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Case management of kwashiorkor: an intervention project at seven nutrition rehabilitation centres in Malawi.

OBJECTIVES: (1) To improve case management of kwashiorkor at seven Nutritional Rehabilitation Centres (NRCs) through 2-4 weekly paediatric supervisory visits. (2) To evaluate the impact of the use of routine tube-feeding and a micronutrient supplement (Nutriset). DESIGN: An intervention project with descriptive clinical data in which Nutriset was introduced halfway through the project, and routine tube-feeding at one NRC was compared to no tube-feeding at a similar one. SETTING: NRCs located at two central hospitals, two district hospitals and three rural clinics in southern Malawi. SUBJECTS: 1625 consecutive kwashiorkor admissions from January-December 1995. RESULTS: The overall case-fatality rate was 24.2% (393/1625), varying by facility level (central 30.5%, district 25.8% and rural 7.5%), reflecting different severity of cases. From ELISA testing and a clinical protocol, we estimate that 21.7% (353/1625) of these kwashiorkor cases were HIV-infected, including 121 breastfed children. Routine tube-feeding was associated with better weight gain (8.24 g/kg/d) than no tube-feeding (4.51 g/kg/d) at central NRCs, but with no reduction in mortality (31.4% vs 30.3%). The introduction of Nutriset was associated with improved weight gain (6.06 vs 4.66 g/kg/d) and a lower mortality (20.8 vs 25.8%), but was confounded by seasonal factors. CONCLUSIONS: From a clinical perspective, HIV infection has transformed kwashiorkor in this part of Africa. Routine tube-feeding was associated with improved body weight gain in the treatment of kwashiorkor. The benefit of paediatric supervision was limited by the infrequency of visits, by constraints of health worker motivation, by a lack of resources and by the severity of disease. Efforts need to focus-not just on case management protocols-but on how to actually improve clinical practice in this setting.

Case Management↗

Dermatosis in a child with kwashiorkor secondary to food aversion.

Kwashiorkor is a common affliction of children worldwide. It occurs less often in developed countries, but has been reported under a variety of circumstances, including poverty, neurologic disease, and malabsorption. Because of its rare occurrence in the United States and because the affected child has an edematous rather than wasted appearance, physicians often do not consider it as a diagnostic entity. This article describes a case of kwashiorkor in a child with food aversion that manifested as "flaky paint dermatitis." Our discussion will attempt to delineate underlying conditions that may predispose to kwashiorkor. In addition, biochemical and cellular etiologic factors that may be linked with classical and nonclassical skin findings of kwashiorkor are considered. Finally, we present a differential diagnosis for any child with a generalized eczematous or desquamative rash. Our aim is to increase the ability of health care providers to identify and treat children with kwashiorkor in a timely manner.

Child, Preschool↗

Of sick turkeys, kwashiorkor, malaria, perinatal mortality, heroin addicts and food poisoning: research on the influence of aflatoxins on child health in the tropics.

Similarities between the geographical and climatic prevalences of kwashiorkor and of exposure to dietary aflatoxins, and between the biochemical, metabolic and immunological derangements in kwashiorkor and those in animals exposed to aflatoxins, prompted investigation of the associations between kwashiorkor and aflatoxins. Studies in Africa in the 1980s indicated a role for these toxins in the pathogenesis of the disease. Paediatric cases of kwashiorkor are less prone to severe Plasmodium falciparum malaria than normal children. In mice infected with P. berghei, aflatoxin exposure inhibits parasite growth and ameliorates morbidity. Aflatoxins occur in < or = 40% of samples of breast milk from tropical Africa, usually as low concentrations of the relatively non-toxic derivatives of aflatoxin B1 (AFB1) but sometimes as high concentrations of the very toxic AFB1. This could explain kwashiorkor in breast-fed babies. Aflatoxin exposure occurs in > or = 30% of pregnancies in tropical Africa and the toxins are often in cord blood, sometimes at extremely high concentrations. Aflatoxins are now incriminated in neonatal jaundice and there is circumstantial evidence that they cause perinatal death and reduced birthweight. Aflatoxin-induced immunosuppresion may explain the aggressive behaviour of HIV infection in Africa. There are similarities between observations on HIV cases in Africa and those on heroin addicts in Europe, where 'street' heroin is frequently contaminated with aflatoxin. Aflatoxins were found in 20% of random urine samples from heroin addicts in the U.K. and the Netherlands. Aflatoxins have also been incriminated in episodes of food poisoning which have been associated with serious morbidity and mortality, particularly among young children.

