Severe Protein-calorie Malnutrition Research Articles

Xerophthalmia, protein-calorie malnutrition, and infections in children

All children with evidence of xerophthalmia who were admitted to an inpatient facility for treatment of severe protein-calorie malnutrition and its complications were compared to other inpatients with severe PCM but free from signs or symptoms of vitamin A deficiency. Xerophthalmic inpatients were older and had more severe hypoproteinemia than inpatients without eye signs, and were more undernourished by anthropometric criteria than a comparison group matched for age, sex, and type of PCM. Children with more severe eye lesions were more retarded in growth than those with minimal ocular signs. All inpatients had high rates of bacterial infections, regardless of their vitamin status. However, xerophthalmic children had a highly significant increase in the rate of positive urine cultures. Mortality rates were similar in all study groups.

The pattern of severe protein-calorie malnutrition in Sudanese children attending a large hospital in The Sudan

One hundred fifty patients suffering from severe protein-calorie malnutrition, admitted in 1 month to the Pediatric wards of Wad Medani Hospital, Sudan, were classified according to the Wellcome classification. Marasmus was the prevailing type. It was common in the 2nd year of life, while kwashiorkor occurred mainly under the age of 12 months. Anthropometric measurements showed that kwashiorkor was an acute disease while marasmus and marasmic kwashiorkor were more chronic. The triceps skinfold was unexpectedly low in kwashiorkor. Of the simple measurements and ratios used for assessing the nutritional status, the head/chest ratio applied to children over 1 year was not found to be reliable and the weight for head circumference correlated poorly with deficits in other variables. None of the major clinical features was found to be pathognomonic of any type of severe protein-calorie malnutrition. Megaloblastic anemia was common.

Biochemical evidence of thiamin deficiency in young Ghanaian children

Detailed biochemical studies for nutritional status were carried out on 146 Ghanaian children ages 6 months to 6 years over a 2-year period. Study children comprised three main groups: severe protein-calorie malnutrition; mild to moderate protein-calorie malnutrition and apparently healthy children. Erythrocyte transketolase activity and the percentage of erythrocyte transketolase pyrophosphate effect were also determined. In the first year of the study elevated percentage of transketolase pyrophosphate effect indicative of thiamin deficiency was found in all three of the above-mentioned groups, with the most widespread deficiency in the normal groups. In year 2, repeat studies of the severely malnourished group after 2 weeks of nutritional therapy with the administration of vitamin capsules, which included thiamin, resulted in the normalization of transketolase pyrophosphate effect. Apoenzymc activity was comparable in all groups studied. There were no obvious clinical signs of thiamin deficiency, although sensory testing was not performed. A relatively large number of children with high percentage of transketolase pyrophosphate effect also had serum folic acid deficiency. This evidence of widespread biochemical thiamin deficiency is indicative of an at-risk population among young children for clinical thiamin deficiency. Further studies are needed to identify whether the problem is inadequate thiamin intake, destruction of thiamin by thiaminases or food preparation methods, or malabsorption of thiamin.

688 CELL MEDIATED IMMUNE DEFECTS IN MALNOURISHED HOSPITALIZED U.S. CHILDREN

Severe protein calorie malnutrition is characterized by profound depression of cell mediated immunity. We studied 28 hospitalized U.S. children with various degrees of malnutrition to determine if similar defects existed. Ages ranged from 6 wks to 20 yrs. All had weights less than the fifth percentile for age. Chief diagnoses were chronic diarrhea(7), gastroesophageal reflux (4), Crohn's disease(4), and anorexia nervosa(3). Thirteen/28 eventually required hyperalimentation. 10/28 (36%) had marked depression (<50%) of T lymphocytes(E-Rosette Forming Cells - E-RFC). 5/10 had depressed PHA transformation (Index <40). 8/10 were <2 years. 3 pts had albumin <3gm/dl, 5 had hgb <10gm%. One 2 month old boy had decreased lymphoid tissue, decreased granulocytes and severe infection. 5/28 (18%) had mild decrease of E-RFC(50-60%). PHA index was low in 3 of these pts. 2 had hgb <10gm%, and 1 had alb <3gm/dl. No severe infections were seen. 13/18 (46%) had initially normal E-RFCs. All these had normal albumins; 3 had low hgb. E-RFC decreased to <50% in 3 pts, including one who had candida sepsis. We conclude that depressed T cell function occurs in malnourished U.S. children, may precede clinical infection, and is associated with young age, chronic diarrhea, and wts less than the fifth percentile. Hyperalimentation may be of value in correcting this defect.

