Nutritional Regulation of Host Resistance and Predictive Value of Immunologic Tests in Assessment of Outcome

Symposium on Nutrition

Nutritional Regulation of Host Resistance and Predictive Value of Immunologic Tests in Assessment of Outcome Shakuntla Puri, M.D.,* and R. K. Chandra, M.D., F.R.C.P.(C)t

The historic association of malnutrition and infection has been substaniated by recent epidemiologic surveys. 51 Impaired immunologic and nonimmunologic defense mechanisms, such as absent or reduced delayed cutaneous hypersensitivity response to common microbial antigens, decreased number of thymus-dependent T lymphocytes, reduced bactericidal capacity of neutrophils, lower mucosal secretory IgA antibody titer, and depressed complement system, have been consistently documented in several studies among undernourished children and adults. 2, 14, 25, 32 In smallfor-gestation infants, impaired cell-mediated immunity may persist for several months and years,16 contributing to higher morbidity. The problem of nutritional deficiency is not restricted to developing countries. Children attending hospitals in North America have been documented to show frequent presence of associated malnutrition. In one of our surveys of patients admitted to a pediatric facility, we found approximately 18 per cent to have two or more indices indicating nutritional deficiency (Table 1). Malnutrition may develop or get aggravated during hospitalization, and can in its turn increase the risk of complications, thereby increasing the duration of hospital stay (Fig. 1). Some of the nutrition-associated complications may be expected to be prevented by early diagnosis and . effective correction of nutritional problems. This is well documented in adult patients, such as those with gastrointestinal carcinoma. 4o Similar data for young children are not available and are urgently needed. The diagnosis of undernutrition has traditionally been made on clinical, anthropometric, and biochemical evaluation (Table 2). While many of these tests are simple and useful,36 they are static measures of nutritional status *Resident in Pediatrics and Postdoctoral Clinical Fellow in Immunology, Memorial University of Newfoundland, and Janeway Child Health Centre, St. John's, Newfoundland, Canada tProfessor, Departments of Pediatrics, Medicine, and Biochemistry, Memorial University of Newfoundland, and Janeway Child Health Centre, St. John's, Newfoundland, Canada

Pediatric Clinics of North American-VoL 32, No, 2, April 1985

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Table 1. Prevalence of Undernutrition in 300 Randomly Selected Children Attending Hospital (Day Care, Inpatients, Both Medical and Surgical Diagnosis)* PER CENT SHOWING ABNORMAL TEST

VALUE

PER CENT SHOWING ABNORMAL TEST

VALUE

Weight-for-height Mid-upper arm circumference Serum albumin <3.0 mg/dl

5.5 6.0

Ferritin < 18 ng/ml Zinc < 70 fLg/dl

9.5

3.5

Delayed cutaneous hypersensitivity (anergy)

7.5

Serum transferrin < 150 mg/dl Hemoglobin < 10 gm/dl

7.0 Lymphopenia < 1,500/mm3

4.0

3.5

5.5

*Data collected in collaboration with Drs. Delores Doherty, John Dearlove, Zeny Antonio, and Eileen Tomas. and may not be helpful in predicting outcome. For example, although malnutrition enhanced the risk of death, use of weight-for-height less than 77 per cent of standard predicted only a small fraction of the mortality in infants and young children in rural Bangladesh. 20 To this battery of tests of nutritional assessment, one might now add functional indices. Infection is the most frequent cause of death in the malnourished, and nutritional deficiency commonly impairs immune responses, often prior to clinical signs (Fig. 2); thus, it is logical to think of tests of immunocompetence as a practical and functional index of nutritional status. 12. 19 This is now documented in adult surgical patients in whom adverse outcome in terms of sepsis and/or death is several-fold higher among those who are anergic preoperatively compared with those who do show a positive delayed hypersensitivity response. 14, 15 In this review, we briefly describe the current information on nutritional modulation of immunity, enumerate the various immunologic tests that are potentially useful in nutritional assessment, examine the reliability of tests predicting disease and complications, and how immunologic evaluation may help in the decision process regarding nutritional support. Table 2. Methods of Nutritional Assessment Clinical Dietary intake Physical examination

Anthropometric Weight-for-height Mid-upper arm circumference Skin-fold thickness Hematologic Hemoglobin Red cell morphology Ferritin

Biochemical Serum albumin Serum transferrin Creatinine/height index Zinc Immunologic Delayed cutaneous hypersensitivity Lymphocyte count Terminal transferase activity T cells Miscellaneous Hand grip strength Dark adaptation Taste acuity

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Figure 1. The duration of hospital stay of young children, aged 1-4 years, admitted with the clinical and radiologic diagnosis of pneumonia. Undernutrition was diagnosed on the basis of at least two abnormal results of nutritional assessment from two separate categories of tests.

