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.

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.

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.

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.

Misdiagnosed food allergy resulting in severe malnutrition in an infant.

As food allergies become increasingly prevalent and testing methods to identify "food allergy" increase in number, the importance of careful diagnosis has become even more critical. Misdiagnosis of food allergy and inappropriate use of unproven testing modalities may lead to a harmful food-elimination diet. This case is an example of an infant who was placed on an overly restrictive elimination diet at the recommendation of her health care providers, resulting in kwashiorkor and acquired acrodermatitis enteropathica.

Gut microbiomes of Malawian twin pairs discordant for kwashiorkor.

Kwashiorkor, an enigmatic form of severe acute malnutrition, is the consequence of inadequate nutrient intake plus additional environmental insults. To investigate the role of the gut microbiome, we studied 317 Malawian twin pairs during the first 3 years of life. During this time, half of the twin pairs remained well nourished, whereas 43% became discordant, and 7% manifested concordance for acute malnutrition. Both children in twin pairs discordant for kwashiorkor were treated with a peanut-based, ready-to-use therapeutic food (RUTF). Time-series metagenomic studies revealed that RUTF produced a transient maturation of metabolic functions in kwashiorkor gut microbiomes that regressed when administration of RUTF was stopped. Previously frozen fecal communities from several discordant pairs were each transplanted into gnotobiotic mice. The combination of Malawian diet and kwashiorkor microbiome produced marked weight loss in recipient mice, accompanied by perturbations in amino acid, carbohydrate, and intermediary metabolism that were only transiently ameliorated with RUTF. These findings implicate the gut microbiome as a causal factor in kwashiorkor.

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.

Using of WHO guidelines for the management of severe malnutrition to cases of marasmus and kwashiorkor in a Colombia children's hospital.

BACKGROUND: In 2007, the Hospital Infantil Los Ángeles (HILA) in Colombia implemented a slightly-modified version of the WHO guidelines for the diagnosis and management of malnutrition during childhood. OBJECTIVE: To evaluate the efficacy of the WHO-HILA protocol in children hospitalized with severe, chronic marasmus and kwashiorkor malnutrition (MS-KWK) in 2007 and 2008. MATERIAL AND METHODS: In this descriptive retrospective study the records of 100 children hospitalized with MSKWK were initially evaluated. Of these, 30 fulfilled the inclusion criteria: children of both sexes with a primary diagnosis of MS-KWK. Patients with any chronic disease liable to cause malnutrition were excluded. Anthropometric parameters, clinical signs and biochemical indicators of malnutrition were assessed upon admission and again at discharge following application of the WHO guidelines. Univariate analysis was performed for each study variable; serum hemoglobin and albumin levels on admission and at discharge were compared, and data were subjected to bivariate analysis. RESULTS: Marasmus was diagnosed in 23.3% of children, kwashiorkor in 73.3% and marasmic kwashiorkor in 3.3%. The major clinical findings were: edema (70%), emaciation (40%), "flag sign" hair (42.86%), low serum albumin (93%) and anemia (80%). Thirteen children following the WHO-HILA protocol showed a significant nutritional status improvement (p<0.05), whereas no improvement was noted in the 17 children not treated according to the protocol. CONCLUSIONS: Application of the WHO-HILA protocol was associated with reduced morbimortality in children with marasmus-kwashiorkor malnutrition. Implementation of this protocol should therefore be considered in all children´s hospitals in countries where this disease is prevalent.

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.

Protein energy malnutrition.

Protein energy malnutrition (PEM) is a common problem worldwide and occurs in both developing and industrialized nations. In the developing world, it is frequently a result of socioeconomic, political, or environmental factors. In contrast, protein energy malnutrition in the developed world usually occurs in the context of chronic disease. There remains much variation in the criteria used to define malnutrition, with each method having its own limitations. Early recognition, prompt management, and robust follow up are critical for best outcomes in preventing and treating PEM.

The use of home-based therapy with ready-to-use therapeutic food to treat malnutrition in a rural area during a food crisis.

When the international community declared a famine in Malawi in January of 2006, emergency food aid reached only populations with pre-existing health care services. To treat the widespread childhood malnutrition in Machinga district, a rural area lacking health care facilities, in February 2006 five outpatient therapeutic programs were implemented that utilized home-based therapy and ready-to-use therapeutic food. Children with severe malnutrition, defined as the presence of edema and/or a weight-for-height less than 70% of the reference standard, were enrolled in the program. Two senior clinical nurses trained village health aides in each of the five communities. Children visited the health aides biweekly. During the visits, health aides collected demographic and anthropometric information and distributed a 2-week supply of ready-to-use therapeutic food, providing 175 kcal/kg/d. Treatment continued for 8 weeks; children were discharged before 8 weeks if they reached a weight-for-height more than 100% of the reference standard, or required admission to the hospital due to systemic infection or recurrence of edema. Of the 826 children enrolled, 775 (93.7%) recovered, 13 (1.8%) remained malnourished, 30 (3.6%) defaulted, and 8 (0.9%) died. Mean weight gained was 2.7+/-3.7 g/kg/d, height gained 0.3+/-0.9 mm/d, and mid-upper arm circumference gained 0.2+/-0.3 mm/d. Home-based therapy with ready-to-use therapeutic food administered by village health aides is an effective approach to treating malnutrition during food crises in areas lacking health services.

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

Combination of type 2 diabetes and malnutrition worsened by anastomotic stenosis and pancreas atrophy following resection of pancreas head.

A 77-year-old Japanese man was admitted due to hypoglycemia induced by small amount of insulin. He was diagnosed type 2 diabetes in 1978 and the pancreatic cancer in 1993. Resection of the pancreas head and duodenum was performed. Subsequently, anastomotic stenosis appeared to induce appetite loss. His flavor for carbohydrate-rich food accelerated protein malnutrition. Fatty liver and pancreas atrophy were diagnosed in 1999. After he was diagnosed as secondary kwashiorkor, nasal feeding of protein-rich food improved his fatty liver as well as his general condition rapidly. Anastomotic stenosis and pancreas atrophy contributed to a combination of type 2 diabetes and kwashiorkor.

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.

A large-scale operational study of home-based therapy with ready-to-use therapeutic food in childhood malnutrition in Malawi.

Home-based therapy with ready-to-use therapeutic food (RUTF) for the treatment of malnutrition has better outcomes in the research setting than standard therapy. This study examined outcomes of malnourished children aged 6-60 months enrolled in operational home-based therapy with RUTF. Children enrolled in 12 rural centres in southern Malawi were diagnosed with moderate or severe malnutrition according to the World Health Organization guidelines. They were treated with 733 kJ kg(-1) day(-1) of RUTF and followed fortnightly for up to 8 weeks. Staff at each centre followed one of three models: medical professionals administered treatment (5 centres), patients were referred by medical professionals and treated by community health aids (4 centres), or community health aids administered treatment (3 centres). The primary outcome of the study was clinical status, defined as recovered, failed, died or dropped out. Regression modelling was conducted to determine what aspects of the centre (formal training of staff, location along a main road) contributed to the outcome. Of 2131 severely malnourished children and 806 moderately malnourished, 89% and 85% recovered, respectively. Thirty-four (4%) of the moderately malnourished children failed, with 20 (2%) deaths, and 61 (3%) of the severely malnourished children failed, with 29 (1%) deaths. Centre location along a road was associated with a poor outcome. Outcomes for severely malnourished children were acceptable with respect to both the Sphere guidelines and the Prudhon case fatality index. Home-based therapy with RUTF yields acceptable results without requiring formally medically trained personnel; further implementation in comparable settings should be considered.