7.2.3 POOR GROWTH AND RISK OF INFECTION

(A) Prospective Studies

James JW. Longitudinal study of the morbidity of diarrhoeal and respiratory infections in malnourished children. Am J Clin Nutr 1972;25:690-94.

From poor areas of San Jose, Costa Rica, 137 children under 5 years of age were selected randomly. Each child was weighed at the outset of the study and then every month for 1 year. Homes were visited weekly and information collected on the morbidity of the child over the previous 7 days. Children were classified as normal weight or low weight (Iowa standard and standards of INCAP). The incidence of diarrhoeal attacks was higher in low weight compared to normal weight subjects and the attack duration was significantly longer in low weight compared to other children. The number of severe diarrhoeal attacks was also higher in the low weight group. The incidence of respiratory tract infections did not differ between groups, but the average duration and severity of the attacks were significantly different. There were 4 deaths during the study, all in the low weight group.

Comments

Although the normal and low weight groups were matched by socioeconomic group, they were not comparable in age structure; the low weight group had a higher percentage of subjects under 12 months and fewer over 36 months. There is no information on sex distribution of the 2 groups. It is unclear what the definition of normal and low weight is based upon.

Lang T, Lafaix C, Fassin D, Arnaut I, Salmon B, Baudon D, Ezekiel J. Acute respiratory infections: a study of 151 children in Burkina Faso. Int J Epidemiol 1986;15:553-61.

Morbidity in all children under 5 years of age in Bana village was studied during two 3-month periods: one during the cool, wet season and one during the hot, dry season. During a preliminary period the children’s nutritional status was assessed by means of weight for height and mid upper arm circumference. Morbidity was then assessed by means of regular home visits. In both the wet and the dry seasons, acute respiratory infections (ARI) accounted for more than half of all illnesses. Using 80% weight for height as a cut-off point, neither incidence nor prevalence of ARI was significantly associated with malnutrition. However, among those with low arm circumference there was an increase in both incidence and duration of lower respiratory tract infection (LRI). Birth rank was also positively correlated with LRI.

Comments

Neither the season in which nutritional status assessment was carried out nor the standard used for calculating weight for height are specified.

Palmer Dl, Koster FT, Alam AKMJ, Islam MR. Nutritional status: A determinant of severity of diarrhoea in patients with cholera. J Infect Dis 1976;134:8-14.

In a prospective study, 97 male patients over 1 year of age hospitalised with cholera in Dhaka, Bangladesh were followed. Patients were assigned sequentially either to a group receiving tetracycline or not receiving tetracycline. Stool volume was recorded every 8 hours. Growth was assessed at the time of discharge. Each age group (child and adult) was divided into two groups; those with weights for height above the median for the sample were the “better nutrition” group and those below were the “poorer nutrition” group. Ninety five percent of both adults and children were below their respective medians in weight as related to height. Duration of diarrhoea, but not volume of stool per hour, was prolonged by 30%-70% in those adults and children in the “poorer nutrition” group. The increased stool loss was unrelated to antibiotic usage, to presence of intestinal parasites, or to the refeeding diet given.

Comments

As parent’s estimate of age were judged to be unreliable, weight for height was used to define nutritional status. Instead of using a cut off point (e.g., 80%) to separate “better” and “poorer” nutrition groups, the median weight for height value within each subgroup is used. This makes comparison with other studies difficult.

Sinha DP. Measles and malnutrition in a West Bengal village. Trop Geogr Med 1977;29:125-34.

The occurrence of measles over a 3 year period was observed in 310 children, aged 2 months to 4.5 years in a West Bengal village. All children were clinically examined every 4 weeks and measured every 3 months. Most of the cases were in children between 2-6 years and occurred between May and August each year. Severely malnourished children (below 10th percentile local West Bengal weight percentile curve, or less than 0.25 mid arm to head circumference) were significantly less likely to develop the measles rash than better nourished children.

Tomkins A. Nutritional status and severity of diarrhoea among preschool children in rural Nigeria. Lancet 1981;l:860-862.

Attack rate and duration of diarrhoea were assessed in 343 children aged 6-32 months at the beginning of the rainy season in Northern Nigeria. Children were measured at baseline and field workers made weekly visits for 3 months and interviewed mothers about the occurrence of diarrhoea. There were 1.4 attacks of diarrhoea per child during the 3 month rainy season and children spent 10.5% of the time with diarrhoea. The frequency of diarrhoea was not increased in underweight (below 75% weight for age) or stunted (below 90% height for age) children, but those who were wasted (below 80% weight for height) experienced 47% more episodes of diarrhoea than those who were not wasted. However, pre-existing malnutrition affected the duration of diarrhoea, which was 33% longer in underweight children, 37% longer in stunted children and 79% longer in wasted children.

