increases free radical exposure. The first aim in the treatment of kwashiorkor is to stabilise the dysfunctional metabolism and prevent further oxidative stress.

Question 19

Classification of undernutrition Kwashiorkor

Answer 19

This requires thevery gradual re-feeding with a low to moderate protein diet; providing antibiotic treatment; andwithholdingiron supplementation, due to lack of a carrier protein; and careful fluid management/restriction (Golden 2010). The oedema is the result of a salt-water imbalance and this must be carefully managed. Only when the oedema resolves, can normal metabolic functionality be presumed, and the treatment shift to the higher intake of feed. The child’s appetite tends to increase once they stabilise.

Question 20

Classification of undernutrition Marasmus

Answer 20

The term ‘marasmus’ is derived from the Greek word meaning ‘dying away’ and is applied to severe undernutrition in children. Absence of oedema in the presence of severe muscle wasting is characteristic of marasmus.Note: starvation, irritability, prominent stomach, Wt/Ht <90%, MUAC <11.5cm. The small bowel microbiome will change during undernutrition and ‘bad’ bacterial overgrowth can result. The protruding belly is due to a combination of the gases from the microbiome and worms.

Question 21

Classification of undernutrition Stunting

Answer 21

Persistent sub-optimal food intake associated with recurrent and episodic undernutrition in children can result in short stature. A restricted diet can prevent a child reaching their maximum genetic potential for growth, furthermore any future ‘catch up’ growth is improbable if limited food access remains even if the child remains free from infection.

Question 22

Classification of undernutrition Stunting

Answer 22

Stunting can occasionally be encountered in affluent societies as a result of clinical conditions. For example, coeliac disease can cause severe malabsorption, following intestinal surgery or in children with a chronic and severe anorexia secondary to some other pathology e.g. chronic infection. Stunting is difficult to detect by eye as children may visually look younger than they are; they may also exhibit slower sexual maturation.

Question 23

Activity 1 Turn back to Section 1, Assessment of nutritional status. Review the session and make notes about how undernutrition is assessed in infants, children, adults and the elderly.

Question 24

Infection and undernutrition in children

Answer 24

The interaction between infection and undernutrition is complex and it is not always possible or easy to separate the effects of infection on undernutrition from the effects of nutrition on infection. It can, however, be helpful to do so and in this section the role of infections as an immediate and direct cause undernutrition is discussed.

Question 25

Infection and undernutrition in children

Answer 25

Many investigators have reported how an infective episode serves as a stimulus to precipitate frank undernutrition in a child who may either appear to be well nourished, or marginally or mildly undernourished but growing normally in a poor environment.  More often, in the latter case, the child may grow optimally for the first six months or so after birth as long as it is breast-fed but no sooner are other foods (weaning) introduced than the child develops infections and shows growth faltering.  These patterns have been well recorded by Leonardo Mata and his colleagues from Guatemala and the body-weight record of one of the male children he followed up illustrates this very well (Figure 1).

Question 26

Infection and undernutrition in children

Answer 26

Figure 1 indicates the number and duration of the frequent infections which resulted in undernutrition.  From birth to 6 months of age, the child demonstrated normal weight gain despite some infections of the eyes and mouth, diarrhoea and upper respiratory illness (URI).  Between the ages of 6 and 12 months the child experienced repeated bouts of diarrhoea, URIs and an episode of measles that served to halt his weight gain and resulted in undernutrition.  From 12 to 36 months of age the child continued to have several bouts of serious illness which did not permit him to regain a normal trajectory of weight gain and growth. This case illustrates how frequent infections cause growth faltering and prevent ‘catch-up’ growth, leading to chronic undernutrition.

Question 27

Undernutrition, infection and mortality in children

Answer 27

Mortality from undernutrition is most common in young children and regrettably this is still a commonplace reality today.   The link between undernutrition and mortality was first quantified by Pelletier in 1995.  Pelletier’s work, from 53 low-income countries, indicated ‘that 56% of child deaths were attributable to malnutrition's potentiating effects, and 83% of these were attributable to mild-to-moderate as opposed to severe malnutrition’.

