Kwashiorkor Children Research Articles

Mechanisms of Kwashiorkor-Associated Immune Suppression: Insights From Human, Mouse, and Pig Studies.

Malnutrition refers to inadequate energy and/or nutrient intake. Malnutrition exhibits a bidirectional relationship with infections whereby malnutrition increases risk of infections that further aggravates malnutrition. Severe malnutrition (SM) is the main cause of secondary immune deficiency and mortality among children in developing countries. SM can manifest as marasmus (non-edematous), observed most often (68.6% of all malnutrition cases), kwashiorkor (edematous), detected in 23.8% of cases, and marasmic kwashiorkor, identified in ~7.6% of SM cases. Marasmus and kwashiorkor occur due to calorie-energy and protein-calorie deficiency (PCD), respectively. Kwashiorkor and marasmic kwashiorkor present with reduced protein levels, protein catabolism rates, and altered levels of micronutrients leading to uncontrolled oxidative stress, exhaustion of anaerobic commensals, and proliferation of pathobionts. Due to these alterations, kwashiorkor children present with profoundly impaired immune function, compromised intestinal barrier, and secondary micronutrient deficiencies. Kwashiorkor-induced alterations contribute to growth stunting and reduced efficacy of oral vaccines. SM is treated with antibiotics and ready-to-use therapeutic foods with variable efficacy. Kwashiorkor has been extensively investigated in gnotobiotic (Gn) mice and piglet models to understand its multiple immediate and long-term effects on children health. Due to numerous physiological and immunological similarities between pigs and humans, pig represents a highly relevant model to study kwashiorkor pathophysiology and immunology. Here we summarize the impact of kwashiorkor on children’s health, immunity, and gut functions and review the relevant findings from human and animal studies. We also discuss the reciprocal interactions between PCD and rotavirus—a highly prevalent enteric childhood pathogen due to which pathogenesis and immunity are affected by childhood SM.

Frequency of Hypoglycemia in Severe Acute Malnutrition

Malnutrition is a major health problem throughout the world and contributes to at least one third of all children deaths worldwide. Hypoglycemia is a basic metabolic complication in pediatric patients which can be easily prevented by proper care and management. Objective of this study was to determine the frequency of hypoglycemia in sever acute Malnurished children (SAM). The study was conducted in nutritional division of Nangarhar University Teaching Hospital pediatric department. For 8 months, all the patients were subjected for measurement of blood glucose level by glucose oxidase method .Hypoglycemia was labeled according to value mentioned in operational definition. The study included a total of 252 patients with SAM. 137 (54.4%) were Males and 115 (45.6%) females with no significant difference in the number of gender and with an average age of (Mean± SD) 16.20±11.74 (6 months to 60 months). Out of 252 patients 54.80% (138) were hypoglycemic, and 85.70% (216) suffering from Marasmus. 38.9% of children’s caregivers were illiterate and 86.5% poor and middle-level of socioeconomic status. 12.7%( 32) of the SAM children with hypoglycemia were dying, most of the patient from Nangarhar province.
 Sever acute malnutrition (SAM) constitutes a significant health problem and important cause of mortality and morbidity in children, in marasmus patients the hypoglycemia is more common than kwashiorkor children; early diagnosis and treatment can prevent and decrease the morbidity and mortality of Sever acute malnutrition (SAM) in children significantly, education, socioecnomic status of caregivers are important in prevention of sever acute malnutrition (SAM) and their complications.

Assessment of calcium and phosphate levels among Sudanese children with malnutrition: A pilot study in Khartoum state Primary tabs

Malnutrition is a public health problem of significant importance in developing countries, it generally affects everyone in a community, but infants and children are the most vulnerable because of their high nutritional needs for growth and development. This study aimed to assess the levels of calcium and phosphate among Sudanese children with malnutrition. This case control study was conducted in Omdurman hospital in Khartoum, Sudan, during the period from April 2019 to May 2019. Fifty children with malnutrition (case) and 50 healthy children (control) were enrolled in this study; both groups were matched in age and sex. Blood samples were analyzed for calcium and phosphate levels using Mindray BS-200 automated analyzer. There was a significant decrease in phosphate level in malnourished children when compared with healthy children (P-value = 0.00). According to the type of malnutrition, there were significant differences in mean of calcium level; marasmic children had lower mean level (7.1 mg/dL) compared with kwashiorkor and under-nutrition children (9.4 mg/dL). In addition, there was no correlation between serum calcium and phosphate levels with the duration of malnutrition. (r =-0.071. P-value = 0,624) (r = 00.077. P-value = 0.593) respectively. In conclusion: Hypophosphatemia is a common finding among Sudanese malnourished children and marasmic children had decreased level of calcium when compared to other types of malnutrition. Accordingly, it is better to monitor serum phosphate level and other nutritional status within the recovery period.