Comments

Although this study showed an increased incidence of diarrhoea in the wasted children this might have been due to pre-existing illness. Subsequent analysis suggests that a high proportion of the wasted children had been infected with measles. Their diarrhoea might therefore have been more related to the post measles syndrome than to nutrition.

Chen LC, Huq E, Huffman SL. A prospective study of the risk of diarrhoeal diseases according to the nutritional status of children. Am J Epid 1981;114:284-92.

A total of 2,019 Bangladeshi children from the Matlab area aged 12-23 months were classified according to weight for age, weight for height and height for age. Over a 24 month prospective period, diarrhoeal hospitalisation rates among the children were matched to their initial anthropometric assessment. No differences in diarrhoeal hospitalisation rates were noted for the children according to initial nutritional status. A second group of 207 children under 5 years of age were visited at home over a 1 year period. Diarrhoeal morbidity data were collected every week and anthropometric measures were repeated monthly. Again, no differences in field diarrhoeal attack rates were noted between children of varying nutritional status categories. The nutritional status of the children was then defined as monthly growth velocity (Kg change in body weight, per cent change of initial body weight, and percent change in weight for age) and the diarrhoeal attack rate for the subsequent 1 month period was observed. No differences in attack rates were noted between nutritional groups.

Comments

This study only focused on episodes of diarrhoea that were severe enough to require attendance at a treatment centre.

Delgado HL, Valverde V, Belizan JM, Klein RE. Diarrhoeal diseases, nutritional status and health care: Analyses of their interrelationships. Ecol Food Nutr 1983;12:229-34.

A prospective study of Guatemalan Indian children below two years of age was carried out in 12 coffee plantations. Morbidity information was gathered fortnightly from mothers or carers. Anthropometric data was obtained at birth and every 3 months up to 24 months of age. Data collected were analysed by season. The incidence of diarrhoea was significantly more frequent in children with low weight for age (below 75%) and low weight for length (below 90%), but not for children with low length for age (below 90%). The duration of diarrhoea was significantly longer in children only with low length for age.

Comments

No information is given on the total number of children who took part in the survey or how thorough coverage was. It was assumed that the socioeconomic characteristics of plantation families were homogeneous. The recall period for morbidity was relatively long (2 weeks) and the definition of diarrhoea, as any change in frequency or consistency of stools was vague. This may have blurred distinction between episodes.

Black RE, Brown KH, Becker S. Malnutrition is a determining factor in diarrhoeal duration, but not incidence, among young children in a longitudinal study in rural Bangladesh. Am J Clin Nutr 1984;37:87-94.

One hundred and ninety seven children aged 2-48 months took part in a longitudinal study of 1 year in the Matlab field research area in rural Bangladesh. Monthly anthropometric and weekly diarrhoea morbidity data were collected. Children with low weight for length (below 80%) had longer durations of diarrhoea than other children, but there were no differences in incidence of diarrhoea between children of normal or poor growth by any of the anthropometric measures. Duration of diarrhoea increased progressively as nutritional status indicators worsened.

Mathur R, Reddy V, Naidu AN, Krishnamachari R, Krishnamachari KAVR. Nutritional status and diarrhoeal morbidity: a longitudinal study in rural Indian preschool children. Hum Nutr: Clin Nutr 1985;39C:447-54.

A total of 721 children below 5 years living in two villages outside Hyderabad, India were involved in the study. A household survey was conducted initially to obtain information on socioeconomic and environmental conditions. Anthropometric measurements were made on the children. Data on diarrhoea related morbidity was collected by trained field investigators who visited the households twice a week for the study period of 1 year. The incidence and duration of diarrhoea was similar in children regardless of their nutritional status (height of age, weight for height). However, the percentage incidence of episodes leading to severe dehydration was significantly higher in children of weight for age below 60%.

Bhan MK, Arora NK, Ghai OP, Ramachandran K, Khoshoo V, Bhandari N. Major factors in diarrhoea related mortality among rural children. Indian J PMed Res 1986;83:9-12.

A total of 1467 children under 5 years of age in Haryana, India were visited every 10 days for 20 months. Data on diarrhoeal morbidity and mortality was collected and the children were weighed at baseline, 11 and 20 months. Four nutritional status categories were defined based on weight for age. Although diarrhoeal attack rates were similar in different nutritional groups, the case fatality rate was significantly higher in severe malnutrition (below 60% weight for age) as compared to other children.

