Nutritional Treatment of a Young Infant with Cystic Fibrosis Presenting with Severe Kwashiorkor Dermatosis.

Kwashiorkor in infancy is typically associated to an underlying disease. Edema, a striking feature of this type of malnutrition, can be difficult to assess in this age group. The typical dermatosis of Kwashiorkor is not fully explained the deficiency of one isolated vitamin or micronutrient. This article presents an infant with cystic fibrosis, who developed Kwashiorkor in the third month of life with extensive cutaneous manifestations. An early, individualized and aggressive nutritional intervention with optimized supplementationof sulfur amino acids, vitamins and micronutrients was established, with impressively recovery of overall nutrition and skin manifestations in a relatively short period of time.

Management of severe acute malnutrition by cow milk in resource constraints settings: experience of the Nutritional Centre of the University Clinics of Graben.

BACKGROUND: Severe acute malnutrition is defined as a weight for height z-score < - 3 standard deviation. Since 2000, joint efforts of the World Health Organization and United Nations Children's Fund allowed to standardize the management of acute malnutrition by improving outcome and preventing complications with the introduction of therapeutic milk and ready-to-use therapeutic foods. However, in the Democratic Republic of Congo, many health facilities face therapeutic milk shortage while managing severe acute malnutrition. At the University Clinics of Graben, cow milk with porridge made of maize, soybean, vegetal oil and sugar is used during stockouts periods. This study was carried out to analyse the efficiency and safety of this treatment compared to the conventional one in SAM patients. METHODS: This study is based on the experience of the University Clinics of Graben in eastern Democratic Republic of Congo whose nutritional centre is often confronted with stockouts in nutritional supplements. During a three months shortage in 2015, patients received cow milk alternating with preparations made from sugar-maize-soybean- vegetal oil. The study compared the evolution of these children with those who had previously been treated with the WHO conventional preparations by analysing weight changes, oedema resolution, gastrointestinal tolerability and clinical outcome over 21 days. Data were analysed with SPSS 20. We used the ANOVA, Chi-square test, odd ratio and p-value to compare the differences. RESULTS: Seventy-nine patients had received cow milk while fifty-seven were submitted to classical therapeutic milk. There was no significant difference between the two groups regardless the type of malnutrition in terms of weight changes, oedema resolution, gastrointestinal tolerability and clinical outcome over 21 days. CONCLUSION: Cow milk alternately with sugar-maize-soybean- vegetal oil preparations is an acceptable alternative in case of stockouts in conventional therapeutic milk in these settings.

The Rise and Fall of Protein Malnutrition in Global Health.

BACKGROUND: From the 1950s to the mid-1970s, United Nations (UN) agencies were focused on protein malnutrition as the major worldwide nutritional problem. The goal of this review is to examine this era of protein malnutrition, the reasons for its demise, and the aftermath. SUMMARY: The UN Protein Advisory Group was established in 1955. International conferences were largely concerned about protein malnutrition in children. By the early 1970s, UN agencies were ringing the alarm about a 'protein gap'. In The Lancet in 1974, Donald McLaren branded these efforts as 'The Great Protein Fiasco', declaring that the 'protein gap' was a fallacy. The following year, John Waterlow, the scientist who led most of the efforts on protein malnutrition, admitted that a 'protein gap' did not exist and that young children in developing countries only needed sufficient energy intake. The emphasis on protein malnutrition waned. It is recently apparent that quality protein and essential amino acids are missing in the diet and may have adverse consequences for child growth and the reduction of child stunting. Key Messages: It may be time to re-include protein and return protein malnutrition in the global health agenda using a balanced approach that includes all protective nutrients.

Dietary supplementation with aromatic amino acids increases protein synthesis in children with severe acute malnutrition.

