The Journal of Nutrition Vol. 127 No. 1 January 1997, pp. 51-54
Copyright ©1997 by the American Society for Nutritional Sciences

Early Feeding of an Energy Dense Diet during Acute Shigellosis Enhances Growth in Malnourished Children^1,2

Ramendra N. Mazumder³, Syed S. Hoque, Hasan Ashraf, Iqbal Kabir, and Mohammad A. Wahed

Clinical Sciences Division, International Centre for Diarrhoeal Disease Research, Dhaka 1000, Bangladesh

ABSTRACT

INTRODUCTION

SUBJECTS AND METHODS

RESULTS

DISCUSSION

FOOTNOTES

LITERATURE CITED

ABSTRACT

In a controlled clinical trial, we examined the effect of the short-term feeding of an energy-dense milk cereal formula in malnourished children with clinically severe dysentery due to acute shigellosis. Seventy-five malnourished children, aged 12-48 mo, passing blood or blood with mucous in the stool for 96 h, were offered a hospital diet. In addition, study children (n = 36) were offered a milk-cereal formula with an energy of 5 kJ/g (an 11% protein diet); similarly, control children (n = 39) were offered a milk-cereal formula with an energy content of 2.5 kJ/g (an 11% protein diet). Patients were admitted to the metabolic ward of the Clinical Research and Service Centre, Dhaka, at the International Centre for Diarrhoeal Disease Research, Bangladesh. Patients were studied for 10 hospital days and were then followed up at home after 30 d. After 10 d of dietary intervention, children in the study group had a significantly greater increase vs. controls in weight-for-age (6 vs. 3%, P < 0.001) and in weight-for-height ( 7 vs. 3%, P < 0.001). Serum prealbumin concentrations were significantly higher (study vs. control) after 5 d (0.214 vs. 0.170 g/L, P = 0.01) and after 10 d (0.244 vs. 0.193 g/L, P = 0.006) of the study. Greater weight-for-age was sustained at home 1 mo after discharge (8 vs. 5%, P = 0.005) from the hospital. Similarly, higher weight-for-height was sustained 1 mo after discharge (8 vs. 5%, P = 0.01). During their stay at home, there was no dietary intervention. The results of this study suggest that short-term feeding of an energy-dense diet enhances growth in malnourished children with acute dysentery due to shigellosis.

INTRODUCTION

Dysentery (bloody diarrhea) is a common problem in children, and about 10% of diarrheal episodes in children <5 y of age have visible blood in the stool. Dysentery accounts for about 15% of diarrhea-associated deaths in this age group world wide (Victora et al. 1993). In developing countries, including Bangladesh, the problem is particularly acute. Among the children in Bangladesh, shigella infection is most frequent at age 1-4 y and the fatality rate in this group is 3.5% (Stoll et al. 1982). Shigellosis causes a profound loss of blood from the ulcerated colon that continues even after the eradication of the pathogen with appropriate antibiotics (Speelman et al. 1984); this is reflected in body micro- and macronutrient status (Scrimshaw 1977). Anorexia, a frequent symptom of shigellosis, persists for days or weeks after recovery (Speelman et al. 1987) and vomiting or food withdrawal is an important constraint to adequate feeding. Substantial loss of serum protein from the ulcerated colon is responsible for hypoproteinemia (Black and Levine 1991). Growth retardation following diarrheal diseases has been documented in several studies (Briend et al. 1989, Martorell et al. 1975, Rowland et al. 1977 and 1988, Tomkins 1981). In Bangladeshi children, shigellosis has a significant negative effect on linear growth (Black et al. 1984). This is particularly important for those children who do not die of shigellosis but whose nutritional status worsens further (Briend et al. 1986, Katz 1986). Malnutrition is a risk factor for death in shigellosis and stunting is its aftermath (Duncan et al. 1981, Henry et al. 1987, Strulens et al. 1985). Present management of shigellosis has focused mainly on antibiotic therapy, and less attention has been paid to the dietary management of shigellosis in children. Therefore, we hypothesized that early intervention with an energy-dense diet in the early phase of shigellosis may be effective in producing greater growth and reducing the consequences of poor growth. To evaluate this possibility, we conducted a randomized clinical trial to study whether feeding an energy-dense high protein diet (in addition to antibiotics) during the acute phase of shigellosis can accelerate growth following shigellosis.

Day 0, admission day; CI, confidence interval.