Malnutrition and Child Feeding Practices in Western Samoa

Mild protein-calorie malnutrition is common in Western Samoa. Severe protein-calorie malnutrition is also an important cause of death in infants and toddlers, and anemia is frequently found in small children. This paper investigates child feeding practices because of its possible relationship with the occurrence of severe early malnutrition. Data on infant and toddler feeding practices were collected from 90 mothers from the town of Apia and 38 mothers from the island is Savai'i. Average age of mothers in Apia was 29.0 years and in Savai'i, 30 years. Most belonged to the low income group. Average interval between births in Apia was 22.3 months, in Savai'i, 25.7 months. The proportion of bottlefed children was much lower in Savai'i than in urban Apia, 28.2 vs. 57.9%. 31.3% of Apian mothers weaned their last child abruptly compared with 41.6% of Savai'i mothers. In Apia, weaning foods consisted of milk, meat, and other protein-rich foods; in Savai'i, taro, orange leaf tea, rice, and other were the main weaning foods. Generally, semisolids were not introduced before the child was more than 6 months of age. Some mothers in Savai'i appeared to give their children monotonous diet. A number of cultural taboos appear to affect the children's diet as well as that of pregnant and lactating mothers. Many women believed in them and would not eat or do certain things. Overall, it appears that many of the mothers are ignorant about the nutritional needs of their children. Almost 7% of the 0-5 year old children suffered from borderline malnutrition. 9% of the total number of admissions during the period October 1968 to April 1972 were malnourished children. The increase in borderline malnutrition and severe malnutrition among the children towards the end of the 1st year is attributed mainly to the late introduction of semisolid and solid foods. Other causes of malnutrition include lack of money, especially in urban areas, large families, changes in the diet because of higher consumption of imported foods (soft drinks, refined foods), decline in breastfeeding, and increase in early bottlefeeding.

Chromosomal abnormalities in protein-calorie malnutrition

Cytogenetic studies were carried out in five children suffering from moderate to severe protein calorie malnutrition and five healthy controls, using direct preparations of bone marrow using conventional techniques. In the control group there were two abnormalities out of 152 plates analyzed, and in the malnutrition group there were 16 out of 186. This difference is statistically significant, P less than 0.005, implying that chromosomal abnormalities are more frequent in protein calorie malnutrition.

Energy Metabolism of Brain in Human Protein-Calorie Malnutrition

Cerebral blood flow (CBF) and carbohydrate metabolism were studied in 5 normal children and 25 children, aged 40 months or less, with varying degrees of protein-calorie malnutrition (PCM). CBF in normal children and those suffering from grade I PCM was 90.3 +/- 5.7 ml/100 g/min, a value comparable with that obtained by other investigators, but the proportion of glucose taken up by the brain which combined with oxygen, the oxygen/glucose index (OGI), was 65.8%, indicating significant conversion of glucose into lactic acid. Cerebral lactic acid production was 45.3 micronM/100 g/min, and the respiratory quotient (R.Q.) was 1.00. With increasing severity of PCM, there was increased glucose utilization and a progressive reduction in the OGI. In grade IV PCM, CBF was 68.7 +/- 5.4ml/100g/min, and the OGI was 34.7%. Cerebral lactic acid production was 27.4 micronM/100 g/min, and the R.Q. rose to 1.52. These findings suggest that in severe human PCM the proportion of glucose undergoing aerobic oxidation is reduced, and that in addition to being converted to lactic acid, a significant proportion of glucose is transformed by the brain into long chain fatty acids.