Question 28

Undernutrition, infection and mortality in children

Answer 28

Pelletiers study has been repeated many times and now most countries have country specific data.  A key feature to note is that the majority of deaths occur in children who are only mildly to moderately undernourished. In 2021 WHO estimate that 45% of deaths among children under 5 years of age are linked to undernutrition, mostly occurring in low- and middle-income countries.

Question 29

Undernutrition, infection and mortality in children

Answer 29

Fighting infections and launching the immune system is an energy intensive process; and if body temperature increases by 1oC the basal metabolic rate increases by 10%. The undernourished, by definition, don’t have the required energy stores to fight the infection adequately.

Question 30

Undernutrition, infection and mortality in children

Answer 30

The lack of energy to fight infection is however only half of the story.  Quantitative estimates suggest that children can have a reduction in food intake of about 20% during illness.  This food deficit has been estimated as 150kcal (630 kJ) per day and a calculated weight deficit of 30–40 g per day (Rowland et al, 1977).  Data from several clinical studies of children in low-income countries suggest similar levels of deficit in weight gain over time, corresponding with infectious events. These events have a significant impact on growth, even in well-nourished infants, as a period of catch-up growth after the illness is needed to recoup the loss.  This rapid growth requires increased nutritional intake which may be unlikely to be fulfilled especially if illness episodes occur frequently.  When nutritional intake is inadequate, optimal catch-up growth cannot take place, and will over time result in a height deficit (stunting). The failure to replace lost weight, especially of lean body mass, results in an increased risk of death.

Question 31

Undernutrition, infection and mortality in children

Answer 31

It is clear that the predominant cause of mortality in undernourished children is from infections caused by a wide range of pathogens, Table 1 presents a range of pathogens.  The most important illnesses that cause morbidity, and subsequent case fatality, include diarrhoeal disease, measles, acute respiratory infections (ARI’s), malaria, TB and HIV/AIDS.

Question 32

Undernutrition, infection and mortality in children

Answer 32

Overall, undernutrition and infection interact in a vicious cycle whereby undernutrition weakens the body’s immune response, predisposing an individual to increased frequency, duration and severity of episodes of infection.  Infections, in turn predispose individuals to poor nutritional status through reduction in appetite, decreased absorption of nutrients and an increased demand for nutrients. This can be conceptualised as a vicious cycle (see Figure 2).

Question 33

Activity 2 Turn to Dewey and Mayers (2011) Early child growth: how do nutrition and infection interact? And read up until The ‘dirty chicken’ experiment. This paper reviews the evidence regarding the interaction between nutrition and infection with respect to child growth and introduces the idea of environmental enteropathy.

Question 34

Undernutrition, infection and mortality in children

Answer 34

Scrimshaw presents many examples that provide reasonable evidence to show that deaths due to infectious diseases depend on the nutritional status of the child; for example: in Uganda, the risk of death from diarrhoeal disease increased tenfold in children who were undernourished (measured as underweight and decreased arm circumference); in Bangladesh, children with body weight at 55% of the reference weight for age had a death rate of 14% within 3 months of discharge following diarrhoeal disease compared to 1% in children with weight for age of 75% the reference value; and in Senegal, the case fatality rate due to diarrhoea in hospitalized patients was increased twofold if weight for height was less than 80% of the reference value (and increased six-fold if the children had severe undernutrition with oedema i.e. presented with kwashiorkor).

Question 35

Undernutrition, infection and mortality in children

Answer 35

Table 1 summarises the pathogenic organisms and the infections they cause, for which Scrimshaw concluded there was good evidence to support that nutritional status was important in determining susceptibility and/or outcome of infection.

