0.1 Historical context of nutrition and infection

Question 1

Overview

Answer 1

At the start of the 18th century social conditions in Britain were very poor. Mortality rates were high, malnutrition was widespread and infectious diseases rampant. However, the Industrial Revolution began around 1750 leading to an increase in economic productivity. There was a subsequent improvement in living conditions, improved nutritional status and a decline in mortality; though at the time it was not clear which factors were the drivers and which were the outcomes during this period of rapid change.

Question 2

Overview

Answer 2

It is now known that undernutrition leads to increased risk and susceptibility to infection. Equally, it is true that infection can precipitate undernutrition. There is a strong synergistic relationship between infection and nutritional status, even if specific metabolic mechanisms can be difficult to test scientifically. (This is because it isn’t typically moral, or easy to gain ethical clearance, to deliberately starve or feed people a depleted diet in order to expose them to infection). In this session, we look back at some of the studies published in the twentieth century that shed light on the associations between nutrition and infection.

Question 3

Learning objectives

Answer 3

After working through this session, you will be better able to: describe the problems of studying nutrition and infection; discuss the reasons for the decline in infectious mortality that occurred in England and Wales during the 19th century; understand the impacts of nutrition and infection on children; and Consider the merits of different types of study design.

Question 4

Key Terms Prospective study

Answer 4

A study in which the subjects are identified and followed forward in time.

Question 5

The Industrial Revolution (1750 – 1900)

Answer 5

In pre-industrial Britain life expectancy was low, no better than that of the rest of the world and possibly much worse. The living conditions for the majority were very poor, mortality rates were high and malnutrition was widespread. The historical crop yields were much lower than warmer countries such as Egypt, Iraq, India, China, South East Asia and meso-America.

Question 6

The Industrial Revolution (1750 – 1900)

Answer 6

However, the rapid developments of the Industrial Revolution made Britain richer and saw technological advances in agriculture; which were in part driven by the need to feed the growing industrial work force. Within 100 years, around 1830, life expectancy had increased and was greater than that in many parts of the world.

Question 7

ACTIVITY 1

Answer 7

Examine Figure 1 (overleaf), redrawn from the World Development Report (1993). This compares the structure of the population in England and Wales in 1891 and 1966. The median age at death is that age below which half of all deaths in year occur. Now answer these questions.

Question 8

ACTIVITY 1 1 Briefly describe what the figure shows.

Answer 8

1 Comparison of the data from 1891 with that for 1966 clearly shows the reduction in infant mortality and the consequent survival of more people to an older age. Most people now reach old age as judged by the median age at death. When the two years are compared it is clear that the age structure of the population has changed. Young people no longer predominate in the population and the number of those of older age has increased.

Question 9

ACTIVITY 1 2 How might the trends be explained?

Answer 9

2 These differences are the result of the control of infectious diseases and the reduction of the birth rate. The effect of the control of infection is clear to see but the influence of the reduction of birth rate is often neglected. As more children survive the need for large families is reduced and the consequent reduction in fertility and family size also effects the age distribution in the population.

Question 10

The decline in mortality came during the 1800’s

Answer 10

Mortality levels declined and life expectancy increased during the 1800’s in England and Wales. Examination of data has shown that the decline in overall mortality in largely due to a reduction in infectious disease mortality. However, during this period there were no major medical advances in the treatment or prevention of infectious disease.

Question 11

The decline in mortality came during the 1800’s

Answer 11

The main contribution was from the decline in tuberculosis which was attributed to improved nutrition. The improvement was found to be due mainly to a decline in mortality from infection among young adults and children; there was no improvement in infant mortality at that time. Figure 1 Evolving patterns of age distribution and mortality in England and
Wales

Question 12

ACTIVITY 2

Answer 12

Turn to the article by McKeown T and Record RG (1963) in the Moodle Reading List. Now answer these questions.

Question 13

ACTIVITY 2 1 Refer to pages 96, 102-104 and 109-115. Mortality from which infectious diseases declined during this period?