RETRACTED ARTICLE: Gut Microbiota Alteration is Characterized by a Proteobacteria and Fusobacteria Bloom in Kwashiorkor and a Bacteroidetes Paucity in Marasmus

Kwashiorkor and marasmus are considered to be two different clinical diseases resulting from severe malnutrition, but this distinction has been questioned. In a previous study comparing children with kwashiorkor and healthy children from Niger and Senegal, we found a dramatic gut microbiota alteration with a predominant depletion of anaerobes and enrichment in Proteobacteria and Fusobacteria in kwashiorkor. However, it remained unknown whether this association was related to malnutrition or was a specific feature of kwashiorkor. In this continuation study, we added 7 new marasmus subjects and 71,162 new colonies from the same countries. Our results showed that, compared to marasmus, the kwashiorkor gut microbiota was characterized by an increased proportion of Proteobacteria (culturomics, Marasmus 5.0%, Kwashiorkor 16.7%, p < 0.0001; metagenomics, Marasmus 14.7%, Kwashiorkor 22.0%, p = 0.001), but there was a decreased proportion of Bacteroidetes in marasmus (culturomics, Marasmus 0.8%, Kwashiorkor 6.5%, p = 0.001; metagenomics, Marasmus 5.4%, Kwashiorkor 7.0%, p = 0.03). Fusobacterium was more frequently cultured from kwashiorkor. All detected potential pathogenic species were enriched in the kwashiorkor gut microbiota. These results provide a biological basis to support the usage of an antibiotic therapy more effective in suppressing the overgrowth of bacterial communities resistant to penicillin, combined with antioxidants and probiotics for nutritional recovery therapies, particularly for kwashiorkor.

Gut Bacteria Missing in Severe Acute Malnutrition, Can We Identify Potential Probiotics by Culturomics?

Severe acute malnutrition is the world-leading cause of children under-five's death. Recent metagenomics studies have established a link between gut microbiota and severe acute malnutrition, describing an immaturity with a striking depletion in oxygen-sensitive prokaryotes. Amoxicillin and therapeutic diet cure most of the children with severe acute malnutrition but an irreversible disruption of the gut microbiota is suspected in the refractory and most severe cases. In these cases, therapeutic diet may be unable to reverse the microbiota alteration leading to persistent impaired development or death. In addition, as enteric sepsis is a major cause of death in this context, identification of missing gut microbes to be tested as probiotics (live bacteria that confer a benefit to the host) to restore rapidly the healthy gut microbiota and prevent the gut pathogenic invasion is of foremost importance. In this study, stool samples of malnourished patients with kwashiorkor and healthy children were collected from Niger and Senegal and analyzed by culturomics and metagenomics. We found a globally decreased diversity, a decrease in the hitherto unknown diversity (new species isolation), a depletion in oxygen-sensitive prokaryotes including Methanobrevibacter smithii and an enrichment in potentially pathogenic Proteobacteria, Fusobacteria and Streptococcus gallolyticus. A complex of 12 species identified only in healthy children using culturomics and metagenomics were identified as probiotics candidates, providing a possible, defined, reproducible, safe, and convenient alternative to fecal transplantation to restore a healthy gut microbiota in malnourished children. Microbiotherapy based on selected strains has the potential to improve the current treatment of severe acute malnutrition and prevent relapse and death by reestablishing a healthy gut microbiota.