Adolescent↗

Aflatoxins and kwashiorkor in Kenya: a hospital based study in a rural area of Kenya.

Aflatoxin analyses were undertaken on sera and urines of 41 children admitted to a rural hospital in Kenya with kwashiorkor, marasmus, marasmic kwashiorkor or normal nutrition (Wellcome Classification). Aflatoxins were detected most frequently and at highest concentrations in the sera of kwashiorkors who, conversely, showed aflatoxins least frequently in their urine and in concentrations that were disproportionately low compared with serum/urine aflatoxin levels in other groups. These findings indicate altered aflatoxin metabolism in kwashiorkor and support the hypothesis that there are special relationships between aflatoxins and kwashiorkor.

Aflatoxins↗

Red blood cell antioxidant enzyme concentrations in kwashiorkor and marasmus.

Kwashiorkor may occur when an imbalance between pro- and antioxidants in malnourished children results in an excess of free radicals. The concentrations of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH) and glutathione peroxidase (GPX) were measured in erythrocytes of 22 children with kwashiorkor on admission to hospital and repeated on days 5, 10 and 30 of recovery. The concentrations were compared with those in 22 children with marasmus and in 20 children who were normally nourished but had infective illness necessitating their hospitalization. CAT and SOD were similar in all groups and did not change during recovery. GSH and GPX were significantly lower in kwashiorkor than in the other groups. Concentrations of thiobarbituric acid-reactive substances (TBARS), a marker of lipid peroxidation, were significantly elevated in children with kwashiorkor. During clinical recovery, GSH but not GPX concentrations rose despite an increase in plasma selenium levels and decreased concentrations of TBARS. These findings suggest that the antioxidant status of children with kwashiorkor differs from that of well nourished and marasmic children. Whether these differences are the cause of the consequence of the clinical picture is unresolved.

Case-Control Studies↗

Two unusual cases of kwashiorkor: can protein deficiency explain the mystery?

Two children with unusual features of kwashiorkor are reported. One, an exclusively breastfed 7-month-old girl, had been admitted earlier, treated for pneumonia and discharged 3 weeks before she presented with kwashiorkor. The other was an identical twin who was admitted for kwashiorkor and gastro-enteritis. The twin sister was underweight but relatively well. Both children died. Potent aflatoxins were detected in the organs of these children on post-mortem examination. The occurrence of kwashiorkor in a fully breastfed infant and in an identical twin does not accord with the extant belief that the aetiology of kwashiorkor is wholly nutritional, but suggests a disease probably of multifactorial origin.

Aflatoxins↗

The distribution of kwashiorkor in the southern region of Malawi.

Using existing nutritional survey data collected over an 11-month period during the recent drought, we sought to determine the distribution of kwashiorkor in the ten districts of the Southern Region of Malawi. Sampling and survey methods were identical and considerable efforts were made to ensure comparability. In 23 surveys, 25,824 children were weighed and measured and oedema was recorded. The district-adjusted prevalence of kwashiorkor was 18/1000. The northernmost districts of the Southern Region had rates five to ten times higher than the southernmost districts. Prevalence peaked at 18-23 months and was similar in boys and girls. Dysentery was associated with the presence of kwashiorkor while diarrhoea was not. The distinctive pattern of kwashiorkor in the region suggests that there are characteristics specific to the northern districts that place children in these areas at greater risk of kwashiorkor.