Hemodynamic findings in severe protein-calorie malnutrition

This study was undertaken because circulatory distrubances had been advanced as a possible cause of death during initial renourishing of protein-calorie deprived children. Body weight, plasma albumin concentration, intravascular volumes (radiochromium), cardiac index (dye dilution technique), intravascular pressures (flow-guided catheterization), and related hemodynamic parameters were determined at rest in 43 infection-free African children with a form of protein-calorie malnutrition known as marasmic kwashiokor, and were compared with values observed in 24 convalescent children. The malnourished children showed a prolonged circulation time with a tendency to bradycardia and hypotension; cardiac index, stroke index, and heart work were significantly reduced, as were the intravascular volumes. Hemodynamic data correlated with either body weight or plasma albumin and cardiac index bore a direct relation to red cell volume. In the most severely malnourished subjects, ventricle filling pressures were low and vascular resistances were high. It is inferred that most patients were in an adaptive hypocirculatory state comparable to hypothroidism, while the most severely malnourished children showed frank peripheral circulatory failure comparable to hypovolemic shock. Circulatory failure on admission was associated with high death rate during treatment but the relation between cause and effect could not be clearly demonstrated.

Secretory IgA in protein-calorie malnutrition.

The secretory IgA system was investigated in children with protein-calorie malnutrition (PCM). The results of the study indicated that in children suffering from kwashiorkor and marasmus the concentration of IgA in duodenal fluid, saliva, nasal secretions, and tears was significantly reduced on admission and returned to normal 4 weeks after treatment. However, the concentration of secretory IgA in children with mild to moderate PCM was similar to that of normal children. Secretory IgA deficiency may be an important factor in promoting bacterial growth and this may account for the increased incidence and severity of mucosal infections in children with severe PCM.

Complement activity in children with protein-calorie malnutrition

Using the hemolytic complement (CH50) assay, we evaluated the complement system of 28 children with severe protein calorie malnutrition (PCM) during their hospital admission and recovery. The mean CH50 activity in children with kwashiorkor was significantly less on hospital days 1 and 4 than in 17 healthy control subjects. On day 8 it rose to normal, and by day 50 it was significantly higher than the controls. The mean CH50 titer of 16 well-nourished febrile children was, in contrast to that of untreated PCM, significantly greater than the healthy controls. Of the children with PCM, 11 (40%) evidenced anticomplementary (AC) activity in their serum on either day or 1 or 4, but only two (7%) had detectable serum AC activity during later convalescence. Significantly, the CH50 titer in a PCM serum correlated inversely to the amount of AC activity in that serum (P less than 0.01). These results indicate that, in children with PCM, the complement system is compromised functionally, and that its repair coincides with intake of adequate diet. The presence of AC activity provides a possible mechanism for depressed complement activity in some untreated PCM children.

Hydrogen peroxide production by leukocytes in protein-calorie malnutrition

Hydrogen peroxide (H 2O 2) production during phagocytosis was studied in polymorphonuclear leukocytes obtained from children suffering from severe protein-calorie malnutrition. Formation of H 2O 2 was significantly reduced both in the resting condition and during phagocytosis. Improvement in this function of leukocytes was observed following nutritional rehabilitation. Sub-optimal H 2O 2 production during phagocytosis may be one of the reasons for impaired bactericidal activity of leukocytes seen in children with protein-calorie malnutrition.

An evaluation of the use of changes in hair root morphology in the assessment of protein-calorie malnutrition

A study was carried out to evaluate the use of changes in hair root morphology in the assessment of protein-calorie malnutrition (PCM) among a group of black West Indian children. The following five hair root characteristics were measured: percentage of anagen (the growing phase), percentage of telogen (the resting phase), percentage of atrophy, diameter of anagen bulbs, and shaft diameter. Significant differences in shaft diameter, percentage of anagen, and percentage of telogen were found only between well-nourished and severely malnourished children. Significant correlation coefficients were obtained between both bulb diameter and percentage of atrophy and muscle circumference. No significant differences in any of the hair root characteristics were obtained between children with nutritional marasmus and those with kwashiorkor. The method was found to be time-consuming; it can be used for differentiating well-nourished children only from those with severe PCM; and it is unsuitable for determining the prevalence of the three degrees of PCM. For these reasons, the method is not recommended for use in the field assessment of protein-calorie malnutrition.