Effect of Short-Term of Nutrition Rehabilitation on Catch-up Growth in Marasmus and Kwashiorkor Children

Effect of Short-Term of Nutrition Rehabilitation on Catch-up Growth in Marasmus and Kwashiorkor Children About 149 million children under 5 years of age in developing countries are undernourished. The goal in nutrition rehabilitation of these children is the restoration of body weight to the normal range by a rapid catch-up growth. The present study aims to compare the effects of short-term phase of nutrition rehabilitation (21 days) in marasmus and kwashiorkor children, on catch-up growth.

Aflatoxin contamination in food and body fluids in relation to malnutrition and cancer status in Cameroon.

Aflatoxins are food contaminants usually associated with hepatitis, immunodepression, impairment of fertility and cancer. The present work was to determine the presence of aflatoxins in eggs, milk, urine, and blood samples that were collected from various sources and periods; and hepatitis B virus antigen in blood samples. Aflatoxin was found in eggs (45.2%), cow raw milk (15.9%), breast milk (4.8%), urine from kwashiorkor and marasmic kwashiorkor children (45.5%), and sera from primary liver cancer patients (63.9%); HbsAg was also detected in 69.4% of the serum samples, but there was no association between both factors. Both AF and hepatitis B virus seem to be risk factors that could increase the incidence and prevalence rates of malnutrition and cancer in Cameroon.

Prediction of nutritional status by chemical analysis of urine and anthropometric methods.

A combination of anthropometric and chemical indices was used to investigate the nutritional status of 26 healthy (H) and kwashiorkor (K) children aged 2-5 years and possibly predict the onset of malnutrition. The healthy children had significantly (p>0.05) higher values for weight, height, middle upper arm circumference and weight/height ratio than kwashiorkor children. The healthy children had significantly higher urinary concentrations of urea, inorganic sulphate and sulphate relative to creatinine, but significantly lower thiocyanate and thiocyanate relative to creatinine than the kwashiorkor children. The results of the present study would tend to indicate that a chemical analysis especially of urea, inorganic sulphate or thiocyanate alone or the urea/creatinine, inorganic sulphate/creatinine or thiocynate/creatinine ratio could be used to predict malnutrition after the initial anthropometric measurements. This study should however be repeated with a large population of volunteers to determine the specific cut-off points for each anthropometric and chemical analysis.

Relationship between nutritional status and histologic findings in small bowel mucosa of children presenting with diarrhoea of more than 14 days' duration.

In order to study the eventual effects of malnutrition on small intestinal mucosa, we evaluated 85 children with diarrhoea of more than 14 days' duration, aged from 4 to 114 months (median 17 months). A proximal small intestinal biopsy was obtained and villus height, crypt depth, mucosal thickness, and total mucosal thickness were measured. Gomez, Waterlow, and Z score criteria were applied. Statistical analyses were performed with the Spearman correlation test and the non-parametrical tests of Wilcoxon, Mann-Whitney, and Kruskal-Wallis. A value of p < 0.05 was considered significant. Average villus height was 269.2 microns (+/- 87.5 microns); crypt depth 113.0 microns (+/- 33.8 microns); mucosal thickness 210.5 microns (+/- 73.2 microns); total mucosal thickness 485.9 microns (+/- 111.8 microns); and villus height/crypt depth ratio 2.5:1 (+/- 0.8:1). Five children had kwashiorkor and 13 had marasmus. Villus height for kwashiorkor children ranged from 151 microns to 353.3 microns (average 286.7 microns), crypt depth from 90.3 microns to 154 microns (average 111.11 microns). According to Gomez criteria, as malnutrition increased, mucosal thickness and the villus/crypt ratio decreased. Waterlow criteria had no relation to mucosal sizes. When distributed in sequential decrease according to their nutritional state, the Z score for weight for age and weight for height indices showed a positive correlation with villus height, total mucosal thickness, and villus/crypt ratio.

AFLATOXINS IN AUTOPSY KIDNEY SPECIMENS FROM CHILDREN IN NIGERIA

Autopsy kidney specimens from 24 children with kwashiorkor and 21 with other miscellaneous diseases, at the Obafemi Awolowo Teaching Hospital Complex, Ile-Ife, Nigeria, were analyzed for the presence of aflatoxins using high-performance liquid chromatography. Aflatoxins were detected in 14 children who died of kwashiorkor and in 13 of those who died from miscellaneous diseases. Aflatoxicol was detected in 10 specimens, 7 of which had severe gastroenteritis. Seven kidney specimens demonstrated the presence of more than one type of aflatoxin; four of these were kidneys of patients with kwashiorkor and the remaining three died from renal failure. No difference was found between the frequency of detection, type of aflatoxin detected, or mean concentrations of total aflatoxins in the kidney specimens of the kwashiorkor children when compared to the kidney specimens of children who died from miscellaneous diseases. These findings demonstrate that aflatoxins can be detected in the kidneys of children exposed to aflatoxins.