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NUTRITION AND IMMUNITY Malnutrition is the most common cause of secondary immunodeficiency. This impairment of immune responses occurs both with generalized undernutrition as well as with deficiencies or excesses of single nutrients. The causal interaction between nutritional status and immunologic function is a complex one and depends upon a variety of factors, including the age of the subject, the type and duration of malnutrition, presence of specific nutrient deficiencies, nature of the underlying disease, and the presence of concurrent infection. The most prominent effects of nutritional deficien-

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Figure 3. The host protective umbrella consists of anatomic barriers and nonspecific and antigen-specific mechanisms. Malnutrition produces defects in many of these factors.

cies are observed on cell-mediated immunity, number of T lymphocytes, helper T cell function, complement system, mucosal IgA response, neutrophil bacterial killing capacity, and antibody affinityll (Fig. 3). Depression of host immune responses in malnutrition is generally reversible. Appropriate nutritional rehabilitation restores the immune function. However, critical data about the rates of functional recovery of different components of the immune system, upon nutritional repletion, are only limited. Cell-Mediated Immunity The impact of protein-energy malnutrition (PEM) is greatest and universal on T cell number and function and on cell-mediated immunity. Children who die of PEM show marked atrophy of the thymus. There is depletion of lymphocytes, particularly from cortical areas of the thymus and thymus-dependent areas of peripheral lymphoid tissues. 10, 47 The severity of thymic involution in PEM varies from the mild to the extreme depending upon the duration, speed, and severity of malnutrition. Extreme thymic atrophy severe enough to be called "nutritional thymectomy" has also been

NUTRITIONAL REGULATION OF HOST RESISTANCE

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observed in animal models of PEM.4 The profound adverse effect of malnutrition on lymphoid tissues is out of proportion to changes in most other parts of the body because of the rapid rate of cellular growth and proliferation in these organs. In PEM, the lack of availability of essential substrates and cofactors may depress DNA synthesis. Alternatively, high free corticosteroid levels may result in depletion of T lymphocytes and produce changes in the relative proportion ofT and B lymphocytes. T cells in the peripheral blood are decreased with a correlation between the degree of weight deficit and the depression of T cell number. 8 Nutritional repletion results in improvement in the number of circulating T cells. "Null" cells, lymphocytes that do not carry surface markers for mature T or B cells, are increased. 30 Their exact functional significance is unknown. However, they are increased in many disorders associated with decreased cell-mediated immunity such as leprosy, primary immunodeficiency, and cancer. Both T4 helper cells and T8 suppressor cells are reduced in number, particularly the former, thereby resulting in a low T4/T8 ratio. 15 Lymphocytes from children with PEM show depressed proliferation response to mitogens, especially in the presence of autologous serum. Presence of some inhibitory factors in the plasma of the malnourished or the lack of factor(s) essential for proliferation may be responsible for this depressed response. 1 Delayed cutaneous hypersensitivity (DCH) using a variety of recall antigens has been shown to be impaired in malnourished children. Impairment of DCH correlates with the degree of nutritional deficit4I and nutritional therapy results in improved response. Antibody Response Circulating B lymphocytes are either normal or decreased in number. 55 Most studies have documented either normal or increased levels of immunoglobulins in PEM.5 Hyperimmunoglobulinemia in PEM is apparently secondary to repeated infections and/or decreased suppressor T cell function. In fetal malnutrition, infants have low levels of IgG at birth and for several months later. This may be a result of the negative impact of nutritional deprivation on maturation of the immune system during the critical period of its development, or impaired placental transfer, or both. Serum antibody response is a measure of the functional adequacy of humoral immunity. The results of the specific serum antibody responses in malnutrition are, however, conflicting. This may be explained on the basis of differences, in the nature and dose of the antigen, route of administration, age of the host, severity of malnutrition, and presence of concomitant infections. Depending on these factors, the antibody responses may be normal or decreased. 38 Complement System Protein-energy malnutrition results in significant decrease in total hemolytic complement activity and reduced levels of many complement components particularly C3. 7• 54. 56 Complement component C4 is usually normal. Levels of complement components correlate with the degree of clinical malnutrition and with biochemical parameters. 33 Alternate pathway of complement activation and Factor B concentration are depressed in PEM. Decreased synthesis or secretion and/or increased consumption or