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SUBJECTS AND METHODS

The study was conducted in the metabolic ward of the International Centre for Diarrheal Disease Research, Dhaka, Bangladesh (ICDDR,B) which provides care and service to ~114,000 patients annually; of these ~10% have shigellosis (Annual Report 1994). Boys or girls aged 12-48 mo with visible blood or blood with mucous in the stool for 96 h, and weight-for-age <80% of the National Center for Health Statistics reference median were considered eligible for the study (Hamill 1977); a stool sample was sent to the pathological laboratory for microscopic examination. Patients were enrolled if fecal leukocytes were >20 per high power field on stool microscopy and if informed consent was obtained from the parents for participation of their children in the study. This protocol was approved by the Research Review Committee and the Ethical Review Committee of the ICDDR, B. Patients with kwashiorkor or systemic illnesses such as septicemia and paralytic ileus were not included in the study. Patients were admitted by an investigator and evaluated daily during their hospital stay. On admission, a stool sample was collected for culture of shigella species. Concentrations of serum albumin and prealbumin were measured on admission and on d 5 and 10 by standard laboratory techniques (Seaton et al. 1984). Anthropometry was carried out by a trained nutritionist. Every day during the study period, at 10:00 h, weight was measured on a weighing scale (Detecto Scale, Brooklyn, NY) to the nearest 20 g with patients wearing a minimum of clothing. Body weight was measured on admission (d 1) and daily for 10 hospital days. Supine length was measured on admission and on d 5 and 10 on a locally made wooden length board with a precision of 1 mm. At least five measurements were taken and the mean of five was recorded. Patients were followed up after 1 mo and anthropometric measurements were repeated. All measurements were recorded immediately on a precoded form. All children received nalidixic acid orally [55 mg/(kg·d), divided in four equal doses, for 5 d] for shigellosis after collection of stool for culture. If a patient was found to be suffering from a shigella species resistant to nalidixic acid, he or she was treated with pivmecillinam [60 mg/(kg·d), divided in four equal doses, for 5 d] after receiving the antibiogram (within 48 h). Patients were randomly allocated either to study or control groups according to a randomization schedule. A sealed envelope containing treatment allocation was opened after the entry of the subject to the study.

Details of the diet are given in Table 1. Diet was offered from 4 h after admission and consisted of bread and sugar for breakfast; rice, dal (lentil) and chicken curry for lunch and dinner, if appropriate for age and the child was used to solid foods. The intention was not to deviate from the existing hospital practices. The children in the study (high energy and protein) group were offered an additional energy-dense milk-cereal diet (energy 496 kJ/100 g) composed of milk powder (Dano), 120 g; rice powder, 30 g; sugar, 50 g; and soya oil, 30 g. The ingredients were thoroughly mixed and water was added up to 1000 mL, then boiled for 6-8 min. However, cooking volume was maintained at 1000 mL by adding water (if required). Patients in the study group were offered this formula every 2 h from 6:00 to 22:00 h. Control patients also received a similar milk-cereal formula (milk powder, Dano, 60 g; rice powder, 15 g; sugar, 25 g; and soya oil, 15 g; energy 248 kJ/100 g) with a similar feeding frequency throughout the study period. The amount of supplemental diet offered in both groups was 125 g/(kg·d). Mothers fed their babies and health assistants observed the feedings closely and recorded events such as vomiting. Food ingestion was computed by subtracting the weight of leftovers from the amounts served. For breast-fed babies, mothers were encouraged to continue breast-feeding and intake was measured by test weighing. If a patient left the hospital before completion of the study or developed complications that prevented the planned study to continue, data up to that point were included in the analysis.

Table 1. Composition of study and control diets1 [View Table]

All data were entered in an ASCII file with a personal computer using StatPack Gold version 3.1 (Walnock Associates, Minneapolis, MN). Data were analyzed with the SPSS PC+ statistical package, version 4.01 (SPSS, Chicago, IL). The significance of difference between study and control values was tested by Student's t test for normally distributed data and by the Mann-Whitney U test for non-normally distributed data (Armitage 1971). All tests of significance were two tailed. Probabilities of <0.05 were considered to be statistically significant.

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RESULTS

Of the 88 children suspected to be suffering from shigellosis, feces of 13 patients failed to grow shigella organisms and were not included in the analysis. Data from 36 children in the study group and 39 children in the control group were analyzed. Clinical characteristics on admission are shown in Table 2. The mean age, body weight, height, nutritional status, fever, anorexia and distribution of pathogens were comparable in the study and control groups. All of the children were malnourished (weight-for-age <80% of NCHS reference median). Seventy-five percent of the patients were febrile; 82% of the children were anorectic (not willing to take food compared with before the illness as stated by mother or attendant), and 32% of total patients had a history of vomiting. There was a history of straining during defecation in 72% of all patients, and 12% of the children presented with a rectal prolapse. Shigella flexneri was the predominant species (53%). Nine subjects were resistant to nalidixic acid in the control group and seven in the study group (P = 0.91). Food ingestion [g/(kg·d)] from all sources in the study vs. control groups was (mean ± SEM) 112 ± 2.28 vs.116 ± 3.48 (P = 0.16), 118 ± 2.72 vs.107 ± 3.13 (P = 0.04) and 120 ± 2.25 vs. 100 ± 3.83 (P = 0.04) on d 1, 5 and 10, respectively. Energy intake [kJ/(kg·d)] of study vs. control groups was (mean ± SEM) 622 ± 13.2 vs. 315 ±11.3 (P < 0.05), 655 ± 15.1 vs. 311 ± 7.98 (P < 0.05) and 672 ± 14.7 vs. 294 ± 11.1 (P < 0.05) on d 1, 5 and 10, respectively. Nine children were breast-fed in the study group and six in the control group. Intake (g/kg) of breast milk (mean ± SEM) was 75 ± 11 in the study group and 121 ± 30 in the control group (P = 0.23, Mann-Whitney U test). The mean increment in weight-for-age was significantly higher in the study than in the control group. Similarly, the increment in weight-for-height was higher in the study children than in controls. This weight and height increase continued to be significantly higher in the study group than in controls during the acute phase of illness and after discharge (Table 3). Serum total protein concentration (g/L) of study vs. control groups was: 68 vs. 67 (P = 0.64), 69 vs. 67 (P = 0.21), and 70 vs. 69 (P = 0.72) on d 1, 5, and 10, respectively. Serum prealbumin concentrations (g/L) were (study vs. control) 118 vs. 112 (P = 0.49), 214 vs. 170 (P = 0.01), 244 vs. 193 (P = 0.006) on d 1, 5, and 10, respectively (Table 4).