Impaired dietary lipid oxidation in kwashiorkor

Energy substrate oxidation studies were performed on 12 kwashiorkor children and five well-nourished children fed on a standard recovery diet for kwashiorkor. 13C labeled leucine, Glucose, and hiolein were administered orally on three consecutive days. The recovery of 13C from the breath air was monitored after administration of each feed. The mean cumulative percent dose (CUMPD) recovery of 13C seven hours after the ingestion of labeled leucine was 22.0 ± 1.7% (mean ± SEM) for the kwashiorkor children as compared to 32.7 ± 3.7% for the well-nourished children (p<0.05). The CUMPD recovery of 13C 12 hours after ingestion of labeled glucose was 58.3 ± 4.7% as compared to 70.2 ± 6.0% in the well-nourished children (p<0.05). The CUMPD recovery of 13C 16 hours after the ingestion of labeled hiolein was 4.8 ± 1.1% for the kwashiorkor children as compared to 19.0 ± 2.1% for the well-nourished children (p<0.0001). 13C recovery following hiolein ingestion was inversely correlated to the weight/expected weight for age and sex ratio (r = −0.93; p< 0.001). It is concluded that the well-nourished children oxidize more exogenous energy substrate than do the kwashiorkor children, and that the kwashiorkor children have a grossly impaired capacity to oxidize exogenous lipids.

Humoral and cell-mediated immunity in malnourished children in Ghana.

To examine the relationship between immunological variables and the different types and severity of malnutrition in Ghanaian children. Case-control study. The study was done at Princess Marie Louise Hospital, Accra, Ghana. One hundred and seventy children, aged 8-36 months, were recruited at the clinical ward and public health service section of the hospital: 61 normal children, 49 moderately malnourished (underweight) children and 60 severely malnourished children (19 kwashiorkor, 30 marasmus, and 11 marasmic kwashiorkor children). The children underwent clinical observations, anthropometric measurements and blood sampling for biochemical analysis to evaluate their nutritional and immunological status. Serum immunoglobulins (IgA subclasses, IgG subclasses and IgM), complements (C3 and C4) and lymphocyte subpopulations (T cells, B cells, CD4+, CD8+, NK cells and HLADR) were determined for the assessment of humoral and cell-mediated immunity. Serum levels of IgA1, IgA2 and C4 tended to be higher in severely malnourished children than in normal children, while serum level of C3 and the proportion of B cells were significantly lower in the severely malnourished children than in the normal children (P < 0.05). There were no notable differences in most immunological parameters among the three severely malnourished groups. No differences were observed in the immunological parameters except for the proportion of B cells between normal and moderately malnourished children. Factor analysis revealed that C3 levels were positively correlated with a factor which was strongly associated with weight-for-height z-score and biochemical indicators for evaluating protein nutrition. In addition, IgA2, IgG1 and IgM levels were positively correlated with a factor which was associated with C-reactive protein. Several immunological variables responded positively or negatively with the different levels of severity of malnutrition, but most variables did not on the different types of malnutrition. The changes of C3 level were more associated with the severity of malnutrition.

Aflatoxins in the autopsy brain tissue of children in Nigeria

Autopsy brain (cerebrum) specimens from 18 kwashiorkor children and 19 children who had died from a variety of other diseases, at the Obafemi Awolowo Teaching Hospital complex, Ile-Ife, Nigeria, were analysed for the presence of aflatoxins using high-performance liquid chromatography. Aflatoxins were detected in 81%, 15 specimens in each group. More than one type of aflatoxin was detected in 14 (37.8%) of all the specimens. Aflatoxin B1 and its reversible metabolite, aflatoxicol, were detected in 11 brain specimens of patients with kwashiorkor and 6 of those who died of other miscellaneous diseases; out of these 6, two died from measles and its complications. The frequent detection of aflatoxins in the brains of these children and sometimes in multiple forms may suggest that aflatoxins are stored in the brain tissue which could be related to the lipophilic nature of these compounds. These findings also suggest that although many children in the tropics are exposed to aflatoxins, the accumulation of aflatoxin B1 and aflatoxicol in the brains of kwashiorkor children may be a result of an impaired metabolism of these compounds by these children.