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destruction of the complement components via activation may underlie changes observed in PEM. This is supported by the observation of metabolic fragments of C3 in the serum of severely malnourished patients, who also often have associated infection. 7. 33 Phagocyte Function Polymorphonuclear leukocytes (PMN) and macrophages constitute an integral part of nonspecific barrier to infections. A number of studies have reported that the increased severity of infection in the malnourished may be due at least in part to the defective phagocyte function. Mobilization of mononuclear cells has been demonstrated to be delayed and reduced in PEM.28 In BCG-induced lesions in rodents, dietary protein depletion resulted in marked retardation of macrophage mobilization so that granuloma formation was poor. 3 Random mobility and chemotactic migration of PMN is normal in PEM, except when gross infection is present. 50 Opsonic activity of plasma and phagocytosis of opsonized particles is normal when plasma concentration is 10 per cent or higher but it is reduced at lower concentration in PEM sera.lO The bacterial killing capacity of PMN is reduced in children with PEM 23. 53 and is promptly corrected after nutritional therapy. The abnormality may be due to reduced activity of NADPH oxidase and hexose-monophosphate shunt. 52 Mucosal Immunity Malnutrition suppresses the normal functioning of secretory immunity. Secretory IgA (sIgA) is low in PEM. 6 , 49 Selective depression ofIgA synthesis in the submucosa may be one of the causes of low sIgA, because IgAcontaining plasma cells are decreased in number in the intestines of PEM children. Impaired production and/or function of the secretory component may be another factor. The secretory IgA antibody response to viral immunization is depressed in children with malnutrition. 6 These changes may have clinical significance in terms of incidence of septicemia, absorption of macromolecules, severity of infections, and effectiveness of vaccineinduced immunity.

MALNUTRITION AND INFECTIONS Nutrition, through its modulation of specific and nonspecific immune responses, appears to be a critical determinant of susceptibility to infections. Most of the mortality associated with progressive malnutrition is due to complicating infection (Fig. 4). There are clinical and epidemiologic data to suggest that malnutrition increased the frequency, the severity, and perhaps the incidence of infections. Critically ill patients with depleted energy stores, increased metabolism, and documented malnutrition have a higher than average susceptibility to infections. Studies in Asia and Africa have shown that 30 to 65 per cent of children admitted with moderatesevere malnutrition had active infection, and there was a high sepsis-related mortality.39 Scrimshaw et al. 51 and Chandra and Newberne 18 have provided a critical review of infections among individuals having multiple nutritional deficiencies.

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Bacterial Infections Palmer and associates 44 studied 70,000 white men recruited for the United States. Navy from 1949-1951 for evidence of malnutrition and its relation to morbidity rates for tuberculosis and found that persons who were 15 per cent or more underweight in relation to their height were affected four times as often as persons of normal weight. The prognosis of advanced pulmonary tuberculosis can be improved by providing highprotein diets. 59 Malnutrition also predisposes to higher frequency and severity of respiratory infections. Bronchopneumonia was reported to be the most frequent cause of death in both kwashiorkor and marasmus. 22, 46 In a necropsy study of children dying of kwashiorkor in Guatemala, Tejada and coworkers 57 found bronchopneumonia in two thirds. Viral Infections In undernourished children, viral infections are more disseminated and severe. In measles, the prodromal symptoms are more severe and there are confluent widespread skin lesions. Because of impaired cellmediated immunity, there is more extensive viral invasion of tissues, resulting in widespread inflammation, cell death, and consequent secondary bacterial invasion. In Mrica, measles infection has a mortality of 25 to 50 per cent in severely malnourished infants and children. Parasitic Infections

Pneumocystis carinii pneumonia is more frequently seen in children with marasmus and kwashiorkor. 24, 34 This is similar to P. carinii infection seen in lymphoproliferative disorders, primary immunodeficiency, and