Although 2 earlier studies reported that aromatic amino acid (AAA) supplementation of children with severe acute malnutrition (SAM) improved whole-body protein anabolism during the early postadmission (maintenance) phase of rehabilitation, it is not known whether this positive effect was maintained during the catch-up growth and recovery phases of treatment. This study aimed to determine whether supplementation with an AAA cocktail (330 mg · kg(-1) · d(-1)) vs. isonitrogenous Ala would improve measures of protein kinetics in 22 children, aged 4-31 mo, during the catch-up growth and recovery phases of treatment for SAM. Protein kinetics were assessed by measuring leucine, phenylalanine, and urea kinetics with the use of standard stable isotope tracer methods in the fed state. Supplementation started at the end of the maintenance period when the children were clinically/metabolically stable and continued up to full nutritional recovery. Three experiments were performed: at the end of maintenance (at ∼13 d postadmission), at mid-catch-up growth (at ∼23 d post- admission when the children had replenished 50% of their weight deficit), and at recovery (at ∼48 d postadmission when they had achieved at least 90% weight for length). Children in the AAA group had significantly faster protein synthesis compared with those in the Ala group at mid-catch-up growth (101 ± 10 vs. 72 ± 7 µmol phenylalanine · kg(-1) · h(-1); P < 0.05) and better protein balance at mid-catch-up growth (49 ± 5 vs. 30 ± 2 µmol phenylalanine · kg(-1) · h(-1); P < 0.05) and at recovery (37 ± 8 vs. 11 ± 3 µmol phenylalanine · kg(-1) · h(-1); P < 0.05). We conclude that dietary supplementation with AAA accelerates net protein synthesis in children during nutritional rehabilitation for SAM.

Dermatosis in children with oedematous malnutrition (Kwashiorkor): a review of the literature.

Children with oedematous malnutrition, known as kwashiorkor, may develop a characteristic skin lesion, named 'Dermatosis of Kwashiorkor' (DoK). Only a few studies have been concerned with this condition, and the reason for the development of DoK remains unexplained. This study review the existing studies concerning DoK, including its clinical manifestations, histopathology, suggested pathophysiology, current treatment and prognosis for children of the age of 6 months to 5 years. Standardized clinical studies are needed to further understand the implications of DoK. Such studies would suffer from the lack of consistency concerning the terminology and scoring of the lesions in DoK. We therefore stress the need for a standardized scoring of the degree of DoK. This would facilitate valid and comparable studies and the development of better treatment for this vulnerable group of patients.

Acute inpatient presentation of kwashiorkor: not just a diagnosis of the developing world.

We present the case of an infant with presumed Stevens-Johnson syndrome. Through a history, physical, and histopathology, we were able to diagnose the patient with kwashiorkor. Physicians should be aware of this disorder, which is commonly thought of as a developing world problem, because it is increasing in incidence in industrialized nations because of changing dietary habits.

INCAP studies of kwashiorkor and marasmus.

This article summarizes thirty years of intensive clinical metabolic and therapeutic studies of the consequences of severe protein deficiency relative to calories, which results in kwashiorkor, and of a balanced deficiency of protein and calories that results in marasmus. Evidence is provided that these are two different metabolic diseases, but kwashiorkor is usually superimposed on some degree of chronic marasmus and hence most cases studied were marasmic kwashiorkor. The value of the creatinine/height index to indicate the degree of lean body cell mass with any disease is demonstrated.

Hypo-phosphataemia in children under five years with kwashiorkor and marasmic kwashiorkor.