Comments

The relationship between duration of diarrhoeal bout and degree of malnutrition was not explored in this study.

Tomkins AM, Dunn DT, Hayes RJ. Nutritional status and risk of morbidity among young Gambian children allowing for social and environmental factors. Trans Royal Soc Trop Med Hyg 1989;83:282-7.

A prospective study of over 600 children aged 6-35 months of age was conducted during two seasons in an urban Gambian community. Anthropometric measurements (weight and height) were made on children at the end of the dry season and again at the end of the rainy season. Monthly visits were made to the home to gather morbidity data. At the beginning of the rainy season, the overall prevalence of illness and the prevalences of diarrhoea and fever increased steeply and significantly with decreasing height for age. The prevalences of diarrhoea and fever in children with height for age SD score below -3 (approximately 88% NCHS standards) were estimated to be twice those of children with SD scores above 0. The significant effects remained after controlling for the possible confounding effects of a range of social, economic and environmental factors. The associations with weight for age and during the dry season were weaker. There was no clear threshold value above which the association between morbidity and nutritional status flattened out.

Henry FJ, Alam N, Aziz KMS, Rahaman MM. Dysentery, not watery diarrhoea, is associated with stunting in Bangladeshi children. Hum Nutr:Clin Nutr 1987;41:243-9.

To study the interaction between diarrhoea and malnutrition, diarrhoeal episodes, differentiated according to stool appearance, were recorded weekly for 300 children aged 5 to 24 months in villages around Teknaf, Bangladesh. Weight and height measurements of the same children were made every six months during the 2-year study period. None of the nutritional status indices (weight for age, weight for height or height for age) were related to the overall diarrhoeal attack rate or the duration of watery diarrhoea during the 60 days following anthropometric assessment. However, children with weight for age less than 60% of the NCHS standard value and those with height for age less than 85% of standard experienced significantly longer episodes of dysentery than better-nourished children. The association between stunting and duration of dysentery persisted after the data were disaggregated by season.

El Samani EFZ, Willett WC, Ware JH. Association of malnutrition and diarrhea in children aged under 5 five years: a prospective follow-up study in a rural Sudanese community. Am J Epidemiol 1988;128:93-105.

To test the hypothesis that malnutrition increases the incidence of diarrhoeal disease, all children under five years of age in a village north of Khartoum were studied for one year. The 445 children were weighed and measured at two-month intervals. Information on diarrhoea was collected once every two weeks by an interviewer who visited the subjects’ parents in their homes. During 2-month intervals that followed a prior episode of diarrhoea, weight for age less than 90% of NCHS standard value was associated with a higher incidence of diarrhoea after adjusting for potential confounding effects of age and socio-economic factors. During 2-month intervals with no diarrhoea in the preceding interval, the association with low weight for age was weaker, but in these instances height for age below 95% of standard value was significantly associated with increased diarrhoea incidence. After adjustment for age, socio-economic factors and diarrhoea in the previous interval, weight for age below 75% of standard was associated with a doubling of risk of diarrhoea in the subsequent interval, regardless of whether or not there had been diarrhoea in the preceding interval.

Comments

The data are consistent with the hypothesis that malnutrition increases the prevalence of diarrhoea, but the study did not differentiate between attack rate and duration.

Sepulveda J, Willett W, Munoz A. Malnutrition and diarrhea: a longitudinal study among urban Mexican children. Am J Epidemiol 1988;127:365-76.

In order to test whether malnutrition is associated with an increased risk of diarrhoea, a cohort of 284 urban Mexican children under 2 years of age were followed for one year. The cohort was deliberately chosen in such a way as to ensure equal representation of the following weight for age categories at the start of the study: 90% of NCHS standard or greater; 75 to 89% of standard; 60 to 74% of standard. Anthropometric assessment was repeated every 3 months, and occurrence of diarrhoea was assessed by interviews with parents at weekly home visits. Of the anthropometric indices considered (weight for age, length for age, weight-for-length), weight-for age was the strongest predictor of diarrhoea during the subsequent 3-month interval. In comparison with well-nourished children, mildly malnourished (75 to 89% weight for age) and moderately malnourished (60 to 74% weight for age) children had relative risks of diarrhoea of 1.1 and 1.8 respectively. Adjustment for demographic, seasonal and socio-economic variables only slightly reduced this association.

Comments

These results are consistent with the hypothesis that malnutrition predisposes to diarrhoea in young children, but do not distinguish between effect on attack rate and effect on duration.

Macfarlane DE, Horner-Bryce J. Cryptosporidiosis in wellnourished and malnourished children. Acta Paediatr Scand 1987;474-7.