Prolonged breastfeeding without the introduction of supplementary feeding.

A study on the determinants of nutritional marasmus (NM) and kwashiorkor (K) was conducted using Sudanese children aged 6-36 months. The hypotheses tested were related to the specific circumstances leading to the development of NM and K. Subjects consisted of 55 children with NM and 55 with K, admitted to the Children's Emergency Hospital in Khartoum. This paper presents the results of the association between NM and prolonged breastfeeding without introduction of supplementary feeding between the ages of 6 and 24 months. Mothers were interviewed in hospital, and information on duration of breastfeeding, age at introduction of supplementary foods, and weaning foods was obtained. Observations were made in 20 per cent of homes of study children. The results suggest a positive association between prolonged breastfeeding without introduction of supplementary feeding between the ages of 6 and 24 months, and NM. Using multivariate analysis the data show that late introduction of supplementary foods produces an increase of 1.4-fold the odds of developing nutritional marasmus, rather than kwashiorkor. In contrast the odds ratio is 1.9 for the two conditions in terms of age of cessation of breastfeeding, the kwashiorkor children breastfeeding for fewer months. Results suggest strategies to reduce the prevalence of NM and K, plus mild and moderate PEM.

Aflatoxin, kwashiorkor, and morbidity.

Children suffering from kwashiorkor could be grouped as those in whom aflatoxin was detectable in both serum and urine, and those in whom this mycotoxin was undetectable. Examination of the clinical records of the aflatoxin-positive and -negative children (58% and 42% of the sample, respectively) showed several other differences between the two groups. Compared with the aflatoxin-negative group, the children scored as aflatoxin-positive showed a significantly lower haemoglobin level (P = 0.02), a longer duration of oedema (P = 0.057), an increased number of infections (P = 0.037), and a longer duration of hospital stay (P = 0.008). The present findings suggest that the consumption of a staple food such as maize that is contaminated with the fungus Aspergillus flavus exposes susceptible kwashiorkor children to the metabolic hazards of aflatoxins, resulting in a greater risk of frequent infections.

Fatty acid composition of erythrocyte membrane lipid obtained from children suffering from kwashiorkor and marasmus

The fatty acid composition of erythrocyte membrane (EM) lipids obtained from normal, kwashiokor, and marasmic children was analyzed by gas chromatography. The proportion of palmitic acid (16:0) was lower and of oleic acid (18:1) higher in the kwashiorkor group than in the control group. The marasmic group showed lower proportions of eicosatrienoic acid (20:3) and arachidonic acid (20:4) and a higher proportion of oleic acid (18:1) than the control group. A significant difference was found between the marasmic and kwashiorkor groups with respect to arachidonic acid (20:4), which showed a lower proportion in the former group than the latter. The ratio of arachidonic acid to linoleic acid ( 20:4 18:2 ) was markedly lower in the marasmic group than the control group, suggesting a possible impairment in the conversion of linoleic acid to arachidonic acid in marasmic children. The ratio of unsaturated fatty acids to saturated fatty acids was markedly elevated in the kwashiorkor group over that of control group, indicating increased fluidity of EM in kwashiorkor. It is suggested that the altered membrane fatty acid composition reflects deranged lipid metabolism and affects the physical and physiological properties of EM and could contribute to changes in the activities of several red blood cell membrane-bound enzymes reported earlier in kwashiorkor children.