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DIARRHOEA MORBIDITY •

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organ transplantation--conditions associated with depressed cell-mediated immunity. Several studies have reported malnutrition as a predisposing cause of amebic disease. 26, 48 They have also suggested that high-energy content diet, low in protein, enhances this susceptibility. Similar results are reported in animal models of amebic disease. Giardia infestation is more prevalent in malnourished populations. Decreased sIgA and T lymphocytes in the gut in association with hypochlorhydria may be responsible for poor host eradication of the parasite. This, together with increased infestation load because of poor sanitation, so commonly present in malnourished impoverished societies, contributes to high incidence of these infections. Susceptibility to Trypanosoma and possibly to malaria may be decreased or unchanged. 35, 51 Diarrheal Disease In developing countries, ignorance, poverty, poor sanitation, and malnutrition contribute to the high prevalence of diarrheal disease and resultant mortality. The coexistence of diarrhea and malnutrition leads to a self-perpetuating cycle seriously affecting the health, growth, and development of young children. In a study of Guatemalan children, Gomez and associates 29 showed that the occurrence of diarrheal disease was significantly greater in the malnourished, that the number of attack rates correlated with the degree of malnutrition, and that this relationship persisted at all preschool ages. There was also greater severity of the disease in the malnourished. Similar data have been reported recently from Nigeria58 and India13 (Fig. 5). Specific Nutrient Deficiencies and Infections Studies on the effect of single nutrient deficiencies on the incidence of infections in man have sometimes shown inconsistent and controversial

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results. Most of these studies were done in low socioeconomic groups in which several nutritional deficiencies may coexist, and it may be impossible to separate their effects. Furthermore, during nutritional repletion, diet greatly deficient in many nutrients may be given instead of just the nutrient under study. The relationship between iron nutrition and risk of infection has been the subject of much recent debate and is extensively reviewed elsewhere. 60 Infections are a common occurrence in acrodermatitis enteropathica and in zinc deficiency associated with a variety of medical conditions. Rats fed a copper-deficient diet have shortened survival time and severalfold increase in mortality following infection with Salmonella typhimurium. 43 Copper has been shown to be important for the functioning of reticuloendothelial system. Low content of soil selenium in the Keshan region of China has been linked to cardiomyopathy seen in that population. Animals challenged with viral infections were more likely to develop cardiomyopathy if they were selenium deficient. 17 A similar explanation may be true for cardiomyopathy of Keshan disease. Excesses and deficiencies of dietary fats and vitamins have also been linked to increased susceptibility to infections in experimental animals.

IMMUNOCOMPETENCE IN NUTRITIONAL ASSESSMENT AND AS A PREDICTOR OF MORBIDITY AND MORTALITY

The concept of nutritional modulation of risk of disease has generated renewed interest in newer approaches to nutritional surveillance and assessment of hospitalized patients, unselected population groups, and individuals. Dietary history, physical assessment, anthropometric measures, biochemical and hematologic tests are the broad types of approaches that can be used in nutritional evaluation. However, these classic methods measure body size, and mass and weight and their compartmental distribution, but not function. Moreover, the relative significance of these observations, measures, or tests has not been clearly defined. Progressive imbalance of nutrition results, successively, in biochemical and physiologic adaption, changes in the size of various body compartments, altered concentration of tissue constituents, biochemical abnormalities, disordered physicochemical organ function, histomorphologic changes in tissues, and finally clinical manifestations (Fig. 2). Immunologic changes (disease vulnerability) may be expected to precede symptoms and signs. Studies that include data on these relatively late indices thus cannot be compared with those that examined earlier subclinical stages of nutritional deficiency. Assessment of immunocompetence provides a functional index of nutritional status. These are simple tests to perform and can be used as one of the indicators to predict the need for nutritional support. They provide a prognostic index of morbidity and mortality from surgery, infections, malignancy and other medical conditions. T Lymphocytes

T cells are involved in cell-mediated immunity and can be identified by their ability to form rosettes with sheep red blood cells or by the use of

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monoclonal antibodies. The proportion and absolute number of these rosette-forming T lymphocytes is reduced in PEM and the reduction correlates with the degree of weight deficit. 9, 27 This abnormality is rapidly and completely reversed by nutritional repletion and this can be used as an index of nutritional recovery in hospitalized patients (Fig. 6). In recent years, the characterization of different subsets of T cells on the basis of surface membrane antigens as well as function has permitted their identification by monoclonal antibodies. In PEM as well as zinc deficiency, the number of T4 helper cells is significantly reduced. IS, 17 The frequency with which this change occurs in the malnourished has not yet been established. Leukocyte Terminal Deoxynucleotidyl Transferase (Tdt) Leukocyte Tdt is an index of T lymphocyte maturation and terminal differentiation. It can be estimated by enzyme-linked immunoassay or radioimmunoassay or semiquantitatively by immunofluorescence. Low thymic hormone activity in PEM is responsible for high Tdt levels in these patients, reflecting incomplete differentiation of lymphocytes to mature