BACKGROUND: Severe malnutrition contributes up to 50% of childhood mortality in developing countries is frequently characterised by electrolyte depletion, including low total body phosphate. During therapeutic re-feeding, electrolyte shift from extracellular to intra-cellular compartments may induce hypo-phosphataemia (hypo-P) with resultant increased morbidity and mortality. This biochemical imbalance is under-recognised, and the frequency of this problem among African malnourished children is unclear. OBJECTIVES: To determine the magnitude of hypo-phosphataemia in children under five years of age presenting to Kenyatta National Hospital with kwashiorkor and marasmic kwashiorkor and to evaluate the relationship between hypo-phosphataemia and nutritional intervention during the first five days of treatment. DESIGN: Short longitudinal survey. SETTING: The General Paediatric wards of the Kenyatta National Hospital (KNH), Nairobi. SUBJECTS: Children under five years of age presenting with kwashiorkor or marasmic kwashiorkor at KNH were recruited into the study. MAIN OUTCOME MEASURES: Low serum phosphate level (< 1.20 mmol/l) and patient outcome (survival or death) during the first five days of treatment. RESULTS: One hundred and sixty five children were enrolled between June 2005 and February 2006 of which 107 (64%) had kwashiorkor and 58 (36%) had marasmic kwashiorkor. They were of mean age 20 months (range 3-60), and 95 (58%) were male. The prevalence of hypo-phosphataemia was 86% on admission, increased to 90% and 93% on day one and two respectively, and then declined to 90% by the fourth day. At admission 6% were hypo-phosphataemic, increasing to 18% and 22% on day one and two respectively, and declining to 11% by day four. On admission mean serum phosphate was below normal at 0.91 mmol/l, declined significantly to 0.67 mmol/l and to a nadir of 0.63 mmol/l after the first and second day of treatment respectively, then rose slightly to 0.75 mmol/l on the fourth day (p < 0.001 comparing each follow-up mean level with the admission level). There was a positive association between severity of nadir serum phosphate level and mortality (p = 0.028). There were no deaths among children with normal nadir serum phosphate levels. However, among children with mild, moderate and severe nadir hypo-phosphataemia, 8,14 and 21% died respectively. Children with dermatosis and hypomagnesaemia showed a trend for association with mortality (p = 0.082 and 0.099 respectively). CONCLUSION: Hypo-phosphataemia is frequent among children with kwashiorkor and marasmic kwashiorkor presenting at KNH. Serum phosphate levels decline significantly during the first two days of nutritional intervention, and severity of

Switching to normal diet reverses kwashiorkor-induced salivary impairments via increased nitric oxide level and expression of aquaporin 5 in the submandibular glands of male Wistar rats.

Kwashiorkor, a form of malnutrition, has been shown to cause impaired salivary secretion. However, there is dearth of information on the mechanism that underlies this complication. Also, whether returning to normal diet after kwashiorkor will reverse these complications or not is yet to be discerned. Thus, this study aimed at assessing the mechanisms that underlie kwashiorkor-induced salivary impairments and to evaluate the effects of switching back to normal-diet on kwashiorkor-induced salivary impairments. Weaning rats were randomly divided into 3 groups (control group, kwashiorkor group (KG), re-fed kwashiorkor group (RKG)) of 7 rats each. The control group had standard rat chow while the KG and RKG were fed 2% protein diet for 6 weeks to induce kwashiorkor. The RKG had their diet changed to standard rat-chow for another 6 weeks. Blood and stimulated saliva samples were collected for the analysis of total protein, electrolytes, amylase, immunoglobulin A (IgA) secretion rate, leptin, and ghrelin. Tissue total protein, nitric oxide level, expressions of Na+/K+-ATPase, muscarinic (M3) receptor, and aquaporin 5 in the submandibular glands were also determined. Data were presented as means ± SEM and compared using ANOVA with Tukey's post hoc test. RKG showed improved salivary function evidenced by reduced salivary lag-time and potassium and increased flow rate, sodium, amylase, IgA secretion rate, leptin, submandibular nitric oxide level, and aquaporin 5 expression compared with KG. This study for the first time demonstrated that kwashiorkor caused significant reduction in salivary secretion through reduction of nitric oxide level and aquaporin 5 expression in submandibular salivary glands. Normal-diet re-feeding after kwashiorkor returned salivary secretion to normal.

Improving the management of severe acute malnutrition in an area of high HIV prevalence.

AIM: To assess the clinical outcomes of a combined approach to the treatment of severe acute malnutrition in an area of high HIV prevalence using: (i) an initial inpatient phase, based on WHO guidelines and (ii) an outpatient recovery phase using ready-to-use therapeutic food. METHODS: An operational prospective cohort study implemented in a referral hospital in Southern Malawi between May 2003 and 2004. Patient outcomes were compared with international standards and with audits carried out during the year preceding the study. RESULTS: Inpatient mortality was 18% compared to 29% the previous year. Programme recovery rate was 58.1% compared to 45% the previous year. The overall programme mortality rate was 25.7%. Of the total known HIV seropositive children, 49.5% died. CONCLUSIONS: Inpatient mortality and cure rates improved compared to pre-study data but the overall mortality rate did not meet international standards. Additional interventions will be needed if these standards are to be achieved.