Child, Preschool↗

Serum concentrations of sex hormone binding globulin are elevated in kwashiorkor and anorexia nervosa but not in marasmus.

BACKGROUND: Customary blood protein markers for malnutrition are of limited value in the diagnosis of protein-energy malnutrition or anorexia nervosa in children and in the follow-up to refeeding in such children. OBJECTIVES: For these diseases, we compared the diagnostic value of sex hormone binding globulin (SHBG) with that of albumin, transferrin, transthyretin, and retinal binding protein and determined the relations between concentrations of insulin, insulin-like growth factor I, and SHBG. DESIGN: SHBG was assayed in children with protein-energy malnutrition (29 children with kwashiorkor and 28 with marasmus), in 29 anorectic girls (before and after refeeding), and in age- and sex-matched control subjects. RESULTS: Mean (+/-SE) serum SHBG concentrations were higher in the children with kwashiorkor (0.18 +/- 0.07 micromol/L) than in the children with marasmus (0.11 +/- 0.05 micromol/L, P < 0.0001) or the control subjects (0.11 +/- 0.03 micromol/L, P < 0.0005). In the children with anorexia nervosa before weight gain, serum SHBG concentrations were significantly higher (0.10 +/- 0.04 micromol/L) than in the age-matched control subjects (0.06 +/- 0.03 micromol/L, P < 0.001) and decreased significantly after 30 d of refeeding (0.04 +/- 0.01 micromol/L, P < 0.0001). This decrease was negatively correlated with insulin-like growth factor I but not with insulin. Mean serum SHBG concentrations were influenced neither by inflammation, as indicated when C-reactive protein was used as a marker (0.27 +/- 0.27, 0.34 +/- 0.42, and <0.04 micromol/L in the children with marasmus, kwashiorkor, and anorexia nervosa, respectively), nor by glomerular filtration, as indicated when cystatin-C was used as a marker (68.46 +/- 23.08, 66.90 +/- 43.08, and 49.23 +/- 7.69 micromol/L, respectively). CONCLUSIONS: The high SHBG concentration observed in anorexia nervosa and kwashiorkor seems to be of multifactorial origin. For these 2 diseases, SHBG is a reliable marker of nutritional status, is unrelated to either C-reactive protein or cystatin-C, and may be helpful in distinguishing kwashiorkor from marasmus and as a follow-up marker after refeeding.

Adolescent↗

Plasma urea appearance rate is lower when children with kwashiorkor and infection are fed egg white-tryptophan rather than milk protein.

In kwashiorkor, there is less endogenous proteolysis in response to acute infection than in a well-nourished state. Thus the amino acid composition of dietary protein may be more important in facilitating the acute phase response in kwashiorkor. This study tested the hypothesis that during the treatment of kwashiorkor with infection, there is a lower rate of urea appearance when the dietary intake of amino acids more closely resembles the amino acid composition of acute phase proteins. Thirty children in Malawi with kwashiorkor and acute infection were fed isoenergetic, isonitrogenous meals containing either egg white-tryptophan or milk as a protein source. After 24 h, the rates of urea appearance and whole-body protein breakdown and synthesis were measured with the use of 1-13C-leucine and 15N2-urea tracers. Plasma concentrations of seven acute phase proteins, interleukin 6 and tumor necrosis factor-alpha were measured on admission, and at 24 and 48 h. The 16 children who received egg white-tryptophan had lower rates of urea appearance than those who received milk [57+/-30 vs. 87+/-36 micromol/(kg x h), mean +/- SD, P<0.02]. No significant differences were found in the rates of whole-body protein turnover or in the concentration of any of the acute phase proteins or cytokines. The concentration of interleukin 6 was consistent with an appropriate proinflammatory response and correlated directly with the concentrations of C-reactive protein (r = 0.67, P<0.01) and alpha1-antitrypsin (r = 0.40, P<0.05). The findings suggest that egg white-tryptophan is associated with less amino acid oxidation in kwashiorkor and acute infection than is milk.