Answer 13

1 Tuberculosis, typhus, typhoid, scarlet fever, cholera and smallpox declined. The decline in typhus was attributed to improved hygiene and improved diet. Scarlet fever had no nutritional link. Cholera reduction was due to improved hygiene.

Question 14

ACTIVITY 2 2 Refer to pages 96, 102-104 and 109-115. Which disease contributed the most to this decline? Why did the decline occur?

Answer 14

2 Tuberculosis contributed 47% of the decline. Overcrowding and exposure to TB infection would have increased during this period. No significant medical progress nor changes to the infective agent occurred. On page 115 this paper concludes that an improved diet was the most significant environmental influence and reason for the decline in TB.

Question 15

ACTIVITY 2 3 Refer to pages 100 and 101. What age groups were particularly affected by the decline?

Answer 15

3 The ages 3 – 34 years benefited most from the decline. Infant mortality was not much improved nor was the death rate among those aged 45 or over. The decline in mortality was greatest among children and young adults.

Question 16

Nutrition and infection

Answer 16

In 1968 Scrimshaw et al. published a comprehensive review of the information available concerning the interactions of nutrition and infection. Table 1 below summarises their findings. Table 1 Studies showing a synergy between nutritional deficiencies and infection in humans. Multiple deficiencies, referred to in the first column of Table 1, means those with obvious signs of malnutrition – the clinically malnourished and/or ‘wasted’. These findings have been further reinforced by many studies since 1968 (see Tomkins, 2002).

Question 17

Nutrition and the immune response

Answer 17

Though many studies had shown the interaction between nutrition and infection, ascribing the susceptibility of malnourished people to infection to a failure of the immune response proved difficult.

Question 18

ACTIVITY 3

Answer 18

In 1946 Gell (1948) examined the immune response of severely undernourished people in Germany. Now turn to Gell (1948) in the Moodle Reading List and read the paper. Now answer these questions.

Question 19

ACTIVITY 3 1 Describe the design of the study.

Answer 19

1 The study compares the immune response in terms of antibody production of malnourished and adequately fed adults. The immune response was quantified by measuring the production of antibodies in an agglutination test.

Question 20

ACTIVITY 3 2 Why do you think the particular antigens were chosen?

Answer 20

2 The antigens were chosen to minimize the possibility of prior exposure and thus a pre-existing immune response.

Question 21

ACTIVITY 3 3 What are some of the deficiencies of the study?

Answer 21

3 There are two types of problem with the study:1 Ethical objections – an ethics committee might have difficulty with this study because there are no benefits to the subjects; and 2 Immunological problems - since this study was undertaken the knowledge of the immune system and the role different components play in resisting infection has advanced. If such a study was to be performed today a wider range of tests would be expected. For example, to examine cell mediated systems, cytokines etc. Nevertheless, the findings of this study provide a challenge to easy assumptions as to the interactions of nutrition and the immune response.

Question 22

The children of Santa María Cauqué

Answer 22

The study conducted by Mata and his co-workers (Mata, 1978) on the children of the village of Santa María Cauqué in Guatemala is one of the most famous early studies on nutrition and infection. It was a prospective study on a small group of children recruited at birth and studied by a multi-disciplinary team. The study was designed to minimize the disruption to the life of the village.

Question 23

The children of Santa María Cauqué

Answer 23

The development of the children: The weight and height of the children were measured and compared to the international standard. The results of these investigations are set out in the following figures.

Question 24

ACTIVITY 4

Answer 24

Examine Figures 2 and 3 and answer these questions. Figure 2 Mean values and standard deviations for weight, all cohort children, 1964-1972 Figure 3 Mean values and standard deviations for height, all cohort children, 1964-1972

Question 25

ACTIVITY 4 1 How does the development of these children compare to the international standard?

Answer 25

1 The children are both smaller and lighter than the international standard. The whole cohort seems to have been affected. All the children could be said to be stunted.

Question 26

ACTIVITY 4 2 What do you think is special about the first 3 months of life?

Answer 26

2 The growth in the first three months of life approximates to the international standard. This probably illustrates the effect of breast feeding (see Tomkins pages 396-400, in the Moodle Reading List). It seems likely that children in the study cohort were intrinsically able to reach the international standards for growth but that a setback occurred at weaning.