Choline Supplementation Prevents a Hallmark Disturbance of Kwashiorkor in Weanling Mice Fed a Maize Vegetable Diet: Hepatic Steatosis of Undernutrition.

Hepatic steatosis is a hallmark feature of kwashiorkor malnutrition. However, the pathogenesis of hepatic steatosis in kwashiorkor is uncertain. Our objective was to develop a mouse model of childhood undernutrition in order to test the hypothesis that feeding a maize vegetable diet (MVD), like that consumed by children at risk for kwashiorkor, will cause hepatic steatosis which is prevented by supplementation with choline. A MVD was developed with locally sourced organic ingredients, and fed to weanling mice (n = 9) for 6 or 13 days. An additional group of mice (n = 4) were fed a choline supplemented MVD. Weight, body composition, and liver changes were compared to control mice (n = 10) at the beginning and end of the study. The MVD resulted in reduced weight gain and hepatic steatosis. Choline supplementation prevented hepatic steatosis and was associated with increased hepatic concentrations of the methyl donor betaine. Our findings show that (1) feeding a MVD to weanling mice rapidly induces hepatic steatosis, which is a hallmark disturbance of kwashiorkor; and that (2) hepatic steatosis associated with feeding a MVD is prevented by choline supplementation. These findings support the concept that insufficient choline intake may contribute to the pathogenesis of hepatic steatosis in kwashiorkor.

Therapeutic feeding at a rural hospital in Zimbabwe.

OBJECTIVE: The purpose of this audit was to review treatment outcomes of participants in the Cooperazione e sviluppo/Cooperation and Development (CESVI), Therapeutic Feeding Programme (TFP) (i.e., death vs cure vs absconded) and to make recommendations for improving this and other similar programmes. DESIGN: This study was a retrospective chart review. The charts of all patients admitted to the TFP from 1 January 2005 to 31 December 2005 were analyzed. SETTING: The Salvation Army Howard Hospital is a district hospital in rural Zimbabwe. The hospital provides both inpatient and outpatient paediatric care. SUBJECTS: 132 consecutive children were enrolled in the TFP in 2005. INTERVENTION: The objectives of the TFP included identification of children with severe malnutrition; treating complications associated with severe malnutrition and prescribing appropriate dietary treatment. MAIN OUTCOME MEASURES: The main outcome of interest was whether TFP participants died, were cured, or absconded. We assessed factors that may be associated with these outcomes such as age, gender, comorbidities and length of stay. RESULTS: Female children and children with marasmus were more likely to abscond from the programme than male children and children with kwashiorkor (p = 0.041, 0.039 respectively). The majority of children who died while in the programme did so within the first week of their admission. The majority of children who were cured while in the programme achieved this goal after two weeks of hospitalization (p < 0.0001). CONCLUSION: Given the contextual factors in rural African settings that could potentially impede the healthy growth and development of children, this review has produced programmatic recommendations and suggestions for future research directions.

Lipid kinetic differences between children with kwashiorkor and those with marasmus.

BACKGROUND: It has been hypothesized that one factor associated with poor prognosis in kwashiorkor, but not in marasmus, is impaired lipid catabolism, which limits the supply of energy that is essential for survival when dietary intake is inadequate. However, this hypothesis has not been tested. OBJECTIVE: The objective was to measure lipid kinetics in malnourished children with kwashiorkor or marasmus. DESIGN: Glycerol concentration and flux (index of total lipolysis), palmitate concentration and flux (index of net lipolysis), and palmitate oxidation rate (index of fatty acid oxidation) were measured in 8 children (n = 5 boys and 3 girls) with kwashiorkor and 7 (n = 4 boys and 3 girls) with marasmus, aged 4-20 mo, in the postabsorptive state. The measurements were made approximately 3 d after admission, when the children were malnourished, and after the children attained normal weight-for-length, ie, at recovery. RESULTS: The glycerol concentration was higher in the malnourished stage than at recovery for the marasmus and kwashiorkor groups combined. Glycerol flux tended to be lower (P = 0.067) and palmitate flux significantly lower (P < 0.05) in the kwashiorkor group than in the marasmus group. Palmitate oxidation was significantly lower in the malnourished stage than at recovery in the kwashiorkor group but not in the marasmus group. In the malnourished stage, palmitate oxidation was slower in the kwashiorkor group than in the marasmus group, but no significant differences between groups were observed at recovery. CONCLUSIONS: Children with kwashiorkor break down fat and oxidize fatty acids less efficiently than do children with marasmus; this factor may explain the better survival rate in marasmus.