Question 36

Undernutrition, infection and mortality in children Infectious agents and diseases infeluenced by nutritional status

Answer 36

M tuberculosis (TB in humans), S pyogenes (Rheumatic fever in children), B pertussis (Whooping cough in infants), Shigella (dysentery in Japanese prisoners of war), Rickettsia prowazeki (Typhus in Russian soldiers), Hepatitis A (more severe among malnourished children), Measles (more severe among malnourished children), HSV (severe herpes and more deaths in children with malnutrition), E histolytica (dysentery rare in well nourished), O volvulus (eye lesions more common in patients with low Vitamin A intake). Overall diarrhoea and respiratory infections more common in the malnourished

Question 37

Undernutrition, infection and morbidity in adults

Answer 37

Malnutrition increases the risk of individuals developing clinical diseases but a causal relationship is difficult to prove in human studies due to the ethical implications of withholding food in order to cause disease.   Cross-sectional studies cannot demonstrate causation and the relationship is synergistic.  Tuberculosis, and other infections, can lead to malnutrition and reduced micronutrient status through increased requirements and suppression of appetite, see Figure 1.

Question 38

Undernutrition, infection and morbidity in adults

Answer 38

However, historical events can provide supporting evidence such as the periods of acute food shortages that occurred during the German blockade of Denmark during the 2nd World War.  The food blockade coincided with a TB epidemic that was only reduced once the blockade was lifted.  The fact that food became more freely available provides some convincing evidence of the reality of this phenomenon.

Question 39

Undernutrition, infection and morbidity in adults

Answer 39

The relationship between poor nutritional status and TB infection and poorer clinical outcomes has been noted for many years; with TB being commonly referred to as ‘consumption’.  TB is a good example of a disease in which many people are “infected” but only a small proportion ever develop clinical disease (a latent infection).  Various micronutrient deficiencies have been associated with latent TB infections including vitamin A and D (cod liver oil is traditionally given to protect household contacts of TB patients), whilst iron surplus may also be associated with an increased risk.

Question 40

Undernutrition, infection and morbidity in adults

Answer 40

An area of increasing interest is the observation that many of the new, more virulent strains of viral infections, such as H1N1 flu virus, SARS and bird flu have first arisen in populations with a high prevalence of malnutrition.  There is now evidence to suggest that poor nutritional status of the host, and in particular of antioxidant nutrients, can influence not only host immune responses, but allow faster mutation rates of viruses, and thus the potential for new strains to develop (Levander, 1997).

Question 41

Undernutrition, infection and morbidity in adults

Answer 41

Finally, some of the effects of poor nutritional status on increasing risk of infectious disease may be due to specific deficiencies of some vitamins or minerals or trace elements. The roles of vitamins A & D, zinc and iron and the risk of infection are discussed elsewhere in this study guide. These are the commonest micronutrient deficiencies associated with increased morbidity and mortality from infections.

Question 42

Summary

Answer 42

Undernutrition in children is associate with an increase in morbidity and mortality due to an increase in the severity and duration of infections from a variety of bacterial, viral and other infectious agents. Adult undernutrition is associated with increased risk, duration and severity of infections.  Undernutrition and poverty make convalescence more difficult and more prolonged, with a high-risk of complications and failure to recover. Micronutrient deficiencies – of vitamins and minerals – compromise several aspects of the immune response.  This can increase the risk, severity and duration of infection, resulting in increased morbidity and mortality.

Question 43

Question 1 Undernourished children are at an increased risk of infection because: a) all of the above b) repeated infections exacerbate undernutrition c) their immune function is compromised d) they are likely to be living in poor environments prone to infectious diseases

Answer 43

d) they are likely to be living in poor environments prone to infectious diseases

Question 44

Question 2 Catch-up' growth occurs: a) in wasted children b) following a period of acute malnutrition or severe illness, and once sufficient food is available to support it c) during the third trimester of pregnancy d) only in adults

Answer 44

b) following a period of acute malnutrition or severe illness, and once sufficient food is available to support it

Question 45

Question 3 Environmental enteropathy is: a) a subclinical condition typified by flattened intestinal villi b) a subclinical condition typified by chronically increased intestinal inflammation and associated high cytokine levels c) more common than overt diarrhoea and a determinant of stunting

Answer 45

all of the above are correct

Question 46

Question 4 Adults are at an increased risk of adverse outcomes from infection if they have: a) low BMI, b) low lean-body mass, c) high skinfold thickness

Answer 46

c) high skinfold thickness