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forms. This is suggested by the correlation of high leucocyte Tdt with the number of null cells in the peripheral blood of undernourished children. Delayed Cutaneous Hypersensitivity The administration into epidermis of previously encountered antigens produces an induration and erythema that is maximum at 48 hours to 72 hours. The standard method is injection by the use of a hypodermic gauge 26 needle with a short bevel and syringe. The recent commercial introduction of a disposable, ready-to-use plastic device with antigens already mounted is easy to use but it is expensive and has not been validated by adequately controlled studies. The recall antigens used depend on the age and the previous medical history. The battery of antigens commonly used is comprised of candida, streptokinase-streptodornase, mumps, tetanus toxoid, trichophyton, phytohemagglutinin, and purified protein derivative. If responses to these are negative, one could use 2,4 dinitrochlorobenzene. Many investigators have found frequent depression of DCH responses during undernutrition. This has been extensively used in the assessment of surgical patients. A correlation between the extent of anergy and the severity of nutritional deficiency and also prognosis in terms of sepsis and mortality has been reported. 21 , 31, 37 Opsonic Function The neutrophil ability to take up particles is facilitated by "opsonins," a group of protein molecules, including antibody, complement components, Factor B, properdin, and others. In the malnourished, estimation of opsonic function using 1.25 to 2.50 per cent plasma reveals abnormality in over two thirds of patients. The test is simple and can be automated. Complement Component C3 Total hemolytic complement activity and the serum concentration of many complement factors is reduced in malnutrition, and, since a high frequency of sepsis has been shown to be present in association with inherited deficiencies of C3, C5, and other fragments, an estimation of complement components should provide an index of risk to infection in malnourished subjects. C3 concentration is decreased and its level correlates with morbidity. 7, 54 C3 can be estimated by immunodiffusion in agar gel, nephelometry, or rocket electrophoresis using commercially available antiserum. Salivary IgA Secretory IgA affords protection against invasion by microorganisms at mucosal surfaces, and demonstration of low levels of sIgA in secretions would indicate enhanced susceptibility to respiratory and gastrointestinal tract infections. Low levels of sIgA in tears and saliva have been reported in moderate to severe malnutrition, and the secretory antibody response to live attenuated virus immunization has been shown to be reduced. Salivary sIgA can be estimated by immunodiffusion in agar, nephelometry, ELISA, or rocket electrophoresis. However, specific antisera are not easily available.

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Lymphocyte Count Nutritional deprivation is detrimental to structural and functional integrity of lymphoid tissues. Thymus and tonsils are small with a corresponding decrease in circulating lymphocyte number. Lymphopenia, an absolute lymphocyte count of less than 2500/mm 3 , was reported in 15 per cent of young Indian patients with PEM.5 In a study of severely malnourished children, Neumann et al. 42 found profound lymphopenia (cell count below lOOO/mm 3 ) in 9 per cent of cases. Superimposed infections, especially of the acute and fulminating type, can further depress the lymphocyte number. Validation of Immunocompetence in Nutritional Assessment Since the recognition of the impact of nutritional status on the immune system, tests of immunocompetence are increasingly being used to assess the presence of undernutrition. In order to evaluate the usefulness of these tests, it is important to examine their ability to identifY patients with malnutrition and to predict the ultimate outcome in terms of morbidity and mortality, especially that due to infection. Sensitivity and specificity of test gives the quantitative estimates of the proportion of patients developing disease who will be diagnosed or missed by using that test and also the proportion of those patients who will be falsely identified as positive. Positive predictive value provides the estimation of patients with disease among those who are test positive while the negative predictive value gives the estimate of the patients who will not develop the disease. The methods of calculating these indices are given in Table 3. Almost all of the work on the use of immunologic tests in assessment of prognosis has been done in adult surgical patients. There is an obvious need for extending such observations to patients with medical diagnoses and to younger age groups, including children. Two examples of the application of immunocompetence testing to assessment of the risk of nutrition-relation complications are given in Figure 7 and Table 4. Our experience with the use of the seven indices of immunity function described above is shown in Figure 7. The choice of one or more of these tests would depend upon the patient setting and laboratory facilities available. Table 3. Estimates of Reliability of Diagnostic Tests TEST RESULT