Sulfur amino acid metabolism in children with severe childhood undernutrition: cysteine kinetics.

BACKGROUND: Children with edematous but not nonedematous severe childhood undernutrition (SCU) have lower plasma and erythrocyte-free concentrations of cysteine, the rate-limiting precursor of glutathione synthesis. We propose that these lower cysteine concentrations are due to reduced production secondary to slower de novo synthesis plus decreased release from protein breakdown. OBJECTIVE: We aimed to measure cysteine production, de novo synthesis, and the rate of cysteine release from protein breakdown in children with SCU. DESIGN: Cysteine flux, de novo synthesis, and release from protein breakdown were measured in 2 groups of children with edematous (n = 11) and nonedematous (n = 11) SCU when they were infected and malnourished (clinical phase 1), when they were still severely malnourished but no longer infected (clinical phase 2), and when they had recovered (clinical phase 3). RESULTS: In clinical phase 1, cysteine production and its release from protein breakdown were slower in both groups of children than were the values in the recovered state. These kinetic variables were significantly slower, however, in the children with edematous SCU than in those with nonedematous SCU. De novo cysteine synthesis in clinical phase 1 was faster than the rate at recovery in the edematous SCU group, and there were no significant differences between the groups at any clinical phase. CONCLUSION: These findings suggest that cysteine production is reduced in all children with SCU because of a decreased contribution from protein breakdown and not from decreased de novo synthesis. The magnitude of this reduction, however, is much greater in children with edematous SCU than in those with nonedematous SCU.

Sulfur amino acid metabolism in children with severe childhood undernutrition: methionine kinetics.

BACKGROUND: Children with edematous but not nonedematous severe childhood undernutrition (SCU) have lower plasma and erythrocyte-free concentrations of cysteine and methionine, which suggests a decreased availability of methionine for cysteine synthesis. We propose that methionine production and metabolism will be slower in children with edematous SCU than in those with nonedematous SCU. OBJECTIVE: We aimed to measure methionine flux, its transmethylation and its transsulfuration, and homocysteine remethylation in children with SCU. DESIGN: Methionine kinetics were measured in 2 groups of children with edematous (n = 11) and nonedematous (n = 11) SCU when they were infected and malnourished (clinical phase 1), when they were still severely malnourished but no longer infected (clinical phase 2), and when they had recovered (clinical phase 3). RESULTS: At clinical phase 1, children with edematous SCU had rates of total methionine flux, flux from protein breakdown, and flux to protein synthesis that were slower than the rates of the nonedematous group. There were no significant differences in homocysteine remethylation or methionine transsulfuration and transmethylation between the groups at clinical phase 1. CONCLUSION: These findings suggest that, in the acutely malnourished and infected state, children with edematous SCU have slower methionine production than do children with nonedematous SCU because of a slower rate of release from protein breakdown. This slower methionine production is not, however, associated with slower rates of methionine transsulfuration and transmethylation or homocysteine remethylation.

Nutrition rehabilitation of undernourished children utilizing Spiruline and Misola.