Acetylator status of kwashiorkor children in Ibadan (South-West Nigeria)

Acetylator status was determined in 25 kwashiorkor children, aged between 8 months and 3 years and in 25 age-matched control group of healthy children after a single oral dose of sulphamethazine (40 mg/kg body weight) and by measuring the acetylated sulphamethazine in blood samples, collected 6 h after the administration of sulphamethazine. The percentage of slow acetylators among kwashiorkor children was 40% while among the control group of children it was 48%. The difference between the two groups was not significant. Therefore, it is probable that the slow acetylator status of the Nigerian African children may not be a contributing factor for the development of kwashiorkor, a syndrome of protein-energy malnutrition. Furthermore, the polymorphic activity of N-acetyl transferase enzyme may not be impaired in kwashiorkor.

Erythrocyte membrane (Ca2++Mg2+)-ATPase in human protein-energy malnutrition

Calmodulin-free ghost membranes were prepared from erythrocytes of kwashiorkor children and from healthy children in the same age bracket. In the absence of calmodulin, the specific activity of Mg2+-dependent Ca2+-pumping ATPase (Ca2+ + Mg2+-ATPase) of kwashiorkor membranes was more than 40 percent lower than the specific activity of the normal enzymes, whose maximum velocity was increased by at least four-fold by the modulator protein. In contrast, the maximum velocity of the enzymes of kwashiorkor membranes was enhanced by calmodulin by about 1 1/2 times the basal activity of the normal enzymes and by 2 times the basal activity of the kwashiorkor enzymes. The affinity of the pump for ATP was lower in the membranes of kwashiorkor children (Km for ATP = 30.6 +/- 2.8 microM ATP) in comparison to normal membranes (Km for ATP = 21.7 +/- 2.0 microM ATP). Similarly, calmodulin-affinity of the enzymes, was lower in kwashiorkor membranes than in the normal membranes irrespective of source of calmodulin. Calmodulin from haemolysates of kwashiorkor red cells activated the enzymes of normal and kwashiorkor membranes to the same degree as calmodulin partially purified from the haemolysate of healthy children. A determination of the dependence of the activity of the pump on calcium in the absence and presence of calmodulin reveals that the affinity of the kwashiorkor enzymes for Ca2+ is at least 70 percent lower than that of enzymes of normal membranes. Altogether, these findings suggest that the Ca2+-pumping ATPase of kwashiorkor membranes is less functional than the enzymes of healthy erythrocytes.

INH and streptomycin in Ethiopian children with tuberculosis and different nutritional status.

The plasma concentration of INH and streptomycin was followed in 45 Ethiopian children with tuberculosis. The children were grouped according to their nutritional status as normal, underweight, marasm and kwashiorkor. INH was well absorbed in all nutritional groups to give therapeutically active plasma levels. When terminal half life (t1/2) of INH was calculated for individual patients there were more children in all nutritional groups with t1/2 greater than or equal to 2 hours than less than 2 hours, indicating a slow acetylation of INH. Streptomycin was well absorbed in all nutritional groups and therapeutic levels were obtained with 20 mg/kg i.m. After 30 mg/kg i.m. of streptomycin kwashiorkor children had an increased t1/2 of streptomycin indicating a decreased renal excretion of the drug in kwashiorkor. The clinical follow-up of the children indicated that serious tuberculosis could be successfully treated with INH and streptomycin in the doses used.

Protein-energy malnutrition in northern Sudan: prevalence, socio-economic factors and family background

The socio-economic and family background and the nutrition of 145 children with kwashiorkor admitted to hospital in Khartoum over a 2-year period were compared with 113 marasmic kwashiorkor, 158 marasmic, and 186 nutritionally normal controls of similar age. Peak admissions for kwashiorkor were in the wet and post-wet season and the mean (SD) age was 1.6 (0.6) months. Mothers of malnourished children were more likely to be pregnant, and had poorer housing, sanitation and water supply, a lower income and food expenditure and less education than controls. Mothers of controls breastfed their children longer, introduced mixed feeding earlier, offered a wider variety of foods, and were more likely to have had their infants immunized. Neither family instability nor cultural practices which result in separation of children from their mothers appear to have an important role in protein-energy malnutrition in the Sudan. Families of kwashiorkor children had a higher food expenditure and better maternal education than marasmic children. There was no significant difference between the two groups in duration of breastfeeding or in the age of introduction of mixed diet. However, kwashiorkor children appeared to be offered more meat. Differences in food availability could account for the relative retardation of growth and lack of subcutaneous fat in marasmus compared to kwashiorkor.