In a Jamaican hospital, Cryptosporidium was detected more frequently than any other enteric pathogen in the stools of malnourished Jamaican children (defined as weight for height 90% of standard or lower). 15 hospitalised children with cryptosporidiosis and varying degrees of malnutrition were compared to 4 well-nourished hospitalised children. In comparison to the malnourished children, fever, vomiting, and dehydration were less common and diarrhoea was less protracted in the well-nourished children. The authors conclude that malnourished children may be particularly predisposed to infection with Cryptosporidium.

Comments

Since there is no indication that the well-nourished and malnourished children were similar with respect to age, socio-economic status or exposure to Cryptosporidium, the observed differences in morbidity were not necessarily related to nutritional status. Since nothing is known about the nutritional status of the children prior to admission, it is not clear whether malnutrition predisposes to cryptosporidiosis or vice versa.

Renton AM, Goldmeier D, Wadsworth J. Dietary influences in HIV infection in homosexual males. (Unpublished).

A total of 75 homosexual men were recruited to take part in a study in London, U.K. Twenty seven subjects were newly tested HIV seropositive while 48 were HIV seronegative. All participants filled in a food frequency questionnaire and a sexual lifestyle questionnaire. The overall intakes of all nutrients except protein, polyunsaturated fat and vegetable fibre were significantly higher among the seropositive group. There was a significantly higher intake of polyunsaturated fat as a ratio of total fat and to total calorie intake. The fat associations remained significant after controlling for differences in history of sexually transmitted disease and number of sexual partners.

Comments

As the data for this study came from food frequency questionnaires, it was not possible to analyse micronutrient intakes. This could yield interesting results. The significance of the low polyunsaturated intakes among seropositive subjects is as yet unknown.

Jain VK, Chandra RK. Does nutritional deficiency predispose to acquired immune deficiency syndrome? Nutr Res 1984;4:537-43.
[REVIEW]

The immunological abnormalities seen with AIDS are listed and striking parallels with the immune changes seen in various nutritional deficiency states noted. It is proposed that AIDS is an opportunistic infection with a retrovirus, such as the human T cell leukaemia virus, that predominantly affects people at high risk due to a variety of underlying factors, including nutritional deficits. Thus patients with poor nutritional status may be more likely to develop the full blown disease than better nourished patients. In addition, once the patient develops the major manifestations of AIDS, there may be mutually detrimental interactions between nutrition, immunity and infections. There is little information on the dietary intake of AIDS patients prior to the development of symptoms. However, many patients are wasted and asthenia and weight loss may precede the occurrence of opportunistic infections and tumours. Nutritional supplementation and treatment of intercurrent infections should improve the immune status and significantly decrease the incidence of AIDS in susceptible populations.

(B) Intervention Studies

Wray JD. Direct nutrition intervention and the control of diarrhoeal diseases in preschool children. Am J Clin Nutr 1978;31:2073-82.

A nutrition intervention programme was carried out in Candelaria, Colombia. A baseline survey of the total under 6 year old population was carried out and 446 malnourished children identified (weight for age below 85%). Mothers of these children attended a nutrition rehabilitation centre once a week and received 1 pound dried skimmed milk for their child and an additional pound for the family. Mothers attended nutrition education sessions and were asked about the occurrence of diarrhoea over the last week. Children were re-weighed monthly. The nutritional status of children enrolled in the study improved. A strong association was found between reported prevalence of acute diarrhoeal disease and nutritional status at baseline, but no association was found between nutritional status and respiratory infection. The number of episodes of diarrhoea significantly decreased throughout the supplementation year, particularly among those of less than 60% weight for age.

Comments

As the study did not set out to look specifically at the effect of nutritional status on infection, the data collection was not rigorous and was incomplete. The definition of diarrhoea was loose and there was no check made on whether children actually received the supplement or not. There was no control group employed in the study, so a number of factors, other than improved growth could account for the decrease in diarrhoeal incidence. For example hygiene may have improved as a result of the nutrition education sessions, family entitlement may have improved due to the food supplements, or health facilities may have improved as a result of the attention received from the intervention project.

Martinez C, Chavez A. Does malnutrition increase infections? XI Congresso Internacional de Nutricao Rio de Janeiro, Brazil 1978.

Two groups of 41 children were visited weekly from birth to 5 years of age in Mexico. The control group received the normal diet of the community, while the experimental group received food supplements, so that almost normal growth occurred. Supplemented children had 1.27 episodes of disease compared to 1.46 episodes in controls. Duration and severity of episodes was more severe in controls, with controls spending 64 days sick per year compared to 41 days in the supplemented group.