Table 2. Clinical characteristics of patients with acute shigellosis on admission1 [View Table]

Table 3. Changes in nutritional status after dietary intervention in malnourished children following acute shigellosis [View Table]

Table 4. Serum total protein and serum prealbumin of study and control groups after dietary intervention1 [View Table]

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DISCUSSION

Children are known to suffer from growth retardation as a result of shigellosis (Black et al. 1984, Henry et al. 1987). Similar findings have been observed in other inflammatory bowel diseases (Cooper et al. 1990, Kanof et al. 1988, Kirschner et al. 1978). Malnutrition causes growth failure and a decrease in serum insulin-like growth factor-I (IGF-I). However, refeeding increases IGF-I (Pucilowska et al. 1993). In an animal model, Butzner and Gall (1991) showed that early re-feeding of infected-malnourished animals increases small intestine weight, suggesting that nutritional rehabilitation is associated with recovery of crypt-villus structure and mucosal mass. Recommendations have been made for additional supplementation in the convalescent stage to compensate for reduced food intake during acute diarrhea (Sarkar et al. 1982). Efforts have been made to supplement children with a high protein diet during the convalescent period of shigellosis (Kabir et al. 1993). Brown et al. (1990) in their early vs. late feeding study documented significantly higher net energy and nutrient absorption from a full strength dietary formula compared with a diluted one in acute diarrhea. They also documented greater weight gain in children receiving full strength formula and recommended continuous feeding to avoid nutritional deterioration of the patients without increasing the risk of complications. In a metabolic balance study, we have documented that in acute shigellosis the efficiency of absorption of nutrients remains similar when a diet is energy-dense. Therefore, total absorption of nutrients is significantly increased from a energy-dense diet in malnourished children in acute shigellosis (Mazumder et al., unpublished). In the present study, feeding a diet concentrated in energy and protein provided some nutritional advantages to malnourished children during the acute phase of shigellosis. There was an increase in weight-for-age and weight-for-height after dietary supplementation. Study group children received more milk compared with controls, so that their higher micronutrient intake from this source may also have influenced growth. Serum total protein concentration did not increase significantly over the study period, because the turnover time of protein is longer. However, serum prealbumin concentration increased significantly in the study group during the dietary intervention. The increment in this rapidly turning over protein suggests that there is no impairment in protein synthesis in acute shigellosis. Thus the study suggests that better absorption of total nutrients from the intestine can occur after a dietary intervention even in an acute colonic inflammatory disease such as shigellosis.

Diarrheal diseases lower food intake by 20-40% (Brown et al. 1990, Khan and Ahmad 1986). There is a lower energy intake during acute shigellosis under normal case management (Molla et al. 1983). Anorexia is the limiting factor, because parents dislike forcing their children to eat during shigellosis. Huffman et al. (1991) recommended that improved complementary foods during diarrhea may be an ideal method to improve weaning practices in children. Therefore, in the acute stage of shigellosis when catabolism is high, increased energy requirements could be met only by offering more energy and protein. Mortality is reported to be higher among children discharged from hospital after treatment for diarrhea including shigellosis (Roy et al. 1983). This may be reduced by feeding a supplementary diet regime during hospitalization. In our study subjects, the weight-for-age and weight-for-height increment persisted for at least 30 more days at home where no nutrition intervention was done. We cannot explain the sustained increase in weight-for-age and weight-for-height at home. However, this could be due to the demonstration of feeding practices to the mothers or attendants during their hospital stay, or to improved absorptive capacity of enterocytes. Also, the children's appetite may have been stimulated during the acute illness. From this study, we may therefore conclude that in malnourished children, energy-protein requirements can be improved by supplementing an energy-dense diet during the acute phase of shigellosis. This will substantially enhance growth following shigellosis and may prevent post-shigella growth faltering.

FOOTNOTES

Manuscript received 20 September 1995. Initial reviews completed 8 December 1995. Revision accepted 23 August 1996.

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