Functional significance of growth retardation in malnutrition

Various functional parameters involved in resistance to infection were investigated in children suffering from varying grades of protein-calorie malnutrition. It was observed that the phagocytic function was impaired in children whose weights were below 80% of the Indian Council of Medical Research standard, whereas the cell-mediated immune response was altered in those with weights below 70% of the standard. Antibody response to typhoid antigen was impaired in children with severe protein-calorie malnutrition, while the response to diphtheria and tetanus toxoids was normal in all. These observations suggest that malnourished children whose weights are below 80% of the Indian standard are likely to suffer from at least one functional handicap which may increase the risk of infection. In any action-oriented program, priority should, therefore, be given to this group of children.

Microenvironmental factors in severe protein-calorie malnutrition.

Protein-calorie malnutrition (PCM) is a disease complex occurring primarily among the poor in preindustrial societies where the social system, consciously or unconsciously, creates malnourished children, generation after generation, through a series of social misfortunes, among which are limited access to goods and services, limited social mobility, and restricted opportunities for social stimuli at crucial points in life (1).

Insulin secretion and glucose tolerance in adults with protein-calorie malnutrition

Glucose tolerance, insulin secretion, and responses to arginine infusion were studied in 17 adults with severe protein-calorie malnutrition (PCM) in Calcutta, India. Patients were selected for the severity of their malnutrition and for absence of other diseases. After 2–4 mo of refeeding there was complete clinical recovery, and control studies were performed. Glucose tolerance, as assessed by intravenous glucose-tolerance test (IVGTT), was reduced in PCM. Insulin response, both to glucose and to arginine infusion, was clearly reduced. The K value of the IVGTT correlated well with the ratio of mean to basal serum insulin during the first 40 min of the test. Basal serum insulin was nearly unchanged in PCM as compared with after recovery, although one patient studied serially showed a temporary drop in basal insulin during the first week of refeeding. In PCM, plasma amino acid levels failed to fall in response to arginine-induced insulin secretion as they did in the control studies. It appears that insulin secretory response is severely reduced in PCM and that a degree of insulin resistance in relation to body weight is present. These changes result in diminished glucose tolerance and probably in a reduced rate of tissue utilization of amino acids. Such alterations may be of adaptive significance in chronic PCM.

The pituitary-gonadal axis in men with protein-calorie malnutrition.

The pituitary-gonadal axis was studied in 28 men with severe protein-calorie malnutrition in a Calcutta hospital. The men were selected for the severity of their malnutrition and for absence of other diseases. They had clinical findings of hypogonadism and low total and unbound plasma testosterone. During 2-5 months of refeeding there was clinical recovery and increase of plasma testosterone to normal. Plasma LH was high in malnutrition, decreased during refeeding, and remained above normal after refeeding. Some patients failed to show LH elevation in malnutrition despite low plasma tesosterone. Plasma FSH was high in malnutrition, decreased during refeeding, and was near the level of normal Indian men after refeeding. HCG 4000 IU im per day for 3 days produced subnormal increments in plasma testosterone both in malnutrition and after refeeding; corresponding decreases in FSH occurred. It is concluded that the hypogonadism of protein-calorie malnutrition is primarily on the basis of diminished Leydig cell function. Appropriate pituitary LH response is intact in some patients, but is either absent or inadequate in others. Subclinical Leydig cell insufficiency, indicated by LH elevation and subnormal response to HCG, persists after refeeding has produced recovery from malnutrition and clinical hypogonadism. FSH elevation in malnutrition may be secondary to the reduced Leydig cell function.

Circulating thyroid hormones and thyrotropin in adult patients with protein-calorie malnutrition.