Comments

Only a brief abstract is available of this study. Details are sparse with no information on sampling, comparability of the two groups, criterion for “normal growth”, or definition of disease.

Feachem RG. Interventions for the control of diarrhoeal diseases among young children: supplementary feeding programmes. Bull WHO 1983;61:967-79.
[REVIEW]

The effect of supplementary feeding programmes on diarrhoeal disease morbidity and mortality among preschool children is reviewed using data from field studies in developing countries. The supplementary feeding programmes considered are those that provide food to preschool children on a continuing and community wide basis. Nutritional rehabilitation of sick children and feeding programmes in disasters and emergencies are not considered. The evidence that poor nutritional status predisposes to increased diarrhoeal disease incidence, or that supplementary feeding programmes can reduce diarrhoeal disease incidence, is not strong. There is evidence that poor nutritional status predisposes to more severe diarrhoea and to higher case fatality, and that supplementary feeding programmes can reduce the severity of the diarrhoea and the mortality. Prospective studies into the effect of nutritional status on the severity of aetiology-specific diarrhoeas and the resulting deaths are warranted.

Feachem RG, Koblinsky MA. Interventions for the control of diarrhoeal diseases among young children: promotion of breast feeding. Bull WHO 1984;62:271-91.
[REVIEW]

The literature on the relative risks of diarrhoea morbidity to infants on different feeding modes suffers from several methodological problems. Thirty five studies from 14 countries were reviewed; 83% of studies found that exclusive breast feeding was protective compared to partial breast feeding, 88% of studies found that exclusive breast feeding was protective compared to no breast feeding. When infants receiving no breast milk are contrasted with infants on exclusive or partial breast feeding, the median relative risks are 3.0 for those aged 0-2 months, 2.4 for those aged 3-5 months, and 1.3-1.5 for those aged 6-11 months. Above 1 year of age no protective effect of breast feeding on diarrhoea morbidity is evident. When infants receiving no breast milk are contrasted with those on exclusive breast feeding, median relative risks are 3.5-4.9 in the first 6 months of life. The literature does not suggest that the relative risks of diarrhoea morbidity for bottle fed infants are higher in poor families than in more wealthy families. The protective effects of breast feeding do not appear to continue after the cessation of breast feeding. There is evidence of considerably increased diarrhoea severity among bottle fed infants.

There is a limited, and mostly pre-1950 literature on the relative risks of diarrhoea mortality to infants on different feeding modes. Nine studies from 5 countries were reviewed, most of which showed that breast feeding protects substantially against death from diarrhoea. When infants receiving no breast milk are contrasted with those on exclusive breast feeding, the median relative risk of death from diarrhoea during the first 6 months of life is 25. When partially and exclusively breast fed infants are contrasted, the median relative risk of death from diarrhoea is 8.6.

The second part of the paper deals with the promotion of breast feeding and the theoretical reductions in diarrhoea morbidity and mortality as a result of increased breast feeding. A recent study in Costa Rica has documented a substantial impact of breast feeding promotion on neonatal diarrhoea and the data from this study show good agreement with theoretical computations.

Tomkins A. Protein energy malnutrition and risk of infection. Proc Nutr Soc 1986;45:289-304.
[REVIEW]

This report focuses on the risk of infection in young children suffering from mild or moderate malnutrition. In the introduction protein energy malnutrition is defined and the significance of different anthropometric measures in the assessment of nutritional status discussed. A simplified model of the outcome of an infectious episode and proposed points at which it may be influenced by nutrition is outlined.

Population based and clinical studies relating malnutrition to the incidence, severity and duration of infection and to mortality are then reviewed and the metabolic mechanisms which affect infection discussed. Finally a model incorporating other factors which co-operate with nutrition in increasing complications from infectious disease, and to mortality is developed. These other factors include aspects of the family which effect outcome such as availability of medical care, feeding and child care practices during illness and the coexistence of other infections which suppress immunity (e.g., measles and malaria). It is concluded that statements about the relation between nutritional status and infection must be made with great caution and take account of the complexity of confounding variables found in the real world.

Thurnham DI. Nutrient deficiencies and malaria: a curse or a blessing? In Proceedings of the XIII International Congress of Nutrition TG Taylor & NK Jenkins Eds pp. 129-31. John Libbey:London 1986.
[REVIEW]

It has been suggested that malnutrition may give man some protection against malaria and refeeding has been associated with recrudescence of latent infections. This paper examines some of the experimental work on the effects of specific nutrient deficiencies on host-parasite relationships and discusses its relevance in man.