Acute-Phase Proteins↗

Potassium supplementation in kwashiorkor.

BACKGROUND: Kwashiorkor is an edimatous form of severe malnutrition and is the predominant form of childhood malnutrition in Malawi. Potassium depletion is common and contributes to the high mortality. The aim of this study was to determine if high potassium supplementation improves the outcome of kwashiorkor treatment. METHODS: We performed a randomised, double-blind, placebo-controlled, clinical trial of high potassium supplementation in 99 children with kwashiorkor. Controls (n = 51) received a standard potassium intake of 4.7 mmol/kg/day. The intervention group (n = 48) received 7.7 mmol/kg/day. All cases (intervention and control groups) were treated in the hospital-based Nutrition Rehabilitation Center and received a standard treatment regime of mild feeds, mineral and vitamin supplements, and antibiotics. RESULTS: There was no significant difference in length of hospitalization, or time for resolution of oedema between groups. The case-fatality rate was reduced by 33% in the high potassium intervention group (13/48) compared to controls (21/51). There was a significant reduction in late deaths (13 in controls vs 3 in intervention group; odds ratio 5.3, 95% confidence interval 1.2-31.0) but no difference in early deaths (0-5 days). The intervention group also had significantly fewer presumed septic episodes (3 vs 18, odds ratio 8.9, confidence interval 2.2-50.9), respiratory symptoms, and new skin ulcerations than controls. CONCLUSIONS: The high potassium supplementation reduced mortality and significant morbidity in kwashiorkor. This may be due to improved myocardial and immune function from earlier repletion of intracellular potassium. We recommend that the standard potassium supplement for the initial phase of treatment of kwashiorkor be increased from 4 to 8 mmol/kg/day.

Administration, Oral↗

A social score for kwashiorkor: explaining the look in the child's eyes.

Following the observation that many children with kwashiorkor had a deprived look in their eyes, the guardians of 107 children with kwashiorkor and 111 controls were interviewed about their home life, in a survey made at New Mulago Hospital, Kampala, between 1969 and 1972. A child's age, sex and tribe were found to have an influence on the nutritional state, therefore 50 of each group were matched for these variables. Ten significant associations were found which distinguished kwashiorkor patients from the control group. Children with kwashiorkor were more likely to be attended by someone other than the mother; to have changed attendants when ill; to have a pregnant mother; and to have separated parents. Further to these, singletons of split partnerships were at special risk; breast-feeding had stopped; weaning was begun for bad reasons; a child was more often living away from the parents and had been sent away coincident with weaning. The fathers tended to be poor. It is suggested that these 10 factors could be used as a social scoring system in assessing the risk of incipient kwashiorkor.

Age Factors↗

Comparison of milk and maize based diets in kwashiorkor.

UNLABELLED: The dual sugar test of intestinal permeability is a reliable non-invasive way of assessing the response of the small intestinal mucosa to nutritional rehabilitation. AIM: To compare a local mix of maize-soya-egg to the standard milk diet in the treatment of kwashiorkor. DESIGN: The diets were alternated three monthly in the sequence milk-maize-milk. There were a total of 533 kwashiorkor admissions of at least five days during the study who received either milk or maize. Intestinal permeability was assessed at weekly intervals by the lactulose-rhamnose test in 100 kwashiorkor cases, including 55 on milk and 45 on the maize diet. RESULTS: Permeability ratios (95% confidence interval) on the milk diet improved by a mean of 6.4 (1.7 to 11.1) compared with -6.8 (-16.8 to 5.0) in the maize group. The improved permeability on milk occurred despite more diarrhoea, which constituted 34.8% of hospital days (29.8 to 39.8) compared with 24.3% (17.8 to 30.8) in the maize group. Case fatality rates for all 533 kwashiorkor admissions were 13.6% v 20.9%, respectively, giving a relative risk of death in the maize group of 1.54 (1.04 to 2.28). The maize group also had more clinical sepsis (60% v 31%) and less weight gain (2.9 v 4.4 g/kg/day) than the milk group. IMPLICATIONS: Milk is superior to a local maize based diet in the treatment of kwashiorkor in terms of mortality, weight gain, clinical sepsis, and improvement in intestinal permeability.