We studied plasma concentrations of thyroxine (T4), triiodothyronine (T3), free T4, free T3, thyrotropin (TSH), albumin and thyroxine-binding globulin (TBG) before and following 56 to 145 days (mean, 85) of refeeding in ten Indian patients who had severe protein-calorie malnutrition (PCM). The mean baseline plasma T4 concentration of 8.2 mug per 100 ml in these patients was comparable to the corresponding post-treatment value of 7.7 mug per 100 ml. However, since the dialyzable fraction of T4 (DFT4) was considerably higher (0.048 vs 0.029%), the mean baseline plasma free T4 concentration, 3.8 ng per 100 ml, was significantly greater than the mean post-treatment value of 2.2 ng per 100 ml. The mean baseline plasma concentration of T3, 21 ng per 100 ml, was markedly lower than the corresponding value of 96 ng per 100 ml after treatment. The mean plasma concentration of free T3, 94 pg per 100 ml, was also significantly lower than the post-treatment value of 303 pg per 100 ml. This was the case even when the mean DFT3 prior to treatment was significantly higher than that following treatment (0.46 vs 0.32%). The mean baseline ratio of plasma concentrations of total T3 and T4 (T3/T4 X 100) of 0.25 was significantly lower than the corresponding normal value of 1.3 after treatment. The mean plasma TSH concentration of 6.0 muU per ml in patients prior to treatment was comparable to the mean value of 5.5 muU per ml following treatment. The mean baseline plasma concentration of TBG of 3.3 mg per 100 ml was also comparable to the mean post-treatment value of 3.6 mg per 100 ml. The data on thyroid hormone levels in PCM can be explained if there were i) a selective increase in metabolic clearance rate of T3 without a change or a decrease in that of T4 and ii) a reversible defect in extrathyroidal conversion of T4 to T3. The latter possibility appears more likely.

Emergency treatment of large numbers of children with severe protein-calorie malnutrition

Dried skimmed milk is the accepted food for the initial treatment of severe protein-calorie malnutrition. Major drawbacks of dried skimmed milk include tendency to provoke or aggravate severe diarrhea (presumably due to lactose intolerance) and its low caloric content predisposing to hypoglycemia and slow rate of weight gain. Kwashiorkor food mix, prepared from dried skimmed milk, calcium casinate, sucrose and reinforced with vegetable oil, was designed to overcome these handicaps with the dried skimmed milk. It was used in treating thousands of children with severe protein-calorie malnutrition during the Nigeria-Biafra War. The results of treatment show that compared with dried skimmed milk, kwashior food mix lowered the rate of severe diarrhea, hypoglycemia and case-fatality; and the patients thus treated showed a faster gain in weight. Furthermore, its combination with postkwashiorkor food mix at a later stage of treatment maintained the initial improvement.

Protein Status of General Surgical Patients

In a survey of the protein nutritional status of all patients on the surgical wards of an urban municipal hospital, accepted standards indicated moderate to severe protein-calorie malnutrition (PCM) in one half of these patients as judged by triceps skin fold and arm muscle circumference measurements. Weight for height was less severely affected. Although serum albumin levels were recorded in only 43% during the perisurvey periods, the correlation between arm muscle circumference and serum albumin level was highly significant, suggesting that this measurement would substantiate a rate of approximately 50% malnutrition. (<i>JAMA</i>230:858-860, 1974)

Decreased rosette-forming lymphocytes in malnutrition and intrauterine growth retardation

The percentage of peripheral blood lymphocytes which spontaneously form rosettes with sheep red blood cells (thymus-dependent lymphocytes) was studied as a sensitive measure of cellular immunity in patients with two forms of malnutrition. The percentage and absolute number of rosette-forming cells was markedly decreased in 10 children with severe protein-calorie malnutrition (16.6%±2.7 SE) p<0.001, compared to normal children (59.7%±1.4 SE) and Caucasian adults (64.5%±1.0 SE). Delayed cutaneous hypersensitivity was also diminished, but total lymphocyte counts and in vitro lymphocyte response to phytohemaglutinin were normal. Therapy with a high-protein, high-calorie diet resulted in recovery of delayed cutaneous hypersensitivity and return to normal numbers of rosette-forming cells within 1 to 3 weeks. The percentage of rosette-forming cells was moderately reduced (49.2%±2.0 SE) p<0.001, in 10 newborn infants who were small for gestational age, mean birth weight 1,660 gm, compared to those whose weights were appropriate for gestation (65.1%±1.4 SE), mean birth weight 2,005 gm, an observation in keeping with prior studies of diminished spleen and thymus size in such infants. The interrelation of cellular immunity and malnutrition is emphasized, since this may be of great importance in the host response to infection and immunization, and in persisting defects of cellular immunity in the developing newborn infant.