Question 27

Infant infections

Answer 27

There are two key factors at play here: 1 Putting food into an infant’s mouth directly introduces pathogens, particularly so if good hygiene is challenging; and 2 Other foodstuffs displace both the nutritional and protective immunological factors of breast milk. The patterns of infection and their influence on growth in two individual children are set out below. The results for a boy are set out in Figure 3 and for a girl in Figure 4.

Question 28

ACTIVITY 5

Answer 28

Look at Figure 4 and answer these questions.

Question 29

ACTIVITY 5 1 Describe the patterns of infection.

Answer 29

1 From 3 months of age the child is continually infected with a variety of intestinal pathogens. In addition, there is evidence of upper respiratory infections, measles and other infections.

Question 30

ACTIVITY 5 2 What is the impact on the growth of the child?

Answer 30

2 The growth of the child was suppressed. It is not possible to tell if the malnourishment consequent on infection also increased the susceptibility to infection.

Question 31

ACTIVITY 6

Answer 31

Look at Figure 5. Now answer these questions:

Question 32

ACTIVITY 6 1 Describe the pattern of infection.

Answer 32

1 The child was continually infected from birth, even in the first month when growth was good. Eventually the child died of bronchopneumonia.

Question 33

ACTIVITY 6 2 What was the result of the infection?

Answer 33

2 The result of the infections was to inhibit the growth and development of the child. From 12 months there was a catastrophic weight loss until death occurred. At this stage the child would undoubtedly have been wasted. This weight loss contrasts with the child illustrated in Figure 4 who, in spite of infection, continued to gain weight.

Question 34

ACTIVITY 7

Answer 34

During the central African drought in the 1970s, Murray (1975) observed that attacks of falciparum malaria were common in patients and their relatives soon after they arrived at hospital in Eastern Niger. In a group of 181 individuals, 74 attacks of falciparum malaria were recorded soon after arrival with a peak number of episodes on day 5 after arrival. Investigations conducted on arrival measured serum iron and percentage saturation of the iron-binding protein in blood, transferrin and also indicated a low level of parasitaemia. The parasitaemia increased soon after arrival and peaked on day 5; while the serum iron levels increased dramatically and the transferrin saturation reached maximum levels within 48 hours of arrival. Now answer the following questions.

Question 35

ACTIVITY 7 1 Can you explain why multiplication of malarial parasites and the increase in episodes of malarial fever occurred soon after arrival in hospital during a drought?

Answer 35

1 One possible explanation is that providing adequate food to individuals who had previously had inadequate food during drought increases their susceptibility to infectious agents.

Question 36

ACTIVITY 7 2 Is there an association between increasing parasite levels in blood and the changes in serum iron and transferrin saturation in these individuals?

Answer 36

2 Re-feeding (the feeding of undernourished individuals) or resumption of feeding possibly mobilizes iron stores, increasing serum iron levels, thereby promoting the multiplication of infectious agents like the malarial parasite by making more iron available to them. The hyperferraemia (high serum iron levels) may be an important factor precipitating these attacks. The level of unsaturated transferrin indicates that sufficient capacity to bind iron is available, thus making less free iron available for pathogenic organisms. With maximal saturation of transferrin, excess iron is in the free, unbound ionic form and may thus be readily available to the invading organism. This explains why infections such as malaria may be dormant in an individual during starvation and may become manifest following resumption of feeding.

Question 37

Summary

Answer 37

1 Undernutrition and infections have a strong synergistic relationship. 2 The introduction of complementary foods to infants (weaning) increases the likelihood of infections. 3 Prospective studies of children in Guatemala have documented the effects of infection on the development of malnutrition when nutrient intake is only marginally adequate.

Question 38

Self-assessment question What are the advantages of a prospective study in investigating the interactions of nutrition and infection in humans?

Answer 38

In a prospective study it is possible to determine if nutrition was adequate before the infection occurred. The growth charts show that the child illustrated in Figure 4 was adequately nourished before being infected. If the assessments had started only when the infections were established the child would have seemed to be malnourished all the time.