Animals↗

Antioxidant supplementation for the prevention of kwashiorkor in Malawian children: randomised, double blind, placebo controlled trial.

OBJECTIVE: To evaluate the efficacy of antioxidant supplementation in preventing kwashiorkor in a population of Malawian children at high risk of developing kwashiorkor. DESIGN: Prospective, double blind, placebo controlled trial randomised by household. SETTING: 8 villages in rural southern Malawi. PARTICIPANTS: 2372 children in 2156 households aged 1-4 years were enrolled; 2332 completed the trial. INTERVENTION: Daily supplementation with an antioxidant powder containing riboflavin, vitamin E, selenium, and N-acetylcysteine in a dose that provided about three times the recommended dietary allowance of each nutrient or placebo for 20 weeks. MAIN OUTCOME MEASURES: The primary outcome was the incidence of oedema. Secondary outcomes were the rates of change for weight and length and the number of days of infectious symptoms. RESULTS: 62 children developed kwashiorkor (defined by the presence of oedema); 39/1184 (3.3%) were in the antioxidant group and 23/1188 (1.9%) were in the placebo group (relative risk 1.70, 95% confidence interval 0.98 to 2.42). The two groups did not differ in rates of weight or height gain. Children who received antioxidant supplementation did not experience less fever, cough, or diarrhoea. CONCLUSIONS: Antioxidant supplementation at the dose provided did not prevent the onset of kwashiorkor. This finding does not support the hypothesis that depletion of vitamin E, selenium, cysteine, or riboflavin has a role in the development of kwashiorkor.

Acetylcysteine↗

Effects of antioxidants on glutathione levels and clinical recovery from the malnutrition syndrome kwashiorkor--a pilot study.

Kwashiorkor is a severe edematous form of malnutrition with high prevalence and lethality in many African countries, and repeatedly has been reported to be associated with oxidative stress. The therapy of kwashiorkor is still ineffective. In this pilot study, we tested the hypothesis that oral application of thiol-containing antioxidants increases glutathione status and is beneficial for the clinical recovery of kwashiorkor patients. The longitudinal clinical intervention study was carried out at St Joseph's Hospital, Jirapa, Ghana. Children with severe kwashiorkor were randomly assigned to either a standard treatment (ST) receiving a therapeutic protocol based on the recommendations of the WHO or to one of three study groups receiving in addition 2 x 600 mg reduced glutathione or 2 x 50 mg alpha-lipoic acid or 2 x 100 mg N-acetylcysteine per day. Patients were followed up clinically and biochemically for 20 days and compared with 37 healthy controls. Both glutathione and alpha-lipoic acid supplementation had positive effects on survival. Also, the blood glutathione concentrations correlated positively with survival rates. Furthermore, the initial skin lesions, glutathione and total protein concentrations were found to be strong predictors of survival. The data strongly suggest that a therapy restoring the antioxidative capacity by applying cysteine equivalents in the form of glutathione and/or alpha-lipoic acid is beneficial for biochemical and clinical recovery of kwashiorkor patients.

Acetylcysteine↗

Kwashiorkor in the United States: fad diets, perceived and true milk allergy, and nutritional ignorance.