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OUTCOME

Adverse outcome or disease Favorable outcome or no disease Sensitivity % = a ~ b

X

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Table 4 gives the value of various statistical parameters calculated from a number of studies that have used different immunocompetence tests (primarily cutaneous delayed hypersensitivity) as parameters of nutritional assessment. These studies generally show that the incidence of postoperative sepsis and mortality correlates with the presence of abnormal tests either preoperatively or at some time during the postoperative period. However, from the table it is apparent that the values of sensitivity and specificity of these tests and their positive and negative value in predicting the development of infection and mortality varies considerably from one study to another. This could be due to a number of factors, including the total number of cases in a study, the prevalence of malnutrition in the group studied, selection of the cut-off point for a test to be considered abnormal, the primary diagnosis, and the antigen used for DeH. For example, a reanalysis of results reported in a recent study gave widely different values depending upon whether anergy or relative anergy was used as an index of immunoincompetence (Table 5). We feel that a positive even reaction to Table 4. Reliability of Preoperative Anergy (Absence of Delayed Cutaneous Hypersensitivity) to Predict Postoperative Malnutrition and Associated Complications* POSITIVE

OUTCOME

Sepsis Mortality

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NEGATIVE PREDICTIVE

SENSITIVITY

SPECIFICITY

VALUE

VALUE

(%)

(%)

(%)

(%)

61 (50--80) 49 (37-60)

74 (62-90) 74 (60--88)

28 (14-39) 25 (21-29)

92 (84-97) 91 (90-92)

*Data are shown as mean (and range) of values obtained from several reported studies, largely based on adults undergoing major surgery for a variety of primary diagnoses. 14,21,31, 37, 45

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Table 5. Sensitivity, Specificity, and Values of Predictive Indices Depending Upon the Use of Anergy or Relative Anergy as the Index Test* POSITIVE PREDICTIVE

NEGATIVE PREDICTIVE

SENSITIVITY

SPECIFICITY

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VALUE

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(%)

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54

70

39

84

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30

92

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CRITERION

*Data derived from Griffith, C. D. M., and McLean Ross, A. H.: Delayed hypersensitivity skin testing in elective colorectal surgery and relationship to postoperative sepsis. J. Parent. Ent. Nutr., 8:279-280, 1984. The prior test probability of disease was 26 per cent, calculated by the formula a + b For explanation of symbols, see Table 3. a+b+c+d'

one antigen is proof enough of adequate DCH and normal cell-mediated immunity. If a low cut-off point (for example, serum albumin concentration ::5 3.0 gm/dl) is used to define an abnormal test, the index of sensitivity decreases but specificity improves. The reverse will happen if a high cut-off point (for example, serum albumin concentration ::5 3.5 gm/dl) is employed. Another application of immunologic tests is in follow-up of infants in populations at high-risk of developing both malnutrition and infection. Impaired immune responses may precede documented reduction in growth velocity. An example is illustrated in Figure 8.

CONCLUSIONS The causal interaction between nutrition, infection, and immunity is well established. Malnutrition is not an all-or-none phenomenon. Rather it is a broad spectrum from life-threatening kwashiorkor and marasmus, so often seen in underprivileged countries, to subclinical deficiencies of selected dietary elements. Subclinical deficiencies of calories and single nutrients alone or in combination are not uncommon in hospitalized patients in North America. An association between the presence of these deficiencies and the course of disease, complicating infections, duration of hospital stay and ultimate morbidity and mortality have been reported in many studies. Global nutritional assessment based on close clinical observation and selected laboratory parameters is highly desirable and could identifY those patients who require nutritional support to prevent the development of malnutrition-associated complications. History of dietary intake, anthropometric measurements, and biochemical and hematologic tests provide useful information of the nutritional

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status. However, no one group of tests is satisfactory for obtaining a complete picture of the individual's ability to resist disease. Tests of immunocompetence are altered early in the development of undernutrition and therefore provide a functional measure of mild deviations from normal nutritional health. They reflect a broad measure of nutrition without being specific for any given nutrient. Assessment of immunocompetence by currently available methods in conjunction with other methods of nutritional assessment can identifY individuals who are most in need of appropriate nutritional support, and thus provide crucial prognostic information in terms of risk of disease, duration of hospitalization, and chances of survival. And survival, after all, is what preventive and therapeutic medicine is all about.

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