BACKGROUND: Malnutrition constitutes a public health problem throughout the world and particularly in developing countries. AIMS: The objective of the study is to assess the impact of an elementary integrator composed of Spiruline (Spirulina platensis) and Misola (millet, soja, peanut) produced at the Centre Medical St Camille (CMSC) of Ouagadougou, Burkina Faso, on the nutritional status of undernourished children. MATERIALS AND METHODS: 550 undernourished children of less than 5 years old were enrolled in this study, 455 showed severe marasma, 57 marasma of medium severity and 38 kwashiorkor plus marasma. We divided the children randomly into four groups: 170 were given Misola (731 +/- 7 kcal/day), 170 were given Spiruline plus traditional meals (748 +/- 6 kcal/day), 170 were given Spiruline plus Misola (767 +/- 5 kcal/day). Forty children received only traditional meals (722 +/- 8 kcal/day) and functioned as the control group. The duration of this study was eight weeks. RESULTS AND DISCUSSION: Anthropometrics and haematological parameters allowed us to appreciate both the nutritional and biological evolution of these children. The rehabilitation with Spiruline plus Misola (this association gave an energy intake of 767 +/- 5 kcal/day with a protein assumption of 33.3 +/- 1.2 g a day), both greater than Misola or Spiruline alone, seems to correct weight loss more quickly. CONCLUSION: Our results indicate that Misola, Spiruline plus traditional meals or Spiruline plus Misola are all a good food supplement for undernourished children, but the rehabilitation by Spiruline plus Misola seems synergically favour the nutrition rehabilitation better than the simple addition of protein and energy intake.

Comparison of home-based therapy with ready-to-use therapeutic food with standard therapy in the treatment of malnourished Malawian children: a controlled, clinical effectiveness trial.

BACKGROUND: Childhood malnutrition is common in Malawi, and the standard treatment, which follows international guidelines, results in poor recovery rates. Higher recovery rates have been seen in pilot studies of home-based therapy with ready-to-use therapeutic food (RUTF). OBJECTIVE: The objective was to compare the recovery rates among children with moderate and severe wasting, kwashiorkor, or both receiving either home-based therapy with RUTF or standard inpatient therapy. DESIGN: A controlled, comparative, clinical effectiveness trial was conducted in southern Malawi with 1178 malnourished children. Children were systematically allocated to either standard therapy (186 children) or home-based therapy with RUTF (992 children) according to a stepped wedge design to control for bias introduced by the season of the year. Recovery, defined as reaching a weight-for-height z score > -2, and relapse or death were the primary outcomes. The rate of weight gain and the prevalence of fever, cough, and diarrhea were the secondary outcomes. RESULTS: Children who received home-based therapy with RUTF were more likely to achieve a weight-for-height z score > -2 than were those who received standard therapy (79% compared with 46%; P < 0.001) and were less likely to relapse or die (8.7% compared with 16.7%; P < 0.001). Children who received home-based therapy with RUTF had greater rates of weight gain (3.5 compared with 2.0 g . kg(-1) . d(-1); difference: 1.5; 95% CI: 1.0, 2.0 g . kg(-1) . d(-1)) and a lower prevalence of fever, cough, and diarrhea than did children who received standard therapy. CONCLUSION: Home-based therapy with RUTF is associated with better outcomes for childhood malnutrition than is standard therapy.

Rice nightmare: Kwashiorkor in 2 Philadelphia-area infants fed Rice Dream beverage.

A 14-month-old girl and a 7-month-old boy each presented with a diffuse dermatitis, whole body edema, and hypoalbuminemia. The diets of both infants consisted almost entirely of Rice Dream, a rice-based, protein-poor beverage. Both infants were diagnosed with kwashiorkor, which resolved with protein supplementation. Clues from the physical examination, a diet history, appropriate laboratory examinations, and an index of suspicion are crucial in promptly diagnosing and treating infants with kwashiorkor. Manufacturers of rice beverages should appropriately warn parents about the dangers of using their products as infant nourishment.

Antipyrine pharmacokinetics and D-glucaric excretion in kwashiorkor.

Hepatic microsomal oxidation and glucuronidation were studied in 15 children with kwashiorkor on admission to the hospital and again after 3 weeks of nutritional rehabilitation. Microsomal oxidation as measured by antipyrine half-life and clearance was shown to be depressed in the acute phase of malnutrition (T 1/2 = 7.9 +/- 5.0 hr, clearance = 8.4 +/- 5.1 ml/min) improving with nutritional rehabilitation (T 1/2 = 4.3 +/- 2.3 hr, clearance = 15.5 +/- 8.7 ml/min). Urinary D-glucaric acid excretion increased from 60.6 +/- 42.2 mumoles/24 hr to 121.8 +/- 105.0 mumoles/24 hr over the same time period. Evidence is thus presented that both hepatic microsomal oxidation and glucuronidation are depressed in the acute phase of kwashiorkor but recover with nutritional rehabilitation.