BACKGROUND: Kwashiorkor is the edematous form of protein-energy malnutrition. It is associated with extreme poverty in developing countries and with chronic malabsorptive conditions such as cystic fibrosis in developed countries. Rare cases of kwashiorkor in affluent countries unrelated to chronic illness have been reported. We present 12 cases of kwashiorkor unrelated to chronic illness seen over 9 years by pediatric dermatologists throughout the United States, and discuss common causative themes in this easily preventable condition. OBSERVATIONS: Twelve children were diagnosed as having kwashiorkor in 7 tertiary referral centers throughout the United States. The diagnoses were based on the characteristic rash and the overall clinical presentation. The rash consisted of an erosive, crusting, desquamating dermatitis sometimes with classic "pasted-on" scale-the so-called flaky paint sign. Most cases were due to nutritional ignorance, perceived milk intolerance, or food faddism. Half of the cases were the result of a deliberate deviation to a protein-deficient diet because of a perceived intolerance of formula or milk. Financial and social stresses were a factor in only 2 cases, and in both cases social chaos was more of a factor than an absolute lack of financial resources. Misleading dietary histories and the presence of edema masking growth failure obscured the clinical picture in some cases. CONCLUSIONS: Physicians should consider the diagnosis of kwashiorkor in children with perceived milk allergies resulting in frequent dietary manipulations, in children following fad or unorthodox diets, or in children living in homes with significant social chaos. The presence of edema and "flaky paint" dermatitis should prompt a careful dietary investigation.

Diet Fads↗

Secretory IgA synthesis in Kwashiorkor.

The synthesis of intestinal secretory IgA was studied in in vitro cultures of duodenal mucosal biopsies from children with Kwashiorkor. Production of secretory IgA was measured by the incorporation of radioactive label and visualized following PAGE and autoradiography. Results obtained before and after nutritional rehabilitation demonstrate an enhanced synthesis of sIgA in children with acute Kwashiorkor. Histological examination of plasma cells in the biopsy tissue confirms a twofold increase in IgA staining plasma cells in acute Kwashiorkor. Peripheral blood B lymphocytes in acute Kwashiorkor however, showed a reduction in IgA synthesis in the acute stage. These results suggest an effective mucosal sIgA response to the increased intestinal antigen load in Kwashiorkor.

Cells, Cultured↗

[Vitamin e supplementation in Senegalese children with kwashiorkor].

Kwashiorkor continues to be a major cause of infant mortality in the developing world. It has recently been suggesting that this form of malnutrition is due to oxidizing aggression. Vitamin E is a powerful natural anti-oxidant, and we therefore investigated the extent to which its supplementation in the diet contributed to treating child kwashiorkor. Vitamin E was also administered to children suffering from marasmus. The study was conducted from October 1993 to July 1994 and included 79 children (38 cases of kwashiorkor and 41 of marasmus). The treatment resulted in a 76% success rate, with the best results for marasmus (89.5% cure). However, the supplement did not have any effect on the nutritional status for either the kwashiorkor or marasmus patients. In the kwashiorkor group, the weight increase, after disappearance of edema was 15.2 +/- 4.9 g/kg/d in the supplemented group as compared to 16.4 +/- 3.6 g/kg/d in the control group. The duration of edema along treatment was similar for the two groups (supplemented: 8.6 +/- 3.1 days, control group: 7.1 +/- 3.9 days). Possible reasons for vitamin E supplementation having no effect are discussed.

Antioxidants↗

The binding of antituberculous drugs to normal and kwashiorkor serum.

The protein binding of 6 antituberculous drugs--ethambutol, ethionamide, isoniazid, para-aminosalicylic acid, rifampicin and streptomycin--to normal and kwashiorkor serum has been investigated. The binding of these drugs was mildly decreased in kwashiorkor serum, but not to such an extent as to be of therapeutic importance, except for streptomycin and possibly para-aminosalicylic acid (PAS). With streptomycin there was a 15% increase in the free component in kwashiorkor serum, while with PAS there was a 12% increase in the free component. Of interest is the observation that rifampicin is predominantly bound to the gamma-globulin fraction, both in normal and in kwashiorkor serum. Secondary binding, predominantly to the alpha 1-, alpha 2-and gamma-globulin fractions, was seen quite commonly in kwashiorkor serum in association with diminished albumin binding.

Aminosalicylic Acid↗